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Conserved domains on  [gi|62362414|ref|NP_005148|]
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tyrosine-protein kinase ABL1 isoform a [Homo sapiens]

Protein Classification

tyrosine-protein kinase ABL( domain architecture ID 10185641)

tyrosine-protein kinase ABL catalyzes the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates, and may play fundamental roles in the development and function of the central nervous system

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PTKc_Abl cd05052
Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of ...
235-497 0e+00

Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Abl (or c-Abl) is a ubiquitously-expressed cytoplasmic (or nonreceptor) PTK that contains SH3, SH2, and tyr kinase domains in its N-terminal region, as well as nuclear localization motifs, a putative DNA-binding domain, and F- and G-actin binding domains in its C-terminal tail. It also contains a short autoinhibitory cap region in its N-terminus. Abl function depends on its subcellular localization. In the cytoplasm, Abl plays a role in cell proliferation and survival. In response to DNA damage or oxidative stress, Abl is transported to the nucleus where it induces apoptosis. In chronic myelogenous leukemia (CML) patients, an aberrant translocation results in the replacement of the first exon of Abl with the BCR (breakpoint cluster region) gene. The resulting BCR-Abl fusion protein is constitutively active and associates into tetramers, resulting in a hyperactive kinase sending a continuous signal. This leads to uncontrolled proliferation, morphological transformation and anti-apoptotic effects. BCR-Abl is the target of selective inhibitors, such as imatinib (Gleevec), used in the treatment of CML. Abl2, also known as ARG (Abelson-related gene), is thought to play a cooperative role with Abl in the proper development of the nervous system. The Tel-ARG fusion protein, resulting from reciprocal translocation between chromosomes 1 and 12, is associated with acute myeloid leukemia (AML). The TEL gene is a frequent fusion partner of other tyr kinase oncogenes, including Tel/Abl, Tel/PDGFRbeta, and Tel/Jak2, found in patients with leukemia and myeloproliferative disorders. The Abl subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


:

Pssm-ID: 270645 [Multi-domain]  Cd Length: 263  Bit Score: 599.02  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  235 WEMERTDITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYII 314
Cdd:cd05052    1 WEIERTDITMKHKLGGGQYGEVYEGVWKKYNLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYII 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  315 TEFMTYGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYT 394
Cdd:cd05052   81 TEFMPYGNLLDYLRECNREELNAVVLLYMATQIASAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYT 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  395 AHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRA 474
Cdd:cd05052  161 AHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKGYRMERPEGCPPKVYELMRA 240
                        250       260
                 ....*....|....*....|...
gi 62362414  475 CWQWNPSDRPSFAEIHQAFETMF 497
Cdd:cd05052  241 CWQWNPSDRPSFAEIHQALETMF 263
SH2_ABL cd09935
Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ...
123-216 4.23e-61

Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ABL-family proteins are highly conserved tyrosine kinases. Each ABL protein contains an SH3-SH2-TK (Src homology 3-Src homology 2-tyrosine kinase) domain cassette, which confers autoregulated kinase activity and is common among nonreceptor tyrosine kinases. Several types of posttranslational modifications control ABL catalytic activity, subcellular localization, and stability, with consequences for both cytoplasmic and nuclear ABL functions. Binding partners provide additional regulation of ABL catalytic activity, substrate specificity, and downstream signaling. By combining this cassette with actin-binding and -bundling domain, ABL proteins are capable of connecting phosphoregulation with actin-filament reorganization. Vertebrate paralogs, ABL1 and ABL2, have evolved to perform specialized functions. ABL1 includes nuclear localization signals and a DNA binding domain which is used to mediate DNA damage-repair functions, while ABL2 has additional binding capacity for actin and for microtubules to enhance its cytoskeletal remodeling functions. SH2 is involved in several autoinhibitory mechanism that constrain the enzymatic activity of the ABL-family kinases. In one mechanism SH2 and SH3 cradle the kinase domain while a cap sequence stabilizes the inactive conformation resulting in a locked inactive state. Another involves phosphatidylinositol 4,5-bisphosphate (PIP2) which binds the SH2 domain through residues normally required for phosphotyrosine binding in the linker segment between the SH2 and kinase domains. The SH2 domain contributes to ABL catalytic activity and target site specificity. It is thought that the ABL catalytic site and SH2 pocket have coevolved to recognize the same sequences. Recent work now supports a hierarchical processivity model in which the substrate target site most compatible with ABL kinase domain preferences is phosphorylated with greatest efficiency. If this site is compatible with the ABL SH2 domain specificity, it will then reposition and dock in the SH2 pocket. This mechanism also explains how ABL kinases phosphorylates poor targets on the same substrate if they are properly positioned and how relatively poor substrate proteins might be recruited to ABL through a complex with strong substrates that can also dock with the SH2 pocket. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


:

Pssm-ID: 198189  Cd Length: 94  Bit Score: 203.00  E-value: 4.23e-61
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  123 EKHSWYHGPVSRNAAEYLLSSGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTASDGKLYVSSESRFNTLAELVHHH 202
Cdd:cd09935    1 EKHSWYHGPISRNAAEYLLSSGINGSFLVRESESSPGQYSISLRYDGRVYHYRISEDSDGKVYVTQEHRFNTLAELVHHH 80
                         90
                 ....*....|....
gi 62362414  203 STVADGLITTLHYP 216
Cdd:cd09935   81 SKNADGLITTLRYP 94
FABD smart00808
F-actin binding domain (FABD); FABD is the F-actin binding domain of Bcr-Abl and its cellular ...
1006-1130 7.56e-49

F-actin binding domain (FABD); FABD is the F-actin binding domain of Bcr-Abl and its cellular counterpart c-Abl. The Bcr-Abl tyrosine kinase causes different forms of leukemia in humans. Depending on its position within the cell, Bcr-Abl differentially affects cellular growth. The FABD forms a compact left-handed four-helix bundle in solution.


:

Pssm-ID: 197885  Cd Length: 126  Bit Score: 169.21  E-value: 7.56e-49
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414    1006 ISTRVSLRKTR--QPPERIASGAITKGVVLDSTEALCLAISRNSEQMASHSAVLEAGKNLYTFCVSYVDSIQQMRNKFAF 1083
Cdd:smart00808    1 IKTKVALRKTRtqQAAERIPSDAISKDMILELTELLESALVALSETPASHSQWLDKGHQLHSTCSGYADQIPQPRSKFQF 80
                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*..
gi 62362414    1084 REAINKLENNLRELQIcPATAGSGPAATQDFSKLLSSVKEISDIVQR 1130
Cdd:smart00808   81 RELVSRLELQLRELRF-SAGSRNVPGATQDFSKLLSSVKEISDVVQR 126
SH3_Abl cd11850
Src homology 3 domain of the Protein Tyrosine Kinase, Abelson kinase; Abl (or c-Abl) is a ...
65-118 6.73e-28

Src homology 3 domain of the Protein Tyrosine Kinase, Abelson kinase; Abl (or c-Abl) is a ubiquitously-expressed cytoplasmic (or nonreceptor) PTK that contains SH3, SH2, and tyr kinase domains in its N-terminal region, as well as nuclear localization motifs, a putative DNA-binding domain, and F- and G-actin binding domains in its C-terminal tail. It also contains a short autoinhibitory cap region in its N-terminus. Abl function depends on its subcellular localization. In the cytoplasm, Abl plays a role in cell proliferation and survival. In response to DNA damage or oxidative stress, Abl is transported to the nucleus where it induces apoptosis. In chronic myelogenous leukemia (CML) patients, an aberrant translocation results in the replacement of the first exon of Abl with the BCR (breakpoint cluster region) gene. The resulting BCR-Abl fusion protein is constitutively active and associates into tetramers, resulting in a hyperactive kinase sending a continuous signal. This leads to uncontrolled proliferation, morphological transformation and anti-apoptotic effects. BCR-Abl is the target of selective inhibitors, such as imatinib (Gleevec), used in the treatment of CML. Abl2, also known as ARG (Abelson-related gene), is thought to play a cooperative role with Abl in the proper development of the nervous system. The Tel-ARG fusion protein, resulting from reciprocal translocation between chromosomes 1 and 12, is associated with acute myeloid leukemia (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


:

Pssm-ID: 212784  Cd Length: 56  Bit Score: 107.11  E-value: 6.73e-28
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 62362414   65 LFVALYDFVASGDNTLSITKGEKLRVLGYNHNGEWCEAQTKN--GQGWVPSNYITP 118
Cdd:cd11850    1 LFVALYDFVASGENQLSIKKGEQLRVLGYNKNGEWCEAESKStgGQGWVPSNYITP 56
 
Name Accession Description Interval E-value
PTKc_Abl cd05052
Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of ...
235-497 0e+00

Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Abl (or c-Abl) is a ubiquitously-expressed cytoplasmic (or nonreceptor) PTK that contains SH3, SH2, and tyr kinase domains in its N-terminal region, as well as nuclear localization motifs, a putative DNA-binding domain, and F- and G-actin binding domains in its C-terminal tail. It also contains a short autoinhibitory cap region in its N-terminus. Abl function depends on its subcellular localization. In the cytoplasm, Abl plays a role in cell proliferation and survival. In response to DNA damage or oxidative stress, Abl is transported to the nucleus where it induces apoptosis. In chronic myelogenous leukemia (CML) patients, an aberrant translocation results in the replacement of the first exon of Abl with the BCR (breakpoint cluster region) gene. The resulting BCR-Abl fusion protein is constitutively active and associates into tetramers, resulting in a hyperactive kinase sending a continuous signal. This leads to uncontrolled proliferation, morphological transformation and anti-apoptotic effects. BCR-Abl is the target of selective inhibitors, such as imatinib (Gleevec), used in the treatment of CML. Abl2, also known as ARG (Abelson-related gene), is thought to play a cooperative role with Abl in the proper development of the nervous system. The Tel-ARG fusion protein, resulting from reciprocal translocation between chromosomes 1 and 12, is associated with acute myeloid leukemia (AML). The TEL gene is a frequent fusion partner of other tyr kinase oncogenes, including Tel/Abl, Tel/PDGFRbeta, and Tel/Jak2, found in patients with leukemia and myeloproliferative disorders. The Abl subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270645 [Multi-domain]  Cd Length: 263  Bit Score: 599.02  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  235 WEMERTDITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYII 314
Cdd:cd05052    1 WEIERTDITMKHKLGGGQYGEVYEGVWKKYNLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYII 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  315 TEFMTYGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYT 394
Cdd:cd05052   81 TEFMPYGNLLDYLRECNREELNAVVLLYMATQIASAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYT 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  395 AHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRA 474
Cdd:cd05052  161 AHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKGYRMERPEGCPPKVYELMRA 240
                        250       260
                 ....*....|....*....|...
gi 62362414  475 CWQWNPSDRPSFAEIHQAFETMF 497
Cdd:cd05052  241 CWQWNPSDRPSFAEIHQALETMF 263
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
242-493 2.47e-141

Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.


Pssm-ID: 462242 [Multi-domain]  Cd Length: 258  Bit Score: 426.14  E-value: 2.47e-141
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414    242 ITMKHKLGGGQYGEVYEGVWKKYS----LTVAVKTLKEDTME--VEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIIT 315
Cdd:pfam07714    1 LTLGEKLGEGAFGEVYKGTLKGEGentkIKVAVKTLKEGADEeeREDFLEEASIMKKLDHPNIVKLLGVCTQGEPLYIVT 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414    316 EFMTYGNLLDYLREcNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR-LMTGDTYT 394
Cdd:pfam07714   81 EYMPGGDLLDFLRK-HKRKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVVKISDFGLSRdIYDDDYYR 159
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414    395 AHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRA 474
Cdd:pfam07714  160 KRGGGKLPIKWMAPESLKDGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEFLEDGYRLPQPENCPDELYDLMKQ 239
                          250
                   ....*....|....*....
gi 62362414    475 CWQWNPSDRPSFAEIHQAF 493
Cdd:pfam07714  240 CWAYDPEDRPTFSELVEDL 258
STYKc smart00221
Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class ...
242-493 1.22e-138

Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class of kinases can not be predicted. Possible dual-specificity Ser/Thr/Tyr kinase.


Pssm-ID: 214568 [Multi-domain]  Cd Length: 258  Bit Score: 418.88  E-value: 1.22e-138
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414     242 ITMKHKLGGGQYGEVYEGVWKKYS----LTVAVKTLKEDTM--EVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIIT 315
Cdd:smart00221    1 LTLGKKLGEGAFGEVYKGTLKGKGdgkeVEVAVKTLKEDASeqQIEEFLREARIMRKLDHPNIVKLLGVCTEEEPLMIVM 80
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414     316 EFMTYGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTA 395
Cdd:smart00221   81 EYMPGGDLLDYLRKNRPKELSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRDLYDDDYYK 160
                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414     396 HAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRAC 475
Cdd:smart00221  161 VKGGKLPIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEEPYPGMSNAEVLEYLKKGYRLPKPPNCPPELYKLMLQC 240
                           250
                    ....*....|....*...
gi 62362414     476 WQWNPSDRPSFAEIHQAF 493
Cdd:smart00221  241 WAEDPEDRPTFSELVEIL 258
SH2_ABL cd09935
Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ...
123-216 4.23e-61

Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ABL-family proteins are highly conserved tyrosine kinases. Each ABL protein contains an SH3-SH2-TK (Src homology 3-Src homology 2-tyrosine kinase) domain cassette, which confers autoregulated kinase activity and is common among nonreceptor tyrosine kinases. Several types of posttranslational modifications control ABL catalytic activity, subcellular localization, and stability, with consequences for both cytoplasmic and nuclear ABL functions. Binding partners provide additional regulation of ABL catalytic activity, substrate specificity, and downstream signaling. By combining this cassette with actin-binding and -bundling domain, ABL proteins are capable of connecting phosphoregulation with actin-filament reorganization. Vertebrate paralogs, ABL1 and ABL2, have evolved to perform specialized functions. ABL1 includes nuclear localization signals and a DNA binding domain which is used to mediate DNA damage-repair functions, while ABL2 has additional binding capacity for actin and for microtubules to enhance its cytoskeletal remodeling functions. SH2 is involved in several autoinhibitory mechanism that constrain the enzymatic activity of the ABL-family kinases. In one mechanism SH2 and SH3 cradle the kinase domain while a cap sequence stabilizes the inactive conformation resulting in a locked inactive state. Another involves phosphatidylinositol 4,5-bisphosphate (PIP2) which binds the SH2 domain through residues normally required for phosphotyrosine binding in the linker segment between the SH2 and kinase domains. The SH2 domain contributes to ABL catalytic activity and target site specificity. It is thought that the ABL catalytic site and SH2 pocket have coevolved to recognize the same sequences. Recent work now supports a hierarchical processivity model in which the substrate target site most compatible with ABL kinase domain preferences is phosphorylated with greatest efficiency. If this site is compatible with the ABL SH2 domain specificity, it will then reposition and dock in the SH2 pocket. This mechanism also explains how ABL kinases phosphorylates poor targets on the same substrate if they are properly positioned and how relatively poor substrate proteins might be recruited to ABL through a complex with strong substrates that can also dock with the SH2 pocket. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198189  Cd Length: 94  Bit Score: 203.00  E-value: 4.23e-61
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  123 EKHSWYHGPVSRNAAEYLLSSGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTASDGKLYVSSESRFNTLAELVHHH 202
Cdd:cd09935    1 EKHSWYHGPISRNAAEYLLSSGINGSFLVRESESSPGQYSISLRYDGRVYHYRISEDSDGKVYVTQEHRFNTLAELVHHH 80
                         90
                 ....*....|....
gi 62362414  203 STVADGLITTLHYP 216
Cdd:cd09935   81 SKNADGLITTLRYP 94
FABD smart00808
F-actin binding domain (FABD); FABD is the F-actin binding domain of Bcr-Abl and its cellular ...
1006-1130 7.56e-49

F-actin binding domain (FABD); FABD is the F-actin binding domain of Bcr-Abl and its cellular counterpart c-Abl. The Bcr-Abl tyrosine kinase causes different forms of leukemia in humans. Depending on its position within the cell, Bcr-Abl differentially affects cellular growth. The FABD forms a compact left-handed four-helix bundle in solution.


Pssm-ID: 197885  Cd Length: 126  Bit Score: 169.21  E-value: 7.56e-49
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414    1006 ISTRVSLRKTR--QPPERIASGAITKGVVLDSTEALCLAISRNSEQMASHSAVLEAGKNLYTFCVSYVDSIQQMRNKFAF 1083
Cdd:smart00808    1 IKTKVALRKTRtqQAAERIPSDAISKDMILELTELLESALVALSETPASHSQWLDKGHQLHSTCSGYADQIPQPRSKFQF 80
                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*..
gi 62362414    1084 REAINKLENNLRELQIcPATAGSGPAATQDFSKLLSSVKEISDIVQR 1130
Cdd:smart00808   81 RELVSRLELQLRELRF-SAGSRNVPGATQDFSKLLSSVKEISDVVQR 126
F_actin_bind pfam08919
F-actin binding; The F-actin binding domain forms a compact bundle of four antiparallel ...
1025-1130 2.00e-37

F-actin binding; The F-actin binding domain forms a compact bundle of four antiparallel alpha-helices, which are arranged in a left-handed topology. Binding of F-actin to the F-actin binding domain may result in cytoplasmic retention and subcellular distribution of the protein, as well as possible inhibition of protein function.


Pssm-ID: 462633  Cd Length: 108  Bit Score: 135.95  E-value: 2.00e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   1025 GAITKGVVLDSTEALCLAISRNSEQMASH--SAVLEAGKNLYTFCVSYVDSIQQmRNKFAFREAINKLENNLRELQICPA 1102
Cdd:pfam08919    1 GPVSKESILELSEDLESALVNLKESLASSqtSQLSDKVGQLHSYCSGYADSIPP-HAKFAFRELLSRLESQSRQLRICSA 79
                           90       100
                   ....*....|....*....|....*....
gi 62362414   1103 TAGS-GPAATQDFSKLLSSVKEISDIVQR 1130
Cdd:pfam08919   80 GGSRnSPGNSKLFSDLHNTVKEISNVVQR 108
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
247-687 1.65e-36

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 145.16  E-value: 1.65e-36
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLK----EDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGN 322
Cdd:COG0515   14 LLGRGGMGVVYLARDLRLGRPVALKVLRpelaADPEARERFRREARALARLNHPNIVRVYDVGEEDGRPYLVMEYVEGES 93
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLRECNRQEVNAVvlLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFP 402
Cdd:COG0515   94 LADLLRRRGPLPPAEA--LRILAQLAEALAAAHAAGIVHRDIKPANILLTPDGRVKLIDFGIARALGGATLTQTGTVVGT 171
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  403 IKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEKDYRM---ERPEGCPEKVYELMRACWQWN 479
Cdd:COG0515  172 PGYMAPEQARGEPVDPRSDVYSLGVTLYELLT-GRPPFDGDSPAELLRAHLREPPPppsELRPDLPPALDAIVLRALAKD 250
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  480 PSDRP-SFAEIHQAFETMFQES---SISDEVEKELGKQGVRGAVSTLLQAPELPTKTRTSRRAAEHRDTTDVPEMPHSKG 555
Cdd:COG0515  251 PEERYqSAAELAAALRAVLRSLaaaAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAPAAAAAAA 330
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  556 QGESDPLDHEPAVSPLLPRKERGPPEGGLNEDERLLPKDKKTNLFSALIKKKKKTAPTPPKRSSSFREMDGQPERRGAGE 635
Cdd:COG0515  331 AAAAALAAAAAAAAAAAAAALLAAAAALAAAAAAAAAAAAAAAAAAAAAAAAAALAAAAAAAAAAAAAALAAAAAAAAAA 410
                        410       420       430       440       450
                 ....*....|....*....|....*....|....*....|....*....|..
gi 62362414  636 EEGRDISNGALAFTPLDTADPAKSPKPSNGAGVPNGALRESGGSGFRSPHLW 687
Cdd:COG0515  411 AAAAAAAAALAAAAAAAAAAAAAAAAAAAAAARLLAAAAAAAAAAAAAPLLA 462
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
125-208 2.94e-30

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.


Pssm-ID: 214585 [Multi-domain]  Cd Length: 84  Bit Score: 114.63  E-value: 2.94e-30
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414     125 HSWYHGPVSRNAAEYLLSSGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTASDGKLYVSSESRFNTLAELVHHHST 204
Cdd:smart00252    1 QPWYHGFISREEAEKLLKNEGDGDFLVRDSESSPGDYVLSVRVKGKVKHYRIRRNEDGKFYLEGGRKFPSLVELVEHYQK 80

                    ....
gi 62362414     205 VADG 208
Cdd:smart00252   81 NSLG 84
SH2 pfam00017
SH2 domain;
127-202 5.26e-30

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 113.46  E-value: 5.26e-30
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 62362414    127 WYHGPVSRNAAE-YLLSSGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTASDGKLYVSSESRFNTLAELVHHH 202
Cdd:pfam00017    1 WYHGKISRQEAErLLLNGKPDGTFLVRESESTPGGYTLSVRDDGKVKHYKIQSTDNGGYYISGGVKFSSLAELVEHY 77
SH3_Abl cd11850
Src homology 3 domain of the Protein Tyrosine Kinase, Abelson kinase; Abl (or c-Abl) is a ...
65-118 6.73e-28

Src homology 3 domain of the Protein Tyrosine Kinase, Abelson kinase; Abl (or c-Abl) is a ubiquitously-expressed cytoplasmic (or nonreceptor) PTK that contains SH3, SH2, and tyr kinase domains in its N-terminal region, as well as nuclear localization motifs, a putative DNA-binding domain, and F- and G-actin binding domains in its C-terminal tail. It also contains a short autoinhibitory cap region in its N-terminus. Abl function depends on its subcellular localization. In the cytoplasm, Abl plays a role in cell proliferation and survival. In response to DNA damage or oxidative stress, Abl is transported to the nucleus where it induces apoptosis. In chronic myelogenous leukemia (CML) patients, an aberrant translocation results in the replacement of the first exon of Abl with the BCR (breakpoint cluster region) gene. The resulting BCR-Abl fusion protein is constitutively active and associates into tetramers, resulting in a hyperactive kinase sending a continuous signal. This leads to uncontrolled proliferation, morphological transformation and anti-apoptotic effects. BCR-Abl is the target of selective inhibitors, such as imatinib (Gleevec), used in the treatment of CML. Abl2, also known as ARG (Abelson-related gene), is thought to play a cooperative role with Abl in the proper development of the nervous system. The Tel-ARG fusion protein, resulting from reciprocal translocation between chromosomes 1 and 12, is associated with acute myeloid leukemia (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212784  Cd Length: 56  Bit Score: 107.11  E-value: 6.73e-28
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 62362414   65 LFVALYDFVASGDNTLSITKGEKLRVLGYNHNGEWCEAQTKN--GQGWVPSNYITP 118
Cdd:cd11850    1 LFVALYDFVASGENQLSIKKGEQLRVLGYNKNGEWCEAESKStgGQGWVPSNYITP 56
PTZ00263 PTZ00263
protein kinase A catalytic subunit; Provisional
230-483 2.57e-20

protein kinase A catalytic subunit; Provisional


Pssm-ID: 140289 [Multi-domain]  Cd Length: 329  Bit Score: 93.34  E-value: 2.57e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   230 PNYDKWEMerTDITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM----EVEEFLKEAAVMKEIKHPNLVQLLGVC 305
Cdd:PTZ00263   10 PDTSSWKL--SDFEMGETLGTGSFGRVRIAKHKGTGEYYAIKCLKKREIlkmkQVQHVAQEKSILMELSHPFIVNMMCSF 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   306 TREPPFYIITEFMTYGNLLDYLRECNRQEvNAVVLLYMAtQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLS 385
Cdd:PTZ00263   88 QDENRVYFLLEFVVGGELFTHLRKAGRFP-NDVAKFYHA-ELVLAFEYLHSKDIIYRDLKPENLLLDNKGHVKVTDFGFA 165
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   386 RLMTGDTYTAHAGAKFpikwTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYE-LLEKdyRMERPEGC 464
Cdd:PTZ00263  166 KKVPDRTFTLCGTPEY----LAPEVIQSKGHGKAVDWWTMGVLLYEFIA-GYPPFFDDTPFRIYEkILAG--RLKFPNWF 238
                         250
                  ....*....|....*....
gi 62362414   465 PEKVYELMRACWQWNPSDR 483
Cdd:PTZ00263  239 DGRARDLVKGLLQTDHTKR 257
PknB_PASTA_kin NF033483
Stk1 family PASTA domain-containing Ser/Thr kinase;
247-442 5.57e-17

Stk1 family PASTA domain-containing Ser/Thr kinase;


Pssm-ID: 468045 [Multi-domain]  Cd Length: 563  Bit Score: 85.62  E-value: 5.57e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   247 KLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLK----EAAVMKEIKHPNLVQLLGVCTREPPFYIITEF---MT 319
Cdd:NF033483   14 RIGRGGMAEVYLAKDTRLDRDVAVKVLRPDLARDPEFVArfrrEAQSAASLSHPNIVSVYDVGEDGGIPYIVMEYvdgRT 93
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   320 ygnLLDYLRECNRQEVNAVVllYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYT----- 394
Cdd:NF033483   94 ---LKDYIREHGPLSPEEAV--EIMIQILSALEHAHRNGIVHRDIKPQNILITKDGRVKVTDFGIARALSSTTMTqtnsv 168
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 62362414   395 ---AHagakfpikWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPG 442
Cdd:NF033483  169 lgtVH--------YLSPEQARGGTVDARSDIYSLGIVLYEMLT-GRPPFDG 210
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
62-117 2.96e-13

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.


Pssm-ID: 214620 [Multi-domain]  Cd Length: 56  Bit Score: 65.25  E-value: 2.96e-13
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*..
gi 62362414      62 DPNLFVALYDFVASGDNTLSITKGEKLRVLGyNHNGEWCEAQTKNGQ-GWVPSNYIT 117
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLE-KSDDGWWKGRLGRGKeGLFPSNYVE 56
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
67-113 1.60e-11

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 394975 [Multi-domain]  Cd Length: 47  Bit Score: 59.91  E-value: 1.60e-11
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 62362414     67 VALYDFVASGDNTLSITKGEKLRVLGYNhNGEWCEAQTKNGQ-GWVPS 113
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLEKS-EDGWWKGRNKGGKeGLIPS 47
 
Name Accession Description Interval E-value
PTKc_Abl cd05052
Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of ...
235-497 0e+00

Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Abl (or c-Abl) is a ubiquitously-expressed cytoplasmic (or nonreceptor) PTK that contains SH3, SH2, and tyr kinase domains in its N-terminal region, as well as nuclear localization motifs, a putative DNA-binding domain, and F- and G-actin binding domains in its C-terminal tail. It also contains a short autoinhibitory cap region in its N-terminus. Abl function depends on its subcellular localization. In the cytoplasm, Abl plays a role in cell proliferation and survival. In response to DNA damage or oxidative stress, Abl is transported to the nucleus where it induces apoptosis. In chronic myelogenous leukemia (CML) patients, an aberrant translocation results in the replacement of the first exon of Abl with the BCR (breakpoint cluster region) gene. The resulting BCR-Abl fusion protein is constitutively active and associates into tetramers, resulting in a hyperactive kinase sending a continuous signal. This leads to uncontrolled proliferation, morphological transformation and anti-apoptotic effects. BCR-Abl is the target of selective inhibitors, such as imatinib (Gleevec), used in the treatment of CML. Abl2, also known as ARG (Abelson-related gene), is thought to play a cooperative role with Abl in the proper development of the nervous system. The Tel-ARG fusion protein, resulting from reciprocal translocation between chromosomes 1 and 12, is associated with acute myeloid leukemia (AML). The TEL gene is a frequent fusion partner of other tyr kinase oncogenes, including Tel/Abl, Tel/PDGFRbeta, and Tel/Jak2, found in patients with leukemia and myeloproliferative disorders. The Abl subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270645 [Multi-domain]  Cd Length: 263  Bit Score: 599.02  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  235 WEMERTDITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYII 314
Cdd:cd05052    1 WEIERTDITMKHKLGGGQYGEVYEGVWKKYNLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYII 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  315 TEFMTYGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYT 394
Cdd:cd05052   81 TEFMPYGNLLDYLRECNREELNAVVLLYMATQIASAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYT 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  395 AHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRA 474
Cdd:cd05052  161 AHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKGYRMERPEGCPPKVYELMRA 240
                        250       260
                 ....*....|....*....|...
gi 62362414  475 CWQWNPSDRPSFAEIHQAFETMF 497
Cdd:cd05052  241 CWQWNPSDRPSFAEIHQALETMF 263
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
242-493 2.47e-141

Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.


Pssm-ID: 462242 [Multi-domain]  Cd Length: 258  Bit Score: 426.14  E-value: 2.47e-141
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414    242 ITMKHKLGGGQYGEVYEGVWKKYS----LTVAVKTLKEDTME--VEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIIT 315
Cdd:pfam07714    1 LTLGEKLGEGAFGEVYKGTLKGEGentkIKVAVKTLKEGADEeeREDFLEEASIMKKLDHPNIVKLLGVCTQGEPLYIVT 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414    316 EFMTYGNLLDYLREcNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR-LMTGDTYT 394
Cdd:pfam07714   81 EYMPGGDLLDFLRK-HKRKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVVKISDFGLSRdIYDDDYYR 159
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414    395 AHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRA 474
Cdd:pfam07714  160 KRGGGKLPIKWMAPESLKDGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEFLEDGYRLPQPENCPDELYDLMKQ 239
                          250
                   ....*....|....*....
gi 62362414    475 CWQWNPSDRPSFAEIHQAF 493
Cdd:pfam07714  240 CWAYDPEDRPTFSELVEDL 258
STYKc smart00221
Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class ...
242-493 1.22e-138

Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class of kinases can not be predicted. Possible dual-specificity Ser/Thr/Tyr kinase.


Pssm-ID: 214568 [Multi-domain]  Cd Length: 258  Bit Score: 418.88  E-value: 1.22e-138
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414     242 ITMKHKLGGGQYGEVYEGVWKKYS----LTVAVKTLKEDTM--EVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIIT 315
Cdd:smart00221    1 LTLGKKLGEGAFGEVYKGTLKGKGdgkeVEVAVKTLKEDASeqQIEEFLREARIMRKLDHPNIVKLLGVCTEEEPLMIVM 80
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414     316 EFMTYGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTA 395
Cdd:smart00221   81 EYMPGGDLLDYLRKNRPKELSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRDLYDDDYYK 160
                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414     396 HAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRAC 475
Cdd:smart00221  161 VKGGKLPIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEEPYPGMSNAEVLEYLKKGYRLPKPPNCPPELYKLMLQC 240
                           250
                    ....*....|....*...
gi 62362414     476 WQWNPSDRPSFAEIHQAF 493
Cdd:smart00221  241 WAEDPEDRPTFSELVEIL 258
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
242-493 1.48e-137

Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.


Pssm-ID: 197581 [Multi-domain]  Cd Length: 257  Bit Score: 416.16  E-value: 1.48e-137
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414     242 ITMKHKLGGGQYGEVYEGVWK----KYSLTVAVKTLKEDTME--VEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIIT 315
Cdd:smart00219    1 LTLGKKLGEGAFGEVYKGKLKgkggKKKVEVAVKTLKEDASEqqIEEFLREARIMRKLDHPNVVKLLGVCTEEEPLYIVM 80
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414     316 EFMTYGNLLDYLREcNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTA 395
Cdd:smart00219   81 EYMEGGDLLSYLRK-NRPKLSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRDLYDDDYYR 159
                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414     396 HAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRAC 475
Cdd:smart00219  160 KRGGKLPIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEYLKNGYRLPQPPNCPPELYDLMLQC 239
                           250
                    ....*....|....*...
gi 62362414     476 WQWNPSDRPSFAEIHQAF 493
Cdd:smart00219  240 WAEDPEDRPTFSELVEIL 257
PTKc cd00192
Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
247-494 1.62e-132

Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. They can be classified into receptor and non-receptor tyr kinases. PTKs play important roles in many cellular processes including, lymphocyte activation, epithelium growth and maintenance, metabolism control, organogenesis regulation, survival, proliferation, differentiation, migration, adhesion, motility, and morphogenesis. Receptor tyr kinases (RTKs) are integral membrane proteins which contain an extracellular ligand-binding region, a transmembrane segment, and an intracellular tyr kinase domain. RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain, leading to intracellular signaling. Some RTKs are orphan receptors with no known ligands. Non-receptor (or cytoplasmic) tyr kinases are distributed in different intracellular compartments and are usually multi-domain proteins containing a catalytic tyr kinase domain as well as various regulatory domains such as SH3 and SH2. PTKs are usually autoinhibited and require a mechanism for activation. In many PTKs, the phosphorylation of tyr residues in the activation loop is essential for optimal activity. Aberrant expression of PTKs is associated with many development abnormalities and cancers.The PTK family is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270623 [Multi-domain]  Cd Length: 262  Bit Score: 403.07  E-value: 1.62e-132
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWK---KYSLTVAVKTLKEDTM--EVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYG 321
Cdd:cd00192    2 KLGEGAFGEVYKGKLKggdGKTVDVAVKTLKEDASesERKDFLKEARVMKKLGHPNVVRLLGVCTEEEPLYLVMEYMEGG 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  322 NLLDYLREC-------NRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLM-TGDTY 393
Cdd:cd00192   82 DLLDFLRKSrpvfpspEPSTLSLKDLLSFAIQIAKGMEYLASKKFVHRDLAARNCLVGEDLVVKISDFGLSRDIyDDDYY 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  394 TAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMR 473
Cdd:cd00192  162 RKKTGGKLPIRWMAPESLKDGIFTSKSDVWSFGVLLWEIFTLGATPYPGLSNEEVLEYLRKGYRLPKPENCPDELYELML 241
                        250       260
                 ....*....|....*....|.
gi 62362414  474 ACWQWNPSDRPSFAEIHQAFE 494
Cdd:cd00192  242 SCWQLDPEDRPTFSELVERLE 262
PTKc_Src_like cd05034
Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
247-494 9.60e-131

Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, and Yes. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, and Lyn show a limited expression pattern. The Src-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270630 [Multi-domain]  Cd Length: 248  Bit Score: 397.81  E-value: 9.60e-131
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKySLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDY 326
Cdd:cd05034    2 KLGAGQFGEVWMGVWNG-TTKVAVKTLKPGTMSPEAFLQEAQIMKKLRHDKLVQLYAVCSDEEPIYIVTELMSKGSLLDY 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  327 LRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPIKWT 406
Cdd:cd05034   81 LRTGEGRALRLPQLIDMAAQIASGMAYLESRNYIHRDLAARNILVGENNVCKVADFGLARLIEDDEYTAREGAKFPIKWT 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  407 APESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQWNPSDRPSF 486
Cdd:cd05034  161 APEAALYGRFTIKSDVWSFGILLYEIVTYGRVPYPGMTNREVLEQVERGYRMPKPPGCPDELYDIMLQCWKKEPEERPTF 240

                 ....*...
gi 62362414  487 AEIHQAFE 494
Cdd:cd05034  241 EYLQSFLE 248
PTKc_Frk_like cd05068
Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
233-498 1.32e-124

Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Frk and Srk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Frk, also known as Rak, is specifically expressed in liver, lung, kidney, intestine, mammary glands, and the islets of Langerhans. Rodent homologs were previously referred to as GTK (gastrointestinal tyr kinase), BSK (beta-cell Src-like kinase), or IYK (intestinal tyr kinase). Studies in mice reveal that Frk is not essential for viability. It plays a role in the signaling that leads to cytokine-induced beta-cell death in Type I diabetes. It also regulates beta-cell number during embryogenesis and early in life. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Frk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270653 [Multi-domain]  Cd Length: 267  Bit Score: 382.53  E-value: 1.32e-124
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  233 DKWEMERTDITMKHKLGGGQYGEVYEGVWKKySLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFY 312
Cdd:cd05068    1 DQWEIDRKSLKLLRKLGSGQFGEVWEGLWNN-TTPVAVKTLKPGTMDPEDFLREAQIMKKLRHPKLIQLYAVCTLEEPIY 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  313 IITEFMTYGNLLDYLRECNRQeVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRL-MTGD 391
Cdd:cd05068   80 IITELMKHGSLLEYLQGKGRS-LQLPQLIDMAAQVASGMAYLESQNYIHRDLAARNVLVGENNICKVADFGLARViKVED 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  392 TYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYEL 471
Cdd:cd05068  159 EYEAREGAKFPIKWTAPEAANYNRFSIKSDVWSFGILLTEIVTYGRIPYPGMTNAEVLQQVERGYRMPCPPNCPPQLYDI 238
                        250       260
                 ....*....|....*....|....*..
gi 62362414  472 MRACWQWNPSDRPSFAEIHQAFETMFQ 498
Cdd:cd05068  239 MLECWKADPMERPTFETLQWKLEDFFV 265
PTKc_Csk_like cd05039
Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
235-495 3.04e-110

Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of Csk, Chk, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, Csk and Chk are translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. Csk catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. Chk inhibit Src kinases using a noncatalytic mechanism by simply binding to them. As negative regulators of Src kinases, Csk and Chk play important roles in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. The Csk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270635 [Multi-domain]  Cd Length: 256  Bit Score: 343.95  E-value: 3.04e-110
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  235 WEMERTDITMKHKLGGGQYGEVYEGVWKKYslTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYII 314
Cdd:cd05039    1 WAINKKDLKLGELIGKGEFGDVMLGDYRGQ--KVAVKCLKDDSTAAQAFLAEASVMTTLRHPNLVQLLGVVLEGNGLYIV 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  315 TEFMTYGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRlmtgDTYT 394
Cdd:cd05039   79 TEYMAKGSLVDYLRSRGRAVITRKDQLGFALDVCEGMEYLESKKFVHRDLAARNVLVSEDNVAKVSDFGLAK----EASS 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  395 AHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRA 474
Cdd:cd05039  155 NQDGGKLPIKWTAPEALREKKFSTKSDVWSFGILLWEIYSFGRVPYPRIPLKDVVPHVEKGYRMEAPEGCPPEVYKVMKN 234
                        250       260
                 ....*....|....*....|.
gi 62362414  475 CWQWNPSDRPSFAEIHQAFET 495
Cdd:cd05039  235 CWELDPAKRPTFKQLREKLEH 255
PTKc_Tec_like cd05059
Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
241-489 8.67e-105

Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Tec-like subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases form the second largest subfamily of nonreceptor PTKs and are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. Tec kinases play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. Mutations in Btk cause the severe B-cell immunodeficiency, X-linked agammaglobulinaemia (XLA). The Tec-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173637 [Multi-domain]  Cd Length: 256  Bit Score: 329.41  E-value: 8.67e-105
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  241 DITMKHKLGGGQYGEVYEGVWKKySLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTY 320
Cdd:cd05059    5 ELTFLKELGSGQFGVVHLGKWRG-KIDVAIKMIKEGSMSEDDFIEEAKVMMKLSHPKLVQLYGVCTKQRPIFIVTEYMAN 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  321 GNLLDYLREcNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAK 400
Cdd:cd05059   84 GCLLNYLRE-RRGKFQTEQLLEMCKDVCEAMEYLESNGFIHRDLAARNCLVGEQNVVKVSDFGLARYVLDDEYTSSVGTK 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  401 FPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQWNP 480
Cdd:cd05059  163 FPVKWSPPEVFMYSKFSSKSDVWSFGVLMWEVFSEGKMPYERFSNSEVVEHISQGYRLYRPHLAPTEVYTIMYSCWHEKP 242

                 ....*....
gi 62362414  481 SDRPSFAEI 489
Cdd:cd05059  243 EERPTFKIL 251
PTKc_Lck_Blk cd05067
Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs ...
234-497 1.27e-98

Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Lck and Blk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lck is expressed in T-cells and natural killer cells. It plays a critical role in T-cell maturation, activation, and T-cell receptor (TCR) signaling. Lck phosphorylates ITAM (immunoreceptor tyr activation motif) sequences on several subunits of TCRs, leading to the activation of different second messenger cascades. Phosphorylated ITAMs serve as binding sites for other signaling factor such as Syk and ZAP-70, leading to their activation and propagation of downstream events. In addition, Lck regulates drug-induced apoptosis by interfering with the mitochondrial death pathway. The apototic role of Lck is independent of its primary function in T-cell signaling. Blk is expressed specifically in B-cells. It is involved in pre-BCR (B-cell receptor) signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Lck/Blk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270652 [Multi-domain]  Cd Length: 264  Bit Score: 313.36  E-value: 1.27e-98
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  234 KWEMERTDITMKHKLGGGQYGEVYEGVWKKYSlTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPpFYI 313
Cdd:cd05067    1 EWEVPRETLKLVERLGAGQFGEVWMGYYNGHT-KVAIKSLKQGSMSPDAFLAEANLMKQLQHQRLVRLYAVVTQEP-IYI 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  314 ITEFMTYGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTY 393
Cdd:cd05067   79 ITEYMENGSLVDFLKTPSGIKLTINKLLDMAAQIAEGMAFIEERNYIHRDLRAANILVSDTLSCKIADFGLARLIEDNEY 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  394 TAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMR 473
Cdd:cd05067  159 TAREGAKFPIKWTAPEAINYGTFTIKSDVWSFGILLTEIVTHGRIPYPGMTNPEVIQNLERGYRMPRPDNCPEELYQLMR 238
                        250       260
                 ....*....|....*....|....
gi 62362414  474 ACWQWNPSDRPSFAEIHQAFETMF 497
Cdd:cd05067  239 LCWKERPEDRPTFEYLRSVLEDFF 262
PTKc_Fes_like cd05041
Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; ...
247-491 3.76e-98

Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; Fes subfamily; catalytic (c) domain. Fes subfamily members include Fes (or Fps), Fer, and similar proteins. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fes subfamily proteins are cytoplasmic (or nonreceptor) tyr kinases containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. The genes for Fes (feline sarcoma) and Fps (Fujinami poultry sarcoma) were first isolated from tumor-causing retroviruses. The viral oncogenes encode chimeric Fes proteins consisting of Gag sequences at the N-termini, resulting in unregulated tyr kinase activity. Fes and Fer kinases play roles in haematopoiesis, inflammation and immunity, growth factor signaling, cytoskeletal regulation, cell migration and adhesion, and the regulation of cell-cell interactions. Fes and Fer show redundancy in their biological functions.


Pssm-ID: 270637 [Multi-domain]  Cd Length: 251  Bit Score: 311.69  E-value: 3.76e-98
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEV--EEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLL 324
Cdd:cd05041    2 KIGRGNFGDVYRGVLKPDNTEVAVKTCRETLPPDlkRKFLQEARILKQYDHPNIVKLIGVCVQKQPIMIVMELVPGGSLL 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  325 DYLREcNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAK-FPI 403
Cdd:cd05041   82 TFLRK-KGARLTVKQLLQMCLDAAAGMEYLESKNCIHRDLAARNCLVGENNVLKISDFGMSREEEDGEYTVSDGLKqIPI 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  404 KWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQWNPSDR 483
Cdd:cd05041  161 KWTAPEALNYGRYTSESDVWSFGILLWEIFSLGATPYPGMSNQQTREQIESGYRMPAPELCPEAVYRLMLQCWAYDPENR 240

                 ....*...
gi 62362414  484 PSFAEIHQ 491
Cdd:cd05041  241 PSFSEIYN 248
PTKc_Srm_Brk cd05148
Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal ...
235-491 4.62e-97

Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristylation sites (Srm) and Breast tumor kinase (Brk); PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Srm and Brk (also called protein tyrosine kinase 6) are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Brk has been found to be overexpressed in a majority of breast tumors. Src kinases in general contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr; they are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Srm and Brk however, lack the N-terminal myristylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. The Srm/Brk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133248 [Multi-domain]  Cd Length: 261  Bit Score: 308.98  E-value: 4.62e-97
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  235 WEMERTDITMKHKLGGGQYGEVYEGVWKKySLTVAVKTLK-EDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYI 313
Cdd:cd05148    1 WERPREEFTLERKLGSGYFGEVWEGLWKN-RVRVAIKILKsDDLLKQQDFQKEVQALKRLRHKHLISLFAVCSVGEPVYI 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  314 ITEFMTYGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTY 393
Cdd:cd05148   80 ITELMEKGSLLAFLRSPEGQVLPVASLIDMACQVAEGMAYLEEQNSIHRDLAARNILVGEDLVCKVADFGLARLIKEDVY 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  394 TAHAgAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMR 473
Cdd:cd05148  160 LSSD-KKIPYKWTAPEAASHGTFSTKSDVWSFGILLYEMFTYGQVPYPGMNNHEVYDQITAGYRMPCPAKCPQEIYKIML 238
                        250
                 ....*....|....*...
gi 62362414  474 ACWQWNPSDRPSFAEIHQ 491
Cdd:cd05148  239 ECWAAEPEDRPSFKALRE 256
PTKc_Lyn cd05072
Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the ...
235-499 6.24e-97

Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Lyn is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lyn is expressed in B lymphocytes and myeloid cells. It exhibits both positive and negative regulatory roles in B cell receptor (BCR) signaling. Lyn, as well as Fyn and Blk, promotes B cell activation by phosphorylating ITAMs (immunoreceptor tyr activation motifs) in CD19 and in Ig components of BCR. It negatively regulates signaling by its unique ability to phosphorylate ITIMs (immunoreceptor tyr inhibition motifs) in cell surface receptors like CD22 and CD5. Lyn also plays an important role in G-CSF receptor signaling by phosphorylating a variety of adaptor molecules. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Lyn subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270657 [Multi-domain]  Cd Length: 272  Bit Score: 309.28  E-value: 6.24e-97
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  235 WEMERTDITMKHKLGGGQYGEVYEGVWKKySLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYII 314
Cdd:cd05072    2 WEIPRESIKLVKKLGAGQFGEVWMGYYNN-STKVAVKTLKPGTMSVQAFLEEANLMKTLQHDKLVRLYAVVTKEEPIYII 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  315 TEFMTYGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYT 394
Cdd:cd05072   81 TEYMAKGSLLDFLKSDEGGKVLLPKLIDFSAQIAEGMAYIERKNYIHRDLRAANVLVSESLMCKIADFGLARVIEDNEYT 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  395 AHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRA 474
Cdd:cd05072  161 AREGAKFPIKWTAPEAINFGSFTIKSDVWSFGILLYEIVTYGKIPYPGMSNSDVMSALQRGYRMPRMENCPDELYDIMKT 240
                        250       260       270
                 ....*....|....*....|....*....|..
gi 62362414  475 CWQWNPSDRPSF-------AEIHQAFETMFQE 499
Cdd:cd05072  241 CWKEKAEERPTFdylqsvlDDFYTATEGQYQQ 272
PTKc_Syk_like cd05060
Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
246-493 1.29e-93

Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Syk-like subfamily is composed of Syk, ZAP-70, Shark, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. They are involved in the signaling downstream of activated receptors (including B-cell, T-cell, and Fc receptors) that contain ITAMs (immunoreceptor tyr activation motifs), leading to processes such as cell proliferation, differentiation, survival, adhesion, migration, and phagocytosis. Syk is important in B-cell receptor signaling, while Zap-70 is primarily expressed in T-cells and NK cells, and is a crucial component in T-cell receptor signaling. Syk also plays a central role in Fc receptor-mediated phagocytosis in the adaptive immune system. Shark is exclusively expressed in ectodermally derived epithelia, and is localized preferentially to the apical surface of the epithelial cells, it may play a role in a signaling pathway for epithelial cell polarity. The Syk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270650 [Multi-domain]  Cd Length: 257  Bit Score: 299.65  E-value: 1.29e-93
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  246 HKLGGGQYGEVYEGVWKKYS---LTVAVKTLKEDTMEV--EEFLKEAAVMKEIKHPNLVQLLGVCtREPPFYIITEFMTY 320
Cdd:cd05060    1 KELGHGNFGSVRKGVYLMKSgkeVEVAVKTLKQEHEKAgkKEFLREASVMAQLDHPCIVRLIGVC-KGEPLMLVMELAPL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  321 GNLLDYLRecNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLM-TGDT-YTAHAG 398
Cdd:cd05060   80 GPLLKYLK--KRREIPVSDLKELAHQVAMGMAYLESKHFVHRDLAARNVLLVNRHQAKISDFGMSRALgAGSDyYRATTA 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  399 AKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQW 478
Cdd:cd05060  158 GRWPLKWYAPECINYGKFSSKSDVWSYGVTLWEAFSYGAKPYGEMKGPEVIAMLESGERLPRPEECPQEIYSIMLSCWKY 237
                        250
                 ....*....|....*
gi 62362414  479 NPSDRPSFAEIHQAF 493
Cdd:cd05060  238 RPEDRPTFSELESTF 252
PTKc_Src_Fyn_like cd14203
Catalytic domain of a subset of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
247-493 1.56e-93

Catalytic domain of a subset of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily includes a subset of Src-like PTKs including Src, Fyn, Yrk, and Yes, which are all widely expressed. Yrk has been detected only in chickens. It is primarily found in neuronal and epithelial cells and in macrophages. It may play a role in inflammation and in response to injury. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. They are also implicated in acute inflammatory responses and osteoclast function. The Src/Fyn-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271105 [Multi-domain]  Cd Length: 248  Bit Score: 299.14  E-value: 1.56e-93
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKySLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPpFYIITEFMTYGNLLDY 326
Cdd:cd14203    2 KLGQGCFGEVWMGTWNG-TTKVAIKTLKPGTMSPEAFLEEAQIMKKLRHDKLVQLYAVVSEEP-IYIVTEFMSKGSLLDF 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  327 LRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPIKWT 406
Cdd:cd14203   80 LKDGEGKYLKLPQLVDMAAQIASGMAYIERMNYIHRDLRAANILVGDNLVCKIADFGLARLIEDNEYTARQGAKFPIKWT 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  407 APESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQWNPSDRPSF 486
Cdd:cd14203  160 APEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMNNREVLEQVERGYRMPCPPGCPESLHELMCQCWRKDPEERPTF 239

                 ....*..
gi 62362414  487 aEIHQAF 493
Cdd:cd14203  240 -EYLQSF 245
PTKc_InsR_like cd05032
Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer ...
235-489 1.22e-91

Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The InsR subfamily is composed of InsR, Insulin-like Growth Factor-1 Receptor (IGF-1R), and similar proteins. InsR and IGF-1R are receptor PTKs (RTKs) composed of two alphabeta heterodimers. Binding of the ligand (insulin, IGF-1, or IGF-2) to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, stimulating downstream kinase activities, which initiate signaling cascades and biological function. InsR and IGF-1R, which share 84% sequence identity in their kinase domains, display physiologically distinct yet overlapping functions in cell growth, differentiation, and metabolism. InsR activation leads primarily to metabolic effects while IGF-1R activation stimulates mitogenic pathways. In cells expressing both receptors, InsR/IGF-1R hybrids are found together with classical receptors. Both receptors can interact with common adaptor molecules such as IRS-1 and IRS-2. The InsR-like subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173625 [Multi-domain]  Cd Length: 277  Bit Score: 295.02  E-value: 1.22e-91
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  235 WEMERTDITMKHKLGGGQYGEVYEGVWKKYS-----LTVAVKTLKED-TM-EVEEFLKEAAVMKEIKHPNLVQLLGVCTR 307
Cdd:cd05032    1 WELPREKITLIRELGQGSFGMVYEGLAKGVVkgepeTRVAIKTVNENaSMrERIEFLNEASVMKEFNCHHVVRLLGVVST 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  308 EPPFYIITEFMTYGNLLDYLRECNRQEVNAVVL--------LYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKV 379
Cdd:cd05032   81 GQPTLVVMELMAKGDLKSYLRSRRPEAENNPGLgpptlqkfIQMAAEIADGMAYLAAKKFVHRDLAARNCMVAEDLTVKI 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  380 ADFGLSRLM-TGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRM 458
Cdd:cd05032  161 GDFGMTRDIyETDYYRKGGKGLLPVRWMAPESLKDGVFTTKSDVWSFGVVLWEMATLAEQPYQGLSNEEVLKFVIDGGHL 240
                        250       260       270
                 ....*....|....*....|....*....|.
gi 62362414  459 ERPEGCPEKVYELMRACWQWNPSDRPSFAEI 489
Cdd:cd05032  241 DLPENCPDKLLELMRMCWQYNPKMRPTFLEI 271
PTKc_FGFR cd05053
Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs ...
234-496 1.85e-90

Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The FGFR subfamily consists of FGFR1, FGFR2, FGFR3, FGFR4, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, and to heparin/heparan sulfate (HS) results in the formation of a ternary complex, which leads to receptor dimerization and activation, and intracellular signaling. There are at least 23 FGFs and four types of FGFRs. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. FGF/FGFR signaling is important in the regulation of embryonic development, homeostasis, and regenerative processes. Depending on the cell type and stage, FGFR signaling produces diverse cellular responses including proliferation, growth arrest, differentiation, and apoptosis. Aberrant signaling leads to many human diseases such as skeletal, olfactory, and metabolic disorders, as well as cancer. The FGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase .


Pssm-ID: 270646 [Multi-domain]  Cd Length: 294  Bit Score: 292.40  E-value: 1.85e-90
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  234 KWEMERTDITMKHKLGGGQYGEVYEGVWK------KYSLTVAVKTLKEDTMEVE--EFLKEAAVMKEI-KHPNLVQLLGV 304
Cdd:cd05053    6 EWELPRDRLTLGKPLGEGAFGQVVKAEAVgldnkpNEVVTVAVKMLKDDATEKDlsDLVSEMEMMKMIgKHKNIINLLGA 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  305 CTREPPFYIITEFMTYGNLLDYLR-------ECN-------RQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCL 370
Cdd:cd05053   86 CTQDGPLYVVVEYASKGNLREFLRarrppgeEASpddprvpEEQLTQKDLVSFAYQVARGMEYLASKKCIHRDLAARNVL 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  371 VGENHLVKVADFGLSR-LMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVY 449
Cdd:cd05053  166 VTEDNVMKIADFGLARdIHHIDYYRKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIPVEELF 245
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*..
gi 62362414  450 ELLEKDYRMERPEGCPEKVYELMRACWQWNPSDRPSFAEIHQAFETM 496
Cdd:cd05053  246 KLLKEGHRMEKPQNCTQELYMLMRDCWHEVPSQRPTFKQLVEDLDRI 292
PTKc_FAK cd05056
Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the ...
235-501 4.24e-88

Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. FAK is a cytoplasmic (or nonreceptor) PTK that contains an autophosphorylation site and a FERM domain at the N-terminus, a central tyr kinase domain, proline-rich regions, and a C-terminal FAT (focal adhesion targeting) domain. FAK activity is dependent on integrin-mediated cell adhesion, which facilitates N-terminal autophosphorylation. Full activation is achieved by the phosphorylation of its two adjacent A-loop tyrosines. FAK is important in mediating signaling initiated at sites of cell adhesions and at growth factor receptors. Through diverse molecular interactions, FAK functions as a biosensor or integrator to control cell motility. It is a key regulator of cell survival, proliferation, migration and invasion, and thus plays an important role in the development and progression of cancer. Src binds to autophosphorylated FAK forming the FAK-Src dual kinase complex, which is activated in a wide variety of tumor cells and generates signals promoting growth and metastasis. FAK is being developed as a target for cancer therapy. The FAK subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133187 [Multi-domain]  Cd Length: 270  Bit Score: 285.08  E-value: 4.24e-88
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  235 WEMERTDITMKHKLGGGQYGEVYEGVWKKY---SLTVAVKTLKEDTME--VEEFLKEAAVMKEIKHPNLVQLLGVCTrEP 309
Cdd:cd05056    1 YEIQREDITLGRCIGEGQFGDVYQGVYMSPeneKIAVAVKTCKNCTSPsvREKFLQEAYIMRQFDHPHIVKLIGVIT-EN 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  310 PFYIITEFMTYGNLLDYLrECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMT 389
Cdd:cd05056   80 PVWIVMELAPLGELRSYL-QVNKYSLDLASLILYAYQLSTALAYLESKRFVHRDIAARNVLVSSPDCVKLGDFGLSRYME 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  390 GDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVY 469
Cdd:cd05056  159 DESYYKASKGKLPIKWMAPESINFRRFTSASDVWMFGVCMWEILMLGVKPFQGVKNNDVIGRIENGERLPMPPNCPPTLY 238
                        250       260       270
                 ....*....|....*....|....*....|..
gi 62362414  470 ELMRACWQWNPSDRPSFAEIHQAFETMFQESS 501
Cdd:cd05056  239 SLMTKCWAYDPSKRPRFTELKAQLSDILQEEK 270
PTKc_Hck cd05073
Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the ...
233-494 4.81e-88

Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Hck is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Hck is present in myeloid and lymphoid cells that play a role in the development of cancer. It may be important in the oncogenic signaling of the protein Tel-Abl, which induces a chronic myelogenous leukemia (CML)-like disease. Hck also acts as a negative regulator of G-CSF-induced proliferation of granulocytic precursors, suggesting a possible role in the development of acute myeloid leukemia (AML). In addition, Hck is essential in regulating the degranulation of polymorphonuclear leukocytes. Genetic polymorphisms affect the expression level of Hck, which affects PMN mediator release and influences the development of chronic obstructive pulmonary disease (COPD). Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Hck subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270658 [Multi-domain]  Cd Length: 265  Bit Score: 284.61  E-value: 4.81e-88
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  233 DKWEMERTDITMKHKLGGGQYGEVYEGVWKKYSlTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPpFY 312
Cdd:cd05073    4 DAWEIPRESLKLEKKLGAGQFGEVWMATYNKHT-KVAVKTMKPGSMSVEAFLAEANVMKTLQHDKLVKLHAVVTKEP-IY 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  313 IITEFMTYGNLLDYLR--ECNRQEVNAvvLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTG 390
Cdd:cd05073   82 IITEFMAKGSLLDFLKsdEGSKQPLPK--LIDFSAQIAEGMAFIEQRNYIHRDLRAANILVSASLVCKIADFGLARVIED 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  391 DTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYE 470
Cdd:cd05073  160 NEYTAREGAKFPIKWTAPEAINFGSFTIKSDVWSFGILLMEIVTYGRIPYPGMSNPEVIRALERGYRMPRPENCPEELYN 239
                        250       260
                 ....*....|....*....|....
gi 62362414  471 LMRACWQWNPSDRPSFAEIHQAFE 494
Cdd:cd05073  240 IMMRCWKNRPEERPTFEYIQSVLD 263
PTKc_Itk cd05112
Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs ...
240-487 8.12e-88

Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Itk, also known as Tsk or Emt, is a member of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Itk contains the Tec homology (TH) domain containing one proline-rich region and a zinc-binding region. Itk is expressed in T-cells and mast cells, and is important in their development and differentiation. Of the three Tec kinases expressed in T-cells, Itk plays the predominant role in T-cell receptor (TCR) signaling. It is activated by phosphorylation upon TCR crosslinking and is involved in the pathway resulting in phospholipase C-gamma1 activation and actin polymerization. It also plays a role in the downstream signaling of the T-cell costimulatory receptor CD28, the T-cell surface receptor CD2, and the chemokine receptor CXCR4. In addition, Itk is crucial for the development of T-helper(Th)2 effector responses. The Itk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133243 [Multi-domain]  Cd Length: 256  Bit Score: 283.76  E-value: 8.12e-88
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  240 TDITMKHKLGGGQYGEVYEGVWKKYSlTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMT 319
Cdd:cd05112    4 SELTFVQEIGSGQFGLVHLGYWLNKD-KVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFME 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  320 YGNLLDYLREcNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGA 399
Cdd:cd05112   83 HGCLSDYLRT-QRGLFSAETLLGMCLDVCEGMAYLEEASVIHRDLAARNCLVGENQVVKVSDFGMTRFVLDDQYTSSTGT 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  400 KFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQWN 479
Cdd:cd05112  162 KFPVKWSSPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDINAGFRLYKPRLASTHVYEIMNHCWKER 241

                 ....*...
gi 62362414  480 PSDRPSFA 487
Cdd:cd05112  242 PEDRPSFS 249
PTKc_DDR cd05051
Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze ...
236-491 9.71e-88

Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The DDR subfamily consists of homologs of mammalian DDR1, DDR2, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDRs results in a slow but sustained receptor activation. DDRs regulate cell adhesion, proliferation, and extracellular matrix remodeling. They have been linked to a variety of human cancers including breast, colon, ovarian, brain, and lung. There is no evidence showing that DDRs act as transforming oncogenes. They are more likely to play a role in the regulation of tumor growth and metastasis. The DDR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270644 [Multi-domain]  Cd Length: 297  Bit Score: 285.00  E-value: 9.71e-88
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  236 EMERTDITMKHKLGGGQYGEV---------------YEGVWKKYSLT-VAVKTLKEDTME--VEEFLKEAAVMKEIKHPN 297
Cdd:cd05051    1 EFPREKLEFVEKLGEGQFGEVhlceanglsdltsddFIGNDNKDEPVlVAVKMLRPDASKnaREDFLKEVKIMSQLKDPN 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  298 LVQLLGVCTREPPFYIITEFMTYGNLLDYLREC----------NRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAAR 367
Cdd:cd05051   81 IVRLLGVCTRDEPLCMIVEYMENGDLNQFLQKHeaetqgasatNSKTLSYGTLLYMATQIASGMKYLESLNFVHRDLATR 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  368 NCLVGENHLVKVADFGLSR-LMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYG-MSPYPGIDL 445
Cdd:cd05051  161 NCLVGPNYTIKIADFGMSRnLYSGDYYRIEGRAVLPIRWMAWESILLGKFTTKSDVWAFGVTLWEILTLCkEQPYEHLTD 240
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|...
gi 62362414  446 SQVYE---LLEKDYRME----RPEGCPEKVYELMRACWQWNPSDRPSFAEIHQ 491
Cdd:cd05051  241 EQVIEnagEFFRDDGMEvylsRPPNCPKEIYELMLECWRRDEEDRPTFREIHL 293
PTKc_Btk_Bmx cd05113
Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow ...
237-489 3.54e-87

Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow kinase on the X chromosome; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Btk and Bmx (also named Etk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Btk contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Btk is expressed in B-cells, and a variety of myeloid cells including mast cells, platelets, neutrophils, and dendrictic cells. It interacts with a variety of partners, from cytosolic proteins to nuclear transcription factors, suggesting a diversity of functions. Stimulation of a diverse array of cell surface receptors, including antigen engagement of the B-cell receptor, leads to PH-mediated membrane translocation of Btk and subsequent phosphorylation by Src kinase and activation. Btk plays an important role in the life cycle of B-cells including their development, differentiation, proliferation, survival, and apoptosis. Mutations in Btk cause the primary immunodeficiency disease, X-linked agammaglobulinaemia (XLA) in humans. Bmx is primarily expressed in bone marrow and the arterial endothelium, and plays an important role in ischemia-induced angiogenesis. It facilitates arterial growth, capillary formation, vessel maturation, and bone marrow-derived endothelial progenitor cell mobilization. The Btk/Bmx subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173657 [Multi-domain]  Cd Length: 256  Bit Score: 282.15  E-value: 3.54e-87
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  237 MERTDITMKHKLGGGQYGEVYEGVWK-KYSltVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIIT 315
Cdd:cd05113    1 IDPKDLTFLKELGTGQFGVVKYGKWRgQYD--VAIKMIKEGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIIT 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  316 EFMTYGNLLDYLREcNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTA 395
Cdd:cd05113   79 EYMANGCLLNYLRE-MRKRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVLDDEYTS 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  396 HAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRAC 475
Cdd:cd05113  158 SVGSKFPVRWSPPEVLMYSKFSSKSDVWAFGVLMWEVYSLGKMPYERFTNSETVEHVSQGLRLYRPHLASEKVYTIMYSC 237
                        250
                 ....*....|....
gi 62362414  476 WQWNPSDRPSFAEI 489
Cdd:cd05113  238 WHEKADERPTFKIL 251
PTKc_EphR cd05033
Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
240-496 5.69e-86

Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EphRs comprise the largest subfamily of receptor PTKs (RTKs). They can be classified into two classes (EphA and EphB), according to their extracellular sequences, which largely correspond to binding preferences for either GPI-anchored ephrin-A ligands or transmembrane ephrin-B ligands. Vertebrates have ten EphA and six EphB receptors, which display promiscuous ligand interactions within each class. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. This allows ephrin/EphR dimers to form, leading to the activation of the intracellular tyr kinase domain. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). The main effect of ephrin/EphR interaction is cell-cell repulsion or adhesion. Ephrin/EphR signaling is important in neural development and plasticity, cell morphogenesis and proliferation, cell-fate determination, embryonic development, tissue patterning, and angiogenesis.The EphR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270629 [Multi-domain]  Cd Length: 266  Bit Score: 279.26  E-value: 5.69e-86
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  240 TDITMKHKLGGGQYGEVYEGVWK---KYSLTVAVKTLKEDTMEVE--EFLKEAAVMKEIKHPNLVQLLGVCTREPPFYII 314
Cdd:cd05033    4 SYVTIEKVIGGGEFGEVCSGSLKlpgKKEIDVAIKTLKSGYSDKQrlDFLTEASIMGQFDHPNVIRLEGVVTKSRPVMIV 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  315 TEFMTYGNLLDYLREcNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLM--TGDT 392
Cdd:cd05033   84 TEYMENGSLDKFLRE-NDGKFTVTQLVGMLRGIASGMKYLSEMNYVHRDLAARNILVNSDLVCKVSDFGLSRRLedSEAT 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  393 YTAhAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELM 472
Cdd:cd05033  163 YTT-KGGKIPIRWTAPEAIAYRKFTSASDVWSFGIVMWEVMSYGERPYWDMSNQDVIKAVEDGYRLPPPMDCPSALYQLM 241
                        250       260
                 ....*....|....*....|....
gi 62362414  473 RACWQWNPSDRPSFAEIHQAFETM 496
Cdd:cd05033  242 LDCWQKDRNERPTFSQIVSTLDKM 265
PTKc_Fer cd05085
Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; ...
248-491 1.54e-85

Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; Fer kinase; catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fer kinase is a member of the Fes subfamily of proteins which are cytoplasmic (or nonreceptor) tyr kinases containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. Fer kinase is expressed in a wide variety of tissues, and is found to reside in both the cytoplasm and the nucleus. It plays important roles in neuronal polarization and neurite development, cytoskeletal reorganization, cell migration, growth factor signaling, and the regulation of cell-cell interactions mediated by adherens junctions and focal adhesions. Fer kinase also regulates cell cycle progression in malignant cells.


Pssm-ID: 270668 [Multi-domain]  Cd Length: 251  Bit Score: 277.27  E-value: 1.54e-85
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSlTVAVKTLKED-TMEVE-EFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLD 325
Cdd:cd05085    4 LGKGNFGEVYKGTLKDKT-PVAVKTCKEDlPQELKiKFLSEARILKQYDHPNIVKLIGVCTQRQPIYIVMELVPGGDFLS 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  326 YLREcNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPIKW 405
Cdd:cd05085   83 FLRK-KKDELKTKQLVKFSLDAAAGMAYLESKNCIHRDLAARNCLVGENNALKISDFGMSRQEDDGVYSSSGLKQIPIKW 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  406 TAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQWNPSDRPS 485
Cdd:cd05085  162 TAPEALNYGRYSSESDVWSFGILLWETFSLGVCPYPGMTNQQAREQVEKGYRMSAPQRCPEDIYKIMQRCWDYNPENRPK 241

                 ....*.
gi 62362414  486 FAEIHQ 491
Cdd:cd05085  242 FSELQK 247
PTKc_Yes cd05069
Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the ...
233-497 1.75e-85

Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Yes (or c-Yes) is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. c-Yes kinase is the cellular homolog of the oncogenic protein (v-Yes) encoded by the Yamaguchi 73 and Esh sarcoma viruses. It displays functional overlap with other Src subfamily members, particularly Src. It also shows some unique functions such as binding to occludins, transmembrane proteins that regulate extracellular interactions in tight junctions. Yes also associates with a number of proteins in different cell types that Src does not interact with, like JAK2 and gp130 in pre-adipocytes, and Pyk2 in treated pulmonary vein endothelial cells. Although the biological function of Yes remains unclear, it appears to have a role in regulating cell-cell interactions and vesicle trafficking in polarized cells. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Yes subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270654 [Multi-domain]  Cd Length: 279  Bit Score: 278.49  E-value: 1.75e-85
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  233 DKWEMERTDITMKHKLGGGQYGEVYEGVWKKySLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPpFY 312
Cdd:cd05069    5 DAWEIPRESLRLDVKLGQGCFGEVWMGTWNG-TTKVAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEP-IY 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  313 IITEFMTYGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDT 392
Cdd:cd05069   83 IVTEFMGKGSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGDNLVCKIADFGLARLIEDNE 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  393 YTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELM 472
Cdd:cd05069  163 YTARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMVNREVLEQVERGYRMPCPQGCPESLHELM 242
                        250       260
                 ....*....|....*....|....*
gi 62362414  473 RACWQWNPSDRPSFAEIHQAFETMF 497
Cdd:cd05069  243 KLCWKKDPDERPTFEYIQSFLEDYF 267
PTKc_Tec_Rlk cd05114
Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular ...
240-489 8.52e-85

Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular carcinoma and Resting lymphocyte kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tec and Rlk (also named Txk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. Instead of PH, Rlk contains an N-terminal cysteine-rich region. In addition to PH, Tec also contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Tec kinases are expressed mainly by haematopoietic cells. Tec is more widely-expressed than other Tec-like subfamily kinases. It is found in endothelial cells, both B- and T-cells, and a variety of myeloid cells including mast cells, erythroid cells, platelets, macrophages and neutrophils. Rlk is expressed in T-cells and mast cell lines. Tec and Rlk are both key components of T-cell receptor (TCR) signaling. They are important in TCR-stimulated proliferation, IL-2 production and phopholipase C-gamma1 activation. The Tec/Rlk subfamily is part of a larger superfamily, that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270685 [Multi-domain]  Cd Length: 260  Bit Score: 275.59  E-value: 8.52e-85
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  240 TDITMKHKLGGGQYGEVYEGVWKKySLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMT 319
Cdd:cd05114    4 SELTFMKELGSGLFGVVRLGKWRA-QYKVAIKAIREGAMSEEDFIEEAKVMMKLTHPKLVQLYGVCTQQKPIYIVTEFME 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  320 YGNLLDYLREcNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGA 399
Cdd:cd05114   83 NGCLLNYLRQ-RRGKLSRDMLLSMCQDVCEGMEYLERNNFIHRDLAARNCLVNDTGVVKVSDFGMTRYVLDDQYTSSSGA 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  400 KFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQWN 479
Cdd:cd05114  162 KFPVKWSPPEVFNYSKFSSKSDVWSFGVLMWEVFTEGKMPFESKSNYEVVEMVSRGHRLYRPKLASKSVYEVMYSCWHEK 241
                        250
                 ....*....|
gi 62362414  480 PSDRPSFAEI 489
Cdd:cd05114  242 PEGRPTFADL 251
PTKc_Csk cd05082
Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the ...
235-494 5.87e-84

Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Csk catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. Csk is expressed in a wide variety of tissues. As a negative regulator of Src, Csk plays a role in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. Csk is a cytoplasmic (or nonreceptor) PTK containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. To inhibit Src kinases, Csk is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. In addition, Csk also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. The Csk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133213 [Multi-domain]  Cd Length: 256  Bit Score: 273.40  E-value: 5.87e-84
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  235 WEMERTDITMKHKLGGGQYGEVYEGVWKkySLTVAVKTLKEDTMeVEEFLKEAAVMKEIKHPNLVQLLGVCTREP-PFYI 313
Cdd:cd05082    1 WALNMKELKLLQTIGKGEFGDVMLGDYR--GNKVAVKCIKNDAT-AQAFLAEASVMTQLRHSNLVQLLGVIVEEKgGLYI 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  314 ITEFMTYGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLM--TGD 391
Cdd:cd05082   78 VTEYMAKGSLVDYLRSRGRSVLGGDCLLKFSLDVCEAMEYLEGNNFVHRDLAARNVLVSEDNVAKVSDFGLTKEAssTQD 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  392 TytahagAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYEL 471
Cdd:cd05082  158 T------GKLPVKWTAPEALREKKFSTKSDVWSFGILLWEIYSFGRVPYPRIPLKDVVPRVEKGYKMDAPDGCPPAVYDV 231
                        250       260
                 ....*....|....*....|...
gi 62362414  472 MRACWQWNPSDRPSFAEIHQAFE 494
Cdd:cd05082  232 MKNCWHLDAAMRPSFLQLREQLE 254
PTKc_Fyn cd05070
Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the ...
233-497 1.93e-82

Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fyn and Yrk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Fyn, together with Lck, plays a critical role in T-cell signal transduction by phosphorylating ITAM (immunoreceptor tyr activation motif) sequences on T-cell receptors, ultimately leading to the proliferation and differentiation of T-cells. In addition, Fyn is involved in the myelination of neurons, and is implicated in Alzheimer's and Parkinson's diseases. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Fyn/Yrk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase.


Pssm-ID: 270655 [Multi-domain]  Cd Length: 274  Bit Score: 270.02  E-value: 1.93e-82
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  233 DKWEMERTDITMKHKLGGGQYGEVYEGVWKKySLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPpFY 312
Cdd:cd05070    2 DVWEIPRESLQLIKRLGNGQFGEVWMGTWNG-NTKVAIKTLKPGTMSPESFLEEAQIMKKLKHDKLVQLYAVVSEEP-IY 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  313 IITEFMTYGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDT 392
Cdd:cd05070   80 IVTEYMSKGSLLDFLKDGEGRALKLPNLVDMAAQVAAGMAYIERMNYIHRDLRSANILVGNGLICKIADFGLARLIEDNE 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  393 YTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELM 472
Cdd:cd05070  160 YTARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMNNREVLEQVERGYRMPCPQDCPISLHELM 239
                        250       260
                 ....*....|....*....|....*
gi 62362414  473 RACWQWNPSDRPSFAEIHQAFETMF 497
Cdd:cd05070  240 IHCWKKDPEERPTFEYLQGFLEDYF 264
PTKc_Src cd05071
Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the ...
233-500 6.55e-81

Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Src (or c-Src) is a cytoplasmic (or non-receptor) PTK, containing an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region with a conserved tyr. It is activated by autophosphorylation at the tyr kinase domain, and is negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). c-Src is the vertebrate homolog of the oncogenic protein (v-Src) from Rous sarcoma virus. Together with other Src subfamily proteins, it is involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. Src also play a role in regulating cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. Elevated levels of Src kinase activity have been reported in a variety of human cancers. Several inhibitors of Src have been developed as anti-cancer drugs. Src is also implicated in acute inflammatory responses and osteoclast function. The Src subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270656 [Multi-domain]  Cd Length: 277  Bit Score: 265.78  E-value: 6.55e-81
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  233 DKWEMERTDITMKHKLGGGQYGEVYEGVWKKySLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPpFY 312
Cdd:cd05071    2 DAWEIPRESLRLEVKLGQGCFGEVWMGTWNG-TTRVAIKTLKPGTMSPEAFLQEAQVMKKLRHEKLVQLYAVVSEEP-IY 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  313 IITEFMTYGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDT 392
Cdd:cd05071   80 IVTEYMSKGSLLDFLKGEMGKYLRLPQLVDMAAQIASGMAYVERMNYVHRDLRAANILVGENLVCKVADFGLARLIEDNE 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  393 YTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELM 472
Cdd:cd05071  160 YTARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELTTKGRVPYPGMVNREVLDQVERGYRMPCPPECPESLHDLM 239
                        250       260
                 ....*....|....*....|....*...
gi 62362414  473 RACWQWNPSDRPSFAEIHQAFETMFQES 500
Cdd:cd05071  240 CQCWRKEPEERPTFEYLQAFLEDYFTST 267
STKc_MAP3K-like cd13999
Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine ...
248-491 1.47e-80

Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed mainly of MAP3Ks and similar proteins, including TGF-beta Activated Kinase-1 (TAK1, also called MAP3K7), MAP3K12, MAP3K13, Mixed lineage kinase (MLK), MLK-Like mitogen-activated protein Triple Kinase (MLTK), and Raf (Rapidly Accelerated Fibrosarcoma) kinases. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Also included in this subfamily is the pseudokinase Kinase Suppressor of Ras (KSR), which is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway.


Pssm-ID: 270901 [Multi-domain]  Cd Length: 245  Bit Score: 263.24  E-value: 1.47e-80
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYslTVAVKTLKEDTME---VEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLL 324
Cdd:cd13999    1 IGSGSFGEVYKGKWRGT--DVAIKKLKVEDDNdelLKEFRREVSILSKLRHPNIVQFIGACLSPPPLCIVTEYMPGGSLY 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  325 DYLREcNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRL-------MTGDTYTAHa 397
Cdd:cd13999   79 DLLHK-KKIPLSWSLRLKIALDIARGMNYLHSPPIIHRDLKSLNILLDENFTVKIADFGLSRIknsttekMTGVVGTPR- 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  398 gakfpikWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQV-YELLEKDYRMERPEGCPEKVYELMRACW 476
Cdd:cd13999  157 -------WMAPEVLRGEPYTEKADVYSFGIVLWELLT-GEVPFKELSPIQIaAAVVQKGLRPPIPPDCPPELSKLIKRCW 228
                        250
                 ....*....|....*
gi 62362414  477 QWNPSDRPSFAEIHQ 491
Cdd:cd13999  229 NEDPEKRPSFSEIVK 243
PTKc_EGFR_like cd05057
Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs ...
248-496 1.88e-80

Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EGFR (HER, ErbB) subfamily members include EGFR (HER1, ErbB1), HER2 (ErbB2), HER3 (ErbB3), HER4 (ErbB4), and similar proteins. They are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, resulting in the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Collectively, they can recognize a variety of ligands including EGF, TGFalpha, and neuregulins, among others. All four subfamily members can form homo- or heterodimers. HER3 contains an impaired kinase domain and depends on its heterodimerization partner for activation. EGFR subfamily members are involved in signaling pathways leading to a broad range of cellular responses including cell proliferation, differentiation, migration, growth inhibition, and apoptosis. Gain of function alterations, through their overexpression, deletions, or point mutations in their kinase domains, have been implicated in various cancers. These receptors are targets of many small molecule inhibitors and monoclonal antibodies used in cancer therapy. The EGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270648 [Multi-domain]  Cd Length: 279  Bit Score: 264.66  E-value: 1.88e-80
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWK----KYSLTVAVKTLKEDTMEV--EEFLKEAAVMKEIKHPNLVQLLGVCTREPpFYIITEFMTYG 321
Cdd:cd05057   15 LGSGAFGTVYKGVWIpegeKVKIPVAIKVLREETGPKanEEILDEAYVMASVDHPHLVRLLGICLSSQ-VQLITQLMPLG 93
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  322 NLLDYLREcNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHA-GAK 400
Cdd:cd05057   94 CLLDYVRN-HRDNIGSQLLLNWCVQIAKGMSYLEEKRLVHRDLAARNVLVKTPNHVKITDFGLAKLLDVDEKEYHAeGGK 172
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  401 FPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQWNP 480
Cdd:cd05057  173 VPIKWMALESIQYRIYTHKSDVWSYGVTVWELMTFGAKPYEGIPAVEIPDLLEKGERLPQPPICTIDVYMVLVKCWMIDA 252
                        250
                 ....*....|....*.
gi 62362414  481 SDRPSFAEIHQAFETM 496
Cdd:cd05057  253 ESRPTFKELANEFSKM 268
PTKc_Ack_like cd05040
Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs ...
247-489 2.22e-80

Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily includes Ack1, thirty-eight-negative kinase 1 (Tnk1), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing an N-terminal catalytic domain, an SH3 domain, a Cdc42-binding CRIB domain, and a proline-rich region. They are mainly expressed in brain and skeletal tissues and are involved in the regulation of cell adhesion and growth, receptor degradation, and axonal guidance. Ack1 is also associated with androgen-independent prostate cancer progression. Tnk1 regulates TNFalpha signaling and may play an important role in cell death. The Ack-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270636 [Multi-domain]  Cd Length: 258  Bit Score: 263.43  E-value: 2.22e-80
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYS---LTVAVKTLKEDTME----VEEFLKEAAVMKEIKHPNLVQLLGVcTREPPFYIITEFMT 319
Cdd:cd05040    2 KLGDGSFGVVRRGEWTTPSgkvIQVAVKCLKSDVLSqpnaMDDFLKEVNAMHSLDHPNLIRLYGV-VLSSPLMMVTELAP 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  320 YGNLLDYLREcNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLM--TGDTYTAHA 397
Cdd:cd05040   81 LGSLLDRLRK-DQGHFLISTLCDYAVQIANGMAYLESKRFIHRDLAARNILLASKDKVKIGDFGLMRALpqNEDHYVMQE 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  398 GAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDY-RMERPEGCPEKVYELMRACW 476
Cdd:cd05040  160 HRKVPFAWCAPESLKTRKFSHASDVWMFGVTLWEMFTYGEEPWLGLNGSQILEKIDKEGeRLERPDDCPQDIYNVMLQCW 239
                        250
                 ....*....|...
gi 62362414  477 QWNPSDRPSFAEI 489
Cdd:cd05040  240 AHKPADRPTFVAL 252
PTKc_TAM cd05035
Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer ...
248-494 1.13e-79

Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The TAM subfamily consists of Tyro3 (or Sky), Axl, Mer (or Mertk), and similar proteins. TAM subfamily members are receptor tyr kinases (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. TAM proteins are implicated in a variety of cellular effects including survival, proliferation, migration, and phagocytosis. They are also associated with several types of cancer as well as inflammatory, autoimmune, vascular, and kidney diseases. The TAM subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270631 [Multi-domain]  Cd Length: 273  Bit Score: 262.09  E-value: 1.13e-79
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKK---YSLTVAVKTLKEDTM---EVEEFLKEAAVMKEIKHPNLVQLLGVCTRE------PPFYIIT 315
Cdd:cd05035    7 LGEGEFGSVMEAQLKQddgSQLKVAVKTMKVDIHtysEIEEFLSEAACMKDFDHPNVMRLIGVCFTAsdlnkpPSPMVIL 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  316 EFMTYGNLLDYL----RECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR-LMTG 390
Cdd:cd05035   87 PFMKHGDLHSYLlysrLGGLPEKLPLQTLLKFMVDIAKGMEYLSNRNFIHRDLAARNCMLDENMTVCVADFGLSRkIYSG 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  391 DTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYE 470
Cdd:cd05035  167 DYYRQGRISKMPVKWIALESLADNVYTSKSDVWSFGVTMWEIATRGQTPYPGVENHEIYDYLRNGNRLKQPEDCLDEVYF 246
                        250       260
                 ....*....|....*....|....
gi 62362414  471 LMRACWQWNPSDRPSFAEIHQAFE 494
Cdd:cd05035  247 LMYFCWTVDPKDRPTFTKLREVLE 270
PTKc_Ror cd05048
Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan ...
246-491 1.14e-79

Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Ror subfamily consists of Ror1, Ror2, and similar proteins. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. Ror kinases are expressed in many tissues during development. They play important roles in bone and heart formation. Mutations in human Ror2 result in two different bone development genetic disorders, recessive Robinow syndrome and brachydactyly type B. Drosophila Ror is expressed only in the developing nervous system during neurite outgrowth and neuronal differentiation, suggesting a role for Drosophila Ror in neural development. More recently, mouse Ror1 and Ror2 have also been found to play an important role in regulating neurite growth in central neurons. Ror1 and Ror2 are believed to have some overlapping and redundant functions. The Ror subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270642 [Multi-domain]  Cd Length: 283  Bit Score: 262.31  E-value: 1.14e-79
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  246 HKLGGGQYGEVYEGVWKKYS-----LTVAVKTLKED-TMEV-EEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFM 318
Cdd:cd05048   11 EELGEGAFGKVYKGELLGPSseesaISVAIKTLKENaSPKTqQDFRREAELMSDLQHPNIVCLLGVCTKEQPQCMLFEYM 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  319 TYGNLLDYL-RECNRQEVNAVV-------------LLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGL 384
Cdd:cd05048   91 AHGDLHEFLvRHSPHSDVGVSSdddgtassldqsdFLHIAIQIAAGMEYLSSHHYVHRDLAARNCLVGDGLTVKISDFGL 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  385 SRLM-TGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEG 463
Cdd:cd05048  171 SRDIySSDYYRVQSKSLLPVRWMPPEAILYGKFTTESDVWSFGVVLWEIFSYGLQPYYGYSNQEVIEMIRSRQLLPCPED 250
                        250       260
                 ....*....|....*....|....*...
gi 62362414  464 CPEKVYELMRACWQWNPSDRPSFAEIHQ 491
Cdd:cd05048  251 CPARVYSLMVECWHEIPSRRPRFKEIHT 278
PTKc_Chk cd05083
Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the ...
235-496 8.31e-79

Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Chk is also referred to as megakaryocyte-associated tyrosine kinase (Matk). Chk inhibits Src kinases using a noncatalytic mechanism by simply binding to them. As a negative regulator of Src kinases, Chk may play important roles in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. Chk is expressed in brain and hematopoietic cells. Like Csk, it is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. To inhibit Src kinases that are anchored to the plasma membrane, Chk is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. Studies in mice reveal that Chk is not functionally redundant with Csk and that it plays an important role as a regulator of immune responses. Chk also plays a role in neural differentiation in a manner independent of Src by enhancing Mapk activation via Ras-mediated signaling. The Chk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270666 [Multi-domain]  Cd Length: 254  Bit Score: 259.04  E-value: 8.31e-79
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  235 WEMERTDITMKHKLGGGQYGEVYEGVWkkYSLTVAVKTLKEDtMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPpFYII 314
Cdd:cd05083    1 WLLNLQKLTLGEIIGEGEFGAVLQGEY--MGQKVAVKNIKCD-VTAQAFLEETAVMTKLQHKNLVRLLGVILHNG-LYIV 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  315 TEFMTYGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR--LMTGDT 392
Cdd:cd05083   77 MELMSKGNLVNFLRSRGRALVPVIQLLQFSLDVAEGMEYLESKKLVHRDLAARNILVSEDGVAKISDFGLAKvgSMGVDN 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  393 ytahagAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELM 472
Cdd:cd05083  157 ------SRLPVKWTAPEALKNKKFSSKSDVWSYGVLLWEVFSYGRAPYPKMSVKEVKEAVEKGYRMEPPEGCPPDVYSIM 230
                        250       260
                 ....*....|....*....|....
gi 62362414  473 RACWQWNPSDRPSFAEIHQAFETM 496
Cdd:cd05083  231 TSCWEAEPGKRPSFKKLREKLEKE 254
PTKc_c-ros cd05044
Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the ...
248-489 1.03e-78

Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily contains c-ros, Sevenless, and similar proteins. The proto-oncogene c-ros encodes an orphan receptor PTK (RTK) with an unknown ligand. RTKs contain an extracellular ligand-binding domain, a transmembrane region, and an intracellular tyr kinase domain. RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. C-ros is expressed in embryonic cells of the kidney, intestine and lung, but disappears soon after birth. It persists only in the adult epididymis. Male mice bearing inactive mutations of c-ros lack the initial segment of the epididymis and are infertile. The Drosophila protein, Sevenless, is required for the specification of the R7 photoreceptor cell during eye development. The c-ros subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270640 [Multi-domain]  Cd Length: 268  Bit Score: 259.27  E-value: 1.03e-78
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWK------KYSLTVAVKTLKEDTM--EVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMT 319
Cdd:cd05044    3 LGSGAFGEVFEGTAKdilgdgSGETKVAVKTLRKGATdqEKAEFLKEAHLMSNFKHPNILKLLGVCLDNDPQYIILELME 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  320 YGNLLDYLREcNRQEVNAVVLLYMATQISSAM------EYLEKKNFIHRDLAARNCLVGEN----HLVKVADFGLSR-LM 388
Cdd:cd05044   83 GGDLLSYLRA-ARPTAFTPPLLTLKDLLSICVdvakgcVYLEDMHFVHRDLAARNCLVSSKdyreRVVKIGDFGLARdIY 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  389 TGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKV 468
Cdd:cd05044  162 KNDYYRKEGEGLLPVRWMAPESLVDGVFTTQSDVWAFGVLMWEILTLGQQPYPARNNLEVLHFVRAGGRLDQPDNCPDDL 241
                        250       260
                 ....*....|....*....|.
gi 62362414  469 YELMRACWQWNPSDRPSFAEI 489
Cdd:cd05044  242 YELMLRCWSTDPEERPSFARI 262
PTKc_Fes cd05084
Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the ...
247-491 7.82e-78

Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fes (or Fps) is a cytoplasmic (or nonreceptor) PTK containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. The genes for Fes (feline sarcoma) and Fps (Fujinami poultry sarcoma) were first isolated from tumor-causing retroviruses. The viral oncogenes encode chimeric Fes proteins consisting of Gag sequences at the N-termini, resulting in unregulated PTK activity. Fes kinase is expressed in myeloid, vascular endothelial, epithelial, and neuronal cells. It plays important roles in cell growth and differentiation, angiogenesis, inflammation and immunity, and cytoskeletal regulation. A recent study implicates Fes kinase as a tumor suppressor in colorectal cancer. The Fes subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270667 [Multi-domain]  Cd Length: 252  Bit Score: 256.40  E-value: 7.82e-78
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLKEdTMEVE---EFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNL 323
Cdd:cd05084    3 RIGRGNFGEVFSGRLRADNTPVAVKSCRE-TLPPDlkaKFLQEARILKQYSHPNIVRLIGVCTQKQPIYIVMELVQGGDF 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  324 LDYLR-ECNRQEVNAvvLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAK-F 401
Cdd:cd05084   82 LTFLRtEGPRLKVKE--LIRMVENAAAGMEYLESKHCIHRDLAARNCLVTEKNVLKISDFGMSREEEDGVYAATGGMKqI 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  402 PIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQWNPS 481
Cdd:cd05084  160 PVKWTAPEALNYGRYSSESDVWSFGILLWETFSLGAVPYANLSNQQTREAVEQGVRLPCPENCPDEVYRLMEQCWEYDPR 239
                        250
                 ....*....|
gi 62362414  482 DRPSFAEIHQ 491
Cdd:cd05084  240 KRPSFSTVHQ 249
PTKc_Musk cd05050
Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the ...
236-494 3.68e-77

Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Musk is a receptor PTK (RTK) containing an extracellular region with four immunoglobulin-like domains and a cysteine-rich cluster, a transmembrane segment, and an intracellular catalytic domain. Musk is expressed and concentrated in the postsynaptic membrane in skeletal muscle. It is essential for the establishment of the neuromuscular junction (NMJ), a peripheral synapse that conveys signals from motor neurons to muscle cells. Agrin, a large proteoglycan released from motor neurons, stimulates Musk autophosphorylation and activation, leading to the clustering of acetylcholine receptors (AChRs). To date, there is no evidence to suggest that agrin binds directly to Musk. Mutations in AChR, Musk and other partners are responsible for diseases of the NMJ, such as the autoimmune syndrome myasthenia gravis. The Musk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133181 [Multi-domain]  Cd Length: 288  Bit Score: 255.91  E-value: 3.68e-77
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  236 EMERTDITMKHKLGGGQYGEVYEG-----VWKKYSLTVAVKTLKEDT---MEvEEFLKEAAVMKEIKHPNLVQLLGVCTR 307
Cdd:cd05050    1 EYPRNNIEYVRDIGQGAFGRVFQArapglLPYEPFTMVAVKMLKEEAsadMQ-ADFQREAALMAEFDHPNIVKLLGVCAV 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  308 EPPFYIITEFMTYGNLLDYLREC--------------------NRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAAR 367
Cdd:cd05050   80 GKPMCLLFEYMAYGDLNEFLRHRspraqcslshstssarkcglNPLPLSCTEQLCIAKQVAAGMAYLSERKFVHRDLATR 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  368 NCLVGENHLVKVADFGLSR-LMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLS 446
Cdd:cd05050  160 NCLVGENMVVKIADFGLSRnIYSADYYKASENDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGMQPYYGMAHE 239
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*...
gi 62362414  447 QVYELLEKDYRMERPEGCPEKVYELMRACWQWNPSDRPSFAEIHQAFE 494
Cdd:cd05050  240 EVIYYVRDGNVLSCPDNCPLELYNLMRLCWSKLPSDRPSFASINRILQ 287
PTKc_ALK_LTK cd05036
Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte ...
236-489 1.98e-76

Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte Tyrosine Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyr residues in protein substrates. ALK and LTK are orphan receptor PTKs (RTKs) whose ligands are not yet well-defined. ALK appears to play an important role in mammalian neural development as well as visceral muscle differentiation in Drosophila. ALK is aberrantly expressed as fusion proteins, due to chromosomal translocations, in about 60% of anaplastic large cell lymphomas (ALCLs). ALK fusion proteins are also found in rare cases of diffuse large B cell lymphomas (DLBCLs). LTK is mainly expressed in B lymphocytes and neuronal tissues. It is important in cell proliferation and survival. Transgenic mice expressing TLK display retarded growth and high mortality rate. In addition, a polymorphism in mouse and human LTK is implicated in the pathogenesis of systemic lupus erythematosus. RTKs contain an extracellular ligand-binding domain, a transmembrane region, and an intracellular tyr kinase domain. They are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The ALK/LTK subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270632 [Multi-domain]  Cd Length: 277  Bit Score: 253.46  E-value: 1.98e-76
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  236 EMERTDITMKHKLGGGQYGEVYEGVWK-----KYSLTVAVKTLKEDTMEVEE--FLKEAAVMKEIKHPNLVQLLGVCTRE 308
Cdd:cd05036    2 EVPRKNLTLIRALGQGAFGEVYEGTVSgmpgdPSPLQVAVKTLPELCSEQDEmdFLMEALIMSKFNHPNIVRCIGVCFQR 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  309 PPFYIITEFMTYGNLLDYLREC----NR-QEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLV---GENHLVKVA 380
Cdd:cd05036   82 LPRFILLELMAGGDLKSFLRENrprpEQpSSLTMLDLLQLAQDVAKGCRYLEENHFIHRDIAARNCLLtckGPGRVAKIG 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  381 DFGLSR-LMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRME 459
Cdd:cd05036  162 DFGMARdIYRADYYRKGGKAMLPVKWMPPEAFLDGIFTSKTDVWSFGVLLWEIFSLGYMPYPGKSNQEVMEFVTSGGRMD 241
                        250       260       270
                 ....*....|....*....|....*....|
gi 62362414  460 RPEGCPEKVYELMRACWQWNPSDRPSFAEI 489
Cdd:cd05036  242 PPKNCPGPVYRIMTQCWQHIPEDRPNFSTI 271
PTKc_PDGFR cd05055
Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; ...
232-496 2.72e-76

Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The PDGFR subfamily consists of PDGFR alpha, PDGFR beta, KIT, CSF-1R, the mammalian FLT3, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. PDGFR kinase domains are autoinhibited by their juxtamembrane regions containing tyr residues. The binding to their ligands leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR subfamily receptors are important in the development of a variety of cells. PDGFRs are expressed in a many cells including fibroblasts, neurons, endometrial cells, mammary epithelial cells, and vascular smooth muscle cells. PDGFR signaling is critical in normal embryonic development, angiogenesis, and wound healing. Kit is important in the development of melanocytes, germ cells, mast cells, hematopoietic stem cells, the interstitial cells of Cajal, and the pacemaker cells of the GI tract. CSF-1R signaling is critical in the regulation of macrophages and osteoclasts. Mammalian FLT3 plays an important role in the survival, proliferation, and differentiation of stem cells. The PDGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase .


Pssm-ID: 133186 [Multi-domain]  Cd Length: 302  Bit Score: 253.95  E-value: 2.72e-76
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  232 YD-KWEMERTDITMKHKLGGGQYGEVYE----GVWKK-YSLTVAVKTLKE--DTMEVEEFLKEAAVMKEI-KHPNLVQLL 302
Cdd:cd05055   26 YDlKWEFPRNNLSFGKTLGAGAFGKVVEatayGLSKSdAVMKVAVKMLKPtaHSSEREALMSELKIMSHLgNHENIVNLL 105
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  303 GVCTREPPFYIITEFMTYGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADF 382
Cdd:cd05055  106 GACTIGGPILVITEYCCYGDLLNFLRRKRESFLTLEDLLSFSYQVAKGMAFLASKNCIHRDLAARNVLLTHGKIVKICDF 185
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  383 GLSR-LMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDL-SQVYELLEKDYRMER 460
Cdd:cd05055  186 GLARdIMNDSNYVVKGNARLPVKWMAPESIFNCVYTFESDVWSYGILLWEIFSLGSNPYPGMPVdSKFYKLIKEGYRMAQ 265
                        250       260       270
                 ....*....|....*....|....*....|....*.
gi 62362414  461 PEGCPEKVYELMRACWQWNPSDRPSFAEIHQAFETM 496
Cdd:cd05055  266 PEHAPAEIYDIMKTCWDADPLKRPTFKQIVQLIGKQ 301
PTKc_Mer cd14204
Catalytic Domain of the Protein Tyrosine Kinase, Mer; PTKs catalyze the transfer of the ...
237-498 4.48e-76

Catalytic Domain of the Protein Tyrosine Kinase, Mer; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Mer (or Mertk) is named after its original reported expression pattern (monocytes, epithelial, and reproductive tissues). It is required for the ingestion of apoptotic cells by phagocytes such as macrophages, retinal pigment epithelial cells, and dendritic cells. Mer is also important in maintaining immune homeostasis. Mer is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Mer subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271106 [Multi-domain]  Cd Length: 284  Bit Score: 252.55  E-value: 4.48e-76
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  237 MERTDITMKHKLGGGQYGEVYEGVWKK---YSLTVAVKTLKEDTM---EVEEFLKEAAVMKEIKHPNLVQLLGVCT---- 306
Cdd:cd14204    4 IDRNLLSLGKVLGEGEFGSVMEGELQQpdgTNHKVAVKTMKLDNFsqrEIEEFLSEAACMKDFNHPNVIRLLGVCLevgs 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  307 -REPPFYIITEFMTYGNLLDYL----RECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVAD 381
Cdd:cd14204   84 qRIPKPMVILPFMKYGDLHSFLlrsrLGSGPQHVPLQTLLKFMIDIALGMEYLSSRNFLHRDLAARNCMLRDDMTVCVAD 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  382 FGLSR-LMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMER 460
Cdd:cd14204  164 FGLSKkIYSGDYYRQGRIAKMPVKWIAVESLADRVYTVKSDVWAFGVTMWEIATRGMTPYPGVQNHEIYDYLLHGHRLKQ 243
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 62362414  461 PEGCPEKVYELMRACWQWNPSDRPSFAEIHQAFETMFQ 498
Cdd:cd14204  244 PEDCLDELYDIMYSCWRSDPTDRPTFTQLRENLEKLLE 281
PTKc_Trk cd05049
Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze ...
236-490 2.36e-75

Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Trk subfamily consists of TrkA, TrkB, TrkC, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, the nerve growth factor (NGF) family of neutrotrophins, leads to Trk receptor oligomerization and activation of the catalytic domain. Trk receptors are mainly expressed in the peripheral and central nervous systems. They play important roles in cell fate determination, neuronal survival and differentiation, as well as in the regulation of synaptic plasticity. Altered expression of Trk receptors is associated with many human diseases. The Trk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270643 [Multi-domain]  Cd Length: 280  Bit Score: 250.46  E-value: 2.36e-75
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  236 EMERTDITMKHKLGGGQYGEVYEG-----VWKKYSLTVAVKTLKEDTMEV--EEFLKEAAVMKEIKHPNLVQLLGVCTRE 308
Cdd:cd05049    1 HIKRDTIVLKRELGEGAFGKVFLGecynlEPEQDKMLVAVKTLKDASSPDarKDFEREAELLTNLQHENIVKFYGVCTEG 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  309 PPFYIITEFMTYGNLLDYLR------------ECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHL 376
Cdd:cd05049   81 DPLLMVFEYMEHGDLNKFLRshgpdaaflaseDSAPGELTLSQLLHIAVQIASGMVYLASQHFVHRDLATRNCLVGTNLV 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  377 VKVADFGLSR-LMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKD 455
Cdd:cd05049  161 VKIGDFGMSRdIYSTDYYRVGGHTMLPIRWMPPESILYRKFTTESDVWSFGVVLWEIFTYGKQPWFQLSNTEVIECITQG 240
                        250       260       270
                 ....*....|....*....|....*....|....*
gi 62362414  456 YRMERPEGCPEKVYELMRACWQWNPSDRPSFAEIH 490
Cdd:cd05049  241 RLLQRPRTCPSEVYAVMLGCWKREPQQRLNIKDIH 275
PTKc_Axl cd05075
Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the ...
242-499 2.77e-75

Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Axl is widely expressed in a variety of organs and cells including epithelial, mesenchymal, hematopoietic, as well as non-transformed cells. It is important in many cellular functions such as survival, anti-apoptosis, proliferation, migration, and adhesion. Axl was originally isolated from patients with chronic myelogenous leukemia and a chronic myeloproliferative disorder. It is overexpressed in many human cancers including colon, squamous cell, thyroid, breast, and lung carcinomas. Axl is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to its ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Axl subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270660 [Multi-domain]  Cd Length: 277  Bit Score: 250.31  E-value: 2.77e-75
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  242 ITMKHKLGGGQYGEVYEGVWKK--YSLTVAVKTLKE---DTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTRE------PP 310
Cdd:cd05075    2 LALGKTLGEGEFGSVMEGQLNQddSVLKVAVKTMKIaicTRSEMEDFLSEAVCMKEFDHPNVMRLIGVCLQNtesegyPS 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  311 FYIITEFMTYGNLLDYLRECNRQE----VNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR 386
Cdd:cd05075   82 PVVILPFMKHGDLHSFLLYSRLGDcpvyLPTQMLVKFMTDIASGMEYLSSKNFIHRDLAARNCMLNENMNVCVADFGLSK 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  387 -LMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCP 465
Cdd:cd05075  162 kIYNGDYYRQGRISKMPVKWIAIESLADRVYTTKSDVWSFGVTMWEIATRGQTPYPGVENSEIYDYLRQGNRLKQPPDCL 241
                        250       260       270
                 ....*....|....*....|....*....|....
gi 62362414  466 EKVYELMRACWQWNPSDRPSFAEIHQAFETMFQE 499
Cdd:cd05075  242 DGLYELMSSCWLLNPKDRPSFETLRCELEKILKD 275
PTKc_FGFR4 cd05099
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs ...
234-505 1.26e-73

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Unlike other FGFRs, there is only one splice form of FGFR4. It binds FGF1, FGF2, FGF6, FGF19, and FGF23. FGF19 is a selective ligand for FGFR4. Although disruption of FGFR4 in mice causes no obvious phenotype, in vivo inhibition of FGFR4 in cultured skeletal muscle cells resulted in an arrest of muscle progenitor differentiation. FGF6 and FGFR4 are uniquely expressed in myofibers and satellite cells. FGF6/FGFR4 signaling appears to play a key role in the regulation of muscle regeneration. A polymorphism in FGFR4 is found in head and neck squamous cell carcinoma. FGFR4 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR4 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133230 [Multi-domain]  Cd Length: 314  Bit Score: 246.80  E-value: 1.26e-73
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  234 KWEMERTDITMKHKLGGGQYGEVY-------EGVWKKYSLTVAVKTLKEDTME--VEEFLKEAAVMKEI-KHPNLVQLLG 303
Cdd:cd05099    6 KWEFPRDRLVLGKPLGEGCFGQVVraeaygiDKSRPDQTVTVAVKMLKDNATDkdLADLISEMELMKLIgKHKNIINLLG 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  304 VCTREPPFYIITEFMTYGNLLDYLR--------------ECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNC 369
Cdd:cd05099   86 VCTQEGPLYVIVEYAAKGNLREFLRarrppgpdytfditKVPEEQLSFKDLVSCAYQVARGMEYLESRRCIHRDLAARNV 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  370 LVGENHLVKVADFGLSR-LMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQV 448
Cdd:cd05099  166 LVTEDNVMKIADFGLARgVHDIDYYKKTSNGRLPVKWMAPEALFDRVYTHQSDVWSFGILMWEIFTLGGSPYPGIPVEEL 245
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 62362414  449 YELLEKDYRMERPEGCPEKVYELMRACWQWNPSDRPSFAEIHQAFETMFqeSSISDE 505
Cdd:cd05099  246 FKLLREGHRMDKPSNCTHELYMLMRECWHAVPTQRPTFKQLVEALDKVL--AAVSEE 300
PTKc_Tyro3 cd05074
Catalytic domain of the Protein Tyrosine Kinase, Tyro3; PTKs catalyze the transfer of the ...
242-496 2.39e-73

Catalytic domain of the Protein Tyrosine Kinase, Tyro3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tyro3 (or Sky) is predominantly expressed in the central nervous system and the brain, and functions as a neurotrophic factor. It is also expressed in osteoclasts and has a role in bone resorption. Tyro3 is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Tyro3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270659 [Multi-domain]  Cd Length: 284  Bit Score: 245.21  E-value: 2.39e-73
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  242 ITMKHKLGGGQYGEVYEGVWKKYSLT---VAVKTLKED---TMEVEEFLKEAAVMKEIKHPNLVQLLGVCTRE------P 309
Cdd:cd05074   11 FTLGRMLGKGEFGSVREAQLKSEDGSfqkVAVKMLKADifsSSDIEEFLREAACMKEFDHPNVIKLIGVSLRSrakgrlP 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  310 PFYIITEFMTYGNLLDYLRECNRQE----VNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLS 385
Cdd:cd05074   91 IPMVILPFMKHGDLHTFLLMSRIGEepftLPLQTLVRFMIDIASGMEYLSSKNFIHRDLAARNCMLNENMTVCVADFGLS 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  386 R-LMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGC 464
Cdd:cd05074  171 KkIYSGDYYRQGCASKLPVKWLALESLADNVYTTHSDVWAFGVTMWEIMTRGQTPYAGVENSEIYNYLIKGNRLKQPPDC 250
                        250       260       270
                 ....*....|....*....|....*....|..
gi 62362414  465 PEKVYELMRACWQWNPSDRPSFAEIHQAFETM 496
Cdd:cd05074  251 LEDVYELMCQCWSPEPKCRPSFQHLRDQLELI 282
PTKc_RET cd05045
Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs ...
248-496 8.53e-73

Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. RET is a receptor PTK (RTK) containing an extracellular region with four cadherin-like repeats, a calcium-binding site, and a cysteine-rich domain, a transmembrane segment, and an intracellular catalytic domain. It is part of a multisubunit complex that binds glial-derived neurotropic factor (GDNF) family ligands (GFLs) including GDNF, neurturin, artemin, and persephin. GFLs bind RET along with four GPI-anchored coreceptors, bringing two RET molecules together, leading to autophosphorylation, activation, and intracellular signaling. RET is essential for the development of the sympathetic, parasympathetic and enteric nervous systems, and the kidney. RET disruption by germline mutations causes diseases in humans including congenital aganglionosis of the gastrointestinal tract (Hirschsprung's disease) and three related inherited cancers: multiple endocrine neoplasia type 2A (MEN2A), MEN2B, and familial medullary thyroid carcinoma. The RET subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173631 [Multi-domain]  Cd Length: 290  Bit Score: 243.72  E-value: 8.53e-73
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYS-----LTVAVKTLKEDTMEVE--EFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTY 320
Cdd:cd05045    8 LGEGEFGKVVKATAFRLKgragyTTVAVKMLKENASSSElrDLLSEFNLLKQVNHPHVIKLYGACSQDGPLLLIVEYAKY 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  321 GNLLDYLRECNRQE----------------------VNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVK 378
Cdd:cd05045   88 GSLRSFLRESRKVGpsylgsdgnrnssyldnpderaLTMGDLISFAWQISRGMQYLAEMKLVHRDLAARNVLVAEGRKMK 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  379 VADFGLSR-LMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYR 457
Cdd:cd05045  168 ISDFGLSRdVYEEDSYVKRSKGRIPVKWMAIESLFDHIYTTQSDVWSFGVLLWEIVTLGGNPYPGIAPERLFNLLKTGYR 247
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 62362414  458 MERPEGCPEKVYELMRACWQWNPSDRPSFAEIHQAFETM 496
Cdd:cd05045  248 MERPENCSEEMYNLMLTCWKQEPDKRPTFADISKELEKM 286
PTKc_Jak_rpt2 cd05038
Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily ...
247-495 1.09e-71

Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily is composed of Jak1, Jak2, Jak3, TYK2, and similar proteins. They are PTKs, catalyzing the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jaks are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Most Jaks are expressed in a wide variety of tissues, except for Jak3, which is expressed only in hematopoietic cells. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). Jaks are also involved in regulating the surface expression of some cytokine receptors. The Jak-STAT pathway is involved in many biological processes including hematopoiesis, immunoregulation, host defense, fertility, lactation, growth, and embryogenesis. The Jak subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270634 [Multi-domain]  Cd Length: 284  Bit Score: 240.36  E-value: 1.09e-71
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWK----KYSLTVAVKTLKEDTMEV--EEFLKEAAVMKEIKHPNLVQLLGVCTR--EPPFYIITEFM 318
Cdd:cd05038   11 QLGEGHFGSVELCRYDplgdNTGEQVAVKSLQPSGEEQhmSDFKREIEILRTLDHEYIVKYKGVCESpgRRSLRLIMEYL 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  319 TYGNLLDYLREcNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDT--YTAH 396
Cdd:cd05038   91 PSGSLRDYLQR-HRDQIDLKRLLLFASQICKGMEYLGSQRYIHRDLAARNILVESEDLVKISDFGLAKVLPEDKeyYYVK 169
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  397 AGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYG---MSPYPGI-----------DLSQVYELLEKDYRMERPE 462
Cdd:cd05038  170 EPGESPIFWYAPECLRESRFSSASDVWSFGVTLYELFTYGdpsQSPPALFlrmigiaqgqmIVTRLLELLKSGERLPRPP 249
                        250       260       270
                 ....*....|....*....|....*....|...
gi 62362414  463 GCPEKVYELMRACWQWNPSDRPSFAEIHQAFET 495
Cdd:cd05038  250 SCPDEVYDLMKECWEYEPQDRPSFSDLILIIDR 282
PTKc_EphR_B cd05065
Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze ...
248-496 1.38e-71

Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EphB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. One exception is EphB2, which also interacts with ephrin A5. EphB receptors play important roles in synapse formation and plasticity, spine morphogenesis, axon guidance, and angiogenesis. In the intestinal epithelium, EphBs are Wnt signaling target genes that control cell compartmentalization. They function as suppressors of colon cancer progression. EphRs comprise the largest subfamily of receptor PTKs (RTKs). They contain an ephrin-binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion. The EphB subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173638 [Multi-domain]  Cd Length: 269  Bit Score: 239.39  E-value: 1.38e-71
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWK---KYSLTVAVKTLKEDTMEVE--EFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGN 322
Cdd:cd05065   12 IGAGEFGEVCRGRLKlpgKREIFVAIKTLKSGYTEKQrrDFLSEASIMGQFDHPNIIHLEGVVTKSRPVMIITEFMENGA 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLREcNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGD----TYTAHAG 398
Cdd:cd05065   92 LDSFLRQ-NDGQFTVIQLVGMLRGIAAGMKYLSEMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDtsdpTYTSSLG 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  399 AKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQW 478
Cdd:cd05065  171 GKIPIRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSYGERPYWDMSNQDVINAIEQDYRLPPPMDCPTALHQLMLDCWQK 250
                        250
                 ....*....|....*...
gi 62362414  479 NPSDRPSFAEIHQAFETM 496
Cdd:cd05065  251 DRNLRPKFGQIVNTLDKM 268
PTKc_EphR_A2 cd05063
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the ...
236-489 5.22e-71

Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The EphA2 receptor is overexpressed in tumor cells and tumor blood vessels in a variety of cancers including breast, prostate, lung, and colon. As a result, it is an attractive target for drug design since its inhibition could affect several aspects of tumor progression. EphRs comprise the largest subfamily of receptor PTKs (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. The EphA2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 133194 [Multi-domain]  Cd Length: 268  Bit Score: 237.95  E-value: 5.22e-71
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  236 EMERTDITMKHKLGGGQYGEVYEGVWK---KYSLTVAVKTLKEDTMEVE--EFLKEAAVMKEIKHPNLVQLLGVCTREPP 310
Cdd:cd05063    1 EIHPSHITKQKVIGAGEFGEVFRGILKmpgRKEVAVAIKTLKPGYTEKQrqDFLSEASIMGQFSHHNIIRLEGVVTKFKP 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  311 FYIITEFMTYGNLLDYLREcNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTG 390
Cdd:cd05063   81 AMIITEYMENGALDKYLRD-HDGEFSSYQLVGMLRGIAAGMKYLSDMNYVHRDLAARNILVNSNLECKVSDFGLSRVLED 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  391 D---TYTAhAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEK 467
Cdd:cd05063  160 DpegTYTT-SGGKIPIRWTAPEAIAYRKFTSASDVWSFGIVMWEVMSFGERPYWDMSNHEVMKAINDGFRLPAPMDCPSA 238
                        250       260
                 ....*....|....*....|..
gi 62362414  468 VYELMRACWQWNPSDRPSFAEI 489
Cdd:cd05063  239 VYQLMLQCWQQDRARRPRFVDI 260
PTKc_Syk cd05116
Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the ...
247-489 3.08e-70

Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Syk is a cytoplasmic (or nonreceptor) PTK containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. Syk was first cloned from the spleen, and its function in hematopoietic cells is well-established. It is involved in the signaling downstream of activated receptors (including B-cell and Fc receptors) that contain ITAMs (immunoreceptor tyr activation motifs), leading to processes such as cell proliferation, differentiation, survival, adhesion, migration, and phagocytosis. More recently, Syk expression has been detected in other cell types (including epithelial cells, vascular endothelial cells, neurons, hepatocytes, and melanocytes), suggesting a variety of biological functions in non-immune cells. Syk plays a critical role in maintaining vascular integrity and in wound healing during embryogenesis. It also regulates Vav3, which is important in osteoclast function including bone development. In breast epithelial cells, where Syk acts as a negative regulator for EGFR signaling, loss of Syk expression is associated with abnormal proliferation during cancer development suggesting a potential role as a tumor suppressor. In mice, Syk has been shown to inhibit malignant transformation of mammary epithelial cells induced with murine mammary tumor virus (MMTV). The Syk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133247 [Multi-domain]  Cd Length: 257  Bit Score: 235.24  E-value: 3.08e-70
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVW--KKYSLTVAVKTLKEDTMEV---EEFLKEAAVMKEIKHPNLVQLLGVCTREPpFYIITEFMTYG 321
Cdd:cd05116    2 ELGSGNFGTVKKGYYqmKKVVKTVAVKILKNEANDPalkDELLREANVMQQLDNPYIVRMIGICEAES-WMLVMEMAELG 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  322 NLLDYLREcNRQ--EVNAVVLLYmatQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDT--YTAHA 397
Cdd:cd05116   81 PLNKFLQK-NRHvtEKNITELVH---QVSMGMKYLEESNFVHRDLAARNVLLVTQHYAKISDFGLSKALRADEnyYKAQT 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  398 GAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQ 477
Cdd:cd05116  157 HGKWPVKWYAPECMNYYKFSSKSDVWSFGVLMWEAFSYGQKPYKGMKGNEVTQMIEKGERMECPAGCPPEMYDLMKLCWT 236
                        250
                 ....*....|..
gi 62362414  478 WNPSDRPSFAEI 489
Cdd:cd05116  237 YDVDERPGFAAV 248
PTKc_Met_Ron cd05058
Catalytic domain of the Protein Tyrosine Kinases, Met and Ron; PTKs catalyze the transfer of ...
248-499 5.91e-70

Catalytic domain of the Protein Tyrosine Kinases, Met and Ron; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Met and Ron are receptor PTKs (RTKs) composed of an alpha-beta heterodimer. The extracellular alpha chain is disulfide linked to the beta chain, which contains an extracellular ligand-binding region with a sema domain, a PSI domain and four IPT repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. Met binds to the ligand, hepatocyte growth factor/scatter factor (HGF/SF), and is also called the HGF receptor. HGF/Met signaling plays a role in growth, transformation, cell motility, invasion, metastasis, angiogenesis, wound healing, and tissue regeneration. Aberrant expression of Met through mutations or gene amplification is associated with many human cancers including hereditary papillary renal and gastric carcinomas. The ligand for Ron is macrophage stimulating protein (MSP). Ron signaling is important in regulating cell motility, adhesion, proliferation, and apoptosis. Aberrant Ron expression is implicated in tumorigenesis and metastasis. The Met/Ron subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270649 [Multi-domain]  Cd Length: 262  Bit Score: 234.68  E-value: 5.91e-70
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVW---KKYSLTVAVKTLK--EDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTR-EPPFYIITEFMTYG 321
Cdd:cd05058    3 IGKGHFGCVYHGTLidsDGQKIHCAVKSLNriTDIEEVEQFLKEGIIMKDFSHPNVLSLLGICLPsEGSPLVVLPYMKHG 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  322 NLLDYLRECNRqevNAVV--LLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTA---H 396
Cdd:cd05058   83 DLRNFIRSETH---NPTVkdLIGFGLQVAKGMEYLASKKFVHRDLAARNCMLDESFTVKVADFGLARDIYDKEYYSvhnH 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  397 AGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACW 476
Cdd:cd05058  160 TGAKLPVKWMALESLQTQKFTTKSDVWSFGVLLWELMTRGAPPYPDVDSFDITVYLLQGRRLLQPEYCPDPLYEVMLSCW 239
                        250       260
                 ....*....|....*....|...
gi 62362414  477 QWNPSDRPSFAEIHQAFETMFQE 499
Cdd:cd05058  240 HPKPEMRPTFSELVSRISQIFST 262
PTKc_InsR cd05061
Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer ...
235-501 8.25e-69

Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. InsR is a receptor PTK (RTK) that is composed of two alphabeta heterodimers. Binding of the insulin ligand to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, stimulating downstream kinase activities, which initiate signaling cascades and biological function. InsR signaling plays an important role in many cellular processes including glucose homeostasis, glycogen synthesis, lipid and protein metabolism, ion and amino acid transport, cell cycle and proliferation, cell differentiation, gene transcription, and nitric oxide synthesis. Insulin resistance, caused by abnormalities in InsR signaling, has been described in diabetes, hypertension, cardiovascular disease, metabolic syndrome, heart failure, and female infertility. The InsR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133192 [Multi-domain]  Cd Length: 288  Bit Score: 232.55  E-value: 8.25e-69
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  235 WEMERTDITMKHKLGGGQYGEVYEGVWK-----KYSLTVAVKTLKEDTMEVE--EFLKEAAVMKEIKHPNLVQLLGVCTR 307
Cdd:cd05061    1 WEVSREKITLLRELGQGSFGMVYEGNARdiikgEAETRVAVKTVNESASLREriEFLNEASVMKGFTCHHVVRLLGVVSK 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  308 EPPFYIITEFMTYGNLLDYLRECNRQEVNAV--------VLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKV 379
Cdd:cd05061   81 GQPTLVVMELMAHGDLKSYLRSLRPEAENNPgrppptlqEMIQMAAEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVKI 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  380 ADFGLSR-LMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRM 458
Cdd:cd05061  161 GDFGMTRdIYETDYYRKGGKGLLPVRWMAPESLKDGVFTTSSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGYL 240
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*..
gi 62362414  459 ERPEGCPEKVYELMRACWQWNPSDRPSFAEI----HQAFETMFQESS 501
Cdd:cd05061  241 DQPDNCPERVTDLMRMCWQFNPKMRPTFLEIvnllKDDLHPSFPEVS 287
PTKc_EphR_A cd05066
Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze ...
237-489 1.25e-68

Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of most class EphA receptors including EphA3, EphA4, EphA5, and EphA7, but excluding EphA1, EphA2 and EphA10. Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. One exception is EphA4, which also binds ephrins-B2/B3. EphA receptors and ephrin-A ligands are expressed in multiple areas of the developing brain, especially in the retina and tectum. They are part of a system controlling retinotectal mapping. EphRs comprise the largest subfamily of receptor PTKs (RTKs). EphRs contain an ephrin-binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. The EphA subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270651 [Multi-domain]  Cd Length: 267  Bit Score: 231.29  E-value: 1.25e-68
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  237 MERTDITMKHKLGGGQYGEVYEGVWK---KYSLTVAVKTLKEDTMEVE--EFLKEAAVMKEIKHPNLVQLLGVCTREPPF 311
Cdd:cd05066    1 IDASCIKIEKVIGAGEFGEVCSGRLKlpgKREIPVAIKTLKAGYTEKQrrDFLSEASIMGQFDHPNIIHLEGVVTRSKPV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  312 YIITEFMTYGNLLDYLRECNRQeVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGD 391
Cdd:cd05066   81 MIVTEYMENGSLDAFLRKHDGQ-FTVIQLVGMLRGIASGMKYLSDMGYVHRDLAARNILVNSNLVCKVSDFGLSRVLEDD 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  392 TYTAHA--GAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVY 469
Cdd:cd05066  160 PEAAYTtrGGKIPIRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSYGERPYWEMSNQDVIKAIEEGYRLPAPMDCPAALH 239
                        250       260
                 ....*....|....*....|
gi 62362414  470 ELMRACWQWNPSDRPSFAEI 489
Cdd:cd05066  240 QLMLDCWQKDRNERPKFEQI 259
PTKc_DDR2 cd05095
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2; PTKs catalyze ...
236-491 1.31e-68

Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR2 is a receptor PTK (RTK) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDR2 results in a slow but sustained receptor activation. DDR2 binds mostly to fibrillar collagens as well as collagen X. DDR2 is widely expressed in many tissues with the highest levels found in skeletal muscle, skin, kidney and lung. It is important in cell proliferation and development. Mice, with a deletion of DDR2, suffer from dwarfism and delayed healing of epidermal wounds. DDR2 also contributes to collagen (type I) regulation by inhibiting fibrillogenesis and altering the morphology of collagen fibers. It is also expressed in immature dendritic cells (DCs), where it plays a role in DC activation and function. The DDR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270677 [Multi-domain]  Cd Length: 297  Bit Score: 232.19  E-value: 1.31e-68
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  236 EMERTDITMKHKLGGGQYGEVY----EGVWK------------KYSLTVAVKTLKEDTME--VEEFLKEAAVMKEIKHPN 297
Cdd:cd05095    1 EFPRKLLTFKEKLGEGQFGEVHlceaEGMEKfmdkdfalevseNQPVLVAVKMLRADANKnaRNDFLKEIKIMSRLKDPN 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  298 LVQLLGVCTREPPFYIITEFMTYGNLLDYLrecNRQE-------------VNAVVLLYMATQISSAMEYLEKKNFIHRDL 364
Cdd:cd05095   81 IIRLLAVCITDDPLCMITEYMENGDLNQFL---SRQQpegqlalpsnaltVSYSDLRFMAAQIASGMKYLSSLNFVHRDL 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  365 AARNCLVGENHLVKVADFGLSR-LMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGM-SPYPG 442
Cdd:cd05095  158 ATRNCLVGKNYTIKIADFGMSRnLYSGDYYRIQGRAVLPIRWMSWESILLGKFTTASDVWAFGVTLWETLTFCReQPYSQ 237
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 62362414  443 IDLSQVYELLEKDYR-------MERPEGCPEKVYELMRACWQWNPSDRPSFAEIHQ 491
Cdd:cd05095  238 LSDEQVIENTGEFFRdqgrqtyLPQPALCPDSVYKLMLSCWRRDTKDRPSFQEIHT 293
PTKc_DDR_like cd05097
Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the ...
236-495 4.43e-67

Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR-like proteins are members of the DDR subfamily, which are receptor PTKs (RTKs) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDRs results in a slow but sustained receptor activation. DDRs regulate cell adhesion, proliferation, and extracellular matrix remodeling. They have been linked to a variety of human cancers including breast, colon, ovarian, brain, and lung. There is no evidence showing that DDRs act as transforming oncogenes. They are more likely to play a role in the regulation of tumor growth and metastasis. The DDR-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133228 [Multi-domain]  Cd Length: 295  Bit Score: 227.94  E-value: 4.43e-67
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  236 EMERTDITMKHKLGGGQYGEVY----EGV----------WKKYSLTVAVKTLKEDTMEV--EEFLKEAAVMKEIKHPNLV 299
Cdd:cd05097    1 EFPRQQLRLKEKLGEGQFGEVHlceaEGLaeflgegapeFDGQPVLVAVKMLRADVTKTarNDFLKEIKIMSRLKNPNII 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  300 QLLGVCTREPPFYIITEFMTYGNLLDYL--REC--------NRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNC 369
Cdd:cd05097   81 RLLGVCVSDDPLCMITEYMENGDLNQFLsqREIestfthanNIPSVSIANLLYMAVQIASGMKYLASLNFVHRDLATRNC 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  370 LVGENHLVKVADFGLSR-LMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATY-GMSPYPGIDLSQ 447
Cdd:cd05097  161 LVGNHYTIKIADFGMSRnLYSGDYYRIQGRAVLPIRWMAWESILLGKFTTASDVWAFGVTLWEMFTLcKEQPYSLLSDEQ 240
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 62362414  448 VYELLEKDYR-------MERPEGCPEKVYELMRACWQWNPSDRPSFAEIHQAFET 495
Cdd:cd05097  241 VIENTGEFFRnqgrqiyLSQTPLCPSPVFKLMMRCWSRDIKDRPTFNKIHHFLRE 295
PTKc_EGFR cd05108
Catalytic domain of the Protein Tyrosine Kinase, Epidermal Growth Factor Receptor; PTKs ...
237-549 4.59e-67

Catalytic domain of the Protein Tyrosine Kinase, Epidermal Growth Factor Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EGFR (HER1, ErbB1) is a receptor PTK (RTK) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Ligands for EGFR include EGF, heparin binding EGF-like growth factor (HBEGF), epiregulin, amphiregulin, TGFalpha, and betacellulin. Upon ligand binding, EGFR can form homo- or heterodimers with other EGFR subfamily members. The EGFR signaling pathway is one of the most important pathways regulating cell proliferation, differentiation, survival, and growth. Overexpression and mutation in the kinase domain of EGFR have been implicated in the development and progression of a variety of cancers. A number of monoclonal antibodies and small molecule inhibitors have been developed that target EGFR, including the antibodies Cetuximab and Panitumumab, which are used in combination with other therapies for the treatment of colorectal cancer and non-small cell lung carcinoma (NSCLC). The small molecule inhibitors Gefitinib (Iressa) and Erlotinib (Tarceva), already used for NSCLC, are undergoing clinical trials for other types of cancer including gastrointestinal, breast, head and neck, and bladder. The EGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270683 [Multi-domain]  Cd Length: 313  Bit Score: 228.37  E-value: 4.59e-67
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  237 MERTDITMKHKLGGGQYGEVYEGVW----KKYSLTVAVKTLKEDTMEV--EEFLKEAAVMKEIKHPNLVQLLGVCTREPp 310
Cdd:cd05108    4 LKETEFKKIKVLGSGAFGTVYKGLWipegEKVKIPVAIKELREATSPKanKEILDEAYVMASVDNPHVCRLLGICLTST- 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  311 FYIITEFMTYGNLLDYLREcNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTG 390
Cdd:cd05108   83 VQLITQLMPFGCLLDYVRE-HKDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAARNVLVKTPQHVKITDFGLAKLLGA 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  391 DTYTAHA-GAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVY 469
Cdd:cd05108  162 EEKEYHAeGGKVPIKWMALESILHRIYTHQSDVWSYGVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDVY 241
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  470 ELMRACWQWNPSDRPSFAEIHQAFETMFQESSisdeveKELgkqGVRGAVSTLLQAPELPTKTRTSRRAAEHRDTTDVPE 549
Cdd:cd05108  242 MIMVKCWMIDADSRPKFRELIIEFSKMARDPQ------RYL---VIQGDERMHLPSPTDSNFYRALMDEEDMDDVVDADE 312
PTKc_FGFR2 cd05101
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2; PTKs ...
230-489 5.67e-67

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. There are many splice variants of FGFR2 which show differential expression and binding to FGF ligands. Disruption of either FGFR2 or FGFR2b is lethal in mice, due to defects in the placenta or severe impairment of tissue development including lung, limb, and thyroid, respectively. Disruption of FGFR2c in mice results in defective bone and skull development. Genetic alterations of FGFR2 are associated with many human skeletal disorders including Apert syndrome, Crouzon syndrome, Jackson-Weiss syndrome, and Pfeiffer syndrome. FGFR2 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270679 [Multi-domain]  Cd Length: 313  Bit Score: 228.36  E-value: 5.67e-67
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  230 PNYDKWEMERTDITMKHKLGGGQYGEVYE----GVWK---KYSLTVAVKTLKEDTME--VEEFLKEAAVMKEI-KHPNLV 299
Cdd:cd05101   14 PEDPKWEFPRDKLTLGKPLGEGCFGQVVMaeavGIDKdkpKEAVTVAVKMLKDDATEkdLSDLVSEMEMMKMIgKHKNII 93
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  300 QLLGVCTREPPFYIITEFMTYGNLLDYLR-----------ECNR---QEVNAVVLLYMATQISSAMEYLEKKNFIHRDLA 365
Cdd:cd05101   94 NLLGACTQDGPLYVIVEYASKGNLREYLRarrppgmeysyDINRvpeEQMTFKDLVSCTYQLARGMEYLASQKCIHRDLA 173
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  366 ARNCLVGENHLVKVADFGLSRLMTG-DTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGID 444
Cdd:cd05101  174 ARNVLVTENNVMKIADFGLARDINNiDYYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLMWEIFTLGGSPYPGIP 253
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*
gi 62362414  445 LSQVYELLEKDYRMERPEGCPEKVYELMRACWQWNPSDRPSFAEI 489
Cdd:cd05101  254 VEELFKLLKEGHRMDKPANCTNELYMMMRDCWHAVPSQRPTFKQL 298
PTKc_Tie cd05047
Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
248-498 1.15e-66

Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie proteins, consisting of Tie1 and Tie2, are receptor PTKs (RTKs) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie receptors are specifically expressed in endothelial cells and hematopoietic stem cells. The angiopoietins (Ang-1 to Ang-4) serve as ligands for Tie2, while no specific ligand has been identified for Tie1. The binding of Ang-1 to Tie2 leads to receptor autophosphorylation and activation, promoting cell migration and survival. In contrast, Ang-2 binding to Tie2 does not result in the same response, suggesting that Ang-2 may function as an antagonist. In vivo studies of Tie1 show that it is critical in vascular development. The Tie subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270641 [Multi-domain]  Cd Length: 270  Bit Score: 225.69  E-value: 1.15e-66
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKK--YSLTVAVKTLKEDTMEVE--EFLKEAAVMKEI-KHPNLVQLLGVCTREPPFYIITEFMTYGN 322
Cdd:cd05047    3 IGEGNFGQVLKARIKKdgLRMDAAIKRMKEYASKDDhrDFAGELEVLCKLgHHPNIINLLGACEHRGYLYLAIEYAPHGN 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLRECNRQEVNAVV--------------LLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRlm 388
Cdd:cd05047   83 LLDFLRKSRVLETDPAFaianstastlssqqLLHFAADVARGMDYLSQKQFIHRDLAARNILVGENYVAKIADFGLSR-- 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  389 TGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKV 468
Cdd:cd05047  161 GQEVYVKKTMGRLPVRWMAIESLNYSVYTTNSDVWSYGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYRLEKPLNCDDEV 240
                        250       260       270
                 ....*....|....*....|....*....|
gi 62362414  469 YELMRACWQWNPSDRPSFAEIHQAFETMFQ 498
Cdd:cd05047  241 YDLMRQCWREKPYERPSFAQILVSLNRMLE 270
PTKc_Tie1 cd05089
Catalytic domain of the Protein Tyrosine Kinase, Tie1; Protein Tyrosine Kinase (PTK) family; ...
235-498 1.73e-66

Catalytic domain of the Protein Tyrosine Kinase, Tie1; Protein Tyrosine Kinase (PTK) family; Tie1; catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie1 is a receptor tyr kinase (RTK) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie receptors are specifically expressed in endothelial cells and hematopoietic stem cells. No specific ligand has been identified for Tie1, although the angiopoietin, Ang-1, binds to Tie1 through integrins at high concentrations. In vivo studies of Tie1 show that it is critical in vascular development.


Pssm-ID: 270671 [Multi-domain]  Cd Length: 297  Bit Score: 226.42  E-value: 1.73e-66
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  235 WEmertDITMKHKLGGGQYGEVYEGVWKK--YSLTVAVKTLKEDTMEVE--EFLKEAAVMKEI-KHPNLVQLLGVCTREP 309
Cdd:cd05089    1 WE----DIKFEDVIGEGNFGQVIKAMIKKdgLKMNAAIKMLKEFASENDhrDFAGELEVLCKLgHHPNIINLLGACENRG 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  310 PFYIITEFMTYGNLLDYLRECNRQEVNAVV--------------LLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENH 375
Cdd:cd05089   77 YLYIAIEYAPYGNLLDFLRKSRVLETDPAFakehgtastltsqqLLQFASDVAKGMQYLSEKQFIHRDLAARNVLVGENL 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  376 LVKVADFGLSRlmTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKD 455
Cdd:cd05089  157 VSKIADFGLSR--GEEVYVKKTMGRLPVRWMAIESLNYSVYTTKSDVWSFGVLLWEIVSLGGTPYCGMTCAELYEKLPQG 234
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|...
gi 62362414  456 YRMERPEGCPEKVYELMRACWQWNPSDRPSFAEIHQAFETMFQ 498
Cdd:cd05089  235 YRMEKPRNCDDEVYELMRQCWRDRPYERPPFSQISVQLSRMLE 277
PTKc_HER2 cd05109
Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the ...
237-501 1.76e-66

Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. HER2 (ErbB2, HER2/neu) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. HER2 does not bind to any known EGFR subfamily ligands, but contributes to the kinase activity of all possible heterodimers. It acts as the preferred partner of other ligand-bound EGFR proteins and functions as a signal amplifier, with the HER2-HER3 heterodimer being the most potent pair in mitogenic signaling. HER2 plays an important role in cell development, proliferation, survival and motility. Overexpression of HER2 results in its activation and downstream signaling, even in the absence of ligand. HER2 overexpression, mainly due to gene amplification, has been shown in a variety of human cancers. Its role in breast cancer is especially well-documented. HER2 is up-regulated in about 25% of breast tumors and is associated with increases in tumor aggressiveness, recurrence and mortality. HER2 is a target for monoclonal antibodies and small molecule inhibitors, which are being developed as treatments for cancer. The first humanized antibody approved for clinical use is Trastuzumab (Herceptin), which is being used in combination with other therapies to improve the survival rates of patients with HER2-overexpressing breast cancer. The HER2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270684 [Multi-domain]  Cd Length: 279  Bit Score: 225.67  E-value: 1.76e-66
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  237 MERTDITMKHKLGGGQYGEVYEGVW----KKYSLTVAVKTLKEDTMEV--EEFLKEAAVMKEIKHPNLVQLLGVCTREPp 310
Cdd:cd05109    4 LKETELKKVKVLGSGAFGTVYKGIWipdgENVKIPVAIKVLRENTSPKanKEILDEAYVMAGVGSPYVCRLLGICLTST- 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  311 FYIITEFMTYGNLLDYLREcNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTG 390
Cdd:cd05109   83 VQLVTQLMPYGCLLDYVRE-NKDRIGSQDLLNWCVQIAKGMSYLEEVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDI 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  391 DTYTAHA-GAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVY 469
Cdd:cd05109  162 DETEYHAdGGKVPIKWMALESILHRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVY 241
                        250       260       270
                 ....*....|....*....|....*....|..
gi 62362414  470 ELMRACWQWNPSDRPSFAEIHQAFETMFQESS 501
Cdd:cd05109  242 MIMVKCWMIDSECRPRFRELVDEFSRMARDPS 273
S_TKc smart00220
Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or ...
243-491 2.15e-66

Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or threonine-specific kinase subfamily.


Pssm-ID: 214567 [Multi-domain]  Cd Length: 254  Bit Score: 224.33  E-value: 2.15e-66
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414     243 TMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM--EVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTY 320
Cdd:smart00220    2 EILEKLGEGSFGKVYLARDKKTGKLVAIKVIKKKKIkkDRERILREIKILKKLKHPNIVRLYDVFEDEDKLYLVMEYCEG 81
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414     321 GNLLDYLRECNRqeVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAH-AGA 399
Cdd:smart00220   82 GDLFDLLKKRGR--LSEDEARFYLRQILSALEYLHSKGIVHRDLKPENILLDEDGHVKLADFGLARQLDPGEKLTTfVGT 159
                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414     400 KFpikWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGID-LSQVYELLEKDYR--MERPEGCPEKVYELMRACW 476
Cdd:smart00220  160 PE---YMAPEVLLGKGYGKAVDIWSLGVILYELLT-GKPPFPGDDqLLELFKKIGKPKPpfPPPEWDISPEAKDLIRKLL 235
                           250
                    ....*....|....*
gi 62362414     477 QWNPSDRPSFAEIHQ 491
Cdd:smart00220  236 VKDPEKRLTAEEALQ 250
PTKc_FGFR1 cd05098
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs ...
230-501 4.93e-66

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Alternative splicing of FGFR1 transcripts produces a variety of isoforms, which are differentially expressed in cells. FGFR1 binds the ligands, FGF1 and FGF2, with high affinity and has also been reported to bind FGF4, FGF6, and FGF9. FGFR1 signaling is critical in the control of cell migration during embryo development. It promotes cell proliferation in fibroblasts. Nuclear FGFR1 plays a role in the regulation of transcription. Mutations, insertions or deletions of FGFR1 have been identified in patients with Kallman's syndrome (KS), an inherited disorder characterized by hypogonadotropic hypogonadism and loss of olfaction. Aberrant FGFR1 expression has been found in some human cancers including 8P11 myeloproliferative syndrome (EMS), breast cancer, and pancreatic adenocarcinoma. FGFR1 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270678 [Multi-domain]  Cd Length: 302  Bit Score: 225.28  E-value: 4.93e-66
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  230 PNYDKWEMERTDITMKHKLGGGQYGEVY--EGVW----KKYSLT-VAVKTLKEDTME--VEEFLKEAAVMKEI-KHPNLV 299
Cdd:cd05098    3 PEDPRWELPRDRLVLGKPLGEGCFGQVVlaEAIGldkdKPNRVTkVAVKMLKSDATEkdLSDLISEMEMMKMIgKHKNII 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  300 QLLGVCTREPPFYIITEFMTYGNLLDYLR-------------ECNRQEVNAVV-LLYMATQISSAMEYLEKKNFIHRDLA 365
Cdd:cd05098   83 NLLGACTQDGPLYVIVEYASKGNLREYLQarrppgmeycynpSHNPEEQLSSKdLVSCAYQVARGMEYLASKKCIHRDLA 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  366 ARNCLVGENHLVKVADFGLSR-LMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGID 444
Cdd:cd05098  163 ARNVLVTEDNVMKIADFGLARdIHHIDYYKKTTNGRLPVKWMAPEALFDRIYTHQSDVWSFGVLLWEIFTLGGSPYPGVP 242
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 62362414  445 LSQVYELLEKDYRMERPEGCPEKVYELMRACWQWNPSDRPSFAEIHQAFETMFQESS 501
Cdd:cd05098  243 VEELFKLLKEGHRMDKPSNCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRIVALTS 299
PTKc_TrkA cd05092
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze ...
237-490 1.14e-65

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkA is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkA to its ligand, nerve growth factor (NGF), results in receptor oligomerization and activation of the catalytic domain. TrkA is expressed mainly in neural-crest-derived sensory and sympathetic neurons of the peripheral nervous system, and in basal forebrain cholinergic neurons of the central nervous system. It is critical for neuronal growth, differentiation and survival. Alternative TrkA splicing has been implicated as a pivotal regulator of neuroblastoma (NB) behavior. Normal TrkA expression is associated with better NB prognosis, while the hypoxia-regulated TrkAIII splice variant promotes NB pathogenesis and progression. Aberrant TrkA expression has also been demonstrated in non-neural tumors including prostate, breast, lung, and pancreatic cancers. The TrkA subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270674 [Multi-domain]  Cd Length: 280  Bit Score: 223.30  E-value: 1.14e-65
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  237 MERTDITMKHKLGGGQYGEVYegVWKKYSLT-------VAVKTLKEDTMEV-EEFLKEAAVMKEIKHPNLVQLLGVCTRE 308
Cdd:cd05092    2 IKRRDIVLKWELGEGAFGKVF--LAECHNLLpeqdkmlVAVKALKEATESArQDFQREAELLTVLQHQHIVRFYGVCTEG 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  309 PPFYIITEFMTYGNLLDYLR----------ECNRQ---EVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENH 375
Cdd:cd05092   80 EPLIMVFEYMRHGDLNRFLRshgpdakildGGEGQapgQLTLGQMLQIASQIASGMVYLASLHFVHRDLATRNCLVGQGL 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  376 LVKVADFGLSR-LMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEK 454
Cdd:cd05092  160 VVKIGDFGMSRdIYSTDYYRVGGRTMLPIRWMPPESILYRKFTTESDIWSFGVVLWEIFTYGKQPWYQLSNTEAIECITQ 239
                        250       260       270
                 ....*....|....*....|....*....|....*.
gi 62362414  455 DYRMERPEGCPEKVYELMRACWQWNPSDRPSFAEIH 490
Cdd:cd05092  240 GRELERPRTCPPEVYAIMQGCWQREPQQRHSIKDIH 275
PTKc_VEGFR cd05054
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
234-489 1.71e-65

Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The VEGFR subfamily consists of VEGFR1 (Flt1), VEGFR2 (Flk1), VEGFR3 (Flt4), and similar proteins. VEGFR subfamily members are receptor PTKss (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. In VEGFR3, the fifth Ig-like domain is replaced by a disulfide bridge. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. There are five VEGF ligands in mammals, which bind, in an overlapping pattern to the three VEGFRs, which can form homo or heterodimers. VEGFRs regulate the cardiovascular system. They are critical for vascular development during embryogenesis and blood vessel formation in adults. They induce cellular functions common to other growth factor receptors such as cell migration, survival, and proliferation. The VEGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270647 [Multi-domain]  Cd Length: 298  Bit Score: 223.52  E-value: 1.71e-65
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  234 KWEMERTDITMKHKLGGGQYGEVYE----GVWKKYSL-TVAVKTLKEDTMEVEEflkeAAVMKEIK-------HPNLVQL 301
Cdd:cd05054    1 KWEFPRDRLKLGKPLGRGAFGKVIQasafGIDKSATCrTVAVKMLKEGATASEH----KALMTELKilihighHLNVVNL 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  302 LGVCTR-EPPFYIITEFMTYGNLLDYL---REC---NRQEVNAVV------------------LLYMATQISSAMEYLEK 356
Cdd:cd05054   77 LGACTKpGGPLMVIVEFCKFGNLSNYLrskREEfvpYRDKGARDVeeeedddelykepltledLICYSFQVARGMEFLAS 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  357 KNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGD-TYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATY 435
Cdd:cd05054  157 RKCIHRDLAARNILLSENNVVKICDFGLARDIYKDpDYVRKGDARLPLKWMAPESIFDKVYTTQSDVWSFGVLLWEIFSL 236
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 62362414  436 GMSPYPGIDLSQ-VYELLEKDYRMERPEGCPEKVYELMRACWQWNPSDRPSFAEI 489
Cdd:cd05054  237 GASPYPGVQMDEeFCRRLKEGTRMRAPEYTTPEIYQIMLDCWHGEPKERPTFSEL 291
PTKc_FGFR3 cd05100
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs ...
230-505 2.85e-65

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Many FGFR3 splice variants have been reported with the IIIb and IIIc isoforms being the predominant forms. FGFR3 IIIc is the isoform expressed in chondrocytes, the cells affected in dwarfism, while IIIb is expressed in epithelial cells. FGFR3 ligands include FGF1, FGF2, FGF4, FGF8, FGF9, and FGF23. It is a negative regulator of long bone growth. In the cochlear duct and in the lens, FGFR3 is involved in differentiation while it appears to have a role in cell proliferation in epithelial cells. Germline mutations in FGFR3 are associated with skeletal disorders including several forms of dwarfism. Some missense mutations are associated with multiple myeloma and carcinomas of the bladder and cervix. Overexpression of FGFR3 is found in thyroid carcinoma. FGFR3 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173652 [Multi-domain]  Cd Length: 334  Bit Score: 224.13  E-value: 2.85e-65
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  230 PNYDKWEMERTDITMKHKLGGGQYGEVYE----GVWKKYS---LTVAVKTLKEDTME--VEEFLKEAAVMKEI-KHPNLV 299
Cdd:cd05100    2 PADPKWELSRTRLTLGKPLGEGCFGQVVMaeaiGIDKDKPnkpVTVAVKMLKDDATDkdLSDLVSEMEMMKMIgKHKNII 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  300 QLLGVCTREPPFYIITEFMTYGNLLDYLRE------------CN--RQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLA 365
Cdd:cd05100   82 NLLGACTQDGPLYVLVEYASKGNLREYLRArrppgmdysfdtCKlpEEQLTFKDLVSCAYQVARGMEYLASQKCIHRDLA 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  366 ARNCLVGENHLVKVADFGLSR-LMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGID 444
Cdd:cd05100  162 ARNVLVTEDNVMKIADFGLARdVHNIDYYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIP 241
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 62362414  445 LSQVYELLEKDYRMERPEGCPEKVYELMRACWQWNPSDRPSFAEIHQAFETMFQESSiSDE 505
Cdd:cd05100  242 VEELFKLLKEGHRMDKPANCTHELYMIMRECWHAVPSQRPTFKQLVEDLDRVLTVTS-TDE 301
PTK_Ryk cd05043
Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase ...
239-491 5.94e-65

Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase (RTK) containing an extracellular region with two leucine-rich motifs, a transmembrane segment, and an intracellular inactive pseudokinase domain, which shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. The extracellular region of Ryk shows homology to the N-terminal domain of Wnt inhibitory factor-1 (WIF) and serves as the ligand (Wnt) binding domain of Ryk. Ryk is expressed in many different tissues both during development and in adults, suggesting a widespread function. It acts as a chemorepulsive axon guidance receptor of Wnt glycoproteins and is responsible for the establishment of axon tracts during the development of the central nervous system. In addition, studies in mice reveal that Ryk is essential in skeletal, craniofacial, and cardiac development. Thus, it appears Ryk is involved in signal transduction despite its lack of kinase activity. Ryk may function as an accessory protein that modulates the signals coming from catalytically active partner RTKs such as the Eph receptors. The Ryk subfamily is part of a larger superfamily that includes other pseudokinases and the catalytic domains of active kinases including PTKs, protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270639 [Multi-domain]  Cd Length: 279  Bit Score: 221.17  E-value: 5.94e-65
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  239 RTDITMKHKLGGGQYGEVYEGVW---KKYSLTVAVKTLKEDT--MEVEEFLKEAAVMKEIKHPNLVQLLGVCTR--EPPF 311
Cdd:cd05043    5 RERVTLSDLLQEGTFGRIFHGILrdeKGKEEEVLVKTVKDHAseIQVTMLLQESSLLYGLSHQNLLPILHVCIEdgEKPM 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  312 yIITEFMTYGNLLDYLREC------NRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLS 385
Cdd:cd05043   85 -VLYPYMNWGNLKLFLQQCrlseanNPQALSTQQLVHMALQIACGMSYLHRRGVIHKDIAARNCVIDDELQVKITDNALS 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  386 R-LMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGC 464
Cdd:cd05043  164 RdLFPMDYHCLGDNENRPIKWMSLESLVNKEYSSASDVWSFGVLLWELMTLGQTPYVEIDPFEMAAYLKDGYRLAQPINC 243
                        250       260
                 ....*....|....*....|....*..
gi 62362414  465 PEKVYELMRACWQWNPSDRPSFAEIHQ 491
Cdd:cd05043  244 PDELFAVMACCWALDPEERPSFQQLVQ 270
PTK_CCK4 cd05046
Pseudokinase domain of the Protein Tyrosine Kinase, Colon Carcinoma Kinase 4; CCK4, also ...
248-494 3.06e-64

Pseudokinase domain of the Protein Tyrosine Kinase, Colon Carcinoma Kinase 4; CCK4, also called protein tyrosine kinase 7 (PTK7), is an orphan receptor PTK (RTK) containing an extracellular region with seven immunoglobulin domains, a transmembrane segment, and an intracellular inactive pseudokinase domain, which shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. Studies in mice reveal that CCK4 is essential for neural development. Mouse embryos containing a truncated CCK4 die perinatally and display craniorachischisis, a severe form of neural tube defect. The mechanism of action of the CCK4 pseudokinase is still unknown. Other pseudokinases such as HER3 rely on the activity of partner RTKs. The CCK4 subfamily is part of a larger superfamily that includes other pseudokinases and the catalytic domains of active kinases including PTKs, protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133178 [Multi-domain]  Cd Length: 275  Bit Score: 219.26  E-value: 3.06e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLT-----VAVKTLKE--DTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTY 320
Cdd:cd05046   13 LGRGEFGEVFLAKAKGIEEEggetlVLVKALQKtkDENLQSEFRRELDMFRKLSHKNVVRLLGLCREAEPHYMILEYTDL 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  321 GNLLDYLR-------ECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTY 393
Cdd:cd05046   93 GDLKQFLRatkskdeKLKPPPLSTKQKVALCTQIALGMDHLSNARFVHRDLAARNCLVSSQREVKVSLLSLSKDVYNSEY 172
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  394 TAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGI-DLSQVYELLEKDYRMERPEGCPEKVYELM 472
Cdd:cd05046  173 YKLRNALIPLRWLAPEAVQEDDFSTKSDVWSFGVLMWEVFTQGELPFYGLsDEEVLNRLQAGKLELPVPEGCPSRLYKLM 252
                        250       260
                 ....*....|....*....|..
gi 62362414  473 RACWQWNPSDRPSFAEIHQAFE 494
Cdd:cd05046  253 TRCWAVNPKDRPSFSELVSALG 274
PTKc_Ror1 cd05090
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
236-490 3.56e-64

Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Ror kinases are expressed in many tissues during development. Avian Ror1 was found to be involved in late limb development. Studies in mice reveal that Ror1 is important in the regulation of neurite growth in central neurons, as well as in respiratory development. Loss of Ror1 also enhances the heart and skeletal abnormalities found in Ror2-deficient mice. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The Ror1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270672 [Multi-domain]  Cd Length: 283  Bit Score: 219.11  E-value: 3.56e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  236 EMERTDITMKHKLGGGQYGEVYEGVW----KKYSLTVAVKTLKE--DTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREP 309
Cdd:cd05090    1 ELPLSAVRFMEELGECAFGKIYKGHLylpgMDHAQLVAIKTLKDynNPQQWNEFQQEASLMTELHHPNIVCLLGVVTQEQ 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  310 PFYIITEFMTYGNLLDYL--RE------CNRQEVNAVV-------LLYMATQISSAMEYLEKKNFIHRDLAARNCLVGEN 374
Cdd:cd05090   81 PVCMLFEFMNQGDLHEFLimRSphsdvgCSSDEDGTVKssldhgdFLHIAIQIAAGMEYLSSHFFVHKDLAARNILVGEQ 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  375 HLVKVADFGLSR-LMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLE 453
Cdd:cd05090  161 LHVKISDLGLSReIYSSDYYRVQNKSLLPIRWMPPEAIMYGKFSSDSDIWSFGVVLWEIFSFGLQPYYGFSNQEVIEMVR 240
                        250       260       270
                 ....*....|....*....|....*....|....*..
gi 62362414  454 KDYRMERPEGCPEKVYELMRACWQWNPSDRPSFAEIH 490
Cdd:cd05090  241 KRQLLPCSEDCPPRMYSLMTECWQEIPSRRPRFKDIH 277
PTKc_IGF-1R cd05062
Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs ...
235-489 6.89e-64

Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. IGF-1R is a receptor PTK (RTK) that is composed of two alphabeta heterodimers. Binding of the ligand (IGF-1 or IGF-2) to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, which stimulates downstream kinase activities and biological function. IGF-1R signaling is important in the differentiation, growth, and survival of normal cells. In cancer cells, where it is frequently overexpressed, IGF-1R is implicated in proliferation, the suppression of apoptosis, invasion, and metastasis. IGF-1R is being developed as a therapeutic target in cancer treatment. The IGF-1R subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133193 [Multi-domain]  Cd Length: 277  Bit Score: 218.36  E-value: 6.89e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  235 WEMERTDITMKHKLGGGQYGEVYEGVWK-----KYSLTVAVKTLKEDTMEVE--EFLKEAAVMKEIKHPNLVQLLGVCTR 307
Cdd:cd05062    1 WEVAREKITMSRELGQGSFGMVYEGIAKgvvkdEPETRVAIKTVNEAASMREriEFLNEASVMKEFNCHHVVRLLGVVSQ 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  308 EPPFYIITEFMTYGNLLDYLRECNRQEVNAVV--------LLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKV 379
Cdd:cd05062   81 GQPTLVIMELMTRGDLKSYLRSLRPEMENNPVqappslkkMIQMAGEIADGMAYLNANKFVHRDLAARNCMVAEDFTVKI 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  380 ADFGLSR-LMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRM 458
Cdd:cd05062  161 GDFGMTRdIYETDYYRKGGKGLLPVRWMSPESLKDGVFTTYSDVWSFGVVLWEIATLAEQPYQGMSNEQVLRFVMEGGLL 240
                        250       260       270
                 ....*....|....*....|....*....|.
gi 62362414  459 ERPEGCPEKVYELMRACWQWNPSDRPSFAEI 489
Cdd:cd05062  241 DKPDNCPDMLFELMRMCWQYNPKMRPSFLEI 271
PTKc_Zap-70 cd05115
Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs ...
247-497 1.85e-63

Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Zap-70 is a cytoplasmic (or nonreceptor) PTK containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. Zap-70 is primarily expressed in T-cells and NK cells, and is a crucial component in T-cell receptor (TCR) signaling. Zap-70 binds the phosphorylated ITAM (immunoreceptor tyr activation motif) sequences of the activated TCR zeta-chain through its SH2 domains, leading to its phosphorylation and activation. It then phosphorylates target proteins, which propagate the signals to downstream pathways. Zap-70 is hardly detected in normal peripheral B-cells, but is present in some B-cell malignancies. It is used as a diagnostic marker for chronic lymphocytic leukemia (CLL) as it is associated with the more aggressive subtype of the disease. The Zap-70 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270686 [Multi-domain]  Cd Length: 269  Bit Score: 216.74  E-value: 1.85e-63
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWK--KYSLTVAVKTLKEDTMEV--EEFLKEAAVMKEIKHPNLVQLLGVCTREPpFYIITEFMTYGN 322
Cdd:cd05115   11 ELGSGNFGCVKKGVYKmrKKQIDVAIKVLKQGNEKAvrDEMMREAQIMHQLDNPYIVRMIGVCEAEA-LMLVMEMASGGP 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLrECNRQEV---NAVVLLYmatQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDT--YTAHA 397
Cdd:cd05115   90 LNKFL-SGKKDEItvsNVVELMH---QVSMGMKYLEEKNFVHRDLAARNVLLVNQHYAKISDFGLSKALGADDsyYKARS 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  398 GAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQ 477
Cdd:cd05115  166 AGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEAFSYGQKPYKKMKGPEVMSFIEQGKRMDCPAECPPEMYALMSDCWI 245
                        250       260
                 ....*....|....*....|
gi 62362414  478 WNPSDRPSFAEIHQAFETMF 497
Cdd:cd05115  246 YKWEDRPNFLTVEQRMRTYY 265
PTKc_DDR1 cd05096
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze ...
236-490 6.46e-63

Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR1 is a receptor PTK (RTK) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDR1 results in a slow but sustained receptor activation. DDR1 binds to all collagens tested to date (types I-IV). It is widely expressed in many tissues. It is abundant in the brain and is also found in keratinocytes, colonic mucosa epithelium, lung epithelium, thyroid follicles, and the islets of Langerhans. During embryonic development, it is found in the developing neuroectoderm. DDR1 is a key regulator of cell morphogenesis, differentiation and proliferation. It is important in the development of the mammary gland, the vasculator and the kidney. DDR1 is also found in human leukocytes, where it facilitates cell adhesion, migration, maturation, and cytokine production. The DDR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133227 [Multi-domain]  Cd Length: 304  Bit Score: 216.34  E-value: 6.46e-63
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  236 EMERTDITMKHKLGGGQYGEVYE----------------GVWKKYSLTVAVKTLKEDTME--VEEFLKEAAVMKEIKHPN 297
Cdd:cd05096    1 KFPRGHLLFKEKLGEGQFGEVHLcevvnpqdlptlqfpfNVRKGRPLLVAVKILRPDANKnaRNDFLKEVKILSRLKDPN 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  298 LVQLLGVCTREPPFYIITEFMTYGNLLDYL--RECNRQEVNAV---------------VLLYMATQISSAMEYLEKKNFI 360
Cdd:cd05096   81 IIRLLGVCVDEDPLCMITEYMENGDLNQFLssHHLDDKEENGNdavppahclpaisysSLLHVALQIASGMKYLSSLNFV 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  361 HRDLAARNCLVGENHLVKVADFGLSR-LMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMS- 438
Cdd:cd05096  161 HRDLATRNCLVGENLTIKIADFGMSRnLYAGDYYRIQGRAVLPIRWMAWECILMGKFTTASDVWAFGVTLWEILMLCKEq 240
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 62362414  439 PYPGIDLSQVYELLEKDYR-------MERPEGCPEKVYELMRACWQWNPSDRPSFAEIH 490
Cdd:cd05096  241 PYGELTDEQVIENAGEFFRdqgrqvyLFRPPPCPQGLYELMLQCWSRDCRERPSFSDIH 299
PTKc_HER4 cd05110
Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the ...
237-499 3.20e-61

Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. HER4 (ErbB4) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Ligands that bind HER4 fall into two groups, the neuregulins (or heregulins) and some EGFR (HER1) ligands including betacellulin, HBEGF, and epiregulin. All four neuregulins (NRG1-4) interact with HER4. Upon ligand binding, HER4 forms homo- or heterodimers with other HER proteins. HER4 is essential in embryonic development. It is implicated in mammary gland, cardiac, and neural development. As a postsynaptic receptor of NRG1, HER4 plays an important role in synaptic plasticity and maturation. The impairment of NRG1/HER4 signaling may contribute to schizophrenia. The HER4 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173655 [Multi-domain]  Cd Length: 303  Bit Score: 211.46  E-value: 3.20e-61
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  237 MERTDITMKHKLGGGQYGEVYEGVW----KKYSLTVAVKTLKEDTMEVE--EFLKEAAVMKEIKHPNLVQLLGVCTrEPP 310
Cdd:cd05110    4 LKETELKRVKVLGSGAFGTVYKGIWvpegETVKIPVAIKILNETTGPKAnvEFMDEALIMASMDHPHLVRLLGVCL-SPT 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  311 FYIITEFMTYGNLLDYLREcNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTG 390
Cdd:cd05110   83 IQLVTQLMPHGCLLDYVHE-HKDNIGSQLLLNWCVQIAKGMMYLEERRLVHRDLAARNVLVKSPNHVKITDFGLARLLEG 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  391 DTYTAHA-GAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVY 469
Cdd:cd05110  162 DEKEYNAdGGKMPIKWMALECIHYRKFTHQSDVWSYGVTIWELMTFGGKPYDGIPTREIPDLLEKGERLPQPPICTIDVY 241
                        250       260       270
                 ....*....|....*....|....*....|
gi 62362414  470 ELMRACWQWNPSDRPSFAEIHQAFETMFQE 499
Cdd:cd05110  242 MVMVKCWMIDADSRPKFKELAAEFSRMARD 271
SH2_ABL cd09935
Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ...
123-216 4.23e-61

Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ABL-family proteins are highly conserved tyrosine kinases. Each ABL protein contains an SH3-SH2-TK (Src homology 3-Src homology 2-tyrosine kinase) domain cassette, which confers autoregulated kinase activity and is common among nonreceptor tyrosine kinases. Several types of posttranslational modifications control ABL catalytic activity, subcellular localization, and stability, with consequences for both cytoplasmic and nuclear ABL functions. Binding partners provide additional regulation of ABL catalytic activity, substrate specificity, and downstream signaling. By combining this cassette with actin-binding and -bundling domain, ABL proteins are capable of connecting phosphoregulation with actin-filament reorganization. Vertebrate paralogs, ABL1 and ABL2, have evolved to perform specialized functions. ABL1 includes nuclear localization signals and a DNA binding domain which is used to mediate DNA damage-repair functions, while ABL2 has additional binding capacity for actin and for microtubules to enhance its cytoskeletal remodeling functions. SH2 is involved in several autoinhibitory mechanism that constrain the enzymatic activity of the ABL-family kinases. In one mechanism SH2 and SH3 cradle the kinase domain while a cap sequence stabilizes the inactive conformation resulting in a locked inactive state. Another involves phosphatidylinositol 4,5-bisphosphate (PIP2) which binds the SH2 domain through residues normally required for phosphotyrosine binding in the linker segment between the SH2 and kinase domains. The SH2 domain contributes to ABL catalytic activity and target site specificity. It is thought that the ABL catalytic site and SH2 pocket have coevolved to recognize the same sequences. Recent work now supports a hierarchical processivity model in which the substrate target site most compatible with ABL kinase domain preferences is phosphorylated with greatest efficiency. If this site is compatible with the ABL SH2 domain specificity, it will then reposition and dock in the SH2 pocket. This mechanism also explains how ABL kinases phosphorylates poor targets on the same substrate if they are properly positioned and how relatively poor substrate proteins might be recruited to ABL through a complex with strong substrates that can also dock with the SH2 pocket. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198189  Cd Length: 94  Bit Score: 203.00  E-value: 4.23e-61
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  123 EKHSWYHGPVSRNAAEYLLSSGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTASDGKLYVSSESRFNTLAELVHHH 202
Cdd:cd09935    1 EKHSWYHGPISRNAAEYLLSSGINGSFLVRESESSPGQYSISLRYDGRVYHYRISEDSDGKVYVTQEHRFNTLAELVHHH 80
                         90
                 ....*....|....
gi 62362414  203 STVADGLITTLHYP 216
Cdd:cd09935   81 SKNADGLITTLRYP 94
PTKc_TrkC cd05094
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze ...
237-496 1.03e-60

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkC is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkC to its ligand, neurotrophin 3 (NT3), results in receptor oligomerization and activation of the catalytic domain. TrkC is broadly expressed in the nervous system and in some non-neural tissues including the developing heart. NT3/TrkC signaling plays an important role in the innervation of the cardiac conducting system and the development of smooth muscle cells. Mice deficient with NT3 and TrkC have multiple heart defects. NT3/TrkC signaling is also critical for the development and maintenance of enteric neurons that are important for the control of gut peristalsis. The TrkC subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270676 [Multi-domain]  Cd Length: 287  Bit Score: 209.48  E-value: 1.03e-60
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  237 MERTDITMKHKLGGGQYGEV-----YEGVWKKYSLTVAVKTLKEDTMEV-EEFLKEAAVMKEIKHPNLVQLLGVCTREPP 310
Cdd:cd05094    2 IKRRDIVLKRELGEGAFGKVflaecYNLSPTKDKMLVAVKTLKDPTLAArKDFQREAELLTNLQHDHIVKFYGVCGDGDP 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  311 FYIITEFMTYGNLLDYLRE--------------CNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHL 376
Cdd:cd05094   82 LIMVFEYMKHGDLNKFLRAhgpdamilvdgqprQAKGELGLSQMLHIATQIASGMVYLASQHFVHRDLATRNCLVGANLL 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  377 VKVADFGLSR-LMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKD 455
Cdd:cd05094  162 VKIGDFGMSRdVYSTDYYRVGGHTMLPIRWMPPESIMYRKFTTESDVWSFGVILWEIFTYGKQPWFQLSNTEVIECITQG 241
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|.
gi 62362414  456 YRMERPEGCPEKVYELMRACWQWNPSDRPSFAEIHQAFETM 496
Cdd:cd05094  242 RVLERPRVCPKEVYDIMLGCWQREPQQRLNIKEIYKILHAL 282
PTKc_CSF-1R cd05106
Catalytic domain of the Protein Tyrosine Kinase, Colony-Stimulating Factor-1 Receptor; PTKs ...
230-496 1.42e-60

Catalytic domain of the Protein Tyrosine Kinase, Colony-Stimulating Factor-1 Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. CSF-1R, also called c-Fms, is a member of the Platelet Derived Growth Factor Receptor (PDGFR) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of CSF-1R to its ligand, CSF-1, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. CSF-1R signaling is critical in the regulation of macrophages and osteoclasts. It leads to increases in gene transcription and protein translation, and induces cytoskeletal remodeling. CSF-1R signaling leads to a variety of cellular responses including survival, proliferation, and differentiation of target cells. It plays an important role in innate immunity, tissue development and function, and the pathogenesis of some diseases including atherosclerosis and cancer. CSF-1R signaling is also implicated in mammary gland development during pregnancy and lactation. Aberrant CSF-1/CSF-1R expression correlates with tumor cell invasiveness, poor clinical prognosis, and bone metastasis in breast cancer. Although the structure of the human CSF-1R catalytic domain is known, it is excluded from this specific alignment model because it contains a deletion in its sequence. The CSF-1R subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133237 [Multi-domain]  Cd Length: 374  Bit Score: 212.40  E-value: 1.42e-60
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  230 PNYDKWEMERTDITMKHKLGGGQYGEVYE----GVWKKYS-LTVAVKTLKE--DTMEVEEFLKEAAVMKEI-KHPNLVQL 301
Cdd:cd05106   28 PYNEKWEFPRDNLQFGKTLGAGAFGKVVEatafGLGKEDNvLRVAVKMLKAsaHTDEREALMSELKILSHLgQHKNIVNL 107
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  302 LGVCTREPPFYIITEFMTYGNLLDYLRECNRQEVNAVV------------------------------------------ 339
Cdd:cd05106  108 LGACTHGGPVLVITEYCCYGDLLNFLRKKAETFLNFVMalpeisetssdyknitlekkyirsdsgfssqgsdtyvemrpv 187
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  340 --------------------------LLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR-LMTGDT 392
Cdd:cd05106  188 sssssqssdskdeedtedswpldlddLLRFSSQVAQGMDFLASKNCIHRDVAARNVLLTDGRVAKICDFGLARdIMNDSN 267
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  393 YTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDL-SQVYELLEKDYRMERPEGCPEKVYEL 471
Cdd:cd05106  268 YVVKGNARLPVKWMAPESIFDCVYTVQSDVWSYGILLWEIFSLGKSPYPGILVnSKFYKMVKRGYQMSRPDFAPPEIYSI 347
                        330       340
                 ....*....|....*....|....*
gi 62362414  472 MRACWQWNPSDRPSFAEIHQAFETM 496
Cdd:cd05106  348 MKMCWNLEPTERPTFSQISQLIQRQ 372
PTKc_TrkB cd05093
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze ...
237-502 9.07e-60

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkB is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkB to its ligands, brain-derived neurotrophic factor (BDNF) or neurotrophin 4 (NT4), results in receptor oligomerization and activation of the catalytic domain. TrkB is broadly expressed in the nervous system and in some non-neural tissues. It plays important roles in cell proliferation, differentiation, and survival. BDNF/Trk signaling plays a key role in regulating activity-dependent synaptic plasticity. TrkB also contributes to protection against gp120-induced neuronal cell death. TrkB overexpression is associated with poor prognosis in neuroblastoma (NB) and other human cancers. It acts as a suppressor of anoikis (detachment-induced apoptosis) and contributes to tumor metastasis. The TrkB subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270675 [Multi-domain]  Cd Length: 288  Bit Score: 206.81  E-value: 9.07e-60
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  237 MERTDITMKHKLGGGQYGEV-----YEGVWKKYSLTVAVKTLKEDTMEV-EEFLKEAAVMKEIKHPNLVQLLGVCTREPP 310
Cdd:cd05093    2 IKRHNIVLKRELGEGAFGKVflaecYNLCPEQDKILVAVKTLKDASDNArKDFHREAELLTNLQHEHIVKFYGVCVEGDP 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  311 FYIITEFMTYGNLLDYLR----------ECNR-QEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKV 379
Cdd:cd05093   82 LIMVFEYMKHGDLNKFLRahgpdavlmaEGNRpAELTQSQMLHIAQQIAAGMVYLASQHFVHRDLATRNCLVGENLLVKI 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  380 ADFGLSR-LMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRM 458
Cdd:cd05093  162 GDFGMSRdVYSTDYYRVGGHTMLPIRWMPPESIMYRKFTTESDVWSLGVVLWEIFTYGKQPWYQLSNNEVIECITQGRVL 241
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....
gi 62362414  459 ERPEGCPEKVYELMRACWQWNPSDRPSFAEIHQAFETMFQESSI 502
Cdd:cd05093  242 QRPRTCPKEVYDLMLGCWQREPHMRLNIKEIHSLLQNLAKASPV 285
PTKc_Tie2 cd05088
Catalytic domain of the Protein Tyrosine Kinase, Tie2; PTKs catalyze the transfer of the ...
237-499 1.77e-59

Catalytic domain of the Protein Tyrosine Kinase, Tie2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie2 is a receptor PTK (RTK) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie2 is expressed mainly in endothelial cells and hematopoietic stem cells. It is also found in a subset of tumor-associated monocytes and eosinophils. The angiopoietins (Ang-1 to Ang-4) serve as ligands for Tie2. The binding of Ang-1 to Tie2 leads to receptor autophosphorylation and activation, promoting cell migration and survival. In contrast, Ang-2 binding to Tie2 does not result in the same response, suggesting that Ang-2 may function as an antagonist. Tie2 signaling plays key regulatory roles in vascular integrity and quiescence, and in inflammation. The Tie2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133219 [Multi-domain]  Cd Length: 303  Bit Score: 206.77  E-value: 1.77e-59
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  237 MERTDITMKHKLGGGQYGEVYEGVWKKYSLTV--AVKTLKEDTMEVE--EFLKEAAVMKEI-KHPNLVQLLGVCTREPPF 311
Cdd:cd05088    4 LEWNDIKFQDVIGEGNFGQVLKARIKKDGLRMdaAIKRMKEYASKDDhrDFAGELEVLCKLgHHPNIINLLGACEHRGYL 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  312 YIITEFMTYGNLLDYLRECNRQEVNAVV--------------LLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLV 377
Cdd:cd05088   84 YLAIEYAPHGNLLDFLRKSRVLETDPAFaianstastlssqqLLHFAADVARGMDYLSQKQFIHRDLAARNILVGENYVA 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  378 KVADFGLSRlmTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYR 457
Cdd:cd05088  164 KIADFGLSR--GQEVYVKKTMGRLPVRWMAIESLNYSVYTTNSDVWSYGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYR 241
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 62362414  458 MERPEGCPEKVYELMRACWQWNPSDRPSFAEIHQAFETMFQE 499
Cdd:cd05088  242 LEKPLNCDDEVYDLMRQCWREKPYERPSFAQILVSLNRMLEE 283
PTKc_Jak2_rpt2 cd14205
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the ...
246-489 1.94e-58

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak2 is widely expressed in many tissues and is essential for the signaling of hormone-like cytokines such as growth hormone, erythropoietin, thrombopoietin, and prolactin, as well as some IFNs and cytokines that signal through the IL-3 and gp130 receptors. Disruption of Jak2 in mice results in an embryonic lethal phenotype with multiple defects including erythropoietic and cardiac abnormalities. It is the only Jak gene that results in a lethal phenotype when disrupted in mice. A mutation in the pseudokinase domain of Jak2, V617F, is present in many myeloproliferative diseases, including almost all patients with polycythemia vera, and 50% of patients with essential thrombocytosis and myelofibrosis. Jak2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271107 [Multi-domain]  Cd Length: 284  Bit Score: 202.94  E-value: 1.94e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  246 HKLGGGQYGEV----YEGVWKKYSLTVAVKTLKEDTME-VEEFLKEAAVMKEIKHPNLVQLLGVCTR--EPPFYIITEFM 318
Cdd:cd14205   10 QQLGKGNFGSVemcrYDPLQDNTGEVVAVKKLQHSTEEhLRDFEREIEILKSLQHDNIVKYKGVCYSagRRNLRLIMEYL 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  319 TYGNLLDYLREcNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDT--YTAH 396
Cdd:cd14205   90 PYGSLRDYLQK-HKERIDHIKLLQYTSQICKGMEYLGTKRYIHRDLATRNILVENENRVKIGDFGLTKVLPQDKeyYKVK 168
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  397 AGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATY---GMSPyPGIDLSQV-------------YELLEKDYRMER 460
Cdd:cd14205  169 EPGESPIFWYAPESLTESKFSVASDVWSFGVVLYELFTYiekSKSP-PAEFMRMIgndkqgqmivfhlIELLKNNGRLPR 247
                        250       260
                 ....*....|....*....|....*....
gi 62362414  461 PEGCPEKVYELMRACWQWNPSDRPSFAEI 489
Cdd:cd14205  248 PDGCPDEIYMIMTECWNNNVNQRPSFRDL 276
PTKc_Ror2 cd05091
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
236-495 2.84e-57

Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Ror2 plays important roles in skeletal and heart formation. Ror2-deficient mice show widespread bone abnormalities, ventricular defects in the heart, and respiratory dysfunction. Mutations in human Ror2 result in two different bone development genetic disorders, recessive Robinow syndrome and brachydactyly type B. Ror2 is also implicated in neural development. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The Ror2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270673 [Multi-domain]  Cd Length: 284  Bit Score: 199.47  E-value: 2.84e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  236 EMERTDITMKHKLGGGQYGEVYEG-----VWKKYSLTVAVKTLKeDTMEV---EEFLKEAAVMKEIKHPNLVQLLGVCTR 307
Cdd:cd05091    2 EINLSAVRFMEELGEDRFGKVYKGhlfgtAPGEQTQAVAIKTLK-DKAEGplrEEFRHEAMLRSRLQHPNIVCLLGVVTK 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  308 EPPFYIITEFMTYGNLLDYL--------------RECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGE 373
Cdd:cd05091   81 EQPMSMIFSYCSHGDLHEFLvmrsphsdvgstddDKTVKSTLEPADFLHIVTQIAAGMEYLSSHHVVHKDLATRNVLVFD 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  374 NHLVKVADFGLSR-LMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELL 452
Cdd:cd05091  161 KLNVKISDLGLFReVYAADYYKLMGNSLLPIRWMSPEAIMYGKFSIDSDIWSYGVVLWEVFSYGLQPYCGYSNQDVIEMI 240
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|...
gi 62362414  453 EKDYRMERPEGCPEKVYELMRACWQWNPSDRPSFAEIHQAFET 495
Cdd:cd05091  241 RNRQVLPCPDDCPAWVYTLMLECWNEFPSRRPRFKDIHSRLRT 283
PTKc_EphR_A10 cd05064
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the ...
236-496 2.92e-57

Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EphA10, which contains an inactive tyr kinase domain, may function to attenuate signals of co-clustered active receptors. EphA10 is mainly expressed in the testis. Ephrin/EphR interaction results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. EphRs comprise the largest subfamily of receptor tyr kinases (RTKs). In general, class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). The EphA10 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133195 [Multi-domain]  Cd Length: 266  Bit Score: 198.99  E-value: 2.92e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  236 EMERTDITMKHKLGGGQYGEVYEGVWK---KYSLTVAVKTLKEDTMEVEE--FLKEAAVMKEIKHPNLVQLLGVCTREPP 310
Cdd:cd05064    1 ELDNKSIKIERILGTGRFGELCRGCLKlpsKRELPVAIHTLRAGCSDKQRrgFLAEALTLGQFDHSNIVRLEGVITRGNT 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  311 FYIITEFMTYGNLLDYLRECNRQeVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFG-LSRLMT 389
Cdd:cd05064   81 MMIVTEYMSNGALDSFLRKHEGQ-LVAGQLMGMLPGLASGMKYLSEMGYVHKGLAAHKVLVNSDLVCKISGFRrLQEDKS 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  390 GDTYTAHAGaKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVY 469
Cdd:cd05064  160 EAIYTTMSG-KSPVLWAAPEAIQYHHFSSASDVWSFGIVMWEVMSYGERPYWDMSGQDVIKAVEDGFRLPAPRNCPNLLH 238
                        250       260
                 ....*....|....*....|....*..
gi 62362414  470 ELMRACWQWNPSDRPSFAEIHQAFETM 496
Cdd:cd05064  239 QLMLDCWQKERGERPRFSQIHSILSKM 265
PTKc_Kit cd05104
Catalytic domain of the Protein Tyrosine Kinase, Kit; PTKs catalyze the transfer of the ...
232-494 3.58e-57

Catalytic domain of the Protein Tyrosine Kinase, Kit; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Kit is important in the development of melanocytes, germ cells, mast cells, hematopoietic stem cells, the interstitial cells of Cajal, and the pacemaker cells of the GI tract. Kit signaling is involved in major cellular functions including cell survival, proliferation, differentiation, adhesion, and chemotaxis. Mutations in Kit, which result in constitutive ligand-independent activation, are found in human cancers such as gastrointestinal stromal tumor (GIST) and testicular germ cell tumor (TGCT). The aberrant expression of Kit and/or SCF is associated with other tumor types such as systemic mastocytosis and cancers of the breast, neurons, lung, prostate, colon, and rectum. Although the structure of the human Kit catalytic domain is known, it is excluded from this specific alignment model because it contains a deletion in its sequence. Kit is a member of the Platelet Derived Growth Factor Receptor (PDGFR) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of Kit to its ligand, the stem-cell factor (SCF), leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. The Kit subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270682 [Multi-domain]  Cd Length: 375  Bit Score: 202.44  E-value: 3.58e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  232 YD-KWEMERTDITMKHKLGGGQYGEVYE----GVWKKYS-LTVAVKTLKEDTMEVEeflKEAaVMKEIK-------HPNL 298
Cdd:cd05104   26 YDhKWEFPRDRLRFGKTLGAGAFGKVVEatayGLAKADSaMTVAVKMLKPSAHSTE---REA-LMSELKvlsylgnHINI 101
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  299 VQLLGVCTREPPFYIITEFMTYGNLLDYLRE------CNRQEVNAVVLLY------------------------------ 342
Cdd:cd05104  102 VNLLGACTVGGPTLVITEYCCYGDLLNFLRRkrdsfiCPKFEDLAEAALYrnllhqremacdslneymdmkpsvsyvvpt 181
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  343 -------------------------------------MATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLS 385
Cdd:cd05104  182 kadkrrgvrsgsyvdqdvtseileedelaldtedllsFSYQVAKGMEFLASKNCIHRDLAARNILLTHGRITKICDFGLA 261
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  386 RLMTGDT-YTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDL-SQVYELLEKDYRMERPEG 463
Cdd:cd05104  262 RDIRNDSnYVVKGNARLPVKWMAPESIFECVYTFESDVWSYGILLWEIFSLGSSPYPGMPVdSKFYKMIKEGYRMDSPEF 341
                        330       340       350
                 ....*....|....*....|....*....|.
gi 62362414  464 CPEKVYELMRACWQWNPSDRPSFAEIHQAFE 494
Cdd:cd05104  342 APSEMYDIMRSCWDADPLKRPTFKQIVQLIE 372
PKc cd00180
Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group ...
248-489 1.38e-56

Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. PKs make up a large family of serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins. Majority of protein phosphorylation occurs on serine residues while only 1% occurs on tyrosine residues. Protein phosphorylation is a mechanism by which a wide variety of cellular proteins, such as enzymes and membrane channels, are reversibly regulated in response to certain stimuli. PKs often function as components of signal transduction pathways in which one kinase activates a second kinase, which in turn, may act on other kinases; this sequential action transmits a signal from the cell surface to target proteins, which results in cellular responses. The PK family is one of the largest known protein families with more than 100 homologous yeast enzymes and more than 500 human proteins. A fraction of PK family members are pseudokinases that lack crucial residues for catalytic activity. The mutiplicity of kinases allows for specific regulation according to substrate, tissue distribution, and cellular localization. PKs regulate many cellular processes including proliferation, division, differentiation, motility, survival, metabolism, cell-cycle progression, cytoskeletal rearrangement, immunity, and neuronal functions. Many kinases are implicated in the development of various human diseases including different types of cancer. The PK family is part of a larger superfamily that includes the catalytic domains of RIO kinases, aminoglycoside phosphotransferase, choline kinase, phosphoinositide 3-kinase (PI3K), and actin-fragmin kinase.


Pssm-ID: 270622 [Multi-domain]  Cd Length: 215  Bit Score: 194.80  E-value: 1.38e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLK--EDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLD 325
Cdd:cd00180    1 LGKGSFGKVYKARDKETGKKVAVKVIPkeKLKKLLEELLREIEILKKLNHPNIVKLYDVFETENFLYLVMEYCEGGSLKD 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  326 YLRECNRQeVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMT-GDTYTAHAGAKFPIK 404
Cdd:cd00180   81 LLKENKGP-LSEEEALSILRQLLSALEYLHSNGIIHRDLKPENILLDSDGTVKLADFGLAKDLDsDDSLLKTTGGTTPPY 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  405 WTAPESLAYNKFSIKSDVWAFGVLLWEIatygmspypgidlsqvyellekdyrmerpegcpEKVYELMRACWQWNPSDRP 484
Cdd:cd00180  160 YAPPELLGGRYYGPKVDIWSLGVILYEL---------------------------------EELKDLIRRMLQYDPKKRP 206

                 ....*
gi 62362414  485 SFAEI 489
Cdd:cd00180  207 SAKEL 211
PTKc_VEGFR3 cd05102
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; ...
234-500 7.78e-55

Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR3 (or Flt4) preferentially binds the ligands VEGFC and VEGFD. VEGFR3 is essential for lymphatic endothelial cell (EC) development and function. It has been shown to regulate adaptive immunity during corneal transplantation. VEGFR3 is upregulated on blood vascular ECs in pathological conditions such as vascular tumors and the periphery of solid tumors. It plays a role in cancer progression and lymph node metastasis. Missense mutations in the VEGFR3 gene are associated with primary human lymphedema. VEGFR3 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. In VEGFR3, the fifth Ig-like domain is replaced by a disulfide bridge. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270680 [Multi-domain]  Cd Length: 336  Bit Score: 194.43  E-value: 7.78e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  234 KWEMERTDITMKHKLGGGQYGEVYE----GVWKKYSL-TVAVKTLKEDTMEVEEflkeAAVMKEIK-------HPNLVQL 301
Cdd:cd05102    1 QWEFPRDRLRLGKVLGHGAFGKVVEasafGIDKSSSCeTVAVKMLKEGATASEH----KALMSELKilihignHLNVVNL 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  302 LGVCTR-EPPFYIITEFMTYGNLLDYLRECN-------------RQEVNAVV---------------------------- 339
Cdd:cd05102   77 LGACTKpNGPLMVIVEFCKYGNLSNFLRAKRegfspyrersprtRSQVRSMVeavradrrsrqgsdrvasftestsstnq 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  340 -----------------LLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGD-TYTAHAGAKF 401
Cdd:cd05102  157 prqevddlwqspltmedLICYSFQVARGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLARDIYKDpDYVRKGSARL 236
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  402 PIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVY-ELLEKDYRMERPEGCPEKVYELMRACWQWNP 480
Cdd:cd05102  237 PLKWMAPESIFDKVYTTQSDVWSFGVLLWEIFSLGASPYPGVQINEEFcQRLKDGTRMRAPEYATPEIYRIMLSCWHGDP 316
                        330       340
                 ....*....|....*....|
gi 62362414  481 SDRPSFAEIHQAFETMFQES 500
Cdd:cd05102  317 KERPTFSDLVEILGDLLQEN 336
PTKc_VEGFR1 cd14207
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
234-489 8.55e-55

Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR1 (or Flt1) binds VEGFA, VEGFB, and placenta growth factor (PLGF). It regulates monocyte and macrophage migration, vascular permeability, haematopoiesis, and the recruitment of haematopietic progenitor cells from the bone marrow. VEGFR1 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271109 [Multi-domain]  Cd Length: 340  Bit Score: 194.45  E-value: 8.55e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  234 KWEMERTDITMKHKLGGGQYGEVYE----GVWKKYSL-TVAVKTLKEDTMEVEEflkeAAVMKEIK-------HPNLVQL 301
Cdd:cd14207    1 KWEFARERLKLGKSLGRGAFGKVVQasafGIKKSPTCrVVAVKMLKEGATASEY----KALMTELKilihighHLNVVNL 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  302 LGVCTREP-PFYIITEFMTYGNLLDYLR----------------------------ECNRQEVNAVV------------- 339
Cdd:cd14207   77 LGACTKSGgPLMVIVEYCKYGNLSNYLKskrdffvtnkdtslqeelikekkeaeptGGKKKRLESVTssesfassgfqed 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  340 -------------------------LLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR-LMTGDTY 393
Cdd:cd14207  157 kslsdveeeeedsgdfykrpltmedLISYSFQVARGMEFLSSRKCIHRDLAARNILLSENNVVKICDFGLARdIYKNPDY 236
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  394 TAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVY-ELLEKDYRMERPEGCPEKVYELM 472
Cdd:cd14207  237 VRKGDARLPLKWMAPESIFDKIYSTKSDVWSYGVLLWEIFSLGASPYPGVQIDEDFcSKLKEGIRMRAPEFATSEIYQIM 316
                        330
                 ....*....|....*..
gi 62362414  473 RACWQWNPSDRPSFAEI 489
Cdd:cd14207  317 LDCWQGDPNERPRFSEL 333
PTKc_Jak1_rpt2 cd05079
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the ...
248-496 2.84e-54

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak1 is widely expressed in many tissues. Many cytokines are dependent on Jak1 for signaling, including those that use the shared receptor subunits common gamma chain (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21) and gp130 (IL-6, IL-11, oncostatin M, G-CSF, and IFNs, among others). The many varied interactions of Jak1 and its ubiquitous expression suggest many biological roles. Jak1 is important in neurological development, as well as in lymphoid development and function. It also plays a role in the pathophysiology of cardiac hypertrophy and heart failure. A mutation in the ATP-binding site of Jak1 was identified in a human uterine leiomyosarcoma cell line, resulting in defective cytokine induction and antigen presentation, thus allowing the tumor to evade the immune system. Jak1 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Jak1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173644 [Multi-domain]  Cd Length: 284  Bit Score: 190.91  E-value: 2.84e-54
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEV----YEGVWKKYSLTVAVKTLKEDTME--VEEFLKEAAVMKEIKHPNLVQLLGVCTREP--PFYIITEFMT 319
Cdd:cd05079   12 LGEGHFGKVelcrYDPEGDNTGEQVAVKSLKPESGGnhIADLKKEIEILRNLYHENIVKYKGICTEDGgnGIKLIMEFLP 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  320 YGNLLDYLREcNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDT--YTAHA 397
Cdd:cd05079   92 SGSLKEYLPR-NKNKINLKQQLKYAVQICKGMDYLGSRQYVHRDLAARNVLVESEHQVKIGDFGLTKAIETDKeyYTVKD 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  398 GAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDL--------------SQVYELLEKDYRMERPEG 463
Cdd:cd05079  171 DLDSPVFWYAPECLIQSKFYIASDVWSFGVTLYELLTYCDSESSPMTLflkmigpthgqmtvTRLVRVLEEGKRLPRPPN 250
                        250       260       270
                 ....*....|....*....|....*....|...
gi 62362414  464 CPEKVYELMRACWQWNPSDRPSFAEIHQAFETM 496
Cdd:cd05079  251 CPEEVYQLMRKCWEFQPSKRTTFQNLIEGFEAI 283
PTK_HER3 cd05111
Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR ...
248-496 7.68e-54

Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. HER3 contains an impaired tyr kinase domain, which lacks crucial residues for catalytic activity against exogenous substrates but is still able to bind ATP and autophosphorylate. HER3 binds the neuregulin ligands, NRG1 and NRG2, and it relies on its heterodimerization partners for activity following ligand binding. The HER2-HER3 heterodimer constitutes a high affinity co-receptor capable of potent mitogenic signaling. HER3 participates in a signaling pathway involved in the proliferation, survival, adhesion, and motility of tumor cells. The HER3 subfamily is part of a larger superfamily that includes other pseudokinases and the the catalytic domains of active kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173656 [Multi-domain]  Cd Length: 279  Bit Score: 189.78  E-value: 7.68e-54
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVW----KKYSLTVAVKTLKEDT--MEVEEFLKEAAVMKEIKHPNLVQLLGVCTrEPPFYIITEFMTYG 321
Cdd:cd05111   15 LGSGVFGTVHKGIWipegDSIKIPVAIKVIQDRSgrQSFQAVTDHMLAIGSLDHAYIVRLLGICP-GASLQLVTQLLPLG 93
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  322 NLLDYLREcNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLM-TGDTYTAHAGAK 400
Cdd:cd05111   94 SLLDHVRQ-HRGSLGPQLLLNWCVQIAKGMYYLEEHRMVHRNLAARNVLLKSPSQVQVADFGVADLLyPDDKKYFYSEAK 172
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  401 FPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQWNP 480
Cdd:cd05111  173 TPIKWMALESIHFGKYTHQSDVWSYGVTVWEMMTFGAEPYAGMRLAEVPDLLEKGERLAQPQICTIDVYMVMVKCWMIDE 252
                        250
                 ....*....|....*.
gi 62362414  481 SDRPSFAEIHQAFETM 496
Cdd:cd05111  253 NIRPTFKELANEFTRM 268
PTKc_PDGFR_beta cd05107
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta; ...
232-489 1.06e-53

Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. PDGFR beta is a receptor PTK (RTK) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding to its ligands, the PDGFs, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR beta forms homodimers or heterodimers with PDGFR alpha, depending on the nature of the PDGF ligand. PDGF-BB and PDGF-DD induce PDGFR beta homodimerization. PDGFR signaling plays many roles in normal embryonic development and adult physiology. PDGFR beta signaling leads to a variety of cellular effects including the stimulation of cell growth and chemotaxis, as well as the inhibition of apoptosis and GAP junctional communication. It is critical in normal angiogenesis as it is involved in the recruitment of pericytes and smooth muscle cells essential for vessel stability. Aberrant PDGFR beta expression is associated with some human cancers. The continuously-active fusion proteins of PDGFR beta with COL1A1 and TEL are associated with dermatofibrosarcoma protuberans (DFSP) and a subset of chronic myelomonocytic leukemia (CMML), respectively. The PDGFR beta subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133238 [Multi-domain]  Cd Length: 401  Bit Score: 193.30  E-value: 1.06e-53
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  232 YD-KWEMERTDITMKHKLGGGQYGEVYEGV-----WKKYSLTVAVKTLKEDTMEVEEflkeAAVMKEIK-------HPNL 298
Cdd:cd05107   28 YDsAWEMPRDNLVLGRTLGSGAFGRVVEATahglsHSQSTMKVAVKMLKSTARSSEK----QALMSELKimshlgpHLNI 103
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  299 VQLLGVCTREPPFYIITEFMTYGNLLDYLR-----------ECNRQEVNAV----------------------------- 338
Cdd:cd05107  104 VNLLGACTKGGPIYIITEYCRYGDLVDYLHrnkhtflqyylDKNRDDGSLIsggstplsqrkshvslgsesdggymdmsk 183
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  339 ---------------------------------------------------VLLYM-----ATQISSAMEYLEKKNFIHR 362
Cdd:cd05107  184 desadyvpmqdmkgtvkyadiessnyespydqylpsapertrrdtlinespALSYMdlvgfSYQVANGMEFLASKNCVHR 263
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  363 DLAARNCLVGENHLVKVADFGLSR-LMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYP 441
Cdd:cd05107  264 DLAARNVLICEGKLVKICDFGLARdIMRDSNYISKGSTFLPLKWMAPESIFNNLYTTLSDVWSFGILLWEIFTLGGTPYP 343
                        330       340       350       360
                 ....*....|....*....|....*....|....*....|....*....
gi 62362414  442 GIDLS-QVYELLEKDYRMERPEGCPEKVYELMRACWQWNPSDRPSFAEI 489
Cdd:cd05107  344 ELPMNeQFYNAIKRGYRMAKPAHASDEIYEIMQKCWEEKFEIRPDFSQL 392
PTKc_VEGFR2 cd05103
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; ...
234-500 3.47e-53

Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR2 (or Flk1) binds the ligands VEGFA, VEGFC, VEGFD and VEGFE. VEGFR2 signaling is implicated in all aspects of normal and pathological vascular endothelial cell biology. It induces a variety of cellular effects including migration, survival, and proliferation. It is critical in regulating embryonic vascular development and angiogenesis. VEGFR2 is the major signal transducer in pathological angiogenesis including cancer and diabetic retinopathy, and is a target for inhibition in cancer therapy. The carboxyl terminus of VEGFR2 plays an important role in its autophosphorylation and activation. VEGFR2 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270681 [Multi-domain]  Cd Length: 343  Bit Score: 189.81  E-value: 3.47e-53
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  234 KWEMERTDITMKHKLGGGQYGEVYE----GVWKKYSL-TVAVKTLKEDTMEVEEflkeAAVMKEIK-------HPNLVQL 301
Cdd:cd05103    1 KWEFPRDRLKLGKPLGRGAFGQVIEadafGIDKTATCrTVAVKMLKEGATHSEH----RALMSELKilihighHLNVVNL 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  302 LGVCTREP-PFYIITEFMTYGNLLDYLRE--------------------------------------------------- 329
Cdd:cd05103   77 LGACTKPGgPLMVIVEFCKFGNLSAYLRSkrsefvpyktkgarfrqgkdyvgdisvdlkrrldsitssqssassgfveek 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  330 --CNRQEVNAVV------------LLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGD-TYT 394
Cdd:cd05103  157 slSDVEEEEAGQedlykdfltledLICYSFQVAKGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLARDIYKDpDYV 236
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  395 AHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVY-ELLEKDYRMERPEGCPEKVYELMR 473
Cdd:cd05103  237 RKGDARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFcRRLKEGTRMRAPDYTTPEMYQTML 316
                        330       340
                 ....*....|....*....|....*..
gi 62362414  474 ACWQWNPSDRPSFAEIHQAFETMFQES 500
Cdd:cd05103  317 DCWHGEPSQRPTFSELVEHLGNLLQAN 343
PTKc_PDGFR_alpha cd05105
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor alpha; ...
232-497 6.65e-53

Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor alpha; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. PDGFR alpha is a receptor PTK (RTK) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding to its ligands, the PDGFs, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR alpha forms homodimers or heterodimers with PDGFR beta, depending on the nature of the PDGF ligand. PDGF-AA, PDGF-AB, and PDGF-CC induce PDGFR alpha homodimerization. PDGFR signaling plays many roles in normal embryonic development and adult physiology. PDGFR alpha signaling is important in the formation of lung alveoli, intestinal villi, mesenchymal dermis, and hair follicles, as well as in the development of oligodendrocytes, retinal astrocytes, neural crest cells, and testicular cells. Aberrant PDGFR alpha expression is associated with some human cancers. Mutations in PDGFR alpha have been found within a subset of gastrointestinal stromal tumors (GISTs). An active fusion protein FIP1L1-PDGFR alpha, derived from interstitial deletion, is associated with idiopathic hypereosinophilic syndrome and chronic eosinophilic leukemia. The PDGFR alpha subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173653 [Multi-domain]  Cd Length: 400  Bit Score: 191.01  E-value: 6.65e-53
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  232 YD-KWEMERTDITMKHKLGGGQYGEVYEGVWKKYS-----LTVAVKTLKEDTMEVEEflkeAAVMKEIK-------HPNL 298
Cdd:cd05105   28 YDsRWEFPRDGLVLGRILGSGAFGKVVEGTAYGLSrsqpvMKVAVKMLKPTARSSEK----QALMSELKimthlgpHLNI 103
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  299 VQLLGVCTREPPFYIITEFMTYGNLLDYL--------------------------------------------------- 327
Cdd:cd05105  104 VNLLGACTKSGPIYIITEYCFYGDLVNYLhknrdnflsrhpekpkkdldifginpadestrsyvilsfenkgdymdmkqa 183
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  328 -------------------------------RECNRQEVNAVV------------LLYMATQISSAMEYLEKKNFIHRDL 364
Cdd:cd05105  184 dttqyvpmleikeaskysdiqrsnydrpasyKGSNDSEVKNLLsddgseglttldLLSFTYQVARGMEFLASKNCVHRDL 263
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  365 AARNCLVGENHLVKVADFGLSR-LMTGDTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGI 443
Cdd:cd05105  264 AARNVLLAQGKIVKICDFGLARdIMHDSNYVSKGSTFLPVKWMAPESIFDNLYTTLSDVWSYGILLWEIFSLGGTPYPGM 343
                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 62362414  444 DL-SQVYELLEKDYRMERPEGCPEKVYELMRACWQWNPSDRPSFAEIHQAFETMF 497
Cdd:cd05105  344 IVdSTFYNKIKSGYRMAKPDHATQEVYDIMVKCWNSEPEKRPSFLHLSDIVESLL 398
PTKc_Jak3_rpt2 cd05081
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the ...
248-496 2.20e-52

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak3 is expressed only in hematopoietic cells. It binds the shared receptor subunit common gamma chain and thus, is essential in the signaling of cytokines that use it such as IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Jak3 is important in lymphoid development and myeloid cell differentiation. Inactivating mutations in Jak3 have been reported in humans with severe combined immunodeficiency (SCID). Jak3 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270665 [Multi-domain]  Cd Length: 283  Bit Score: 185.48  E-value: 2.20e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEV----YEGVWKKYSLTVAVKTLKEDTME-VEEFLKEAAVMKEIKHPNLVQLLGVCTR--EPPFYIITEFMTY 320
Cdd:cd05081   12 LGKGNFGSVelcrYDPLGDNTGALVAVKQLQHSGPDqQRDFQREIQILKALHSDFIVKYRGVSYGpgRRSLRLVMEYLPS 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  321 GNLLDYLREcNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDT--YTAHAG 398
Cdd:cd05081   92 GCLRDFLQR-HRARLDASRLLLYSSQICKGMEYLGSRRCVHRDLAARNILVESEAHVKIADFGLAKLLPLDKdyYVVREP 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  399 AKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYG-------------MSPY-PGIDLSQVYELLEKDYRMERPEGC 464
Cdd:cd05081  171 GQSPIFWYAPESLSDNIFSRQSDVWSFGVVLYELFTYCdkscspsaeflrmMGCErDVPALCRLLELLEEGQRLPAPPAC 250
                        250       260       270
                 ....*....|....*....|....*....|..
gi 62362414  465 PEKVYELMRACWQWNPSDRPSFAEIHQAFETM 496
Cdd:cd05081  251 PAEVHELMKLCWAPSPQDRPSFSALGPQLDML 282
STKc_MLK cd14061
Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the ...
248-496 1.93e-50

Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270963 [Multi-domain]  Cd Length: 258  Bit Score: 179.13  E-value: 1.93e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKkySLTVAVKTLKEDTME-----VEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGN 322
Cdd:cd14061    2 IGVGGFGKVYRGIWR--GEEVAVKAARQDPDEdisvtLENVRQEARLFWMLRHPNIIALRGVCLQPPNLCLVMEYARGGA 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLdylRECNRQEVNAVVLLYMATQISSAMEYLEKKN---FIHRDLAARNCLVGE--------NHLVKVADFGLSRLMTGD 391
Cdd:cd14061   80 LN---RVLAGRKIPPHVLVDWAIQIARGMNYLHNEApvpIIHRDLKSSNILILEaienedleNKTLKITDFGLAREWHKT 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  392 TYTAHAGAkfpIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGID-LSQVYELLEKDYRMERPEGCPEKVYE 470
Cdd:cd14061  157 TRMSAAGT---YAWMAPEVIKSSTFSKASDVWSYGVLLWELLT-GEVPYKGIDgLAVAYGVAVNKLTLPIPSTCPEPFAQ 232
                        250       260
                 ....*....|....*....|....*.
gi 62362414  471 LMRACWQWNPSDRPSFAEIHQAFETM 496
Cdd:cd14061  233 LMKDCWQPDPHDRPSFADILKQLENI 258
FABD smart00808
F-actin binding domain (FABD); FABD is the F-actin binding domain of Bcr-Abl and its cellular ...
1006-1130 7.56e-49

F-actin binding domain (FABD); FABD is the F-actin binding domain of Bcr-Abl and its cellular counterpart c-Abl. The Bcr-Abl tyrosine kinase causes different forms of leukemia in humans. Depending on its position within the cell, Bcr-Abl differentially affects cellular growth. The FABD forms a compact left-handed four-helix bundle in solution.


Pssm-ID: 197885  Cd Length: 126  Bit Score: 169.21  E-value: 7.56e-49
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414    1006 ISTRVSLRKTR--QPPERIASGAITKGVVLDSTEALCLAISRNSEQMASHSAVLEAGKNLYTFCVSYVDSIQQMRNKFAF 1083
Cdd:smart00808    1 IKTKVALRKTRtqQAAERIPSDAISKDMILELTELLESALVALSETPASHSQWLDKGHQLHSTCSGYADQIPQPRSKFQF 80
                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*..
gi 62362414    1084 REAINKLENNLRELQIcPATAGSGPAATQDFSKLLSSVKEISDIVQR 1130
Cdd:smart00808   81 RELVSRLELQLRELRF-SAGSRNVPGATQDFSKLLSSVKEISDVVQR 126
PTKc_Tyk2_rpt2 cd05080
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze ...
242-496 1.04e-48

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tyk2 is widely expressed in many tissues. It is involved in signaling via the cytokine receptors IFN-alphabeta, IL-6, IL-10, IL-12, IL-13, and IL-23. It mediates cell surface urokinase receptor (uPAR) signaling and plays a role in modulating vascular smooth muscle cell (VSMC) functional behavior in response to injury. Tyk2 is also important in dendritic cell function and T helper (Th)1 cell differentiation. A homozygous mutation of Tyk2 was found in a patient with hyper-IgE syndrome (HIES), a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and elevated serum IgE. This suggests that Tyk2 may play important roles in multiple cytokine signaling involved in innate and adaptive immunity. Tyk2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Tyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270664 [Multi-domain]  Cd Length: 283  Bit Score: 175.09  E-value: 1.04e-48
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  242 ITMKHKLGGGQYGEV----YEGVWKKYSLTVAVKTLKED--TMEVEEFLKEAAVMKEIKHPNLVQLLGVCTR--EPPFYI 313
Cdd:cd05080    6 LKKIRDLGEGHFGKVslycYDPTNDGTGEMVAVKALKADcgPQHRSGWKQEIDILKTLYHENIVKYKGCCSEqgGKSLQL 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  314 ITEFMTYGNLLDYLrecNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLM-TGDT 392
Cdd:cd05080   86 IMEYVPLGSLRDYL---PKHSIGLAQLLLFAQQICEGMAYLHSQHYIHRDLAARNVLLDNDRLVKIGDFGLAKAVpEGHE 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  393 -YTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATY---GMSP-----------YPGIDLSQVYELLEKDYR 457
Cdd:cd05080  163 yYRVREDGDSPVFWYAPECLKEYKFYYASDVWSFGVTLYELLTHcdsSQSPptkflemigiaQGQMTVVRLIELLERGER 242
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 62362414  458 MERPEGCPEKVYELMRACWQWNPSDRPSFAEIHQAFETM 496
Cdd:cd05080  243 LPCPDKCPQEVYHLMKNCWETEASFRPTFENLIPILKTV 281
STKc_MAP3K12_13 cd14059
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase ...
248-489 2.80e-48

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinases 12 and 13; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K12 is also called MAPK upstream kinase (MUK), dual leucine zipper-bearing kinase (DLK) or leucine-zipper protein kinase (ZPK). It is involved in the c-Jun N-terminal kinase (JNK) pathway that directly regulates axonal regulation through the phosphorylation of microtubule-associated protein 1B (MAP1B). It also regulates the differentiation of many cell types including adipocytes and may play a role in adipogenesis. MAP3K13, also called leucine zipper-bearing kinase (LZK), directly phosphorylates and activates MKK7, which in turn activates the JNK pathway. It also activates NF-kB through IKK activation and this activity is enhanced by antioxidant protein-1 (AOP-1). MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAP2Ks (MAPKKs or MKKs), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The MAP3K12/13 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270961 [Multi-domain]  Cd Length: 237  Bit Score: 171.91  E-value: 2.80e-48
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKkySLTVAVKTLKEdtmeveefLKEAAV--MKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLD 325
Cdd:cd14059    1 LGSGAQGAVFLGKFR--GEEVAVKKVRD--------EKETDIkhLRKLNHPNIIKFKGVCTQAPCYCILMEYCPYGQLYE 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  326 YLREcnRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMT-GDTYTAHAGAkfpIK 404
Cdd:cd14059   71 VLRA--GREITPSLLVDWSKQIASGMNYLHLHKIIHRDLKSPNVLVTYNDVLKISDFGTSKELSeKSTKMSFAGT---VA 145
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  405 WTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQV-YELLEKDYRMERPEGCPEKVYELMRACWQWNPSDR 483
Cdd:cd14059  146 WMAPEVIRNEPCSEKVDIWSFGVVLWELLT-GEIPYKDVDSSAIiWGVGSNSLQLPVPSTCPDGFKLLMKQCWNSKPRNR 224

                 ....*.
gi 62362414  484 PSFAEI 489
Cdd:cd14059  225 PSFRQI 230
STKc_MLTK cd14060
Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated ...
249-496 2.60e-47

Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated protein Triple Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLTK, also called zipper sterile-alpha-motif kinase (ZAK), contains a catalytic kinase domain and a leucine zipper. There are two alternatively-spliced variants, MLTK-alpha and MLTK-beta. MLTK-alpha contains a sterile-alpha-motif (SAM) at the C-terminus. MLTK regulates the c-Jun N-terminal kinase, extracellular signal-regulated kinase, p38 MAPK, and NF-kB pathways. ZAK is the MAP3K involved in the signaling cascade that leads to the ribotoxic stress response initiated by cellular damage due to Shiga toxins and ricin. It may also play a role in cell transformation and cancer development. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals.The MLTK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270962 [Multi-domain]  Cd Length: 242  Bit Score: 169.37  E-value: 2.60e-47
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  249 GGGQYGEVYEGVWKKYSLTVAVKTLKEdtMEveeflKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDYLR 328
Cdd:cd14060    2 GGGSFGSVYRAIWVSQDKEVAVKKLLK--IE-----KEAEILSVLSHRNIIQFYGAILEAPNYGIVTEYASYGSLFDYLN 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  329 ECNRQEVNAVVLLYMATQISSAMEYLEKK---NFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAkFPikW 405
Cdd:cd14060   75 SNESEEMDMDQIMTWATDIAKGMHYLHMEapvKVIHRDLKSRNVVIAADGVLKICDFGASRFHSHTTHMSLVGT-FP--W 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  406 TAPESLAYNKFSIKSDVWAFGVLLWEIATYGMsPYPGIDLSQV-YELLEKDYRMERPEGCPEKVYELMRACWQWNPSDRP 484
Cdd:cd14060  152 MAPEVIQSLPVSETCDTYSYGVVLWEMLTREV-PFKGLEGLQVaWLVVEKNERPTIPSSCPRSFAELMRRCWEADVKERP 230
                        250
                 ....*....|..
gi 62362414  485 SFAEIHQAFETM 496
Cdd:cd14060  231 SFKQIIGILESM 242
STKc_MLK4 cd14146
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the ...
248-489 3.01e-45

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK4 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation.The MLK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271048 [Multi-domain]  Cd Length: 268  Bit Score: 164.44  E-value: 3.01e-45
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSltVAVKTLKEDTME-----VEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGN 322
Cdd:cd14146    2 IGVGGFGKVYRATWKGQE--VAVKAARQDPDEdikatAESVRQEAKLFSMLRHPNIIKLEGVCLEEPNLCLVMEFARGGT 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLRECNR-------QEVNAVVLLYMATQISSAMEYLEKKNF---IHRDLAARNCLVGE--------NHLVKVADFGL 384
Cdd:cd14146   80 LNRALAAANAapgprraRRIPPHILVNWAVQIARGMLYLHEEAVvpiLHRDLKSSNILLLEkiehddicNKTLKITDFGL 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  385 SRLMTGDTYTAHAGAkfpIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGID-LSQVYELLEKDYRMERPEG 463
Cdd:cd14146  160 AREWHRTTKMSAAGT---YAWMAPEVIKSSLFSKGSDIWSYGVLLWELLT-GEVPYRGIDgLAVAYGVAVNKLTLPIPST 235
                        250       260
                 ....*....|....*....|....*.
gi 62362414  464 CPEKVYELMRACWQWNPSDRPSFAEI 489
Cdd:cd14146  236 CPEPFAKLMKECWEQDPHIRPSFALI 261
STKc_MLK2 cd14148
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the ...
248-496 2.57e-44

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK2 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK) and is also called MAP3K10. MAP3Ks phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLK2 is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK2 also binds to normal huntingtin (Htt), which is important in neuronal transcription, development, and survival. MLK2 does not bind to the polyglutamine-expanded Htt, which is implicated in the pathogeneis of Huntington's disease, leading to neuronal toxicity. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 271050 [Multi-domain]  Cd Length: 258  Bit Score: 161.31  E-value: 2.57e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSltVAVKTLKEDTME-----VEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGN 322
Cdd:cd14148    2 IGVGGFGKVYKGLWRGEE--VAVKAARQDPDEdiavtAENVRQEARLFWMLQHPNIIALRGVCLNPPHLCLVMEYARGGA 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLdylRECNRQEVNAVVLLYMATQISSAMEYLEKKNF---IHRDLAARNCLV---GENH-----LVKVADFGLSRLMTGD 391
Cdd:cd14148   80 LN---RALAGKKVPPHVLVNWAVQIARGMNYLHNEAIvpiIHRDLKSSNILIlepIENDdlsgkTLKITDFGLAREWHKT 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  392 TYTAHAGAkfpIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGID-LSQVYELLEKDYRMERPEGCPEKVYE 470
Cdd:cd14148  157 TKMSAAGT---YAWMAPEVIRLSLFSKSSDVWSFGVLLWELLT-GEVPYREIDaLAVAYGVAMNKLTLPIPSTCPEPFAR 232
                        250       260
                 ....*....|....*....|....*.
gi 62362414  471 LMRACWQWNPSDRPSFAEIHQAFETM 496
Cdd:cd14148  233 LLEECWDPDPHGRPDFGSILKRLEDI 258
STKc_MLK1 cd14145
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the ...
236-489 8.99e-44

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK1 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK) and is also called MAP3K9. MAP3Ks phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Little is known about the specific function of MLK1. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. There could be redundancy in the function of MLKs. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271047 [Multi-domain]  Cd Length: 270  Bit Score: 160.21  E-value: 8.99e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  236 EMERTDITMKHKLGGGQYGEVYEGVWKKYSltVAVKTLKEDTME-----VEEFLKEAAVMKEIKHPNLVQLLGVCTREPP 310
Cdd:cd14145    2 EIDFSELVLEEIIGIGGFGKVYRAIWIGDE--VAVKAARHDPDEdisqtIENVRQEAKLFAMLKHPNIIALRGVCLKEPN 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  311 FYIITEFMTYGNLLdylRECNRQEVNAVVLLYMATQISSAMEYLEKKNF---IHRDLAARNCLVGE--------NHLVKV 379
Cdd:cd14145   80 LCLVMEFARGGPLN---RVLSGKRIPPDILVNWAVQIARGMNYLHCEAIvpvIHRDLKSSNILILEkvengdlsNKILKI 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  380 ADFGLSRLMTGDTYTAHAGAkfpIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGID-LSQVYELLEKDYRM 458
Cdd:cd14145  157 TDFGLAREWHRTTKMSAAGT---YAWMAPEVIRSSMFSKGSDVWSYGVLLWELLT-GEVPFRGIDgLAVAYGVAMNKLSL 232
                        250       260       270
                 ....*....|....*....|....*....|.
gi 62362414  459 ERPEGCPEKVYELMRACWQWNPSDRPSFAEI 489
Cdd:cd14145  233 PIPSTCPEPFARLMEDCWNPDPHSRPPFTNI 263
PTKc_Aatyk1 cd05087
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 1; PTKs ...
247-490 7.79e-43

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk1 (or simply Aatyk) is also called lemur tyrosine kinase 1 (Lmtk1). It is a cytoplasmic (or nonreceptor) kinase containing a long C-terminal region. The expression of Aatyk1 is upregulated during growth arrest and apoptosis in myeloid cells. Aatyk1 has been implicated in neural differentiation, and is a regulator of the Na-K-2Cl cotransporter, a membrane protein involved in cell proliferation and survival, epithelial transport, and blood pressure control. The Aatyk1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270670 [Multi-domain]  Cd Length: 271  Bit Score: 157.46  E-value: 7.79e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEG-VWKKYSLT-VAVKTLK-----EDTMEveeFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMT 319
Cdd:cd05087    4 EIGHGWFGKVFLGeVNSGLSSTqVVVKELKasasvQDQMQ---FLEEAQPYRALQHTNLLQCLAQCAEVTPYLLVMEFCP 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  320 YGNLLDYLRECNRQEVNA---VVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAH 396
Cdd:cd05087   81 LGDLKGYLRSCRAAESMApdpLTLQRMACEVACGLLHLHRNNFVHSDLALRNCLLTADLTVKIGDYGLSHCKYKEDYFVT 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  397 AGAKF-PIKWTAPE-------SLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQV--YELLEKDYRMERPE---G 463
Cdd:cd05087  161 ADQLWvPLRWIAPElvdevhgNLLVVDQTKQSNVWSLGVTIWELFELGNQPYRHYSDRQVltYTVREQQLKLPKPQlklS 240
                        250       260
                 ....*....|....*....|....*..
gi 62362414  464 CPEKVYELMRACWqWNPSDRPSFAEIH 490
Cdd:cd05087  241 LAERWYEVMQFCW-LQPEQRPTAEEVH 266
STKc_MLK3 cd14147
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the ...
241-496 4.33e-42

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK3 is a mitogen-activated protein kinase kinase kinases (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLK3 activates multiple MAPK pathways and plays a role in apoptosis, proliferation, migration, and differentiation, depending on the cellular context. It is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. MLK3 also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and consequently, it also impacts inflammation and immunity. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation.The MLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271049 [Multi-domain]  Cd Length: 267  Bit Score: 155.19  E-value: 4.33e-42
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  241 DITMKHKLGGGQYGEVYEGVWKkySLTVAVKTLKED-----TMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIIT 315
Cdd:cd14147    4 ELRLEEVIGIGGFGKVYRGSWR--GELVAVKAARQDpdediSVTAESVRQEARLFAMLAHPNIIALKAVCLEEPNLCLVM 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  316 EFMTYGNLLdylRECNRQEVNAVVLLYMATQISSAMEYLEKKNF---IHRDLAARNCLVG--------ENHLVKVADFGL 384
Cdd:cd14147   82 EYAAGGPLS---RALAGRRVPPHVLVNWAVQIARGMHYLHCEALvpvIHRDLKSNNILLLqpienddmEHKTLKITDFGL 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  385 SRLMTGDTYTAHAGAkfpIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGID-LSQVYELLEKDYRMERPEG 463
Cdd:cd14147  159 AREWHKTTQMSAAGT---YAWMAPEVIKASTFSKGSDVWSFGVLLWELLT-GEVPYRGIDcLAVAYGVAVNKLTLPIPST 234
                        250       260       270
                 ....*....|....*....|....*....|...
gi 62362414  464 CPEKVYELMRACWQWNPSDRPSFAEIHQAFETM 496
Cdd:cd14147  235 CPEPFAQLMADCWAQDPHRRPDFASILQQLEAL 267
STKc_PknB_like cd14014
Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs ...
246-495 3.53e-41

Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes many bacterial eukaryotic-type STKs including Staphylococcus aureus PknB (also called PrkC or Stk1), Bacillus subtilis PrkC, and Mycobacterium tuberculosis Pkn proteins (PknB, PknD, PknE, PknF, PknL, and PknH), among others. S. aureus PknB is the only eukaryotic-type STK present in this species, although many microorganisms encode for several such proteins. It is important for the survival and pathogenesis of S. aureus as it is involved in the regulation of purine and pyrimidine biosynthesis, cell wall metabolism, autolysis, virulence, and antibiotic resistance. M. tuberculosis PknB is essential for growth and it acts on diverse substrates including proteins involved in peptidoglycan synthesis, cell division, transcription, stress responses, and metabolic regulation. B. subtilis PrkC is located at the inner membrane of endospores and functions to trigger spore germination. Bacterial STKs in this subfamily show varied domain architectures. The well-characterized members such as S. aureus and M. tuberculosis PknB, and B. subtilis PrkC, contain an N-terminal cytosolic kinase domain, a transmembrane (TM) segment, and mutliple C-terminal extracellular PASTA domains. The PknB subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270916 [Multi-domain]  Cd Length: 260  Bit Score: 152.36  E-value: 3.53e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  246 HKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTME----VEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYG 321
Cdd:cd14014    6 RLLGRGGMGEVYRARDTLLGRPVAIKVLRPELAEdeefRERFLREARALARLSHPNIVRVYDVGEDDGRPYIVMEYVEGG 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  322 NLLDYLREcnRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKF 401
Cdd:cd14014   86 SLADLLRE--RGPLPPREALRILAQIADALAAAHRAGIVHRDIKPANILLTEDGRVKLTDFGIARALGDSGLTQTGSVLG 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  402 PIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQV-YELLEKDYRMERPE--GCPEKVYELMRACWQW 478
Cdd:cd14014  164 TPAYMAPEQARGGPVDPRSDIYSLGVVLYELLT-GRPPFDGDSPAAVlAKHLQEAPPPPSPLnpDVPPALDAIILRALAK 242
                        250
                 ....*....|....*...
gi 62362414  479 NPSDRP-SFAEIHQAFET 495
Cdd:cd14014  243 DPEERPqSAAELLAALRA 260
STKc_TAK1 cd14058
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated ...
248-498 2.65e-40

Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated Kinase-1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAK1 is also known as mitogen-activated protein kinase kinase kinase 7 (MAPKKK7 or MAP3K7), TAK, or MEKK7. As a MAPKKK, it is an important mediator of cellular responses to extracellular signals. It regulates both the c-Jun N-terminal kinase and p38 MAPK cascades by activating the MAPK kinases, MKK4 and MKK3/6. In addition, TAK1 plays diverse roles in immunity and development, in different biological contexts, through many signaling pathways including TGFbeta/BMP, Wnt/Fz, and NF-kB. It is also implicated in the activation of the tumor suppressor kinase, LKB1. The TAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270960 [Multi-domain]  Cd Length: 253  Bit Score: 149.51  E-value: 2.65e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKkySLTVAVKTLKEDTmEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDYL 327
Cdd:cd14058    1 VGRGSFGVVCKARWR--NQIVAVKIIESES-EKKAFEVEVRQLSRVDHPNIIKLYGACSNQKPVCLVMEYAEGGSLYNVL 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  328 RECNRQ-EVNAVVLLYMATQISSAMEYL---EKKNFIHRDLAARNCLVGENH-LVKVADFGL----SRLMTGDTYTAhag 398
Cdd:cd14058   78 HGKEPKpIYTAAHAMSWALQCAKGVAYLhsmKPKALIHRDLKPPNLLLTNGGtVLKICDFGTacdiSTHMTNNKGSA--- 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  399 akfpiKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYgMSPYPGIDlSQVYELLEKDYRMERP---EGCPEKVYELMRAC 475
Cdd:cd14058  155 -----AWMAPEVFEGSKYSEKCDVFSWGIILWEVITR-RKPFDHIG-GPAFRIMWAVHNGERPpliKNCPKPIESLMTRC 227
                        250       260
                 ....*....|....*....|...
gi 62362414  476 WQWNPSDRPSFAEIHQAFETMFQ 498
Cdd:cd14058  228 WSKDPEKRPSMKEIVKIMSHLMQ 250
PKc_LIMK_like cd14065
Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of ...
248-491 4.87e-40

Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. Members of this subfamily include LIMK, Testicular or testis-specific protein kinase (TESK), and similar proteins. LIMKs are characterized as serine/threonine kinases (STKs) while TESKs are dual-specificity protein kinases. Both LIMK and TESK phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They are implicated in many cellular functions including cell spreading, motility, morphogenesis, meiosis, mitosis, and spermatogenesis. The LIMK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270967 [Multi-domain]  Cd Length: 252  Bit Score: 148.79  E-value: 4.87e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTmEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDYL 327
Cdd:cd14065    1 LGKGFFGEVYKVTHRETGKVMVMKELKRFD-EQRSFLKEVKLMRRLSHPNILRFIGVCVKDNKLNFITEYVNGGTLEELL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  328 RECNRQeVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGE---NHLVKVADFGLSRLMtGDTYTAHAGAKFPIK 404
Cdd:cd14065   80 KSMDEQ-LPWSQRVSLAKDIASGMAYLHSKNIIHRDLNSKNCLVREanrGRNAVVADFGLAREM-PDEKTKKPDRKKRLT 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  405 ------WTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQW 478
Cdd:cd14065  158 vvgspyWMAPEMLRGESYDEKVDVFSFGIVLCEIIGRVPADPDYLPRTMDFGLDVRAFRTLYVPDCPPSFLPLAIRCCQL 237
                        250
                 ....*....|...
gi 62362414  479 NPSDRPSFAEIHQ 491
Cdd:cd14065  238 DPEKRPSFVELEH 250
PTKc_Aatyk cd05042
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs ...
247-490 5.44e-40

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Aatyk subfamily is also referred to as the lemur tyrosine kinase (Lmtk) subfamily. It consists of Aatyk1 (Lmtk1), Aatyk2 (Lmtk2, Brek), Aatyk3 (Lmtk3), and similar proteins. Aatyk proteins are mostly receptor PTKs (RTKs) containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. Aatyk1 does not contain a transmembrane segment and is a cytoplasmic (or nonreceptor) kinase. Aatyk proteins are classified as PTKs based on overall sequence similarity and the phylogenetic tree. However, analysis of catalytic residues suggests that Aatyk proteins may be multispecific kinases, functioning also as serine/threonine kinases. They are involved in neural differentiation, nerve growth factor (NGF) signaling, apoptosis, and spermatogenesis. The Aatyk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270638 [Multi-domain]  Cd Length: 269  Bit Score: 149.28  E-value: 5.44e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEG-VWKKYSLT-VAVKTLKEDT--MEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGN 322
Cdd:cd05042    2 EIGNGWFGKVLLGeIYSGTSVAqVVVKELKASAnpKEQDTFLKEGQPYRILQHPNILQCLGQCVEAIPYLLVMEFCDLGD 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLRECNRQEVNA---VVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGA 399
Cdd:cd05042   82 LKAYLRSEREHERGDsdtRTLQRMACEVAAGLAHLHKLNFVHSDLALRNCLLTSDLTVKIGDYGLAHSRYKEDYIETDDK 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  400 K-FPIKWTAPESLA--YNKF-----SIKSDVWAFGVLLWEIATYGMSPYPGIDLSQV--YELLEKDYRMERPE---GCPE 466
Cdd:cd05042  162 LwFPLRWTAPELVTefHDRLlvvdqTKYSNIWSLGVTLWELFENGAQPYSNLSDLDVlaQVVREQDTKLPKPQlelPYSD 241
                        250       260
                 ....*....|....*....|....
gi 62362414  467 KVYELMRACWQwNPSDRPSFAEIH 490
Cdd:cd05042  242 RWYEVLQFCWL-SPEQRPAAEDVH 264
STKc_MAPKKK cd06606
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase ...
246-488 9.00e-40

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKKKs (MKKKs or MAP3Ks) are also called MAP/ERK kinase kinases (MEKKs) in some cases. They phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. This subfamily is composed of the Apoptosis Signal-regulating Kinases ASK1 (or MAPKKK5) and ASK2 (or MAPKKK6), MEKK1, MEKK2, MEKK3, MEKK4, as well as plant and fungal MAPKKKs. Also included in this subfamily are the cell division control proteins Schizosaccharomyces pombe Cdc7 and Saccharomyces cerevisiae Cdc15. The MAPKKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270783 [Multi-domain]  Cd Length: 258  Bit Score: 148.44  E-value: 9.00e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  246 HKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM---EVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGN 322
Cdd:cd06606    6 ELLGKGSFGSVYLALNLDTGELMAVKEVELSGDseeELEALEREIRILSSLKHPNIVRYLGTERTENTLNIFLEYVPGGS 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLRECNR-QEvnAVVLLYmATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMtGDTYTAHAGAKF 401
Cdd:cd06606   86 LASLLKKFGKlPE--PVVRKY-TRQILEGLEYLHSNGIVHRDIKGANILVDSDGVVKLADFGCAKRL-AEIATGEGTKSL 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  402 ---PIkWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPgiDLSQVYELLEK----DYRMERPEGCPEKVYELMRA 474
Cdd:cd06606  162 rgtPY-WMAPEVIRGEGYGRAADIWSLGCTVIEMAT-GKPPWS--ELGNPVAALFKigssGEPPPIPEHLSEEAKDFLRK 237
                        250
                 ....*....|....
gi 62362414  475 CWQWNPSDRPSFAE 488
Cdd:cd06606  238 CLQRDPKKRPTADE 251
STKc_RIP cd13978
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze ...
248-488 7.68e-39

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP kinases serve as essential sensors of cellular stress. They are involved in regulating NF-kappaB and MAPK signaling, and are implicated in mediating cellular processes such as apoptosis, necroptosis, differentiation, and survival. RIP kinases contain a homologous N-terminal kinase domain and varying C-terminal domains. Higher vertebrates contain multiple RIP kinases, with mammals harboring at least five members. RIP1 and RIP2 harbor C-terminal domains from the Death domain (DD) superfamily while RIP4 contains ankyrin (ANK) repeats. RIP3 contain a RIP homotypic interaction motif (RHIM) that facilitates binding to RIP1. RIP1 and RIP3 are important in apoptosis and necroptosis, while RIP2 and RIP4 play roles in keratinocyte differentiation and inflammatory immune responses. The RIP subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270880 [Multi-domain]  Cd Length: 263  Bit Score: 145.67  E-value: 7.68e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDT---MEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNlL 324
Cdd:cd13978    1 LGSGGFGTVSKARHVSWFGMVAIKCLHSSPnciEERKALLKEAEKMERARHSYVLPLLGVCVERRSLGLVMEYMENGS-L 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  325 DYLRECNRQEVNAVVLLYMATQISSAMEYLE--KKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFP 402
Cdd:cd13978   80 KSLLEREIQDVPWSLRFRIIHEIALGMNFLHnmDPPLLHHDLKPENILLDNHFHVKISDFGLSKLGMKSISANRRRGTEN 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  403 ----IKWTAPESL--AYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVyeLLEKDYRMERP-----------EGCP 465
Cdd:cd13978  160 lggtPIYMAPEAFddFNKKPTSKSDVYSFAIVIWAVLT-RKEPFENAINPLL--IMQIVSKGDRPslddigrlkqiENVQ 236
                        250       260
                 ....*....|....*....|...
gi 62362414  466 EKVyELMRACWQWNPSDRPSFAE 488
Cdd:cd13978  237 ELI-SLMIRCWDGNPDARPTFLE 258
PTKc_Aatyk3 cd14206
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 3; PTKs ...
246-490 1.89e-37

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk3, also called lemur tyrosine kinase 3 (Lmtk3) is a receptor kinase containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. The function of Aatyk3 is still unknown. The Aatyk3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 271108 [Multi-domain]  Cd Length: 276  Bit Score: 142.40  E-value: 1.89e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  246 HKLGGGQYGEVYEG-VWKKYSLT-VAVKTLKEDT--MEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYG 321
Cdd:cd14206    3 QEIGNGWFGKVILGeIFSDYTPAqVVVKELRVSAgpLEQRKFISEAQPYRSLQHPNILQCLGLCTETIPFLLIMEFCQLG 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  322 NLLDYLRECNRQE--------VNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRL-MTGDT 392
Cdd:cd14206   83 DLKRYLRAQRKADgmtpdlptRDLRTLQRMAYEITLGLLHLHKNNYIHSDLALRNCLLTSDLTVRIGDYGLSHNnYKEDY 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  393 YTAHAGAKFPIKWTAPE-------SLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQV--YELLEKDYRMERPE- 462
Cdd:cd14206  163 YLTPDRLWIPLRWVAPElldelhgNLIVVDQSKESNVWSLGVTIWELFEFGAQPYRHLSDEEVltFVVREQQMKLAKPRl 242
                        250       260       270
                 ....*....|....*....|....*....|
gi 62362414  463 --GCPEKVYELMRACWQwNPSDRPSFAEIH 490
Cdd:cd14206  243 klPYADYWYEIMQSCWL-PPSQRPSVEELH 271
F_actin_bind pfam08919
F-actin binding; The F-actin binding domain forms a compact bundle of four antiparallel ...
1025-1130 2.00e-37

F-actin binding; The F-actin binding domain forms a compact bundle of four antiparallel alpha-helices, which are arranged in a left-handed topology. Binding of F-actin to the F-actin binding domain may result in cytoplasmic retention and subcellular distribution of the protein, as well as possible inhibition of protein function.


Pssm-ID: 462633  Cd Length: 108  Bit Score: 135.95  E-value: 2.00e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   1025 GAITKGVVLDSTEALCLAISRNSEQMASH--SAVLEAGKNLYTFCVSYVDSIQQmRNKFAFREAINKLENNLRELQICPA 1102
Cdd:pfam08919    1 GPVSKESILELSEDLESALVNLKESLASSqtSQLSDKVGQLHSYCSGYADSIPP-HAKFAFRELLSRLESQSRQLRICSA 79
                           90       100
                   ....*....|....*....|....*....
gi 62362414   1103 TAGS-GPAATQDFSKLLSSVKEISDIVQR 1130
Cdd:pfam08919   80 GGSRnSPGNSKLFSDLHNTVKEISNVVQR 108
STKc_IRAK cd14066
Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases ...
248-494 1.53e-36

Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. Some IRAKs may also play roles in T- and B-cell signaling, and adaptive immunity. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK-1, -2, and -4 are ubiquitously expressed and are active kinases, while IRAK-M is only induced in monocytes and macrophages and is an inactive kinase. Variations in IRAK genes are linked to diverse diseases including infection, sepsis, cancer, and autoimmune diseases. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain (a pseudokinase domain in the case of IRAK3), and a C-terminal domain; IRAK-4 lacks the C-terminal domain. This subfamily includes plant receptor-like kinases (RLKs) including Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1). BAK1 functions in BR (brassinosteroid)-regulated plant development and in pathways involved in plant resistance to pathogen infection and herbivore attack. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The IRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270968 [Multi-domain]  Cd Length: 272  Bit Score: 139.33  E-value: 1.53e-36
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKySLTVAVKTLKE--DTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLD 325
Cdd:cd14066    1 IGSGGFGTVYKGVLEN-GTVVAVKRLNEmnCAASKKEFLTELEMLGRLRHPNLVRLLGYCLESDEKLLVYEYMPNGSLED 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  326 YLReCNRqevNAVVL-----LYMATQISSAMEYL---EKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHA 397
Cdd:cd14066   80 RLH-CHK---GSPPLpwpqrLKIAKGIARGLEYLheeCPPPIIHGDIKSSNILLDEDFEPKLTDFGLARLIPPSESVSKT 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  398 G-AKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIAT------YGMSPYPGIDLSQVYELLEKDYRME----------- 459
Cdd:cd14066  156 SaVKGTIGYLAPEYIRTGRVSTKSDVYSFGVVLLELLTgkpavdENRENASRKDLVEWVESKGKEELEDildkrlvdddg 235
                        250       260       270
                 ....*....|....*....|....*....|....*
gi 62362414  460 RPEGCPEKVYELMRACWQWNPSDRPSFAEIHQAFE 494
Cdd:cd14066  236 VEEEEVEALLRLALLCTRSDPSLRPSMKEVVQMLE 270
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
247-687 1.65e-36

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 145.16  E-value: 1.65e-36
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLK----EDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGN 322
Cdd:COG0515   14 LLGRGGMGVVYLARDLRLGRPVALKVLRpelaADPEARERFRREARALARLNHPNIVRVYDVGEEDGRPYLVMEYVEGES 93
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLRECNRQEVNAVvlLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFP 402
Cdd:COG0515   94 LADLLRRRGPLPPAEA--LRILAQLAEALAAAHAAGIVHRDIKPANILLTPDGRVKLIDFGIARALGGATLTQTGTVVGT 171
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  403 IKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEKDYRM---ERPEGCPEKVYELMRACWQWN 479
Cdd:COG0515  172 PGYMAPEQARGEPVDPRSDVYSLGVTLYELLT-GRPPFDGDSPAELLRAHLREPPPppsELRPDLPPALDAIVLRALAKD 250
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  480 PSDRP-SFAEIHQAFETMFQES---SISDEVEKELGKQGVRGAVSTLLQAPELPTKTRTSRRAAEHRDTTDVPEMPHSKG 555
Cdd:COG0515  251 PEERYqSAAELAAALRAVLRSLaaaAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAPAAAAAAA 330
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  556 QGESDPLDHEPAVSPLLPRKERGPPEGGLNEDERLLPKDKKTNLFSALIKKKKKTAPTPPKRSSSFREMDGQPERRGAGE 635
Cdd:COG0515  331 AAAAALAAAAAAAAAAAAAALLAAAAALAAAAAAAAAAAAAAAAAAAAAAAAAALAAAAAAAAAAAAAALAAAAAAAAAA 410
                        410       420       430       440       450
                 ....*....|....*....|....*....|....*....|....*....|..
gi 62362414  636 EEGRDISNGALAFTPLDTADPAKSPKPSNGAGVPNGALRESGGSGFRSPHLW 687
Cdd:COG0515  411 AAAAAAAAALAAAAAAAAAAAAAAAAAAAAAARLLAAAAAAAAAAAAAPLLA 462
PKc_STE cd05122
Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the ...
245-488 1.69e-36

Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. This family is composed of STKs, and some dual-specificity PKs that phosphorylate both threonine and tyrosine residues of target proteins. Most members are kinases involved in mitogen-activated protein kinase (MAPK) signaling cascades, acting as MAPK kinases (MAPKKs), MAPKK kinases (MAPKKKs), or MAPKKK kinases (MAP4Ks). The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPKK, which itself is phosphorylated and activated by a MAPKKK. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAPKKK to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Other STE family members include p21-activated kinases (PAKs) and class III myosins, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain, which can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, as well as autophosphorylate the C-terminal motor domain. They play an important role in maintaining the structural integrity of photoreceptor cell microvilli. The STE family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270692 [Multi-domain]  Cd Length: 254  Bit Score: 138.88  E-value: 1.69e-36
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  245 KHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTME-VEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNL 323
Cdd:cd05122    5 LEKIGKGGFGVVYKARHKKTGQIVAIKKINLESKEkKESILNEIAILKKCKHPNIVKYYGSYLKKDELWIVMEFCSGGSL 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  324 LDYLRECNR--QEVN-AVVLLymatQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAH-AGA 399
Cdd:cd05122   85 KDLLKNTNKtlTEQQiAYVCK----EVLKGLEYLHSHGIIHRDIKAANILLTSDGEVKLIDFGLSAQLSDGKTRNTfVGT 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  400 KFpikWTAPESLAYNKFSIKSDVWAFGVLLWEIAtYGMSPYPGIDLSQVYELLEKD--YRMERPEGCPEKVYELMRACWQ 477
Cdd:cd05122  161 PY---WMAPEVIQGKPYGFKADIWSLGITAIEMA-EGKPPYSELPPMKALFLIATNgpPGLRNPKKWSKEFKDFLKKCLQ 236
                        250
                 ....*....|.
gi 62362414  478 WNPSDRPSFAE 488
Cdd:cd05122  237 KDPEKRPTAEQ 247
STKc_AMPK-like cd14003
Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze ...
246-491 2.47e-35

Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The AMPK-like subfamily is composed of AMPK, MARK, BRSK, NUAK, MELK, SNRK, TSSK, and SIK, among others. LKB1 serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. BRSKs play important roles in establishing neuronal polarity. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. The AMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270905 [Multi-domain]  Cd Length: 252  Bit Score: 135.34  E-value: 2.47e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  246 HKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLK---EAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGN 322
Cdd:cd14003    6 KTLGEGSFGKVKLARHKLTGEKVAIKIIDKSKLKEEIEEKikrEIEIMKLLNHPNIIKLYEVIETENKIYLVMEYASGGE 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLRECNR-QEVNAvvLLYMAtQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTY------TA 395
Cdd:cd14003   86 LFDYIVNNGRlSEDEA--RRFFQ-QLISAVDYCHSNGIVHRDLKLENILLDKNGNLKIIDFGLSNEFRGGSLlktfcgTP 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  396 HagakfpikWTAPESLAYNKF-SIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEKdYRMERPEGCPEKVYELMRA 474
Cdd:cd14003  163 A--------YAAPEVLLGRKYdGPKADVWSLGVILYAMLT-GYLPFDDDNDSKLFRKILK-GKYPIPSHLSPDARDLIRR 232
                        250
                 ....*....|....*..
gi 62362414  475 CWQWNPSDRPSFAEIHQ 491
Cdd:cd14003  233 MLVVDPSKRITIEEILN 249
Pkinase pfam00069
Protein kinase domain;
245-489 1.30e-34

Protein kinase domain;


Pssm-ID: 459660 [Multi-domain]  Cd Length: 217  Bit Score: 131.98  E-value: 1.30e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414    245 KHKLGGGQYGEVYEGVWKKYSLTVAVKTLK---EDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYG 321
Cdd:pfam00069    4 LRKLGSGSFGTVYKAKHRDTGKIVAIKKIKkekIKKKKDKNILREIKILKKLNHPNIVRLYDAFEDKDNLYLVLEYVEGG 83
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414    322 NLLDYLRE-CNRQEvnAVVLLYMAtQISSAMEYLEKKNfihrdlaarnCLVGenhlvkvadfglsrlmtgdTYTahagak 400
Cdd:pfam00069   84 SLFDLLSEkGAFSE--REAKFIMK-QILEGLESGSSLT----------TFVG-------------------TPW------ 125
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414    401 fpikWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYE--LLEKDYRMERPEGCPEKVYELMRACWQW 478
Cdd:pfam00069  126 ----YMAPEVLGGNPYGPKVDVWSLGCILYELLT-GKPPFPGINGNEIYEliIDQPYAFPELPSNLSEEAKDLLKKLLKK 200
                          250
                   ....*....|.
gi 62362414    479 NPSDRPSFAEI 489
Cdd:pfam00069  201 DPSKRLTATQA 211
STKc_CAMK cd05117
The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of ...
243-488 3.78e-34

The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. CAMKIV is implicated in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors, as well as in T-cell development and signaling. The CAMK family also consists of other related kinases including the Phosphorylase kinase Gamma subunit (PhKG), the C-terminal kinase domains of Ribosomal S6 kinase (RSK) and Mitogen and stress-activated kinase (MSK), Doublecortin-like kinase (DCKL), and the MAPK-activated protein kinases MK2, MK3, and MK5, among others. The CAMK family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270687 [Multi-domain]  Cd Length: 258  Bit Score: 131.83  E-value: 3.78e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  243 TMKHKLGGGQYGEVYEGVWKKYSLTVAVKTL---KEDTMEVEEFLKEAAVMKEIKHPNLVQLLGV-CTREPpFYIITEFM 318
Cdd:cd05117    3 ELGKVLGRGSFGVVRLAVHKKTGEEYAVKIIdkkKLKSEDEEMLRREIEILKRLDHPNIVKLYEVfEDDKN-LYLVMELC 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  319 TYGNLLDYLRECNR---QEVNAVVllymaTQISSAMEYLEKKNFIHRDLAARNCLV---GENHLVKVADFGLSRLMTGDT 392
Cdd:cd05117   82 TGGELFDRIVKKGSfseREAAKIM-----KQILSAVAYLHSQGIVHRDLKPENILLaskDPDSPIKIIDFGLAKIFEEGE 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  393 Y------TAHagakfpikWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYEL-LEKDYRMERPEGcp 465
Cdd:cd05117  157 KlktvcgTPY--------YVAPEVLKGKGYGKKCDIWSLGVILYILLC-GYPPFYGETEQELFEKiLKGKYSFDSPEW-- 225
                        250       260
                 ....*....|....*....|....*..
gi 62362414  466 EKVYE----LMRACWQWNPSDRPSFAE 488
Cdd:cd05117  226 KNVSEeakdLIKRLLVVDPKKRLTAAE 252
PTK_Jak_rpt1 cd05037
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak ...
242-489 5.17e-34

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily is composed of Jak1, Jak2, Jak3, TYK2, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. In the case of Jak2, the presumed pseudokinase (repeat 1) domain exhibits dual-specificity kinase activity, phosphorylating two negative regulatory sites in Jak2: Ser523 and Tyr570. Most Jaks are expressed in a wide variety of tissues, except for Jak3, which is expressed only in hematopoietic cells. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). Jaks are also involved in regulating the surface expression of some cytokine receptors. The Jak-STAT pathway is involved in many biological processes including hematopoiesis, immunoregulation, host defense, fertility, lactation, growth, and embryogenesis. The Jak subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270633 [Multi-domain]  Cd Length: 259  Bit Score: 131.83  E-value: 5.17e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  242 ITMKHKLGGGQYGEVYEGVWKKYS------LTVAVKTLKEDTMEV-EEFLKEAAVMKEIKHPNLVQLLGVCTRePPFYII 314
Cdd:cd05037    1 ITFHEHLGQGTFTNIYDGILREVGdgrvqeVEVLLKVLDSDHRDIsESFFETASLMSQISHKHLVKLYGVCVA-DENIMV 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  315 TEFMTYGNLLDYLREcNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLV------GENHLVKVADFGLSRLM 388
Cdd:cd05037   80 QEYVRYGPLDKYLRR-MGNNVPLSWKLQVAKQLASALHYLEDKKLIHGNVRGRNILLaregldGYPPFIKLSDPGVPITV 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  389 TGDTYTAHagakfPIKWTAPESL--AYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEgCPE 466
Cdd:cd05037  159 LSREERVD-----RIPWIAPECLrnLQANLTIAADKWSFGTTLWEICSGGEEPLSALSSQEKLQFYEDQHQLPAPD-CAE 232
                        250       260
                 ....*....|....*....|...
gi 62362414  467 kVYELMRACWQWNPSDRPSFAEI 489
Cdd:cd05037  233 -LAELIMQCWTYEPTKRPSFRAI 254
PK_GC cd13992
Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows ...
255-489 8.00e-34

Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs lack a critical aspartate involved in ATP binding and does not exhibit kinase activity. It functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270894 [Multi-domain]  Cd Length: 268  Bit Score: 131.36  E-value: 8.00e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  255 EVYEGVWKKYslTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDYLRecNR-Q 333
Cdd:cd13992   17 VKKVGVYGGR--TVAIKHITFSRTEKRTILQELNQLKELVHDNLNKFIGICINPPNIAVVTEYCTRGSLQDVLL--NReI 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  334 EVNAVVLLYMATQISSAMEYLEKKNFI-HRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPIK--WTAPES 410
Cdd:cd13992   93 KMDWMFKSSFIKDIVKGMNYLHSSSIGyHGRLKSSNCLVDSRWVVKLTDFGLRNLLEEQTNHQLDEDAQHKKllWTAPEL 172
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  411 LAYNKF----SIKSDVWAFGVLLWEIATYgMSPYPGID---LSQVYELLEKDYRmeRPE------GCPEKVYELMRACWQ 477
Cdd:cd13992  173 LRGSLLevrgTQKGDVYSFAIILYEILFR-SDPFALERevaIVEKVISGGNKPF--RPElavlldEFPPRLVLLVKQCWA 249
                        250
                 ....*....|..
gi 62362414  478 WNPSDRPSFAEI 489
Cdd:cd13992  250 ENPEKRPSFKQI 261
STKc_Raf cd14062
Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) ...
248-494 8.43e-34

Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Raf kinases act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. Aberrant expression or activation of components in this pathway are associated with tumor initiation, progression, and metastasis. Raf proteins contain a Ras binding domain, a zinc finger cysteine-rich domain, and a catalytic kinase domain. Vertebrates have three Raf isoforms (A-, B-, and C-Raf) with different expression profiles, modes of regulation, and abilities to function in the ERK cascade, depending on cellular context and stimuli. They have essential and non-overlapping roles during embryo- and organogenesis. Knockout of each isoform results in a lethal phenotype or abnormality in most mouse strains. The Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270964 [Multi-domain]  Cd Length: 253  Bit Score: 130.98  E-value: 8.43e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKyslTVAVKTLKEDT---MEVEEFLKEAAVMKEIKHPNLVQLLGVCTrEPPFYIITEFMTYGNLL 324
Cdd:cd14062    1 IGSGSFGTVYKGRWHG---DVAVKKLNVTDptpSQLQAFKNEVAVLRKTRHVNILLFMGYMT-KPQLAIVTQWCEGSSLY 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  325 DYLRECNRQ-EVNAvvLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTgdTYTAHAGAKFP- 402
Cdd:cd14062   77 KHLHVLETKfEMLQ--LIDIARQTAQGMDYLHAKNIIHRDLKSNNIFLHEDLTVKIGDFGLATVKT--RWSGSQQFEQPt 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  403 --IKWTAPESLAY---NKFSIKSDVWAFGVLLWEIATyGMSPYPGID-----LSQV-YELLEKDYRMERPEgCPEKVYEL 471
Cdd:cd14062  153 gsILWMAPEVIRMqdeNPYSFQSDVYAFGIVLYELLT-GQLPYSHINnrdqiLFMVgRGYLRPDLSKVRSD-TPKALRRL 230
                        250       260
                 ....*....|....*....|...
gi 62362414  472 MRACWQWNPSDRPSFAEIHQAFE 494
Cdd:cd14062  231 MEDCIKFQRDERPLFPQILASLE 253
STKc_LIMK cd14154
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer ...
248-496 1.30e-33

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. Vertebrate have two members, LIMK1 and LIMK2. The LIMK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271056 [Multi-domain]  Cd Length: 272  Bit Score: 131.09  E-value: 1.30e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKyslTVAVKTLKEDTMEVEE----FLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNL 323
Cdd:cd14154    1 LGKGFFGQAIKVTHRE---TGEVMVMKELIRFDEEaqrnFLKEVKVMRSLDHPNVLKFIGVLYKDKKLNLITEYIPGGTL 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  324 LDYLRECNR-----QEVNavvllyMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRL----------M 388
Cdd:cd14154   78 KDVLKDMARplpwaQRVR------FAKDIASGMAYLHSMNIIHRDLNSHNCLVREDKTVVVADFGLARLiveerlpsgnM 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  389 TGDTYTAHAGAKFPIK---------WTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRME 459
Cdd:cd14154  152 SPSETLRHLKSPDRKKrytvvgnpyWMAPEMLNGRSYDEKVDIFSFGIVLCEIIGRVEADPDYLPRTKDFGLNVDSFREK 231
                        250       260       270
                 ....*....|....*....|....*....|....*..
gi 62362414  460 RPEGCPEKVYELMRACWQWNPSDRPSFAEIHQAFETM 496
Cdd:cd14154  232 FCAGCPPPFFKLAFLCCDLDPEKRPPFETLEEWLEAL 268
PTKc_Aatyk2 cd05086
Catalytic domain of the Protein Tyrosine Kinase, Apoptosis-associated tyrosine kinase 2; PTKs ...
246-491 3.51e-33

Catalytic domain of the Protein Tyrosine Kinase, Apoptosis-associated tyrosine kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk2 is a member of the Aatyk subfamily of proteins, which are receptor kinases containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. Aatyk2 is also called lemur tyrosine kinase 2 (Lmtk2) or brain-enriched kinase (Brek). It is expressed at high levels in early postnatal brain, and has been shown to play a role in nerve growth factor (NGF) signaling. Studies with knockout mice reveal that Aatyk2 is essential for late stage spermatogenesis. Although it is classified as a PTK based on sequence similarity and the phylogenetic tree, Aatyk2 has been functionally characterized as a serine/threonine kinase. The Aatyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270669 [Multi-domain]  Cd Length: 271  Bit Score: 129.60  E-value: 3.51e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  246 HKLGGGQYGEVYEG-VWKKYSLT-VAVKTLKE--DTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYG 321
Cdd:cd05086    3 QEIGNGWFGKVLLGeIYTGTSVArVVVKELKAsaNPKEQDDFLQQGEPYYILQHPNILQCVGQCVEAIPYLLVFEFCDLG 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  322 NLLDYL---RECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAG 398
Cdd:cd05086   83 DLKTYLanqQEKLRGDSQIMLLQRMACEIAAGLAHMHKHNFLHSDLALRNCYLTSDLTVKVGDYGIGFSRYKEDYIETDD 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  399 AKF-PIKWTAPE----------SLAYNKFsikSDVWAFGVLLWEIATYGMSPYPGIDLSQVYE--LLEKDYRMERP---E 462
Cdd:cd05086  163 KKYaPLRWTAPElvtsfqdgllAAEQTKY---SNIWSLGVTLWELFENAAQPYSDLSDREVLNhvIKERQVKLFKPhleQ 239
                        250       260
                 ....*....|....*....|....*....
gi 62362414  463 GCPEKVYELMRACWqWNPSDRPSFAEIHQ 491
Cdd:cd05086  240 PYSDRWYEVLQFCW-LSPEKRPTAEEVHR 267
STKc_B-Raf cd14151
Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) ...
233-499 2.46e-32

Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. B-Raf activates ERK with the strongest magnitude, compared with other Raf kinases. Mice embryos deficient in B-Raf die around midgestation due to vascular hemorrhage caused by apoptotic endothelial cells. Mutations in B-Raf have been implicated in initiating tumorigenesis and tumor progression, and are found in malignant cutaneous melanoma, papillary thyroid cancer, as well as in ovarian and colorectal carcinomas. Most oncogenic B-Raf mutations are located at the activation loop of the kinase and surrounding regions; the V600E mutation accounts for around 90% of oncogenic mutations. The V600E mutant constitutively activates MEK, resulting in sustained activation of ERK. B-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The B-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271053 [Multi-domain]  Cd Length: 274  Bit Score: 127.48  E-value: 2.46e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  233 DKWEMERTDITMKHKLGGGQYGEVYEGVWKKyslTVAVKTLK---EDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTReP 309
Cdd:cd14151    1 DDWEIPDGQITVGQRIGSGSFGTVYKGKWHG---DVAVKMLNvtaPTPQQLQAFKNEVGVLRKTRHVNILLFMGYSTK-P 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  310 PFYIITEFMTYGNLLDYLrECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGL----S 385
Cdd:cd14151   77 QLAIVTQWCEGSSLYHHL-HIIETKFEMIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGLatvkS 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  386 RLMTGDTYTAHAGAkfpIKWTAPESLAY---NKFSIKSDVWAFGVLLWEIATyGMSPYPGI-DLSQVYELLEKDY----R 457
Cdd:cd14151  156 RWSGSHQFEQLSGS---ILWMAPEVIRMqdkNPYSFQSDVYAFGIVLYELMT-GQLPYSNInNRDQIIFMVGRGYlspdL 231
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 62362414  458 MERPEGCPEKVYELMRACWQWNPSDRPSFAEIHQAFETMFQE 499
Cdd:cd14151  232 SKVRSNCPKAMKRLMAECLKKKRDERPLFPQILASIELLARS 273
STKc_Cdc7_like cd06627
Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs ...
247-488 8.79e-32

Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include Schizosaccharomyces pombe Cdc7, Saccharomyces cerevisiae Cdc15, Arabidopsis thaliana mitogen-activated protein kinase kinase kinase (MAPKKK) epsilon, and related proteins. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Cdc7 is essential for cell division by playing a key role in the initiation of septum formation and cytokinesis. Budding yeast Cdc15 functions to coordinate mitotic exit with cytokinesis. Arabidopsis MAPKKK epsilon is required for pollen development in the plasma membrane. The Cdc7-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270797 [Multi-domain]  Cd Length: 254  Bit Score: 125.03  E-value: 8.79e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM---EVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNL 323
Cdd:cd06627    7 LIGRGAFGSVYKGLNLNTGEFVAIKQISLEKIpksDLKSVMGEIDLLKKLNHPNIVKYIGSVKTKDSLYIILEYVENGSL 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  324 LDYLRECNRQEVNaVVLLYMAtQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPi 403
Cdd:cd06627   87 ASIIKKFGKFPES-LVAVYIY-QVLEGLAYLHEQGVIHRDIKGANILTTKDGLVKLADFGVATKLNEVEKDENSVVGTP- 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  404 KWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYpgIDLSQVYELLE--KDYRMERPEGCPEKVYELMRACWQWNPS 481
Cdd:cd06627  164 YWMAPEVIEMSGVTTASDIWSVGCTVIELLT-GNPPY--YDLQPMAALFRivQDDHPPLPENISPELRDFLLQCFQKDPT 240

                 ....*..
gi 62362414  482 DRPSFAE 488
Cdd:cd06627  241 LRPSAKE 247
STKc_A-Raf cd14150
Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) ...
241-500 2.20e-31

Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. A-Raf cooperates with C-Raf in regulating ERK transient phosphorylation that is associated with cyclin D expression and cell cycle progression. Mice deficient in A-Raf are born alive but show neurological and intestinal defects. A-Raf demonstrates low kinase activity to MEK, compared with B- and C-Raf, and may also have alternative functions other than in the ERK signaling cascade. It regulates the M2 type pyruvate kinase, a key glycolytic enzyme. It also plays a role in endocytic membrane trafficking. A-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. It functions in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The A-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271052 [Multi-domain]  Cd Length: 265  Bit Score: 124.36  E-value: 2.20e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  241 DITMKHKLGGGQYGEVYEGVWKKyslTVAVKTLK--EDTME-VEEFLKEAAVMKEIKHPNLVQLLGVCTRePPFYIITEF 317
Cdd:cd14150    1 EVSMLKRIGTGSFGTVFRGKWHG---DVAVKILKvtEPTPEqLQAFKNEMQVLRKTRHVNILLFMGFMTR-PNFAIITQW 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  318 MTYGNLLDYLRECNRQeVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTgdTYTAHA 397
Cdd:cd14150   77 CEGSSLYRHLHVTETR-FDTMQLIDVARQTAQGMDYLHAKNIIHRDLKSNNIFLHEGLTVKIGDFGLATVKT--RWSGSQ 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  398 GAKFP---IKWTAPESLAY---NKFSIKSDVWAFGVLLWEIATyGMSPYPGID-LSQVYELLEKDYRM----ERPEGCPE 466
Cdd:cd14150  154 QVEQPsgsILWMAPEVIRMqdtNPYSFQSDVYAYGVVLYELMS-GTLPYSNINnRDQIIFMVGRGYLSpdlsKLSSNCPK 232
                        250       260       270
                 ....*....|....*....|....*....|....
gi 62362414  467 KVYELMRACWQWNPSDRPSFAEIHQAFEtMFQES 500
Cdd:cd14150  233 AMKRLLIDCLKFKREERPLFPQILVSIE-LLQRL 265
STKc_RIP1 cd14027
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze ...
248-493 2.83e-31

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP1 harbors a C-terminal Death domain (DD), which binds death receptors (DRs) including TNF receptor 1, Fas, TNF-related apoptosis-inducing ligand receptor 1 (TRAILR1), and TRAILR2. It also interacts with other DD-containing adaptor proteins such as TRADD and FADD. RIP1 can also recruit other kinases including MEKK1, MEKK3, and RIP3 through an intermediate domain (ID) that bears a RIP homotypic interaction motif (RHIM). RIP1 plays a crucial role in determining a cell's fate, between survival or death, following exposure to stress signals. It is important in the signaling of NF-kappaB and MAPKs, and it links DR-associated signaling to reactive oxygen species (ROS) production. Abnormal RIP1 function may result in ROS accummulation affecting inflammatory responses, innate immunity, stress responses, and cell survival. RIP kinases serve as essential sensors of cellular stress. The RIP1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270929 [Multi-domain]  Cd Length: 267  Bit Score: 124.15  E-value: 2.83e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVaVKTLKEDTMEVE---EFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLL 324
Cdd:cd14027    1 LDSGGFGKVSLCFHRTQGLVV-LKTVYTGPNCIEhneALLEEGKMMNRLRHSRVVKLLGVILEEGKYSLVMEYMEKGNLM 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  325 DYLRecnRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGL------SRLMTGD------- 391
Cdd:cd14027   80 HVLK---KVSVPLSVKGRIILEIIEGMAYLHGKGVIHKDLKPENILVDNDFHIKIADLGLasfkmwSKLTKEEhneqrev 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  392 --TYTAHAGAKFpikWTAPESL--AYNKFSIKSDVWAFGVLLWEIATyGMSPYP-GIDLSQVYELLEKDYR---MERPEG 463
Cdd:cd14027  157 dgTAKKNAGTLY---YMAPEHLndVNAKPTEKSDVYSFAIVLWAIFA-NKEPYEnAINEDQIIMCIKSGNRpdvDDITEY 232
                        250       260       270
                 ....*....|....*....|....*....|
gi 62362414  464 CPEKVYELMRACWQWNPSDRPSFAEIHQAF 493
Cdd:cd14027  233 CPREIIDLMKLCWEANPEARPTFPGIEEKF 262
PKc_TNNI3K cd14064
Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting kinase; ...
248-489 2.83e-31

Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TNNI3K, also called cardiac ankyrin repeat kinase (CARK), is a cardiac-specific troponin I-interacting kinase that promotes cardiac myogenesis, improves cardiac performance, and protects the myocardium from ischemic injury. It contains N-terminal ankyrin repeats, a catalytic kinase domain, and a C-terminal serine-rich domain. TNNI3K exerts a disease-accelerating effect on cardiac dysfunction and reduced survival in mouse models of cardiomyopathy. The TNNI3K subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270966 [Multi-domain]  Cd Length: 254  Bit Score: 123.79  E-value: 2.83e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKkySLTVAVKTLKEDTM----EVEEFLKEAAVMKEIKHPNLVQLLGVCTREPP-FYIITEFMTYGN 322
Cdd:cd14064    1 IGSGSFGKVYKGRCR--NKIVAIKRYRANTYcsksDVDMFCREVSILCRLNHPCVIQFVGACLDDPSqFAIVTQYVSGGS 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLREcNRQEVNAVVLLYMATQISSAMEYLEK--KNFIHRDLAARNCLVGENHLVKVADFGLSRL---MTGDTYTAHA 397
Cdd:cd14064   79 LFSLLHE-QKRVIDLQSKLIIAVDVAKGMEYLHNltQPIIHRDLNSHNILLYEDGHAVVADFGESRFlqsLDEDNMTKQP 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  398 GAkfpIKWTAPESLAYN-KFSIKSDVWAFGVLLWEIATyGMSPYPgiDLSQVYELLEKDYRMERPE---GCPEKVYELMR 473
Cdd:cd14064  158 GN---LRWMAPEVFTQCtRYSIKADVFSYALCLWELLT-GEIPFA--HLKPAAAAADMAYHHIRPPigySIPKPISSLLM 231
                        250
                 ....*....|....*.
gi 62362414  474 ACWQWNPSDRPSFAEI 489
Cdd:cd14064  232 RGWNAEPESRPSFVEI 247
STKc_Nek cd08215
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; ...
247-491 5.92e-31

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek family is composed of 11 different mammalian members (Nek1-11) with similarity to the catalytic domain of Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants that were prevented from entering mitosis. Neks contain a conserved N-terminal catalytic domain and a more divergent C-terminal regulatory region of various sizes and structures. They are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270855 [Multi-domain]  Cd Length: 258  Bit Score: 122.96  E-value: 5.92e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM---EVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNL 323
Cdd:cd08215    7 VIGKGSFGSAYLVRRKSDGKLYVLKEIDLSNMsekEREEALNEVKLLSKLKHPNIVKYYESFEENGKLCIVMEYADGGDL 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  324 LDYLRECNRQEVN---AVVLLYMaTQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHagak 400
Cdd:cd08215   87 AQKIKKQKKKGQPfpeEQILDWF-VQICLALKYLHSRKILHRDLKTQNIFLTKDGVVKLGDFGISKVLESTTDLAK---- 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  401 fpikwT--------APE---SLAYNKfsiKSDVWAFGVLLWEIATyGMSPYPGIDLSQ-VYELLEKDYRMeRPEGCPEKV 468
Cdd:cd08215  162 -----TvvgtpyylSPElceNKPYNY---KSDIWALGCVLYELCT-LKHPFEANNLPAlVYKIVKGQYPP-IPSQYSSEL 231
                        250       260
                 ....*....|....*....|...
gi 62362414  469 YELMRACWQWNPSDRPSFAEIHQ 491
Cdd:cd08215  232 RDLVNSMLQKDPEKRPSANEILS 254
STKc_LIMK2 cd14222
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the ...
248-496 1.53e-30

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMK2 activation is induced by transforming growth factor-beta l (TGFb-l) and shares the same subcellular location as the cofilin family member twinfilin, which may be its biological substrate. LIMK2 plays a role in spermatogenesis, and may contribute to tumor progression and metastasis formation in some cancer cells. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. The LIMK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271124 [Multi-domain]  Cd Length: 272  Bit Score: 121.97  E-value: 1.53e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTL-KEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDY 326
Cdd:cd14222    1 LGKGFFGQAIKVTHKATGKVMVMKELiRCDEETQKTFLTEVKVMRSLDHPNVLKFIGVLYKDKRLNLLTEFIEGGTLKDF 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  327 LRECN----RQEVNavvllyMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAgAKFP 402
Cdd:cd14222   81 LRADDpfpwQQKVS------FAKGIASGMAYLHSMSIIHRDLNSHNCLIKLDKTVVVADFGLSRLIVEEKKKPPP-DKPT 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  403 IK--------------------WTAPESLAYNKFSIKSDVWAFGVLLWEIatygmspypgidLSQVY---ELLEK--DYR 457
Cdd:cd14222  154 TKkrtlrkndrkkrytvvgnpyWMAPEMLNGKSYDEKVDIFSFGIVLCEI------------IGQVYadpDCLPRtlDFG 221
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*..
gi 62362414  458 ME--------RPEGCPEKVYELMRACWQWNPSDRPSFAEIHQAFETM 496
Cdd:cd14222  222 LNvrlfwekfVPKDCPPAFFPLAAICCRLEPDSRPAFSKLEDSFEAL 268
STKc_MST3_like cd06609
Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs ...
247-485 1.57e-30

Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST3, MST4, STK25, Schizosaccharomyces pombe Nak1 and Sid1, Saccharomyces cerevisiae sporulation-specific protein 1 (SPS1), and related proteins. Nak1 is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Sid1 is a component in the septation initiation network (SIN) signaling pathway, and plays a role in cytokinesis. SPS1 plays a role in regulating proteins required for spore wall formation. MST4 plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. STK25 may play a role in the regulation of cell migration and polarization. The MST3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270786 [Multi-domain]  Cd Length: 274  Bit Score: 121.97  E-value: 1.57e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKT--LKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLL 324
Cdd:cd06609    8 RIGKGSFGEVYKGIDKRTNQVVAIKVidLEEAEDEIEDIQQEIQFLSQCDSPYITKYYGSFLKGSKLWIIMEYCGGGSVL 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  325 DYLRECNRQEVNAVVLLYmatQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAH--AGAKFp 402
Cdd:cd06609   88 DLLKPGPLDETYIAFILR---EVLLGLEYLHSEGKIHRDIKAANILLSEEGDVKLADFGVSGQLTSTMSKRNtfVGTPF- 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  403 ikWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEKDY--RMERPEGCPEkVYELMRACWQWNP 480
Cdd:cd06609  164 --WMAPEVIKQSGYDEKADIWSLGITAIELAK-GEPPLSDLHPMRVLFLIPKNNppSLEGNKFSKP-FKDFVELCLNKDP 239

                 ....*
gi 62362414  481 SDRPS 485
Cdd:cd06609  240 KERPS 244
STKc_ATG1_ULK_like cd14009
Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like ...
248-489 1.80e-30

Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes yeast ATG1 and metazoan homologs including vertebrate ULK1-3. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. It is involved in nutrient sensing and signaling, the assembly of autophagy factors and the execution of autophagy. In metazoans, ATG1 homologs display additional functions. Unc-51 and ULKs have been implicated in neuronal and axonal development. The ATG1/ULK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270911 [Multi-domain]  Cd Length: 251  Bit Score: 121.18  E-value: 1.80e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTME---VEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLL 324
Cdd:cd14009    1 IGRGSFATVWKGRHKQTGEVVAIKEISRKKLNkklQENLESEIAILKSIKHPNIVRLYDVQKTEDFIYLVLEYCAGGDLS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  325 DYLREcnRQEVN-AVVLLYMaTQISSAMEYLEKKNFIHRDLAARNCLV---GENHLVKVADFGLSRLMTGDTYtAHAGAK 400
Cdd:cd14009   81 QYIRK--RGRLPeAVARHFM-QQLASGLKFLRSKNIIHRDLKPQNLLLstsGDDPVLKIADFGFARSLQPASM-AETLCG 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  401 FPIkWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPG---IDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQ 477
Cdd:cd14009  157 SPL-YMAPEILQFQKYDAKADLWSVGAILFEMLV-GKPPFRGsnhVQLLRNIERSDAVIPFPIAAQLSPDCKDLLRRLLR 234
                        250
                 ....*....|..
gi 62362414  478 WNPSDRPSFAEI 489
Cdd:cd14009  235 RDPAERISFEEF 246
STKc_AGC cd05123
Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
248-491 2.61e-30

Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AGC kinases regulate many cellular processes including division, growth, survival, metabolism, motility, and differentiation. Many are implicated in the development of various human diseases. Members of this family include cAMP-dependent Protein Kinase (PKA), cGMP-dependent Protein Kinase (PKG), Protein Kinase C (PKC), Protein Kinase B (PKB), G protein-coupled Receptor Kinase (GRK), Serum- and Glucocorticoid-induced Kinase (SGK), and 70 kDa ribosomal Protein S6 Kinase (p70S6K or S6K), among others. AGC kinases share an activation mechanism based on the phosphorylation of up to three sites: the activation loop (A-loop), the hydrophobic motif (HM) and the turn motif. Phosphorylation at the A-loop is required of most AGC kinases, which results in a disorder-to-order transition of the A-loop. The ordered conformation results in the access of substrates and ATP to the active site. A subset of AGC kinases with C-terminal extensions containing the HM also requires phosphorylation at this site. Phosphorylation at the HM allows the C-terminal extension to form an ordered structure that packs into the hydrophobic pocket of the catalytic domain, which then reconfigures the kinase into an active bi-lobed state. In addition, growth factor-activated AGC kinases such as PKB, p70S6K, RSK, MSK, PKC, and SGK, require phosphorylation at the turn motif (also called tail or zipper site), located N-terminal to the HM at the C-terminal extension. The AGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and Phosphoinositide 3-Kinase.


Pssm-ID: 270693 [Multi-domain]  Cd Length: 250  Bit Score: 120.70  E-value: 2.61e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEgVWKKYSLTV-AVKTLKEDTM----EVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGN 322
Cdd:cd05123    1 LGKGSFGKVLL-VRKKDTGKLyAMKVLRKKEIikrkEVEHTLNERNILERVNHPFIVKLHYAFQTEEKLYLVLDYVPGGE 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLRECNR-QEvnAVVLLYMAtQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAH--AGa 399
Cdd:cd05123   80 LFSHLSKEGRfPE--ERARFYAA-EIVLALEYLHSLGIIYRDLKPENILLDSDGHIKLTDFGLAKELSSDGDRTYtfCG- 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  400 kfpikwT----APESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYEL-LEKDYRMerPEGCPEKVYELMRA 474
Cdd:cd05123  156 ------TpeylAPEVLLGKGYGKAVDWWSLGVLLYEMLT-GKPPFYAENRKEIYEKiLKSPLKF--PEYVSPEAKSLISG 226
                        250       260
                 ....*....|....*....|
gi 62362414  475 CWQWNPSDR---PSFAEIHQ 491
Cdd:cd05123  227 LLQKDPTKRlgsGGAEEIKA 246
PKc_LIMK_like_unk cd14156
Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs ...
248-496 2.71e-30

Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. This group is composed of uncharacterized proteins with similarity to LIMK and Testicular or testis-specific protein kinase (TESK). LIMKs are characterized as serine/threonine kinases (STKs) while TESKs are dual-specificity protein kinases. Both LIMK and TESK phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They are implicated in many cellular functions including cell spreading, motility, morphogenesis, meiosis, mitosis, and spermatogenesis. The LIMK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271058 [Multi-domain]  Cd Length: 256  Bit Score: 120.70  E-value: 2.71e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEvEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDYL 327
Cdd:cd14156    1 IGSGFFSKVYKVTHGATGKVMVVKIYKNDVDQ-HKIVREISLLQKLSHPNIVRYLGICVKDEKLHPILEYVSGGCLEELL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  328 RE-----CNRQEVNavvllyMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVK---VADFGLSRLM------TGDTY 393
Cdd:cd14156   80 AReelplSWREKVE------LACDISRGMVYLHSKNIYHRDLNSKNCLIRVTPRGReavVTDFGLAREVgempanDPERK 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  394 TAHAGAKFpikWTAPESLAYNKFSIKSDVWAFGVLLWEIAtyGMSPYPGIDL--SQVYELLEKDYRmERPEGCPEKVYEL 471
Cdd:cd14156  154 LSLVGSAF---WMAPEMLRGEPYDRKVDVFSFGIVLCEIL--ARIPADPEVLprTGDFGLDVQAFK-EMVPGCPEPFLDL 227
                        250       260
                 ....*....|....*....|....*
gi 62362414  472 MRACWQWNPSDRPSFAEIHQAFETM 496
Cdd:cd14156  228 AASCCRMDAFKRPSFAELLDELEDI 252
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
125-208 2.94e-30

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.


Pssm-ID: 214585 [Multi-domain]  Cd Length: 84  Bit Score: 114.63  E-value: 2.94e-30
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414     125 HSWYHGPVSRNAAEYLLSSGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTASDGKLYVSSESRFNTLAELVHHHST 204
Cdd:smart00252    1 QPWYHGFISREEAEKLLKNEGDGDFLVRDSESSPGDYVLSVRVKGKVKHYRIRRNEDGKFYLEGGRKFPSLVELVEHYQK 80

                    ....
gi 62362414     205 VADG 208
Cdd:smart00252   81 NSLG 84
STKc_TSSK-like cd14080
Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs ...
243-489 3.37e-30

Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK1 and TSSK2 are expressed specifically in meiotic and postmeiotic spermatogenic cells, respectively. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. TSSK6, also called SSTK, is expressed at the head of elongated sperm. TSSK1/TSSK2 double knock-out and TSSK6 null mice are sterile without manifesting other defects, making these kinases viable targets for male contraception. The TSSK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270982 [Multi-domain]  Cd Length: 262  Bit Score: 120.75  E-value: 3.37e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  243 TMKHKLGGGQYGEVYEGVWKKYSL--TVAVKTLkeDTM-----EVEEFL-KEAAVMKEIKHPNLVQLLGVCTREPPFYII 314
Cdd:cd14080    3 RLGKTIGEGSYSKVKLAEYTKSGLkeKVACKII--DKKkapkdFLEKFLpRELEILRKLRHPNIIQVYSIFERGSKVFIF 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  315 TEFMTYGNLLDYLRECNR-QEVNAVVllyMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGD-- 391
Cdd:cd14080   81 MEYAEHGDLLEYIQKRGAlSESQARI---WFRQLALAVQYLHSLDIAHRDLKCENILLDSNNNVKLSDFGFARLCPDDdg 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  392 -----TYTAHAGakfpikWTAPESL---AYNKFsiKSDVWAFGVLLWeIATYGMSPYPGIDLSQVYE-LLEKDYRM-ERP 461
Cdd:cd14080  158 dvlskTFCGSAA------YAAPEILqgiPYDPK--KYDIWSLGVILY-IMLCGSMPFDDSNIKKMLKdQQNRKVRFpSSV 228
                        250       260
                 ....*....|....*....|....*...
gi 62362414  462 EGCPEKVYELMRACWQWNPSDRPSFAEI 489
Cdd:cd14080  229 KKLSPECKDLIDQLLEPDPTKRATIEEI 256
SH2 pfam00017
SH2 domain;
127-202 5.26e-30

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 113.46  E-value: 5.26e-30
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 62362414    127 WYHGPVSRNAAE-YLLSSGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTASDGKLYVSSESRFNTLAELVHHH 202
Cdd:pfam00017    1 WYHGKISRQEAErLLLNGKPDGTFLVRESESTPGGYTLSVRDDGKVKHYKIQSTDNGGYYISGGVKFSSLAELVEHY 77
STKc_Nek6 cd08228
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
240-496 1.40e-29

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek6 is required for the transition from metaphase to anaphase. It also plays important roles in mitotic spindle formation and cytokinesis. Activated by Nek9 during mitosis, Nek6 phosphorylates Eg5, a kinesin that is important for spindle bipolarity. Nek6 localizes to spindle microtubules during metaphase and anaphase, and to the midbody during cytokinesis. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270865 [Multi-domain]  Cd Length: 268  Bit Score: 119.36  E-value: 1.40e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  240 TDITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLK----EDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIIT 315
Cdd:cd08228    2 ANFQIEKKIGRGQFSEVYRATCLLDRKPVALKKVQifemMDAKARQDCVKEIDLLKQLNHPNVIKYLDSFIEDNELNIVL 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  316 EFMTYGNL---LDYLRECNRQEVNAVVLLYMaTQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDT 392
Cdd:cd08228   82 ELADAGDLsqmIKYFKKQKRLIPERTVWKYF-VQLCSAVEHMHSRRVMHRDIKPANVFITATGVVKLGDLGLGRFFSSKT 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  393 YTAHAGAKFPIkWTAPESLAYNKFSIKSDVWAFGVLLWEIATYgMSPYPGiDLSQVYELLEKDYRMERP----EGCPEKV 468
Cdd:cd08228  161 TAAHSLVGTPY-YMSPERIHENGYNFKSDIWSLGCLLYEMAAL-QSPFYG-DKMNLFSLCQKIEQCDYPplptEHYSEKL 237
                        250       260
                 ....*....|....*....|....*...
gi 62362414  469 YELMRACWQWNPSDRPSFAEIHQAFETM 496
Cdd:cd08228  238 RELVSMCIYPDPDQRPDIGYVHQIAKQM 265
STKc_Aurora cd14007
Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of ...
241-489 3.74e-29

Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Yeast contains only one Aurora kinase while most higher eukaryotes have two. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2. Aurora-B is most active at the transition during metaphase to the end of mitosis. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270909 [Multi-domain]  Cd Length: 253  Bit Score: 117.58  E-value: 3.74e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  241 DITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM----EVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITE 316
Cdd:cd14007    1 DFEIGKPLGKGKFGNVYLAREKKSGFIVALKVISKSQLqksgLEHQLRREIEIQSHLRHPNILRLYGYFEDKKRIYLILE 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  317 FMTYGNLLDYLRECNR-QEVNAVVllYMAtQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSrlmtgdtytA 395
Cdd:cd14007   81 YAPNGELYKELKKQKRfDEKEAAK--YIY-QLALALDYLHSKNIIHRDIKPENILLGSNGELKLADFGWS---------V 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  396 HAGAKFP------IKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYE-LLEKDYRMerpegcPEKV 468
Cdd:cd14007  149 HAPSNRRktfcgtLDYLPPEMVEGKEYDYKVDIWSLGVLCYELLV-GKPPFESKSHQETYKrIQNVDIKF------PSSV 221
                        250       260
                 ....*....|....*....|....*
gi 62362414  469 YE----LMRACWQWNPSDRPSFAEI 489
Cdd:cd14007  222 SPeakdLISKLLQKDPSKRLSLEQV 246
STKc_BRSK1_2 cd14081
Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the ...
235-491 8.44e-29

Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BRSK1, also called SAD-B or SAD1 (Synapses of Amphids Defective homolog 1), and BRSK2, also called SAD-A, are highly expressed in mammalian forebrain. They play important roles in establishing neuronal polarity. BRSK1/2 double knock-out mice die soon after birth, showing thin cerebral cortices due to disordered subplate layers and neurons that lack distinct axons and dendrites. BRSK1 regulates presynaptic neurotransmitter release. Its activity fluctuates during cell cysle progression and it acts as a regulator of centrosome duplication. BRSK2 is also abundant in pancreatic islets, where it is involved in the regulation of glucose-stimulated insulin secretion. The BRSK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270983 [Multi-domain]  Cd Length: 255  Bit Score: 116.58  E-value: 8.44e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  235 WEMERTditmkhkLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFL----KEAAVMKEIKHPNLVQLLGVCTREPP 310
Cdd:cd14081    3 YRLGKT-------LGKGQTGLVKLAKHCVTGQKVAIKIVNKEKLSKESVLmkveREIAIMKLIEHPNVLKLYDVYENKKY 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  311 FYIITEFMTYGNLLDYLRECNR-QEVNAVVLLYmatQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMT 389
Cdd:cd14081   76 LYLVLEYVSGGELFDYLVKKGRlTEKEARKFFR---QIISALDYCHSHSICHRDLKPENLLLDEKNNIKIADFGMASLQP 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  390 GD----TY--TAHagakfpikWTAPESLAYNKF-SIKSDVWAFGVLLWEIATyGMSPYPGIDLSQvyeLLEK----DYRM 458
Cdd:cd14081  153 EGslleTScgSPH--------YACPEVIKGEKYdGRKADIWSCGVILYALLV-GALPFDDDNLRQ---LLEKvkrgVFHI 220
                        250       260       270
                 ....*....|....*....|....*....|...
gi 62362414  459 erPEGCPEKVYELMRACWQWNPSDRPSFAEIHQ 491
Cdd:cd14081  221 --PHFISPDAQDLLRRMLEVNPEKRITIEEIKK 251
STKc_Nek11 cd08222
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
247-489 1.12e-28

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 11; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek11 is involved, through direct phosphorylation, in regulating the degradation of Cdc25A (Cell Division Cycle 25 homolog A), which plays a role in cell cycle progression and in activating cyclin dependent kinases. Nek11 is activated by CHK1 (CHeckpoint Kinase 1) and may be involved in the G2/M checkpoint. Nek11 may also play a role in the S-phase checkpoint as well as in DNA replication and genotoxic stress responses. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270861 [Multi-domain]  Cd Length: 260  Bit Score: 116.37  E-value: 1.12e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVY---------EGVWKKYSlTVAVKTLKEDtmEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEF 317
Cdd:cd08222    7 KLGSGNFGTVYlvsdlkataDEELKVLK-EISVGELQPD--ETVDANREAKLLSKLDHPAIVKFHDSFVEKESFCIVTEY 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  318 MTYGNLLDYLREC--NRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVgENHLVKVADFGLSRLMTG--DTY 393
Cdd:cd08222   84 CEGGDLDDKISEYkkSGTTIDENQILDWFIQLLLAVQYMHERRILHRDLKAKNIFL-KNNVIKVGDFGISRILMGtsDLA 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  394 TAHAGAKFpikWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSpYPGID-LSQVYELLEKDYRmERPEGCPEKVYELM 472
Cdd:cd08222  163 TTFTGTPY---YMSPEVLKHEGYNSKSDIWSLGCILYEMCCLKHA-FDGQNlLSVMYKIVEGETP-SLPDKYSKELNAIY 237
                        250
                 ....*....|....*..
gi 62362414  473 RACWQWNPSDRPSFAEI 489
Cdd:cd08222  238 SRMLNKDPALRPSAAEI 254
PK_KSR cd14063
Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to ...
241-496 1.62e-28

Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. KSR is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. KSR proteins regulate the assembly and activation of the Raf/MEK/ERK module upon Ras activation at the membrane by direct association of its components. They are widely regarded as pseudokinases, but there is some debate in this designation as a few groups have reported detecting kinase catalytic activity for KSRs, specifically KSR1. Vertebrates contain two KSR proteins, KSR1 and KSR2. The KSR subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270965 [Multi-domain]  Cd Length: 271  Bit Score: 116.29  E-value: 1.62e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  241 DITMKHKLGGGQYGEVYEGVWKKyslTVAVKTLKEDTM---EVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEF 317
Cdd:cd14063    1 ELEIKEVIGKGRFGRVHRGRWHG---DVAIKLLNIDYLneeQLEAFKEEVAAYKNTRHDNLVLFMGACMDPPHLAIVTSL 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  318 MTYGNLLDYLREcNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVgENHLVKVADFGLSRLM-TGDTYTAH 396
Cdd:cd14063   78 CKGRTLYSLIHE-RKEKFDFNKTVQIAQQICQGMGYLHAKGIIHKDLKSKNIFL-ENGRVVITDFGLFSLSgLLQPGRRE 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  397 AGAKFPIKWT---APE---SLAYNK-------FSIKSDVWAFGVLLWEIATYGMsPYPGIDLSQVYELLEKDYRMERPE- 462
Cdd:cd14063  156 DTLVIPNGWLcylAPEiirALSPDLdfeeslpFTKASDVYAFGTVWYELLAGRW-PFKEQPAESIIWQVGCGKKQSLSQl 234
                        250       260       270
                 ....*....|....*....|....*....|....
gi 62362414  463 GCPEKVYELMRACWQWNPSDRPSFAEIHQAFETM 496
Cdd:cd14063  235 DIGREVKDILMQCWAYDPEKRPTFSDLLRMLERL 268
STKc_LIMK1 cd14221
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the ...
248-496 1.87e-28

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMK1 activation is induced by bone morphogenic protein, vascular endothelial growth factor, and thrombin. It plays roles in microtubule disassembly and cell cycle progression, and is critical in the regulation of neurite outgrowth. LIMK1 knockout mice show abnormalities in dendritic spine morphology and synaptic function. LIMK1 is one of the genes deleted in patients with Williams Syndrome, which is characterized by distinct craniofacial features, cardiovascular problems, as well as behavioral and neurological abnormalities. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. The LIMK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271123 [Multi-domain]  Cd Length: 267  Bit Score: 115.82  E-value: 1.87e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTL-KEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDY 326
Cdd:cd14221    1 LGKGCFGQAIKVTHRETGEVMVMKELiRFDEETQRTFLKEVKVMRCLEHPNVLKFIGVLYKDKRLNFITEYIKGGTLRGI 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  327 LRECNR-----QEVNavvllyMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKF 401
Cdd:cd14221   81 IKSMDShypwsQRVS------FAKDIASGMAYLHSMNIIHRDLNSHNCLVRENKSVVVADFGLARLMVDEKTQPEGLRSL 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  402 PIK-------------WTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYrMER--PEGCPE 466
Cdd:cd14221  155 KKPdrkkrytvvgnpyWMAPEMINGRSYDEKVDVFSFGIVLCEIIGRVNADPDYLPRTMDFGLNVRGF-LDRycPPNCPP 233
                        250       260       270
                 ....*....|....*....|....*....|
gi 62362414  467 KVYELMRACWQWNPSDRPSFAEIHQAFETM 496
Cdd:cd14221  234 SFFPIAVLCCDLDPEKRPSFSKLEHWLETL 263
STKc_MEKK1_plant cd06632
Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP) ...
248-489 2.38e-28

Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of plant MAPK kinase kinases (MAPKKKs) including Arabidopsis thaliana MEKK1 and MAPKKK3. Arabidopsis thaliana MEKK1 activates MPK4, a MAPK that regulates systemic acquired resistance. MEKK1 also participates in the regulation of temperature-sensitive and tissue-specific cell death. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The plant MEKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270802 [Multi-domain]  Cd Length: 259  Bit Score: 115.19  E-value: 2.38e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTL------KEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYG 321
Cdd:cd06632    8 LGSGSFGSVYEGFNGDTGDFFAVKEVslvdddKKSRESVKQLEQEIALLSKLRHPNIVQYYGTEREEDNLYIFLEYVPGG 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  322 NLLDYLRECNRQEVNaVVLLYmATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR-LMTGDTYTAHAGAK 400
Cdd:cd06632   88 SIHKLLQRYGAFEEP-VIRLY-TRQILSGLAYLHSRNTVHRDIKGANILVDTNGVVKLADFGMAKhVEAFSFAKSFKGSP 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  401 FpikWTAPESLA--YNKFSIKSDVWAFGVLLWEIATyGMSPYPgiDLSQVYELLEKDYRMERPEgCPE----KVYELMRA 474
Cdd:cd06632  166 Y---WMAPEVIMqkNSGYGLAVDIWSLGCTVLEMAT-GKPPWS--QYEGVAAIFKIGNSGELPP-IPDhlspDAKDFIRL 238
                        250
                 ....*....|....*
gi 62362414  475 CWQWNPSDRPSFAEI 489
Cdd:cd06632  239 CLQRDPEDRPTASQL 253
STKc_MAK_like cd07830
Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs ...
243-489 2.54e-28

Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of human MAK and MAK-related kinase (MRK), Saccharomyces cerevisiae Ime2p, Schizosaccharomyces pombe Mei4-dependent protein 3 (Mde3) and Pit1, Caenorhabditis elegans dyf-5, Arabidopsis thaliana MHK, and similar proteins. These proteins play important roles during meiosis. MAK is highly expressed in testicular cells specifically in the meiotic phase, but is not essential for spermatogenesis and fertility. It functions as a coactivator of the androgen receptor in prostate cells. MRK, also called Intestinal Cell Kinase (ICK), is expressed ubiquitously, with highest expression in the ovary and uterus. A missense mutation in MRK causes endocrine-cerebro-osteodysplasia, suggesting that this protein plays an important role in the development of many organs. MAK and MRK may be involved in regulating cell cycle and cell fate. Ime2p is a meiosis-specific kinase that is important during meiotic initiation and during the later stages of meiosis. Mde3 functions downstream of the transcription factor Mei-4 which is essential for meiotic prophase I. The MAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270824 [Multi-domain]  Cd Length: 283  Bit Score: 115.71  E-value: 2.54e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  243 TMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKeaavMKEIK-------HPNLVQLLGVCTREPPFYIIT 315
Cdd:cd07830    2 KVIKQLGDGTFGSVYLARNKETGELVAIKKMKKKFYSWEECMN----LREVKslrklneHPNIVKLKEVFRENDELYFVF 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  316 EFMTyGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR-LMTGDTYT 394
Cdd:cd07830   78 EYME-GNLYQLMKDRKGKPFSESVIRSIIYQILQGLAHIHKHGFFHRDLKPENLLVSGPEVVKIADFGLAReIRSRPPYT 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  395 AHAGAkfpiKW-TAPESLAYNKF-SIKSDVWAFGVLLWEIATygMSP-YPG---ID-LSQVYELLEKDYRMERPEGC--- 464
Cdd:cd07830  157 DYVST----RWyRAPEILLRSTSySSPVDIWALGCIMAELYT--LRPlFPGsseIDqLYKICSVLGTPTKQDWPEGYkla 230
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*..
gi 62362414  465 -------PEKV---------------YELMRACWQWNPSDRPSFAEI 489
Cdd:cd07830  231 sklgfrfPQFAptslhqlipnaspeaIDLIKDMLRWDPKKRPTASQA 277
PKc_MAPKK cd06605
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase ...
241-489 2.54e-28

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MAPKKs are dual-specificity PKs that phosphorylate their downstream targets, MAPKs, at specific threonine and tyrosine residues. The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising the MAPK, which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK or MAP2K), which itself is phosphorylated and activated by a MAPKK kinase (MAPKKK or MKKK or MAP3K). There are three MAPK subfamilies: extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. In mammalian cells, there are seven MAPKKs (named MKK1-7) and 20 MAPKKKs. Each MAPK subfamily can be activated by at least two cognate MAPKKs and by multiple MAPKKKs. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270782 [Multi-domain]  Cd Length: 265  Bit Score: 115.52  E-value: 2.54e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  241 DITMKHKLGGGQYGEVYEGVWKKYSLTVAVKT--LKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFM 318
Cdd:cd06605    2 DLEYLGELGEGNGGVVSKVRHRPSGQIMAVKVirLEIDEALQKQILRELDVLHKCNSPYIVGFYGAFYSEGDISICMEYM 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  319 TYGNLLDYLRECNRqeVNAVVLLYMATQISSAMEYL-EKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHA 397
Cdd:cd06605   82 DGGSLDKILKEVGR--IPERILGKIAVAVVKGLIYLhEKHKIIHRDVKPSNILVNSRGQVKLCDFGVSGQLVDSLAKTFV 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  398 GAKfpiKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQ---VYELLEKDYRMERP----EGCPEKVYE 470
Cdd:cd06605  160 GTR---SYMAPERISGGKYTVKSDIWSLGLSLVELAT-GRFPYPPPNAKPsmmIFELLSYIVDEPPPllpsGKFSPDFQD 235
                        250
                 ....*....|....*....
gi 62362414  471 LMRACWQWNPSDRPSFAEI 489
Cdd:cd06605  236 FVSQCLQKDPTERPSYKEL 254
PKc_MAPKK_plant_like cd06623
Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and ...
241-488 5.08e-28

Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and similar proteins; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include MAPKKs from plants, kinetoplastids, alveolates, and mycetozoa. The MAPKK, LmxPK4, from Leishmania mexicana, is important in differentiation and virulence. Dictyostelium discoideum MEK1 is required for proper chemotaxis; MEK1 null mutants display severe defects in cell polarization and directional movement. Plants contain multiple MAPKKs like other eukaryotes. The Arabidopsis genome encodes for 10 MAPKKs while poplar and rice contain 13 MAPKKs each. The functions of these proteins have not been fully elucidated. There is evidence to suggest that MAPK cascades are involved in plant stress responses. In Arabidopsis, MKK3 plays a role in pathogen signaling; MKK2 is involved in cold and salt stress signaling; MKK4/MKK5 participates in innate immunity; and MKK7 regulates basal and systemic acquired resistance. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132954 [Multi-domain]  Cd Length: 264  Bit Score: 114.61  E-value: 5.08e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  241 DITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLK--EDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFM 318
Cdd:cd06623    2 DLERVKVLGQGSSGVVYKVRHKPTGKIYALKKIHvdGDEEFRKQLLRELKTLRSCESPYVVKCYGAFYKEGEISIVLEYM 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  319 TYGNLLDYLRECNRqeVNAVVLLYMATQISSAMEYL-EKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTG-----DT 392
Cdd:cd06623   82 DGGSLADLLKKVGK--IPEPVLAYIARQILKGLDYLhTKRHIIHRDIKPSNLLINSKGEVKIADFGISKVLENtldqcNT 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  393 Y--TAhagakfpiKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEK-----DYRMErPEGCP 465
Cdd:cd06623  160 FvgTV--------TYMSPERIQGESYSYAADIWSLGLTLLECAL-GKFPFLPPGQPSFFELMQAicdgpPPSLP-AEEFS 229
                        250       260
                 ....*....|....*....|...
gi 62362414  466 EKVYELMRACWQWNPSDRPSFAE 488
Cdd:cd06623  230 PEFRDFISACLQKDPKKRPSAAE 252
SH3_Abl cd11850
Src homology 3 domain of the Protein Tyrosine Kinase, Abelson kinase; Abl (or c-Abl) is a ...
65-118 6.73e-28

Src homology 3 domain of the Protein Tyrosine Kinase, Abelson kinase; Abl (or c-Abl) is a ubiquitously-expressed cytoplasmic (or nonreceptor) PTK that contains SH3, SH2, and tyr kinase domains in its N-terminal region, as well as nuclear localization motifs, a putative DNA-binding domain, and F- and G-actin binding domains in its C-terminal tail. It also contains a short autoinhibitory cap region in its N-terminus. Abl function depends on its subcellular localization. In the cytoplasm, Abl plays a role in cell proliferation and survival. In response to DNA damage or oxidative stress, Abl is transported to the nucleus where it induces apoptosis. In chronic myelogenous leukemia (CML) patients, an aberrant translocation results in the replacement of the first exon of Abl with the BCR (breakpoint cluster region) gene. The resulting BCR-Abl fusion protein is constitutively active and associates into tetramers, resulting in a hyperactive kinase sending a continuous signal. This leads to uncontrolled proliferation, morphological transformation and anti-apoptotic effects. BCR-Abl is the target of selective inhibitors, such as imatinib (Gleevec), used in the treatment of CML. Abl2, also known as ARG (Abelson-related gene), is thought to play a cooperative role with Abl in the proper development of the nervous system. The Tel-ARG fusion protein, resulting from reciprocal translocation between chromosomes 1 and 12, is associated with acute myeloid leukemia (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212784  Cd Length: 56  Bit Score: 107.11  E-value: 6.73e-28
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 62362414   65 LFVALYDFVASGDNTLSITKGEKLRVLGYNHNGEWCEAQTKN--GQGWVPSNYITP 118
Cdd:cd11850    1 LFVALYDFVASGENQLSIKKGEQLRVLGYNKNGEWCEAESKStgGQGWVPSNYITP 56
STKc_C-Raf cd14149
Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) ...
235-496 7.53e-28

Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. C-Raf, also known as Raf-1 or c-Raf-1, is ubiquitously expressed and was the first Raf identified. It was characterized as the acquired oncogene from an acutely transforming murine sarcoma virus (3611-MSV) and the transforming agent from the avian retrovirus MH2. C-Raf-deficient mice embryos die around midgestation with increased apoptosis of embryonic tissues, especially in the fetal liver. One of the main functions of C-Raf is restricting caspase activation to promote survival in response to specific stimuli such as Fas stimulation, macrophage apoptosis, and erythroid differentiation. C-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. It functions in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The C-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271051 [Multi-domain]  Cd Length: 283  Bit Score: 114.74  E-value: 7.53e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  235 WEMERTDITMKHKLGGGQYGEVYEGVWKKyslTVAVKTLK--EDTME-VEEFLKEAAVMKEIKHPNLVQLLGVCTREpPF 311
Cdd:cd14149    7 WEIEASEVMLSTRIGSGSFGTVYKGKWHG---DVAVKILKvvDPTPEqFQAFRNEVAVLRKTRHVNILLFMGYMTKD-NL 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  312 YIITEFMTYGNLLDYLR--ECNRQEVNavvLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMT 389
Cdd:cd14149   83 AIVTQWCEGSSLYKHLHvqETKFQMFQ---LIDIARQTAQGMDYLHAKNIIHRDMKSNNIFLHEGLTVKIGDFGLATVKS 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  390 gdTYTAHAGAKFP---IKWTAPESLAY---NKFSIKSDVWAFGVLLWEIATyGMSPYPGI-DLSQVYELLEKDYRM---- 458
Cdd:cd14149  160 --RWSGSQQVEQPtgsILWMAPEVIRMqdnNPFSFQSDVYSYGIVLYELMT-GELPYSHInNRDQIIFMVGRGYASpdls 236
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 62362414  459 ERPEGCPEKVYELMRACWQWNPSDRPSFAEIHQAFETM 496
Cdd:cd14149  237 KLYKNCPKAMKRLVADCIKKVKEERPLFPQILSSIELL 274
STKc_CDKL cd07833
Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs ...
246-493 8.38e-28

Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDKL1-5 and similar proteins. Some CDKLs, like CDKL1 and CDKL3, may be implicated in transformation and others, like CDKL3 and CDKL5, are associated with mental retardation when impaired. CDKL2 plays a role in learning and memory. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270827 [Multi-domain]  Cd Length: 288  Bit Score: 114.72  E-value: 8.38e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  246 HKLGGGQYGEVYEGVWKKYSLTVAVKTLK--EDTMEVEEF-LKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYgN 322
Cdd:cd07833    7 GVVGEGAYGVVLKCRNKATGEIVAIKKFKesEDDEDVKKTaLREVKVLRQLRHENIVNLKEAFRRKGRLYLVFEYVER-T 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLRECNRQEVNAVVLLYMaTQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTG------DTYTAh 396
Cdd:cd07833   86 LLELLEASPGGLPPDAVRSYI-WQLLQAIAYCHSHNIIHRDIKPENILVSESGVLKLCDFGFARALTArpasplTDYVA- 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  397 agakfpIKW-TAPESL-AYNKFSIKSDVWAFGVLLWEIATyGMSPYPG-IDLSQVY--------------ELLEKDYRM- 458
Cdd:cd07833  164 ------TRWyRAPELLvGDTNYGKPVDVWAIGCIMAELLD-GEPLFPGdSDIDQLYliqkclgplppshqELFSSNPRFa 236
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|..
gi 62362414  459 --------------ERPEG-CPEKVYELMRACWQWNPSDRPSFAEI--HQAF 493
Cdd:cd07833  237 gvafpepsqpesleRRYPGkVSSPALDFLKACLRMDPKERLTCDELlqHPYF 288
STKc_CMGC cd05118
Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
246-493 1.02e-27

Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The CMGC family consists of Cyclin-Dependent protein Kinases (CDKs), Mitogen-activated protein kinases (MAPKs) such as Extracellular signal-regulated kinase (ERKs), c-Jun N-terminal kinases (JNKs), and p38, and other kinases. CDKs belong to a large subfamily of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Other members of the CMGC family include casein kinase 2 (CK2), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK), Glycogen Synthase Kinase 3 (GSK3), among many others. The CMGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270688 [Multi-domain]  Cd Length: 249  Bit Score: 113.10  E-value: 1.02e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  246 HKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIK----HPNLVQLLGVCTREPP--FYIITEFMT 319
Cdd:cd05118    5 RKIGEGAFGTVWLARDKVTGEKVAIKKIKNDFRHPKAALREIKLLKHLNdvegHPNIVKLLDVFEHRGGnhLCLVFELMG 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  320 YgNLLDYLRECNRQEVNAVVLLYMaTQISSAMEYLEKKNFIHRDLAARNCLV-GENHLVKVADFGLSRLMTGDTYTaHAG 398
Cdd:cd05118   85 M-NLYELIKDYPRGLPLDLIKSYL-YQLLQALDFLHSNGIIHRDLKPENILInLELGQLKLADFGLARSFTSPPYT-PYV 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  399 AkfPIKWTAPES-LAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDlsqvyellEKDY--RMERPEGcPEKVYELMRAC 475
Cdd:cd05118  162 A--TRWYRAPEVlLGAKPYGSSIDIWSLGCILAELLT-GRPLFPGDS--------EVDQlaKIVRLLG-TPEALDLLSKM 229
                        250       260
                 ....*....|....*....|
gi 62362414  476 WQWNPSDRPSFAEI--HQAF 493
Cdd:cd05118  230 LKYDPAKRITASQAlaHPYF 249
STKc_ULK3 cd14121
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the ...
247-488 4.01e-27

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK3 mRNA is up-regulated in fibroblasts after Ras-induced senescence, and its overexpression induces both autophagy and senescence in a fibroblast cell line. ULK3, through its kinase activity, positively regulates Gli proteins, mediators of the Sonic hedgehog (Shh) signaling pathway that is implicated in tissue homeostasis maintenance and neurogenesis. It is inhibited by binding to Suppressor of Fused (Sufu). The ULK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271023 [Multi-domain]  Cd Length: 252  Bit Score: 111.61  E-value: 4.01e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLT-VAVKTLKEDTME---VEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGN 322
Cdd:cd14121    2 KLGSGTYATVYKAYRKSGAREvVAVKCVSKSSLNkasTENLLTEIELLKKLKHPHIVELKDFQWDEEHIYLIMEYCSGGD 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLRecNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLV--GENHLVKVADFGLSRLMT-GDTYTAHAGA 399
Cdd:cd14121   82 LSRFIR--SRRTLPESTVRRFLQQLASALQFLREHNISHMDLKPQNLLLssRYNPVLKLADFGFAQHLKpNDEAHSLRGS 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  400 kfPIkWTAPESLAYNKFSIKSDVWAFGVLLWEiATYGMSPYPgidlSQVYELLEKDYRMERPEGCP------EKVYELMR 473
Cdd:cd14121  160 --PL-YMAPEMILKKKYDARVDLWSVGVILYE-CLFGRAPFA----SRSFEELEEKIRSSKPIEIPtrpelsADCRDLLL 231
                        250
                 ....*....|....*
gi 62362414  474 ACWQWNPSDRPSFAE 488
Cdd:cd14121  232 RLLQRDPDRRISFEE 246
STKc_CDK_like cd07829
Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs ...
247-485 5.51e-27

Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. CDKs are partly regulated by their subcellular localization, which defines substrate phosphorylation and the resulting specific function. CDK1, CDK2, CDK4, and CDK6 have well-defined functions in the cell cycle, such as the regulation of the early G1 phase by CDK4 or CDK6, the G1/S phase transition by CDK2, or the entry of mitosis by CDK1. They also exhibit overlapping cyclin specificity and functions in certain conditions. Knockout mice with a single CDK deleted remain viable with specific phenotypes, showing that some CDKs can compensate for each other. For example, CDK4 can compensate for the loss of CDK6, however, double knockout mice with both CDK4 and CDK6 deleted die in utero. CDK8 and CDK9 are mainly involved in transcription while CDK5 is implicated in neuronal function. CDK7 plays essential roles in both the cell cycle as a CDK-Activating Kinase (CAK) and in transcription as a component of the general transcription factor TFIIH. The CDK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270823 [Multi-domain]  Cd Length: 282  Bit Score: 111.81  E-value: 5.51e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTmEVEEF----LKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYgN 322
Cdd:cd07829    6 KLGEGTYGVVYKAKDKKTGEIVALKKIRLDN-EEEGIpstaLREISLLKELKHPNIVKLLDVIHTENKLYLVFEYCDQ-D 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLRECNRQEVNAVVLLYMaTQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTgdtytahagakFP 402
Cdd:cd07829   84 LKKYLDKRPGPLPPNLIKSIM-YQLLRGLAYCHSHRILHRDLKPQNLLINRDGVLKLADFGLARAFG-----------IP 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  403 IK---------W-TAPESL-AYNKFSIKSDVWAFGVLLWEIATygMSP-YPG---ID-LSQVYELL----EKDY------ 456
Cdd:cd07829  152 LRtythevvtlWyRAPEILlGSKHYSTAVDIWSVGCIFAELIT--GKPlFPGdseIDqLFKIFQILgtptEESWpgvtkl 229
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|...
gi 62362414  457 -----RMERPEGCP-EKV--------YELMRACWQWNPSDRPS 485
Cdd:cd07829  230 pdykpTFPKWPKNDlEKVlprldpegIDLLSKMLQYNPAKRIS 272
STKc_OSR1_SPAK cd06610
Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and ...
247-489 9.62e-27

Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and Ste20-related proline alanine-rich kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SPAK is also referred to as STK39 or PASK (proline-alanine-rich STE20-related kinase). OSR1 and SPAK regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. They are also implicated in cytoskeletal rearrangement, cell differentiation, transformation and proliferation. OSR1 and SPAK contain a conserved C-terminal (CCT) domain, which recognizes a unique motif ([RK]FX[VI]) present in their activating kinases (WNK1/WNK4) and their substrates. The OSR1 and SPAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270787 [Multi-domain]  Cd Length: 267  Bit Score: 110.91  E-value: 9.62e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM--EVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLL 324
Cdd:cd06610    8 VIGSGATAVVYAAYCLPKKEKVAIKRIDLEKCqtSMDELRKEIQAMSQCNHPNVVSYYTSFVVGDELWLVMPLLSGGSLL 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  325 DYLRECNRQEVN-----AVVLlymaTQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR-LMTGDTYTAHAG 398
Cdd:cd06610   88 DIMKSSYPRGGLdeaiiATVL----KEVLKGLEYLHSNGQIHRDVKAGNILLGEDGSVKIADFGVSAsLATGGDRTRKVR 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  399 AKF---PIkWTAPESLAYNK-FSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVY----- 469
Cdd:cd06610  164 KTFvgtPC-WMAPEVMEQVRgYDFKADIWSFGITAIELAT-GAAPYSKYPPMKVLMLTLQNDPPSLETGADYKKYsksfr 241
                        250       260
                 ....*....|....*....|
gi 62362414  470 ELMRACWQWNPSDRPSFAEI 489
Cdd:cd06610  242 KMISLCLQKDPSKRPTAEEL 261
STKc_MST1_2 cd06612
Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; ...
247-443 1.13e-26

Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST1, MST2, and related proteins including Drosophila Hippo and Dictyostelium discoideum Krs1 (kinase responsive to stress 1). MST1/2 and Hippo are involved in a conserved pathway that governs cell contact inhibition, organ size control, and tumor development. MST1 activates the mitogen-activated protein kinases (MAPKs) p38 and c-Jun N-terminal kinase (JNK) through MKK7 and MEKK1 by acting as a MAPK kinase kinase kinase. Activation of JNK by MST1 leads to caspase activation and apoptosis. MST1 has also been implicated in cell proliferation and differentiation. Krs1 may regulate cell growth arrest and apoptosis in response to cellular stress. The MST1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132943 [Multi-domain]  Cd Length: 256  Bit Score: 110.43  E-value: 1.13e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTmEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDY 326
Cdd:cd06612   10 KLGEGSYGSVYKAIHKETGQVVAIKVVPVEE-DLQEIIKEISILKQCDSPYIVKYYGSYFKNTDLWIVMEYCGAGSVSDI 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  327 LRECNRQ--EVNAVVLLYmatQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAH--AGAKFp 402
Cdd:cd06612   89 MKITNKTltEEEIAAILY---QTLKGLEYLHSNKKIHRDIKAGNILLNEEGQAKLADFGVSGQLTDTMAKRNtvIGTPF- 164
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 62362414  403 ikWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGI 443
Cdd:cd06612  165 --WMAPEVIQEIGYNNKADIWSLGITAIEMAE-GKPPYSDI 202
STKc_SLK_like cd06611
Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the ...
228-524 1.50e-26

Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of the subfamily include SLK, STK10 (also called LOK for Lymphocyte-Oriented Kinase), SmSLK (Schistosoma mansoni SLK), and related proteins. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It also plays a role in mediating actin reorganization. STK10 is responsible in regulating the CD28 responsive element in T cells, as well as leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. SmSLK is capable of activating the MAPK Jun N-terminal kinase (JNK) pathway in human embryonic kidney cells as well as in Xenopus oocytes. It may participate in regulating MAPK cascades during host-parasite interactions. The SLK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132942 [Multi-domain]  Cd Length: 280  Bit Score: 110.60  E-value: 1.50e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  228 VSPNyDKWEMertditmKHKLGGGQYGEVYEGVWKKYSLTVAVKTLK-EDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCT 306
Cdd:cd06611    1 VNPN-DIWEI-------IGELGDGAFGKVYKAQHKETGLFAAAKIIQiESEEELEDFMVEIDILSECKHPNIVGLYEAYF 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  307 REPPFYIITEFMTYGNLLDYLRECNRQeVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR 386
Cdd:cd06611   73 YENKLWILIEFCDGGALDSIMLELERG-LTEPQIRYVCRQMLEALNFLHSHKVIHRDLKAGNILLTLDGDVKLADFGVSA 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  387 LMTGDTYTAHAGAKFPiKWTAPESLAYNKFS-----IKSDVWAFGVLLWEIATygMSPyPGIDLSQVYELLE----KDYR 457
Cdd:cd06611  152 KNKSTLQKRDTFIGTP-YWMAPEVVACETFKdnpydYKADIWSLGITLIELAQ--MEP-PHHELNPMRVLLKilksEPPT 227
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 62362414  458 MERPEGCPEKVYELMRACWQWNPSDRPSFAEihqafetMFQESSISDevekelgkQGVRGAVSTLLQ 524
Cdd:cd06611  228 LDQPSKWSSSFNDFLKSCLVKDPDDRPTAAE-------LLKHPFVSD--------QSDNKAIKDLLA 279
PKc_TESK cd14155
Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; ...
248-499 2.23e-26

Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TESK proteins phosphorylate cofilin and induce actin cytoskeletal reorganization. In the Drosphila eye, TESK is required for epithelial cell organization. Mammals contain two TESK proteins, TESK1 and TESK2, which are highly expressed in testis and play roles in spermatogenesis. TESK1 is found in testicular germ cells while TESK2 is expressed mainly in nongerminal Sertoli cells. TESK1 is stimulated by integrin-mediated signaling pathways. It regulates cell spreading and focal adhesion formation. The TESK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271057 [Multi-domain]  Cd Length: 253  Bit Score: 109.49  E-value: 2.23e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEgvwKKYSLTVAVKTLKEDTMEVEE--FLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLD 325
Cdd:cd14155    1 IGSGFFSEVYK---VRHRTSGQVMALKMNTLSSNRanMLREVQLMNRLSHPNILRFMGVCVHQGQLHALTEYINGGNLEQ 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  326 YLRecNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLV--GENHLVK-VADFGLSRLM----TGDTYTAHAG 398
Cdd:cd14155   78 LLD--SNEPLSWTVRVKLALDIARGLSYLHSKGIFHRDLTSKNCLIkrDENGYTAvVGDFGLAEKIpdysDGKEKLAVVG 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  399 AKFpikWTAPESLAYNKFSIKSDVWAFGVLLWEI-----ATYGMSPYP---GIDLSQVYELLEKdyrmerpegCPEKVYE 470
Cdd:cd14155  156 SPY---WMAPEVLRGEPYNEKADVFSYGIILCEIiariqADPDYLPRTedfGLDYDAFQHMVGD---------CPPDFLQ 223
                        250       260
                 ....*....|....*....|....*....
gi 62362414  471 LMRACWQWNPSDRPSFAEIHQAFETMFQE 499
Cdd:cd14155  224 LAFNCCNMDPKSRPSFHDIVKTLEEILEK 252
STKc_NAK1_like cd06917
Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of ...
248-489 2.82e-26

Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Nak1, Saccharomyces cerevisiae Kic1p (kinase that interacts with Cdc31p) and related proteins. Nak1 (also called N-rich kinase 1), is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Kic1p is required by budding yeast for cell integrity and morphogenesis. Kic1p interacts with Cdc31p, the yeast homologue of centrin, and phosphorylates substrates in a Cdc31p-dependent manner. The Nak1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270822 [Multi-domain]  Cd Length: 277  Bit Score: 109.87  E-value: 2.82e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDT--MEVEEFLKEAAVMKEIKH---PNLVQLLGVCTREPPFYIITEFMTYGN 322
Cdd:cd06917    9 VGRGSYGAVYRGYHVKTGRVVALKVLNLDTddDDVSDIQKEVALLSQLKLgqpKNIIKYYGSYLKGPSLWIIMDYCEGGS 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLRECNRQEVNAVVLLymaTQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFP 402
Cdd:cd06917   89 IRTLMRAGPIAERYIAVIM---REVLVALKFIHKDGIIHRDIKAANILVTNTGNVKLCDFGVAASLNQNSSKRSTFVGTP 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  403 IkWTAPESLAYNK-FSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEKdyrmERPEGCPEKVY-----ELMRACW 476
Cdd:cd06917  166 Y-WMAPEVITEGKyYDTKADIWSLGITTYEMAT-GNPPYSDVDALRAVMLIPK----SKPPRLEGNGYspllkEFVAACL 239
                        250
                 ....*....|...
gi 62362414  477 QWNPSDRPSFAEI 489
Cdd:cd06917  240 DEEPKDRLSADEL 252
STKc_NUAK cd14073
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze ...
246-489 3.53e-26

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK1, also called ARK5 (AMPK-related protein kinase 5), regulates cell proliferation and displays tumor suppression through direct interaction and phosphorylation of p53. It is also involved in cell senescence and motility. High NUAK1 expression is associated with invasiveness of nonsmall cell lung cancer (NSCLC) and breast cancer cells. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. The NUAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270975 [Multi-domain]  Cd Length: 254  Bit Score: 109.01  E-value: 3.53e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  246 HKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFL----KEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYG 321
Cdd:cd14073    7 ETLGKGTYGKVKLAIERATGREVAIKSIKKDKIEDEQDMvrirREIEIMSSLNHPHIIRIYEVFENKDKIVIVMEYASGG 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  322 NLLDYLRECNRQEVNAVVLLYmaTQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTY-TAHAGAk 400
Cdd:cd14073   87 ELYDYISERRRLPEREARRIF--RQIVSAVHYCHKNGVVHRDLKLENILLDQNGNAKIADFGLSNLYSKDKLlQTFCGS- 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  401 fPIkWTAPE---SLAYNKFSIksDVWAFGVLLWEIaTYGMSPYPGIDL-SQVYELLEKDYRMERPegcPEKVYELMRACW 476
Cdd:cd14073  164 -PL-YASPEivnGTPYQGPEV--DCWSLGVLLYTL-VYGTMPFDGSDFkRLVKQISSGDYREPTQ---PSDASGLIRWML 235
                        250
                 ....*....|...
gi 62362414  477 QWNPSDRPSFAEI 489
Cdd:cd14073  236 TVNPKRRATIEDI 248
STKc_Nek6_7 cd08224
Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related ...
247-491 3.91e-26

Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related kinase 6 and 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek6 and Nek7 are the shortest Neks, consisting only of the catalytic domain and a very short N-terminal extension. They show distinct expression patterns and both appear to be downstream substrates of Nek9. They are required for mitotic spindle formation and cytokinesis. They may also be regulators of the p70 ribosomal S6 kinase. Nek6/7 is part of a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270863 [Multi-domain]  Cd Length: 262  Bit Score: 108.90  E-value: 3.91e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM----EVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGN 322
Cdd:cd08224    7 KIGKGQFSVVYRARCLLDGRLVALKKVQIFEMmdakARQDCLKEIDLLQQLNHPNIIKYLASFIENNELNIVLELADAGD 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLRECNRQEV---NAVVLLYMaTQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGA 399
Cdd:cd08224   87 LSRLIKHFKKQKRlipERTIWKYF-VQLCSALEHMHSKRIMHRDIKPANVFITANGVVKLGDLGLGRFFSSKTTAAHSLV 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  400 KFPIkWTAPESLAYNKFSIKSDVWAFGVLLWEIATYgMSPY--PGIDLSQVYELLEK-DYRMERPEGCPEKVYELMRACW 476
Cdd:cd08224  166 GTPY-YMSPERIREQGYDFKSDIWSLGCLLYEMAAL-QSPFygEKMNLYSLCKKIEKcEYPPLPADLYSQELRDLVAACI 243
                        250
                 ....*....|....*
gi 62362414  477 QWNPSDRPSFAEIHQ 491
Cdd:cd08224  244 QPDPEKRPDISYVLD 258
STKc_ULK1 cd14202
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the ...
234-493 5.43e-26

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. It associates with three autophagy-related proteins (Atg13, FIP200 amd Atg101) to form the ULK1 complex. All fours proteins are essential for autophagosome formation. ULK1 is regulated by both mammalian target-of rapamycin complex 1 (mTORC1) and AMP-activated protein kinase (AMPK). mTORC1 negatively regulates the ULK1 complex in a nutrient-dependent manner while AMPK stimulates autophagy by inhibiting mTORC1. ULK1 also plays neuron-specific roles and is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, neurite extension, and axon branching. The ULK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271104 [Multi-domain]  Cd Length: 267  Bit Score: 108.56  E-value: 5.43e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  234 KWEMERTDItmkhkLGGGQYGEVYEGVWK-KYSLTVAVKTLKEDTMEVEEFL--KEAAVMKEIKHPNLVQLLGVCTREPP 310
Cdd:cd14202    1 KFEFSRKDL-----IGHGAFAVVFKGRHKeKHDLEVAVKCINKKNLAKSQTLlgKEIKILKELKHENIVALYDFQEIANS 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  311 FYIITEFMTYGNLLDYLRECNRQEVNAVVLLYMatQISSAMEYLEKKNFIHRDLAARNCLVG---------ENHLVKVAD 381
Cdd:cd14202   76 VYLVMEYCNGGDLADYLHTMRTLSEDTIRLFLQ--QIAGAMKMLHSKGIIHRDLKPQNILLSysggrksnpNNIRIKIAD 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  382 FGLSRLMTGDTYTAHAGAKfPIkWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEKDYRME-- 459
Cdd:cd14202  154 FGFARYLQNNMMAATLCGS-PM-YMAPEVIMSQHYDAKADLWSIGTIIYQCLT-GKAPFQASSPQDLRLFYEKNKSLSpn 230
                        250       260       270
                 ....*....|....*....|....*....|....*..
gi 62362414  460 --RPEGCPEKvyELMRACWQWNPSDRPSFAE-IHQAF 493
Cdd:cd14202  231 ipRETSSHLR--QLLLGLLQRNQKDRMDFDEfFHHPF 265
PK_GC-A_B cd14042
Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The ...
268-489 6.38e-26

Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-A binds and is activated by the atrial and B-type natriuretic peptides, ANP and BNP, which are important in blood pressure regulation and cardiac pathophysiology. GC-B binds the C-type natriuretic peptide, CNP, which is a potent vasorelaxant and functions in vascular remodeling and bone growth regulation. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-A/B subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270944 [Multi-domain]  Cd Length: 279  Bit Score: 108.84  E-value: 6.38e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  268 VAVKTLKEDTMEVE-EFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDYLRecNRQ-EVNAVVLLYMAT 345
Cdd:cd14042   33 VAIKKVNKKRIDLTrEVLKELKHMRDLQHDNLTRFIGACVDPPNICILTEYCPKGSLQDILE--NEDiKLDWMFRYSLIH 110
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  346 QISSAMEYLEKKNFI-HRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPIK-WTAPESLAYNKFSI----K 419
Cdd:cd14042  111 DIVKGMHYLHDSEIKsHGNLKSSNCVVDSRFVLKITDFGLHSFRSGQEPPDDSHAYYAKLlWTAPELLRDPNPPPpgtqK 190
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  420 SDVWAFGVLLWEIAT----YGMSpypGIDLSQVYELLEKDYRMERP--------EGCPEKVYELMRACWQWNPSDRPSFA 487
Cdd:cd14042  191 GDVYSFGIILQEIATrqgpFYEE---GPDLSPKEIIKKKVRNGEKPpfrpsldeLECPDEVLSLMQRCWAEDPEERPDFS 267

                 ..
gi 62362414  488 EI 489
Cdd:cd14042  268 TL 269
STKc_IRAK4 cd14158
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; ...
228-496 1.72e-25

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain, and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK4 plays a critical role in NFkB activation by its interaction with MyD88, which acts as a scaffold that enables IRAK4 to phosphorylate and activate IRAK1 and/or IRAK2. It also plays an important role in type I IFN production induced by TLR7/8/9. The IRAK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271060 [Multi-domain]  Cd Length: 288  Bit Score: 107.97  E-value: 1.72e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  228 VSPNYDkwemERTDITMKHKLGGGQYGEVYEGVWKkySLTVAVKTLKE-DTMEVEE----FLKEAAVMKEIKHPNLVQLL 302
Cdd:cd14158    7 MTNNFD----ERPISVGGNKLGEGGFGVVFKGYIN--DKNVAVKKLAAmVDISTEDltkqFEQEIQVMAKCQHENLVELL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  303 GVCTREPPFYIITEFMTYGNLLDYLRECNRQEVNAVVL-LYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVAD 381
Cdd:cd14158   81 GYSCDGPQLCLVYTYMPNGSLLDRLACLNDTPPLSWHMrCKIAQGTANGINYLHENNHIHRDIKSANILLDETFVPKISD 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  382 FGLSRLMTGDTYTAH----AGAKfpiKWTAPESLAyNKFSIKSDVWAFGVLLWEIATyGMSPY-----PGIDLSQVYELL 452
Cdd:cd14158  161 FGLARASEKFSQTIMteriVGTT---AYMAPEALR-GEITPKSDIFSFGVVLLEIIT-GLPPVdenrdPQLLLDIKEEIE 235
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|...
gi 62362414  453 EK--------DYRM-ERPEGCPEKVYELMRACWQWNPSDRPSFAEIHQAFETM 496
Cdd:cd14158  236 DEektiedyvDKKMgDWDSTSIEAMYSVASQCLNDKKNRRPDIAKVQQLLQEL 288
STKc_PAK cd06614
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the ...
246-440 2.05e-25

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. PAK deregulation is associated with tumor development. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). Group II PAKs contain a PBD and a catalytic domain, but lack other motifs found in group I PAKs. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. Group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX; no such binding has been demonstrated for group II PAKs. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270789 [Multi-domain]  Cd Length: 255  Bit Score: 106.53  E-value: 2.05e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  246 HKLGGGQYGEVYEGVWKKYSLTVAVK--TLKEDTMEVeeFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNL 323
Cdd:cd06614    6 EKIGEGASGEVYKATDRATGKEVAIKkmRLRKQNKEL--IINEILIMKECKHPNIVDYYDSYLVGDELWVVMEYMDGGSL 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  324 LDYLRECNRqEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFG----LSRL------MTGDTY 393
Cdd:cd06614   84 TDIITQNPV-RMNESQIAYVCREVLQGLEYLHSQNVIHRDIKSDNILLSKDGSVKLADFGfaaqLTKEkskrnsVVGTPY 162
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 62362414  394 tahagakfpikWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPY 440
Cdd:cd06614  163 -----------WMAPEVIKRKDYGPKVDIWSLGIMCIEMAE-GEPPY 197
STKc_LKB1_CaMKK cd14008
Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent ...
248-491 2.61e-25

Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent Protein Kinase Kinase, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Both LKB1 and CaMKKs can phosphorylate and activate AMP-activated protein kinase (AMPK). LKB1, also called STK11, serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMPK. Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The LKB1/CaMKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270910 [Multi-domain]  Cd Length: 267  Bit Score: 106.48  E-value: 2.61e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVwKKYSLT-VAVKTL-----------KEDTMEVEEFL----KEAAVMKEIKHPNLVQLLGVCtrEPPF 311
Cdd:cd14008    1 LGRGSFGKVKLAL-DTETGQlYAIKIFnksrlrkrregKNDRGKIKNALddvrREIAIMKKLDHPNIVRLYEVI--DDPE 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  312 ----YIITEFMTYGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRL 387
Cdd:cd14008   78 sdklYLVLEYCEGGPVMELDSGDRVPPLPEETARKYFRDLVLGLEYLHENGIVHRDIKPENLLLTADGTVKISDFGVSEM 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  388 MTG--DTYTAHAG--AkFpikwTAPESLAYNKFSI---KSDVWAFGVLLWEIAtYGMSPYPGIDLSQVYELLEKDYRM-E 459
Cdd:cd14008  158 FEDgnDTLQKTAGtpA-F----LAPELCDGDSKTYsgkAADIWALGVTLYCLV-FGRLPFNGDNILELYEAIQNQNDEfP 231
                        250       260       270
                 ....*....|....*....|....*....|..
gi 62362414  460 RPEGCPEKVYELMRACWQWNPSDRPSFAEIHQ 491
Cdd:cd14008  232 IPPELSPELKDLLRRMLEKDPEKRITLKEIKE 263
STKc_TSSK4-like cd14162
Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs ...
248-440 8.73e-25

Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. It phosphorylates Cre-Responsive Element Binding protein (CREB), facilitating the binding of CREB to the specific cis cAMP responsive element (CRE), which is important in activating genes related to germ cell differentiation. Mutations in the human TSSK4 gene is associated with infertile Chinese men with impaired spermatogenesis. The TSSK4-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271064 [Multi-domain]  Cd Length: 259  Bit Score: 105.07  E-value: 8.73e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEdTMEVEEFL-----KEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGN 322
Cdd:cd14162    8 LGHGSYAVVKKAYSTKHKCKVAIKIVSK-KKAPEDYLqkflpREIEVIKGLKHPNLICFYEAIETTSRVYIIMELAENGD 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLR-ECNRQEVNAVVLLYmatQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRlmtgDTYTAHAGAKF 401
Cdd:cd14162   87 LLDYIRkNGALPEPQARRWFR---QLVAGVEYCHSKGVVHRDLKCENLLLDKNNNLKITDFGFAR----GVMKTKDGKPK 159
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 62362414  402 PIK-------WTAPESL---AYNKFSikSDVWAFGVLLWEIaTYGMSPY 440
Cdd:cd14162  160 LSEtycgsyaYASPEILrgiPYDPFL--SDIWSMGVVLYTM-VYGRLPF 205
STKc_NUAK2 cd14161
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs ...
244-489 1.74e-24

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. NUAK2 is implicated in regulating actin stress fiber assembly through its association with myosin phosphatase Rho-interacting protein (MRIP), which leads to an increase in myosin regulatory light chain (MLC) phosphorylation. It is also associated with tumor growth, migration, and oncogenicity of melanoma cells. The NUAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271063 [Multi-domain]  Cd Length: 255  Bit Score: 103.88  E-value: 1.74e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  244 MKHK------LGGGQYGEVYEGVWKKYSLtVAVKTLKEDTMEVEEFL----KEAAVMKEIKHPNLVQLLGVCTREPPFYI 313
Cdd:cd14161    1 LKHRyefletLGKGTYGRVKKARDSSGRL-VAIKSIRKDRIKDEQDLlhirREIEIMSSLNHPHIISVYEVFENSSKIVI 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  314 ITEFMTYGNLLDYLreCNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTY 393
Cdd:cd14161   80 VMEYASRGDLYDYI--SERQRLSELEARHFFRQIVSAVHYCHANGIVHRDLKLENILLDANGNIKIADFGLSNLYNQDKF 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  394 -TAHAGAKFpikWTAPESLAYNKFS-IKSDVWAFGVLLWeIATYGMSPYPGIDLSQ-VYELLEKDYRmERPEgcPEKVYE 470
Cdd:cd14161  158 lQTYCGSPL---YASPEIVNGRPYIgPEVDSWSLGVLLY-ILVHGTMPFDGHDYKIlVKQISSGAYR-EPTK--PSDACG 230
                        250
                 ....*....|....*....
gi 62362414  471 LMRACWQWNPSDRPSFAEI 489
Cdd:cd14161  231 LIRWLLMVNPERRATLEDV 249
STKc_MST3 cd06641
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs ...
247-489 2.00e-24

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. It may also regulate paxillin and consequently, cell migration. MST3 is present in human placenta, where it plays an essential role in the oxidative stress-induced apoptosis of trophoblasts in normal spontaneous delivery. Dysregulation of trophoblast apoptosis may result in pregnancy complications such as preeclampsia and intrauterine growth retardation. The MST3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270809 [Multi-domain]  Cd Length: 277  Bit Score: 104.38  E-value: 2.00e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKT--LKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLL 324
Cdd:cd06641   11 KIGKGSFGEVFKGIDNRTQKVVAIKIidLEEAEDEIEDIQQEITVLSQCDSPYVTKYYGSYLKDTKLWIIMEYLGGGSAL 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  325 DYLRECNRQEVNAVVLLymaTQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPIk 404
Cdd:cd06641   91 DLLEPGPLDETQIATIL---REILKGLDYLHSEKKIHRDIKAANVLLSEHGEVKLADFGVAGQLTDTQIKRN*FVGTPF- 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  405 WTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQWNPSDRP 484
Cdd:cd06641  167 WMAPEVIKQSAYDSKADIWSLGITAIELAR-GEPPHSELHPMKVLFLIPKNNPPTLEGNYSKPLKEFVEACLNKEPSFRP 245

                 ....*
gi 62362414  485 SFAEI 489
Cdd:cd06641  246 TAKEL 250
PK_GC_unk cd14045
Pseudokinase domain of the unknown subfamily of membrane Guanylate Cyclase receptors; The ...
267-496 2.19e-24

Pseudokinase domain of the unknown subfamily of membrane Guanylate Cyclase receptors; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs lack a critical aspartate involved in ATP binding and does not exhibit kinase activity. It functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270947 [Multi-domain]  Cd Length: 269  Bit Score: 104.17  E-value: 2.19e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  267 TVAVKTLKEDTMEVEEFL-KEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDYLreCNRQ-EVNAVVLLYMA 344
Cdd:cd14045   32 TVAIKKIAKKSFTLSKRIrKEVKQVRELDHPNLCKFIGGCIEVPNVAIITEYCPKGSLNDVL--LNEDiPLNWGFRFSFA 109
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  345 TQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPIK--WTAPE--SLAYNKFSIKS 420
Cdd:cd14045  110 TDIARGMAYLHQHKIYHGRLKSSNCVIDDRWVCKIADYGLTTYRKEDGSENASGYQQRLMqvYLPPEnhSNTDTEPTQAT 189
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  421 DVWAFGVLLWEIATYGmSPYPGIDLSqvyelLEKDYRMERPE----------GCPEKVYELMRACWQWNPSDRPSFAEIH 490
Cdd:cd14045  190 DVYSYAIILLEIATRN-DPVPEDDYS-----LDEAWCPPLPElisgktenscPCPADYVELIRRCRKNNPAQRPTFEQIK 263

                 ....*.
gi 62362414  491 QAFETM 496
Cdd:cd14045  264 KTLHKI 269
STKc_STK36 cd14002
Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the ...
246-440 2.35e-24

Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK36, also called Fused (or Fu) kinase, is involved in the Hedgehog signaling pathway. It is activated by the Smoothened (SMO) signal transducer, resulting in the stabilization of GLI transcription factors and the phosphorylation of SUFU to facilitate the nuclear accumulation of GLI. In Drosophila, Fused kinase is maternally required for proper segmentation during embryonic development and for the development of legs and wings during the larval stage. In mice, STK36 is not necessary for embryonic development, although mice deficient in STK36 display growth retardation postnatally. The STK36 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270904 [Multi-domain]  Cd Length: 253  Bit Score: 103.49  E-value: 2.35e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  246 HKLGGGQYGEVYEGVWKKYSLTVAVK---TLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTyGN 322
Cdd:cd14002    7 ELIGEGSFGKVYKGRRKYTGQVVALKfipKRGKSEKELRNLRQEIEILRKLNHPNIIEMLDSFETKKEFVVVTEYAQ-GE 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLrECNR----QEVNAVvllymATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAg 398
Cdd:cd14002   86 LFQIL-EDDGtlpeEEVRSI-----AKQLVSALHYLHSNRIIHRDMKPQNILIGKGGVVKLCDFGFARAMSCNTLVLTS- 158
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 62362414  399 akfpIKWT----APESLAYNKFSIKSDVWAFGVLLWEIAtYGMSPY 440
Cdd:cd14002  159 ----IKGTplymAPELVQEQPYDHTADLWSLGCILYELF-VGQPPF 199
STKc_LRRK cd14000
Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the ...
248-489 2.41e-24

Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. Vertebrates contain two members, LRRK1 and LRRK2, which show complementary expression in the brain. Mutations in LRRK2 are linked to both familial and sporadic forms of Parkinson's disease. The normal roles of LRRKs are not clearly defined. They may be involved in mitogen-activated protein kinase (MAPK) pathways, protein translation control, programmed cell death pathways, and cytoskeletal dynamics. The LRRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270902 [Multi-domain]  Cd Length: 275  Bit Score: 104.23  E-value: 2.41e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSltVAVKTLK-----------EDTM-----------EVEEFLKEAAVMKEIKHPNLVQLLGVC 305
Cdd:cd14000    2 LGDGGFGSVYRASYKGEP--VAVKIFNkhtssnfanvpADTMlrhlratdamkNFRLLRQELTVLSHLHHPSIVYLLGIG 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  306 TRepPFYIITEFMTYGNLLDYLRECNRQEVNAVVLLY--MATQISSAMEYLEKKNFIHRDLAARNCLVGE----NHL-VK 378
Cdd:cd14000   80 IH--PLMLVLELAPLGSLDHLLQQDSRSFASLGRTLQqrIALQVADGLRYLHSAMIIYRDLKSHNVLVWTlypnSAIiIK 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  379 VADFGLSRlmtgdtYTAHAGAK----FPiKWTAPESLAYN-KFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLE 453
Cdd:cd14000  158 IADYGISR------QCCRMGAKgsegTP-GFRAPEIARGNvIYNEKVDVFSFGMLLYEILSGGAPMVGHLKFPNEFDIHG 230
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 62362414  454 --KDYRMERPEGCPEKVYELMRACWQWNPSDRPSFAEI 489
Cdd:cd14000  231 glRPPLKQYECAPWPEVEVLMKKCWKENPQQRPTAVTV 268
STKc_PLK cd14099
Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the ...
244-489 2.84e-24

Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. PLKs derive their names from homology to polo, a kinase first identified in Drosophila. There are five mammalian PLKs (PLK1-5) from distinct genes. There is good evidence that PLK1 may function as an oncogene while PLK2-5 have tumor suppressive properties. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. PLK2 functions in G1 progression, S-phase arrest, and centriole duplication. PLK3 regulates angiogenesis and responses to DNA damage. PLK4 is required for late mitotic progression, cell survival, and embryonic development. PLK5 was first identified as a pseudogene containing a stop codon within the kinase domain, however, both murine and human genes encode expressed proteins. PLK5 functions in cell cycle arrest.


Pssm-ID: 271001 [Multi-domain]  Cd Length: 258  Bit Score: 103.40  E-value: 2.84e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  244 MKHK-LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM----EVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFM 318
Cdd:cd14099    4 RRGKfLGKGGFAKCYEVTDMSTGKVYAGKVVPKSSLtkpkQREKLKSEIKIHRSLKHPNIVKFHDCFEDEENVYILLELC 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  319 TYGNLLDYLRECNR---QEVNavvllYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLS-RLMtgdtyt 394
Cdd:cd14099   84 SNGSLMELLKRRKAltePEVR-----YFMRQILSGVKYLHSNRIIHRDLKLGNLFLDENMNVKIGDFGLAaRLE------ 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  395 aHAGAKfpiKWT--------APESLAYNK-FSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEK-DYRMERPEGC 464
Cdd:cd14099  153 -YDGER---KKTlcgtpnyiAPEVLEKKKgHSFEVDIWSLGVILYTLLV-GKPPFETSDVKETYKRIKKnEYSFPSHLSI 227
                        250       260
                 ....*....|....*....|....*
gi 62362414  465 PEKVYELMRACWQWNPSDRPSFAEI 489
Cdd:cd14099  228 SDEAKDLIRSMLQPDPTKRPSLDEI 252
PTK_Jak2_rpt1 cd05078
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 2; Jak2 is widely ...
248-489 4.08e-24

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 2; Jak2 is widely expressed in many tissues. It is essential for the signaling of hormone-like cytokines such as growth hormone, erythropoietin, thrombopoietin, and prolactin, as well as some IFNs and cytokines that signal through the IL-3 and gp130 receptors. Disruption of Jak2 in mice results in an embryonic lethal phenotype with multiple defects including erythropoietic and cardiac abnormalities. It is the only Jak gene that results in a lethal phenotype when disrupted in mice. A mutation in the pseudokinase domain of Jak2, V617F, is present in many myeloproliferative diseases, including almost all patients with polycythemia vera, and 50% of patients with essential thrombocytosis and myelofibrosis. Jak2 is a cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. Despite this, the presumed pseudokinase (repeat 1) domain of Jak2 exhibits dual-specificity kinase activity, phosphorylating two negative regulatory sites in Jak2: Ser523 and Tyr570. Inactivation of the repeat 1 domain increased Jak2 basal activity, suggesting that it modulates the kinase activity of the C-terminal catalytic (repeat 2) domain. The Jak2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270663 [Multi-domain]  Cd Length: 262  Bit Score: 103.10  E-value: 4.08e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKK-------YSLTVAVKTL-KEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMT 319
Cdd:cd05078    7 LGQGTFTKIFKGIRREvgdygqlHETEVLLKVLdKAHRNYSESFFEAASMMSQLSHKHLVLNYGVCVCGDENILVQEYVK 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  320 YGNLLDYLREcNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLV--------GENHLVKVADFGLS-RLMTG 390
Cdd:cd05078   87 FGSLDTYLKK-NKNCINILWKLEVAKQLAWAMHFLEEKTLVHGNVCAKNILLireedrktGNPPFIKLSDPGISiTVLPK 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  391 DTYTAHagakfpIKWTAPESLAYNK-FSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCpeKVY 469
Cdd:cd05078  166 DILLER------IPWVPPECIENPKnLSLATDKWSFGTTLWEICSGGDKPLSALDSQRKLQFYEDRHQLPAPKWT--ELA 237
                        250       260
                 ....*....|....*....|
gi 62362414  470 ELMRACWQWNPSDRPSFAEI 489
Cdd:cd05078  238 NLINNCMDYEPDHRPSFRAI 257
STKc_STK25 cd06642
Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); ...
243-489 4.36e-24

Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK25 is also called Ste20/oxidant stress response kinase 1 (SOK1) or yeast Sps1/Ste20-related kinase 1 (YSK1). It is localized in the Golgi apparatus through its interaction with the Golgi matrix protein GM130. It may be involved in the regulation of cell migration and polarization. STK25 binds and phosphorylates CCM3 (cerebral cavernous malformation 3), also called PCD10 (programmed cell death 10), and may play a role in apoptosis. Human STK25 is a candidate gene responsible for pseudopseudohypoparathyroidism (PPHP), a disease that shares features with the Albright hereditary osteodystrophy (AHO) phenotype. The STK25 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270810 [Multi-domain]  Cd Length: 277  Bit Score: 103.60  E-value: 4.36e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  243 TMKHKLGGGQYGEVYEGVWKKYSLTVAVKT--LKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTY 320
Cdd:cd06642    7 TKLERIGKGSFGEVYKGIDNRTKEVVAIKIidLEEAEDEIEDIQQEITVLSQCDSPYITRYYGSYLKGTKLWIIMEYLGG 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  321 GNLLDYLRECNRQEVnavvllYMAT---QISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHA 397
Cdd:cd06642   87 GSALDLLKPGPLEET------YIATilrEILKGLDYLHSERKIHRDIKAANVLLSEQGDVKLADFGVAGQLTDTQIKRNT 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  398 GAKFPIkWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEKDY--RMERPEGCPEKvyELMRAC 475
Cdd:cd06642  161 FVGTPF-WMAPEVIKQSAYDFKADIWSLGITAIELAK-GEPPNSDLHPMRVLFLIPKNSppTLEGQHSKPFK--EFVEAC 236
                        250
                 ....*....|....
gi 62362414  476 WQWNPSDRPSFAEI 489
Cdd:cd06642  237 LNKDPRFRPTAKEL 250
STKc_HUNK cd14070
Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase ...
247-488 4.91e-24

Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase (also called MAK-V); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HUNK/MAK-V was identified from a mammary tumor in an MMTV-neu transgenic mouse. It is required for the metastasis of c-myc-induced mammary tumors, but is not necessary for c-myc-induced primary tumor formation or normal development. It is required for HER2/neu-induced tumor formation and maintenance of the cells' tumorigenic phenotype. It is over-expressed in aggressive subsets of ovary, colon, and breast carcinomas. HUNK interacts with synaptopodin, and may also play a role in synaptic plasticity. The HUNK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270972 [Multi-domain]  Cd Length: 262  Bit Score: 102.97  E-value: 4.91e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTL-----KEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYG 321
Cdd:cd14070    9 KLGEGSFAKVREGLHAVTGEKVAIKVIdkkkaKKDSYVTKNLRREGRIQQMIRHPNITQLLDILETENSYYLVMELCPGG 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  322 NLLDylRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR----LMTGDTYTAHA 397
Cdd:cd14070   89 NLMH--RIYDKKRLEEREARRYIRQLVSAVEHLHRAGVVHRDLKIENLLLDENDNIKLIDFGLSNcagiLGYSDPFSTQC 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  398 GAKfpiKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYP--GIDLSQVYELLEKDYRMERPEGCPEKVYELMRAC 475
Cdd:cd14070  167 GSP---AYAAPELLARKKYGPKVDVWSIGVNMYAMLT-GTLPFTvePFSLRALHQKMVDKEMNPLPTDLSPGAISFLRSL 242
                        250
                 ....*....|...
gi 62362414  476 WQWNPSDRPSFAE 488
Cdd:cd14070  243 LEPDPLKRPNIKQ 255
STKc_CDKL2_3 cd07846
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; ...
247-493 5.83e-24

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL2, also called p56 KKIAMRE, is expressed in testis, kidney, lung, and brain. It functions mainly in mature neurons and plays an important role in learning and memory. Inactivation of CDKL3, also called NKIAMRE (NKIATRE in rat), by translocation is associated with mild mental retardation. It has been reported that CDKL3 is lost in leukemic cells having a chromosome arm 5q deletion, and may contribute to the transformed phenotype. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270836 [Multi-domain]  Cd Length: 286  Bit Score: 103.27  E-value: 5.83e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTL--KEDTMEVEEF-LKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNL 323
Cdd:cd07846    8 LVGEGSYGMVMKCRHKETGQIVAIKKFleSEDDKMVKKIaMREIKMLKQLRHENLVNLIEVFRRKKRWYLVFEFVDHTVL 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  324 LDYLRECNRQEVNaVVLLYMaTQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMT--GDTYTAHAGAKF 401
Cdd:cd07846   88 DDLEKYPNGLDES-RVRKYL-FQILRGIDFCHSHNIIHRDIKPENILVSQSGVVKLCDFGFARTLAapGEVYTDYVATRW 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  402 pikWTAPESLAYN-KFSIKSDVWAFGVLLWEIATyGMSPYPG-IDLSQVY--------------ELLEKD--------YR 457
Cdd:cd07846  166 ---YRAPELLVGDtKYGKAVDVWAVGCLVTEMLT-GEPLFPGdSDIDQLYhiikclgnliprhqELFQKNplfagvrlPE 241
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*
gi 62362414  458 MERPEGCPEK-------VYELMRACWQWNPSDRPSFAEI--HQAF 493
Cdd:cd07846  242 VKEVEPLERRypklsgvVIDLAKKCLHIDPDKRPSCSELlhHEFF 286
STKc_DCKL cd14095
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called ...
243-454 6.18e-24

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called Doublecortin-like and CAM kinase-like); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL (or DCAMKL) proteins belong to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL proteins contain a C-terminal kinase domain with similarity to CAMKs. They are involved in the regulation of cAMP signaling. Vertebrates contain three DCKL proteins (DCKL1-3); DCKL1 and 2 also contain a serine, threonine, and proline rich domain (SP), while DCKL3 contains only a single DCX domain instead of tandem domains. The DCKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270997 [Multi-domain]  Cd Length: 258  Bit Score: 102.40  E-value: 6.18e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  243 TMKHKLGGGQYGEVYEGVWKKYSLTVAVKTL-------KEDTMEveeflKEAAVMKEIKHPNLVQLLGVCTREPPFYIIT 315
Cdd:cd14095    3 DIGRVIGDGNFAVVKECRDKATDKEYALKIIdkakckgKEHMIE-----NEVAILRRVKHPNIVQLIEEYDTDTELYLVM 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  316 EFMTYGNLLDYLRECNR-QEVNAVVllyMATQISSAMEYLEKKNFIHRDLAARNCLVGENHL----VKVADFGLSRLMTG 390
Cdd:cd14095   78 ELVKGGDLFDAITSSTKfTERDASR---MVTDLAQALKYLHSLSIVHRDIKPENLLVVEHEDgsksLKLADFGLATEVKE 154
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 62362414  391 DTYTAhAGAkfPiKWTAPESLAYNKFSIKSDVWAFGVLLWeIATYGMSPYPGIDLSQvYELLEK 454
Cdd:cd14095  155 PLFTV-CGT--P-TYVAPEILAETGYGLKVDIWAAGVITY-ILLCGFPPFRSPDRDQ-EELFDL 212
STKc_Nek7 cd08229
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
241-496 1.04e-23

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek7 is required for mitotic spindle formation and cytokinesis. It is enriched in the centrosome and is critical for microtubule nucleation. Nek7 is activated by Nek9 during mitosis, and may regulate the p70 ribosomal S6 kinase. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270866 [Multi-domain]  Cd Length: 292  Bit Score: 102.80  E-value: 1.04e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  241 DITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLK----EDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITE 316
Cdd:cd08229   25 NFRIEKKIGRGQFSEVYRATCLLDGVPVALKKVQifdlMDAKARADCIKEIDLLKQLNHPNVIKYYASFIEDNELNIVLE 104
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  317 FMTYGNLLDYLRECNRQE--VNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYT 394
Cdd:cd08229  105 LADAGDLSRMIKHFKKQKrlIPEKTVWKYFVQLCSALEHMHSRRVMHRDIKPANVFITATGVVKLGDLGLGRFFSSKTTA 184
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  395 AHAGAKFPIkWTAPESLAYNKFSIKSDVWAFGVLLWEIATYgMSPYPGiDLSQVYELLEK----DYRMERPEGCPEKVYE 470
Cdd:cd08229  185 AHSLVGTPY-YMSPERIHENGYNFKSDIWSLGCLLYEMAAL-QSPFYG-DKMNLYSLCKKieqcDYPPLPSDHYSEELRQ 261
                        250       260
                 ....*....|....*....|....*.
gi 62362414  471 LMRACWQWNPSDRPSFAEIHQAFETM 496
Cdd:cd08229  262 LVNMCINPDPEKRPDITYVYDVAKRM 287
PTK_Tyk2_rpt1 cd05076
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; Tyk2 is ...
242-489 1.40e-23

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; Tyk2 is widely expressed in many tissues. It is involved in signaling via the cytokine receptors IFN-alphabeta, IL-6, IL-10, IL-12, IL-13, and IL-23. It mediates cell surface urokinase receptor (uPAR) signaling and plays a role in modulating vascular smooth muscle cell (VSMC) functional behavior in response to injury. Tyk2 is also important in dendritic cell function and T helper (Th)1 cell differentiation. A homozygous mutation of Tyk2 was found in a patient with hyper-IgE syndrome (HIES), a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and elevated serum IgE. This suggests that Tyk2 may play important roles in multiple cytokine signaling involved in innate and adaptive immunity. Tyk2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. The Tyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270661 [Multi-domain]  Cd Length: 273  Bit Score: 101.91  E-value: 1.40e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  242 ITMKHKLGGGQYGEVYEGVW-------------------KKYSLTVAVKTLKEDTMEVE-EFLKEAAVMKEIKHPNLVQL 301
Cdd:cd05076    1 ITQLSHLGQGTRTNIYEGRLlvegsgepeedkelvpgrdRGQELRVVLKVLDPSHHDIAlAFFETASLMSQVSHTHLVFV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  302 LGVCTREPPFYIITEFMTYGNLLDYLREcNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLV-------GEN 374
Cdd:cd05076   81 HGVCVRGSENIMVEEFVEHGPLDVWLRK-EKGHVPMAWKFVVARQLASALSYLENKNLVHGNVCAKNILLarlgleeGTS 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  375 HLVKVADFGLsrlmtGDTYTAHAGAKFPIKWTAPESL-AYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLE 453
Cdd:cd05076  160 PFIKLSDPGV-----GLGVLSREERVERIPWIAPECVpGGNSLSTAADKWGFGATLLEICFNGEAPLQSRTPSEKERFYQ 234
                        250       260       270
                 ....*....|....*....|....*....|....*.
gi 62362414  454 KDYRMERPEgCPEkVYELMRACWQWNPSDRPSFAEI 489
Cdd:cd05076  235 RQHRLPEPS-CPE-LATLISQCLTYEPTQRPSFRTI 268
STKc_PDK1 cd05581
Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs ...
248-485 4.29e-23

Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PDK1 carries an N-terminal catalytic domain and a C-terminal pleckstrin homology (PH) domain that binds phosphoinositides. It phosphorylates the activation loop of AGC kinases that are regulated by PI3K such as PKB, SGK, and PKC, among others, and is crucial for their activation. Thus, it contributes in regulating many processes including metabolism, growth, proliferation, and survival. PDK1 also has the ability to autophosphorylate and is constitutively active in mammalian cells. It is essential for normal embryo development and is important in regulating cell volume. The PDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270733 [Multi-domain]  Cd Length: 278  Bit Score: 100.37  E-value: 4.29e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTL------KEdtMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYG 321
Cdd:cd05581    9 LGEGSYSTVVLAKEKETGKEYAIKVLdkrhiiKE--KKVKYVTIEKEVLSRLAHPGIVKLYYTFQDESKLYFVLEYAPNG 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  322 NLLDYLRECNRQEVNAVVLlYMAtQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGD-------TYT 394
Cdd:cd05581   87 DLLEYIRKYGSLDEKCTRF-YTA-EIVLALEYLHSKGIIHRDLKPENILLDEDMHIKITDFGTAKVLGPDsspestkGDA 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  395 AHAGAKFPIK---------WTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGidlSQVYELLEK----DYrmERP 461
Cdd:cd05581  165 DSQIAYNQARaasfvgtaeYVSPELLNEKPAGKSSDLWALGCIIYQMLT-GKPPFRG---SNEYLTFQKivklEY--EFP 238
                        250       260
                 ....*....|....*....|....
gi 62362414  462 EGCPEKVYELMRACWQWNPSDRPS 485
Cdd:cd05581  239 ENFPPDAKDLIQKLLVLDPSKRLG 262
STKc_MST4 cd06640
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs ...
243-489 6.76e-23

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST4 is sometimes referred to as MASK (MST3 and SOK1-related kinase). It plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. It influences cell growth and transformation by modulating the extracellular signal-regulated kinase (ERK) pathway. MST4 may also play a role in tumor formation and progression. It localizes in the Golgi apparatus by interacting with the Golgi matrix protein GM130 and may play a role in cell migration. The MST4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132971 [Multi-domain]  Cd Length: 277  Bit Score: 100.13  E-value: 6.76e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  243 TMKHKLGGGQYGEVYEGVWKKYSLTVAVKT--LKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTY 320
Cdd:cd06640    7 TKLERIGKGSFGEVFKGIDNRTQQVVAIKIidLEEAEDEIEDIQQEITVLSQCDSPYVTKYYGSYLKGTKLWIIMEYLGG 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  321 GNLLDYLRECNRQEVNAVVLLymaTQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAK 400
Cdd:cd06640   87 GSALDLLRAGPFDEFQIATML---KEILKGLDYLHSEKKIHRDIKAANVLLSEQGDVKLADFGVAGQLTDTQIKRNTFVG 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  401 FPIkWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQWNP 480
Cdd:cd06640  164 TPF-WMAPEVIQQSAYDSKADIWSLGITAIELAK-GEPPNSDMHPMRVLFLIPKNNPPTLVGDFSKPFKEFIDACLNKDP 241

                 ....*....
gi 62362414  481 SDRPSFAEI 489
Cdd:cd06640  242 SFRPTAKEL 250
SH2_Src_family cd09933
Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src ...
127-216 7.11e-23

Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src family kinases are nonreceptor tyrosine kinases that have been implicated in pathways regulating proliferation, angiogenesis, invasion and metastasis, and bone metabolism. It is thought that transforming ability of Src is linked to its ability to activate key signaling molecules in these pathways, rather than through direct activity. As such blocking Src activation has been a target for drug companies. Src family members can be divided into 3 groups based on their expression pattern: 1) Src, Fyn, and Yes; 2) Blk, Fgr, Hck, Lck, and Lyn; and 3) Frk-related kinases Frk/Rak and Iyk/Bsk Of these, cellular c-Src is the best studied and most frequently implicated in oncogenesis. The c-Src contains five distinct regions: a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Src exists in both active and inactive conformations. Negative regulation occurs through phosphorylation of Tyr, resulting in an intramolecular association between phosphorylated Tyr and the SH2 domain of SRC, which locks the protein in a closed conformation. Further stabilization of the inactive state occurs through interactions between the SH3 domain and a proline-rich stretch of residues within the kinase domain. Conversely, dephosphorylation of Tyr allows SRC to assume an open conformation. Full activity requires additional autophosphorylation of a Tyr residue within the catalytic domain. Loss of the negative-regulatory C-terminal segment has been shown to result in increased activity and transforming potential. Phosphorylation of the C-terminal Tyr residue by C-terminal Src kinase (Csk) and Csk homology kinase results in increased intramolecular interactions and consequent Src inactivation. Specific phosphatases, protein tyrosine phosphatase a (PTPa) and the SH-containing phosphatases SHP1/SHP2, have also been shown to take a part in Src activation. Src is also activated by direct binding of focal adhesion kinase (Fak) and Crk-associated substrate (Cas) to the SH2 domain. SRC activity can also be regulated by numerous receptor tyrosine kinases (RTKs), such as Her2, epidermal growth factor receptor (EGFR), fibroblast growth factor receptor, platelet-derived growth factor receptor (PDGFR), and vascular endothelial growth factor receptor (VEGFR). In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199827  Cd Length: 101  Bit Score: 94.19  E-value: 7.11e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  127 WYHGPVSRNAAE-YLLSSGIN-GSFLVRESESSPGQRSISLR-----YEGRVYHYRINTASDGKLYVSSESRFNTLAELV 199
Cdd:cd09933    5 WFFGKIKRKDAEkLLLAPGNPrGTFLIRESETTPGAYSLSVRdgddaRGDTVKHYRIRKLDNGGYYITTRATFPTLQELV 84
                         90
                 ....*....|....*..
gi 62362414  200 HHHSTVADGLITTLHYP 216
Cdd:cd09933   85 QHYSKDADGLCCRLTVP 101
STKc_Bck1_like cd06629
Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein ...
244-489 7.32e-23

Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Saccharomyces cerevisiae Bck1 and Schizosaccharomyces pombe Mkh1, and related proteins. Budding yeast Bck1 is part of the cell integrity MAPK pathway, which is activated by stresses and aggressions to the cell wall. The MAPKKK Bck1, MAPKKs Mkk1 and Mkk2, and the MAPK Slt2 make up the cascade that is important in the maintenance of cell wall homeostasis. Fission yeast Mkh1 is involved in MAPK cascades regulating cell morphology, cell wall integrity, salt resistance, and filamentous growth in response to stress. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The Bck1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270799 [Multi-domain]  Cd Length: 270  Bit Score: 99.76  E-value: 7.32e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  244 MKHKL-GGGQYGEVYEGVWKKYSLTVAVKTL------------KEDTMeVEEFLKEAAVMKEIKHPNLVQLLGVCTREPP 310
Cdd:cd06629    4 VKGELiGKGTYGRVYLAMNATTGEMLAVKQVelpktssdradsRQKTV-VDALKSEIDTLKDLDHPNIVQYLGFEETEDY 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  311 FYIITEFMTYGNLLDYLRECNRQEVNavVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRlMTG 390
Cdd:cd06629   83 FSIFLEYVPGGSIGSCLRKYGKFEED--LVRFFTRQILDGLAYLHSKGILHRDLKADNILVDLEGICKISDFGISK-KSD 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  391 DTYTAHAGA--KFPIKWTAPESLAYNK--FSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQV-YELLEKDYRMERPEG-- 463
Cdd:cd06629  160 DIYGNNGATsmQGSVFWMAPEVIHSQGqgYSAKVDIWSLGCVVLEMLA-GRRPWSDDEAIAAmFKLGNKRSAPPVPEDvn 238
                        250       260
                 ....*....|....*....|....*..
gi 62362414  464 -CPEKVyELMRACWQWNPSDRPSFAEI 489
Cdd:cd06629  239 lSPEAL-DFLNACFAIDPRDRPTAAEL 264
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
126-202 9.01e-23

Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they bind pTyr-containing polypeptide ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. They are present in a wide array of proteins including: adaptor proteins (Nck1, Crk, Grb2), scaffolds (Slp76, Shc, Dapp1), kinases (Src, Syk, Fps, Tec), phosphatases (Shp-1, Shp-2), transcription factors (STAT1), Ras signaling molecules (Ras-Gap), ubiquitination factors (c-Cbl), cytoskeleton regulators (Tensin), signal regulators (SAP), and phospholipid second messengers (PLCgamma), amongst others.


Pssm-ID: 198173 [Multi-domain]  Cd Length: 79  Bit Score: 93.29  E-value: 9.01e-23
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 62362414  126 SWYHGPVSRNAAEYLLSSGINGSFLVRESESSPGQRSISLRYE-GRVYHYRINTASDGKLYVSSESR-FNTLAELVHHH 202
Cdd:cd00173    1 PWFHGSISREEAERLLRGKPDGTFLVRESSSEPGDYVLSVRSGdGKVKHYLIERNEGGYYLLGGSGRtFPSLPELVEHY 79
STKc_MAP4K3_like cd06613
Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like ...
246-489 1.06e-22

Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAP4K3, MAP4K1, MAP4K2, MAP4K5, and related proteins. Vertebrate members contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K1, also called haematopoietic progenitor kinase 1 (HPK1), is a hematopoietic-specific STK involved in many cellular signaling cascades including MAPK, antigen receptor, apoptosis, growth factor, and cytokine signaling. It participates in the regulation of T cell receptor signaling and T cell-mediated immune responses. MAP4K2 was referred to as germinal center (GC) kinase because of its preferred location in GC B cells. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. It is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). The MAP4K3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270788 [Multi-domain]  Cd Length: 259  Bit Score: 98.92  E-value: 1.06e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  246 HKLGGGQYGEVYEGVWKKYSLTVAVKTLK-EDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLL 324
Cdd:cd06613    6 QRIGSGTYGDVYKARNIATGELAAVKVIKlEPGDDFEIIQQEISMLKECRHPNIVAYFGSYLRRDKLWIVMEYCGGGSLQ 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  325 D---YLRECNRQEVNavvllYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMT----------GD 391
Cdd:cd06613   86 DiyqVTGPLSELQIA-----YVCRETLKGLAYLHSTGKIHRDIKGANILLTEDGDVKLADFGVSAQLTatiakrksfiGT 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  392 TYtahagakfpikWTAPESLAYNK---FSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEKdyRMERPEGCPEK- 467
Cdd:cd06613  161 PY-----------WMAPEVAAVERkggYDGKCDIWALGITAIELAE-LQPPMFDLHPMRALFLIPK--SNFDPPKLKDKe 226
                        250       260
                 ....*....|....*....|....*..
gi 62362414  468 -----VYELMRACWQWNPSDRPSFAEI 489
Cdd:cd06613  227 kwspdFHDFIKKCLTKNPKKRPTATKL 253
STKc_Byr2_like cd06628
Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein ...
248-489 1.08e-22

Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Schizosaccharomyces pombe Byr2, Saccharomyces cerevisiae and Cryptococcus neoformans Ste11, and related proteins. They contain an N-terminal SAM (sterile alpha-motif) domain, which mediates protein-protein interaction, and a C-terminal catalytic domain. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Byr2 is regulated by Ras1. It responds to pheromone signaling and controls mating through the MAPK pathway. Budding yeast Ste11 functions in MAPK cascades that regulate mating, high osmolarity glycerol, and filamentous growth responses. The Byr2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270798 [Multi-domain]  Cd Length: 267  Bit Score: 99.15  E-value: 1.08e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTME----------VEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEF 317
Cdd:cd06628    8 IGSGSFGSVYLGMNASSGELMAVKQVELPSVSaenkdrkksmLDALQREIALLRELQHENIVQYLGSSSDANHLNIFLEY 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  318 MTYGNLLDYLRecNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR-----LMTGDT 392
Cdd:cd06628   88 VPGGSVATLLN--NYGAFEESLVRNFVRQILKGLNYLHNRGIIHRDIKGANILVDNKGGIKISDFGISKkleanSLSTKN 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  393 YTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELM 472
Cdd:cd06628  166 NGARPSLQGSVFWMAPEVVKQTSYTRKADIWSLGCLVVEMLT-GTHPFPDCTQMQAIFKIGENASPTIPSNISSEARDFL 244
                        250
                 ....*....|....*..
gi 62362414  473 RACWQWNPSDRPSFAEI 489
Cdd:cd06628  245 EKTFEIDHNKRPTADEL 261
PKc_MKK7 cd06618
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
234-491 1.11e-22

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 7; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK7 is a dual-specificity PK that phosphorylates and activates its downstream target, c-Jun N-terminal kinase (JNK), on specific threonine and tyrosine residues. Although MKK7 is capable of dual phosphorylation, it prefers to phosphorylate the threonine residue of JNK. Thus, optimal activation of JNK requires both MKK4 and MKK7. MKK7 is primarily activated by cytokines. MKK7 is essential for liver formation during embryogenesis. It plays roles in G2/M cell cycle arrest and cell growth. In addition, it is involved in the control of programmed cell death, which is crucial in oncogenesis, cancer chemoresistance, and antagonism to TNFalpha-induced killing, through its inhibition by Gadd45beta and the subsequent suppression of the JNK cascade. The MKK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270791 [Multi-domain]  Cd Length: 295  Bit Score: 99.76  E-value: 1.11e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  234 KWEMERTDITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTL-----KEDT----MEVEeflkeaAVMKEIKHPNLVQLLGV 304
Cdd:cd06618    9 KYKADLNDLENLGEIGSGTCGQVYKMRHKKTGHVMAVKQMrrsgnKEENkrilMDLD------VVLKSHDCPYIVKCYGY 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  305 CTREPPFYIITEFMtyGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYL-EKKNFIHRDLAARNCLVGENHLVKVADFG 383
Cdd:cd06618   83 FITDSDVFICMELM--STCLDKLLKRIQGPIPEDILGKMTVSIVKALHYLkEKHGVIHRDVKPSNILLDESGNVKLCDFG 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  384 LS-RLMTGDTYTAHAGAKfpiKWTAPESLAYNKFS---IKSDVWAFGVLLWEIATyGMSPYPGIDLSqvYELLEKDYRME 459
Cdd:cd06618  161 ISgRLVDSKAKTRSAGCA---AYMAPERIDPPDNPkydIRADVWSLGISLVELAT-GQFPYRNCKTE--FEVLTKILNEE 234
                        250       260       270
                 ....*....|....*....|....*....|....*..
gi 62362414  460 RPEGCPEKVY-----ELMRACWQWNPSDRPSFAEIHQ 491
Cdd:cd06618  235 PPSLPPNEGFspdfcSFVDLCLTKDHRYRPKYRELLQ 271
STKc_cGK cd05572
Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); ...
248-494 1.29e-22

Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mammals have two cGK isoforms from different genes, cGKI and cGKII. cGKI exists as two splice variants, cGKI-alpha and cGKI-beta. cGK consists of an N-terminal regulatory domain containing a dimerization and an autoinhibitory pseudosubstrate region, two cGMP-binding domains, and a C-terminal catalytic domain. Binding of cGMP to both binding sites releases the inhibition of the catalytic center by the pseudosubstrate region, allowing autophosphorylation and activation of the kinase. cGKI is a soluble protein expressed in all smooth muscles, platelets, cerebellum, and kidney. It is also expressed at lower concentrations in other tissues. cGKII is a membrane-bound protein that is most abundantly expressed in the intestine. It is also present in the brain nuclei, adrenal cortex, kidney, lung, and prostate. cGKI is involved in the regulation of smooth muscle tone, smooth cell proliferation, and platelet activation. cGKII plays a role in the regulation of secretion, such as renin secretion by the kidney and aldosterone secretion by the adrenal. It also regulates bone growth and the circadian rhythm. The cGK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270724 [Multi-domain]  Cd Length: 262  Bit Score: 98.84  E-value: 1.29e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKE----DTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNL 323
Cdd:cd05572    1 LGVGGFGRVELVQLKSKGRTFALKCVKKrhivQTRQQEHIFSEKEILEECNSPFIVKLYRTFKDKKYLYMLMEYCLGGEL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  324 LDYLRECNRQEvNAVVLLYMAtQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTahagakfpi 403
Cdd:cd05572   81 WTILRDRGLFD-EYTARFYTA-CVVLAFEYLHSRGIIYRDLKPENLLLDSNGYVKLVDFGFAKKLGSGRKT--------- 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  404 kWT--------APESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQ--VYEL-LEKDYRMERPEGCPEKVYELM 472
Cdd:cd05572  150 -WTfcgtpeyvAPEIILNKGYDFSVDYWSLGILLYELLT-GRPPFGGDDEDPmkIYNIiLKGIDKIEFPKYIDKNAKNLI 227
                        250       260
                 ....*....|....*....|....*....
gi 62362414  473 RACWQWNPSDR-----PSFAEI--HQAFE 494
Cdd:cd05572  228 KQLLRRNPEERlgylkGGIRDIkkHKWFE 256
STK_BAK1_like cd14664
Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; ...
248-494 1.50e-22

Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes three leucine-rich repeat receptor-like kinases (LRR-RLKs): Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1), and Physcomitrella patens CLL1B clavata1-like receptor S/T protein kinase. BAK1 functions in various signaling pathways. It plays a role in BR (brassinosteroid)-regulated plant development as a co-receptor of BRASSINOSTEROID (BR) INSENSITIVE 1 (BRI1), the receptor for BRs, and is required for full activation of BR signaling. It also modulates pathways involved in plant resistance to pathogen infection (pattern-triggered immunity, PTI) and herbivore attack (wound- or herbivore feeding-induced accumulation of jasmonic acid (JA) and JA-isoleucine. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The STK_BAK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271134 [Multi-domain]  Cd Length: 270  Bit Score: 98.72  E-value: 1.50e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLtVAVKTLKEDTMEVEE--FLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLD 325
Cdd:cd14664    1 IGRGGAGTVYKGVMPNGTL-VAVKRLKGEGTQGGDhgFQAEIQTLGMIRHRNIVRLRGYCSNPTTNLLVYEYMPNGSLGE 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  326 YLREcnrQEVNAVVLLY-----MATQISSAMEYLEKK---NFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHA 397
Cdd:cd14664   80 LLHS---RPESQPPLDWetrqrIALGSARGLAYLHHDcspLIIHRDVKSNNILLDEEFEAHVADFGLAKLMDDKDSHVMS 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  398 GAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPY------PGIDLSQVYELLEKDYRME-----RPEGCP- 465
Cdd:cd14664  157 SVAGSYGYIAPEYAYTGKVSEKSDVYSYGVVLLELIT-GKRPFdeafldDGVDIVDWVRGLLEEKKVEalvdpDLQGVYk 235
                        250       260       270
                 ....*....|....*....|....*....|...
gi 62362414  466 -EKVYELMRA---CWQWNPSDRPSFAEIHQAFE 494
Cdd:cd14664  236 lEEVEQVFQVallCTQSSPMERPTMREVVRMLE 268
STKc_MLCK-like cd14006
Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs ...
248-488 1.52e-22

Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This family is composed of MLCKs and related MLCK-like kinase domains from giant STKs such as titin, obscurin, SPEG, Unc-89, Trio, kalirin, and Twitchin. Also included in this family are Death-Associated Protein Kinases (DAPKs) and Death-associated protein kinase-Related Apoptosis-inducing protein Kinase (DRAKs). MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. Titin, obscurin, Twitchin, and SPEG are muscle proteins involved in the contractile apparatus. The giant STKs are multidomain proteins containing immunoglobulin (Ig), fibronectin type III (FN3), SH3, RhoGEF, PH and kinase domains. Titin, obscurin, Twitchin, and SPEG contain many Ig domain repeats at the N-terminus, while Trio and Kalirin contain spectrin-like repeats. The MLCK-like family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270908 [Multi-domain]  Cd Length: 247  Bit Score: 98.11  E-value: 1.52e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDYL 327
Cdd:cd14006    1 LGRGRFGVVKRCIEKATGREFAAKFIPKRDKKKEAVLREISILNQLQHPRIIQLHEAYESPTELVLILELCSGGELLDRL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  328 REcnRQEVN-AVVLLYMaTQISSAMEYLEKKNFIHRDLAARNCLVGENH--LVKVADFGLSRLMTGDTYTAHagakfpIK 404
Cdd:cd14006   81 AE--RGSLSeEEVRTYM-RQLLEGLQYLHNHHILHLDLKPENILLADRPspQIKIIDFGLARKLNPGEELKE------IF 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  405 WT----APESLAYNKFSIKSDVWAFGVLlweiaTY----GMSPYPGIDlsqVYELLEK----DYRMERP--EGCPEKVYE 470
Cdd:cd14006  152 GTpefvAPEIVNGEPVSLATDMWSIGVL-----TYvllsGLSPFLGED---DQETLANisacRVDFSEEyfSSVSQEAKD 223
                        250
                 ....*....|....*...
gi 62362414  471 LMRACWQWNPSDRPSFAE 488
Cdd:cd14006  224 FIRKLLVKEPRKRPTAQE 241
STKc_MEKK4 cd06626
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
246-491 2.03e-22

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK4 is a MAPK kinase kinase that phosphorylates and activates the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. MEKK4 also plays roles in the re-polarization of the actin cytoskeleton in response to osmotic stress, in the proper closure of the neural tube, in cardiovascular development, and in immune responses. The MEKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270796 [Multi-domain]  Cd Length: 265  Bit Score: 98.14  E-value: 2.03e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  246 HKLGGGQYGEVYEGVWKKYSLTVAVKTLK---EDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGN 322
Cdd:cd06626    6 NKIGEGTFGKVYTAVNLDTGELMAMKEIRfqdNDPKTIKEIADEMKVLEGLDHPNLVRYYGVEVHREEVYIFMEYCQEGT 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLREcNRQEVNAVVLLYmATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGlSRLMTGDTYTAHAGAKF- 401
Cdd:cd06626   86 LEELLRH-GRILDEAVIRVY-TLQLLEGLAYLHENGIVHRDIKPANIFLDSNGLIKLGDFG-SAVKLKNNTTTMAPGEVn 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  402 -----PIkWTAPESLAYNKFSIK---SDVWAFGVLLWEIATyGMSPYPgiDLSQVYELLEKDYRMERPEgCPEKV----- 468
Cdd:cd06626  163 slvgtPA-YMAPEVITGNKGEGHgraADIWSLGCVVLEMAT-GKRPWS--ELDNEWAIMYHVGMGHKPP-IPDSLqlspe 237
                        250       260
                 ....*....|....*....|....
gi 62362414  469 -YELMRACWQWNPSDRPSFAEIHQ 491
Cdd:cd06626  238 gKDFLSRCLESDPKKRPTASELLD 261
STKc_RIP2 cd14026
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2; STKs catalyze ...
246-486 3.24e-22

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP2, also called RICK or CARDIAK, harbors a C-terminal Caspase Activation and Recruitment domain (CARD) belonging to the Death domain (DD) superfamily. It functions as an effector kinase downstream of the pattern recognition receptors from the Nod-like (NLR) family, Nod1 and Nod2, which recognizes bacterial peptidoglycans released upon infection. RIP2 may also be involved in regulating wound healing and keratinocyte proliferation. RIP kinases serve as essential sensors of cellular stress. The RIP2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270928 [Multi-domain]  Cd Length: 284  Bit Score: 98.07  E-value: 3.24e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  246 HKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM----EVEEFLKEAAVMKEIKHPNLVQLLGVCTrEPPFY-IITEFMTY 320
Cdd:cd14026    3 RYLSRGAFGTVSRARHADWRVTVAIKCLKLDSPvgdsERNCLLKEAEILHKARFSYILPILGICN-EPEFLgIVTEYMTN 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  321 GNLLDYLRECNRQEVNAVVLLY-MATQISSAMEYLEKKN--FIHRDLAARNCLVGENHLVKVADFGLSRL----MTGDTY 393
Cdd:cd14026   82 GSLNELLHEKDIYPDVAWPLRLrILYEIALGVNYLHNMSppLLHHDLKTQNILLDGEFHVKIADFGLSKWrqlsISQSRS 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  394 TAHAGAKFPIKWTAPESlaYN-----KFSIKSDVWAFGVLLWEIATygmSPYPGIDLSQVYELLEKDYRMERP----EGC 464
Cdd:cd14026  162 SKSAPEGGTIIYMPPEE--YEpsqkrRASVKHDIYSYAIIMWEVLS---RKIPFEEVTNPLQIMYSVSQGHRPdtgeDSL 236
                        250       260
                 ....*....|....*....|....*...
gi 62362414  465 P------EKVYELMRACWQWNPSDRPSF 486
Cdd:cd14026  237 PvdiphrATLINLIESGWAQNPDERPSF 264
STKc_EIF2AK cd13996
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
247-489 3.60e-22

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: General Control Non-derepressible-2 (GCN2) which is activated during amino acid or serum starvation; protein kinase regulated by RNA (PKR) which is activated by double stranded RNA; heme-regulated inhibitor kinase (HRI) which is activated under heme-deficient conditions; and PKR-like endoplasmic reticulum kinase (PERK) which is activated when misfolded proteins accumulate in the ER. The EIF2AK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270898 [Multi-domain]  Cd Length: 273  Bit Score: 97.75  E-value: 3.60e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKT--LKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLL 324
Cdd:cd13996   13 LLGSGGFGSVYKVRNKVDGVTYAIKKirLTEKSSASEKVLREVKALAKLNHPNIVRYYTAWVEEPPLYIQMELCEGGTLR 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  325 DYLRECNRQE-VNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLV-GENHLVKVADFGLSRLMTGDT---------- 392
Cdd:cd13996   93 DWIDRRNSSSkNDRKLALELFKQILKGVSYIHSKGIVHRDLKPSNIFLdNDDLQVKIGDFGLATSIGNQKrelnnlnnnn 172
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  393 ------YTAHAGAKFpikWTAPESLAYNKFSIKSDVWAFGVLLWEIatygmspypgidlsqvyeLLEKDYRMER------ 460
Cdd:cd13996  173 ngntsnNSVGIGTPL---YASPEQLDGENYNEKADIYSLGIILFEM------------------LHPFKTAMERstiltd 231
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 62362414  461 ------PEGCPEKVYE---LMRACWQWNPSDRPSFAEI 489
Cdd:cd13996  232 lrngilPESFKAKHPKeadLIQSLLSKNPEERPSAEQL 269
STKc_SnRK3 cd14663
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
234-491 4.01e-22

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK3 is represented in this cd. The SnRK3 group contains members also known as CBL-interacting protein kinase, salt overly sensitive 2, SOS3-interacting proteins and protein kinase S. These kinases interact with calcium-binding proteins such as SOS3, SCaBPs, and CBL proteins, and are involved in responses to salt stress and in sugar and ABA signaling. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271133 [Multi-domain]  Cd Length: 256  Bit Score: 97.09  E-value: 4.01e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  234 KWEMERTditmkhkLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTME----VEEFLKEAAVMKEIKHPNLVQLLGVCTREP 309
Cdd:cd14663    1 RYELGRT-------LGEGTFAKVKFARNTKTGESVAIKIIDKEQVAregmVEQIKREIAIMKLLRHPNIVELHEVMATKT 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  310 PFYIITEFMTYGNLLDYLRECNR-QEVNAvvlLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLM 388
Cdd:cd14663   74 KIFFVMELVTGGELFSKIAKNGRlKEDKA---RKYFQQLIDAVDYCHSRGVFHRDLKPENLLLDEDGNLKISDFGLSALS 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  389 TG--DTYTAHAGAKFPiKWTAPESLAYNKF-SIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEK-DYRMerPEGC 464
Cdd:cd14663  151 EQfrQDGLLHTTCGTP-NYVAPEVLARRGYdGAKADIWSCGVILFVLLA-GYLPFDDENLMALYRKIMKgEFEY--PRWF 226
                        250       260
                 ....*....|....*....|....*..
gi 62362414  465 PEKVYELMRACWQWNPSDRPSFAEIHQ 491
Cdd:cd14663  227 SPGAKSLIKRILDPNPSTRITVEQIMA 253
STKc_MARK cd14072
Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; ...
268-489 4.61e-22

Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MARKs, also called Partitioning-defective 1 (Par1) proteins, function as regulators of diverse cellular processes in nematodes, Drosophila, yeast, and vertebrates. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. Vertebrates contain four isoforms, namely MARK1 (or Par1c), MARK2 (or Par1b), MARK3 (Par1a), and MARK4 (or MARKL1). Known substrates of MARKs include the cell cycle-regulating phosphatase Cdc25, tyrosine phosphatase PTPH1, MAPK scaffolding protein KSR1, class IIa histone deacetylases, and plakophilin 2. The MARK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270974 [Multi-domain]  Cd Length: 253  Bit Score: 96.82  E-value: 4.61e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  268 VAVKTLKEDTME---VEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDYLRECNR-QEVNAVVLLym 343
Cdd:cd14072   28 VAIKIIDKTQLNpssLQKLFREVRIMKILNHPNIVKLFEVIETEKTLYLVMEYASGGEVFDYLVAHGRmKEKEARAKF-- 105
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  344 aTQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMT-GDTYTAHAGAKfpiKWTAPESLAYNKFS-IKSD 421
Cdd:cd14072  106 -RQIVSAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFGFSNEFTpGNKLDTFCGSP---PYAAPELFQGKKYDgPEVD 181
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 62362414  422 VWAFGVLLWEIATyGMSPYPGIDLSQVYE-LLEKDYRMerPEGCPEKVYELMRACWQWNPSDRPSFAEI 489
Cdd:cd14072  182 VWSLGVILYTLVS-GSLPFDGQNLKELRErVLRGKYRI--PFYMSTDCENLLKKFLVLNPSKRGTLEQI 247
PKc_MKK4 cd06616
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
235-448 5.46e-22

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 4; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK4 is a dual-specificity PK that phosphorylates and activates the downstream targets, c-Jun N-terminal kinase (JNK) and p38 MAPK, on specific threonine and tyrosine residues. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. Their activation is associated with the induction of cell death. Mice deficient in MKK4 die during embryogenesis and display anemia, severe liver hemorrhage, and abnormal hepatogenesis. MKK4 may also play roles in the immune system and in cardiac hypertrophy. It plays a major role in cancer as a tumor and metastasis suppressor. Under certain conditions, MKK4 is pro-oncogenic. The MKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270790 [Multi-domain]  Cd Length: 291  Bit Score: 97.44  E-value: 5.46e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  235 WEMERTDITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKE--DTMEVEEFLKEA-AVMKEIKHPNLVQLLGVCTREPPF 311
Cdd:cd06616    1 YEFTAEDLKDLGEIGRGAFGTVNKMLHKPSGTIMAVKRIRStvDEKEQKRLLMDLdVVMRSSDCPYIVKFYGALFREGDC 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  312 YIITEFMT--YGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKK-NFIHRDLAARNCLVGENHLVKVADFGLS-RL 387
Cdd:cd06616   81 WICMELMDisLDKFYKYVYEVLDSVIPEEILGKIAVATVKALNYLKEElKIIHRDVKPSNILLDRNGNIKLCDFGISgQL 160
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  388 MTGDTYTAHAGAKfpiKWTAPESLAYN----KFSIKSDVWAFGVLLWEIATyGMSPYPGID-----LSQV 448
Cdd:cd06616  161 VDSIAKTRDAGCR---PYMAPERIDPSasrdGYDVRSDVWSLGITLYEVAT-GKFPYPKWNsvfdqLTQV 226
PTK_Jak1_rpt1 cd05077
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 1; Jak1 is widely ...
242-489 5.84e-22

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 1; Jak1 is widely expressed in many tissues. Many cytokines are dependent on Jak1 for signaling, including those that use the shared receptor subunits, common gamma chain (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21) and gp130 (IL-6, IL-11, oncostatin M, G-CSF, and IFNs, among others). The many varied interactions of Jak1 and its ubiquitous expression suggest many biological roles. Jak1 is important in neurological development, as well as in lymphoid development and function. It also plays a role in the pathophysiology of cardiac hypertrophy and heart failure. A mutation in the ATP-binding site of Jak1 was identified in a human uterine leiomyosarcoma cell line, resulting in defective cytokine induction and antigen presentation, thus allowing the tumor to evade the immune system. Jak1 is a cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. The Jak1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270662 [Multi-domain]  Cd Length: 266  Bit Score: 96.93  E-value: 5.84e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  242 ITMKHKLGGGQYGEVYEGVWKKYS------------LTVAVKTLKEDTMEVE-EFLKEAAVMKEIKHPNLVQLLGVCTRE 308
Cdd:cd05077    1 IVQGEHLGRGTRTQIYAGILNYKDddedegysyekeIKVILKVLDPSHRDISlAFFETASMMRQVSHKHIVLLYGVCVRD 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  309 PPFYIITEFMTYGNLLDYLREcnRQEVNAVVLLY-MATQISSAMEYLEKKNFIHRDLAARNCLVGENHL-------VKVA 380
Cdd:cd05077   81 VENIMVEEFVEFGPLDLFMHR--KSDVLTTPWKFkVAKQLASALSYLEDKDLVHGNVCTKNILLAREGIdgecgpfIKLS 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  381 DFG-----LSRLMTGDTytahagakfpIKWTAPESLAYNK-FSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEK 454
Cdd:cd05077  159 DPGipitvLSRQECVER----------IPWIAPECVEDSKnLSIAADKWSFGTTLWEICYNGEIPLKDKTLAEKERFYEG 228
                        250       260       270
                 ....*....|....*....|....*....|....*
gi 62362414  455 DYRMERPEgCPEkVYELMRACWQWNPSDRPSFAEI 489
Cdd:cd05077  229 QCMLVTPS-CKE-LADLMTHCMNYDPNQRPFFRAI 261
STKc_NIM1 cd14075
Catalytic domain of the Serine/Threonine Kinase, NIM1; STKs catalyze the transfer of the ...
243-489 6.73e-22

Catalytic domain of the Serine/Threonine Kinase, NIM1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NIM1 is a widely-expressed kinase belonging to the AMP-activated protein kinase (AMPK) subfamily. Although present in most tissues, NIM1 kinase activity is only observed in the brain and testis. NIM1 is capable of autophosphorylating and activating itself, but may be present in other tissues in the inactive form. The physiological function of NIM1 has yet to be elucidated. The NIM1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270977 [Multi-domain]  Cd Length: 255  Bit Score: 96.25  E-value: 6.73e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  243 TMKHKLGGGQYGEVYEGVwkkYSLT---VAVKTLKEDTME--VEEFL-KEAAVMKEIKHPNLVQLLGVCTREPPFYIITE 316
Cdd:cd14075    5 RIRGELGSGNFSQVKLGI---HQLTkekVAIKILDKTKLDqkTQRLLsREISSMEKLHHPNIIRLYEVVETLSKLHLVME 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  317 FMTYGNLLDYLRECNR-QEVNAVVLLymaTQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMT-GDTYT 394
Cdd:cd14075   82 YASGGELYTKISTEGKlSESEAKPLF---AQIVSAVKHMHENNIIHRDLKAENVFYASNNCVKVGDFGFSTHAKrGETLN 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  395 AHAGAkfPiKWTAPESLA-YNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYE-LLEKDYRMerPEGCPEKVYELM 472
Cdd:cd14075  159 TFCGS--P-PYAAPELFKdEHYIGIYVDIWALGVLLYFMVT-GVMPFRAETVAKLKKcILEGTYTI--PSYVSEPCQELI 232
                        250
                 ....*....|....*..
gi 62362414  473 RACWQWNPSDRPSFAEI 489
Cdd:cd14075  233 RGILQPVPSDRYSIDEI 249
STKc_STK10 cd06644
Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase ...
228-510 1.00e-21

Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase or LOK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK10/LOK is also called polo-like kinase kinase 1 in Xenopus (xPlkk1). It is highly expressed in lymphocytes and is responsible in regulating leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. It plays a role in regulating the CD28 responsive element in T cells, and may also function as a regulator of polo-like kinase 1 (Plk1), a protein which is overexpressed in multiple tumor types. The STK10 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132975 [Multi-domain]  Cd Length: 292  Bit Score: 97.02  E-value: 1.00e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  228 VSPNyDKWEMertditmKHKLGGGQYGEVYEGVWKKYSLTVAVKTLK-EDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCT 306
Cdd:cd06644    8 LDPN-EVWEI-------IGELGDGAFGKVYKAKNKETGALAAAKVIEtKSEEELEDYMVEIEILATCNHPYIVKLLGAFY 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  307 REPPFYIITEFMTYGNLLDYLRECNR--QEVNAVVLlymATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGL 384
Cdd:cd06644   80 WDGKLWIMIEFCPGGAVDAIMLELDRglTEPQIQVI---CRQMLEALQYLHSMKIIHRDLKAGNVLLTLDGDIKLADFGV 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  385 S--RLMTGDTYTAHAGAKFpikWTAP-----ESLAYNKFSIKSDVWAFGVLLWEIATygMSPyPGIDLSQVYELLeKDYR 457
Cdd:cd06644  157 SakNVKTLQRRDSFIGTPY---WMAPevvmcETMKDTPYDYKADIWSLGITLIEMAQ--IEP-PHHELNPMRVLL-KIAK 229
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 62362414  458 MERPE-GCPEK----VYELMRACWQWNPSDRPSFAeihQAFETMFQESSISDEVEKEL 510
Cdd:cd06644  230 SEPPTlSQPSKwsmeFRDFLKTALDKHPETRPSAA---QLLEHPFVSSVTSNRPLREL 284
STKc_TSSK6-like cd14164
Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs ...
248-489 1.04e-21

Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK6, also called SSTK, is expressed at the head of elongated sperm. It can phosphorylate histones and associate with heat shock protens HSP90 and HSC70. Male mice deficient in TSSK6 are infertile, showing spermatogenic impairment including reduced sperm counts, impaired DNA condensation, abnormal morphology and decreased motility rates. The TSSK6-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271066 [Multi-domain]  Cd Length: 256  Bit Score: 96.08  E-value: 1.04e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLkeDTME-----VEEFL-KEAAVMKEIKHPNLVQL---LGVCTREppFYIITEfM 318
Cdd:cd14164    8 IGEGSFSKVKLATSQKYCCKVAIKIV--DRRRaspdfVQKFLpRELSILRRVNHPNIVQMfecIEVANGR--LYIVME-A 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  319 TYGNLLDYLRECNRQEVNAVVLLYmaTQISSAMEYLEKKNFIHRDLAARNCLV-GENHLVKVADFGLSRLMTG--DTYTA 395
Cdd:cd14164   83 AATDLLQKIQEVHHIPKDLARDMF--AQMVGAVNYLHDMNIVHRDLKCENILLsADDRKIKIADFGFARFVEDypELSTT 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  396 HAGAKfpiKWTAPESLAYNKFSIKS-DVWAFGVLLWEIATyGMSPYPGiDLSQVYELLEKDYRMERPEGCPEKVYELMRA 474
Cdd:cd14164  161 FCGSR---AYTPPEVILGTPYDPKKyDVWSLGVVLYVMVT-GTMPFDE-TNVRRLRLQQRGVLYPSGVALEEPCRALIRT 235
                        250
                 ....*....|....*
gi 62362414  475 CWQWNPSDRPSFAEI 489
Cdd:cd14164  236 LLQFNPSTRPSIQQV 250
STKc_TGFbR_I cd14056
Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta family Type ...
246-485 1.20e-21

Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta family Type I Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of type I receptors for the TGFbeta family of secreted signaling molecules including TGFbeta, bone morphogenetic proteins, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation through trans-phosphorylation by type II receptors, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. They are inhibited by the immunophilin FKBP12, which is thought to control leaky signaling caused by receptor oligomerization in the absence of ligand. The TGFbR-I subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270958 [Multi-domain]  Cd Length: 287  Bit Score: 96.57  E-value: 1.20e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  246 HKLGGGQYGEVYEGVWKKYslTVAVKTLkeDTMEVEEFLKEA----AVMkeIKHPNLVQL-------LGVCTReppFYII 314
Cdd:cd14056    1 KTIGKGRYGEVWLGKYRGE--KVAVKIF--SSRDEDSWFRETeiyqTVM--LRHENILGFiaadiksTGSWTQ---LWLI 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  315 TEFMTYGNLLDYLRecnRQEVNAVVLLYMATQISSAMEYL-------EKKNFI-HRDLAARNCLVGENHLVKVADFGLSR 386
Cdd:cd14056   72 TEYHEHGSLYDYLQ---RNTLDTEEALRLAYSAASGLAHLhteivgtQGKPAIaHRDLKSKNILVKRDGTCCIADLGLAV 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  387 LMTGDTYT------AHAGAKfpiKWTAPE----SLAYNKFS--IKSDVWAFGVLLWEIAT---------------YGMSP 439
Cdd:cd14056  149 RYDSDTNTidippnPRVGTK---RYMAPEvlddSINPKSFEsfKMADIYSFGLVLWEIARrceiggiaeeyqlpyFGMVP 225
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 62362414  440 Y-PGIDLSQVYELLEKdyrmERPE------GCPE--KVYELMRACWQWNPSDRPS 485
Cdd:cd14056  226 SdPSFEEMRKVVCVEK----LRPPipnrwkSDPVlrSMVKLMQECWSENPHARLT 276
STKc_Aurora-A cd14116
Catalytic domain of the Serine/Threonine kinase, Aurora-A kinase; STKs catalyze the transfer ...
234-489 1.74e-21

Catalytic domain of the Serine/Threonine kinase, Aurora-A kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2, which also localizes the kinase to spindle microtubules. Aurora-A is overexpressed in many cancer types such as prostate, ovarian, breast, bladder, gastric, and pancreatic. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271018 [Multi-domain]  Cd Length: 258  Bit Score: 95.41  E-value: 1.74e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  234 KWEMErtDITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTME---VEEFLK-EAAVMKEIKHPNLVQLLGVCTREP 309
Cdd:cd14116    1 QWALE--DFEIGRPLGKGKFGNVYLAREKQSKFILALKVLFKAQLEkagVEHQLRrEVEIQSHLRHPNILRLYGYFHDAT 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  310 PFYIITEFMTYGNLLDYLRECNRQEvNAVVLLYMaTQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMT 389
Cdd:cd14116   79 RVYLILEYAPLGTVYRELQKLSKFD-EQRTATYI-TELANALSYCHSKRVIHRDIKPENLLLGSAGELKIADFGWSVHAP 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  390 GDTYTAHAGAkfpIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEKdYRMERPEGCPEKVY 469
Cdd:cd14116  157 SSRRTTLCGT---LDYLPPEMIEGRMHDEKVDLWSLGVLCYEFLV-GKPPFEANTYQETYKRISR-VEFTFPDFVTEGAR 231
                        250       260
                 ....*....|....*....|
gi 62362414  470 ELMRACWQWNPSDRPSFAEI 489
Cdd:cd14116  232 DLISRLLKHNPSQRPMLREV 251
STKc_Nek4 cd08223
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
248-489 2.11e-21

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek4 is highly abundant in the testis. Its specific function is unknown. Neks are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. Nek4 is one in a family of 11 different Neks (Nek1-11). The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270862 [Multi-domain]  Cd Length: 257  Bit Score: 95.20  E-value: 2.11e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTL---KEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPF-YIITEFMTYGNL 323
Cdd:cd08223    8 IGKGSYGEVWLVRHKRDRKQYVIKKLnlkNASKRERKAAEQEAKLLSKLKHPNIVSYKESFEGEDGFlYIVMGFCEGGDL 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  324 LDYLRECNRQ--EVNAVVLLYMatQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTG--DTYTAHAGA 399
Cdd:cd08223   88 YTRLKEQKGVllEERQVVEWFV--QIAMALQYMHERNILHRDLKTQNIFLTKSNIIKVGDLGIARVLESssDMATTLIGT 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  400 KFpikWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSpYPGIDL-SQVYELLE-------KDYrmeRPEGCpekvyEL 471
Cdd:cd08223  166 PY---YMSPELFSNKPYNHKSDVWALGCCVYEMATLKHA-FNAKDMnSLVYKILEgklppmpKQY---SPELG-----EL 233
                        250
                 ....*....|....*...
gi 62362414  472 MRACWQWNPSDRPSFAEI 489
Cdd:cd08223  234 IKAMLHQDPEKRPSVKRI 251
STKc_DCKL3 cd14185
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called ...
274-453 2.20e-21

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called Doublecortin-like and CAM kinase-like 3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL3 (or DCAMKL3) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. DCKL3 contains a single DCX domain (instead of a tandem) and a C-terminal kinase domain with similarity to CAMKs. It has been shown to interact with tubulin and JIP1/2. The DCKL3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271087 [Multi-domain]  Cd Length: 258  Bit Score: 95.01  E-value: 2.20e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  274 KEDTMEveeflKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDYLRECNR-QEVNAVVllyMATQISSAME 352
Cdd:cd14185   41 KEDMIE-----SEILIIKSLSHPNIVKLFEVYETEKEIYLILEYVRGGDLFDAIIESVKfTEHDAAL---MIIDLCEALV 112
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  353 YLEKKNFIHRDLAARNCLVGENH----LVKVADFGLSRLMTGDTYTAHAGAKFpikwTAPESLAYNKFSIKSDVWAFGVL 428
Cdd:cd14185  113 YIHSKHIVHRDLKPENLLVQHNPdkstTLKLADFGLAKYVTGPIFTVCGTPTY----VAPEILSEKGYGLEVDMWAAGVI 188
                        170       180
                 ....*....|....*....|....*..
gi 62362414  429 LWeIATYGMSPY--PGIDLSQVYELLE 453
Cdd:cd14185  189 LY-ILLCGFPPFrsPERDQEELFQIIQ 214
STKc_ULK1_2-like cd14120
Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar ...
248-488 2.52e-21

Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. ULK2 is ubiquitously expressed and is essential in autophagy induction. ULK1 and ULK2 have unique and cell-type specific roles, but also display partially redundant roles in starvation-induced autophagy. They both display neuron-specific functions: ULK1 is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, and axon branching; ULK2 plays a role in axon development. The ULK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271022 [Multi-domain]  Cd Length: 256  Bit Score: 94.74  E-value: 2.52e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEG-VWKKYSLTVAVKTL-KEDTMEVEEFL-KEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLL 324
Cdd:cd14120    1 IGHGAFAVVFKGrHRKKPDLPVAIKCItKKNLSKSQNLLgKEIKILKELSHENVVALLDCQETSSSVYLVMEYCNGGDLA 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  325 DYLREcnRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENH---------LVKVADFGLSRLMTGDTYTA 395
Cdd:cd14120   81 DYLQA--KGTLSEDTIRVFLQQIAAAMKALHSKGIVHRDLKPQNILLSHNSgrkpspndiRLKIADFGFARFLQDGMMAA 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  396 H-AGAkfPIkWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPY----PGiDLSQVYElLEKDYRMERPEGCPEKVYE 470
Cdd:cd14120  159 TlCGS--PM-YMAPEVIMSLQYDAKADLWSIGTIVYQCLT-GKAPFqaqtPQ-ELKAFYE-KNANLRPNIPSGTSPALKD 232
                        250
                 ....*....|....*...
gi 62362414  471 LMRACWQWNPSDRPSFAE 488
Cdd:cd14120  233 LLLGLLKRNPKDRIDFED 250
STKc_CDK1_euk cd07861
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher ...
241-434 2.53e-21

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher eukaryotes; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression. CDK1/cyclin A2 has also been implicated as an important regulator of S phase events. The CDK1/cyclin B complex is critical for G2 to M phase transition. It induces mitosis by activating nuclear enzymes that regulate chromatin condensation, nuclear membrane degradation, mitosis-specific microtubule and cytoskeletal reorganization. CDK1 also associates with cyclin E and plays a role in the entry into S phase. CDK1 transcription is stable throughout the cell cycle but is modulated in some pathological conditions. It may play a role in regulating apoptosis under these conditions. In breast cancer cells, HER2 can mediate apoptosis by inactivating CDK1. Activation of CDK1 may contribute to HIV-1 induced apoptosis as well as neuronal apoptosis in neurodegenerative diseases. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270845 [Multi-domain]  Cd Length: 285  Bit Score: 95.56  E-value: 2.53e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  241 DITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKedtMEVEE------FLKEAAVMKEIKHPNLVQLLGVCTREPPFYII 314
Cdd:cd07861    1 DYTKIEKIGEGTYGVVYKGRNKKTGQIVAMKKIR---LESEEegvpstAIREISLLKELQHPNIVCLEDVLMQENRLYLV 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  315 TEFMTYgNLLDYLRECNR-QEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMtGDTY 393
Cdd:cd07861   78 FEFLSM-DLKKYLDSLPKgKYMDAELVKSYLYQILQGILFCHSRRVLHRDLKPQNLLIDNKGVIKLADFGLARAF-GIPV 155
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 62362414  394 TAHAGAKFPIKWTAPESL-AYNKFSIKSDVWAFGVLLWEIAT 434
Cdd:cd07861  156 RVYTHEVVTLWYRAPEVLlGSPRYSTPVDIWSIGTIFAEMAT 197
STKc_SIK cd14071
Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the ...
235-491 3.67e-21

Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SIKs are part of a complex network that regulates Na,K-ATPase to maintain sodium homeostasis and blood pressure. Vertebrates contain three forms of SIKs (SIK1-3) from three distinct genes, which display tissue-specific effects. SIK1, also called SNF1LK, controls steroidogenic enzyme production in adrenocortical cells. In the brain, both SIK1 and SIK2 regulate energy metabolism. SIK2, also called QIK or SNF1LK2, is involved in the regulation of gluconeogenesis in the liver and lipogenesis in adipose tissues, where it phosphorylates the insulin receptor substrate-1. In the liver, SIK3 (also called QSK) regulates cholesterol and bile acid metabolism. In addition, SIK2 plays an important role in the initiation of mitosis and regulates the localization of C-Nap1, a centrosome linker protein. The SIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270973 [Multi-domain]  Cd Length: 253  Bit Score: 94.38  E-value: 3.67e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  235 WEMERTditmkhkLGGGQYGEVYEGVWKKYSLTVAVKTLKE---DTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPF 311
Cdd:cd14071    2 YDIERT-------IGKGNFAVVKLARHRITKTEVAIKIIDKsqlDEENLKKIYREVQIMKMLNHPHIIKLYQVMETKDML 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  312 YIITEFMTYGNLLDYLRECNR-QEVNAVVLLYmatQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTG 390
Cdd:cd14071   75 YLVTEYASNGEIFDYLAQHGRmSEKEARKKFW---QILSAVEYCHKRHIVHRDLKAENLLLDANMNIKIADFGFSNFFKP 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  391 DTYTAHAGAKFPikWTAPESLAYNKFS-IKSDVWAFGVLLWeIATYGMSPYPGIDLSQVYE-LLEKDYRMerPEGCPEKV 468
Cdd:cd14071  152 GELLKTWCGSPP--YAAPEVFEGKEYEgPQLDIWSLGVVLY-VLVCGALPFDGSTLQTLRDrVLSGRFRI--PFFMSTDC 226
                        250       260
                 ....*....|....*....|...
gi 62362414  469 YELMRACWQWNPSDRPSFAEIHQ 491
Cdd:cd14071  227 EHLIRRMLVLDPSKRLTIEQIKK 249
STKc_RIP4_like cd14025
Catalytic domain of the Serine/Threonine kinases, Receptor Interacting Protein 4 and similar ...
247-489 3.71e-21

Catalytic domain of the Serine/Threonine kinases, Receptor Interacting Protein 4 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of RIP4, ankyrin (ANK) repeat and kinase domain containing 1 (ANKK1), and similar proteins, all of which harbor C-terminal ANK repeats. RIP4, also called Protein Kinase C-associated kinase (PKK), regulates keratinocyte differentiation and cutaneous inflammation. It activates NF-kappaB and is important in the survival of diffuse large B-cell lymphoma cells. The ANKK1 protein, also called PKK2, has not been studied extensively. The ANKK1 gene, located less than 10kb downstream of the D2 dopamine receptor (DRD2) locus, is altered in the Taq1 A1 polymorphism, which is related to a reduced DRD2 binding affinity and consequently, to mental disorders. The RIP4-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270927 [Multi-domain]  Cd Length: 267  Bit Score: 94.48  E-value: 3.71e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVK---TLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTRepPFYIITEFMTYGNL 323
Cdd:cd14025    3 KVGSGGFGQVYKVRHKHWKTWLAIKcppSLHVDDSERMELLEEAKKMEMAKFRHILPVYGICSE--PVGLVMEYMETGSL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  324 LDYL-RECNRQEVNavvlLYMATQISSAMEYLE--KKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYT--AHAG 398
Cdd:cd14025   81 EKLLaSEPLPWELR----FRIIHETAVGMNFLHcmKPPLLHLDLKPANILLDAHYHVKISDFGLAKWNGLSHSHdlSRDG 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  399 AKFPIKWTAPES-LAYNK-FSIKSDVWAFGVLLWEIATYgMSPYPGI----------------DLSQVYEllekdyrmER 460
Cdd:cd14025  157 LRGTIAYLPPERfKEKNRcPDTKHDVYSFAIVIWGILTQ-KKPFAGEnnilhimvkvvkghrpSLSPIPR--------QR 227
                        250       260
                 ....*....|....*....|....*....
gi 62362414  461 PEGCpEKVYELMRACWQWNPSDRPSFAEI 489
Cdd:cd14025  228 PSEC-QQMICLMKRCWDQDPRKRPTFQDI 255
STKc_LKB1 cd14119
Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer ...
248-491 3.82e-21

Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LKB1, also called STK11, was first identified as a tumor suppressor responsible for Peutz-Jeghers syndrome, a disorder that leads to an increased risk of spontaneous epithelial cancer. It serves as a master upstream kinase that activates AMP-activated protein kinase (AMPK) and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. To be activated, LKB1 requires the adaptor proteins STe20-Related ADaptor (STRAD) and mouse protein 25 (MO25). The LKB1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271021 [Multi-domain]  Cd Length: 255  Bit Score: 94.25  E-value: 3.82e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEgVWKKYSLT-VAVKTLKEdtmeveEFLK-----EAAVMKEIK------HPNLVQLLGVCTREPP--FYI 313
Cdd:cd14119    1 LGEGSYGKVKE-VLDTETLCrRAVKILKK------RKLRripngEANVKREIQilrrlnHRNVIKLVDVLYNEEKqkLYM 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  314 ITEFMTyGNLLDYLRECNRQEVNavvlLYMA----TQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFG----LS 385
Cdd:cd14119   74 VMEYCV-GGLQEMLDSAPDKRLP----IWQAhgyfVQLIDGLEYLHSQGIIHKDIKPGNLLLTTDGTLKISDFGvaeaLD 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  386 RLMTGDTYTAHAGAkfPiKWTAPEsLAY--NKFS-IKSDVWAFGVLLWEIATyGMSPYPGidlSQVYELLEK----DYRM 458
Cdd:cd14119  149 LFAEDDTCTTSQGS--P-AFQPPE-IANgqDSFSgFKVDIWSAGVTLYNMTT-GKYPFEG---DNIYKLFENigkgEYTI 220
                        250       260       270
                 ....*....|....*....|....*....|...
gi 62362414  459 erPEGCPEKVYELMRACWQWNPSDRPSFAEIHQ 491
Cdd:cd14119  221 --PDDVDPDLQDLLRGMLEKDPEKRFTIEQIRQ 251
STKc_DCKL1 cd14183
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called ...
248-442 4.83e-21

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called Doublecortin-like and CAM kinase-like 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL1 (or DCAMKL1) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL1 contains a serine, threonine, and proline rich domain (SP) and a C-terminal kinase domain with similarity to CAMKs. DCKL1 interacts with tubulin, glucocorticoid receptor, dynein, JIP1/2, caspases (3 and 8), and calpain, among others. It plays roles in neurogenesis, neuronal migration, retrograde transport, and neuronal apoptosis. The DCKL1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271085 [Multi-domain]  Cd Length: 268  Bit Score: 94.29  E-value: 4.83e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFL--KEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLD 325
Cdd:cd14183   14 IGDGNFAVVKECVERSTGREYALKIINKSKCRGKEHMiqNEVSILRRVKHPNIVLLIEEMDMPTELYLVMELVKGGDLFD 93
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  326 YLRECNR-QEVNAVVLLYmatQISSAMEYLEKKNFIHRDLAARNCLVGENH----LVKVADFGLSRLMTGDTYTAHAGAK 400
Cdd:cd14183   94 AITSTNKyTERDASGMLY---NLASAIKYLHSLNIVHRDIKPENLLVYEHQdgskSLKLGDFGLATVVDGPLYTVCGTPT 170
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 62362414  401 FpikwTAPESLAYNKFSIKSDVWAFGVLLWeIATYGMSPYPG 442
Cdd:cd14183  171 Y----VAPEIIAETGYGLKVDIWAAGVITY-ILLCGFPPFRG 207
STKc_LRRK2 cd14068
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze ...
248-491 4.90e-21

Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRK2 is one of two vertebrate LRRKs which show complementary expression in the brain. Mutations in LRRK2, found in the kinase, ROC-COR, and WD40 domains, are linked to both familial and sporadic forms of Parkinson's disease. The most prevalent mutation, G2019S located in the activation loop of the kinase domain, increases kinase activity. The R1441C/G mutations in the GTPase domain have also been reported to influence kinase activity. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. The LRRK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270970 [Multi-domain]  Cd Length: 252  Bit Score: 93.86  E-value: 4.90e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSltVAVKTLKEDTmEVEEFLKEAAVMKEIKHPNLVQLLGVCTRepPFYIITEFMTYGNLlDYL 327
Cdd:cd14068    2 LGDGGFGSVYRAVYRGED--VAVKIFNKHT-SFRLLRQELVVLSHLHHPSLVALLAAGTA--PRMLVMELAPKGSL-DAL 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  328 RECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLV-----GENHLVKVADFGLSRL---MTGDTYTAHAGA 399
Cdd:cd14068   76 LQQDNASLTRTLQHRIALHVADGLRYLHSAMIIYRDLKPHNVLLftlypNCAIIAKIADYGIAQYccrMGIKTSEGTPGF 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  400 KFPikWTAPESLAYNKfsiKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERP---EGC---PEkVYELMR 473
Cdd:cd14068  156 RAP--EVARGNVIYNQ---QADVYSFGLLLYDILTCGERIVEGLKFPNEFDELAIQGKLPDPvkeYGCapwPG-VEALIK 229
                        250
                 ....*....|....*...
gi 62362414  474 ACWQWNPSDRPSFAEIHQ 491
Cdd:cd14068  230 DCLKENPQCRPTSAQVFD 247
STKc_CDK7 cd07841
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs ...
243-489 6.01e-21

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK7 plays essential roles in the cell cycle and in transcription. It associates with cyclin H and MAT1 and acts as a CDK-Activating Kinase (CAK) by phosphorylating and activating cell cycle CDKs (CDK1/2/4/6). In the brain, it activates CDK5. CDK7 is also a component of the general transcription factor TFIIH, which phosphorylates the C-terminal domain (CTD) of RNA polymerase II when it is bound with unphosphorylated DNA, as present in the pre-initiation complex. Following phosphorylation, the CTD dissociates from the DNA which allows transcription initiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270833 [Multi-domain]  Cd Length: 298  Bit Score: 94.56  E-value: 6.01e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  243 TMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEE------FLKEAAVMKEIKHPNLVQLLGVctreppfyiite 316
Cdd:cd07841    3 EKGKKLGEGTYAVVYKARDKETGRIVAIKKIKLGERKEAKdginftALREIKLLQELKHPNIIGLLDV------------ 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  317 FMTYGNL---LDYLRECNRQEVNAVVLLYMATQISSAM-------EYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR 386
Cdd:cd07841   71 FGHKSNInlvFEFMETDLEKVIKDKSIVLTPADIKSYMlmtlrglEYLHSNWILHRDLKPNNLLIASDGVLKLADFGLAR 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  387 lMTGD---TYTAHAGAKFpikWTAPESL-AYNKFSIKSDVWAFGVLLWEIAT-----YGMSPypgID-LSQVYELLekdy 456
Cdd:cd07841  151 -SFGSpnrKMTHQVVTRW---YRAPELLfGARHYGVGVDMWSVGCIFAELLLrvpflPGDSD---IDqLGKIFEAL---- 219
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 62362414  457 rmerpeGCPEK-----VYELMRAcWQWNPSDRPSFAEI 489
Cdd:cd07841  220 ------GTPTEenwpgVTSLPDY-VEFKPFPPTPLKQI 250
STKc_MLCK cd14103
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the ...
248-442 6.58e-21

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module. MLCK2, MLCK3, and MLCK4 share a simpler domain architecture of a single kinase domain near the C-terminus and the absence of Ig-like or FN3 domains. The MLCK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271005 [Multi-domain]  Cd Length: 250  Bit Score: 93.44  E-value: 6.58e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM-EVEEFLKEAAVMKEIKHPNLVQLLGV--CTREppFYIITEFMTYGNLL 324
Cdd:cd14103    1 LGRGKFGTVYRCVEKATGKELAAKFIKCRKAkDREDVRNEIEIMNQLRHPRLLQLYDAfeTPRE--MVLVMEYVAGGELF 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  325 DYLRECNRQEVNAVVLLYMaTQISSAMEYLEKKNFIHRDLAARN--CLVGENHLVKVADFGLSRLM--TGDTYTAHAGAK 400
Cdd:cd14103   79 ERVVDDDFELTERDCILFM-RQICEGVQYMHKQGILHLDLKPENilCVSRTGNQIKIIDFGLARKYdpDKKLKVLFGTPE 157
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 62362414  401 FpikwTAPESLAYNKFSIKSDVWAFGVLlweiaTY----GMSPYPG 442
Cdd:cd14103  158 F----VAPEVVNYEPISYATDMWSVGVI-----CYvllsGLSPFMG 194
STKc_SBK1 cd13987
Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the ...
248-440 9.06e-21

Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SBK1, also called BSK146, is predominantly expressed in the brain. Its expression is increased in the developing brain during the late embryonic stage, coinciding with dramatic neuronal proliferation, migration, and maturation. SBK1 may play an important role in regulating brain development. The SBK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270889 [Multi-domain]  Cd Length: 259  Bit Score: 93.16  E-value: 9.06e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIK-HPNLVQLLGVCTREPPFYIIT-EFMTYGNLLD 325
Cdd:cd13987    1 LGEGTYGKVLLAVHKGSGTKMALKFVPKPSTKLKDFLREYNISLELSvHPHIIKTYDVAFETEDYYVFAqEYAPYGDLFS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  326 Y------LRECNRQEVnavvllymATQISSAMEYLEKKNFIHRDLAARNCLVGENHL--VKVADFGLSRlMTGDTYTAHA 397
Cdd:cd13987   81 IippqvgLPEERVKRC--------AAQLASALDFMHSKNLVHRDIKPENVLLFDKDCrrVKLCDFGLTR-RVGSTVKRVS 151
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  398 GAkfpIKWTAPE--------SLAYNKfsiKSDVWAFGVLL---------WEIATYGMSPY 440
Cdd:cd13987  152 GT---IPYTAPEvceakkneGFVVDP---SIDVWAFGVLLfccltgnfpWEKADSDDQFY 205
STKc_PKA_like cd05580
Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs ...
240-432 9.18e-21

Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the cAMP-dependent protein kinases, PKA and PRKX, and similar proteins. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. PRKX is also reulated by the R subunit and is is present in many tissues including fetal and adult brain, kidney, and lung. It is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PKA-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270732 [Multi-domain]  Cd Length: 290  Bit Score: 93.80  E-value: 9.18e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  240 TDITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM----EVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIIT 315
Cdd:cd05580    1 DDFEFLKTLGTGSFGRVRLVKHKDSGKYYALKILKKAKIiklkQVEHVLNEKRILSEVRHPFIVNLLGSFQDDRNLYMVM 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  316 EFMTYGNLLDYLRECNRQEVNaVVLLYmATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTA 395
Cdd:cd05580   81 EYVPGGELFSLLRRSGRFPND-VAKFY-AAEVVLALEYLHSLDIVYRDLKPENLLLDSDGHIKITDFGFAKRVKDRTYTL 158
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 62362414  396 HAGAKFpikwTAPE---SLAYNKfsiKSDVWAFGVLLWEI 432
Cdd:cd05580  159 CGTPEY----LAPEiilSKGHGK---AVDWWALGILIYEM 191
STKc_Nek9 cd08221
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
248-489 9.30e-21

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek9, also called Nercc1, is primarily a cytoplasmic protein but can also localize in the nucleus. It is involved in modulating chromosome alignment and splitting during mitosis. It interacts with the gamma-tubulin ring complex and the Ran GTPase, and is implicated in microtubule organization. Nek9 associates with FACT (FAcilitates Chromatin Transcription) and modulates interphase progression. It also interacts with Nek6, and Nek7, during mitosis, resulting in their activation. Nek9 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270860 [Multi-domain]  Cd Length: 256  Bit Score: 93.26  E-value: 9.30e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGE--VYEG-------VWKKYSLTVAVKTLKEDTmeveefLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFM 318
Cdd:cd08221    8 LGRGAFGEavLYRKtednslvVWKEVNLSRLSEKERRDA------LNEIDILSLLNHDNIITYYNHFLDGESLFIEMEYC 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  319 TYGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAG 398
Cdd:cd08221   82 NGGNLHDKIAQQKNQLFPEEVVLWYLYQIVSAVSHIHKAGILHRDIKTLNIFLTKADLVKLGDFGISKVLDSESSMAESI 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  399 AKFPIkWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEgCPEKVYELMRACWQW 478
Cdd:cd08221  162 VGTPY-YMSPELVQGVKYNFKSDIWAVGCVLYELLTLKRTFDATNPLRLAVKIVQGEYEDIDEQ-YSEEIIQLVHDCLHQ 239
                        250
                 ....*....|.
gi 62362414  479 NPSDRPSFAEI 489
Cdd:cd08221  240 DPEDRPTAEEL 250
STKc_nPKC_theta cd05619
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze ...
246-461 9.82e-21

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. Although T-cells also express other PKC isoforms, PKC-theta is unique in that upon antigen stimulation, it is translocated to the plasma membrane at the immunological synapse, where it mediates signals essential for T-cell activation. It is essential for TCR-induced proliferation, cytokine production, T-cell survival, and the differentiation and effector function of T-helper (Th) cells, particularly Th2 and Th17. PKC-theta is being developed as a therapeutic target for Th2-mediated allergic inflammation and Th17-mediated autoimmune diseases. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270770 [Multi-domain]  Cd Length: 331  Bit Score: 94.99  E-value: 9.82e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  246 HK-LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEI-----KHPNLVQLLGVCTREPPFYIITEFMT 319
Cdd:cd05619   10 HKmLGKGSFGKVFLAELKGTNQFFAIKALKKDVVLMDDDVECTMVEKRVlslawEHPFLTHLFCTFQTKENLFFVMEYLN 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  320 YGNLLDYLRECNRQEVNAVVllYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRL-MTGDTYTA-HA 397
Cdd:cd05619   90 GGDLMFHIQSCHKFDLPRAT--FYAAEIICGLQFLHSKGIVYRDLKLDNILLDKDGHIKIADFGMCKEnMLGDAKTStFC 167
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 62362414  398 GAKfpiKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLekdyRMERP 461
Cdd:cd05619  168 GTP---DYIAPEILLGQKYNTSVDWWSFGVLLYEMLI-GQSPFHGQDEEELFQSI----RMDNP 223
STKc_MLCK2 cd14190
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze ...
241-447 1.01e-20

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK2 (or MYLK2) phosphorylates myosin regulatory light chain and controls the contraction of skeletal muscles. MLCK2 contains a single kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site. The MLCK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271092 [Multi-domain]  Cd Length: 261  Bit Score: 93.06  E-value: 1.01e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  241 DITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTL-KEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMT 319
Cdd:cd14190    5 SIHSKEVLGGGKFGKVHTCTEKRTGLKLAAKVInKQNSKDKEMVLLEIQVMNQLNHRNLIQLYEAIETPNEIVLFMEYVE 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  320 YGNLLDYL--RECNRQEVNAVVLLymaTQISSAMEYLEKKNFIHRDLAARN--CLVGENHLVKVADFGLSRlmtgdTYTA 395
Cdd:cd14190   85 GGELFERIvdEDYHLTEVDAMVFV---RQICEGIQFMHQMRVLHLDLKPENilCVNRTGHQVKIIDFGLAR-----RYNP 156
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 62362414  396 HAGAKFPI---KWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQ 447
Cdd:cd14190  157 REKLKVNFgtpEFLSPEVVNYDQVSFPTDMWSMGVITYMLLS-GLSPFLGDDDTE 210
STKc_PKA cd14209
Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze ...
241-458 1.09e-20

Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. The PKA subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271111 [Multi-domain]  Cd Length: 290  Bit Score: 93.62  E-value: 1.09e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  241 DITMKHKLGGGQYGEVY---EGVWKKYsltVAVKTL-KED---TMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYI 313
Cdd:cd14209    2 DFDRIKTLGTGSFGRVMlvrHKETGNY---YAMKILdKQKvvkLKQVEHTLNEKRILQAINFPFLVKLEYSFKDNSNLYM 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  314 ITEFMTYGNLLDYLRECNR-QEVNAVvllYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDT 392
Cdd:cd14209   79 VMEYVPGGEMFSHLRRIGRfSEPHAR---FYAAQIVLAFEYLHSLDLIYRDLKPENLLIDQQGYIKVTDFGFAKRVKGRT 155
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  393 YTAHAGAKFpikwTAPE---SLAYNKfsiKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELL-EKDYRM 458
Cdd:cd14209  156 WTLCGTPEY----LAPEiilSKGYNK---AVDWWALGVLIYEMAA-GYPPFFADQPIQIYEKIvSGKVRF 217
STKc_CNK2-like cd08530
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar ...
241-491 1.10e-20

Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chlamydomonas reinhardtii CNK2 has both cilliary and cell cycle functions. It influences flagellar length through promoting flagellar disassembly, and it regulates cell size, through influencing the size threshold at which cells commit to mitosis. This subfamily belongs to the (NIMA)-related kinase (Nek) family, which includes seven different Chlamydomonas Neks (CNKs 1-6 and Fa2). This subfamily includes CNK1, and -2. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270869 [Multi-domain]  Cd Length: 256  Bit Score: 92.84  E-value: 1.10e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  241 DITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM---EVEEFLKEAAVMKEIKHPNLVqllgvCTREPPF-----Y 312
Cdd:cd08530    1 DFKVLKKLGKGSYGSVYKVKRLSDNQVYALKEVNLGSLsqkEREDSVNEIRLLASVNHPNII-----RYKEAFLdgnrlC 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  313 IITEFMTYGNLLDYL--RECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTG 390
Cdd:cd08530   76 IVMEYAPFGDLSKLIskRKKKRRLFPEDDIWRIFIQMLRGLKALHDQKILHRDLKSANILLSAGDLVKIGDLGISKVLKK 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  391 DTYTAHAGAKFpikWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYE 470
Cdd:cd08530  156 NLAKTQIGTPL---YAAPEVWKGRPYDYKSDIWSLGCLLYEMAT-FRPPFEARTMQELRYKVCRGKFPPIPPVYSQDLQQ 231
                        250       260
                 ....*....|....*....|.
gi 62362414  471 LMRACWQWNPSDRPSFAEIHQ 491
Cdd:cd08530  232 IIRSLLQVNPKKRPSCDKLLQ 252
STKc_Nek10 cd08528
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
248-489 1.23e-20

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. No function has yet been ascribed to Nek10. The gene encoding Nek10 is a putative causative gene for breast cancer; it is located within a breast cancer susceptibility loci on chromosome 3p24. Nek10 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270867 [Multi-domain]  Cd Length: 270  Bit Score: 92.95  E-value: 1.23e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTV-AVK-----------TLKEDTMEVEEFLKEAAVMKE-IKHPNLVQLLGVCTREPPFYII 314
Cdd:cd08528    8 LGSGAFGCVYKVRKKSNGQTLlALKeinmtnpafgrTEQERDKSVGDIISEVNIIKEqLRHPNIVRYYKTFLENDRLYIV 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  315 TEFM---TYGNLLDYLRECNrQEVNAVVLLYMATQISSAMEYLEK-KNFIHRDLAARNCLVGENHLVKVADFGLSRLMTG 390
Cdd:cd08528   88 MELIegaPLGEHFSSLKEKN-EHFTEDRIWNIFVQMVLALRYLHKeKQIVHRDLKPNNIMLGEDDKVTITDFGLAKQKGP 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  391 DTY--TAHAGAkfpIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRmERPEGC-PEK 467
Cdd:cd08528  167 ESSkmTSVVGT---ILYSCPEIVQNEPYGEKADIWALGCILYQMCTLQPPFYSTNMLTLATKIVEAEYE-PLPEGMySDD 242
                        250       260
                 ....*....|....*....|..
gi 62362414  468 VYELMRACWQWNPSDRPSFAEI 489
Cdd:cd08528  243 ITFVIRSCLTPDPEARPDIVEV 264
STKc_CDK2_3 cd07860
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase 2 and 3; ...
247-468 1.38e-20

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. CDK2, together with CDK4, also regulates embryonic cell proliferation. Despite these important roles, mice deleted for the cdk2 gene are viable and normal except for being sterile. This may be due to compensation provided by CDK1 (also called Cdc2), which can also bind cyclin E and drive the G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270844 [Multi-domain]  Cd Length: 284  Bit Score: 93.34  E-value: 1.38e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTmEVEEF----LKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYgN 322
Cdd:cd07860    7 KIGEGTYGVVYKARNKLTGEVVALKKIRLDT-ETEGVpstaIREISLLKELNHPNIVKLLDVIHTENKLYLVFEFLHQ-D 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRL--MTGDTYTAHAgak 400
Cdd:cd07860   85 LKKFMDASALTGIPLPLIKSYLFQLLQGLAFCHSHRVLHRDLKPQNLLINTEGAIKLADFGLARAfgVPVRTYTHEV--- 161
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 62362414  401 FPIKWTAPESLAYNKF-SIKSDVWAFGVLLWEIATYgMSPYPGiDlSQVYELlekdYRMERPEGCPEKV 468
Cdd:cd07860  162 VTLWYRAPEILLGCKYySTAVDIWSLGCIFAEMVTR-RALFPG-D-SEIDQL----FRIFRTLGTPDEV 223
STKc_TLK cd13990
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase; STKs catalyze the ...
243-494 1.50e-20

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. They phosphorylate and regulate Anti-silencing function 1 protein (Asf1), a histone H3/H4 chaperone that helps facilitate the assembly of chromatin following DNA replication during S phase. TLKs also phosphorylate the H3 histone tail and are essential in transcription. Vertebrates contain two subfamily members, TLK1 and TLK2. The TLK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270892 [Multi-domain]  Cd Length: 279  Bit Score: 93.15  E-value: 1.50e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  243 TMKHKLGGGQYGEVyegvWKKYSLT----VAVK------TLKEDTME--VEEFLKEAAVMKEIKHPNLVQLLGVCTREP- 309
Cdd:cd13990    3 LLLNLLGKGGFSEV----YKAFDLVeqryVACKihqlnkDWSEEKKQnyIKHALREYEIHKSLDHPRIVKLYDVFEIDTd 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  310 PFYIITEFMTyGNLLD-YLREC-NRQEVNAVVLLYmatQISSAMEYL-EKKN-FIHRDLAARNCLVGENHL---VKVADF 382
Cdd:cd13990   79 SFCTVLEYCD-GNDLDfYLKQHkSIPEREARSIIM---QVVSALKYLnEIKPpIIHYDLKPGNILLHSGNVsgeIKITDF 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  383 GLSRLMTGDTYTAH--------AGAKFpikWTAPESLAYN----KFSIKSDVWAFGVLLWEIaTYGMSPYpGIDLSQVYE 450
Cdd:cd13990  155 GLSKIMDDESYNSDgmeltsqgAGTYW---YLPPECFVVGktppKISSKVDVWSVGVIFYQM-LYGRKPF-GHNQSQEAI 229
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|
gi 62362414  451 LLEKDYRMERPEGCPEK------VYELMRACWQWNPSDRPsfaEIHQAFE 494
Cdd:cd13990  230 LEENTILKATEVEFPSKpvvsseAKDFIRRCLTYRKEDRP---DVLQLAN 276
STKc_CaMKI_gamma cd14166
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
239-483 1.79e-20

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I gamma; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271068 [Multi-domain]  Cd Length: 285  Bit Score: 93.13  E-value: 1.79e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  239 RTDITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLK-EAAVMKEIKHPNLVQLLGVCTREPPFYIITEF 317
Cdd:cd14166    2 RETFIFMEVLGSGAFSEVYLVKQRSTGKLYALKCIKKSPLSRDSSLEnEIAVLKRIKHENIVTLEDIYESTTHYYLVMQL 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  318 MTYGNLLDYLRECN-RQEVNAVVLLYmatQISSAMEYLEKKNFIHRDLAARNCLV---GENHLVKVADFGLSRLMTGDTY 393
Cdd:cd14166   82 VSGGELFDRILERGvYTEKDASRVIN---QVLSAVKYLHENGIVHRDLKPENLLYltpDENSKIMITDFGLSKMEQNGIM 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  394 TAHAGAKfpiKWTAPESLAYNKFSIKSDVWAFGVLLWeIATYGMSPYPGIDLSQVYE-LLEKDYRMERP--EGCPEKVYE 470
Cdd:cd14166  159 STACGTP---GYVAPEVLAQKPYSKAVDCWSIGVITY-ILLCGYPPFYEETESRLFEkIKEGYYEFESPfwDDISESAKD 234
                        250
                 ....*....|...
gi 62362414  471 LMRACWQWNPSDR 483
Cdd:cd14166  235 FIRHLLEKNPSKR 247
STKc_Nek2 cd08217
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
247-489 1.79e-20

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek2 subfamily includes Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants prevented from entering mitosis. NIMA is essential for mitotic entry and progression through mitosis, and its degradation is essential for mitotic exit. NIMA is involved in nuclear membrane fission. Vertebrate Nek2 is a cell cycle-regulated STK, localized in centrosomes and kinetochores, that regulates centrosome splitting at the G2/M phase. It also interacts with other mitotic kinases such as Polo-like kinase 1 and may play a role in spindle checkpoint. An increase in the expression of the human NEK2 gene is strongly associated with the progression of non-Hodgkin lymphoma. Nek2 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. It The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270857 [Multi-domain]  Cd Length: 265  Bit Score: 92.60  E-value: 1.79e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM---EVEEFLKEAAVMKEIKHPNLVQLLG--VCTREPPFYIITEFMTYG 321
Cdd:cd08217    7 TIGKGSFGTVRKVRRKSDGKILVWKEIDYGKMsekEKQQLVSEVNILRELKHPNIVRYYDriVDRANTTLYIVMEYCEGG 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  322 NLLDYLRECNRQ-----EvnAVVLLYMaTQISSAMEYLEKKN-----FIHRDLAARNCLVGENHLVKVADFGLSRLMTGD 391
Cdd:cd08217   87 DLAQLIKKCKKEnqyipE--EFIWKIF-TQLLLALYECHNRSvgggkILHRDLKPANIFLDSDNNVKLGDFGLARVLSHD 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  392 TYTAHAGAKFPIKWtAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLeKDYRMER-PEGCPEKVYE 470
Cdd:cd08217  164 SSFAKTYVGTPYYM-SPELLNEQSYDEKSDIWSLGCLIYELCA-LHPPFQAANQLELAKKI-KEGKFPRiPSRYSSELNE 240
                        250
                 ....*....|....*....
gi 62362414  471 LMRACWQWNPSDRPSFAEI 489
Cdd:cd08217  241 VIKSMLNVDPDKRPSVEEL 259
SH2_SHIP cd10343
Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and ...
126-219 1.97e-20

Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and SLAM-associated protein (SAP); The SH2-containing inositol-5'-phosphatase, SHIP (also called SHIP1/SHIP1a), is a hematopoietic-restricted phosphatidylinositide phosphatase that translocates to the plasma membrane after extracellular stimulation and hydrolyzes the phosphatidylinositol-3-kinase (PI3K)-generated second messenger PI-3,4,5-P3 (PIP3) to PI-3,4-P2. As a result, SHIP dampens down PIP3 mediated signaling and represses the proliferation, differentiation, survival, activation, and migration of hematopoietic cells. PIP3 recruits lipid-binding pleckstrin homology(PH) domain-containing proteins to the inner wall of the plasma membrane and activates them. PH domain-containing downstream effectors include the survival/proliferation enhancing serine/threonine kinase, Akt (protein kinase B), the tyrosine kinase, Btk, the regulator of protein translation, S6K, and the Rac and cdc42 guanine nucleotide exchange factor, Vav. SHIP is believed to act as a tumor suppressor during leukemogenesis and lymphomagenesis, and may play a role in activating the immune system to combat cancer. SHIP contains an N-terminal SH2 domain, a centrally located phosphatase domain that specifically hydrolyzes the 5'-phosphate from PIP3, PI-4,5-P2 and inositol-1,3,4,5- tetrakisphosphate (IP4), a C2 domain, that is an allosteric activating site when bound by SHIP's enzymatic product, PI-3,4-P2; 2 NPXY motifs that bind proteins with a phosphotyrosine binding (Shc, Dok 1, Dok 2) or an SH2 (p85a, SHIP2) domain; and a proline-rich domain consisting of four PxxP motifs that bind a subset of SH3-containing proteins including Grb2, Src, Lyn, Hck, Abl, PLCg1, and PIAS1. The SH2 domain of SHIP binds to the tyrosine phosphorylated forms of Shc, SHP-2, Doks, Gabs, CD150, platelet-endothelial cell adhesion molecule, Cas, c-Cbl, immunoreceptor tyrosine-based inhibitory motifs (ITIMs), and immunoreceptor tyrosine-based activation motifs (ITAMs). The X-linked lymphoproliferative syndrome (XLP) gene encodes SAP (also called SH2D1A/DSHP) a protein that consists of a 5 residue N-terminus, a single SH2 domain, and a short 25 residue C-terminal tail. XLP is characterized by an extreme sensitivity to Epstein-Barr virus. Both T and natural killer (NK) cell dysfunctions have been seen in XLP patients. SAP binds the cytoplasmic tail of Signaling lymphocytic activation molecule (SLAM), 2B4, Ly-9, and CD84. SAP is believed to function as a signaling inhibitor, by blocking or regulating binding of other signaling proteins. SAP and the SAP-like protein EAT-2 recognize the sequence motif TIpYXX(V/I), which is found in the cytoplasmic domains of a restricted number of T, B, and NK cell surface receptors and are proposed to be natural inhibitors or regulators of the physiological role of a small family of receptors on the surface of these cells. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198206  Cd Length: 103  Bit Score: 87.50  E-value: 1.97e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  126 SWYHGPVSRNAAEYLLS-SGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTASDGKLYV-SSES----RFNTLAELV 199
Cdd:cd10343    4 PWYHGNITRSKAEELLSkAGKDGSFLVRDSESVSGAYALCVLYQNCVHTYRILPNAEDKLSVqASEGvpvrFFTTLPELI 83
                         90       100
                 ....*....|....*....|
gi 62362414  200 HHHSTVADGLITTLHYPAPK 219
Cdd:cd10343   84 EFYQKENMGLVTHLLYPVER 103
STKc_Chk1 cd14069
Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the ...
248-491 2.24e-20

Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chk1 is implicated in many major checkpoints of the cell cycle, providing a link between upstream sensors and the cell cycle engine. It plays an important role in DNA damage response and maintaining genomic stability. Chk1 acts as an effector of the sensor kinase, ATR (ATM and Rad3-related), a member of the PI3K family, which is activated upon DNA replication stress. Chk1 delays mitotic entry in response to replication blocks by inhibiting cyclin dependent kinase (Cdk) activity. In addition, Chk1 contributes to the function of centrosome and spindle-based checkpoints, inhibits firing of origins of DNA replication (Ori), and represses transcription of cell cycle proteins including cyclin B and Cdk1. The Chk1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270971 [Multi-domain]  Cd Length: 261  Bit Score: 92.01  E-value: 2.24e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVK--TLKEDTME-VEEFLKEAAVMKEIKHPNLVQLLGvCTREPPF-YIITEFMTYGNL 323
Cdd:cd14069    9 LGEGAFGEVFLAVNRNTEEAVAVKfvDMKRAPGDcPENIKKEVCIQKMLSHKNVVRFYG-HRREGEFqYLFLEYASGGEL 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  324 LDYLR-ECNRQEVNAVVLLymaTQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLS---------RLMTGDTY 393
Cdd:cd14069   88 FDKIEpDVGMPEDVAQFYF---QQLMAGLKYLHSCGITHRDIKPENLLLDENDNLKISDFGLAtvfrykgkeRLLNKMCG 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  394 TahagakfpIKWTAPESLAYNKF-SIKSDVWAFGVLLWEIATyGMSPY--PgIDLSQVYELLEKDyrmERPEGCPEK--- 467
Cdd:cd14069  165 T--------LPYVAPELLAKKKYrAEPVDVWSCGIVLFAMLA-GELPWdqP-SDSCQEYSDWKEN---KKTYLTPWKkid 231
                        250       260
                 ....*....|....*....|....*.
gi 62362414  468 --VYELMRACWQWNPSDRPSFAEIHQ 491
Cdd:cd14069  232 taALSLLRKILTENPNKRITIEDIKK 257
SH2_csk_like cd09937
Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal ...
127-220 2.34e-20

Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal Src kinase (CSK) and CSK-homologous kinase (CHK) are members of the CSK-family of protein tyrosine kinases. These proteins suppress activity of Src-family kinases (SFK) by selectively phosphorylating the conserved C-terminal tail regulatory tyrosine by a similar mechanism. CHK is also capable of inhibiting SFKs by a non-catalytic mechanism that involves binding of CHK to SFKs to form stable protein complexes. The unphosphorylated form of SFKs is inhibited by CSK and CHK by a two-step mechanism. The first step involves the formation of a complex of SFKs with CSK/CHK with the SFKs in the complex are inactive. The second step, involves the phosphorylation of the C-terminal tail tyrosine of SFKs, which then dissociates and adopt an inactive conformation. The structural basis of how the phosphorylated SFKs dissociate from CSK/CHK to adopt the inactive conformation is not known. The inactive conformation of SFKs is stabilized by two intramolecular inhibitory interactions: (a) the pYT:SH2 interaction in which the phosphorylated C-terminal tail tyrosine (YT) binds to the SH2 domain, and (b) the linker:SH3 interaction of which the SH2-kinase domain linker binds to the SH3 domain. SFKs are activated by multiple mechanisms including binding of the ligands to the SH2 and SH3 domains to displace the two inhibitory intramolecular interactions, autophosphorylation, and dephosphorylation of YT. By selective phosphorylation and the non-catalytic inhibitory mechanism CSK and CHK are able to inhibit the active forms of SFKs. CSK and CHK are regulated by phosphorylation and inter-domain interactions. They both contain SH3, SH2, and kinase domains separated by the SH3-SH2 connector and SH2 kinase linker, intervening segments separating the three domains. They lack a conserved tyrosine phosphorylation site in the kinase domain and the C-terminal tail regulatory tyrosine phosphorylation site. The CSK SH2 domain is crucial for stabilizing the kinase domain in the active conformation. A disulfide bond here regulates CSK kinase activity. The subcellular localization and activity of CSK are regulated by its SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198190  Cd Length: 98  Bit Score: 86.96  E-value: 2.34e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  127 WYHGPVSRNAAEYLLSSGINGSFLVRESESSPGQRSISLRYEGRVYHYRInTASDGKLYVSSESRFNTLAELVHHHSTVA 206
Cdd:cd09937    5 WFHGKISREEAERLLQPPEDGLFLVRESTNYPGDYTLCVSFEGKVEHYRV-IYRNGKLTIDEEEYFENLIQLVEHYTKDA 83
                         90
                 ....*....|....
gi 62362414  207 DGLITTLHYPAPKR 220
Cdd:cd09937   84 DGLCTRLVKPKVKE 97
STKc_TAO3 cd06633
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze ...
246-489 2.48e-20

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO3 is also known as JIK (c-Jun N-terminal kinase inhibitory kinase) or KFC (kinase from chicken). It specifically activates JNK, presumably by phosphorylating and activating MKK4/MKK7. In Saccharomyces cerevisiae, TAO3 is a component of the RAM (regulation of Ace2p activity and cellular morphogenesis) signaling pathway. TAO3 is upregulated in retinal ganglion cells after axotomy, and may play a role in apoptosis. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The TAO3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270803 [Multi-domain]  Cd Length: 313  Bit Score: 93.18  E-value: 2.48e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  246 HKLGGGQYGEVYEGVWKKYSLTVAVKTL----KEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFmTYG 321
Cdd:cd06633   27 HEIGHGSFGAVYFATNSHTNEVVAIKKMsysgKQTNEKWQDIIKEVKFLQQLKHPNTIEYKGCYLKDHTAWLVMEY-CLG 105
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  322 NLLDYLRECNR--QEVNAVVLLYMATQissAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTgdTYTAHAGA 399
Cdd:cd06633  106 SASDLLEVHKKplQEVEIAAITHGALQ---GLAYLHSHNMIHRDIKAGNILLTEPGQVKLADFGSASIAS--PANSFVGT 180
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  400 KFpikWTAPE---SLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACW 476
Cdd:cd06633  181 PY---WMAPEvilAMDEGQYDGKVDIWSLGITCIELAERKPPLFNMNAMSALYHIAQNDSPTLQSNEWTDSFRGFVDYCL 257
                        250
                 ....*....|...
gi 62362414  477 QWNPSDRPSFAEI 489
Cdd:cd06633  258 QKIPQERPSSAEL 270
PTZ00263 PTZ00263
protein kinase A catalytic subunit; Provisional
230-483 2.57e-20

protein kinase A catalytic subunit; Provisional


Pssm-ID: 140289 [Multi-domain]  Cd Length: 329  Bit Score: 93.34  E-value: 2.57e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   230 PNYDKWEMerTDITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM----EVEEFLKEAAVMKEIKHPNLVQLLGVC 305
Cdd:PTZ00263   10 PDTSSWKL--SDFEMGETLGTGSFGRVRIAKHKGTGEYYAIKCLKKREIlkmkQVQHVAQEKSILMELSHPFIVNMMCSF 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   306 TREPPFYIITEFMTYGNLLDYLRECNRQEvNAVVLLYMAtQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLS 385
Cdd:PTZ00263   88 QDENRVYFLLEFVVGGELFTHLRKAGRFP-NDVAKFYHA-ELVLAFEYLHSKDIIYRDLKPENLLLDNKGHVKVTDFGFA 165
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   386 RLMTGDTYTAHAGAKFpikwTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYE-LLEKdyRMERPEGC 464
Cdd:PTZ00263  166 KKVPDRTFTLCGTPEY----LAPEVIQSKGHGKAVDWWTMGVLLYEFIA-GYPPFFDDTPFRIYEkILAG--RLKFPNWF 238
                         250
                  ....*....|....*....
gi 62362414   465 PEKVYELMRACWQWNPSDR 483
Cdd:PTZ00263  239 DGRARDLVKGLLQTDHTKR 257
PTK_Jak3_rpt1 cd14208
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 3; Jak3 is ...
242-489 2.94e-20

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 3; Jak3 is expressed only in hematopoietic cells. It binds the shared receptor subunit, common gamma chain and thus, is essential in the signaling of cytokines that use it such as IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Jak3 is important in lymphoid development and myeloid cell differentiation. Inactivating mutations in Jak3 have been reported in humans with severe combined immunodeficiency (SCID). Jak3 is a cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. Jaks are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Jak3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271110 [Multi-domain]  Cd Length: 260  Bit Score: 91.89  E-value: 2.94e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  242 ITMKHKLGGGQYGEVYEGVW------KKYSLTVAVKTLKEDTMEVEE-FLKEAAVMKEIKHPNLVQLLGVCTREPPFyII 314
Cdd:cd14208    1 LTFMESLGKGSFTKIYRGLRtdeeddERCETEVLLKVMDPTHGNCQEsFLEAASIMSQISHKHLVLLHGVCVGKDSI-MV 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  315 TEFMTYGNLLDYLREcNRQE--VNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLV------GENHLVKVADFGLSR 386
Cdd:cd14208   80 QEFVCHGALDLYLKK-QQQKgpVAISWKLQVVKQLAYALNYLEDKQLVHGNVSAKKVLLsregdkGSPPFIKLSDPGVSI 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  387 LMTGDTYTAHAgakfpIKWTAPESLA-YNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKdyRMERPEGCP 465
Cdd:cd14208  159 KVLDEELLAER-----IPWVAPECLSdPQNLALEADKWGFGATLWEIFSGGHMPLSALDPSKKLQFYND--RKQLPAPHW 231
                        250       260
                 ....*....|....*....|....
gi 62362414  466 EKVYELMRACWQWNPSDRPSFAEI 489
Cdd:cd14208  232 IELASLIQQCMSYNPLLRPSFRAI 255
STKc_CaMKI_alpha cd14167
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
239-461 3.66e-20

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271069 [Multi-domain]  Cd Length: 263  Bit Score: 91.63  E-value: 3.66e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  239 RTDITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEE--FLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITE 316
Cdd:cd14167    2 RDIYDFREVLGTGAFSEVVLAEEKRTQKLVAIKCIAKKALEGKEtsIENEIAVLHKIKHPNIVALDDIYESGGHLYLIMQ 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  317 FMTYGNLLDYLRECN-RQEVNAVVLLYmatQISSAMEYLEKKNFIHRDLAARNCL---VGENHLVKVADFGLSRLM-TGD 391
Cdd:cd14167   82 LVSGGELFDRIVEKGfYTERDASKLIF---QILDAVKYLHDMGIVHRDLKPENLLyysLDEDSKIMISDFGLSKIEgSGS 158
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 62362414  392 TYTAHAGAKfpiKWTAPESLAYNKFSIKSDVWAFGVLLWeIATYGMSPYPGIDLSQVYE-LLEKDYRMERP 461
Cdd:cd14167  159 VMSTACGTP---GYVAPEVLAQKPYSKAVDCWSIGVIAY-ILLCGYPPFYDENDAKLFEqILKAEYEFDSP 225
SH2_Grb2_like cd09941
Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar ...
125-204 4.22e-20

Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar proteins; The adaptor proteins here include homologs Grb2 in humans, Sex muscle abnormal protein 5 (Sem-5) in Caenorhabditis elegans, and Downstream of receptor kinase (drk) in Drosophila melanogaster. They are composed of one SH2 and two SH3 domains. Grb2/Sem-5/drk regulates the Ras pathway by linking the tyrosine kinases to the Ras guanine nucleotide releasing protein Sos, which converts Ras to the active GTP-bound state. The SH2 domain of Grb2/Sem-5/drk binds class II phosphotyrosyl peptides while its SH3 domain binds to Sos and Sos-derived, proline-rich peptides. Besides it function in Ras signaling, Grb2 is also thought to play a role in apoptosis. Unlike most SH2 structures in which the peptide binds in an extended conformation (such that the +3 peptide residue occupies a hydrophobic pocket in the protein, conferring a modest degree of selectivity), Grb2 forms several hydrogen bonds via main chain atoms with the side chain of +2 Asn. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199828  Cd Length: 95  Bit Score: 86.17  E-value: 4.22e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  125 HSWYHGPVSRNAAEYLLSSGIN-GSFLVRESESSPGQRSISLRYEGRVYHYRINTASDGKLYVSSEsRFNTLAELVHHHS 203
Cdd:cd09941    3 HPWFHGKISRAEAEEILMNQRPdGAFLIRESESSPGDFSLSVKFGNDVQHFKVLRDGAGKYFLWVV-KFNSLNELVDYHR 81

                 .
gi 62362414  204 T 204
Cdd:cd09941   82 T 82
STKc_Rad53_Cds1 cd14098
Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the ...
241-489 4.60e-20

Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Rad53 and Cds1 are the checkpoint kinase 2 (Chk2) homologs found in budding and fission yeast, respectively. They play a central role in the cell's response to DNA lesions to prevent genome rearrangements and maintain genome integrity. They are phosphorylated in response to DNA damage and incomplete replication, and are essential for checkpoint control. They help promote DNA repair by stalling the cell cycle prior to mitosis in the presence of DNA damage. The Rad53/Cds1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271000 [Multi-domain]  Cd Length: 265  Bit Score: 91.38  E-value: 4.60e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  241 DITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTL-----KEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIIT 315
Cdd:cd14098    1 KYQIIDRLGSGTFAEVKKAVEVETGKMRAIKQIvkrkvAGNDKNLQLFQREINILKSLEHPGIVRLIDWYEDDQHIYLVM 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  316 EFMTYGNLLDYLRECNrqEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENH--LVKVADFGLSRLMTGDTY 393
Cdd:cd14098   81 EYVEGGDLMDFIMAWG--AIPEQHARELTKQILEAMAYTHSMGITHRDLKPENILITQDDpvIVKISDFGLAKVIHTGTF 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  394 -TAHAGAkfpIKWTAPESL------AYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEKDYRMERPE---G 463
Cdd:cd14098  159 lVTFCGT---MAYLAPEILmskeqnLQGGYSNLVDMWSVGCLVYVMLT-GALPFDGSSQLPVEKRIRKGRYTQPPLvdfN 234
                        250       260
                 ....*....|....*....|....*.
gi 62362414  464 CPEKVYELMRACWQWNPSDRPSFAEI 489
Cdd:cd14098  235 ISEEAIDFILRLLDVDPEKRMTAAQA 260
STKc_Nek5 cd08225
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
247-489 6.87e-20

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Neks are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The specific function of Nek5 is unknown. Nek5 is one in a family of 11 different Neks (Nek1-11). The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173765 [Multi-domain]  Cd Length: 257  Bit Score: 90.79  E-value: 6.87e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEE---FLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNL 323
Cdd:cd08225    7 KIGEGSFGKIYLAKAKSDSEHCVIKEIDLTKMPVKEkeaSKKEVILLAKMKHPNIVTFFASFQENGRLFIVMEYCDGGDL 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  324 ldyLRECNRQE---VNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLV-KVADFGLSRLMTGDTYTAHAGA 399
Cdd:cd08225   87 ---MKRINRQRgvlFSEDQILSWFVQISLGLKHIHDRKILHRDIKSQNIFLSKNGMVaKLGDFGIARQLNDSMELAYTCV 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  400 KFPIkWTAPESLAYNKFSIKSDVWAFGVLLWEIATYgMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQWN 479
Cdd:cd08225  164 GTPY-YLSPEICQNRPYNNKTDIWSLGCVLYELCTL-KHPFEGNNLHQLVLKICQGYFAPISPNFSRDLRSLISQLFKVS 241
                        250
                 ....*....|
gi 62362414  480 PSDRPSFAEI 489
Cdd:cd08225  242 PRDRPSITSI 251
STKc_Mos cd13979
Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze ...
248-485 7.36e-20

Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mos (or c-Mos) is a germ-cell specific kinase that plays roles in both the release of primary arrest and the induction of secondary arrest in oocytes. It is expressed towards the end of meiosis I and is quickly degraded upon fertilization. It is a component of the cytostatic factor (CSF), which is responsible for metaphase II arrest. In addition, Mos activates a phoshorylation cascade that leads to the activation of the p34 subunit of MPF (mitosis-promoting factor or maturation promoting factor), a cyclin-dependent kinase that is responsible for the release of primary arrest in meiosis I. The Mos subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270881 [Multi-domain]  Cd Length: 265  Bit Score: 90.52  E-value: 7.36e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKkySLTVAVKTLK---EDTMEVEEFLKEAAVMKeIKHPNLVQLLG---VCTREPPFYIITEFMTYG 321
Cdd:cd13979   11 LGSGGFGSVYKATYK--GETVAVKIVRrrrKNRASRQSFWAELNAAR-LRHENIVRVLAaetGTDFASLGLIIMEYCGNG 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  322 NLLDYLRECNRQEVNAVVLLYmATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTG----DTYTAHA 397
Cdd:cd13979   88 TLQQLIYEGSEPLPLAHRILI-SLDIARALRFCHSHGIVHLDVKPANILISEQGVCKLCDFGCSVKLGEgnevGTPRSHI 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  398 GAKFpiKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYE----LMR 473
Cdd:cd13979  167 GGTY--TYRAPELLKGERVTPKADIYSFGITLWQMLT-RELPYAGLRQHVLYAVVAKDLRPDLSGLEDSEFGQrlrsLIS 243
                        250
                 ....*....|..
gi 62362414  474 ACWQWNPSDRPS 485
Cdd:cd13979  244 RCWSAQPAERPN 255
STKc_Nek8 cd08220
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
248-434 7.87e-20

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek8 contains an N-terminal kinase catalytic domain and a C-terminal RCC1 (regulator of chromosome condensation) domain. A double point mutation in Nek8 causes cystic kidney disease in mice that genetically resembles human autosomal recessive polycystic kidney disease (ARPKD). Nek8 is also associated with a rare form of juvenile renal cystic disease, nephronophthisis type 9. It has been suggested that a defect in the ciliary localization of Nek8 contributes to the development of cysts manifested by these diseases. Nek8 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270859 [Multi-domain]  Cd Length: 256  Bit Score: 90.56  E-value: 7.87e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEE---FLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLL 324
Cdd:cd08220    8 VGRGAYGTVYLCRRKDDNKLVIIKQIPVEQMTKEErqaALNEVKVLSMLHHPNIIEYYESFLEDKALMIVMEYAPGGTLF 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  325 DYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENH-LVKVADFGLSRLMTGDT--YTAhAGAKF 401
Cdd:cd08220   88 EYIQQRKGSLLSEEEILHFFVQILLALHHVHSKQILHRDLKTQNILLNKKRtVVKIGDFGISKILSSKSkaYTV-VGTPC 166
                        170       180       190
                 ....*....|....*....|....*....|...
gi 62362414  402 PIKWTAPESLAYNKfsiKSDVWAFGVLLWEIAT 434
Cdd:cd08220  167 YISPELCEGKPYNQ---KSDIWALGCVLYELAS 196
STKc_CaMKI cd14083
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
244-428 8.51e-20

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270985 [Multi-domain]  Cd Length: 259  Bit Score: 90.51  E-value: 8.51e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  244 MKHKLGGGQYGEVYEGVWKKYSLTVAVKTL-------KEDTMEveeflKEAAVMKEIKHPNLVQLLGVCTREPPFYIITE 316
Cdd:cd14083    7 FKEVLGTGAFSEVVLAEDKATGKLVAIKCIdkkalkgKEDSLE-----NEIAVLRKIKHPNIVQLLDIYESKSHLYLVME 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  317 FMTYGNLLDYLRE-CNRQEVNAVVLLymaTQISSAMEYLEKKNFIHRDLAARNCLV---GENHLVKVADFGLSRLMTGDT 392
Cdd:cd14083   82 LVTGGELFDRIVEkGSYTEKDASHLI---RQVLEAVDYLHSLGIVHRDLKPENLLYyspDEDSKIMISDFGLSKMEDSGV 158
                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 62362414  393 YTAHAGAKfpiKWTAPESLAYNKFSIKSDVWAFGVL 428
Cdd:cd14083  159 MSTACGTP---GYVAPEVLAQKPYGKAVDCWSIGVI 191
STKc_YSK4 cd06631
Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs ...
248-489 1.05e-19

Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. YSK4 is a putative MAPKKK, whose mammalian gene has been isolated. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The YSK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270801 [Multi-domain]  Cd Length: 266  Bit Score: 90.19  E-value: 1.05e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLtVAVKTLKEDT-------MEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTY 320
Cdd:cd06631    9 LGKGAYGTVYCGLTSTGQL-IAVKQVELDTsdkekaeKEYEKLQEEVDLLKTLKHVNIVGYLGTCLEDNVVSIFMEFVPG 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  321 GNLLDYLRECNRQEvNAVVLLYmATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMT--------GDT 392
Cdd:cd06631   88 GSIASILARFGALE-EPVFCRY-TKQILEGVAYLHNNNVIHRDIKGNNIMLMPNGVIKLIDFGCAKRLCinlssgsqSQL 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  393 YTAHAGAKFpikWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGID-LSQVYELLEKDYRMER-PEGCPEKVYE 470
Cdd:cd06631  166 LKSMRGTPY---WMAPEVINETGHGRKSDIWSIGCTVFEMAT-GKPPWADMNpMAAIFAIGSGRKPVPRlPDKFSPEARD 241
                        250
                 ....*....|....*....
gi 62362414  471 LMRACWQWNPSDRPSFAEI 489
Cdd:cd06631  242 FVHACLTRDQDERPSAEQL 260
STKc_PASK cd14004
Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs ...
241-491 1.08e-19

Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PASK (or PASKIN) is a nutrient and energy sensor and thus, plays an important role in maintaining cellular energy homeostasis. It coordinates the utilization of glucose in response to metabolic demand. It contains an N-terminal PAS domain which directly interacts and inhibits a C-terminal catalytic kinase domain. The PAS domain serves as a sensory module for different environmental signals such as light, redox state, and various metabolites. Binding of ligands to the PAS domain causes structural changes which leads to kinase activation and the phosphorylation of substrates to trigger the appropriate cellular response. The PASK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270906 [Multi-domain]  Cd Length: 256  Bit Score: 90.14  E-value: 1.08e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  241 DITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLK-----EDTMEVEEFLK----EAAVMKEIK---HPNLVQLLGVCTRE 308
Cdd:cd14004    1 DYTILKEMGEGAYGQVNLAIYKSKGKEVVIKFIFkerilVDTWVRDRKLGtvplEIHILDTLNkrsHPNIVKLLDFFEDD 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  309 PPFYIITEFMTYG-NLLDYL-RECNRQEVNAVvllYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR 386
Cdd:cd14004   81 EFYYLVMEKHGSGmDLFDFIeRKPNMDEKEAK---YIFRQVADAVKHLHDQGIVHRDIKDENVILDGNGTIKLIDFGSAA 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  387 LMTGDTYTAHAGAkfpIKWTAPESLAYNKFSIKS-DVWAFGVLLWEIaTYGMSPYPGIDlsqvyELLEKDYRMerPEGCP 465
Cdd:cd14004  158 YIKSGPFDTFVGT---IDYAAPEVLRGNPYGGKEqDIWALGVLLYTL-VFKENPFYNIE-----EILEADLRI--PYAVS 226
                        250       260
                 ....*....|....*....|....*.
gi 62362414  466 EKVYELMRACWQWNPSDRPSFAEIHQ 491
Cdd:cd14004  227 EDLIDLISRMLNRDVGDRPTIEELLT 252
STKc_CDKL1_4 cd07847
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; ...
247-449 1.46e-19

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL1, also called p42 KKIALRE, is a glial protein that is upregulated in gliosis. It is present in neuroblastoma and A431 human carcinoma cells, and may be implicated in neoplastic transformation. The function of CDKL4 is unknown. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL1/4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270837 [Multi-domain]  Cd Length: 286  Bit Score: 90.51  E-value: 1.46e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVK--TLKEDTMEVEEF-LKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYgNL 323
Cdd:cd07847    8 KIGEGSYGVVFKCRNRETGQIVAIKkfVESEDDPVIKKIaLREIRMLKQLKHPNLVNLIEVFRRKRKLHLVFEYCDH-TV 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  324 LDYLrECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTG--DTYTAHAGAKF 401
Cdd:cd07847   87 LNEL-EKNPRGVPEHLIKKIIWQTLQAVNFCHKHNCIHRDVKPENILITKQGQIKLCDFGFARILTGpgDDYTDYVATRW 165
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 62362414  402 pikWTAPESLAYN-KFSIKSDVWAFGVLLWEIATyGMSPYPG-IDLSQVY 449
Cdd:cd07847  166 ---YRAPELLVGDtQYGPPVDVWAIGCVFAELLT-GQPLWPGkSDVDQLY 211
STKc_MLCK3 cd14192
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze ...
248-442 1.47e-19

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK3 (or MYLK3) phosphorylates myosin regulatory light chain 2 and controls the contraction of cardiac muscles. It is expressed specifically in both the atrium and ventricle of the heart and its expression is regulated by the cardiac protein Nkx2-5. MLCK3 plays an important role in cardiogenesis by regulating the assembly of cardiac sarcomeres, the repeating contractile unit of striated muscle. MLCK3 contains a single kinase domain near the C-terminus and a unique N-terminal half, and unlike MLCK1/2, it does not appear to be regulated by Ca2+/calmodulin. The MLCK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271094 [Multi-domain]  Cd Length: 261  Bit Score: 89.64  E-value: 1.47e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM-EVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDY 326
Cdd:cd14192   12 LGGGRFGQVHKCTELSTGLTLAAKIIKVKGAkEREEVKNEINIMNQLNHVNLIQLYDAFESKTNLTLIMEYVDGGELFDR 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  327 LRECNRQ--EVNAVVLlymATQISSAMEYLEKKNFIHRDLAARN--CLVGENHLVKVADFGLSRlmtgdTYTAHAGAKFP 402
Cdd:cd14192   92 ITDESYQltELDAILF---TRQICEGVHYLHQHYILHLDLKPENilCVNSTGNQIKIIDFGLAR-----RYKPREKLKVN 163
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 62362414  403 I---KWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPG 442
Cdd:cd14192  164 FgtpEFLAPEVVNYDFVSFPTDMWSVGVITYMLLS-GLSPFLG 205
STKc_TGFbR-like cd13998
Catalytic domain of Transforming Growth Factor beta Receptor-like Serine/Threonine Kinases; ...
249-483 1.57e-19

Catalytic domain of Transforming Growth Factor beta Receptor-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of receptors for the TGFbeta family of secreted signaling molecules including TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. There are two types of TGFbeta receptors included in this subfamily, I and II, that play different roles in signaling. For signaling to occur, the ligand first binds to the high-affinity type II receptor, which is followed by the recruitment of the low-affinity type I receptor to the complex and its activation through trans-phosphorylation by the type II receptor. The active type I receptor kinase starts intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. Different ligands interact with various combinations of types I and II receptors to elicit a specific signaling pathway. Activins primarily signal through combinations of ACVR1b/ALK7 and ACVR2a/b; myostatin and GDF11 through TGFbR1/ALK4 and ACVR2a/b; BMPs through ACVR1/ALK1 and BMPR2; and TGFbeta through TGFbR1 and TGFbR2. The TGFbR-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270900 [Multi-domain]  Cd Length: 289  Bit Score: 90.19  E-value: 1.57e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  249 GGGQYGEVYEGVWKKYslTVAVKTLkeDTMEVEEFLKEAAVMKE--IKHPNLVQLLGVCTR----EPPFYIITEFMTYGN 322
Cdd:cd13998    4 GKGRFGEVWKASLKNE--PVAVKIF--SSRDKQSWFREKEIYRTpmLKHENILQFIAADERdtalRTELWLVTAFHPNGS 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLRecnRQEVNAVVLLYMATQISSAMEYLE---------KKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTY 393
Cdd:cd13998   80 L*DYLS---LHTIDWVSLCRLALSVARGLAHLHseipgctqgKPAIAHRDLKSKNILVKNDGTCCIADFGLAVRLSPSTG 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  394 T---AHAGAKFPIKWTAPESLA----YNKFS--IKSDVWAFGVLLWEIAT-----------YGMSPYPGIDLSQVYELLE 453
Cdd:cd13998  157 EednANNGQVGTKRYMAPEVLEgainLRDFEsfKRVDIYAMGLVLWEMASrctdlfgiveeYKPPFYSEVPNHPSFEDMQ 236
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 62362414  454 KDYRME--RPE------GCPE--KVYELMRACWQWNPSDR 483
Cdd:cd13998  237 EVVVRDkqRPNipnrwlSHPGlqSLAETIEECWDHDAEAR 276
STKc_PCTAIRE3 cd07871
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-3 kinase; STKs catalyze the transfer ...
247-458 1.65e-19

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-3 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-3 shows a restricted pattern of expression and is present in brain, kidney, and intestine. It is elevated in Alzheimer's disease (AD) and has been shown to associate with paired helical filaments (PHFs) and stimulate Tau phosphorylation. As AD progresses, phosphorylated Tau aggregates and forms PHFs, which leads to the formation of neurofibrillary tangles. In human glioma cells, PCTAIRE-3 induces cell cycle arrest and cell death. PCTAIRE-3 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270853 [Multi-domain]  Cd Length: 288  Bit Score: 90.07  E-value: 1.65e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGvwkKYSLTVAVKTLKEDTMEVEE-----FLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTyG 321
Cdd:cd07871   12 KLGEGTYATVFKG---RSKLTENLVALKEIRLEHEEgapctAIREVSLLKNLKHANIVTLHDIIHTERCLTLVFEYLD-S 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  322 NLLDYLRECNRQEVNAVVLLYMaTQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTaHAGAKF 401
Cdd:cd07871   88 DLKQYLDNCGNLMSMHNVKIFM-FQLLRGLSYCHKRKILHRDLKPQNLLINEKGELKLADFGLARAKSVPTKT-YSNEVV 165
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 62362414  402 PIKWTAPES-LAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGidlSQVYELLEKDYRM 458
Cdd:cd07871  166 TLWYRPPDVlLGSTEYSTPIDMWGVGCILYEMAT-GRPMFPG---STVKEELHLIFRL 219
STKc_CDK9_like cd07840
Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs ...
246-452 1.74e-19

Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK9 and CDK12 from higher eukaryotes, yeast BUR1, C-type plant CDKs (CdkC), and similar proteins. CDK9, BUR1, and CdkC are functionally equivalent. They act as a kinase for the C-terminal domain of RNA polymerase II and participate in regulating mutliple steps of gene expression including transcription elongation and RNA processing. CDK9 and CdkC associate with T-type cyclins while BUR1 associates with the cyclin BUR2. CDK12 is a unique CDK that contains an arginine/serine-rich (RS) domain, which is predominantly found in splicing factors. CDK12 interacts with cyclins L1 and L2, and participates in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270832 [Multi-domain]  Cd Length: 291  Bit Score: 90.32  E-value: 1.74e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  246 HKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTmEVEEF----LKEAAVMKEIKHPNLVQLLGVCTREPP------FYIIT 315
Cdd:cd07840    5 AQIGEGTYGQVYKARNKKTGELVALKKIRMEN-EKEGFpitaIREIKLLQKLDHPNVVRLKEIVTSKGSakykgsIYMVF 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  316 EFMTYGnlLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDtyta 395
Cdd:cd07840   84 EYMDHD--LTGLLDNPEVKFTESQIKCYMKQLLEGLQYLHSNGILHRDIKGSNILINNDGVLKLADFGLARPYTKE---- 157
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 62362414  396 hagakFPIKWT---------APESL-AYNKFSIKSDVWAFGVLLWEIATyGMSPYPGID----LSQVYELL 452
Cdd:cd07840  158 -----NNADYTnrvitlwyrPPELLlGATRYGPEVDMWSVGCILAELFT-GKPIFQGKTeleqLEKIFELC 222
STKc_DCKL2 cd14184
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 2 (also called ...
248-440 1.89e-19

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 2 (also called Doublecortin-like and CAM kinase-like 2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL2 (or DCAMKL2) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL2 contains a serine, threonine, and proline rich domain (SP) and a C-terminal kinase domain with similarity to CAMKs. DCKL2 has been shown to interact with tubulin, JIP1/2, JNK, neurabin 2, and actin. It is associated with the terminal segments of axons and dendrites, and may function as a phosphorylation-dependent switch to control microtubule dynamics in neuronal growth cones. The DCKL2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271086 [Multi-domain]  Cd Length: 259  Bit Score: 89.32  E-value: 1.89e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFL--KEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLD 325
Cdd:cd14184    9 IGDGNFAVVKECVERSTGKEFALKIIDKAKCCGKEHLieNEVSILRRVKHPNIIMLIEEMDTPAELYLVMELVKGGDLFD 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  326 YLRECNR-QEVNAVVLLYmatQISSAMEYLEKKNFIHRDLAARNCLVGE----NHLVKVADFGLSRLMTGDTYTAHAGAK 400
Cdd:cd14184   89 AITSSTKyTERDASAMVY---NLASALKYLHGLCIVHRDIKPENLLVCEypdgTKSLKLGDFGLATVVEGPLYTVCGTPT 165
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 62362414  401 FpikwTAPESLAYNKFSIKSDVWAFGVLLWeIATYGMSPY 440
Cdd:cd14184  166 Y----VAPEIIAETGYGLKVDIWAAGVITY-ILLCGFPPF 200
STKc_GAK_like cd13985
Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of ...
248-494 1.93e-19

Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes cyclin G-Associated Kinase (GAK), Drosophila melanogaster Numb-Associated Kinase (NAK)-like proteins, and similar protein kinases. GAK plays regulatory roles in clathrin-mediated membrane trafficking, the maintenance of centrosome integrity and chromosome congression, neural patterning, survival of neurons, and immune responses. NAK plays a role in asymmetric cell division through its association with Numb. It also regulates the localization of Dlg, a protein essential for septate junction formation. The GAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270887 [Multi-domain]  Cd Length: 272  Bit Score: 89.70  E-value: 1.93e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTME-VEEFLKEAAVMKEI-KHPNLVQLLG--VCTREP--PFYIITEFMTyG 321
Cdd:cd13985    8 LGEGGFSYVYLAHDVNTGRRYALKRMYFNDEEqLRVAIKEIEIMKRLcGHPNIVQYYDsaILSSEGrkEVLLLMEYCP-G 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  322 NLLDYL--RECNRQEVNAVvlLYMATQISSAMEYLEKKN--FIHRDLAARNCLVGENHLVKVADFGlsrlmtgdtyTAHA 397
Cdd:cd13985   87 SLVDILekSPPSPLSEEEV--LRIFYQICQAVGHLHSQSppIIHRDIKIENILFSNTGRFKLCDFG----------SATT 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  398 GAKFPIKWT------------------APESL-AYNKFSI--KSDVWAFGVLLWEIATYGMsPYpgiDLSQVYELLEKDY 456
Cdd:cd13985  155 EHYPLERAEevniieeeiqknttpmyrAPEMIdLYSKKPIgeKADIWALGCLLYKLCFFKL-PF---DESSKLAIVAGKY 230
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 62362414  457 RMERPEGCPEKVYELMRACWQWNPSDRPS-FAEIHQAFE 494
Cdd:cd13985  231 SIPEQPRYSPELHDLIRHMLTPDPAERPDiFQVINIITK 269
STKc_PAK_I cd06647
Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze ...
247-440 2.01e-19

Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group I PAKs, also called conventional PAKs, include PAK1, PAK2, and PAK3. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). They interact with the SH3 domain containing proteins Nck, Grb2 and PIX. Binding of group I PAKs to activated GTPases leads to conformational changes that destabilize the AID, allowing autophosphorylation and full activation of the kinase domain. Known group I PAK substrates include MLCK, Bad, Raf, MEK1, LIMK, Merlin, Vimentin, Myc, Stat5a, and Aurora A, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270814 [Multi-domain]  Cd Length: 261  Bit Score: 89.22  E-value: 2.01e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLK-EDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLD 325
Cdd:cd06647   14 KIGQGASGTVYTAIDVATGQEVAIKQMNlQQQPKKELIINEILVMRENKNPNIVNYLDSYLVGDELWVVMEYLAGGSLTD 93
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  326 YLRECNRQE--VNAVvllymATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGD--TYTAHAGAKF 401
Cdd:cd06647   94 VVTETCMDEgqIAAV-----CRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEqsKRSTMVGTPY 168
                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 62362414  402 pikWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPY 440
Cdd:cd06647  169 ---WMAPEVVTRKAYGPKVDIWSLGIMAIEMVE-GEPPY 203
STKc_ASK cd06624
Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase; STKs ...
234-491 2.05e-19

Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily are mitogen-activated protein kinase (MAPK) kinase kinases (MAPKKKs or MKKKs) and include ASK1, ASK2, and MAPKKK15. ASK1 (also called MAPKKK5) functions in the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. It plays important roles in cytokine and stress responses, as well as in reactive oxygen species-mediated cellular responses. ASK1 is implicated in various diseases mediated by oxidative stress including inschemic heart disease, hypertension, vessel injury, brain ischemia, Fanconi anemia, asthma, and pulmonary edema, among others. ASK2 (also called MAPKKK6) functions only in a heteromeric complex with ASK1, and can activate ASK1 by direct phosphorylation. The function of MAPKKK15 is still unknown. The ASK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270794 [Multi-domain]  Cd Length: 268  Bit Score: 89.39  E-value: 2.05e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  234 KWEMERTDITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKE-DTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFY 312
Cdd:cd06624    2 EYEYEYDESGERVVLGKGTFGVVYAARDLSTQVRIAIKEIPErDSREVQPLHEEIALHSRLSHKNIVQYLGSVSEDGFFK 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  313 IITEFMTYGNLLDYLR-ECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGE-NHLVKVADFGLSRLMTG 390
Cdd:cd06624   82 IFMEQVPGGSLSALLRsKWGPLKDNENTIGYYTKQILEGLKYLHDNKIVHRDIKGDNVLVNTySGVVKISDFGTSKRLAG 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  391 -----DTYTAhagakfPIKWTAPESLAYNK--FSIKSDVWAFGVLLWEIATyGMSPYpgidlsqvYELLEKDYRM----- 458
Cdd:cd06624  162 inpctETFTG------TLQYMAPEVIDKGQrgYGPPADIWSLGCTIIEMAT-GKPPF--------IELGEPQAAMfkvgm 226
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 62362414  459 -----ERPEGCPEKVYELMRACWQWNPSDRPSFAEIHQ 491
Cdd:cd06624  227 fkihpEIPESLSEEAKSFILRCFEPDPDKRATASDLLQ 264
STKc_MLCK4 cd14193
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze ...
248-444 2.19e-19

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. MLCK4 (or MYLK4 or SgK085) contains a single kinase domain near the C-terminus. The MLCK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271095 [Multi-domain]  Cd Length: 261  Bit Score: 89.20  E-value: 2.19e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM-EVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDY 326
Cdd:cd14193   12 LGGGRFGQVHKCEEKSSGLKLAAKIIKARSQkEKEEVKNEIEVMNQLNHANLIQLYDAFESRNDIVLVMEYVDGGELFDR 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  327 LRECNRQEVNAVVLLYMaTQISSAMEYLEKKNFIHRDLAARN--CLVGENHLVKVADFGLS-RLMTGDTYTAHAGAKfpi 403
Cdd:cd14193   92 IIDENYNLTELDTILFI-KQICEGIQYMHQMYILHLDLKPENilCVSREANQVKIIDFGLArRYKPREKLRVNFGTP--- 167
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 62362414  404 KWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGID 444
Cdd:cd14193  168 EFLAPEVVNYEFVSFPTDMWSLGVIAYMLLS-GLSPFLGED 207
PKc_Pek1_like cd06621
Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ...
242-485 2.23e-19

Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Pek1/Skh1 from Schizosaccharomyces pombe and MKK2 from Saccharomyces cerevisiae, and related proteins. Both fission yeast Pek1 and baker's yeast MKK2 are components of the cell integrity MAPK pathway. In fission yeast, Pek1 phosphorylates and activates Pmk1/Spm1 and is regulated by the MAPKK kinase Mkh1. In baker's yeast, the pathway involves the MAPK Slt2, the MAPKKs MKK1 and MKK2, and the MAPKK kinase Bck1. The cell integrity MAPK cascade is activated by multiple stress conditions, and is essential in cell wall construction, morphogenesis, cytokinesis, and ion homeostasis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270793 [Multi-domain]  Cd Length: 287  Bit Score: 89.79  E-value: 2.23e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  242 ITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDT--MEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPP--FYIITEF 317
Cdd:cd06621    3 IVELSSLGEGAGGSVTKCRLRNTKTIFALKTITTDPnpDVQKQILRELEINKSCASPYIVKYYGAFLDEQDssIGIAMEY 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  318 MTYGNLLDYLRECNRQ--EVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSrlmtGDTYTA 395
Cdd:cd06621   83 CEGGSLDSIYKKVKKKggRIGEKVLGKIAESVLKGLSYLHSRKIIHRDIKPSNILLTRKGQVKLCDFGVS----GELVNS 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  396 HA----GAKFpikWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYP--GIDLSQVYELLEKDYRMERPE--GCP-- 465
Cdd:cd06621  159 LAgtftGTSY---YMAPERIQGGPYSITSDVWSLGLTLLEVAQ-NRFPFPpeGEPPLGPIELLSYIVNMPNPElkDEPen 234
                        250       260
                 ....*....|....*....|....*
gi 62362414  466 -----EKVYELMRACWQWNPSDRPS 485
Cdd:cd06621  235 gikwsESFKDFIEKCLEKDGTRRPG 259
PK_GC-2D cd14043
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain ...
254-496 2.45e-19

Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-2D is allso called Retinal Guanylyl Cyclase 1 (RETGC-1) or Rod Outer Segment membrane Guanylate Cyclase (ROS-GC). It is found in the photoreceptors of the retina where it anchors the reciprocal feedback loop between calcium and cGMP, which regulates the dark, light, and recovery phases in phototransduction. It is also found in other sensory neurons and may be a universal transduction component that plays a role in the perception of all senses. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-2D subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270945 [Multi-domain]  Cd Length: 267  Bit Score: 89.39  E-value: 2.45e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  254 GEVYEGVW---KKYSLTVAVKtLKEDTMEVeeFLKeaavMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDYLREc 330
Cdd:cd14043   18 GVAYEGDWvwlKKFPGGSHTE-LRPSTKNV--FSK----LRELRHENVNLFLGLFVDCGILAIVSEHCSRGSLEDLLRN- 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  331 nrQEVNavvLLYM-----ATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPIKW 405
Cdd:cd14043   90 --DDMK---LDWMfksslLLDLIKGMRYLHHRGIVHGRLKSRNCVVDGRFVLKITDYGYNEILEAQNLPLPEPAPEELLW 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  406 TAPESL----AYNKFSIKSDVWAFGVLLWEIATYGmSPYPGIDLSQvYELLEKDYR---MERP----EGCPEKVYELMRA 474
Cdd:cd14043  165 TAPELLrdprLERRGTFPGDVFSFAIIMQEVIVRG-APYCMLGLSP-EEIIEKVRSpppLCRPsvsmDQAPLECIQLMKQ 242
                        250       260
                 ....*....|....*....|..
gi 62362414  475 CWQWNPSDRPSFAEIHQAFETM 496
Cdd:cd14043  243 CWSEAPERRPTFDQIFDQFKSI 264
STKc_PCTAIRE1 cd07873
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer ...
247-458 2.57e-19

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-1 is expressed ubiquitously and is localized in the cytoplasm. Its kinase activity is cell cycle dependent and peaks at the S and G2 phases. PCTAIRE-1 is highly expressed in the brain and may play a role in regulating neurite outgrowth. It can also associate with Trap (Tudor repeat associator with PCTAIRE-2), a physiological partner of PCTAIRE-2; with p11, a small dimeric protein with similarity to S100; and with 14-3-3 proteins, mediators of phosphorylation-dependent interactions in many different proteins. PCTAIRE-1 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270854 [Multi-domain]  Cd Length: 297  Bit Score: 90.06  E-value: 2.57e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGvwkKYSLTVAVKTLKEDTMEVEE-----FLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTyG 321
Cdd:cd07873    9 KLGEGTYATVYKG---RSKLTDNLVALKEIRLEHEEgapctAIREVSLLKDLKHANIVTLHDIIHTEKSLTLVFEYLD-K 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  322 NLLDYLREC-NRQEVNAVVLLYMatQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTahAGAK 400
Cdd:cd07873   85 DLKQYLDDCgNSINMHNVKLFLF--QLLRGLAYCHRRKVLHRDLKPQNLLINERGELKLADFGLARAKSIPTKT--YSNE 160
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  401 FPIKWTAPES--LAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGidlSQVYELLEKDYRM 458
Cdd:cd07873  161 VVTLWYRPPDilLGSTDYSTQIDMWGVGCIFYEMST-GRPLFPG---STVEEQLHFIFRI 216
STKc_cPKC_beta cd05616
Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C beta; STKs ...
248-450 3.73e-19

Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PKC beta isoforms (I and II), generated by alternative splicing of a single gene, are preferentially activated by hyperglycemia-induced DAG (1,2-diacylglycerol) in retinal tissues. This is implicated in diabetic microangiopathy such as ischemia, neovascularization, and abnormal vasodilator function. PKC-beta also plays an important role in VEGF signaling. In addition, glucose regulates proliferation in retinal endothelial cells via PKC-betaI. PKC-beta is also being explored as a therapeutic target in cancer. It contributes to tumor formation and is involved in the tumor host mechanisms of inflammation and angiogenesis. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG, and in most cases, phosphatidylserine (PS) for activation. The cPKC-beta subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270767 [Multi-domain]  Cd Length: 323  Bit Score: 90.06  E-value: 3.73e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEI-----KHPNLVQLLGVCTREPPFYIITEFMTYGN 322
Cdd:cd05616    8 LGKGSFGKVMLAERKGTDELYAVKILKKDVVIQDDDVECTMVEKRVlalsgKPPFLTQLHSCFQTMDRLYFVMEYVNGGD 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLRECNR-QEVNAVvllYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKF 401
Cdd:cd05616   88 LMYHIQQVGRfKEPHAV---FYAAEIAIGLFFLQSKGIIYRDLKLDNVMLDSEGHIKIADFGMCKENIWDGVTTKTFCGT 164
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 62362414  402 PiKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYE 450
Cdd:cd05616  165 P-DYIAPEIIAYQPYGKSVDWWAFGVLLYEMLA-GQAPFEGEDEDELFQ 211
STKc_p38alpha cd07877
Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase ...
223-444 3.84e-19

Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase (also called MAPK14); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38alpha/MAPK14 is expressed in most tissues and is the major isoform involved in the immune and inflammatory response. It is the central p38 MAPK involved in myogenesis. It plays a role in regulating cell cycle check-point transition and promoting cell differentiation. p38alpha also regulates cell proliferation and death through crosstalk with the JNK pathway. Its substrates include MAPK activated protein kinase 2 (MK2), MK5, and the transcription factors ATF2 and Mitf. p38 kinases MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143382 [Multi-domain]  Cd Length: 345  Bit Score: 90.48  E-value: 3.84e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  223 PTVYGVSPNYDKWEMERTDITMKhKLGGGQYGEVYEGVWKKYSLTVAVKTLK---EDTMEVEEFLKEAAVMKEIKHPNLV 299
Cdd:cd07877    1 PTFYRQELNKTIWEVPERYQNLS-PVGSGAYGSVCAAFDTKTGLRVAVKKLSrpfQSIIHAKRTYRELRLLKHMKHENVI 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  300 QLLGVCTREPPF------YIITEFMtyGNLLDYLRECNRQEVNAV-VLLYmatQISSAMEYLEKKNFIHRDLAARNCLVG 372
Cdd:cd07877   80 GLLDVFTPARSLeefndvYLVTHLM--GADLNNIVKCQKLTDDHVqFLIY---QILRGLKYIHSADIIHRDLKPSNLAVN 154
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 62362414  373 ENHLVKVADFGLSRlMTGDTYTAHAGAKFpikWTAPE-SLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGID 444
Cdd:cd07877  155 EDCELKILDFGLAR-HTDDEMTGYVATRW---YRAPEiMLNWMHYNQTVDIWSVGCIMAELLT-GRTLFPGTD 222
STKc_Kin1_2 cd14077
Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the ...
271-489 3.93e-19

Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of yeast Kin1, Kin2, and similar proteins. Fission yeast Kin1 is a membrane-associated kinase that is involved in regulating cell surface cohesiveness during interphase. It also plays a role during mitosis, linking actomyosin ring assembly with septum synthesis and membrane closure to ensure separation of daughter cells. Budding yeast Kin1 and Kin2 act downstream of the Rab-GTPase Sec4 and are associated with the exocytic apparatus; they play roles in the secretory pathway. The Kin1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270979 [Multi-domain]  Cd Length: 267  Bit Score: 88.66  E-value: 3.93e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  271 KTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDY------LRECNRQEvnavvllyMA 344
Cdd:cd14077   48 KRLEKEISRDIRTIREAALSSLLNHPHICRLRDFLRTPNHYYMLFEYVDGGQLLDYiishgkLKEKQARK--------FA 119
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  345 TQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTY-TAHAGAKFpikWTAPESLAYNKFS-IKSDV 422
Cdd:cd14077  120 RQIASALDYLHRNSIVHRDLKIENILISKSGNIKIIDFGLSNLYDPRRLlRTFCGSLY---FAAPELLQAQPYTgPEVDV 196
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 62362414  423 WAFGVLLWEIATyGMSPYPGIDLSQVYELLeKDYRMERPEGCPEKVYELMRACWQWNPSDRPSFAEI 489
Cdd:cd14077  197 WSFGVVLYVLVC-GKVPFDDENMPALHAKI-KKGKVEYPSYLSSECKSLISRMLVVDPKKRATLEQV 261
STKc_AMPK_alpha cd14079
Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein ...
248-430 4.27e-19

Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. In response to decreased ATP levels, it enhances energy-producing processes and inhibits energy-consuming pathways. Once activated, AMPK phosphorylates a broad range of downstream targets, with effects in carbohydrate metabolism and uptake, lipid and fatty acid biosynthesis, carbon energy storage, and inflammation, among others. Defects in energy homeostasis underlie many human diseases including Type 2 diabetes, obesity, heart disease, and cancer. As a result, AMPK has emerged as a therapeutic target in the treatment of these diseases. The AMPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270981 [Multi-domain]  Cd Length: 256  Bit Score: 88.09  E-value: 4.27e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTL---KEDTMEVEEFLK-EAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNL 323
Cdd:cd14079   10 LGVGSFGKVKLAEHELTGHKVAVKILnrqKIKSLDMEEKIRrEIQILKLFRHPHIIRLYEVIETPTDIFMVMEYVSGGEL 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  324 LDYLRECNR-QEVNAVVLLymaTQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMT-GDTYTAHAGAkf 401
Cdd:cd14079   90 FDYIVQKGRlSEDEARRFF---QQIISGVEYCHRHMVVHRDLKPENLLLDSNMNVKIADFGLSNIMRdGEFLKTSCGS-- 164
                        170       180       190
                 ....*....|....*....|....*....|....*
gi 62362414  402 PiKWTAPESLaynkfSIKS------DVWAFGVLLW 430
Cdd:cd14079  165 P-NYAAPEVI-----SGKLyagpevDVWSCGVILY 193
STKc_Chk2 cd14084
Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze ...
243-441 4.48e-19

Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Checkpoint Kinase 2 (Chk2) plays an important role in cellular responses to DNA double-strand breaks and related lesions. It is phosphorylated and activated by ATM kinase, resulting in its dissociation from sites of damage to phosphorylate downstream targets such as BRCA1, p53, cell cycle transcription factor E2F1, the promyelocytic leukemia protein (PML) involved in apoptosis, and CDC25 phosphatases, among others. Mutations in Chk2 is linked to a variety of cancers including familial breast cancer, myelodysplastic syndromes, prostate cancer, lung cancer, and osteosarcomas. Chk2 contains an N-terminal SQ/TQ cluster domain (SCD), a central forkhead-associated (FHA) domain, and a C-terminal catalytic kinase domain. The Chk2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270986 [Multi-domain]  Cd Length: 275  Bit Score: 88.60  E-value: 4.48e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  243 TMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLK------------EDTMEVEeflKEAAVMKEIKHPNLVQLLGVCTREPP 310
Cdd:cd14084    9 IMSRTLGSGACGEVKLAYDKSTCKKVAIKIINkrkftigsrreiNKPRNIE---TEIEILKKLSHPCIIKIEDFFDAEDD 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  311 FYIITEFMTYGNLLDYLRECNRQEvNAVVLLYmATQISSAMEYLEKKNFIHRDLAARNCLVG---ENHLVKVADFGLSRL 387
Cdd:cd14084   86 YYIVLELMEGGELFDRVVSNKRLK-EAICKLY-FYQMLLAVKYLHSNGIIHRDLKPENVLLSsqeEECLIKITDFGLSKI 163
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 62362414  388 MtGDTYTAHAGAKFPIkWTAPESLAY---NKFSIKSDVWAFGVLLWeiatYGMSPYP 441
Cdd:cd14084  164 L-GETSLMKTLCGTPT-YLAPEVLRSfgtEGYTRAVDCWSLGVILF----ICLSGYP 214
STKc_EIF2AK3_PERK cd14048
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
240-432 4.51e-19

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3 or PKR-like Endoplasmic Reticulum Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PERK (or EIF2AK3) is a type-I ER transmembrane protein containing a luminal domain bound with the chaperone BiP under unstressed conditions and a cytoplasmic catalytic kinase domain. In response to the accumulation of misfolded or unfolded proteins in the ER, PERK is activated through the release of BiP, allowing it to dimerize and autophosphorylate. It functions as the central regulator of translational control during the Unfolded Protein Response (UPR) pathway. In addition to the eIF-2 alpha subunit, PERK also phosphorylates Nrf2, a leucine zipper transcription factor which regulates cellular redox status and promotes cell survival during the UPR. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The PERK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270950 [Multi-domain]  Cd Length: 281  Bit Score: 88.78  E-value: 4.51e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  240 TDITMKHKLGGGQYGEVYEGVWKKYSLTVAVK--TLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPP------- 310
Cdd:cd14048    6 TDFEPIQCLGRGGFGVVFEAKNKVDDCNYAVKriRLPNNELAREKVLREVRALAKLDHPGIVRYFNAWLERPPegwqekm 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  311 ----FYIITEFMTYGNLLDYL-RECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLS 385
Cdd:cd14048   86 devyLYIQMQLCRKENLKDWMnRRCTMESRELFVCLNIFKQIASAVEYLHSKGLIHRDLKPSNVFFSLDDVVKVGDFGLV 165
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 62362414  386 RLMTGD-----------TYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEI 432
Cdd:cd14048  166 TAMDQGepeqtvltpmpAYAKHTGQVGTRLYMSPEQIHGNQYSEKVDIFALGLILFEL 223
PKc_MKK3_6 cd06617
Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase ...
240-511 4.70e-19

Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK3 and MKK6 are dual-specificity PKs that phosphorylate and activate their downstream target, p38 MAPK, on specific threonine and tyrosine residues. MKK3/6 play roles in the regulation of cell cycle progression, cytokine- and stress-induced apoptosis, oncogenic transformation, and adult tissue regeneration. In addition, MKK6 plays a critical role in osteoclast survival in inflammatory disease while MKK3 is associated with tumor invasion, progression, and poor patient survival in glioma. The MKK3/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173729 [Multi-domain]  Cd Length: 283  Bit Score: 88.64  E-value: 4.70e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  240 TDITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKE--DTMEVEEFLKEAAV-MKEIKHPNLVQLLGVCTREPPFYIITE 316
Cdd:cd06617    1 DDLEVIEELGRGAYGVVDKMRHVPTGTIMAVKRIRAtvNSQEQKRLLMDLDIsMRSVDCPYTVTFYGALFREGDVWICME 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  317 FMT------YGNLLDylrecNRQEVNAVVLLYMATQISSAMEYL-EKKNFIHRDLAARNCLVGENHLVKVADFGLS-RLM 388
Cdd:cd06617   81 VMDtsldkfYKKVYD-----KGLTIPEDILGKIAVSIVKALEYLhSKLSVIHRDVKPSNVLINRNGQVKLCDFGISgYLV 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  389 TGDTYTAHAGAKfpiKWTAPE----SLAYNKFSIKSDVWAFGVLLWEIATyGMSPY-----PGIDLSQVYEllekdyrmE 459
Cdd:cd06617  156 DSVAKTIDAGCK---PYMAPErinpELNQKGYDVKSDVWSLGITMIELAT-GRFPYdswktPFQQLKQVVE--------E 223
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  460 RPEGCPEKVYEL-----MRACWQWNPSDRPSFAEI--HQAFET-MFQESSISDEVEKELG 511
Cdd:cd06617  224 PSPQLPAEKFSPefqdfVNKCLKKNYKERPNYPELlqHPFFELhLSKNTDVASFVSLILG 283
STKc_MEKK1 cd06630
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
248-493 4.76e-19

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK1 is a MAPK kinase kinase (MAPKKK or MKKK) that phosphorylates and activates activates the ERK1/2 and c-Jun N-terminal kinase (JNK) pathways by activating their respective MAPKKs, MEK1/2 and MKK4/MKK7, respectively. MEKK1 is important in regulating cell survival and apoptosis. MEKK1 also plays a role in cell migration, tissue maintenance and homeostasis, and wound healing. The MEKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270800 [Multi-domain]  Cd Length: 268  Bit Score: 88.26  E-value: 4.76e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLK-------EDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTY 320
Cdd:cd06630    8 LGTGAFSSCYQARDVKTGTLMAVKQVSfcrnsssEQEEVVEAIREEIRMMARLNHPNIVRMLGATQHKSHFNIFVEWMAG 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  321 GNLLDYLRECNRQEvNAVVLLYMaTQISSAMEYLEKKNFIHRDLAARNCLV-GENHLVKVADFG-LSRLMTGDTYTAHAG 398
Cdd:cd06630   88 GSVASLLSKYGAFS-ENVIINYT-LQILRGLAYLHDNQIIHRDLKGANLLVdSTGQRLRIADFGaAARLASKGTGAGEFQ 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  399 AKF--PIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEKDYRMERPEGCPE----KVYELM 472
Cdd:cd06630  166 GQLlgTIAFMAPEVLRGEQYGRSCDVWSVGCVIIEMAT-AKPPWNAEKISNHLALIFKIASATTPPPIPEhlspGLRDVT 244
                        250       260
                 ....*....|....*....|...
gi 62362414  473 RACWQWNPSDRPSFAE--IHQAF 493
Cdd:cd06630  245 LRCLELQPEDRPPAREllKHPVF 267
STKc_MEKK3_like cd06625
Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) ...
248-489 5.45e-19

Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MEKK3, MEKK2, and related proteins; all contain an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are MAPK kinase kinases (MAPKKKs or MKKK) that activate MEK5 (also called MKK5), which activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. MEKK2 and MEKK3 can also activate the MAPKs, c-Jun N-terminal kinase (JNK) and p38, through their respective MAPKKs. The MEKK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270795 [Multi-domain]  Cd Length: 260  Bit Score: 88.18  E-value: 5.45e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTL------KEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYG 321
Cdd:cd06625    8 LGQGAFGQVYLCYDADTGRELAVKQVeidpinTEASKEVKALECEIQLLKNLQHERIVQYYGCLQDEKSLSIFMEYMPGG 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  322 NLLDYLRecNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLS-RLMT----GDTYTAH 396
Cdd:cd06625   88 SVKDEIK--AYGALTENVTRKYTRQILEGLAYLHSNMIVHRDIKGANILRDSNGNVKLGDFGASkRLQTicssTGMKSVT 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  397 aGAKFpikWTAPESLAYNKFSIKSDVWAFGVLLWEIATygMSPyPGIDL---SQVYELLEKDYRMERPEGCPEKVYELMR 473
Cdd:cd06625  166 -GTPY---WMSPEVINGEGYGRKADIWSVGCTVVEMLT--TKP-PWAEFepmAAIFKIATQPTNPQLPPHVSEDARDFLS 238
                        250
                 ....*....|....*.
gi 62362414  474 ACWQWNPSDRPSFAEI 489
Cdd:cd06625  239 LIFVRNKKQRPSAEEL 254
SH2_Tec_family cd09934
Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the ...
120-216 5.74e-19

Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the founding member of a family that includes Btk, Itk, Bmx, and Txk. The members have a PH domain, a zinc-binding motif, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. Btk is involved in B-cell receptor signaling with mutations in Btk responsible for X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice. Itk is involved in T-cell receptor signaling. Tec is expressed in both T and B cells, and is thought to function in activated and effector T lymphocytes to induce the expression of genes regulated by NFAT transcription factors. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198188  Cd Length: 104  Bit Score: 83.22  E-value: 5.74e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  120 NSLEKHSWYHGPVSRNAAEYLL-SSGINGSFLVRESeSSPGQRSISL----RYEGRVYHYRINTASDGKLYVSSESRFNT 194
Cdd:cd09934    1 LNLEKYEWYVGDMSRQRAESLLkQEDKEGCFVVRNS-STKGLYTVSLftkvPGSPHVKHYHIKQNARSEFYLAEKHCFET 79
                         90       100
                 ....*....|....*....|..
gi 62362414  195 LAELVHHHSTVADGLITTLHYP 216
Cdd:cd09934   80 IPELINYHQHNSGGLATRLKYP 101
SH2_C-SH2_Syk_like cd10401
C-terminal Src homology 2 (SH2) domain found in Spleen tyrosine kinase (Syk) proteins; ZAP-70 ...
123-219 6.78e-19

C-terminal Src homology 2 (SH2) domain found in Spleen tyrosine kinase (Syk) proteins; ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the C-terminus SH2 domains of Syk. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198264  Cd Length: 99  Bit Score: 82.63  E-value: 6.78e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  123 EKHSWYHGPVSRNAAEYLLSSG--INGSFLVRESESSpGQRSISLRYEGRVYHYRINTASDGKLYVSSESRFNTLAELVH 200
Cdd:cd10401    1 EKMPWFHGKISREESEQILLIGskTNGKFLIRERDNN-GSYALCLLHDGKVLHYRIDKDKTGKLSIPDGKKFDTLWQLVE 79
                         90
                 ....*....|....*....
gi 62362414  201 HHSTVADGLITTLHYPAPK 219
Cdd:cd10401   80 HYSYKPDGLLRVLTEPCPR 98
STKc_FA2-like cd08529
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar ...
241-435 7.63e-19

Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chlamydomonas reinhardtii FA2 was discovered in a genetic screen for deflagellation-defective mutants. It is essential for basal-body/centriole-associated microtubule severing, and plays a role in cell cycle progression. No cellular function has yet been ascribed to CNK4. The Chlamydomonas reinhardtii FA2-like subfamily belongs to the (NIMA)-related kinase (Nek) family, which includes seven different Chlamydomonas Neks (CNKs 1-6 and Fa2). This subfamily contains FA2 and CNK4. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270868 [Multi-domain]  Cd Length: 256  Bit Score: 87.47  E-value: 7.63e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  241 DITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTL---KEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEF 317
Cdd:cd08529    1 DFEILNKLGKGSFGVVYKVVRKVDGRVYALKQIdisRMSRKMREEAIDEARVLSKLNSPYVIKYYDSFVDKGKLNIVMEY 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  318 MTYGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHA 397
Cdd:cd08529   81 AENGDLHSLIKSQRGRPLPEDQIWKFFIQTLLGLSHLHSKKILHRDIKSMNIFLDKGDNVKIGDLGVAKILSDTTNFAQT 160
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 62362414  398 GAKFPIkWTAPE---SLAYNKfsiKSDVWAFGVLLWEIATY 435
Cdd:cd08529  161 IVGTPY-YLSPElceDKPYNE---KSDVWALGCVLYELCTG 197
SH2_Src_Lck cd10362
Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck); Lck is a member of the Src ...
123-216 9.03e-19

Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck); Lck is a member of the Src non-receptor type tyrosine kinase family of proteins. It is expressed in the brain, T-cells, and NK cells. The unique domain of Lck mediates its interaction with two T-cell surface molecules, CD4 and CD8. It associates with their cytoplasmic tails on CD4 T helper cells and CD8 cytotoxic T cells to assist signaling from the T cell receptor (TCR) complex. When the T cell receptor is engaged by the specific antigen presented by MHC, Lck phosphorylase the intracellular chains of the CD3 and zeta-chains of the TCR complex, allowing ZAP-70 to bind them. Lck then phosphorylates and activates ZAP-70, which in turn phosphorylates Linker of Activated T cells (LAT), a transmembrane protein that serves as a docking site for proteins including: Shc-Grb2-SOS, PI3K, and phospholipase C (PLC). The tyrosine phosphorylation cascade culminates in the intracellular mobilization of a calcium ions and activation of important signaling cascades within the lymphocyte, including the Ras-MEK-ERK pathway, which goes on to activate certain transcription factors such as NFAT, NF-kappaB, and AP-1. These transcription factors regulate the production cytokines such as Interleukin-2 that promote long-term proliferation and differentiation of the activated lymphocytes. The N-terminal tail of Lck is myristoylated and palmitoylated and it tethers the protein to the plasma membrane of the cell. Lck also contains a SH3 domain, a SH2 domain, and a C-terminal tyrosine kinase domain. Lck has 2 phosphorylation sites, the first an autophosphorylation site that is linked to activation of the protein and the second which is phosphorylated by Csk, which inhibits it. Lck is also inhibited by SHP-1 dephosphorylation and by Cbl ubiquitin ligase, which is part of the ubiquitin-mediated pathway. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198225  Cd Length: 101  Bit Score: 82.61  E-value: 9.03e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  123 EKHSWYHGPVSRNAAEYLLSSGIN--GSFLVRESESSPGQRSISLR----YEGR-VYHYRINTASDGKLYVSSESRFNTL 195
Cdd:cd10362    1 EPEPWFFKNLSRNDAERQLLAPGNthGSFLIRESETTAGSFSLSVRdfdqNQGEvVKHYKIRNLDNGGFYISPRITFPGL 80
                         90       100
                 ....*....|....*....|.
gi 62362414  196 AELVHHHSTVADGLITTLHYP 216
Cdd:cd10362   81 HELVRHYTNASDGLCTRLSRP 101
STKc_RCK1-like cd14096
Catalytic domain of RCK1-like Serine/Threonine Kinases; STKs catalyze the transfer of the ...
243-432 9.33e-19

Catalytic domain of RCK1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of fungal STKs including Saccharomyces cerevisiae RCK1 and RCK2, Schizosaccharomyces pombe Sty1-regulated kinase 1 (Srk1), and similar proteins. RCK1, RCK2 (or Rck2p), and Srk1 are MAPK-activated protein kinases. RCK1 and RCK2 are involved in oxidative and metal stress resistance in budding yeast. RCK2 also regulates rapamycin sensitivity in both S. cerevisiae and Candida albicans. Srk1 is activated by Sty1/Spc1 and is involved in negatively regulating cell cycle progression by inhibiting Cdc25. The RCK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270998 [Multi-domain]  Cd Length: 295  Bit Score: 88.26  E-value: 9.33e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  243 TMKHKLGGGQYGEVYEGVWKKYSLT-VAVKTL-KED-------TMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYI 313
Cdd:cd14096    4 RLINKIGEGAFSNVYKAVPLRNTGKpVAIKVVrKADlssdnlkGSSRANILKEVQIMKRLSHPNIVKLLDFQESDEYYYI 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  314 ITEFMTYGNLLDYLrecnrqevnaVVLLYMA--------TQISSAMEYLEKKNFIHRDLAARNCLV-------------- 371
Cdd:cd14096   84 VLELADGGEIFHQI----------VRLTYFSedlsrhviTQVASAVKYLHEIGVVHRDIKPENLLFepipfipsivklrk 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  372 -------------------GENHLVKVADFGLSRLMTGDTYTAHAGAkfpIKWTAPESLAYNKFSIKSDVWAFGVLLWEI 432
Cdd:cd14096  154 adddetkvdegefipgvggGGIGIVKLADFGLSKQVWDSNTKTPCGT---VGYTAPEVVKDERYSKKVDMWALGCVLYTL 230
SH2_N-SH2_Zap70_Syk_like cd09938
N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
127-230 1.01e-18

N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70) and Spleen tyrosine kinase (Syk) proteins; ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the N-terminus SH2 domains of both Syk and Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198191  Cd Length: 104  Bit Score: 82.44  E-value: 1.01e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  127 WYHGPVSRNAAE-YLLSSGIN-GSFLVRESESSPGQRSISLRYEGRVYHYRINTASDGKLYVSSESRFNTLAELVHHHST 204
Cdd:cd09938    3 FFYGSITREEAEeYLKLAGMSdGLFLLRQSLRSLGGYVLSVCHGRKFHHYTIERQLNGTYAIAGGKAHCGPAELCEYHST 82
                         90       100
                 ....*....|....*....|....*.
gi 62362414  205 VADGLITTLHYPApkrNKPTvyGVSP 230
Cdd:cd09938   83 DLDGLVCLLRKPC---NRPP--GVEP 103
STKc_SLK cd06643
Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer ...
247-491 1.06e-18

Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It acts as a MAPK kinase kinase by phosphorylating ASK1, resulting in the phosphorylation of p38. SLK also plays a role in mediating actin reorganization. It is part of a microtubule-associated complex that is targeted at adhesion sites, and is required in focal adhesion turnover and in regulating cell migration. The SLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270811 [Multi-domain]  Cd Length: 283  Bit Score: 87.77  E-value: 1.06e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM-EVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLD 325
Cdd:cd06643   12 ELGDGAFGKVYKAQNKETGILAAAKVIDTKSEeELEDYMVEIDILASCDHPNIVKLLDAFYYENNLWILIEFCAGGAVDA 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  326 YLRECNRQEVNAVVLLyMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSrlmTGDTYTAHAGAKF---P 402
Cdd:cd06643   92 VMLELERPLTEPQIRV-VCKQTLEALVYLHENKIIHRDLKAGNILFTLDGDIKLADFGVS---AKNTRTLQRRDSFigtP 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  403 IkWTAPESLAYNK-----FSIKSDVWAFGVLLWEIATygMSPyPGIDLSQVYELLE----KDYRMERPEGCPEKVYELMR 473
Cdd:cd06643  168 Y-WMAPEVVMCETskdrpYDYKADVWSLGVTLIEMAQ--IEP-PHHELNPMRVLLKiaksEPPTLAQPSRWSPEFKDFLR 243
                        250
                 ....*....|....*...
gi 62362414  474 ACWQWNPSDRPSFAEIHQ 491
Cdd:cd06643  244 KCLEKNVDARWTTSQLLQ 261
SH2_a2chimerin_b2chimerin cd10352
Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins ...
128-211 1.19e-18

Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins are a family of phorbol ester- and diacylglycerol-responsive GTPase-activating proteins. Alpha1-chimerin (formerly known as n-chimerin) and alpha2-chimerin are alternatively spliced products of a single gene, as are beta1- and beta2-chimerin. alpha1- and beta1-chimerin have a relatively short N-terminal region that does not encode any recognizable domains, whereas alpha2- and beta2-chimerin both include a functional SH2 domain that can bind to phosphotyrosine motifs within receptors. All of the isoforms contain a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. Other C1 domain-containing diacylglycerol receptors including: PKC, Munc-13 proteins, phorbol ester binding scaffolding proteins involved in Ca2+-stimulated exocytosis, and RasGRPs, diacylglycerol-activated guanine-nucleotide exchange factors (GEFs) for Ras and Rap1. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198215  Cd Length: 91  Bit Score: 81.64  E-value: 1.19e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  128 YHGPVSRNAAEYLLSSGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTASDGKLYVSSESRFNTLAELvhhhstVAD 207
Cdd:cd10352    9 YHGLISREEAEQLLSGASDGSYLIRESSRDDGYYTLSLRFNGKVKNYKLYYDGKNHYHYVGEKRFDTIHDL------VAD 82

                 ....
gi 62362414  208 GLIT 211
Cdd:cd10352   83 GLIT 86
STKc_BUR1 cd07866
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), ...
247-431 1.22e-18

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), Bypass UAS Requirement 1, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BUR1, also called SGV1, is a yeast CDK that is functionally equivalent to mammalian CDK9. It associates with the cyclin BUR2. BUR genes were orginally identified in a genetic screen as factors involved in general transcription. The BUR1/BUR2 complex phosphorylates the C-terminal domain of RNA polymerase II. In addition, this complex regulates histone modification by phosporylating Rad6 and mediating the association of the Paf1 complex with chromatin. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The BUR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270849 [Multi-domain]  Cd Length: 311  Bit Score: 88.14  E-value: 1.22e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAvktLKEDTMEVEE--F----LKEAAVMKEIKHPNLVQLLGVCTREPP--------FY 312
Cdd:cd07866   15 KLGEGTFGEVYKARQIKTGRVVA---LKKILMHNEKdgFpitaLREIKILKKLKHPNVVPLIDMAVERPDkskrkrgsVY 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  313 IITEFMTYGnlLDYLRECNRQEVN-AVVLLYMaTQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGD 391
Cdd:cd07866   92 MVTPYMDHD--LSGLLENPSVKLTeSQIKCYM-LQLLEGINYLHENHILHRDIKAANILIDNQGILKIADFGLARPYDGP 168
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 62362414  392 TYT-AHAGAKFPIKWT---------APESLAYNK-FSIKSDVWAFGVLLWE 431
Cdd:cd07866  169 PPNpKGGGGGGTRKYTnlvvtrwyrPPELLLGERrYTTAVDIWGIGCVFAE 219
STKc_ULK2 cd14201
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the ...
235-486 1.26e-18

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK2 is ubiquitously expressed and is essential in autophagy induction. It displays partially redundant functions with ULK1 and is able to compensate for the loss of ULK1 in non-selective autophagy. It also displays neuron-specific functions and is important in axon development. The ULK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271103 [Multi-domain]  Cd Length: 271  Bit Score: 87.37  E-value: 1.26e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  235 WEMERTDItmkhkLGGGQYGEVYEGVW-KKYSLTVAVKTLKEDTMEVEEFL--KEAAVMKEIKHPNLVQLLGVCTREPPF 311
Cdd:cd14201    6 FEYSRKDL-----VGHGAFAVVFKGRHrKKTDWEVAIKSINKKNLSKSQILlgKEIKILKELQHENIVALYDVQEMPNSV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  312 YIITEFMTYGNLLDYLREcnRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVG---------ENHLVKVADF 382
Cdd:cd14201   81 FLVMEYCNGGDLADYLQA--KGTLSEDTIRVFLQQIAAAMRILHSKGIIHRDLKPQNILLSyasrkkssvSGIRIKIADF 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  383 GLSRLMTGDTYTAHAGAKfPIkWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPG---IDLSQVYElLEKDYRME 459
Cdd:cd14201  159 GFARYLQSNMMAATLCGS-PM-YMAPEVIMSQHYDAKADLWSIGTVIYQCLV-GKPPFQAnspQDLRMFYE-KNKNLQPS 234
                        250       260
                 ....*....|....*....|....*..
gi 62362414  460 RPEGCPEKVYELMRACWQWNPSDRPSF 486
Cdd:cd14201  235 IPRETSPYLADLLLGLLQRNQKDRMDF 261
STKc_PRKX_like cd05612
Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of ...
241-450 1.27e-18

Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include human PRKX (X chromosome-encoded protein kinase), Drosophila DC2, and similar proteins. PRKX is present in many tissues including fetal and adult brain, kidney, and lung. The PRKX gene is located in the Xp22.3 subregion and has a homolog called PRKY on the Y chromosome. An abnormal interchange between PRKX aand PRKY leads to the sex reversal disorder of XX males and XY females. PRKX is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PRKX-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270763 [Multi-domain]  Cd Length: 292  Bit Score: 87.88  E-value: 1.27e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  241 DITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLK----EDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITE 316
Cdd:cd05612    2 DFERIKTIGTGTFGRVHLVRDRISEHYYALKVMAipevIRLKQEQHVHNEKRVLKEVSHPFIIRLFWTEHDQRFLYMLME 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  317 FMTYGNLLDYLRecNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAH 396
Cdd:cd05612   82 YVPGGELFSYLR--NSGRFSNSTGLFYASEIVCALEYLHSKEIVYRDLKPENILLDKEGHIKLTDFGFAKKLRDRTWTLC 159
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 62362414  397 AGAKFpikwTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYE 450
Cdd:cd05612  160 GTPEY----LAPEVIQSKGHNKAVDWWALGILIYEMLV-GYPPFFDDNPFGIYE 208
PK_ILK cd14057
Pseudokinase domain of Integrin Linked Kinase; The pseudokinase domain shows similarity to ...
246-496 1.27e-18

Pseudokinase domain of Integrin Linked Kinase; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. ILK contains N-terminal ankyrin repeats, a Pleckstrin Homology (PH) domain, and a C-terminal pseudokinase domain. It is a component of the IPP (ILK/PINCH/Parvin) complex that couples beta integrins to the actin cytoskeleton, and plays important roles in cell adhesion, spreading, invasion, and migration. ILK was initially thought to be an active kinase despite the lack of key conserved residues because of in vitro studies showing that it can phosphorylate certain protein substrates. However, in vivo experiments in Caenorhabditis elegans, Drosophila melanogaster, and mice (ILK-null and knock-in) proved that ILK is not an active kinase. In addition to actin cytoskeleton regulation, ILK also influences the microtubule network and mitotic spindle orientation. The pseudokinase domain of ILK binds several adaptor proteins including the parvins and paxillin. The ILK subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270959 [Multi-domain]  Cd Length: 251  Bit Score: 86.77  E-value: 1.27e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  246 HKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEV-EEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLL 324
Cdd:cd14057    1 TKINETHSGELWKGRWQGNDIVAKILKVRDVTTRIsRDFNEEYPRLRIFSHPNVLPVLGACNSPPNLVVISQYMPYGSLY 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  325 DYLRECNRQEVNAVVLLYMATQISSAMEYLEK-KNFIHR-DLAARNCLVGENHLVKV--ADFGLSRLMTGDTYTAhagak 400
Cdd:cd14057   81 NVLHEGTGVVVDQSQAVKFALDIARGMAFLHTlEPLIPRhHLNSKHVMIDEDMTARInmADVKFSFQEPGKMYNP----- 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  401 fpiKWTAPESL--AYNKFSIKS-DVWAFGVLLWEIATygmSPYPGIDLSQV---YELLEKDYRMERPEGCPEKVYELMRA 474
Cdd:cd14057  156 ---AWMAPEALqkKPEDINRRSaDMWSFAILLWELVT---REVPFADLSNMeigMKIALEGLRVTIPPGISPHMCKLMKI 229
                        250       260
                 ....*....|....*....|..
gi 62362414  475 CWQWNPSDRPSFAEIHQAFETM 496
Cdd:cd14057  230 CMNEDPGKRPKFDMIVPILEKM 251
PKc_Byr1_like cd06620
Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; ...
247-490 1.28e-18

Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Byr1 from Schizosaccharomyces pombe, FUZ7 from Ustilago maydis, and related proteins. Byr1 phosphorylates its downstream target, the MAPK Spk1, and is regulated by the MAPKK kinase Byr2. The Spk1 cascade is pheromone-responsive and is essential for sporulation and sexual differentiation in fission yeast. FUZ7 phosphorylates and activates its target, the MAPK Crk1, which is required in mating and virulence in U. maydis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The Byr-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270792 [Multi-domain]  Cd Length: 286  Bit Score: 87.49  E-value: 1.28e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEV--EEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYII-TEFMTYGNL 323
Cdd:cd06620   12 DLGAGNGGSVSKVLHIPTGTIMAKKVIHIDAKSSvrKQILRELQILHECHSPYIVSFYGAFLNENNNIIIcMEYMDCGSL 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  324 LDYLREcnRQEVNAVVLLYMATQISSAMEYL-EKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMT---GDTYTAHAga 399
Cdd:cd06620   92 DKILKK--KGPFPEEVLGKIAVAVLEGLTYLyNVHRIIHRDIKPSNILVNSKGQIKLCDFGVSGELInsiADTFVGTS-- 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  400 kfpiKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPY---PGIDLSQ-----VYELL-----EKDYRMERPEGCPE 466
Cdd:cd06620  168 ----TYMSPERIQGGKYSVKSDVWSLGLSIIELAL-GEFPFagsNDDDDGYngpmgILDLLqrivnEPPPRLPKDRIFPK 242
                        250       260
                 ....*....|....*....|....
gi 62362414  467 KVYELMRACWQWNPSDRPSFAEIH 490
Cdd:cd06620  243 DLRDFVDRCLLKDPRERPSPQLLL 266
STKc_PKC cd05570
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer ...
248-483 1.53e-18

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, classical PKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. Novel PKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. Also included in this subfamily are the PKC-like proteins, called PKNs. The PKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270722 [Multi-domain]  Cd Length: 318  Bit Score: 88.04  E-value: 1.53e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM----EVEEFLKEAAVM-KEIKHPNLVQLlgVCTREPP--FYIITEFMTY 320
Cdd:cd05570    3 LGKGSFGKVMLAERKKTDELYAIKVLKKEVIieddDVECTMTEKRVLaLANRHPFLTGL--HACFQTEdrLYFVMEYVNG 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  321 GNLLDYLRECNR-QEVNAVvllYMATQISSAMEYLEKKNFIHRDLAARNCLV-GENHlVKVADFGLSR--LMTGDTYTAH 396
Cdd:cd05570   81 GDLMFHIQRARRfTEERAR---FYAAEICLALQFLHERGIIYRDLKLDNVLLdAEGH-IKIADFGMCKegIWGGNTTSTF 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  397 AGAkfPiKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYE-LLEKDYRMerPEGCPEKVYELMRAC 475
Cdd:cd05570  157 CGT--P-DYIAPEILREQDYGFSVDWWALGVLLYEMLA-GQSPFEGDDEDELFEaILNDEVLY--PRWLSREAVSILKGL 230

                 ....*...
gi 62362414  476 WQWNPSDR 483
Cdd:cd05570  231 LTKDPARR 238
STKc_TAO cd06607
Catalytic domain of the Serine/Threonine Kinases, Thousand-and-One Amino acids proteins; STKs ...
246-489 1.63e-18

Catalytic domain of the Serine/Threonine Kinases, Thousand-and-One Amino acids proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase activity. They activate the MAPKs, p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating the respective MAP/ERK kinases (MEKs, also known as MKKs or MAPKKs), MEK3/MEK6 and MKK4/MKK7. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. Vertebrates contain three TAO subfamily members, named TAO1, TAO2, and TAO3. The TAO subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270784 [Multi-domain]  Cd Length: 258  Bit Score: 86.73  E-value: 1.63e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  246 HKLGGGQYGEVYEGVWKKYSLTVAVKTL----KEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFmTYG 321
Cdd:cd06607    7 REIGHGSFGAVYYARNKRTSEVVAIKKMsysgKQSTEKWQDIIKEVKFLRQLRHPNTIEYKGCYLREHTAWLVMEY-CLG 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  322 NLLDYLrECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMtgDTYTAHAGAKF 401
Cdd:cd06607   86 SASDIV-EVHKKPLQEVEIAAICHGALQGLAYLHSHNRIHRDVKAGNILLTEPGTVKLADFGSASLV--CPANSFVGTPY 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  402 pikWTAPE---SLAYNKFSIKSDVWAFGVLLWEIATYgMSPYPGID-LSQVYELLEKDYRMERPEGCPEKVYELMRACWQ 477
Cdd:cd06607  163 ---WMAPEvilAMDEGQYDGKVDVWSLGITCIELAER-KPPLFNMNaMSALYHIAQNDSPTLSSGEWSDDFRNFVDSCLQ 238
                        250
                 ....*....|..
gi 62362414  478 WNPSDRPSFAEI 489
Cdd:cd06607  239 KIPQDRPSAEDL 250
STKc_cPKC_alpha cd05615
Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha; STKs ...
229-483 1.69e-18

Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-alpha is expressed in many tissues and is associated with cell proliferation, apoptosis, and cell motility. It plays a role in the signaling of the growth factors PDGF, VEGF, EGF, and FGF. Abnormal levels of PKC-alpha have been detected in many transformed cell lines and several human tumors. In addition, PKC-alpha is required for HER2 dependent breast cancer invasion. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. The cPKC-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270766 [Multi-domain]  Cd Length: 341  Bit Score: 88.13  E-value: 1.69e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  229 SPNYDKWEMerTDITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM----EVEEFLKEAAVMKEI-KHPNLVQLLG 303
Cdd:cd05615    1 SNNLDRVRL--TDFNFLMVLGKGSFGKVMLAERKGSDELYAIKILKKDVViqddDVECTMVEKRVLALQdKPPFLTQLHS 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  304 VCTREPPFYIITEFMTYGNLLDYLRECNR-QEVNAVvllYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADF 382
Cdd:cd05615   79 CFQTVDRLYFVMEYVNGGDLMYHIQQVGKfKEPQAV---FYAAEISVGLFFLHKKGIIYRDLKLDNVMLDSEGHIKIADF 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  383 GLSR--LMTGDTYTAHAGAKfpiKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLeKDYRMER 460
Cdd:cd05615  156 GMCKehMVEGVTTRTFCGTP---DYIAPEIIAYQPYGRSVDWWAYGVLLYEMLA-GQPPFDGEDEDELFQSI-MEHNVSY 230
                        250       260
                 ....*....|....*....|...
gi 62362414  461 PEGCPEKVYELMRACWQWNPSDR 483
Cdd:cd05615  231 PKSLSKEAVSICKGLMTKHPAKR 253
STKc_TSSK1_2-like cd14165
Catalytic domain of testis-specific serine/threonine kinase 1, TSSK2, and similar proteins; ...
248-490 1.75e-18

Catalytic domain of testis-specific serine/threonine kinase 1, TSSK2, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK1 and TSSK2 are expressed specifically in meiotic and postmeiotic spermatogenic cells, respectively. TSSK2 is localized in the sperm neck, equatorial segment, and mid-piece of the sperm tail. Both TSSK1 and TSSK2 phosphorylate their common substrate TSKS (testis-specific-kinase-substrate). TSSK1/TSSK2 double knock-out mice are sterile without manifesting other defects, making these kinases viable targets for male contraception. The TSSK1/2-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271067 [Multi-domain]  Cd Length: 263  Bit Score: 86.76  E-value: 1.75e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTL---KEDTMEVEEFL-KEAAVMKEIKHPNLVQLLGVC-TREPPFYIITEFMTYGN 322
Cdd:cd14165    9 LGEGSYAKVKSAYSERLKCNVAIKIIdkkKAPDDFVEKFLpRELEILARLNHKSIIKTYEIFeTSDGKVYIVMELGVQGD 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLRecNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGD---------TY 393
Cdd:cd14165   89 LLEFIK--LRGALPEDVARKMFHQLSSAIKYCHELDIVHRDLKCENLLLDKDFNIKLTDFGFSKRCLRDengrivlskTF 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  394 TAHAGakfpikWTAPESLAYNKFSIK-SDVWAFGVLLWeIATYGMSPYpgiDLSQVYELL--EKDYRMERPEGCPE--KV 468
Cdd:cd14165  167 CGSAA------YAAPEVLQGIPYDPRiYDIWSLGVILY-IMVCGSMPY---DDSNVKKMLkiQKEHRVRFPRSKNLtsEC 236
                        250       260
                 ....*....|....*....|..
gi 62362414  469 YELMRACWQWNPSDRPSFAEIH 490
Cdd:cd14165  237 KDLIYRLLQPDVSQRLCIDEVL 258
STKc_MLCK1 cd14191
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze ...
244-442 1.76e-18

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK1 (or MYLK1) phosphorylates myosin regulatory light chain and controls the contraction of smooth muscles. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module which results in the expression of telokin in phasic smooth muscles, leading to Ca2+ desensitization by cyclic nucleotides of smooth muscle force. MLCK1 is also responsible for myosin regulatory light chain phosphorylation in nonmuscle cells and may play a role in regulating myosin II ATPase activity. The MLCK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271093 [Multi-domain]  Cd Length: 259  Bit Score: 86.60  E-value: 1.76e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  244 MKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKE-DTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGN 322
Cdd:cd14191    6 IEERLGSGKFGQVFRLVEKKTKKVWAGKFFKAySAKEKENIRQEISIMNCLHHPKLVQCVDAFEEKANIVMVLEMVSGGE 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLRECNRQEVNAVVLLYMaTQISSAMEYLEKKNFIHRDLAARN--CLVGENHLVKVADFGLSRLM--TGDTYTAHAG 398
Cdd:cd14191   86 LFERIIDEDFELTERECIKYM-RQISEGVEYIHKQGIVHLDLKPENimCVNKTGTKIKLIDFGLARRLenAGSLKVLFGT 164
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 62362414  399 AKFpikwTAPESLAYNKFSIKSDVWAFGVLLWeIATYGMSPYPG 442
Cdd:cd14191  165 PEF----VAPEVINYEPIGYATDMWSIGVICY-ILVSGLSPFMG 203
SH2_Src_HCK cd10363
Src homology 2 (SH2) domain found in HCK; HCK is a member of the Src non-receptor type ...
123-216 1.78e-18

Src homology 2 (SH2) domain found in HCK; HCK is a member of the Src non-receptor type tyrosine kinase family of proteins and is expressed in hemopoietic cells. HCK is proposed to couple the Fc receptor to the activation of the respiratory burst. It may also play a role in neutrophil migration and in the degranulation of neutrophils. It has two different translational starts that have different subcellular localization. HCK has been shown to interact with BCR gene, ELMO1 Cbl gene, RAS p21 protein activator 1, RASA3, Granulocyte colony-stimulating factor receptor, ADAM15 and RAPGEF1. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its C-terminal tail. In general SH2 domains are involved in signal transduction. HCK has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198226  Cd Length: 104  Bit Score: 81.93  E-value: 1.78e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  123 EKHSWYHGPVSRNAAE-YLLSSG-INGSFLVRESESSPGQRSISLR-YEGR----VYHYRINTASDGKLYVSSESRFNTL 195
Cdd:cd10363    1 ETEEWFFKGISRKDAErQLLAPGnMLGSFMIRDSETTKGSYSLSVRdYDPQhgdtVKHYKIRTLDNGGFYISPRSTFSTL 80
                         90       100
                 ....*....|....*....|.
gi 62362414  196 AELVHHHSTVADGLITTLHYP 216
Cdd:cd10363   81 QELVDHYKKGNDGLCQKLSVP 101
PKc_MKK5 cd06619
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
241-485 1.86e-18

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 5; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK5 (also called MEK5) is a dual-specificity PK that phosphorylates its downstream target, extracellular signal-regulated kinase 5 (ERK5), on specific threonine and tyrosine residues. MKK5 is activated by MEKK2 and MEKK3 in response to mitogenic and stress stimuli. The ERK5 cascade promotes cell proliferation, differentiation, neuronal survival, and neuroprotection. This cascade plays an essential role in heart development. Mice deficient in either ERK5 or MKK5 die around embryonic day 10 due to cardiovascular defects including underdevelopment of the myocardium. In addition, MKK5 is associated with metastasis and unfavorable prognosis in prostate cancer. The MKK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132950 [Multi-domain]  Cd Length: 279  Bit Score: 86.86  E-value: 1.86e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  241 DITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKED-TMEVE-EFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFM 318
Cdd:cd06619    2 DIQYQEILGHGNGGTVYKAYHLLTRRILAVKVIPLDiTVELQkQIMSELEILYKCDSPYIIGFYGAFFVENRISICTEFM 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  319 TYGNLLDYLRecnrqeVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAG 398
Cdd:cd06619   82 DGGSLDVYRK------IPEHVLGRIAVAVVKGLTYLWSLKILHRDVKPSNMLVNTRGQVKLCDFGVSTQLVNSIAKTYVG 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  399 AKfpiKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEKDYRMERPEGCP--------EKVYE 470
Cdd:cd06619  156 TN---AYMAPERISGEQYGIHSDVWSLGISFMELAL-GRFPYPQIQKNQGSLMPLQLLQCIVDEDPPvlpvgqfsEKFVH 231
                        250
                 ....*....|....*
gi 62362414  471 LMRACWQWNPSDRPS 485
Cdd:cd06619  232 FITQCMRKQPKERPA 246
PK_KSR2 cd14153
Pseudokinase domain of Kinase Suppressor of Ras 2; The pseudokinase domain shows similarity to ...
248-496 1.98e-18

Pseudokinase domain of Kinase Suppressor of Ras 2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. KSR2 interacts with the protein phosphatase calcineurin and functions in calcium-mediated ERK signaling. It also functions in energy metabolism by regulating AMP kinase and AMPK-dependent processes such as glucose uptake and fatty acid oxidation. KSR proteins act as scaffold proteins that function downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. KSR proteins regulate the assembly and activation of the Raf/MEK/ERK module upon Ras activation at the membrane by direct association of its components. They are widely regarded as pseudokinases. The KSR2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271055 [Multi-domain]  Cd Length: 270  Bit Score: 86.60  E-value: 1.98e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDYL 327
Cdd:cd14153    8 IGKGRFGQVYHGRWHGEVAIRLIDIERDNEEQLKAFKREVMAYRQTRHENVVLFMGACMSPPHLAIITSLCKGRTLYSVV 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  328 RECNR-QEVNAVvlLYMATQISSAMEYLEKKNFIHRDLAARNCLVgENHLVKVADFGL-------------SRLMTGDTY 393
Cdd:cd14153   88 RDAKVvLDVNKT--RQIAQEIVKGMGYLHAKGILHKDLKSKNVFY-DNGKVVITDFGLftisgvlqagrreDKLRIQSGW 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  394 TAHAGAKFpIKWTAPESlAYNK--FSIKSDVWAFG-------------------VLLWEIATyGMSPypgiDLSQVyell 452
Cdd:cd14153  165 LCHLAPEI-IRQLSPET-EEDKlpFSKHSDVFAFGtiwyelharewpfktqpaeAIIWQVGS-GMKP----NLSQI---- 233
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....
gi 62362414  453 ekdyrmerpeGCPEKVYELMRACWQWNPSDRPSFAEIHQAFETM 496
Cdd:cd14153  234 ----------GMGKEISDILLFCWAYEQEERPTFSKLMEMLEKL 267
STKc_WNK cd13983
Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze ...
247-489 2.09e-18

Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNKs comprise a subfamily of STKs with an unusual placement of a catalytic lysine relative to all other protein kinases. They are critical in regulating ion balance and are thus, important components in the control of blood pressure. They are also involved in cell signaling, survival, proliferation, and organ development. WNKs are activated by hyperosmotic or low-chloride hypotonic stress and they function upstream of SPAK and OSR1 kinases, which regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. There are four vertebrate WNKs which show varying expression patterns. WNK1 and WNK2 are widely expressed while WNK3 and WNK4 show a more restricted expression pattern. Because mutations in human WNK1 and WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension (due to increased sodium reabsorption) and hyperkalemia (due to impaired renal potassium secretion), there are more studies conducted on these two proteins, compared to WNK2 and WNK3. The WNK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270885 [Multi-domain]  Cd Length: 258  Bit Score: 86.13  E-value: 2.09e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVA---VKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLG----VCTREPPFyiITEFMT 319
Cdd:cd13983    8 VLGRGSFKTVYRAFDTEEGIEVAwneIKLRKLPKAERQRFKQEIEILKSLKHPNIIKFYDswesKSKKEVIF--ITELMT 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  320 YGNLLDYLRECnrQEVNAVVLLYMATQISSAMEYLEKKN--FIHRDLAARNCLV-GENHLVKVADFGLSRLMTGDTYTAH 396
Cdd:cd13983   86 SGTLKQYLKRF--KRLKLKVIKSWCRQILEGLNYLHTRDppIIHRDLKCDNIFInGNTGEVKIGDLGLATLLRQSFAKSV 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  397 AGAkfPiKWTAPEsLAYNKFSIKSDVWAFGVLLWEIATyGMSPY-----PGidlsQVYELLEKDYrmeRPEGCpEKV--- 468
Cdd:cd13983  164 IGT--P-EFMAPE-MYEEHYDEKVDIYAFGMCLLEMAT-GEYPYsectnAA----QIYKKVTSGI---KPESL-SKVkdp 230
                        250       260
                 ....*....|....*....|...
gi 62362414  469 --YELMRACWQwNPSDRPSFAEI 489
Cdd:cd13983  231 elKDFIEKCLK-PPDERPSAREL 252
STKc_Trio_C cd14113
C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide ...
247-487 2.66e-18

C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide Exchange Factor, Triple functional domain protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Triple functional domain protein (Trio), also called PTPRF-interacting protein, is a large multidomain protein containing a series of spectrin-like repeats, two each of RhoGEF and SH3 domains, an immunoglobulin-like (Ig) domain and a C-terminal kinase. Trio plays important roles in neuronal cell migration and axon guidance. It was originally identified as an interacting partner of the of the receptor-like tyrosine phosphatase (RPTP) LAR (leukocyte-antigen-related protein), a family of receptors that function in the signaling to the actin cytoskeleton during development. Trio functions as a GEF for Rac1, RhoG, and RhoA, and is involved in the regulation of lamellipodia formation, mediating Rac1-dependent cell spreading and migration. The Trio subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271015 [Multi-domain]  Cd Length: 263  Bit Score: 86.18  E-value: 2.66e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDY 326
Cdd:cd14113   14 ELGRGRFSVVKKCDQRGTKRAVATKFVNKKLMKRDQVTHELGVLQSLQHPQLVGLLDTFETPTSYILVLEMADQGRLLDY 93
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  327 L-RECNRQEvnAVVLLYMAtQISSAMEYLEKKNFIHRDLAARNCLVGENH---LVKVADFGlSRLMTGDTYTAHAGAKFP 402
Cdd:cd14113   94 VvRWGNLTE--EKIRFYLR-EILEALQYLHNCRIAHLDLKPENILVDQSLskpTIKLADFG-DAVQLNTTYYIHQLLGSP 169
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  403 iKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYpgIDLSqVYEL------LEKDYRMERPEGCPEKVYELMRACW 476
Cdd:cd14113  170 -EFAAPEIILGNPVSLTSDLWSIGVLTYVLLS-GVSPF--LDES-VEETclnicrLDFSFPDDYFKGVSQKAKDFVCFLL 244
                        250
                 ....*....|.
gi 62362414  477 QWNPSDRPSFA 487
Cdd:cd14113  245 QMDPAKRPSAA 255
PTZ00024 PTZ00024
cyclin-dependent protein kinase; Provisional
248-452 2.99e-18

cyclin-dependent protein kinase; Provisional


Pssm-ID: 240233 [Multi-domain]  Cd Length: 335  Bit Score: 87.51  E-value: 2.99e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   248 LGGGQYGEVYEGVWKKYSLTVAVKTLK---------EDTMEVEE------FLKEAAVMKEIKHPNLVQLLGVCTREPPFY 312
Cdd:PTZ00024   17 LGEGTYGKVEKAYDTLTGKIVAIKKVKiieisndvtKDRQLVGMcgihftTLRELKIMNEIKHENIMGLVDVYVEGDFIN 96
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   313 IITEFMTYgNLldylrecnRQEVNAVVLLYMA------TQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR 386
Cdd:PTZ00024   97 LVMDIMAS-DL--------KKVVDRKIRLTESqvkcilLQILNGLNVLHKWYFMHRDLSPANIFINSKGICKIADFGLAR 167
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   387 ----LMTGDTYTAHAGAKFPIKWT---------APESL-AYNKFSIKSDVWAFGVLLWEIATyGMSPYPG---ID-LSQV 448
Cdd:PTZ00024  168 rygyPPYSDTLSKDETMQRREEMTskvvtlwyrAPELLmGAEKYHFAVDMWSVGCIFAELLT-GKPLFPGeneIDqLGRI 246

                  ....
gi 62362414   449 YELL 452
Cdd:PTZ00024  247 FELL 250
STKc_CAMKK cd14118
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; ...
285-489 3.21e-18

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The CaMKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271020 [Multi-domain]  Cd Length: 275  Bit Score: 86.26  E-value: 3.21e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  285 KEAAVMKEIKHPNLVQLLGVC--TREPPFYIITEFMTYGNLLDYLRECNRQEVNA------VVLlymatqissAMEYLEK 356
Cdd:cd14118   63 REIAILKKLDHPNVVKLVEVLddPNEDNLYMVFELVDKGAVMEVPTDNPLSEETArsyfrdIVL---------GIEYLHY 133
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  357 KNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGD----TYTAHAGAkfpikWTAPESLA--YNKFSIKS-DVWAFGVLL 429
Cdd:cd14118  134 QKIIHRDIKPSNLLLGDDGHVKIADFGVSNEFEGDdallSSTAGTPA-----FMAPEALSesRKKFSGKAlDIWAMGVTL 208
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 62362414  430 WEIaTYGMSPYPGIDLSQVYELLEKDyRMERPEGC--PEKVYELMRACWQWNPSDRPSFAEI 489
Cdd:cd14118  209 YCF-VFGRCPFEDDHILGLHEKIKTD-PVVFPDDPvvSEQLKDLILRMLDKNPSERITLPEI 268
STKc_KSR1 cd14152
Catalytic domain of the Serine/Threonine Kinase, Kinase Suppressor of Ras 1; STKs catalyze the ...
242-496 3.82e-18

Catalytic domain of the Serine/Threonine Kinase, Kinase Suppressor of Ras 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. KSR1 functions as a transducer of TNFalpha-stimulated C-Raf activation of ERK1/2 and NF-kB. Detected activity of KSR1 is cell type specific and context dependent. It is inactive in normal colon epithelial cells and becomes activated at the onset of inflammatory bowel disease (IBD). Similarly, KSR1 activity is undetectable prior to stimulation by EGF or ceramide in COS-7 or YAMC cells, respectively. KSR proteins are widely regarded as pseudokinases, however, this matter is up for debate as catalytic activity has been detected for KSR1 in some systems. The KSR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271054 [Multi-domain]  Cd Length: 279  Bit Score: 86.18  E-value: 3.82e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  242 ITMKHKLGGGQYGEVYEGVWKKyslTVAVKTLKEDTMEVEE---FLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFM 318
Cdd:cd14152    2 IELGELIGQGRWGKVHRGRWHG---EVAIRLLEIDGNNQDHlklFKKEVMNYRQTRHENVVLFMGACMHPPHLAIITSFC 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  319 TYGNLLDYLREcNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVgENHLVKVADFGLsrlmTGDTYTAHAG 398
Cdd:cd14152   79 KGRTLYSFVRD-PKTSLDINKTRQIAQEIIKGMGYLHAKGIVHKDLKSKNVFY-DNGKVVITDFGL----FGISGVVQEG 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  399 A-----KFPIKWT---APE---SLAYNK------FSIKSDVWAFGVLLWEIATygmSPYPGIDlsQVYELLekDYRMERP 461
Cdd:cd14152  153 RrenelKLPHDWLcylAPEivrEMTPGKdedclpFSKAADVYAFGTIWYELQA---RDWPLKN--QPAEAL--IWQIGSG 225
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....
gi 62362414  462 EGCPE---------KVYELMRACWQWNPSDRPSFAEIHQAFETM 496
Cdd:cd14152  226 EGMKQvlttislgkEVTEILSACWAFDLEERPSFTLLMDMLEKL 269
STKc_Kin4 cd14076
Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the ...
248-430 4.00e-18

Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Kin4 is a central component of the spindle position checkpoint (SPOC), which monitors spindle position and regulates the mitotic exit network (MEN). Kin4 associates with spindle pole bodies in mother cells to inhibit MEN signaling and delay mitosis until the anaphase nucleus is properly positioned along the mother-bud axis. Kin4 activity is regulated by both the bud neck-associated kinase Elm1 and protein phosphatase 2A. The Kin4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270978 [Multi-domain]  Cd Length: 270  Bit Score: 85.61  E-value: 4.00e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGvWKK------YSLTVAVKTLKEDTMEVE----EFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEF 317
Cdd:cd14076    9 LGEGEFGKVKLG-WPLpkanhrSGVQVAIKLIRRDTQQENcqtsKIMREINILKGLTHPNIVRLLDVLKTKKYIGIVLEF 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  318 MTYGNLLDYLRECNRQEVNAVVLLYmaTQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR---LMTGDTYT 394
Cdd:cd14076   88 VSGGELFDYILARRRLKDSVACRLF--AQLISGVAYLHKKGVVHRDLKLENLLLDKNRNLVITDFGFANtfdHFNGDLMS 165
                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 62362414  395 AHAGAkfPIkWTAPESLAYNKF--SIKSDVWAFGVLLW 430
Cdd:cd14076  166 TSCGS--PC-YAAPELVVSDSMyaGRKADIWSCGVILY 200
SH2_Src_Src42 cd10370
Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the ...
123-216 4.05e-18

Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the Src non-receptor type tyrosine kinase family of proteins. The integration of receptor tyrosine kinase-induced RAS and Src42 signals by Connector eNhancer of KSR (CNK) as a two-component input is essential for RAF activation in Drosophila. Src42 is present in a wide variety of organisms including: California sea hare, pea aphid, yellow fever mosquito, honey bee, Panamanian leafcutter ant, and sea urchin. Src42 has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its C-terminal tail. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198233  Cd Length: 96  Bit Score: 80.63  E-value: 4.05e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  123 EKHSWYHGPVSRNAAE--YLLSSGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTASDGKLYVSSESRFNTLAELVH 200
Cdd:cd10370    1 EAEPWYFGKIKRIEAEkkLLLPENEHGAFLIRDSESRHNDYSLSVRDGDTVKHYRIRQLDEGGFFIARRTTFRTLQELVE 80
                         90
                 ....*....|....*.
gi 62362414  201 HHSTVADGLITTLHYP 216
Cdd:cd10370   81 HYSKDSDGLCVNLRKP 96
STKc_MELK cd14078
Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; ...
244-489 4.35e-18

Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MELK is a cell cycle dependent protein which functions in cytokinesis, cell cycle, apoptosis, cell proliferation, and mRNA processing. It is found upregulated in many types of cancer cells, playing an indispensable role in cancer cell survival. It makes an attractive target in the design of inhibitors for use in the treatment of a wide range of human cancer. The MELK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270980 [Multi-domain]  Cd Length: 257  Bit Score: 85.13  E-value: 4.35e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  244 MKHKLGGGQYGEVYEGVWKKYSLTVAVK-----TLKEDTMEVEeflKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFM 318
Cdd:cd14078    7 LHETIGSGGFAKVKLATHILTGEKVAIKimdkkALGDDLPRVK---TEIEALKNLSHQHICRLYHVIETDNKIFMVLEYC 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  319 TYGNLLDYLRECNR-QEVNAVVLLymaTQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGL---------SRLM 388
Cdd:cd14078   84 PGGELFDYIVAKDRlSEDEARVFF---RQIVSAVAYVHSQGYAHRDLKPENLLLDEDQNLKLIDFGLcakpkggmdHHLE 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  389 TGDTYTAHAgakfpikwtAPE---SLAYnkFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEKDyRMERPEGCP 465
Cdd:cd14078  161 TCCGSPAYA---------APEliqGKPY--IGSEADVWSMGVLLYALLC-GFLPFDDDNVMALYRKIQSG-KYEEPEWLS 227
                        250       260
                 ....*....|....*....|....
gi 62362414  466 EKVYELMRACWQWNPSDRPSFAEI 489
Cdd:cd14078  228 PSSKLLLDQMLQVDPKKRITVKEL 251
SH2_SLAP cd10344
Src homology 2 domain found in Src-like adaptor proteins; SLAP belongs to the subfamily of ...
112-212 5.66e-18

Src homology 2 domain found in Src-like adaptor proteins; SLAP belongs to the subfamily of adapter proteins that negatively regulate cellular signaling initiated by tyrosine kinases. It has a myristylated N-terminus, SH3 and SH2 domains with high homology to Src family tyrosine kinases, and a unique C-terminal tail, which is important for c-Cbl binding. SLAP negatively regulates platelet-derived growth factor (PDGF)-induced mitogenesis in fibroblasts and regulates F-actin assembly for dorsal ruffles formation. c-Cbl mediated SLAP inhibition towards actin remodeling. Moreover, SLAP enhanced PDGF-induced c-Cbl phosphorylation by SFK. In contrast, SLAP mitogenic inhibition was not mediated by c-Cbl, but it rather involved a competitive mechanism with SFK for PDGF-receptor (PDGFR) association and mitogenic signaling. Accordingly, phosphorylation of the Src mitogenic substrates Stat3 and Shc were reduced by SLAP. Thus, we concluded that SLAP regulates PDGFR signaling by two independent mechanisms: a competitive mechanism for PDGF-induced Src mitogenic signaling and a non-competitive mechanism for dorsal ruffles formation mediated by c-Cbl. SLAP is a hematopoietic adaptor containing Src homology (SH)3 and SH2 motifs and a unique carboxy terminus. Unlike c-Src, SLAP lacks a tyrosine kinase domain. Unlike c-Src, SLAP does not impact resorptive function of mature osteoclasts but induces their early apoptosis. SLAP negatively regulates differentiation of osteoclasts and proliferation of their precursors. Conversely, SLAP decreases osteoclast death by inhibiting activation of caspase 3. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198207  Cd Length: 104  Bit Score: 80.23  E-value: 5.66e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  112 PSNYITPVnsleKHSWYHGPVSRNAAEYLLS--SGINGSFLVRESESSPGQRSISLR-----YEGRVYHYRINTASDGKL 184
Cdd:cd10344    1 PSNYVAKV----YHGWLFEGLSREKAEELLMlpGNQVGSFLIRESETRRGCYSLSVRhrgsqSRDSVKHYRIFRLDNGWF 76
                         90       100
                 ....*....|....*....|....*...
gi 62362414  185 YVSSESRFNTLAELVHHHSTVADGLITT 212
Cdd:cd10344   77 YISPRLTFQCLEDMVNHYSESADGLCCV 104
STKc_CaMKI_beta cd14169
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
243-483 6.46e-18

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-beta subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271071 [Multi-domain]  Cd Length: 277  Bit Score: 85.33  E-value: 6.46e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  243 TMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFL--KEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTY 320
Cdd:cd14169    6 ELKEKLGEGAFSEVVLAQERGSQRLVALKCIPKKALRGKEAMveNEIAVLRRINHENIVSLEDIYESPTHLYLAMELVTG 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  321 GNLLDYLRE-CNRQEVNAVVLLYmatQISSAMEYLEKKNFIHRDLAARNCLVG---ENHLVKVADFGLSRLMTGDTYTAH 396
Cdd:cd14169   86 GELFDRIIErGSYTEKDASQLIG---QVLQAVKYLHQLGIVHRDLKPENLLYAtpfEDSKIMISDFGLSKIEAQGMLSTA 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  397 AGAKfpiKWTAPESLAYNKFSIKSDVWAFGVLLWeIATYGMSPYPGIDLSQVY-ELLEKDYRMERP--EGCPEKVYELMR 473
Cdd:cd14169  163 CGTP---GYVAPELLEQKPYGKAVDVWAIGVISY-ILLCGYPPFYDENDSELFnQILKAEYEFDSPywDDISESAKDFIR 238
                        250
                 ....*....|
gi 62362414  474 ACWQWNPSDR 483
Cdd:cd14169  239 HLLERDPEKR 248
STKc_Pat1_like cd13993
Catalytic domain of Fungal Pat1-like Serine/Threonine kinases; STKs catalyze the transfer of ...
245-488 6.85e-18

Catalytic domain of Fungal Pat1-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Pat1 (also called Ran1), Saccharomyces cerevisiae VHS1 and KSP1, and similar fungal STKs. Pat1 blocks Mei2, an RNA-binding protein which is indispensable in the initiation of meiosis. Pat1 is inactivated and Mei2 activated, which initiates meiosis, under nutrient-deprived conditions through a signaling cascade involving Ste11. Meiosis induced by Pat1 inactivation may show different characteristics than normal meiosis including aberrant positioning of centromeres. VHS1 was identified in a screen for suppressors of cell cycle arrest at the G1/S transition, while KSP1 may be involved in regulating PRP20, which is required for mRNA export and maintenance of nuclear structure. The Pat1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270895 [Multi-domain]  Cd Length: 267  Bit Score: 85.09  E-value: 6.85e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  245 KHKLGGGQYGEVYEGVWKKYSLTVAVKTLK---EDTMEVEEFLKEAAvMKEI-------KHPNLVQLLGVCTREPPFYII 314
Cdd:cd13993    5 ISPIGEGAYGVVYLAVDLRTGRKYAIKCLYksgPNSKDGNDFQKLPQ-LREIdlhrrvsRHPNIITLHDVFETEVAIYIV 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  315 TEFMTYGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHL-VKVADFGLSrlMTGDT- 392
Cdd:cd13993   84 LEYCPNGDLFEAITENRIYVGKTELIKNVFLQLIDAVKHCHSLGIYHRDIKPENILLSQDEGtVKLCDFGLA--TTEKIs 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  393 YTAHAGAKFpikWTAPESLAYNKFSIKS------DVWAFGVLL---------WEIAT---------YGMSPypgiDLSQV 448
Cdd:cd13993  162 MDFGVGSEF---YMAPECFDEVGRSLKGypcaagDIWSLGIILlnltfgrnpWKIASesdpifydyYLNSP----NLFDV 234
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 62362414  449 YELLEKDYrmerpegcpekvYELMRACWQWNPSDRPSFAE 488
Cdd:cd13993  235 ILPMSDDF------------YNLLRQIFTVNPNNRILLPE 262
STKc_Nek3 cd08219
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
273-489 7.19e-18

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek3 is primarily localized in the cytoplasm and shows no cell cycle-dependent changes in its activity. It is present in the axons of neurons and affects morphogenesis and polarity through its regulation of microtubule acetylation. Nek3 modulates the signaling of the prolactin receptor through its activation of Vav2 and contributes to prolactin-mediated motility of breast cancer cells. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173759 [Multi-domain]  Cd Length: 255  Bit Score: 84.64  E-value: 7.19e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  273 LKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDYLRECNRQEVNAVVLLYMATQISSAME 352
Cdd:cd08219   35 LPKSSSAVEDSRKEAVLLAKMKHPNIVAFKESFEADGHLYIVMEYCDGGDLMQKIKLQRGKLFPEDTILQWFVQMCLGVQ 114
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  353 YLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTA--HAGAKFPIKWTAPESLAYNKfsiKSDVWAFGVLLW 430
Cdd:cd08219  115 HIHEKRVLHRDIKSKNIFLTQNGKVKLGDFGSARLLTSPGAYActYVGTPYYVPPEIWENMPYNN---KSDIWSLGCILY 191
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 62362414  431 EIATYGMSPYPGIDLSQVYELLEKDYRmERPEGCPEKVYELMRACWQWNPSDRPSFAEI 489
Cdd:cd08219  192 ELCTLKHPFQANSWKNLILKVCQGSYK-PLPSHYSYELRSLIKQMFKRNPRSRPSATTI 249
STKc_ACVR2 cd14053
Catalytic domain of the Serine/Threonine Kinase, Activin Type II Receptor; STKs catalyze the ...
250-476 8.91e-18

Catalytic domain of the Serine/Threonine Kinase, Activin Type II Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR2 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors, such as ACVR2, are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. ACVR2 acts primarily as the receptors for activins, nodal, myostatin, GDF11, and a subset of BMPs. ACVR2 signaling impacts many cellular and physiological processes including reproductive and gonadal functions, myogenesis, bone remodeling and tooth development, kidney organogenesis, apoptosis, fibrosis, inflammation, and neurogenesis. Vertebrates contain two ACVR2 proteins, ACVR2a (or ActRIIA) and ACVR2b (or ActRIIB). The ACVR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270955 [Multi-domain]  Cd Length: 290  Bit Score: 85.07  E-value: 8.91e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  250 GGQYGEVyegvWK-KYS-LTVAVKTLKEdtMEVEEFLKEAAVMKE--IKHPNLVQLLGVCTR----EPPFYIITEFMTYG 321
Cdd:cd14053    5 RGRFGAV----WKaQYLnRLVAVKIFPL--QEKQSWLTEREIYSLpgMKHENILQFIGAEKHgeslEAEYWLITEFHERG 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  322 NLLDYLREcnrQEVNAVVLLYMATQISSAMEYLE----------KKNFIHRDLAARNCLVGENHLVKVADFGLSRLM--- 388
Cdd:cd14053   79 SLCDYLKG---NVISWNELCKIAESMARGLAYLHedipatngghKPSIAHRDFKSKNVLLKSDLTACIADFGLALKFepg 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  389 --TGDTYtAHAGAKfpiKWTAPESL----AYNKFSIKS-DVWAFGVLLWEIAT-----------YgMSPY-------PGI 443
Cdd:cd14053  156 ksCGDTH-GQVGTR---RYMAPEVLegaiNFTRDAFLRiDMYAMGLVLWELLSrcsvhdgpvdeY-QLPFeeevgqhPTL 230
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|.
gi 62362414  444 DLSQVYELLEKdyrmERPEGCPE--------KVYELMRACW 476
Cdd:cd14053  231 EDMQECVVHKK----LRPQIRDEwrkhpglaQLCETIEECW 267
STKc_nPKC_delta cd05620
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze ...
248-496 8.94e-18

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. It slows down cell proliferation, inducing cell cycle arrest and enhancing cell differentiation. PKC-delta is also involved in the regulation of transcription as well as immune and inflammatory responses. It plays a central role in the genotoxic stress response that leads to DNA damaged-induced apoptosis. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-delta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173710 [Multi-domain]  Cd Length: 316  Bit Score: 85.77  E-value: 8.94e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEI-----KHPNLVQLLGVCTREPPFYIITEFMTYGN 322
Cdd:cd05620    3 LGKGSFGKVLLAELKGKGEYFAVKALKKDVVLIDDDVECTMVEKRVlalawENPFLTHLYCTFQTKEHLFFVMEFLNGGD 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLRECNRQEvnavvlLYMAT----QISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAG 398
Cdd:cd05620   83 LMFHIQDKGRFD------LYRATfyaaEIVCGLQFLHSKGIIYRDLKLDNVMLDRDGHIKIADFGMCKENVFGDNRASTF 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  399 AKFPiKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEKDyRMERPEGCPEKVYELMRACWQW 478
Cdd:cd05620  157 CGTP-DYIAPEILQGLKYTFSVDWWSFGVLLYEMLI-GQSPFHGDDEDELFESIRVD-TPHYPRWITKESKDILEKLFER 233
                        250       260
                 ....*....|....*....|.
gi 62362414  479 NPSDRPSFA---EIHQAFETM 496
Cdd:cd05620  234 DPTRRLGVVgniRGHPFFKTI 254
STKc_TAO2 cd06634
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze ...
247-485 9.14e-18

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human TAO2 is also known as prostate-derived Ste20-like kinase (PSK) and was identified in a screen for overexpressed RNAs in prostate cancer. TAO2 possesses mitogen-activated protein kinase (MAPK) kinase kinase activity and activates both p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating their respective MAP/ERK kinases, MEK3/MEK6 and MKK4/MKK7. It contains a long C-terminal extension with autoinhibitory segments, and is activated by the release of this inhibition and the phosphorylation of its activation loop serine. TAO2 functions as a regulator of actin cytoskeletal and microtubule organization. In addition, it regulates the transforming growth factor-activated kinase 1 (TAK1), which is a MAPKKK that plays an essential role in the signaling pathways of tumor necrosis factor, interleukin 1, and Toll-like receptor. The TAO2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270804 [Multi-domain]  Cd Length: 308  Bit Score: 85.46  E-value: 9.14e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTL----KEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFmTYGN 322
Cdd:cd06634   22 EIGHGSFGAVYFARDVRNNEVVAIKKMsysgKQSNEKWQDIIKEVKFLQKLRHPNTIEYRGCYLREHTAWLVMEY-CLGS 100
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLRECNR--QEVNAVVLLYMATQissAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTgdTYTAHAGAK 400
Cdd:cd06634  101 ASDLLEVHKKplQEVEIAAITHGALQ---GLAYLHSHNMIHRDVKAGNILLTEPGLVKLGDFGSASIMA--PANSFVGTP 175
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  401 FpikWTAPE---SLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQ 477
Cdd:cd06634  176 Y---WMAPEvilAMDEGQYDGKVDVWSLGITCIELAERKPPLFNMNAMSALYHIAQNESPALQSGHWSEYFRNFVDSCLQ 252

                 ....*...
gi 62362414  478 WNPSDRPS 485
Cdd:cd06634  253 KIPQDRPT 260
PTZ00426 PTZ00426
cAMP-dependent protein kinase catalytic subunit; Provisional
236-440 9.72e-18

cAMP-dependent protein kinase catalytic subunit; Provisional


Pssm-ID: 173616 [Multi-domain]  Cd Length: 340  Bit Score: 86.19  E-value: 9.72e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   236 EMERTDITMKHKLGGGQYGEVYEGVWKKYSLT-VAVKTLKEDTM----EVEEFLKEAAVMKEIKHPNLVQLLGVCTREPP 310
Cdd:PTZ00426   26 KMKYEDFNFIRTLGTGSFGRVILATYKNEDFPpVAIKRFEKSKIikqkQVDHVFSERKILNYINHPFCVNLYGSFKDESY 105
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   311 FYIITEFMTYGNLLDYLREcNRQEVNAVVLLYmATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTG 390
Cdd:PTZ00426  106 LYLVLEFVIGGEFFTFLRR-NKRFPNDVGCFY-AAQIVLIFEYLQSLNIVYRDLKPENLLLDKDGFIKMTDFGFAKVVDT 183
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 62362414   391 DTYTAHAGAKFpikwTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPY 440
Cdd:PTZ00426  184 RTYTLCGTPEY----IAPEILLNVGHGKAADWWTLGIFIYEILV-GCPPF 228
PK_eIF2AK_GCN2_rpt1 cd14012
Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or ...
256-489 9.77e-18

Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: GCN2, protein kinase regulated by RNA (PKR), heme-regulated inhibitor kinase (HRI), and PKR-like endoplasmic reticulum kinase (PERK). GCN2 is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kappaB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. The degenerate pseudokinase domain of GCN2 may function as a regulatory domain. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270914 [Multi-domain]  Cd Length: 254  Bit Score: 84.33  E-value: 9.77e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  256 VYEGV--WKKYSLTVAVKTLKEDTmevEEFLKEAAV-------MKEIKHPNLVQLLGVCTREPPF------YIITEFMTY 320
Cdd:cd14012   12 VYEVVldNSKKPGKFLTSQEYFKT---SNGKKQIQLlekelesLKKLRHPNLVSYLAFSIERRGRsdgwkvYLLTEYAPG 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  321 GNLLDYLRECNrqEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHL---VKVADFGLSRLMTGDTYTAHA 397
Cdd:cd14012   89 GSLSELLDSVG--SVPLDTARRWTLQLLEALEYLHRNGVVHKSLHAGNVLLDRDAGtgiVKLTDYSLGKTLLDMCSRGSL 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  398 GAKFPIKWTAPE-SLAYNKFSIKSDVWAFGVLLWEIATygmspypGIDLSQVYELLekDYRMErPEGCPEKVYELMRACW 476
Cdd:cd14012  167 DEFKQTYWLPPElAQGSKSPTRKTDVWDLGLLFLQMLF-------GLDVLEKYTSP--NPVLV-SLDLSASLQDFLSKCL 236
                        250
                 ....*....|...
gi 62362414  477 QWNPSDRPSFAEI 489
Cdd:cd14012  237 SLDPKKRPTALEL 249
PKc_like cd13968
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ...
248-383 1.08e-17

Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large family of typical PKs that includes serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins, as well as pseudokinases that lack crucial residues for catalytic activity and/or ATP binding. It also includes phosphoinositide 3-kinases (PI3Ks), aminoglycoside 3'-phosphotransferases (APHs), choline kinase (ChoK), Actin-Fragmin Kinase (AFK), and the atypical RIO and Abc1p-like protein kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to their target substrates; these include serine/threonine/tyrosine residues in proteins for typical or atypical PKs, the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives for PI3Ks, the 4-hydroxyl of PtdIns for PI4Ks, and other small molecule substrates for APH/ChoK and similar proteins such as aminoglycosides, macrolides, choline, ethanolamine, and homoserine.


Pssm-ID: 270870 [Multi-domain]  Cd Length: 136  Bit Score: 80.56  E-value: 1.08e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFL-KEAAVMKEIK--HPNLVQLLGVCTREPPFYIITEFMTYGNLL 324
Cdd:cd13968    1 MGEGASAKVFWAEGECTTIGVAVKIGDDVNNEEGEDLeSEMDILRRLKglELNIPKVLVTEDVDGPNILLMELVKGGTLI 80
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 62362414  325 DYLRECNRQEVNAVVLLYmatQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFG 383
Cdd:cd13968   81 AYTQEEELDEKDVESIMY---QLAECMRLLHSFHLIHRDLNNDNILLSEDGNVKLIDFG 136
STKc_PLK4 cd14186
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the ...
241-489 1.12e-17

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK4, also called SAK or STK18, is structurally different from other PLKs in that it contains only one polo box that can form two adjacent polo boxes and a functional PDB by homodimerization. It is required for late mitotic progression, cell survival, and embryonic development. It localizes to centrosomes and is required for centriole duplication and chromosomal stability. Overexpression of PLK4 may be associated with colon tumors. The PLK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271088 [Multi-domain]  Cd Length: 256  Bit Score: 84.14  E-value: 1.12e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  241 DITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTME----VEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITE 316
Cdd:cd14186    2 DFKVLNLLGKGSFACVYRARSLHTGLEVAIKMIDKKAMQkagmVQRVRNEVEIHCQLKHPSILELYNYFEDSNYVYLVLE 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  317 FMTYGNLLDYLRECNR--QEVNAVVLLYmatQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRL--MTGDT 392
Cdd:cd14186   82 MCHNGEMSRYLKNRKKpfTEDEARHFMH---QIVTGMLYLHSHGILHRDLTLSNLLLTRNMNIKIADFGLATQlkMPHEK 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  393 YTAHAGAKfpiKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYpgiDLSQVYELLEK----DYRMerPEGCPEKV 468
Cdd:cd14186  159 HFTMCGTP---NYISPEIATRSAHGLESDVWSLGCMFYTLLV-GRPPF---DTDTVKNTLNKvvlaDYEM--PAFLSREA 229
                        250       260
                 ....*....|....*....|.
gi 62362414  469 YELMRACWQWNPSDRPSFAEI 489
Cdd:cd14186  230 QDLIHQLLRKNPADRLSLSSV 250
SH2_Src_Frk cd10369
Src homology 2 (SH2) domain found in the Fyn-related kinase (Frk); Frk is a member of the Src ...
123-216 1.22e-17

Src homology 2 (SH2) domain found in the Fyn-related kinase (Frk); Frk is a member of the Src non-receptor type tyrosine kinase family of proteins. The Frk subfamily is composed of Frk/Rak and Iyk/Bsk/Gst. It is expressed primarily epithelial cells. Frk is a nuclear protein and may function during G1 and S phase of the cell cycle and suppress growth. Unlike the other Src members it lacks a glycine at position 2 of SH4 which is important for addition of a myristic acid moiety that is involved in targeting Src PTKs to cellular membranes. FRK and SHB exert similar effects when overexpressed in rat phaeochromocytoma (PC12) and beta-cells, where both induce PC12 cell differentiation and beta-cell proliferation. Under conditions that cause beta-cell degeneration these proteins augment beta-cell apoptosis. The FRK-SHB responses involve FAK and insulin receptor substrates (IRS) -1 and -2. Frk has been demonstrated to interact with retinoblastoma protein. Frk regulates PTEN protein stability by phosphorylating PTEN, which in turn prevents PTEN degradation. Frk also plays a role in regulation of embryonal pancreatic beta cell formation. Frk has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its activation loop. The tryosine involved is at the same site as the tyrosine involved in the autophosphorylation of Src. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199831  Cd Length: 96  Bit Score: 79.15  E-value: 1.22e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  123 EKHSWYHGPVSRNAAE--YLLSSGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTASDGKLYVSSESRFNTLAELVH 200
Cdd:cd10369    1 QAEPWFFGAIKRADAEkqLLYSENQTGAFLIRESESQKGEFSLSVLDGGVVKHYRIRRLDEGGFFLTRRKTFSTLNEFVN 80
                         90
                 ....*....|....*.
gi 62362414  201 HHSTVADGLITTLHYP 216
Cdd:cd10369   81 YYTTTSDGLCVKLGKP 96
STKc_PAK2 cd06655
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the ...
243-491 1.37e-17

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK2 plays a role in pro-apoptotic signaling. It is cleaved and activated by caspases leading to morphological changes during apoptosis. PAK2 is also activated in response to a variety of stresses including DNA damage, hyperosmolarity, serum starvation, and contact inhibition, and may play a role in coordinating the stress response. PAK2 also contributes to cancer cell invasion through a mechanism distinct from that of PAK1. It belongs to the group I PAKs, which contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132986 [Multi-domain]  Cd Length: 296  Bit Score: 84.78  E-value: 1.37e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  243 TMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFL-KEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYG 321
Cdd:cd06655   22 TRYEKIGQGASGTVFTAIDVATGQEVAIKQINLQKQPKKELIiNEILVMKELKNPNIVNFLDSFLVGDELFVVMEYLAGG 101
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  322 NLLDYLRECNRQEVNAVVLLYMATQissAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKF 401
Cdd:cd06655  102 SLTDVVTETCMDEAQIAAVCRECLQ---ALEFLHANQVIHRDIKSDNVLLGMDGSVKLTDFGFCAQITPEQSKRSTMVGT 178
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  402 PIkWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEKD--YRMERPEGCPEKVYELMRACWQWN 479
Cdd:cd06655  179 PY-WMAPEVVTRKAYGPKVDIWSLGIMAIEMVE-GEPPYLNENPLRALYLIATNgtPELQNPEKLSPIFRDFLNRCLEMD 256
                        250
                 ....*....|..
gi 62362414  480 PSDRPSFAEIHQ 491
Cdd:cd06655  257 VEKRGSAKELLQ 268
STKc_TAO1 cd06635
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 1; STKs catalyze ...
247-489 1.43e-17

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO1 is sometimes referred to as prostate-derived sterile 20-like kinase 2 (PSK2). TAO1 activates the p38 MAPK through direct interaction with and activation of MEK3. TAO1 is highly expressed in the brain and may play a role in neuronal apoptosis. TAO1 interacts with the checkpoint proteins BubR1 and Mad2, and plays an important role in regulating mitotic progression, which is required for both chromosome congression and checkpoint-induced anaphase delay. TAO1 may play a role in protecting genomic stability. TAO proteins possess MAPK kinase kinase activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The TAO1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270805 [Multi-domain]  Cd Length: 317  Bit Score: 85.10  E-value: 1.43e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTL----KEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFmTYGN 322
Cdd:cd06635   32 EIGHGSFGAVYFARDVRTSEVVAIKKMsysgKQSNEKWQDIIKEVKFLQRIKHPNSIEYKGCYLREHTAWLVMEY-CLGS 110
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLRECNR--QEVNAVVLLYMATQissAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTgdTYTAHAGAK 400
Cdd:cd06635  111 ASDLLEVHKKplQEIEIAAITHGALQ---GLAYLHSHNMIHRDIKAGNILLTEPGQVKLADFGSASIAS--PANSFVGTP 185
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  401 FpikWTAPE---SLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQ 477
Cdd:cd06635  186 Y---WMAPEvilAMDEGQYDGKVDVWSLGITCIELAERKPPLFNMNAMSALYHIAQNESPTLQSNEWSDYFRNFVDSCLQ 262
                        250
                 ....*....|..
gi 62362414  478 WNPSDRPSFAEI 489
Cdd:cd06635  263 KIPQDRPTSEEL 274
STKc_nPKC_eta cd05590
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta; STKs catalyze the ...
248-483 1.80e-17

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-eta is predominantly expressed in squamous epithelia, where it plays a crucial role in the signaling of cell-type specific differentiation. It is also expressed in pro-B cells and early-stage thymocytes, and acts as a key regulator in early B-cell development. PKC-eta increases glioblastoma multiforme (GBM) proliferation and resistance to radiation, and is being developed as a therapeutic target for the management of GBM. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-eta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270742 [Multi-domain]  Cd Length: 323  Bit Score: 84.96  E-value: 1.80e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM----EVEEFLKEAAVMK-EIKHPNLVQLLgVCTREPP-FYIITEFMTYG 321
Cdd:cd05590    3 LGKGSFGKVMLARLKESGRLYAVKVLKKDVIlqddDVECTMTEKRILSlARNHPFLTQLY-CCFQTPDrLFFVMEFVNGG 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  322 NLLDYLRECNR-QEVNAVvllYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR--LMTGDTYTAHAG 398
Cdd:cd05590   82 DLMFHIQKSRRfDEARAR---FYAAEITSALMFLHDKGIIYRDLKLDNVLLDHEGHCKLADFGMCKegIFNGKTTSTFCG 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  399 AKfpiKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEKDyRMERPEGCPEKVYELMRACWQW 478
Cdd:cd05590  159 TP---DYIAPEILQEMLYGPSVDWWAMGVLLYEMLC-GHAPFEAENEDDLFEAILND-EVVYPTWLSQDAVDILKAFMTK 233

                 ....*
gi 62362414  479 NPSDR 483
Cdd:cd05590  234 NPTMR 238
STKc_CCRK cd07832
Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the ...
247-432 2.35e-17

Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CCRK was previously called p42. It is a Cyclin-Dependent Kinase (CDK)-Activating Kinase (CAK) which is essential for the activation of CDK2. It is indispensable for cell growth and has been implicated in the progression of glioblastoma multiforme. In the heart, a splice variant of CCRK with a different C-terminal half is expressed; this variant promotes cardiac cell growth and survival and is significantly down-regulated during the development of heart failure. The CCRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270826 [Multi-domain]  Cd Length: 287  Bit Score: 83.92  E-value: 2.35e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTL----KEDTMEvEEFLKEAAVMKEIK-HPNLVQLLGVCTREPPFYIITEFMTyG 321
Cdd:cd07832    7 RIGEGAHGIVFKAKDRETGETVALKKValrkLEGGIP-NQALREIKALQACQgHPYVVKLRDVFPHGTGFVLVFEYML-S 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  322 NLLDYLRECNRQEVNAVVLLYMAtQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDT---YTAHAG 398
Cdd:cd07832   85 SLSEVLRDEERPLTEAQVKRYMR-MLLKGVAYMHANRIMHRDLKPANLLISSTGVLKIADFGLARLFSEEDprlYSHQVA 163
                        170       180       190
                 ....*....|....*....|....*....|....*
gi 62362414  399 AKFpikWTAPESL-AYNKFSIKSDVWAFGVLLWEI 432
Cdd:cd07832  164 TRW---YRAPELLyGSRKYDEGVDLWAVGCIFAEL 195
STKc_STK33 cd14097
Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the ...
247-454 2.57e-17

Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK33 is highly expressed in the testis and is present in low levels in most tissues. It may be involved in spermatogenesis and organ ontogenesis. It interacts with and phosphorylates vimentin and may be involved in regulating intermediate filament cytoskeletal dynamics. Its role in promoting the cell viability of KRAS-dependent cancer cells is under debate; some studies have found STK33 to promote cancer cell viability, while other studies have found it to be non-essential. KRAS is the most commonly mutated human oncogene, thus, studies on the role of STK33 in KRAS mutant cancer cells are important. The STK33 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270999 [Multi-domain]  Cd Length: 266  Bit Score: 83.37  E-value: 2.57e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTL---KEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNL 323
Cdd:cd14097    8 KLGQGSFGVVIEATHKETQTKWAIKKInreKAGSSAVKLLEREVDILKHVNHAHIIHLEEVFETPKRMYLVMELCEDGEL 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  324 ---LDYLRECNRQEVNAVVllymaTQISSAMEYLEKKNFIHRDLAARNCLVGENHL-------VKVADFGLSRLMTG--- 390
Cdd:cd14097   88 kelLLRKGFFSENETRHII-----QSLASAVAYLHKNDIVHRDLKLENILVKSSIIdnndklnIKVTDFGLSVQKYGlge 162
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 62362414  391 DTYTAHAGAkfPIkWTAPESLAYNKFSIKSDVWAFGVLLWeIATYGMSPYPGIDLSQVYELLEK 454
Cdd:cd14097  163 DMLQETCGT--PI-YMAPEVISAHGYSQQCDIWSIGVIMY-MLLCGEPPFVAKSEEKLFEEIRK 222
STKc_CDK4_6_like cd07838
Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; ...
248-432 2.97e-17

Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 and CDK6 partner with D-type cyclins to regulate the early G1 phase of the cell cycle. They are the first kinases activated by mitogenic signals to release cells from the G0 arrested state. CDK4 and CDK6 are both expressed ubiquitously, associate with all three D cyclins (D1, D2 and D3), and phosphorylate the retinoblastoma (pRb) protein. They are also regulated by the INK4 family of inhibitors which associate with either the CDK alone or the CDK/cyclin complex. CDK4 and CDK6 show differences in subcellular localization, sensitivity to some inhibitors, timing in activation, tumor selectivity, and possibly substrate profiles. Although CDK4 and CDK6 seem to show some redundancy, they also have discrete, nonoverlapping functions. CDK6 plays an important role in cell differentiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK4/6-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270831 [Multi-domain]  Cd Length: 287  Bit Score: 83.48  E-value: 2.97e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLK----EDTMEVEeFLKEAAVMKEIK---HPNLVQLLGVC-----TREPPFYIIT 315
Cdd:cd07838    7 IGEGAYGTVYKARDLQDGRFVALKKVRvplsEEGIPLS-TIREIALLKQLEsfeHPNVVRLLDVChgprtDRELKLTLVF 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  316 EFMTYgNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRlmtgdTYTA 395
Cdd:cd07838   86 EHVDQ-DLATYLDKCPKPGLPPETIKDLMRQLLRGLDFLHSHRIVHRDLKPQNILVTSDGQVKLADFGLAR-----IYSF 159
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 62362414  396 HAgAKFPIKWT----APESLAYNKFSIKSDVWAFGVLLWEI 432
Cdd:cd07838  160 EM-ALTSVVVTlwyrAPEVLLQSSYATPVDMWSVGCIFAEL 199
STKc_BMPR1a cd14220
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IA Receptor; ...
247-496 2.97e-17

Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IA Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR1a, also called Activin receptor-Like Kinase 3 (ALK3), functions as a receptor for bone morphogenetic proteins (BMPs), which are involved in the regulation of cell proliferation, survival, differentiation, and apoptosis. BMPs are able to induce bone, cartilage, ligament, and tendon formation, and may play roles in bone diseases and tumors. Germline mutations in BMPR1a are associated with an increased risk to Juvenile Polyposis Syndrome, a hamartomatous disorder that may lead to gastrointestinal cancer. BMPR1a may also play an indirect role in the development of hematopoietic stem cells (HSCs) as osteoblasts are a major component of the HSC niche within the bone marrow. BMPR1a belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like BMPR1a, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The BMPR1a subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271122 [Multi-domain]  Cd Length: 287  Bit Score: 83.55  E-value: 2.97e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSltVAVKTLKedTMEVEEFLKEAAVMKEI--KHPNLVQLL-------GVCTReppFYIITEF 317
Cdd:cd14220    2 QIGKGRYGEVWMGKWRGEK--VAVKVFF--TTEEASWFRETEIYQTVlmRHENILGFIaadikgtGSWTQ---LYLITDY 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  318 MTYGNLLDYLReCNRQEVNAvvLLYMATQISSAMEYLE--------KKNFIHRDLAARNCLVGENHLVKVADFGLSRLMT 389
Cdd:cd14220   75 HENGSLYDFLK-CTTLDTRA--LLKLAYSAACGLCHLHteiygtqgKPAIAHRDLKSKNILIKKNGTCCIADLGLAVKFN 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  390 GDTY------TAHAGAKfpiKWTAP----ESLAYNKFS--IKSDVWAFGVLLWEIA----------TYGMSPYPGIDLSQ 447
Cdd:cd14220  152 SDTNevdvplNTRVGTK---RYMAPevldESLNKNHFQayIMADIYSFGLIIWEMArrcvtggiveEYQLPYYDMVPSDP 228
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 62362414  448 VYELLEKDYRME--RP--------EGCPEKVYELMRACWQWNPSDRPSFAEIHQAFETM 496
Cdd:cd14220  229 SYEDMREVVCVKrlRPtvsnrwnsDECLRAVLKLMSECWAHNPASRLTALRIKKTLAKM 287
STKc_DAPK cd14105
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase; STKs ...
244-450 3.75e-17

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK1 is the prototypical member of the subfamily and is also simply referred to as DAPK. DAPK2 is also called DAPK-related protein 1 (DRP-1), while DAPK3 has also been named DAP-like kinase (DLK) and zipper-interacting protein kinase (ZIPk). These proteins are ubiquitously expressed in adult tissues, are capable of cross talk with each other, and may act synergistically in regulating cell death. The DAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271007 [Multi-domain]  Cd Length: 269  Bit Score: 82.92  E-value: 3.75e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  244 MKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEV-------EEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITE 316
Cdd:cd14105    9 IGEELGSGQFAVVKKCREKSTGLEYAAKFIKKRRSKAsrrgvsrEDIEREVSILRQVLHPNIITLHDVFENKTDVVLILE 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  317 FMTYGNLLDYL--RECNRQEvNAVVLLymaTQISSAMEYLEKKNFIHRDLAARNCLVGE----NHLVKVADFGLS-RLMT 389
Cdd:cd14105   89 LVAGGELFDFLaeKESLSEE-EATEFL---KQILDGVNYLHTKNIAHFDLKPENIMLLDknvpIPRIKLIDFGLAhKIED 164
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 62362414  390 GDTYTAHAGAKfpiKWTAPESLAYNKFSIKSDVWAFGVLLWeIATYGMSPYPGIDLSQVYE 450
Cdd:cd14105  165 GNEFKNIFGTP---EFVAPEIVNYEPLGLEADMWSIGVITY-ILLSGASPFLGDTKQETLA 221
STKc_PCTAIRE2 cd07872
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-2 kinase; STKs catalyze the transfer ...
247-442 3.85e-17

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-2 is specifically expressed in neurons in the central nervous system, mainly in terminally differentiated neurons. It associates with Trap (Tudor repeat associator with PCTAIRE-2) and could play a role in regulating mitochondrial function in neurons. PCTAIRE-2 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143377 [Multi-domain]  Cd Length: 309  Bit Score: 83.50  E-value: 3.85e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGvwkKYSLTVAVKTLKEDTMEVEE-----FLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTyG 321
Cdd:cd07872   13 KLGEGTYATVFKG---RSKLTENLVALKEIRLEHEEgapctAIREVSLLKDLKHANIVTLHDIVHTDKSLTLVFEYLD-K 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  322 NLLDYLRECNR--QEVNAVVLLYmatQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTaHAGA 399
Cdd:cd07872   89 DLKQYMDDCGNimSMHNVKIFLY---QILRGLAYCHRRKVLHRDLKPQNLLINERGELKLADFGLARAKSVPTKT-YSNE 164
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 62362414  400 KFPIKWTAPES-LAYNKFSIKSDVWAFGVLLWEIATyGMSPYPG 442
Cdd:cd07872  165 VVTLWYRPPDVlLGSSEYSTQIDMWGVGCIFFEMAS-GRPLFPG 207
STKc_Yank1 cd05578
Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the ...
279-483 3.86e-17

Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily contains uncharacterized STKs with similarity to the human protein designated as Yank1 or STK32A. The Yank1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270730 [Multi-domain]  Cd Length: 257  Bit Score: 82.69  E-value: 3.86e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  279 EVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDYL-RECNRQEvnAVVLLYMAtQISSAMEYLEKK 357
Cdd:cd05578   43 SVRNVLNELEILQELEHPFLVNLWYSFQDEEDMYMVVDLLLGGDLRYHLqQKVKFSE--ETVKFYIC-EIVLALDYLHSK 119
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  358 NFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTY-TAHAGAKfpiKWTAPESLAYNKFSIKSDVWAFGVLLWEIAtYG 436
Cdd:cd05578  120 NIIHRDIKPDNILLDEQGHVHITDFNIATKLTDGTLaTSTSGTK---PYMAPEVFMRAGYSFAVDWWSLGVTAYEML-RG 195
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 62362414  437 MSPYPGID--LSQVYELLEKDYRMERPEGCPEKVYELMRACWQWNPSDR 483
Cdd:cd05578  196 KRPYEIHSrtSIEEIRAKFETASVLYPAGWSEEAIDLINKLLERDPQKR 244
STKc_PCTAIRE_like cd07844
Catalytic domain of PCTAIRE-like Serine/Threonine Kinases; STKs catalyze the transfer of the ...
246-457 3.94e-17

Catalytic domain of PCTAIRE-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-like proteins show unusual expression patterns with high levels in post-mitotic tissues, suggesting that they may be involved in regulating post-mitotic cellular events. They share sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The association of PCTAIRE-like proteins with cyclins has not been widely studied, although PFTAIRE-1 has been shown to function as a CDK which is regulated by cyclin D3 as well as the membrane-associated cyclin Y. The PCTAIRE-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270835 [Multi-domain]  Cd Length: 286  Bit Score: 83.20  E-value: 3.94e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  246 HKLGGGQYGEVYEGVWKkysLTVAVKTLKEDTMEVEE-----FLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMtY 320
Cdd:cd07844    6 DKLGEGSYATVYKGRSK---LTGQLVALKEIRLEHEEgapftAIREASLLKDLKHANIVTLHDIIHTKKTLTLVFEYL-D 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  321 GNLLDYLRECNR--QEVNAVVLLYmatQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRlmtgdtytahag 398
Cdd:cd07844   82 TDLKQYMDDCGGglSMHNVRLFLF---QLLRGLAYCHQRRVLHRDLKPQNLLISERGELKLADFGLAR------------ 146
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 62362414  399 AK-FPIK---------WTAPES--LAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIdlSQVYELLEKDYR 457
Cdd:cd07844  147 AKsVPSKtysnevvtlWYRPPDvlLGSTEYSTSLDMWGVGCIFYEMAT-GRPLFPGS--TDVEDQLHKIFR 214
STKc_IKK_beta cd14038
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
247-440 4.00e-17

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKbeta is involved in the classical pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The classical pathway regulates the majority of genes activated by NF-kB including those encoding cytokines, chemokines, leukocyte adhesion molecules, and anti-apoptotic factors. It involves NEMO (NF-kB Essential MOdulator)- and IKKbeta-dependent phosphorylation and degradation of the Inhibitor of NF-kB (IkB), which liberates NF-kB dimers (typified by the p50-p65 heterodimer) from an inactive IkB/dimeric NF-kB complex, enabling them to migrate to the nucleus where they regulate gene transcription. The IKKbeta subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270940 [Multi-domain]  Cd Length: 290  Bit Score: 83.09  E-value: 4.00e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLKED--TMEVEEFLKEAAVMKEIKHPNLV-------QLLGVCTREPPFyIITEF 317
Cdd:cd14038    1 RLGTGGFGNVLRWINQETGEQVAIKQCRQElsPKNRERWCLEIQIMKRLNHPNVVaardvpeGLQKLAPNDLPL-LAMEY 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  318 MTYGNLLDYLRE----CNRQEVNAVVLLymaTQISSAMEYLEKKNFIHRDLAARNCLV--GENHLV-KVADFGLSR-LMT 389
Cdd:cd14038   80 CQGGDLRKYLNQfencCGLREGAILTLL---SDISSALRYLHENRIIHRDLKPENIVLqqGEQRLIhKIIDLGYAKeLDQ 156
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 62362414  390 GDTYTAHAGAkfpIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPY 440
Cdd:cd14038  157 GSLCTSFVGT---LQYLAPELLEQQKYTVTVDYWSFGTLAFECIT-GFRPF 203
STKc_CDK5 cd07839
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 5; STKs ...
231-445 4.01e-17

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK5 is unusual in that it is regulated by non-cyclin proteins, p35 and p39. It is highly expressed in the nervous system and is critical in normal neural development and function. It plays a role in neuronal migration and differentiation, and is also important in synaptic plasticity and learning. CDK5 also participates in protecting against cell death and promoting angiogenesis. Impaired CDK5 activity is implicated in Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease and acute neuronal injury. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143344 [Multi-domain]  Cd Length: 284  Bit Score: 83.25  E-value: 4.01e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  231 NYDKWEmertditmkhKLGGGQYGEVYEGVWKKYSLTVAVK--TLKEDTMEVEEF-LKEAAVMKEIKHPNLVQLLGVCTR 307
Cdd:cd07839    1 KYEKLE----------KIGEGTYGTVFKAKNRETHEIVALKrvRLDDDDEGVPSSaLREICLLKELKHKNIVRLYDVLHS 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  308 EPPFYIITEFMTYgNLLDYLRECNRQEVNAVVLLYMaTQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRL 387
Cdd:cd07839   71 DKKLTLVFEYCDQ-DLKKYFDSCNGDIDPEIVKSFM-FQLLKGLAFCHSHNVLHRDLKPQNLLINKNGELKLADFGLARA 148
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 62362414  388 MtGDTYTAHAGAKFPIKWTAPESLAYNK-FSIKSDVWAFGVLLWEIATYGMSPYPGIDL 445
Cdd:cd07839  149 F-GIPVRCYSAEVVTLWYRPPDVLFGAKlYSTSIDMWSAGCIFAELANAGRPLFPGNDV 206
STKc_nPKC_theta_like cd05592
Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and ...
248-450 4.05e-17

Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. There are four nPKC isoforms, delta, epsilon, eta, and theta. The nPKC-theta-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270744 [Multi-domain]  Cd Length: 320  Bit Score: 83.59  E-value: 4.05e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM----EVEEFLKEAAVMK-EIKHPNLVQLLGVCTREPPFYIITEFMTYGN 322
Cdd:cd05592    3 LGKGSFGKVMLAELKGTNQYFAIKALKKDVVleddDVECTMIERRVLAlASQHPFLTHLFCTFQTESHLFFVMEYLNGGD 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLRECNRQEVNAVVllYMATQISSAMEYLEKKNFIHRDLAARN-CLVGENHlVKVADFGLSRL-MTGDTyTAHAGAK 400
Cdd:cd05592   83 LMFHIQQSGRFDEDRAR--FYGAEIICGLQFLHSRGIIYRDLKLDNvLLDREGH-IKIADFGMCKEnIYGEN-KASTFCG 158
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 62362414  401 FPiKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYE 450
Cdd:cd05592  159 TP-DYIAPEILKGQKYNQSVDWWSFGVLLYEMLI-GQSPFHGEDEDELFW 206
STKc_myosinIII_N_like cd06608
N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze ...
249-433 4.30e-17

N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class III myosins are motor proteins with an N-terminal kinase catalytic domain and a C-terminal actin-binding motor domain. Class III myosins are present in the photoreceptors of invertebrates and vertebrates and in the auditory hair cells of mammals. The kinase domain of myosin III can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, and can autophosphorylate the C-terminal motor domain. Myosin III may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. It may also function as a cargo carrier during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The Drosophila class III myosin, called NinaC (Neither inactivation nor afterpotential protein C), is critical in normal adaptation and termination of photoresponse. Vertebrates contain two isoforms of class III myosin, IIIA and IIIB. This subfamily also includes mammalian NIK-like embryo-specific kinase (NESK), Traf2- and Nck-interacting kinase (TNIK), and mitogen-activated protein kinase (MAPK) kinase kinase kinase 4/6. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The class III myosin-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270785 [Multi-domain]  Cd Length: 275  Bit Score: 82.74  E-value: 4.30e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  249 GGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEI-KHPNLVQLLGV------CTREPPFYIITEFMTYG 321
Cdd:cd06608   15 GEGTYGKVYKARHKKTGQLAAIKIMDIIEDEEEEIKLEINILRKFsNHPNIATFYGAfikkdpPGGDDQLWLVMEYCGGG 94
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  322 ---NLLDYLRECNRQEVNAVVLlYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTG-----DTY 393
Cdd:cd06608   95 svtDLVKGLRKKGKRLKEEWIA-YILRETLRGLAYLHENKVIHRDIKGQNILLTEEAEVKLVDFGVSAQLDStlgrrNTF 173
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 62362414  394 TahaGAKFpikWTAPESLAYNK-----FSIKSDVWAFGVLLWEIA 433
Cdd:cd06608  174 I---GTPY---WMAPEVIACDQqpdasYDARCDVWSLGITAIELA 212
STKc_CaMKII cd14086
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
244-488 4.55e-17

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type II; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKs contain an N-terminal catalytic domain followed by a regulatory domain that harbors a CaM binding site. In addition, CaMKII contains a C-terminal association domain that facilitates oligomerization. There are four CaMKII proteins (alpha, beta, gamma, delta) encoded by different genes; each gene undergoes alternative splicing to produce more than 30 isoforms. CaMKII-alpha and -beta are enriched in neurons while CaMKII-gamma and -delta are predominant in myocardium. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. It is a major component of the postsynaptic density and is critical in regulating synaptic plasticity including long-term potentiation. It is critical in regulating ion channels and proteins involved in myocardial excitation-contraction and excitation-transcription coupling. Excessive CaMKII activity promotes processes that contribute to heart failure and arrhythmias. The CaMKII subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270988 [Multi-domain]  Cd Length: 292  Bit Score: 83.24  E-value: 4.55e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  244 MKHKLGGGQYGEVYEGVWKKYSLTVAVK---TLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTY 320
Cdd:cd14086    5 LKEELGKGAFSVVRRCVQKSTGQEFAAKiinTKKLSARDHQKLEREARICRLLKHPNIVRLHDSISEEGFHYLVFDLVTG 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  321 GNLLDYL--REcNRQEVNAVVLLYmatQISSAMEYLEKKNFIHRDLAARNCLVG---ENHLVKVADFGLSRLMTGDTYTA 395
Cdd:cd14086   85 GELFEDIvaRE-FYSEADASHCIQ---QILESVNHCHQNGIVHRDLKPENLLLAsksKGAAVKLADFGLAIEVQGDQQAW 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  396 HAGAKFPiKWTAPESLAYNKFSIKSDVWAFGVLLWeIATYGMSPYPGIDLSQVY-ELLEKDYRMERPEG---CPEkVYEL 471
Cdd:cd14086  161 FGFAGTP-GYLSPEVLRKDPYGKPVDIWACGVILY-ILLVGYPPFWDEDQHRLYaQIKAGAYDYPSPEWdtvTPE-AKDL 237
                        250
                 ....*....|....*..
gi 62362414  472 MRACWQWNPSDRPSFAE 488
Cdd:cd14086  238 INQMLTVNPAKRITAAE 254
PKc_TOPK cd14001
Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer ...
269-495 5.27e-17

Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer T-cell-originated protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TOPK, also called PDZ-binding kinase (PBK), is activated at the early stage of mitosis and plays a critical role in cytokinesis. It partly functions as a mitogen-activated protein kinase (MAPK) kinase and is capable of phosphorylating p38, JNK1, and ERK2. TOPK also plays a role in DNA damage sensing and repair through its phosphorylation of histone H2AX. It contributes to cancer development and progression by downregulating the function of tumor suppressor p53 and reducing cell-cycle regulatory proteins. TOPK is found highly expressed in breast and skin cancer cells. The TOPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270903 [Multi-domain]  Cd Length: 292  Bit Score: 82.83  E-value: 5.27e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  269 AVKTL-----KEDTMEVEEFLK-EAAVMKEIKHPNLVQLLGVCTREP-PFYIITEF--MTYGNLLDYLRECNRQEVNAVV 339
Cdd:cd14001   32 AVKKInskcdKGQRSLYQERLKeEAKILKSLNHPNIVGFRAFTKSEDgSLCLAMEYggKSLNDLIEERYEAGLGPFPAAT 111
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  340 LLYMATQISSAMEYL--EKKnFIHRDLAARNCLV-GENHLVKVADFG----LSRLMTGDTY-TAHAGAKFPikWTAPESL 411
Cdd:cd14001  112 ILKVALSIARALEYLhnEKK-ILHGDIKSGNVLIkGDFESVKLCDFGvslpLTENLEVDSDpKAQYVGTEP--WKAKEAL 188
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  412 AYNK-FSIKSDVWAFGVLLWEIATYG-----MSPYPGIDLSQVYELLEKDY------RMERP-------EGCPEKVYELM 472
Cdd:cd14001  189 EEGGvITDKADIFAYGLVLWEMMTLSvphlnLLDIEDDDEDESFDEDEEDEeayygtLGTRPalnlgelDDSYQKVIELF 268
                        250       260
                 ....*....|....*....|...
gi 62362414  473 RACWQWNPSDRPSFAEIHQAFET 495
Cdd:cd14001  269 YACTQEDPKDRPSAAHIVEALEA 291
STKc_RSK1_C cd14175
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 1 (also called ...
243-440 5.39e-17

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 1 (also called Ribosomal protein S6 kinase alpha-1 or 90kDa ribosomal protein S6 kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK1 is also called S6K-alpha-1, RPS6KA1, p90RSK1 or MAPK-activated protein kinase 1a (MAPKAPK-1a). It is a component of the insulin transduction pathway, regulating the function of IRS1. It also interacts with PKA and promotes its inactivation. RSK1 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271077 [Multi-domain]  Cd Length: 291  Bit Score: 82.77  E-value: 5.39e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  243 TMKHKLGGGQYGE----VYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAavmkeiKHPNLVQLLGVCTREPPFYIITEFM 318
Cdd:cd14175    4 VVKETIGVGSYSVckrcVHKATNMEYAVKVIDKSKRDPSEEIEILLRYG------QHPNIITLKDVYDDGKHVYLVTELM 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  319 TYGNLLD-YLRECNRQEVNAVVLLYmatQISSAMEYLEKKNFIHRDLAARNCLV----GENHLVKVADFGLSRLMTGDT- 392
Cdd:cd14175   78 RGGELLDkILRQKFFSEREASSVLH---TICKTVEYLHSQGVVHRDLKPSNILYvdesGNPESLRICDFGFAKQLRAENg 154
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 62362414  393 ------YTAHagakfpikWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPY 440
Cdd:cd14175  155 llmtpcYTAN--------FVAPEVLKRQGYDEGCDIWSLGILLYTMLA-GYTPF 199
PknB_PASTA_kin NF033483
Stk1 family PASTA domain-containing Ser/Thr kinase;
247-442 5.57e-17

Stk1 family PASTA domain-containing Ser/Thr kinase;


Pssm-ID: 468045 [Multi-domain]  Cd Length: 563  Bit Score: 85.62  E-value: 5.57e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   247 KLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLK----EAAVMKEIKHPNLVQLLGVCTREPPFYIITEF---MT 319
Cdd:NF033483   14 RIGRGGMAEVYLAKDTRLDRDVAVKVLRPDLARDPEFVArfrrEAQSAASLSHPNIVSVYDVGEDGGIPYIVMEYvdgRT 93
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   320 ygnLLDYLRECNRQEVNAVVllYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYT----- 394
Cdd:NF033483   94 ---LKDYIREHGPLSPEEAV--EIMIQILSALEHAHRNGIVHRDIKPQNILITKDGRVKVTDFGIARALSSTTMTqtnsv 168
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 62362414   395 ---AHagakfpikWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPG 442
Cdd:NF033483  169 lgtVH--------YLSPEQARGGTVDARSDIYSLGIVLYEMLT-GRPPFDG 210
STKc_MAP4K3 cd06645
Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase ...
239-491 6.46e-17

Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. MAP4K3 is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. mTOR regulates ribosome biogenesis and protein translation, and is frequently deregulated in cancer. MAP4Ks are involved in MAPK signaling pathways by activating a MAPK kinase kinase. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. The MAP4K3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270812 [Multi-domain]  Cd Length: 272  Bit Score: 82.40  E-value: 6.46e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  239 RTDITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLK-EDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEF 317
Cdd:cd06645   10 QEDFELIQRIGSGTYGDVYKARNVNTGELAAIKVIKlEPGEDFAVVQQEIIMMKDCKHSNIVAYFGSYLRRDKLWICMEF 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  318 MTYGNLLDYLRECNrqEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHA 397
Cdd:cd06645   90 CGGGSLQDIYHVTG--PLSESQIAYVSRETLQGLYYLHSKGKMHRDIKGANILLTDNGHVKLADFGVSAQITATIAKRKS 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  398 GAKFPIkWTAPESLAYNK---FSIKSDVWAFGVLLWEIATygMSPyPGIDLSQVYELLEKDYRMERPEGCPEKV------ 468
Cdd:cd06645  168 FIGTPY-WMAPEVAAVERkggYNQLCDIWAVGITAIELAE--LQP-PMFDLHPMRALFLMTKSNFQPPKLKDKMkwsnsf 243
                        250       260
                 ....*....|....*....|...
gi 62362414  469 YELMRACWQWNPSDRPSFAEIHQ 491
Cdd:cd06645  244 HHFVKMALTKNPKKRPTAEKLLQ 266
PKc_PBS2_like cd06622
Catalytic domain of fungal PBS2-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ...
247-489 6.54e-17

Catalytic domain of fungal PBS2-like dual-specificity Mitogen-Activated Protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Polymyxin B resistance protein 2 (PBS2) from Saccharomyces cerevisiae, Wis1 from Schizosaccharomyces pombe, and related proteins. PBS2 and Wis1 are components of stress-activated MAPK cascades in budding and fission yeast, respectively. PBS2 is the specific activator of the MAPK Hog1, which plays a central role in the response of budding yeast to stress including exposure to arsenite and hyperosmotic environments. Wis1 phosphorylates and activates the MAPK Sty1 (also called Spc1 or Phh1), which stimulates a transcriptional response to a wide range of cellular insults through the bZip transcription factors Atf1, Pcr1, and Pap1. The PBS2 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132953 [Multi-domain]  Cd Length: 286  Bit Score: 82.59  E-value: 6.54e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAvktLKEDTMEVEE-----FLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYG 321
Cdd:cd06622    8 ELGKGNYGSVYKVLHRPTGVTMA---MKEIRLELDEskfnqIIMELDILHKAVSPYIVDFYGAFFIEGAVYMCMEYMDAG 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  322 NLLD-YLRECNRQEVNAVVLLYMATQISSAMEYL-EKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGA 399
Cdd:cd06622   85 SLDKlYAGGVATEGIPEDVLRRITYAVVKGLKFLkEEHNIIHRDVKPTNVLVNGNGQVKLCDFGVSGNLVASLAKTNIGC 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  400 KfpiKWTAPESL------AYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEKDYRMERPEGCPE---KVYE 470
Cdd:cd06622  165 Q---SYMAPERIksggpnQNPTYTVQSDVWSLGLSILEMAL-GRYPYPPETYANIFAQLSAIVDGDPPTLPSGysdDAQD 240
                        250
                 ....*....|....*....
gi 62362414  471 LMRACWQWNPSDRPSFAEI 489
Cdd:cd06622  241 FVAKCLNKIPNRRPTYAQL 259
STKc_SNRK cd14074
Catalytic domain of the Serine/Threonine Kinase, SNF1-related kinase; STKs catalyze the ...
268-491 7.29e-17

Catalytic domain of the Serine/Threonine Kinase, SNF1-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SNRK is a kinase highly expressed in testis and brain that is found inactive in cells that lack the LKB1 tumour suppressor protein kinase. The regulatory subunits STRAD and MO25 are required for LKB1 to activate SNRK. The SNRK mRNA is increased 3-fold when granule neurons are cultured in low potassium, and may thus play a role in the survival responses in these cells. In some vertebrates, a second SNRK gene (snrkb or snrk-1) has been sequenced and/or identified. Snrk-1 is expressed specifically in embryonic zebrafish vasculature; it plays an essential role in angioblast differentiation, maintenance, and migration. The SNRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270976 [Multi-domain]  Cd Length: 258  Bit Score: 81.69  E-value: 7.29e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  268 VAVKTL---KEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDYLRECNRQEVNAVVLLYMA 344
Cdd:cd14074   31 VAVKVIdktKLDDVSKAHLFQEVRCMKLVQHPNVVRLYEVIDTQTKLYLILELGDGGDMYDYIMKHENGLNEDLARKYFR 110
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  345 tQISSAMEYLEKKNFIHRDLAARNCLVGENH-LVKVADFGLS-RLMTGDTYTAHAGAkfpIKWTAPESL---AYNkfSIK 419
Cdd:cd14074  111 -QIVSAISYCHKLHVVHRDLKPENVVFFEKQgLVKLTDFGFSnKFQPGEKLETSCGS---LAYSAPEILlgdEYD--APA 184
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 62362414  420 SDVWAFGVLLWEIATyGMSPYPGIDLSqvyELLEK--DYRMERPEGCPEKVYELMRACWQWNPSDRPSFAEIHQ 491
Cdd:cd14074  185 VDIWSLGVILYMLVC-GQPPFQEANDS---ETLTMimDCKYTVPAHVSPECKDLIRRMLIRDPKKRASLEEIEN 254
STKc_SGK3 cd05604
Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced ...
248-510 1.01e-16

Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK3 (also called cytokine-independent survival kinase or CISK) is expressed in most tissues and is most abundant in the embryo and adult heart and spleen. It was originally discovered in a screen for antiapoptotic genes. It phosphorylates and inhibits the proapoptotic proteins, Bad and FKHRL1. SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling. The SGK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270755 [Multi-domain]  Cd Length: 326  Bit Score: 82.70  E-value: 1.01e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM----EVEEFLKEAAVM-KEIKHPNLVQLLGVCTREPPFYIITEFMTYGN 322
Cdd:cd05604    4 IGKGSFGKVLLAKRKRDGKYYAVKVLQKKVIlnrkEQKHIMAERNVLlKNVKHPFLVGLHYSFQTTDKLYFVLDFVNGGE 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYL-RECNRQEVNAvvlLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR--LMTGDTYTAHAGA 399
Cdd:cd05604   84 LFFHLqRERSFPEPRA---RFYAAEIASALGYLHSINIVYRDLKPENILLDSQGHIVLTDFGLCKegISNSDTTTTFCGT 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  400 KfpiKWTAPESLAYNKFSIKSDVWAFGVLLWEIaTYGMSPYPGIDLSQVYE-LLEKDYRMeRPeGCPEKVYELMRACWQW 478
Cdd:cd05604  161 P---EYLAPEVIRKQPYDNTVDWWCLGSVLYEM-LYGLPPFYCRDTAEMYEnILHKPLVL-RP-GISLTAWSILEELLEK 234
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 62362414  479 NPSDR----PSFAEI--HQAFETMfqesSISDEVEKEL 510
Cdd:cd05604  235 DRQLRlgakEDFLEIknHPFFESI----NWTDLVQKKI 268
STKc_Nek1 cd08218
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
247-489 1.18e-16

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek1 is associated with centrosomes throughout the cell cycle. It is involved in the formation of primary cilium and in the maintenance of centrosomes. It cycles through the nucleus and may be capable of relaying signals between the cilium and the nucleus. Nek1 is implicated in the development of polycystic kidney disease, which is characterized by benign polycystic tumors formed by abnormal overgrowth of renal epithelial cells. It appears also to be involved in DNA damage response, and may be important for both correct DNA damage checkpoint activation and DNA repair. Nek1 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270858 [Multi-domain]  Cd Length: 256  Bit Score: 81.01  E-value: 1.18e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM---EVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNL 323
Cdd:cd08218    7 KIGEGSFGKALLVKSKEDGKQYVIKEINISKMspkEREESRKEVAVLSKMKHPNIVQYQESFEENGNLYIVMDYCDGGDL 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  324 ---LDYLRECNRQEVNavvLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAK 400
Cdd:cd08218   87 ykrINAQRGVLFPEDQ---ILDWFVQLCLALKHVHDRKILHRDIKSQNIFLTKDGIIKLGDFGIARVLNSTVELARTCIG 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  401 FPIkWTAPESLAYNKFSIKSDVWAFGVLLWEIATygmspypgidLSQVYE------LLEKDYRMERPEGCPEKVYE---L 471
Cdd:cd08218  164 TPY-YLSPEICENKPYNNKSDIWALGCVLYEMCT----------LKHAFEagnmknLVLKIIRGSYPPVPSRYSYDlrsL 232
                        250
                 ....*....|....*...
gi 62362414  472 MRACWQWNPSDRPSFAEI 489
Cdd:cd08218  233 VSQLFKRNPRDRPSINSI 250
STKc_TNIK cd06637
Catalytic domain of the Serine/Threonine Kinase, Traf2- and Nck-Interacting Kinase; STKs ...
248-489 1.34e-16

Catalytic domain of the Serine/Threonine Kinase, Traf2- and Nck-Interacting Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TNIK is an effector of Rap2, a small GTP-binding protein from the Ras family. TNIK specifically activates the c-Jun N-terminal kinase (JNK) pathway and plays a role in regulating the actin cytoskeleton. The TNIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270807 [Multi-domain]  Cd Length: 296  Bit Score: 81.69  E-value: 1.34e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKH-PNLVQLLGVCTREPP------FYIITEFMTY 320
Cdd:cd06637   14 VGNGTYGQVYKGRHVKTGQLAAIKVMDVTGDEEEEIKQEINMLKKYSHhRNIATYYGAFIKKNPpgmddqLWLVMEFCGA 93
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  321 GNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAK 400
Cdd:cd06637   94 GSVTDLIKNTKGNTLKEEWIAYICREILRGLSHLHQHKVIHRDIKGQNVLLTENAEVKLVDFGVSAQLDRTVGRRNTFIG 173
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  401 FPIkWTAPESLAYNK-----FSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEKDYRME-RPEGCPEKVYELMRA 474
Cdd:cd06637  174 TPY-WMAPEVIACDEnpdatYDFKSDLWSLGITAIEMAE-GAPPLCDMHPMRALFLIPRNPAPRlKSKKWSKKFQSFIES 251
                        250
                 ....*....|....*
gi 62362414  475 CWQWNPSDRPSFAEI 489
Cdd:cd06637  252 CLVKNHSQRPSTEQL 266
STKc_PFTAIRE2 cd07870
Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-2 kinase; STKs catalyze the transfer ...
247-454 1.34e-16

Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PFTAIRE-2 is also referred to as ALS2CR7 (amyotrophic lateral sclerosis 2 (juvenile) chromosome region candidate 7). It may be associated with amyotrophic lateral sclerosis 2 (ALS2), an autosomal recessive form of juvenile ALS. The function of PFTAIRE-2 is not yet known. It shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PFTAIRE-2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270852 [Multi-domain]  Cd Length: 286  Bit Score: 81.55  E-value: 1.34e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEF--LKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMtYGNLL 324
Cdd:cd07870    7 KLGEGSYATVYKGISRINGQLVALKVISMKTEEGVPFtaIREASLLKGLKHANIVLLHDIIHTKETLTFVFEYM-HTDLA 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  325 DY-------LRECNrqevnavVLLYMaTQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRL--MTGDTYTa 395
Cdd:cd07870   86 QYmiqhpggLHPYN-------VRLFM-FQLLRGLAYIHGQHILHRDLKPQNLLISYLGELKLADFGLARAksIPSQTYS- 156
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 62362414  396 hagAKFPIKWTAPES--LAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIdlSQVYELLEK 454
Cdd:cd07870  157 ---SEVVTLWYRPPDvlLGATDYSSALDIWGAGCIFIEMLQ-GQPAFPGV--SDVFEQLEK 211
STKc_BMPR1 cd14144
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type I Receptor; ...
246-483 1.66e-16

Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type I Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR1 functions as a receptor for morphogenetic proteins (BMPs), which are involved in the regulation of cell proliferation, survival, differentiation, and apoptosis. BMPs are able to induce bone, cartilage, ligament, and tendon formation, and may play roles in bone diseases and tumors. Vertebrates contain two type I BMP receptors, BMPR1a and BMPR1b. BMPR1 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that also includes TGFbeta, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like BMPR1, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The BMPR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271046 [Multi-domain]  Cd Length: 287  Bit Score: 81.37  E-value: 1.66e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  246 HKLGGGQYGEVYEGVWKKYSltVAVKTLKedTMEVEEFLKEAAVMKEI--KHPNLVQLL-------GVCTReppFYIITE 316
Cdd:cd14144    1 RSVGKGRYGEVWKGKWRGEK--VAVKIFF--TTEEASWFRETEIYQTVlmRHENILGFIaadikgtGSWTQ---LYLITD 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  317 FMTYGNLLDYLReCNrqEVNAVVLLYMATQISSAMEYLE--------KKNFIHRDLAARNCLVGENHLVKVADFGLSRLM 388
Cdd:cd14144   74 YHENGSLYDFLR-GN--TLDTQSMLKLAYSAACGLAHLHteifgtqgKPAIAHRDIKSKNILVKKNGTCCIADLGLAVKF 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  389 TGDTYTAH------AGAKfpiKWTAPE----SLAYNKFS--IKSDVWAFGVLLWEIA----------TYGMSPYPGIDLS 446
Cdd:cd14144  151 ISETNEVDlppntrVGTK---RYMAPEvldeSLNRNHFDayKMADMYSFGLVLWEIArrcisggiveEYQLPYYDAVPSD 227
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*..
gi 62362414  447 QVYELLEKDYRME--RP--------EGCPEKVYELMRACWQWNPSDR 483
Cdd:cd14144  228 PSYEDMRRVVCVErrRPsipnrwssDEVLRTMSKLMSECWAHNPAAR 274
STKc_CaMKI_delta cd14168
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
235-483 1.68e-16

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-delta subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271070 [Multi-domain]  Cd Length: 301  Bit Score: 81.63  E-value: 1.68e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  235 WEMERTDIT----MKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEE--FLKEAAVMKEIKHPNLVQLLGVCTRE 308
Cdd:cd14168    1 WKKQVEDIKkifeFKEVLGTGAFSEVVLAEERATGKLFAVKCIPKKALKGKEssIENEIAVLRKIKHENIVALEDIYESP 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  309 PPFYIITEFMTYGNLLDYLRECN-RQEVNAVVLLymaTQISSAMEYLEKKNFIHRDLAARNCLV---GENHLVKVADFGL 384
Cdd:cd14168   81 NHLYLVMQLVSGGELFDRIVEKGfYTEKDASTLI---RQVLDAVYYLHRMGIVHRDLKPENLLYfsqDEESKIMISDFGL 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  385 SRLM-TGDTYTAHAGAKfpiKWTAPESLAYNKFSIKSDVWAFGVLLWeIATYGMSPYPGIDLSQVYE-LLEKDYRMERP- 461
Cdd:cd14168  158 SKMEgKGDVMSTACGTP---GYVAPEVLAQKPYSKAVDCWSIGVIAY-ILLCGYPPFYDENDSKLFEqILKADYEFDSPy 233
                        250       260
                 ....*....|....*....|...
gi 62362414  462 -EGCPEKVYELMRACWQWNPSDR 483
Cdd:cd14168  234 wDDISDSAKDFIRNLMEKDPNKR 256
STKc_MAPK cd07834
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs ...
245-509 1.68e-16

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Typical MAPK pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPK kinase (MAP2K or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAP3K or MKKK). Each cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. There are three typical MAPK subfamilies: Extracellular signal-Regulated Kinase (ERK), c-Jun N-terminal Kinase (JNK), and p38. Some MAPKs are atypical in that they are not regulated by MAP2Ks. These include MAPK4, MAPK6, NLK, and ERK7. The MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270828 [Multi-domain]  Cd Length: 329  Bit Score: 82.19  E-value: 1.68e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  245 KHKLGGGQYGEVYEGVWKKYSLTVAVKTLkEDTMEVEEF----LKEAAVMKEIKHPNLVQLLGVCTREPP-----FYIIT 315
Cdd:cd07834    5 LKPIGSGAYGVVCSAYDKRTGRKVAIKKI-SNVFDDLIDakriLREIKILRHLKHENIIGLLDILRPPSPeefndVYIVT 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  316 EFMtyGNLLDYLRECNRQEVNAVV--LLYmatQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDT- 392
Cdd:cd07834   84 ELM--ETDLHKVIKSPQPLTDDHIqyFLY---QILRGLKYLHSAGVIHRDLKPSNILVNSNCDLKICDFGLARGVDPDEd 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  393 ------YTAHagakfpiKW-TAPE-SLAYNKFSIKSDVWAFGVLLWEIAT------------------------------ 434
Cdd:cd07834  159 kgflteYVVT-------RWyRAPElLLSSKKYTKAIDIWSVGCIFAELLTrkplfpgrdyidqlnlivevlgtpseedlk 231
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  435 -----------YGMSPYPGIDLSQVYellekdyrmerpEGCPEKVYELMRACWQWNPSDRPS---------FAEIH-QAF 493
Cdd:cd07834  232 fissekarnylKSLPKKPKKPLSEVF------------PGASPEAIDLLEKMLVFNPKKRITadealahpyLAQLHdPED 299
                        330
                 ....*....|....*.
gi 62362414  494 ETMFQESSISDEVEKE 509
Cdd:cd07834  300 EPVAKPPFDFPFFDDE 315
SH2_C-SH2_Zap70 cd10402
C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
123-218 1.72e-16

C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70); ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the C-terminus SH2 domains of Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198265  Cd Length: 105  Bit Score: 76.11  E-value: 1.72e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  123 EKHSWYHGPVSRNAAEYLLSSGI--NGSFLVRESESSpGQRSISLRYEGRVYHYRINTASDGKLYVSSESRFNTLAELVH 200
Cdd:cd10402    8 ERMPWYHGSIARDEAERRLYSGAqpDGKFLLRERKES-GTYALSLVYGKTVYHYRIDQDKSGKYSIPEGTKFDTLWQLVE 86
                         90
                 ....*....|....*...
gi 62362414  201 HHSTVADGLITTLHYPAP 218
Cdd:cd10402   87 YLKLKPDGLIFVLRESCP 104
SH2_Vav_family cd09940
Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several ...
122-216 1.85e-16

Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, Vav2 and Vav3 are more ubiquitously expressed. The members here include insect and amphibian Vavs. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198193  Cd Length: 102  Bit Score: 75.79  E-value: 1.85e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  122 LEKHSWYHGPVSRNAAEYLLSSGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTASDGKLYVSSESRFNTLAELVH- 200
Cdd:cd09940    2 LSEFLWFVGEMERDTAENRLENRPDGTYLVRVRPQGETQYALSIKYNGDVKHMKIEQRSDGLYYLSESRHFKSLVELVNy 81
                         90       100
                 ....*....|....*....|
gi 62362414  201 --HHSTVAD--GLITTLHYP 216
Cdd:cd09940   82 yeRNSLGENfaGLDTTLKWP 101
STKc_Aurora-B_like cd14117
Catalytic domain of the Serine/Threonine kinase, Aurora-B kinase and similar proteins; STKs ...
241-489 2.66e-16

Catalytic domain of the Serine/Threonine kinase, Aurora-B kinase and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). This subfamily includes Aurora-B and Aurora-C. Aurora-B is most active at the transition during metaphase to the end of mitosis. It associates with centromeres, relocates to the midzone of the central spindle, and concentrates at the midbody during cell division. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. INCENP participates in the activation of Aurora-B in a two-step process: first by binding to form an intermediate state of activation and the phosphorylation of its C-terminal TSS motif to generate the fully active kinase. The Aurora-B subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271019 [Multi-domain]  Cd Length: 270  Bit Score: 80.29  E-value: 2.66e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  241 DITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVE----EFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITE 316
Cdd:cd14117    7 DFDIGRPLGKGKFGNVYLAREKQSKFIVALKVLFKSQIEKEgvehQLRREIEIQSHLRHPNILRLYNYFHDRKRIYLILE 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  317 FMTYGNLLDYLRECNR--QEVNAVVLlymaTQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLS--------R 386
Cdd:cd14117   87 YAPRGELYKELQKHGRfdEQRTATFM----EELADALHYCHEKKVIHRDIKPENLLMGYKGELKIADFGWSvhapslrrR 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  387 LMTGDtytahagakfpIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEK-DYRMerPEGCP 465
Cdd:cd14117  163 TMCGT-----------LDYLPPEMIEGRTHDEKVDLWCIGVLCYELLV-GMPPFESASHTETYRRIVKvDLKF--PPFLS 228
                        250       260
                 ....*....|....*....|....
gi 62362414  466 EKVYELMRACWQWNPSDRPSFAEI 489
Cdd:cd14117  229 DGSRDLISKLLRYHPSERLPLKGV 252
STKc_RSK2_C cd14176
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called ...
225-440 3.24e-16

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called 90kDa ribosomal protein S6 kinase 3 or Ribosomal protein S6 kinase alpha-3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK2 is also called p90RSK3, RPS6KA3, S6K-alpha-3, or MAPK-activated protein kinase 1b (MAPKAPK-1b). RSK2 is expressed highly in the regions of the brain with high synaptic activity. It plays a role in the maintenance and consolidation of excitatory synapses. It is a specific modulator of phospholipase D in calcium-regulated exocytosis. Mutations in the RSK2 gene, RPS6KA3, cause Coffin-Lowry syndrome (CLS), a rare syndromic form of X-linked mental retardation characterized by growth and psychomotor retardation and skeletal abnormalities. RSK2 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271078 [Multi-domain]  Cd Length: 339  Bit Score: 81.22  E-value: 3.24e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  225 VYGVSPNYDKWEMERTD-ITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKED----TMEVEEFLKEAavmkeiKHPNLV 299
Cdd:cd14176    3 VHSIVQQLHRNSIQFTDgYEVKEDIGVGSYSVCKRCIHKATNMEFAVKIIDKSkrdpTEEIEILLRYG------QHPNII 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  300 QLLGVCTREPPFYIITEFMTYGNLLD-YLRECNRQEVNAVVLLYMatqISSAMEYLEKKNFIHRDLAARNCLV----GEN 374
Cdd:cd14176   77 TLKDVYDDGKYVYVVTELMKGGELLDkILRQKFFSEREASAVLFT---ITKTVEYLHAQGVVHRDLKPSNILYvdesGNP 153
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 62362414  375 HLVKVADFGLSR-------LMTGDTYTAHagakfpikWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPY 440
Cdd:cd14176  154 ESIRICDFGFAKqlraengLLMTPCYTAN--------FVAPEVLERQGYDAACDIWSLGVLLYTMLT-GYTPF 217
STKc_CDK12 cd07864
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs ...
243-434 3.30e-16

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK12 is also called Cdc2-related protein kinase 7 (CRK7) or Cdc2-related kinase arginine/serine-rich (CrkRS). It is a unique CDK that contains an RS domain, which is predominantly found in splicing factors. CDK12 is widely expressed in tissues. It interacts with cyclins L1 and L2, and plays roles in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK12 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270847 [Multi-domain]  Cd Length: 302  Bit Score: 80.62  E-value: 3.30e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  243 TMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTmEVEEF----LKEAAVMKEIKHPNLVQLLGVCT----------RE 308
Cdd:cd07864   10 DIIGIIGEGTYGQVYKAKDKDTGELVALKKVRLDN-EKEGFpitaIREIKILRQLNHRSVVNLKEIVTdkqdaldfkkDK 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  309 PPFYIITEFMTY---GNLLDYLRECNRQEVNAVVllymaTQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLS 385
Cdd:cd07864   89 GAFYLVFEYMDHdlmGLLESGLVHFSEDHIKSFM-----KQLLEGLNYCHKKNFLHRDIKCSNILLNNKGQIKLADFGLA 163
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 62362414  386 RLMTGDTYTAHAGAKFPIKWTAPE-SLAYNKFSIKSDVWAFGVLLWEIAT 434
Cdd:cd07864  164 RLYNSEESRPYTNKVITLWYRPPElLLGEERYGPAIDVWSCGCILGELFT 213
STKc_PKB_beta cd05595
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); ...
248-460 4.58e-16

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-beta is the predominant PKB isoform expressed in insulin-responsive tissues. It plays a critical role in the regulation of glucose homeostasis. It is also implicated in muscle cell differentiation. Mice deficient in PKB-beta display normal growth weights but exhibit severe insulin resistance and diabetes, accompanied by lipoatrophy and B-cell failure. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain.The PKB-beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173686 [Multi-domain]  Cd Length: 323  Bit Score: 80.82  E-value: 4.58e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM----EVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNL 323
Cdd:cd05595    3 LGKGTFGKVILVREKATGRYYAMKILRKEVIiakdEVAHTVTESRVLQNTRHPFLTALKYAFQTHDRLCFVMEYANGGEL 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  324 LDYL-RECNRQEVNAvvlLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFP 402
Cdd:cd05595   83 FFHLsRERVFTEDRA---RFYGAEIVSALEYLHSRDVVYRDIKLENLMLDKDGHIKITDFGLCKEGITDGATMKTFCGTP 159
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 62362414  403 iKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYEL-LEKDYRMER 460
Cdd:cd05595  160 -EYLAPEVLEDNDYGRAVDWWGLGVVMYEMMC-GRLPFYNQDHERLFELiLMEEIRFPR 216
STKc_BMPR2_AMHR2 cd14054
Catalytic domain of the Serine/Threonine Kinases, Bone Morphogenetic Protein and ...
248-442 4.73e-16

Catalytic domain of the Serine/Threonine Kinases, Bone Morphogenetic Protein and Anti-Muellerian Hormone Type II Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR2 and AMHR2 belong to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors (GDFs), and AMH, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. BMPR2 and AMHR2 act primarily as a receptor for BMPs and AMH, respectively. BMPs induce bone and cartilage formation, as well as regulate tooth, kidney, skin, hair, haematopoietic, and neuronal development. Mutations in BMPR2A is associated with familial pulmonary arterial hypertension. AMH is mainly responsible for the regression of Mullerian ducts during male sex differentiation. It is expressed exclusively by somatic cells of the gonads. Mutations in either AMH or AMHR2 cause persistent Mullerian duct syndrome (PMDS), a rare form of male pseudohermaphroditism characterized by the presence of Mullerian derivatives (ovary and tubes) in otherwise normally masculine males. The BMPR2/AMHR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270956 [Multi-domain]  Cd Length: 300  Bit Score: 80.10  E-value: 4.73e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGvwkkySLT---VAVKTLKEDtmEVEEFLKEAAVMK--EIKHPNLVQLLGVCTREPP-----FYIITEF 317
Cdd:cd14054    3 IGQGRYGTVWKG-----SLDerpVAVKVFPAR--HRQNFQNEKDIYElpLMEHSNILRFIGADERPTAdgrmeYLLVLEY 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  318 MTYGNLLDYLREcnrQEVNAVVLLYMATQISSAMEYLE---------KKNFIHRDLAARNCLVGENHLVKVADFGLSRLM 388
Cdd:cd14054   76 APKGSLCSYLRE---NTLDWMSSCRMALSLTRGLAYLHtdlrrgdqyKPAIAHRDLNSRNVLVKADGSCVICDFGLAMVL 152
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  389 TGDTY----TAHAGAKFP-----IKWTAPESL--AYNKFSIKS-----DVWAFGVLLWEIATYGMSPYPG 442
Cdd:cd14054  153 RGSSLvrgrPGAAENASIsevgtLRYMAPEVLegAVNLRDCESalkqvDVYALGLVLWEIAMRCSDLYPG 222
SH2_Nck_family cd09943
Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate ...
126-204 4.84e-16

Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198196  Cd Length: 93  Bit Score: 74.47  E-value: 4.84e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  126 SWYHGPVSRNAAEYLLSS-GINGSFLVRESESSPGQRSISLRYEGRVYHYRINTasDGKLYVSSESRFNTLAELVHHHST 204
Cdd:cd09943    2 PWYYGRITRHQAETLLNEhGHEGDFLIRDSESNPGDYSVSLKAPGRNKHFKVQV--VDNVYCIGQRKFHTMDELVEHYKK 79
STKc_RSK_N cd05582
N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase; ...
248-483 5.21e-16

N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), p90-RSKs, or p90S6Ks. The RSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270734 [Multi-domain]  Cd Length: 317  Bit Score: 80.52  E-value: 5.21e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVY---EGVWKKYSLTVAVKTLKEDTMEVEEFLK---EAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYG 321
Cdd:cd05582    3 LGQGSFGKVFlvrKITGPDAGTLYAMKVLKKATLKVRDRVRtkmERDILADVNHPFIVKLHYAFQTEGKLYLILDFLRGG 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  322 NLLDYL-RECNRQEVNavVLLYMAtQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAgak 400
Cdd:cd05582   83 DLFTRLsKEVMFTEED--VKFYLA-ELALALDHLHSLGIIYRDLKPENILLDEDGHIKLTDFGLSKESIDHEKKAYS--- 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  401 F--PIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEKDyRMERPEGCPEKVYELMRACWQW 478
Cdd:cd05582  157 FcgTVEYMAPEVVNRRGHTQSADWWSFGVLMFEMLT-GSLPFQGKDRKETMTMILKA-KLGMPQFLSPEAQSLLRALFKR 234

                 ....*
gi 62362414  479 NPSDR 483
Cdd:cd05582  235 NPANR 239
PHA02988 PHA02988
hypothetical protein; Provisional
268-489 5.70e-16

hypothetical protein; Provisional


Pssm-ID: 165291 [Multi-domain]  Cd Length: 283  Bit Score: 79.79  E-value: 5.70e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   268 VAVKTLKED----TMEVEEFLKEAAVMKEIKHPNLVQLLG----VCTREPPFYIITEFMTYGNLLDYLRecNRQEVNAVV 339
Cdd:PHA02988   46 VIIRTFKKFhkghKVLIDITENEIKNLRRIDSNNILKIYGfiidIVDDLPRLSLILEYCTRGYLREVLD--KEKDLSFKT 123
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   340 LLYMATQISSAMEYLEKK-NFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTY-TAHAGAKFPIKWTapeSLAYNKFS 417
Cdd:PHA02988  124 KLDMAIDCCKGLYNLYKYtNKPYKNLTSVSFLVTENYKLKIICHGLEKILSSPPFkNVNFMVYFSYKML---NDIFSEYT 200
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 62362414   418 IKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEKDYRMER-PEGCPEKVYELMRACWQWNPSDRPSFAEI 489
Cdd:PHA02988  201 IKDDIYSLGVVLWEIFT-GKIPFENLTTKEIYDLIINKNNSLKlPLDCPLEIKCIVEACTSHDSIKRPNIKEI 272
STKc_PAK3 cd06656
Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine ...
247-491 5.83e-16

Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine/threonine kinases (STKs), p21-activated kinase (PAK) 3, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. PAK3 belongs to group I. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAK3 is highly expressed in the brain. It is implicated in neuronal plasticity, synapse formation, dendritic spine morphogenesis, cell cycle progression, neuronal migration, and apoptosis. Inactivating mutations in the PAK3 gene cause X-linked non-syndromic mental retardation, the severity of which depends on the site of the mutation.


Pssm-ID: 132987 [Multi-domain]  Cd Length: 297  Bit Score: 79.77  E-value: 5.83e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLK-EDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLD 325
Cdd:cd06656   26 KIGQGASGTVYTAIDIATGQEVAIKQMNlQQQPKKELIINEILVMRENKNPNIVNYLDSYLVGDELWVVMEYLAGGSLTD 105
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  326 YLRECNRQEVNAVVLLYMATQissAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPIkW 405
Cdd:cd06656  106 VVTETCMDEGQIAAVCRECLQ---ALDFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQSKRSTMVGTPY-W 181
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  406 TAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEKD--YRMERPEGCPEKVYELMRACWQWNPSDR 483
Cdd:cd06656  182 MAPEVVTRKAYGPKVDIWSLGIMAIEMVE-GEPPYLNENPLRALYLIATNgtPELQNPERLSAVFRDFLNRCLEMDVDRR 260

                 ....*...
gi 62362414  484 PSFAEIHQ 491
Cdd:cd06656  261 GSAKELLQ 268
SH2_C-SH2_SHP_like cd09931
C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
127-216 5.84e-16

C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The SH2 domain phosphatases (SHP-1, SHP-2/Syp, Drosophila corkscrew (csw), and Caenorhabditis elegans Protein Tyrosine Phosphatase (Ptp-2)) are cytoplasmic signaling enzymes. They are both targeted and regulated by interactions of their SH2 domains with phosphotyrosine docking sites. These proteins contain two SH2 domains (N-SH2, C-SH2) followed by a tyrosine phosphatase (PTP) domain, and a C-terminal extension. Shp1 and Shp2 have two tyrosyl phosphorylation sites in their C-tails, which are phosphorylated differentially by receptor and nonreceptor PTKs. Csw retains the proximal tyrosine and Ptp-2 lacks both sites. Shp-binding proteins include receptors, scaffolding adapters, and inhibitory receptors. Some of these bind both Shp1 and Shp2 while others bind only one. Most proteins that bind a Shp SH2 domain contain one or more immuno-receptor tyrosine-based inhibitory motifs (ITIMs): [SIVL]xpYxx[IVL]. Shp1 N-SH2 domain blocks the catalytic domain and keeps the enzyme in the inactive conformation, and is thus believed to regulate the phosphatase activity of SHP-1. Its C-SH2 domain is thought to be involved in searching for phosphotyrosine activators. The SHP2 N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. The C-SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation. Csw SH2 domain function is essential, but either SH2 domain can fulfill this requirement. The role of the csw SH2 domains during Sevenless receptor tyrosine kinase (SEV) signaling is to bind Daughter of Sevenless rather than activated SEV. Ptp-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote major sperm protein (MSP)-induced MAP Kinase (MPK-1) phosphorylation. Ptp-2 functions in the oocyte cytoplasm, not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation. It is thought that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation and that secreted MSP domains and Cu/Zn superoxide dismutases function antagonistically to control ROS and MAPK signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198185  Cd Length: 99  Bit Score: 74.24  E-value: 5.84e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  127 WYHGPVSRNAAEYLL-SSGINGSFLVRESESSPGQRSISLRY-EGRVYHYRINtASDGKLYVSSESRFNTLAELVHHHST 204
Cdd:cd09931    2 WFHGHLSGKEAEKLLlEKGKPGSFLVRESQSKPGDFVLSVRTdDDKVTHIMIR-CQGGKYDVGGGEEFDSLTDLVEHYKK 80
                         90
                 ....*....|....*.
gi 62362414  205 V----ADGLITTLHYP 216
Cdd:cd09931   81 NpmveTSGTVVHLKQP 96
STKc_PAK1 cd06654
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the ...
247-491 5.90e-16

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK1 is important in the regulation of many cellular processes including cytoskeletal dynamics, cell motility, growth, and proliferation. Although PAK1 has been regarded mainly as a cytosolic protein, recent reports indicate that PAK1 also exists in significant amounts in the nucleus, where it is involved in transcription modulation and in cell cycle regulatory events. PAK1 is also involved in transformation and tumorigenesis. Its overexpression, hyperactivation and increased nuclear accumulation is correlated to breast cancer invasiveness and progression. Nuclear accumulation is also linked to tamoxifen resistance in breast cancer cells. PAK1 belongs to the group I PAKs, which contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270820 [Multi-domain]  Cd Length: 296  Bit Score: 79.77  E-value: 5.90e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLK-EDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLD 325
Cdd:cd06654   27 KIGQGASGTVYTAMDVATGQEVAIRQMNlQQQPKKELIINEILVMRENKNPNIVNYLDSYLVGDELWVVMEYLAGGSLTD 106
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  326 YLRECNRQEVNAVVLLYMATQissAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPIkW 405
Cdd:cd06654  107 VVTETCMDEGQIAAVCRECLQ---ALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQSKRSTMVGTPY-W 182
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  406 TAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEKD--YRMERPEGCPEKVYELMRACWQWNPSDR 483
Cdd:cd06654  183 MAPEVVTRKAYGPKVDIWSLGIMAIEMIE-GEPPYLNENPLRALYLIATNgtPELQNPEKLSAIFRDFLNRCLEMDVEKR 261

                 ....*...
gi 62362414  484 PSFAEIHQ 491
Cdd:cd06654  262 GSAKELLQ 269
STKc_ACVR1_ALK1 cd14142
Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin ...
242-483 6.25e-16

Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin receptor-Like Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR1, also called Activin receptor-Like Kinase 2 (ALK2), and ALK1 act as receptors for bone morphogenetic proteins (BMPs) and they activate SMAD1/5/8. ACVR1 is widely expressed while ALK1 is limited mainly to endothelial cells. The specificity of BMP binding to type I receptors is affected by type II receptors. ACVR1 binds BMP6/7/9/10 and can also bind anti-Mullerian hormone (AMH) in the presence of AMHR2. ALK1 binds BMP9/10 as well as TGFbeta in endothelial cells. A missense mutation in the GS domain of ACVR1 causes fibrodysplasia ossificans progressiva, a complex and disabling disease characterized by congenital skeletal malformations and extraskeletal bone formation. ACVR1 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors, and AMH, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like ACVR1 and ALK1, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The ACVR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271044 [Multi-domain]  Cd Length: 298  Bit Score: 79.79  E-value: 6.25e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  242 ITMKHKLGGGQYGEVYEGVWKKYSltVAVKTLkeDTMEVEEFLKEAAVMKEI--KHPNLVQLLGV-------CTReppFY 312
Cdd:cd14142    7 ITLVECIGKGRYGEVWRGQWQGES--VAVKIF--SSRDEKSWFRETEIYNTVllRHENILGFIASdmtsrnsCTQ---LW 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  313 IITEFMTYGNLLDYLrecNRQEVNAVVLLYMATQISSAMEYLE--------KKNFIHRDLAARNCLVGENHLVKVADFGL 384
Cdd:cd14142   80 LITHYHENGSLYDYL---QRTTLDHQEMLRLALSAASGLVHLHteifgtqgKPAIAHRDLKSKNILVKSNGQCCIADLGL 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  385 SRLMTGDTYTAHAGAKFPI---KWTAPE----SLAYNKF-SIK-SDVWAFGVLLWEIA----------TYgMSPYpgidl 445
Cdd:cd14142  157 AVTHSQETNQLDVGNNPRVgtkRYMAPEvldeTINTDCFeSYKrVDIYAFGLVLWEVArrcvsggiveEY-KPPF----- 230
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 62362414  446 sqvYELLEKDYRME-----------RPEgCPEK---------VYELMRACWQWNPSDR 483
Cdd:cd14142  231 ---YDVVPSDPSFEdmrkvvcvdqqRPN-IPNRwssdptltaMAKLMKECWYQNPSAR 284
STKc_cPKC cd05587
Catalytic domain of the Serine/Threonine Kinase, Classical (or Conventional) Protein Kinase C; ...
248-444 7.46e-16

Catalytic domain of the Serine/Threonine Kinase, Classical (or Conventional) Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. cPKCs are potent kinases for histones, myelin basic protein, and protamine. They depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. cPKCs contain a calcium-binding C2 region in their regulatory domain. There are four cPKC isoforms, named alpha, betaI, betaII, and gamma. PKC-gamma is mainly expressed in neuronal tissues. It plays a role in protection from ischemia. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. The cPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270739 [Multi-domain]  Cd Length: 320  Bit Score: 80.13  E-value: 7.46e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM----EVEEFLKEAAVMK-EIKHPNLVQLLGVCTREPPFYIITEFMTYGN 322
Cdd:cd05587    4 LGKGSFGKVMLAERKGTDELYAIKILKKDVIiqddDVECTMVEKRVLAlSGKPPFLTQLHSCFQTMDRLYFVMEYVNGGD 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLRECNR-QEVNAVvllYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR--LMTGDTYTAHAGA 399
Cdd:cd05587   84 LMYHIQQVGKfKEPVAV---FYAAEIAVGLFFLHSKGIIYRDLKLDNVMLDAEGHIKIADFGMCKegIFGGKTTRTFCGT 160
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 62362414  400 KfpiKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGID 444
Cdd:cd05587  161 P---DYIAPEIIAYQPYGKSVDWWAYGVLLYEMLA-GQPPFDGED 201
STKc_MAP4K4_6_N cd06636
N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase ...
248-433 7.59e-16

N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 and 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K4 is also called Nck Interacting kinase (NIK). It facilitates the activation of the MAPKs, extracellular signal-regulated kinase (ERK) 1, ERK2, and c-Jun N-terminal kinase (JNK), by phosphorylating and activating MEKK1. MAP4K4 plays a role in tumor necrosis factor (TNF) alpha-induced insulin resistance. MAP4K4 silencing in skeletal muscle cells from type II diabetic patients restores insulin-mediated glucose uptake. MAP4K4, through JNK, also plays a broad role in cell motility, which impacts inflammation, homeostasis, as well as the invasion and spread of cancer. MAP4K4 is found to be highly expressed in most tumor cell lines relative to normal tissue. MAP4K6 (also called MINK for Misshapen/NIKs-related kinase) is activated after Ras induction and mediates activation of p38 MAPK. MAP4K6 plays a role in cell cycle arrest, cytoskeleton organization, cell adhesion, and cell motility. The MAP4K4/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270806 [Multi-domain]  Cd Length: 282  Bit Score: 79.28  E-value: 7.59e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKH-PNLVQLLGVCTREPP------FYIITEFMTY 320
Cdd:cd06636   24 VGNGTYGQVYKGRHVKTGQLAAIKVMDVTEDEEEEIKLEINMLKKYSHhRNIATYYGAFIKKSPpghddqLWLVMEFCGA 103
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  321 GNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLM--TGDTYTAHAG 398
Cdd:cd06636  104 GSVTDLVKNTKGNALKEDWIAYICREILRGLAHLHAHKVIHRDIKGQNVLLTENAEVKLVDFGVSAQLdrTVGRRNTFIG 183
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 62362414  399 AKFpikWTAPESLAYNK-----FSIKSDVWAFGVLLWEIA 433
Cdd:cd06636  184 TPY---WMAPEVIACDEnpdatYDYRSDIWSLGITAIEMA 220
STKc_DAPK1 cd14194
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 1; STKs ...
247-442 9.31e-16

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK1 is the prototypical member of the subfamily and is also simply referred to as DAPK. It is Ca2+/calmodulin (CaM)-regulated and actin-associated protein that contains an N-terminal kinase domain followed by an autoinhibitory CaM binding region and a large C-terminal extension with multiple functional domains including ankyrin (ANK) repeats, a cytoskeletal binding domain, a Death domain, and a serine-rich tail. Loss of DAPK1 expression, usually because of DNA methylation, is implicated in many tumor types. DAPK1 is highly abundant in the brain and has also been associated with neurodegeneration. The DAPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271096 [Multi-domain]  Cd Length: 269  Bit Score: 78.91  E-value: 9.31e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEV-------EEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMT 319
Cdd:cd14194   12 ELGSGQFAVVKKCREKSTGLQYAAKFIKKRRTKSsrrgvsrEDIEREVSILKEIQHPNVITLHEVYENKTDVILILELVA 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  320 YGNLLDYLREcnRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHL----VKVADFGLS-RLMTGDTYT 394
Cdd:cd14194   92 GGELFDFLAE--KESLTEEEATEFLKQILNGVYYLHSLQIAHFDLKPENIMLLDRNVpkprIKIIDFGLAhKIDFGNEFK 169
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 62362414  395 AHAGAKfpiKWTAPESLAYNKFSIKSDVWAFGVLLWeIATYGMSPYPG 442
Cdd:cd14194  170 NIFGTP---EFVAPEIVNYEPLGLEADMWSIGVITY-ILLSGASPFLG 213
STKc_myosinIIIA_N cd06638
N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIA myosin; STKs catalyze ...
218-491 9.87e-16

N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIA myosin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class IIIA myosin is highly expressed in retina and in inner ear hair cells. It is localized to the distal ends of actin-bundled structures. Mutations in human myosin IIIA are responsible for progressive nonsyndromic hearing loss. Human myosin IIIA possesses ATPase and kinase activities, and the ability to move actin filaments in a motility assay. It may function as a cellular transporter capable of moving along actin bundles in sensory cells. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain. Class III myosins may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. In photoreceptor cells, they may also function as cargo carriers during light-dependent translocation of proteins such as transducin and arrestin. The class III myosin subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132969 [Multi-domain]  Cd Length: 286  Bit Score: 78.90  E-value: 9.87e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  218 PKRNKPTVYGVSPN-YDKWEMERTditmkhkLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIK-H 295
Cdd:cd06638    2 PLSGKTIIFDSFPDpSDTWEIIET-------IGKGTYGKVFKVLNKKNGSKAAVKILDPIHDIDEEIEAEYNILKALSdH 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  296 PNLVQLLGVCTREP-----PFYIITEFMTYGNLLD----YLRECNRqeVNAVVLLYMATQISSAMEYLEKKNFIHRDLAA 366
Cdd:cd06638   75 PNVVKFYGMYYKKDvkngdQLWLVLELCNGGSVTDlvkgFLKRGER--MEEPIIAYILHEALMGLQHLHVNKTIHRDVKG 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  367 RNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPIkWTAPESLAYNK-----FSIKSDVWAFGVLLWEIatyGMSPYP 441
Cdd:cd06638  153 NNILLTTEGGVKLVDFGVSAQLTSTRLRRNTSVGTPF-WMAPEVIACEQqldstYDARCDVWSLGITAIEL---GDGDPP 228
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 62362414  442 GIDLSQVYELLE----KDYRMERPEGCPEKVYELMRACWQWNPSDRPSFAEIHQ 491
Cdd:cd06638  229 LADLHPMRALFKiprnPPPTLHQPELWSNEFNDFIRKCLTKDYEKRPTVSDLLQ 282
STKc_BMPR1b cd14219
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IB; STKs ...
242-502 1.03e-15

Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IB; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR1b, also called Activin receptor-Like Kinase 6 (ALK6), functions as a receptor for bone morphogenetic proteins (BMPs), which are involved in the regulation of cell proliferation, survival, differentiation, and apoptosis. BMPs are able to induce bone, cartilage, ligament, and tendon formation, and may play roles in bone diseases and tumors. Mutations in BMPR1b that led to inhibition of chondrogenesis can cause Brachydactyly (BD) type A2, a dominant hand malformation characterized by shortening and lateral deviation of the index fingers. A point mutation in the BMPR1b kinase domain is also associated with the Booroola phenotype, characterized by precocious differentiation of ovarian follicles. BMPR1b belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like BMPR1b, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The BMPR1b subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271121 [Multi-domain]  Cd Length: 305  Bit Score: 79.32  E-value: 1.03e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  242 ITMKHKLGGGQYGEVYEGVWKKYSltVAVKTLKedTMEVEEFLKEAAVMKEI--KHPNLVQLLGVCTREP----PFYIIT 315
Cdd:cd14219    7 IQMVKQIGKGRYGEVWMGKWRGEK--VAVKVFF--TTEEASWFRETEIYQTVlmRHENILGFIAADIKGTgswtQLYLIT 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  316 EFMTYGNLLDYLRECNrqeVNAVVLLYMATQISSAMEYLEKKNF--------IHRDLAARNCLVGENHLVKVADFGLSRL 387
Cdd:cd14219   83 DYHENGSLYDYLKSTT---LDTKAMLKLAYSSVSGLCHLHTEIFstqgkpaiAHRDLKSKNILVKKNGTCCIADLGLAVK 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  388 MTGDT------YTAHAGAKfpiKWTAPE----SLAYNKFS--IKSDVWAFGVLLWEIA----------TYGMSPYPGIDL 445
Cdd:cd14219  160 FISDTnevdipPNTRVGTK---RYMPPEvldeSLNRNHFQsyIMADMYSFGLILWEVArrcvsggiveEYQLPYHDLVPS 236
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 62362414  446 SQVYELLE-----KDYRMERP-----EGCPEKVYELMRACWQWNPSDRPSFAEIHQAFETMFQESSI 502
Cdd:cd14219  237 DPSYEDMReivciKRLRPSFPnrwssDECLRQMGKLMTECWAHNPASRLTALRVKKTLAKMSESQDI 303
STKc_PDIK1L cd13977
Catalytic domain of the Serine/Threonine kinase, PDLIM1 interacting kinase 1 like; STKs ...
247-484 1.07e-15

Catalytic domain of the Serine/Threonine kinase, PDLIM1 interacting kinase 1 like; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PDIK1L is also called STK35 or CLIK-1. It is predominantly a nuclear protein which is capable of autophosphorylation. Through its interaction with the PDZ-LIM protein CLP-36, it is localized to actin stress fibers. The PDIK1L subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270879 [Multi-domain]  Cd Length: 322  Bit Score: 79.52  E-value: 1.07e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTME-VEEFLKEAAVMKEIK--HPNLVQLL-------GVCTR--------- 307
Cdd:cd13977    7 EVGRGSYGVVYEAVVRRTGARVAVKKIRCNAPEnVELALREFWALSSIQrqHPNVIQLEecvlqrdGLAQRmshgssksd 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  308 ------------------EPPFYI--ITEFMTYGNLLDYL--RECNRQEVNAVVLlymatQISSAMEYLEKKNFIHRDLA 365
Cdd:cd13977   87 lylllvetslkgercfdpRSACYLwfVMEFCDGGDMNEYLlsRRPDRQTNTSFML-----QLSSALAFLHRNQIVHRDLK 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  366 ARNCLVGENH---LVKVADFGLSRLMTGDT-------------YTAHAGAKFpikWTAPEsLAYNKFSIKSDVWAFGVLL 429
Cdd:cd13977  162 PDNILISHKRgepILKVADFGLSKVCSGSGlnpeepanvnkhfLSSACGSDF---YMAPE-VWEGHYTAKADIFALGIII 237
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 62362414  430 W---EIATY----------GMSPYPGIDLSQVYELLEKDYRME------RPEGCPEKVYELMRACWQWNPSDRP 484
Cdd:cd13977  238 WamvERITFrdgetkkellGTYIQQGKEIVPLGEALLENPKLElqiplkKKKSMNDDMKQLLRDMLAANPQERP 311
PK_GC-C cd14044
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-C; The pseudokinase domain ...
268-497 1.30e-15

Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-C; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-C binds and is activated by the intestinal hormones, guanylin (GN) and uroguanylin (UGN), which are secreted after salty meals to inhibit sodium absorption and induce the secretion of chloride, bicarbonate, and water. GN and UGN are also present in the kidney, where they induce increased salt and water secretion. This prevents the development of hypernatremia and hypervolemia after ingestion of high amounts of salt. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-C subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270946 [Multi-domain]  Cd Length: 271  Bit Score: 78.39  E-value: 1.30e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  268 VAVKTLKEDTMEVEEFLK-EAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDYLREC----NRQEVNAVVLLY 342
Cdd:cd14044   34 VILKDLKNNEGNFTEKQKiELNKLLQIDYYNLTKFYGTVKLDTMIFGVIEYCERGSLRDVLNDKisypDGTFMDWEFKIS 113
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  343 MATQISSAMEYLEKKNF-IHRDLAARNCLVGENHLVKVADFGLSRLMTgdtytahagakfPIK--WTAPESLAYNKFSIK 419
Cdd:cd14044  114 VMYDIAKGMSYLHSSKTeVHGRLKSTNCVVDSRMVVKITDFGCNSILP------------PSKdlWTAPEHLRQAGTSQK 181
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  420 SDVWAFGVLLWEIATYGMSPYPgidlSQVYELLEKDYRMERPEGC----PE-----------KVYELMRACWQWNPSDRP 484
Cdd:cd14044  182 GDVYSYGIIAQEIILRKETFYT----AACSDRKEKIYRVQNPKGMkpfrPDlnlesagererEVYGLVKNCWEEDPEKRP 257
                        250
                 ....*....|...
gi 62362414  485 SFAEIHQAFETMF 497
Cdd:cd14044  258 DFKKIENTLAKIF 270
STKc_CaMKK2 cd14199
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2; ...
280-489 1.34e-15

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). CaMKK2, also called CaMKK beta, is one of the most versatile CaMKs. It is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. CaMKK2 contains unique N- and C-terminal domains and a central catalytic kinase domain that is followed by a regulatory domain that bears overlapping autoinhibitory and CaM-binding regions. It can be activated by signaling through G-coupled receptors, IP3 receptors, plasma membrane ion channels, and Toll-like receptors. Thus, CaMKK2 acts as a molecular hub that is capable of receiving and decoding signals from diverse pathways. The CaMKK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271101 [Multi-domain]  Cd Length: 286  Bit Score: 78.47  E-value: 1.34e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  280 VEEFLKEAAVMKEIKHPNLVQLLGVCT--REPPFYIITEFMTYGNLLDYLRECNRQEVNAvvLLYMATQISsAMEYLEKK 357
Cdd:cd14199   69 IERVYQEIAILKKLDHPNVVKLVEVLDdpSEDHLYMVFELVKQGPVMEVPTLKPLSEDQA--RFYFQDLIK-GIEYLHYQ 145
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  358 NFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPiKWTAPESLAYNK--FSIKS-DVWAFGVLLWeIAT 434
Cdd:cd14199  146 KIIHRDVKPSNLLVGEDGHIKIADFGVSNEFEGSDALLTNTVGTP-AFMAPETLSETRkiFSGKAlDVWAMGVTLY-CFV 223
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 62362414  435 YGMSPYPGIDLSQVYELLeKDYRMERPE--GCPEKVYELMRACWQWNPSDRPSFAEI 489
Cdd:cd14199  224 FGQCPFMDERILSLHSKI-KTQPLEFPDqpDISDDLKDLLFRMLDKNPESRISVPEI 279
SH2_Fps_family cd10361
Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related ...
121-202 1.40e-15

Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related (Fes/Fps/Fer) proteins; The Fps family consists of members Fps/Fes and Fer/Flk/Tyk3. They are cytoplasmic protein-tyrosine kinases implicated in signaling downstream from cytokines, growth factors and immune receptors. Fes/Fps/Fer contains three coiled-coil regions, an SH2 (Src-homology-2) and a TK (tyrosine kinase catalytic) domain signature. Members here include: Fps/Fes, Fer, Kin-31, and In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198224  Cd Length: 90  Bit Score: 72.95  E-value: 1.40e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  121 SLEKHSWYHGPVSRNAAEYLLSSgiNGSFLVRESESSPGQRS---ISLRYEGRVYHYRINTASDGKLYVSSEsRFNTLAE 197
Cdd:cd10361    2 DLENEPYYHGLLPREDAEELLKN--DGDFLVRKTEPKGGGKRklvLSVRWDGKIRHFVINRDDGGKYYIEGK-SFKSISE 78

                 ....*
gi 62362414  198 LVHHH 202
Cdd:cd10361   79 LINYY 83
pknD PRK13184
serine/threonine-protein kinase PknD;
237-434 1.43e-15

serine/threonine-protein kinase PknD;


Pssm-ID: 183880 [Multi-domain]  Cd Length: 932  Bit Score: 82.13  E-value: 1.43e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   237 MERTDITmkHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVE----EFLKEAAVMKEIKHPNLVQLLGVCTREPPFY 312
Cdd:PRK13184    1 MQRYDII--RLIGKGGMGEVYLAYDPVCSRRVALKKIREDLSENPllkkRFLREAKIAADLIHPGIVPVYSICSDGDPVY 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   313 IITEFM---TYGNLLDYLRECNR-----QEVNAV-VLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFG 383
Cdd:PRK13184   79 YTMPYIegyTLKSLLKSVWQKESlskelAEKTSVgAFLSIFHKICATIEYVHSKGVLHRDLKPDNILLGLFGEVVILDWG 158
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 62362414   384 -----------LSRLMTGDTYTAHAGAKFPIK------WTAPESLAYNKFSIKSDVWAFGVLLWEIAT 434
Cdd:PRK13184  159 aaifkkleeedLLDIDVDERNICYSSMTIPGKivgtpdYMAPERLLGVPASESTDIYALGVILYQMLT 226
STKc_SGK2 cd05603
Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 2; ...
248-450 1.46e-15

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK2 shows a more restricted distribution than SGK1 and is most abundantly expressed in epithelial tissues including kidney, liver, pancreas, and the choroid plexus of the brain. In vitro cellular assays show that SGK2 can stimulate the activity of ion channels, the glutamate transporter EEAT4, and the glutamate receptors, GluR6 and GLUR1. The SGK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270754 [Multi-domain]  Cd Length: 321  Bit Score: 79.24  E-value: 1.46e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM----EVEEFLKEAAVM-KEIKHPNLVQLLGVCTREPPFYIITEFMTYGN 322
Cdd:cd05603    3 IGKGSFGKVLLAKRKCDGKFYAVKVLQKKTIlkkkEQNHIMAERNVLlKNLKHPFLVGLHYSFQTSEKLYFVLDYVNGGE 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYL-RECNRQEVNAvvlLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR--LMTGDTYTAHAGA 399
Cdd:cd05603   83 LFFHLqRERCFLEPRA---RFYAAEVASAIGYLHSLNIIYRDLKPENILLDCQGHVVLTDFGLCKegMEPEETTSTFCGT 159
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 62362414  400 KfpiKWTAPESLAYNKFSIKSDVWAFGVLLWEIaTYGMSPYPGIDLSQVYE 450
Cdd:cd05603  160 P---EYLAPEVLRKEPYDRTVDWWCLGAVLYEM-LYGLPPFYSRDVSQMYD 206
STKc_RSK4_C cd14177
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 4 (also called ...
244-440 1.74e-15

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 4 (also called Ribosomal protein S6 kinase alpha-6 or 90kDa ribosomal protein S6 kinase 6); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK4 is also called S6K-alpha-6, RPS6KA6, p90RSK6 or pp90RSK4. RSK4 is a substrate of ERK and is a modulator of p53-dependent proliferation arrest in human cells. Deletion of the RSK4 gene, RPS6KA6, frequently occurs in patients of X-linked deafness type 3, mental retardation and choroideremia. Studies of RSK4 in cancer cells and tissues suggest that it may be oncogenic or tumor suppressive depending on many factors. RSK4 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271079 [Multi-domain]  Cd Length: 295  Bit Score: 78.52  E-value: 1.74e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  244 MKHKLGGGQYGEVYEGVWKKYSLTVAVKTL---KEDTMEVEEFLkeaavMKEIKHPNLVQLLGVCTREPPFYIITEFMTY 320
Cdd:cd14177    8 LKEDIGVGSYSVCKRCIHRATNMEFAVKIIdksKRDPSEEIEIL-----MRYGQHPNIITLKDVYDDGRYVYLVTELMKG 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  321 GNLLD-YLRECNRQEVNAVVLLYMatqISSAMEYLEKKNFIHRDLAARNCLV----GENHLVKVADFGLSRLMTGDT--- 392
Cdd:cd14177   83 GELLDrILRQKFFSEREASAVLYT---ITKTVDYLHCQGVVHRDLKPSNILYmddsANADSIRICDFGFAKQLRGENgll 159
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 62362414  393 ----YTAHagakfpikWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPY 440
Cdd:cd14177  160 ltpcYTAN--------FVAPEVLMRQGYDAACDIWSLGVLLYTMLA-GYTPF 202
STKc_CaMKK1 cd14200
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 1; ...
280-489 1.87e-15

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). CaMKK1, also called CaMKK alpha, is involved in the regulation of glucose uptake in skeletal muscles, independently of AMPK and PKB activation. It also play roles in learning and memory. Studies on CaMKK1 knockout mice reveal deficits in fear conditioning. The CaMKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271102 [Multi-domain]  Cd Length: 284  Bit Score: 78.07  E-value: 1.87e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  280 VEEFLKEAAVMKEIKHPNLVQLLGVCT--REPPFYIITEFMTYGNLLDYLRECNRQEVNAVVLLymaTQISSAMEYLEKK 357
Cdd:cd14200   67 LERVYQEIAILKKLDHVNIVKLIEVLDdpAEDNLYMVFDLLRKGPVMEVPSDKPFSEDQARLYF---RDIVLGIEYLHYQ 143
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  358 NFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPiKWTAPESLAYNK--FSIKS-DVWAFGVLLWeIAT 434
Cdd:cd14200  144 KIVHRDIKPSNLLLGDDGHVKIADFGVSNQFEGNDALLSSTAGTP-AFMAPETLSDSGqsFSGKAlDVWAMGVTLY-CFV 221
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 62362414  435 YGMSPYPGIDLSQVYELLeKDYRMERPEG--CPEKVYELMRACWQWNPSDRPSFAEI 489
Cdd:cd14200  222 YGKCPFIDEFILALHNKI-KNKPVEFPEEpeISEELKDLILKMLDKNPETRITVPEI 277
STKc_MSK1_C cd14179
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
230-440 1.95e-15

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK1 plays a role in the regulation of translational control and transcriptional activation. It phosphorylates the transcription factors, CREB and NFkB. It also phosphorylates the nucleosomal proteins H3 and HMG-14. Increased phosphorylation of MSK1 is associated with the development of cerebral ischemic/hypoxic preconditioning. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271081 [Multi-domain]  Cd Length: 310  Bit Score: 78.54  E-value: 1.95e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  230 PNYDKWEMERTDitmkHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEdTMEVEEfLKEAAVMKEIK-HPNLVQLLGVCTRE 308
Cdd:cd14179    1 PFYQHYELDLKD----KPLGEGSFSICRKCLHKKTNQEYAVKIVSK-RMEANT-QREIAALKLCEgHPNIVKLHEVYHDQ 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  309 PPFYIITEFMTYGNLLDYLREcnRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLV---GENHLVKVADFGLS 385
Cdd:cd14179   75 LHTFLVMELLKGGELLERIKK--KQHFSETEASHIMRKLVSAVSHMHDVGVVHRDLKPENLLFtdeSDNSEIKIIDFGFA 152
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 62362414  386 RLMTGDTYTAHAGAkFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPY 440
Cdd:cd14179  153 RLKPPDNQPLKTPC-FTLHYAAPELLNYNGYDESCDLWSLGVILYTMLS-GQVPF 205
STKc_DAPK3 cd14195
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 3; STKs ...
244-442 2.04e-15

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK3, also called DAP-like kinase (DLK) and zipper-interacting protein kinase (ZIPk), contains an N-terminal kinase domain and a C-terminal region with nuclear localization signals (NLS) and a leucine zipper motif that mediates homodimerization and interaction with other leucine zipper proteins. It interacts with Par-4, a protein that contains a death domain and interacts with actin filaments. DAPK3 is present in both the cytoplasm and nucleus. Its co-expression with Par-4 results in the co-localization of the two proteins to actin filaments. In addition to cell death, DAPK3 is also implicated in mediating cell motility and the contraction of smooth muscles. The DAPK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271097 [Multi-domain]  Cd Length: 271  Bit Score: 77.74  E-value: 2.04e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  244 MKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEV-------EEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITE 316
Cdd:cd14195    9 MGEELGSGQFAIVRKCREKGTGKEYAAKFIKKRRLSSsrrgvsrEEIEREVNILREIQHPNIITLHDIFENKTDVVLILE 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  317 FMTYGNLLDYLRECNR-QEVNAVVLLymaTQISSAMEYLEKKNFIHRDLAARNCLVGE----NHLVKVADFGLS-RLMTG 390
Cdd:cd14195   89 LVSGGELFDFLAEKESlTEEEATQFL---KQILDGVHYLHSKRIAHFDLKPENIMLLDknvpNPRIKLIDFGIAhKIEAG 165
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 62362414  391 DTYTAHAGAKfpiKWTAPESLAYNKFSIKSDVWAFGVLLWeIATYGMSPYPG 442
Cdd:cd14195  166 NEFKNIFGTP---EFVAPEIVNYEPLGLEADMWSIGVITY-ILLSGASPFLG 213
STKc_Pho85 cd07836
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; ...
247-452 2.11e-15

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Pho85 is a multifunctional CDK in yeast. It is regulated by 10 different cyclins (Pcls) and plays a role in G1 progression, cell polarity, phosphate and glycogen metabolism, gene expression, and in signaling changes in the environment. It is not essential for yeast viability and is the functional homolog of mammalian CDK5, which plays a role in central nervous system development. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The Pho85 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143341 [Multi-domain]  Cd Length: 284  Bit Score: 77.91  E-value: 2.11e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTME--VEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTyGNLL 324
Cdd:cd07836    7 KLGEGTYATVYKGRNRTTGEIVALKEIHLDAEEgtPSTAIREISLMKELKHENIVRLHDVIHTENKLMLVFEYMD-KDLK 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  325 DYLR-ECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMtGDTYTAHAGAKFPI 403
Cdd:cd07836   86 KYMDtHGVRGALDPNTVKSFTYQLLKGIAFCHENRVLHRDLKPQNLLINKRGELKLADFGLARAF-GIPVNTFSNEVVTL 164
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 62362414  404 KWTAPESLAYNK-FSIKSDVWAFGVLLWEIATyGMSPYPGID----LSQVYELL 452
Cdd:cd07836  165 WYRAPDVLLGSRtYSTSIDIWSVGCIMAEMIT-GRPLFPGTNnedqLLKIFRIM 217
STKc_PLK3 cd14189
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the ...
248-493 2.46e-15

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK3, also called Prk or Fnk (FGF-inducible kinase), regulates angiogenesis and responses to DNA damage. Activated PLK3 mediates Chk2 phosphorylation by ATM and the resulting checkpoint activation. PLK3 phosphorylates DNA polymerase delta and may be involved in DNA repair. It also inhibits Cdc25c, thereby regulating the onset of mitosis. The PLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271091 [Multi-domain]  Cd Length: 255  Bit Score: 77.27  E-value: 2.46e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM----EVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNL 323
Cdd:cd14189    9 LGKGGFARCYEMTDLATNKTYAVKVIPHSRVakphQREKIVNEIELHRDLHHKHVVKFSHHFEDAENIYIFLELCSRKSL 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  324 LDYLREcnRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPi 403
Cdd:cd14189   89 AHIWKA--RHTLLEPEVRYYLKQIISGLKYLHLKGILHRDLKLGNFFINENMELKVGDFGLAARLEPPEQRKKTICGTP- 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  404 KWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEK-DYRMerPEGCPEKVYELMRACWQWNPSD 482
Cdd:cd14189  166 NYLAPEVLLRQGHGPESDVWSLGCVMYTLLC-GNPPFETLDLKETYRCIKQvKYTL--PASLSLPARHLLAGILKRNPGD 242
                        250
                 ....*....|...
gi 62362414  483 RPSFAEI--HQAF 493
Cdd:cd14189  243 RLTLDQIleHEFF 255
STKc_TGFbR1_ACVR1b_ACVR1c cd14143
Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta Type I ...
246-483 2.54e-15

Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta Type I Receptor and Activin Type IB/IC Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TGFbR1, also called Activin receptor-Like Kinase 5 (ALK5), functions as a receptor for TGFbeta and phoshorylates SMAD2/3. TGFbeta proteins are cytokines that regulate cell growth, differentiation, and survival, and are critical in the development and progression of many human cancers. Mutations in TGFbR1 (and TGFbR2) can cause aortic aneurysm disorders such as Loeys-Dietz and Marfan syndromes. ACVR1b (also called ALK4) and ACVR1c (also called ALK7) act as receptors for activin A and B, respectively. TGFbR1, ACVR1b, and ACVR1c belong to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like TGFbR1, ACVR1b, and ACVR1c, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The TGFbR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271045 [Multi-domain]  Cd Length: 288  Bit Score: 77.87  E-value: 2.54e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  246 HKLGGGQYGEVYEGVWKKYSltVAVKTLKedTMEVEEFLKEAAVMKEI--KHPNLVQLL-------GVCTReppFYIITE 316
Cdd:cd14143    1 ESIGKGRFGEVWRGRWRGED--VAVKIFS--SREERSWFREAEIYQTVmlRHENILGFIaadnkdnGTWTQ---LWLVSD 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  317 FMTYGNLLDYLrecNRQEVNAVVLLYMATQISSAMEYLE--------KKNFIHRDLAARNCLVGENHLVKVADFGL---- 384
Cdd:cd14143   74 YHEHGSLFDYL---NRYTVTVEGMIKLALSIASGLAHLHmeivgtqgKPAIAHRDLKSKNILVKKNGTCCIADLGLavrh 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  385 -SRLMTGD-TYTAHAGAKfpiKWTAPE----SLAYNKF-SIK-SDVWAFGVLLWEIA----------TYGMsPYpgidls 446
Cdd:cd14143  151 dSATDTIDiAPNHRVGTK---RYMAPEvlddTINMKHFeSFKrADIYALGLVFWEIArrcsiggiheDYQL-PY------ 220
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 62362414  447 qvYELLEKDYRME--RPEGCPEK-----------------VYELMRACWQWNPSDR 483
Cdd:cd14143  221 --YDLVPSDPSIEemRKVVCEQKlrpnipnrwqscealrvMAKIMRECWYANGAAR 274
STKc_LRRK1 cd14067
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 1; STKs catalyze ...
282-484 3.11e-15

Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRK1 is one of two vertebrate LRRKs which show complementary expression in the brain. It can form heterodimers with LRRK2, and may influence the age of onset of LRRK2-associated Parkinson's disease. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. The LRRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270969 [Multi-domain]  Cd Length: 276  Bit Score: 77.31  E-value: 3.11e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  282 EFLKEAAVMKEIKHPNLVQLLGVCTRepPFYIITEFMTYGNLLDYLREcNRQEVNAVVLLYMAT-----QISSAMEYLEK 356
Cdd:cd14067   56 EFRQEASMLHSLQHPCIVYLIGISIH--PLCFALELAPLGSLNTVLEE-NHKGSSFMPLGHMLTfkiayQIAAGLAYLHK 132
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  357 KNFIHRDLAARNCLV-----GENHLVKVADFGLSRlmtgdtYTAHAGA---KFPIKWTAPESLAYNKFSIKSDVWAFGVL 428
Cdd:cd14067  133 KNIIFCDLKSDNILVwsldvQEHINIKLSDYGISR------QSFHEGAlgvEGTPGYQAPEIRPRIVYDEKVDMFSYGMV 206
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 62362414  429 LWEIATyGMSPYPGIDLSQVYELLEKDYrmeRPE-GCPEKV-----YELMRACWQWNPSDRP 484
Cdd:cd14067  207 LYELLS-GQRPSLGHHQLQIAKKLSKGI---RPVlGQPEEVqffrlQALMMECWDTKPEKRP 264
STKc_PLK2 cd14188
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the ...
248-491 3.38e-15

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK2, also called Snk (serum-inducible kinase), functions in G1 progression, S-phase arrest, and centriole duplication. Its gene is responsive to both growth factors and cellular stress, is a transcriptional target of p53, and activates a G2-M checkpoint. The PLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271090 [Multi-domain]  Cd Length: 255  Bit Score: 76.97  E-value: 3.38e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYE----GVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNL 323
Cdd:cd14188    9 LGKGGFAKCYEmtdlTTNKVYAAKIIPHSRVSKPHQREKIDKEIELHRILHHKHVVQFYHYFEDKENIYILLEYCSRRSM 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  324 LDYLREcnRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPi 403
Cdd:cd14188   89 AHILKA--RKVLTEPEVRYYLRQIVSGLKYLHEQEILHRDLKLGNFFINENMELKVGDFGLAARLEPLEHRRRTICGTP- 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  404 KWTAPESLAYNKFSIKSDVWAFGVLLWEIaTYGMSPYPGIDLSQVYELLeKDYRMERPEGCPEKVYELMRACWQWNPSDR 483
Cdd:cd14188  166 NYLSPEVLNKQGHGCESDIWALGCVMYTM-LLGRPPFETTNLKETYRCI-REARYSLPSSLLAPAKHLIASMLSKNPEDR 243

                 ....*...
gi 62362414  484 PSFAEIHQ 491
Cdd:cd14188  244 PSLDEIIR 251
STKc_p38 cd07851
Catalytic domain of the Serine/Threonine Kinase, p38 Mitogen-Activated Protein Kinase; STKs ...
248-453 3.40e-15

Catalytic domain of the Serine/Threonine Kinase, p38 Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They function in the regulation of the cell cycle, cell development, cell differentiation, senescence, tumorigenesis, apoptosis, pain development and pain progression, and immune responses. p38 kinases are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. p38 substrates include other protein kinases and factors that regulate transcription, nuclear export, mRNA stability and translation. p38 kinases are drug targets for the inflammatory diseases psoriasis, rheumatoid arthritis, and chronic pulmonary disease. Vertebrates contain four isoforms of p38, named alpha, beta, gamma, and delta, which show varying substrate specificity and expression patterns. p38alpha and p38beta are ubiquitously expressed, p38gamma is predominantly found in skeletal muscle, and p38delta is found in the heart, lung, testis, pancreas, and small intestine. The p38 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143356 [Multi-domain]  Cd Length: 343  Bit Score: 78.49  E-value: 3.40e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEdTMEVEEFLK----EAAVMKEIKHPNLVQLLGVCTREPP------FYIITEF 317
Cdd:cd07851   23 VGSGAYGQVCSAFDTKTGRKVAIKKLSR-PFQSAIHAKrtyrELRLLKHMKHENVIGLLDVFTPASSledfqdVYLVTHL 101
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  318 MTyGNLLDYLRecnRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRL----MTGdtY 393
Cdd:cd07851  102 MG-ADLNNIVK---CQKLSDDHIQFLVYQILRGLKYIHSAGIIHRDLKPSNLAVNEDCELKILDFGLARHtddeMTG--Y 175
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 62362414  394 TAhagakfpIKW-TAPESL----AYNKfsiKSDVWAFGVLLWEIATyGMSPYPGID-LSQVYELLE 453
Cdd:cd07851  176 VA-------TRWyRAPEIMlnwmHYNQ---TVDIWSVGCIMAELLT-GKTLFPGSDhIDQLKRIMN 230
SH2_Src_Fyn_isoform_a_like cd10418
Src homology 2 (SH2) domain found in Fyn isoform a like proteins; Fyn is a member of the Src ...
127-216 3.44e-15

Src homology 2 (SH2) domain found in Fyn isoform a like proteins; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. This cd contains the SH2 domain found in Fyn isoform a type proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198281  Cd Length: 101  Bit Score: 72.34  E-value: 3.44e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  127 WYHGPVSRNAAE-YLLSSG-INGSFLVRESESSPGQRSISLR----YEG-RVYHYRINTASDGKLYVSSESRFNTLAELV 199
Cdd:cd10418    5 WYFGKLGRKDAErQLLSFGnPRGTFLIRESETTKGAYSLSIRdwddMKGdHVKHYKIRKLDNGGYYITTRAQFETLQQLV 84
                         90
                 ....*....|....*..
gi 62362414  200 HHHSTVADGLITTLHYP 216
Cdd:cd10418   85 QHYSERAAGLCCRLVVP 101
STKc_CDKL5 cd07848
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs ...
248-442 3.63e-15

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mutations in the gene encoding CDKL5, previously called STK9, are associated with early onset epilepsy and severe mental retardation [X-linked infantile spasm syndrome (ISSX) or West syndrome]. In addition, CDKL5 mutations also sometimes cause a phenotype similar to Rett syndrome (RTT), a progressive neurodevelopmental disorder. These pathogenic mutations are located in the N-terminal portion of the protein within the kinase domain. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270838 [Multi-domain]  Cd Length: 287  Bit Score: 77.34  E-value: 3.63e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLK--EDTMEVEEF-LKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTyGNLL 324
Cdd:cd07848    9 VGEGAYGVVLKCRHKETKEIVAIKKFKdsEENEEVKETtLRELKMLRTLKQENIVELKEAFRRRGKLYLVFEYVE-KNML 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  325 DYLRECNRQEVNAVVLLYMaTQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDT---YTAHAGAKF 401
Cdd:cd07848   88 ELLEEMPNGVPPEKVRSYI-YQLIKAIHWCHKNDIVHRDIKPENLLISHNDVLKLCDFGFARNLSEGSnanYTEYVATRW 166
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 62362414  402 pikWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPG 442
Cdd:cd07848  167 ---YRSPELLLGAPYGKAVDMWSVGCILGELSD-GQPLFPG 203
STKc_MAST_like cd05579
Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs ...
250-440 4.60e-15

Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAST kinases, MAST-like (MASTL) kinases (also called greatwall kinase or Gwl), and fungal kinases with similarity to Saccharomyces cerevisiae Rim15 and Schizosaccharomyces pombe cek1. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. MASTL kinases carry only a catalytic domain which contains a long insert relative to other kinases. The fungal kinases in this subfamily harbor other domains in addition to a central catalytic domain, which like in MASTL, also contains an insert relative to MAST kinases. Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MASTL/Gwl is involved in the regulation of mitotic entry, mRNA stabilization, and DNA checkpoint recovery. The fungal proteins Rim15 and cek1 are involved in the regulation of meiosis and mitosis, respectively. The MAST-like kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270731 [Multi-domain]  Cd Length: 272  Bit Score: 76.87  E-value: 4.60e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  250 GGQYGEVYEGVWKKYSLTVAVKTLKEDTM----EVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLD 325
Cdd:cd05579    3 RGAYGRVYLAKKKSTGDLYAIKVIKKRDMirknQVDSVLAERNILSQAQNPFVVKLYYSFQGKKNLYLVMEYLPGGDLYS 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  326 YLRECNR-QEVNAVVllYMAtQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRL-MTGDTYTAHAGAKFPI 403
Cdd:cd05579   83 LLENVGAlDEDVARI--YIA-EIVLALEYLHSHGIIHRDLKPDNILIDANGHLKLTDFGLSKVgLVRRQIKLSIQKKSNG 159
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 62362414  404 KWT-------------APESLAYNKFSIKSDVWAFGVLLWEIATyGMSPY 440
Cdd:cd05579  160 APEkedrrivgtpdylAPEILLGQGHGKTVDWWSLGVILYEFLV-GIPPF 208
SH2_Cterm_shark_like cd10348
C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
127-209 4.65e-15

C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) proteins; These non-receptor protein-tyrosine kinases contain two SH2 domains, five ankyrin (ANK)-like repeats, and a potential tyrosine phosphorylation site in its carboxyl-terminal tail which resembles the phosphorylation site in members of the src family. Like, mammalian non-receptor protein-tyrosine kinases, ZAP-70 and syk proteins, they do not have SH3 domains. However, the presence of ANK makes these unique among protein-tyrosine kinases. Both tyrosine kinases and ANK repeats have been shown to transduce developmental signals, and SH2 domains are known to participate intimately in tyrosine kinase signaling. These tyrosine kinases are believed to be involved in epithelial cell polarity. The members of this family include the shark (SH2 domains, ANK, and kinase domain) gene in Drosophila and yellow fever mosquitos, as well as the hydra protein HTK16. Drosophila Shark is proposed to transduce intracellularly the Crumbs, a protein necessary for proper organization of ectodermal epithelia, intercellular signal. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198211  Cd Length: 86  Bit Score: 71.30  E-value: 4.65e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  127 WYHGPVSRNAAEYLL--SSGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTASDGKLYVSSESRFNTLAELVHHHST 204
Cdd:cd10348    2 WLHGALDRNEAVEILkqKADADGSFLVRYSRRRPGGYVLTLVYENHVYHFEIQNRDDKWFYIDDGPYFESLEHLIEHYTQ 81

                 ....*
gi 62362414  205 VADGL 209
Cdd:cd10348   82 FADGL 86
STKc_GSK3 cd14137
The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze ...
242-426 4.83e-15

The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GSK3 is a mutifunctional kinase involved in many cellular processes including cell division, proliferation, differentiation, adhesion, and apoptosis. In plants, GSK3 plays a role in the response to osmotic stress. In Caenorhabditis elegans, it plays a role in regulating normal oocyte-to-embryo transition and response to oxidative stress. In Chlamydomonas reinhardtii, GSK3 regulates flagellar length and assembly. In mammals, there are two isoforms, GSK3alpha and GSK3beta, which show both distinct and redundant functions. The two isoforms differ mainly in their N-termini. They are both involved in axon formation and in Wnt signaling.They play distinct roles in cardiogenesis, with GSKalpha being essential in cardiomyocyte survival, and GSKbeta regulating heart positioning and left-right symmetry. GSK3beta was first identified as a regulator of glycogen synthesis, but has since been determined to play other roles. It regulates the degradation of beta-catenin and IkB. Beta-catenin is the main effector of Wnt, which is involved in normal haematopoiesis and stem cell function. IkB is a central inhibitor of NF-kB, which is critical in maintaining leukemic cell growth. GSK3beta is enriched in the brain and is involved in regulating neuronal signaling pathways. It is implicated in the pathogenesis of many diseases including Type II diabetes, obesity, mood disorders, Alzheimer's disease, osteoporosis, and some types of cancer, among others. The GSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271039 [Multi-domain]  Cd Length: 293  Bit Score: 77.16  E-value: 4.83e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  242 ITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDT----MEVEeflkeaaVMKEIKHPNLVQLL------GVCTREPPF 311
Cdd:cd14137    6 YTIEKVIGSGSFGVVYQAKLLETGEVVAIKKVLQDKryknRELQ-------IMRRLKHPNIVKLKyffyssGEKKDEVYL 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  312 YIITEFMTYgNLLDYLRECNRQEvNAVVLLYM---ATQISSAMEYLEKKNFIHRDLAARNCLV-GENHLVKVADFGlS-- 385
Cdd:cd14137   79 NLVMEYMPE-TLYRVIRHYSKNK-QTIPIIYVklySYQLFRGLAYLHSLGICHRDIKPQNLLVdPETGVLKLCDFG-Sak 155
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 62362414  386 RLMTGDTYTAHAGAKFpikWTAPESLA----YNkFSIksDVWAFG 426
Cdd:cd14137  156 RLVPGEPNVSYICSRY---YRAPELIFgatdYT-TAI--DIWSAG 194
SH2_Src_Blk cd10371
Src homology 2 (SH2) domain found in B lymphoid kinase (Blk); Blk is a member of the Src ...
123-216 5.63e-15

Src homology 2 (SH2) domain found in B lymphoid kinase (Blk); Blk is a member of the Src non-receptor type tyrosine kinase family of proteins. Blk is expressed in the B-cells. Unlike most other Src members Blk lacks cysteine residues in the SH4 domain that undergo palmitylation. Blk is required for the development of IL-17-producing gamma-delta T cells. Furthermore, Blk is expressed in lymphoid precursors and, in this capacity, plays a role in regulating thymus cellularity during ontogeny. Blk has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198234 [Multi-domain]  Cd Length: 100  Bit Score: 71.59  E-value: 5.63e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  123 EKHSWYHGPVSRNAAEYLLSSGIN--GSFLVRESESSPGQRSISLR---YEGRVY-HYRINTASDGKLYVSSESRFNTLA 196
Cdd:cd10371    1 EVEKWFFRTISRKDAERQLLAPMNkaGSFLIRESESNKGAFSLSVKdvtTQGEVVkHYKIRSLDNGGYYISPRITFPTLQ 80
                         90       100
                 ....*....|....*....|
gi 62362414  197 ELVHHHSTVADGLITTLHYP 216
Cdd:cd10371   81 ALVQHYSKKGDGLCQKLTLP 100
SH2_SHB_SHD_SHE_SHF_like cd09945
Src homology 2 domain found in SH2 domain-containing adapter proteins B, D, E, and F (SHB, SHD, ...
127-204 5.66e-15

Src homology 2 domain found in SH2 domain-containing adapter proteins B, D, E, and F (SHB, SHD, SHE, SHF); SHB, SHD, SHE, and SHF are SH2 domain-containing proteins that play various roles throughout the cell. SHB functions in generating signaling compounds in response to tyrosine kinase activation. SHB contains proline-rich motifs, a phosphotyrosine binding (PTB) domain, tyrosine phosphorylation sites, and a SH2 domain. SHB mediates certain aspects of platelet-derived growth factor (PDGF) receptor-, fibroblast growth factor (FGF) receptor-, neural growth factor (NGF) receptor TRKA-, T cell receptor-, interleukin-2 (IL-2) receptor- and focal adhesion kinase- (FAK) signaling. SRC-like FYN-Related Kinase FRK/RAK (also named BSK/IYK or GTK) and SHB regulate apoptosis, proliferation and differentiation. SHB promotes apoptosis and is also required for proper mitogenicity, spreading and tubular morphogenesis in endothelial cells. SHB also plays a role in preventing early cavitation of embryoid bodies and reduces differentiation to cells expressing albumin, amylase, insulin and glucagon. SHB is a multifunctional protein that has difference responses in different cells under various conditions. SHE is expressed in heart, lung, brain, and skeletal muscle, while expression of SHD is restricted to the brain. SHF is mainly expressed in skeletal muscle, brain, liver, prostate, testis, ovary, small intestine, and colon. SHD may be a physiological substrate of c-Abl and may function as an adapter protein in the central nervous system. It is also thought to be involved in apoptotic regulation. SHD contains five YXXP motifs, a substrate sequence preferred by Abl tyrosine kinases, in addition to a poly-proline rich region and a C-terminal SH2 domain. SHE contains two pTry protein binding domains, protein interaction domain (PID) and a SH2 domain, followed by a glycine-proline rich region, all of which are N-terminal to the phosphotyrosine binding (PTB) domain. SHF contains four putative tyrosine phosphorylation sites and an SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198198  Cd Length: 98  Bit Score: 71.69  E-value: 5.66e-15
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 62362414  127 WYHGPVSRNAAEYLLSSGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTASDGKLYVSSESR-FNTLAELVHHHST 204
Cdd:cd09945    3 WYHGAITRIEAESLLRPCKEGSYLVRNSESTKQDYSLSLKSAKGFMHMRIQRNETGQYILGQFSRpFETIPEMIRHYCL 81
STKc_PKD cd14082
Catalytic domain of the Serine/Threonine kinase, Protein Kinase D; STKs catalyze the transfer ...
248-430 6.02e-15

Catalytic domain of the Serine/Threonine kinase, Protein Kinase D; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKDs are important regulators of many intracellular signaling pathways such as ERK and JNK, and cellular processes including the organization of the trans-Golgi network, membrane trafficking, cell proliferation, migration, and apoptosis. They contain N-terminal cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. Mammals harbor three types of PKDs: PKD1 (or PKCmu), PKD2, and PKD3 (or PKCnu). PKDs are activated in a PKC-dependent manner by many agents including diacylglycerol (DAG), PDGF, neuropeptides, oxidative stress, and tumor-promoting phorbol esters, among others. The PKD subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270984 [Multi-domain]  Cd Length: 260  Bit Score: 76.30  E-value: 6.02e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKT---LKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMtYGNLL 324
Cdd:cd14082   11 LGSGQFGIVYGGKHRKTGRDVAIKVidkLRFPTKQESQLRNEVAILQQLSHPGVVNLECMFETPERVFVVMEKL-HGDML 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  325 DYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENH---LVKVADFGLSRLMtGDTYTAHAGAKF 401
Cdd:cd14082   90 EMILSSEKGRLPERITKFLVTQILVALRYLHSKNIVHCDLKPENVLLASAEpfpQVKLCDFGFARII-GEKSFRRSVVGT 168
                        170       180
                 ....*....|....*....|....*....
gi 62362414  402 PiKWTAPESLAYNKFSIKSDVWAFGVLLW 430
Cdd:cd14082  169 P-AYLAPEVLRNKGYNRSLDMWSVGVIIY 196
STKc_WNK4 cd14033
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze ...
247-483 6.36e-15

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK4 shows a restricted expression pattern and is usually found in epithelial cells. It is expressed in nephrons and in extrarenal tissues including intestine, eye, mammary glands, and prostate. WNK4 regulates a variety of ion transport proteins including apical or basolateral ion transporters, ion channels in the transcellular pathway, and claudins in the paracellular pathway. Mutations in WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension and hyperkalemia. WNK4 inhibits the activity of the thiazide-sensitive Na-Cl cotransporter (NCC), which is responsible for about 15% of NaCl reabsorption in the kidney. It also inhibits the renal outer medullary potassium channel (ROMK) and decreases its surface expression. Hypertension and hyperkalemia in PHAII patients with WNK4 mutations may be partly due to increased NaCl reabsorption through NCC and impaired renal potassium secretion by ROMK, respectively. The WNK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270935 [Multi-domain]  Cd Length: 261  Bit Score: 76.20  E-value: 6.36e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVA---VKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLG---------VCTreppfYII 314
Cdd:cd14033    8 EIGRGSFKTVYRGLDTETTVEVAwceLQTRKLSKGERQRFSEEVEMLKGLQHPNIVRFYDswkstvrghKCI-----ILV 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  315 TEFMTYGNLLDYLRECnrQEVNAVVLLYMATQISSAMEYLEKKN--FIHRDLAARNCLV-GENHLVKVADFGLSRLMTGD 391
Cdd:cd14033   83 TELMTSGTLKTYLKRF--REMKLKLLQRWSRQILKGLHFLHSRCppILHRDLKCDNIFItGPTGSVKIGDLGLATLKRAS 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  392 TYTAHAGAKfpiKWTAPEsLAYNKFSIKSDVWAFGVLLWEIATygmSPYPGIDL---SQVYELLEKD------YRMERPE 462
Cdd:cd14033  161 FAKSVIGTP---EFMAPE-MYEEKYDEAVDVYAFGMCILEMAT---SEYPYSECqnaAQIYRKVTSGikpdsfYKVKVPE 233
                        250       260
                 ....*....|....*....|.
gi 62362414  463 gcpekVYELMRACWQWNPSDR 483
Cdd:cd14033  234 -----LKEIIEGCIRTDKDER 249
STKc_MEKK3_like_u1 cd06653
Catalytic domain of an Uncharacterized subfamily of Mitogen-Activated Protein (MAP) ...
248-489 6.64e-15

Catalytic domain of an Uncharacterized subfamily of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of uncharacterized proteins with similarity to MEKK3, MEKK2, and related proteins; they contain an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are MAPK kinase kinases (MAPKKKs or MKKKs), proteins that phosphorylate and activate MAPK kinases (MAPKKs or MKKs), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MEKK2 and MEKK3 activate MEK5 (also called MKK5), which activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. MEKK2 and MEKK3 can also activate the MAPKs, c-Jun N-terminal kinase (JNK) and p38, through their respective MAPKKs. The MEKK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270819 [Multi-domain]  Cd Length: 264  Bit Score: 76.22  E-value: 6.64e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTL------KEDTMEVEEFLKEAAVMKEIKHPNLVQLLGvCTREP---PFYIITEFM 318
Cdd:cd06653   10 LGRGAFGEVYLCYDADTGRELAVKQVpfdpdsQETSKEVNALECEIQLLKNLRHDRIVQYYG-CLRDPeekKLSIFVEYM 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  319 TYGNLLDYLRECNRQEVNavVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR-----LMTGDTY 393
Cdd:cd06653   89 PGGSVKDQLKAYGALTEN--VTRRYTRQILQGVSYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASKriqtiCMSGTGI 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  394 TAHAGAKFpikWTAPESLAYNKFSIKSDVWAFGVLLWEIATYgMSPYPGID-LSQVYELLEKDYRMERPEGCPEKVYELM 472
Cdd:cd06653  167 KSVTGTPY---WMSPEVISGEGYGRKADVWSVACTVVEMLTE-KPPWAEYEaMAAIFKIATQPTKPQLPDGVSDACRDFL 242
                        250
                 ....*....|....*..
gi 62362414  473 RACWQWNpSDRPSFAEI 489
Cdd:cd06653  243 RQIFVEE-KRRPTAEFL 258
STKc_PhKG cd14093
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs ...
275-430 6.80e-15

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). Each subunit has tissue-specific isoforms or splice variants. Vertebrates contain two isoforms of the gamma subunit (gamma 1 and gamma 2). The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270995 [Multi-domain]  Cd Length: 272  Bit Score: 76.24  E-value: 6.80e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  275 EDTMEVEEFLKEAAVMKEI-KHPNLVQLLGVCTREPPFYIITEFMTYGNLLDYLrecnrqevNAVVLL------YMATQI 347
Cdd:cd14093   47 EAEELREATRREIEILRQVsGHPNIIELHDVFESPTFIFLVFELCRKGELFDYL--------TEVVTLsekktrRIMRQL 118
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  348 SSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLS-RLMTGDTYTAHAGAKfpiKWTAPESLAYNKF------SIKS 420
Cdd:cd14093  119 FEAVEFLHSLNIVHRDLKPENILLDDNLNVKISDFGFAtRLDEGEKLRELCGTP---GYLAPEVLKCSMYdnapgyGKEV 195
                        170
                 ....*....|
gi 62362414  421 DVWAFGVLLW 430
Cdd:cd14093  196 DMWACGVIMY 205
STKc_MAP4K5 cd06646
Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase ...
241-485 7.47e-15

Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). MAP4K5 also facilitates Wnt signaling in B cells, and may therefore be implicated in the control of cell fate, proliferation, and polarity. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. The MAP4K5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270813 [Multi-domain]  Cd Length: 268  Bit Score: 76.22  E-value: 7.47e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  241 DITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLK-EDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMT 319
Cdd:cd06646   10 DYELIQRVGSGTYGDVYKARNLHTGELAAVKIIKlEPGDDFSLIQQEIFMVKECKHCNIVAYFGSYLSREKLWICMEYCG 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  320 YGNLLDY------LRECNrqevnavvLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTY 393
Cdd:cd06646   90 GGSLQDIyhvtgpLSELQ--------IAYVCRETLQGLAYLHSKGKMHRDIKGANILLTDNGDVKLADFGVAAKITATIA 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  394 TAHAGAKFPIkWTAPESLAYNK---FSIKSDVWAFGVLLWEIATygMSPyPGIDLSQVYELLEKDYRMERPEGCPEKV-- 468
Cdd:cd06646  162 KRKSFIGTPY-WMAPEVAAVEKnggYNQLCDIWAVGITAIELAE--LQP-PMFDLHPMRALFLMSKSNFQPPKLKDKTkw 237
                        250       260
                 ....*....|....*....|.
gi 62362414  469 ----YELMRACWQWNPSDRPS 485
Cdd:cd06646  238 sstfHNFVKISLTKNPKKRPT 258
STKc_CDK4 cd07863
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4; STKs ...
247-432 7.70e-15

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 partners with all three D-type cyclins (D1, D2, and D3) and is also regulated by INK4 inhibitors. It is active towards the retinoblastoma (pRb) protein and plays a role in regulating the early G1 phase of the cell cycle. It is expressed ubiquitously and is localized in the nucleus. CDK4 also shows kinase activity towards Smad3, a signal transducer of TGF-beta signaling which modulates transcription and plays a role in cell proliferation and apoptosis. CDK4 is inhibited by the p21 inhibitor and is specifically mutated in human melanoma. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143368 [Multi-domain]  Cd Length: 288  Bit Score: 76.54  E-value: 7.70e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLK----EDTMEVEEfLKEAAVMKEIK---HPNLVQLLGVCT-----REPPFYII 314
Cdd:cd07863    7 EIGVGAYGTVYKARDPHSGHFVALKSVRvqtnEDGLPLST-VREVALLKRLEafdHPNIVRLMDVCAtsrtdRETKVTLV 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  315 TEFMTYgNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLmtgdtYT 394
Cdd:cd07863   86 FEHVDQ-DLRTYLDKVPPPGLPAETIKDLMRQFLRGLDFLHANCIVHRDLKPENILVTSGGQVKLADFGLARI-----YS 159
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 62362414  395 AHAgAKFPIKWT----APESLAYNKFSIKSDVWAFGVLLWEI 432
Cdd:cd07863  160 CQM-ALTPVVVTlwyrAPEVLLQSTYATPVDMWSVGCIFAEM 200
STKc_CDK1_CdkB_like cd07835
Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of ...
247-434 8.02e-15

Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of Plant B-type Cyclin-Dependent protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK, CDK2, and CDK3. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression while the CDK1/cyclin B complex is critical for G2 to M phase transition. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. Studies in knockout mice revealed that CDK1 can compensate for the loss of the cdk2 gene as it can also bind cyclin E and drive G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. The plant-specific B-type CDKs are expressed from the late S to the M phase of the cell cycle. They are characterized by the cyclin binding motif PPT[A/T]LRE. They play a role in controlling mitosis and integrating developmental pathways, such as stomata and leaf development. CdkB has been shown to associate with both cyclin B, which controls G2/M transition, and cyclin D, which acts as a mediator in linking extracellular signals to the cell cycle. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270829 [Multi-domain]  Cd Length: 283  Bit Score: 76.17  E-value: 8.02e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLKedtMEVEE------FLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTY 320
Cdd:cd07835    6 KIGEGTYGVVYKARDKLTGEIVALKKIR---LETEDegvpstAIREISLLKELNHPNIVRLLDVVHSENKLYLVFEFLDL 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  321 gNLLDYLRECNRQEVNA-VVLLYMaTQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMT--GDTYTaHA 397
Cdd:cd07835   83 -DLKKYMDSSPLTGLDPpLIKSYL-YQLLQGIAFCHSHRVLHRDLKPQNLLIDTEGALKLADFGLARAFGvpVRTYT-HE 159
                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 62362414  398 GAKFpikW-TAPESLAYNK-FSIKSDVWAFGVLLWEIAT 434
Cdd:cd07835  160 VVTL---WyRAPEILLGSKhYSTPVDIWSVGCIFAEMVT 195
SH2_Src_Fgr cd10367
Src homology 2 (SH2) domain found in Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene ...
127-216 8.16e-15

Src homology 2 (SH2) domain found in Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog, Fgr; Fgr is a member of the Src non-receptor type tyrosine kinase family of proteins. The protein contains N-terminal sites for myristoylation and palmitoylation, a PTK domain, and SH2 and SH3 domains which are involved in mediating protein-protein interactions with phosphotyrosine-containing and proline-rich motifs, respectively. Fgr is expressed in B-cells and myeloid cells, localizes to plasma membrane ruffles, and functions as a negative regulator of cell migration and adhesion triggered by the beta-2 integrin signal transduction pathway. Multiple alternatively spliced variants, encoding the same protein, have been identified Fgr has been shown to interact with Wiskott-Aldrich syndrome protein. Fgr has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198230  Cd Length: 101  Bit Score: 71.09  E-value: 8.16e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  127 WYHGPVSRNAAEYLLSSGIN--GSFLVRESESSPGQRSISLR-----YEGRVYHYRINTASDGKLYVSSESRFNTLAELV 199
Cdd:cd10367    5 WYFGKIGRKDAERQLLSPGNprGAFLIRESETTKGAYSLSIRdwdqnRGDHVKHYKIRKLDTGGYYITTRAQFDTVQELV 84
                         90
                 ....*....|....*..
gi 62362414  200 HHHSTVADGLITTLHYP 216
Cdd:cd10367   85 QHYMEVNDGLCYLLTAP 101
PTKc_Wee1_fungi cd14052
Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the ...
246-489 8.57e-15

Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of fungal Wee1 proteins, also called Swe1 in budding yeast and Mik1 in fission yeast. Yeast Wee1 is required to control cell size. Wee1 is a cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. The fungal Wee1 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270954 [Multi-domain]  Cd Length: 278  Bit Score: 75.92  E-value: 8.57e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  246 HKLGGGQYGEVYEGVWKKYSLTV-AVKTLKEDTM---EVEEFLKEAAVMKEIK---HPNLVQLLGVCTREPPFYIITEFM 318
Cdd:cd14052    6 ELIGSGEFSQVYKVSERVPTGKVyAVKKLKPNYAgakDRLRRLEEVSILRELTldgHDNIVQLIDSWEYHGHLYIQTELC 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  319 TYGNLLDYLRECNRQEV-NAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHA 397
Cdd:cd14052   86 ENGSLDVFLSELGLLGRlDEFRVWKILVELSLGLRFIHDHHFVHLDLKPANVLITFEGTLKIGDFGMATVWPLIRGIERE 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  398 GAKfpiKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGI--------DLSQVYELLEKD-YRMERPEGCPEKV 468
Cdd:cd14052  166 GDR---EYIAPEILSEHMYDKPADIFSLGLILLEAAANVVLPDNGDawqklrsgDLSDAPRLSSTDlHSASSPSSNPPPD 242
                        250       260       270
                 ....*....|....*....|....*....|..
gi 62362414  469 YELMRAC-------WQW----NPSDRPSFAEI 489
Cdd:cd14052  243 PPNMPILsgsldrvVRWmlspEPDRRPTADDV 274
STKc_WNK3 cd14031
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3; STKs catalyze ...
247-489 9.33e-15

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK3 shows a restricted expression pattern; it is found at high levels in the pituary glands and is also expressed in the kidney and brain. It has been shown to regulate many ion transporters including members of the SLC12A family of cation-chloride cotransporters such as NCC and NKCC2, the renal potassium channel ROMK, and the epithelial calcium channels TRPV5 and TRPV6. WNK3 appears to sense low-chloride hypotonic stress and under these conditions, it activates SPAK, which directly interacts and phosphorylates cation-chloride cotransporters. WNK3 has also been shown to promote cell survival, possibly through interaction with procaspase-3 and HSP70. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. The WNK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270933 [Multi-domain]  Cd Length: 275  Bit Score: 75.91  E-value: 9.33e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM---EVEEFLKEAAVMKEIKHPNLVQLL----GVCTREPPFYIITEFMT 319
Cdd:cd14031   17 ELGRGAFKTVYKGLDTETWVEVAWCELQDRKLtkaEQQRFKEEAEMLKGLQHPNIVRFYdsweSVLKGKKCIVLVTELMT 96
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  320 YGNLLDYLRECnrQEVNAVVLLYMATQISSAMEYLEKKN--FIHRDLAARNCLV-GENHLVKVADFGLSRLMTGDTYTAH 396
Cdd:cd14031   97 SGTLKTYLKRF--KVMKPKVLRSWCRQILKGLQFLHTRTppIIHRDLKCDNIFItGPTGSVKIGDLGLATLMRTSFAKSV 174
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  397 AGAKfpiKWTAPEsLAYNKFSIKSDVWAFGVLLWEIATygmSPYPGIDLSQVYELLEKDYRMERPEGC-----PEkVYEL 471
Cdd:cd14031  175 IGTP---EFMAPE-MYEEHYDESVDVYAFGMCMLEMAT---SEYPYSECQNAAQIYRKVTSGIKPASFnkvtdPE-VKEI 246
                        250
                 ....*....|....*...
gi 62362414  472 MRACWQWNPSDRPSFAEI 489
Cdd:cd14031  247 IEGCIRQNKSERLSIKDL 264
SH2_Srm cd10360
Src homology 2 (SH2) domain found in Src-related kinase lacking C-terminal regulatory tyrosine ...
127-202 9.92e-15

Src homology 2 (SH2) domain found in Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristoylation sites (srm); Srm is a nonreceptor protein kinase that has two SH2 domains, a SH3 domain, and a kinase domain with a tyrosine residue for autophosphorylation. However it lacks an N-terminal glycine for myristoylation and a C-terminal tyrosine which suppresses kinase activity when phosphorylated. Srm is most similar to members of the Tec family who other members include: Tec, Btk/Emb, and Itk/Tsk/Emt. However Srm differs in its N-terminal unique domain it being much smaller than in the Tec family and is closer to Src. Srm is thought to be a new family of nonreceptor tyrosine kinases that may be redundant in function. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198223  Cd Length: 79  Bit Score: 70.37  E-value: 9.92e-15
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 62362414  127 WYHGPVSRNAAEYLLSSGIN--GSFLVRESESSPGQRSISLRYEGRVYHYRINTASDGKLYVSSESRFNTLAELVHHH 202
Cdd:cd10360    2 WYFSGISRTQAQQLLLSPPNepGAFLIRPSESSLGGYSLSVRAQAKVCHYRICMAPSGSLYLQKGRLFPGLEELLAYY 79
STKc_CASK cd14094
Catalytic domain of the Serine/Threonine Kinase, Calcium/calmodulin-dependent serine protein ...
246-488 1.08e-14

Catalytic domain of the Serine/Threonine Kinase, Calcium/calmodulin-dependent serine protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CASK belongs to the MAGUK (membrane-associated guanylate kinase) protein family, which functions as multiple domain adaptor proteins and is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). The enzymatically inactive GuK domain in MAGUK proteins mediates protein-protein interactions and associates intramolecularly with the SH3 domain. In addition, CASK contains a catalytic kinase and two L27 domains. It is highly expressed in the nervous system and plays roles in synaptic protein targeting, neural development, and regulation of gene expression. Binding partners include parkin (a Parkinson's disease molecule), neurexin (adhesion molecule), syndecans, calcium channel proteins, CINAP (nucleosome assembly protein), transcription factor Tbr-1, and the cytoplasmic adaptor proteins Mint1, Veli/mLIN-7/MALS, SAP97, caskin, and CIP98. Deletion or mutations in the CASK gene have been implicated in X-linked mental retardation. The CASK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270996 [Multi-domain]  Cd Length: 300  Bit Score: 76.04  E-value: 1.08e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  246 HKLGGGQYGEVYEGVWKKYSLTVAVKTL------KEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMT 319
Cdd:cd14094    9 EVIGKGPFSVVRRCIHRETGQQFAVKIVdvakftSSPGLSTEDLKREASICHMLKHPHIVELLETYSSDGMLYMVFEFMD 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  320 yGNllDYLRECNRQEVN------AVVLLYMaTQISSAMEYLEKKNFIHRDLAARNCLVG--ENHL-VKVADFGLSRLMTG 390
Cdd:cd14094   89 -GA--DLCFEIVKRADAgfvyseAVASHYM-RQILEALRYCHDNNIIHRDVKPHCVLLAskENSApVKLGGFGVAIQLGE 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  391 DTYTAHAGAKFPiKWTAPESLAYNKFSIKSDVWAFGVLLWeIATYGMSPYPGIDlSQVYELLEK-DYRMERPE--GCPEK 467
Cdd:cd14094  165 SGLVAGGRVGTP-HFMAPEVVKREPYGKPVDVWGCGVILF-ILLSGCLPFYGTK-ERLFEGIIKgKYKMNPRQwsHISES 241
                        250       260
                 ....*....|....*....|.
gi 62362414  468 VYELMRACWQWNPSDRPSFAE 488
Cdd:cd14094  242 AKDLVRRMLMLDPAERITVYE 262
SH2_Nck1 cd10408
Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin ...
127-202 1.22e-14

Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198271  Cd Length: 97  Bit Score: 70.44  E-value: 1.22e-14
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 62362414  127 WYHGPVSRNAAEYLLSS-GINGSFLVRESESSPGQRSISLRYEGRVYHYRINTASDgkLYVSSESRFNTLAELVHHH 202
Cdd:cd10408    3 WYYGKVTRHQAEMALNErGNEGDFLIRDSESSPNDFSVSLKAQGKNKHFKVQLKEC--VYCIGQRKFSSMEELVEHY 77
PKc_MEK1 cd06650
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
236-487 1.25e-14

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 1; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 is a dual-specificity PK and a MAPK kinase (MAPKK or MKK) that phosphorylates and activates the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. MEK1 also plays a role in cell cycle control. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270816 [Multi-domain]  Cd Length: 319  Bit Score: 76.25  E-value: 1.25e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  236 EMERTDITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKedtMEVE-----EFLKEAAVMKEIKHPNLVQLLGVCTREPP 310
Cdd:cd06650    1 ELKDDDFEKISELGAGNGGVVFKVSHKPSGLVMARKLIH---LEIKpairnQIIRELQVLHECNSPYIVGFYGAFYSDGE 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  311 FYIITEFMTYGNLLDYLRECNRqeVNAVVLLYMATQISSAMEYL-EKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMT 389
Cdd:cd06650   78 ISICMEHMDGGSLDQVLKKAGR--IPEQILGKVSIAVIKGLTYLrEKHKIMHRDVKPSNILVNSRGEIKLCDFGVSGQLI 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  390 GDTYTAHAGAKfpiKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVyELLEKDYRMERPEGCPEKVY 469
Cdd:cd06650  156 DSMANSFVGTR---SYMSPERLQGTHYSVQSDIWSMGLSLVEMAV-GRYPIPPPDAKEL-ELMFGCQVEGDAAETPPRPR 230
                        250
                 ....*....|....*...
gi 62362414  470 ELMRACWQWNPSDRPSFA 487
Cdd:cd06650  231 TPGRPLSSYGMDSRPPMA 248
STKc_CDK10 cd07845
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs ...
246-432 1.27e-14

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK10, also called PISSLRE, is essential for cell growth and proliferation, and acts through the G2/M phase of the cell cycle. CDK10 has also been identified as an important factor in endocrine therapy resistance in breast cancer. CDK10 silencing increases the transcription of c-RAF and the activation of the p42/p44 MAPK pathway, which leads to antiestrogen resistance. Patients who express low levels of CDK10 relapse early on tamoxifen. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK10 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173742 [Multi-domain]  Cd Length: 309  Bit Score: 76.25  E-value: 1.27e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  246 HKLGGGQYGEVYEGVWKKYSLTVAVKTLKedtMEVEE------FLKEAAVMKEIKHPNLVQLLGVCT--REPPFYIITEF 317
Cdd:cd07845   13 NRIGEGTYGIVYRARDTTSGEIVALKKVR---MDNERdgipisSLREITLLLNLRHPNIVELKEVVVgkHLDSIFLVMEY 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  318 MTY--GNLLDYL-RECNRQEVNAVVLlymatQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRlmtgdTYT 394
Cdd:cd07845   90 CEQdlASLLDNMpTPFSESQVKCLML-----QLLRGLQYLHENFIIHRDLKVSNLLLTDKGCLKIADFGLAR-----TYG 159
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 62362414  395 AHAGAKFPIKWT----APESLAYNKFSIKS-DVWAFGVLLWEI 432
Cdd:cd07845  160 LPAKPMTPKVVTlwyrAPELLLGCTTYTTAiDMWAVGCILAEL 202
STKc_p38delta cd07879
Catalytic domain of the Serine/Threonine Kinase, p38delta Mitogen-Activated Protein Kinase ...
231-453 1.30e-14

Catalytic domain of the Serine/Threonine Kinase, p38delta Mitogen-Activated Protein Kinase (also called MAPK13); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38delta/MAPK13 is found in skeletal muscle, heart, lung, testis, pancreas, and small intestine. It regulates microtubule function by phosphorylating Tau. It activates the c-jun promoter and plays a role in G2 cell cycle arrest. It also controls the degration of c-Myb, which is associated with myeloid leukemia and poor prognosis in colorectal cancer. p38delta is the main isoform involved in regulating the differentiation and apoptosis of keratinocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38delta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143384 [Multi-domain]  Cd Length: 342  Bit Score: 76.48  E-value: 1.30e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  231 NYDKWEMERTDITMKHkLGGGQYGEVYEGVWKKYSLTVAVKTLKEdTMEVEEFLKEA----AVMKEIKHPNLVQLLGVCT 306
Cdd:cd07879    7 NKTVWELPERYTSLKQ-VGSGAYGSVCSAIDKRTGEKVAIKKLSR-PFQSEIFAKRAyrelTLLKHMQHENVIGLLDVFT 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  307 REPP------FYIITEFMTYGnlldyLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVA 380
Cdd:cd07879   85 SAVSgdefqdFYLVMPYMQTD-----LQKIMGHPLSEDKVQYLVYQMLCGLKYIHSAGIIHRDLKPGNLAVNEDCELKIL 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  381 DFGLSRL----MTGDTYTahagakfpiKW-TAPES-LAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGID-LSQVYELLE 453
Cdd:cd07879  160 DFGLARHadaeMTGYVVT---------RWyRAPEViLNWMHYNQTVDIWSVGCIMAEMLT-GKTLFKGKDyLDQLTQILK 229
SH2_Src_Fyn cd10368
Src homology 2 (SH2) domain found in Fyn; Fyn is a member of the Src non-receptor type ...
127-216 1.41e-14

Src homology 2 (SH2) domain found in Fyn; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198231 [Multi-domain]  Cd Length: 101  Bit Score: 70.44  E-value: 1.41e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  127 WYHGPVSRNAAE-YLLSSG-INGSFLVRESESSPGQRSISLR----YEG-RVYHYRINTASDGKLYVSSESRFNTLAELV 199
Cdd:cd10368    5 WYFGKLGRKDAErQLLSFGnPRGTFLIRESETTKGAYSLSIRdwddMKGdHVKHYKIRKLDNGGYYITTRAQFETLQQLV 84
                         90
                 ....*....|....*..
gi 62362414  200 HHHSTVADGLITTLHYP 216
Cdd:cd10368   85 QHYSETANGLCKVLIVT 101
STKc_PAK_II cd06648
Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze ...
239-440 1.45e-14

Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group II PAKs, also called non-conventional PAKs, include PAK4, PAK5, and PAK6. Group II PAKs contain PBD (p21-binding domain) and catalytic domains, but lack other motifs found in group I PAKs, such as an AID (autoinhibitory domain) and SH3 binding sites. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. While group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX, no such binding has been demonstrated for group II PAKs. Some known substrates of group II PAKs are also substrates of group I PAKs such as Raf, BAD, LIMK and GEFH1. Unique group II substrates include MARK/Par-1 and PDZ-RhoGEF. Group II PAKs play important roles in filopodia formation, neuron extension, cytoskeletal organization, and cell survival. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270815 [Multi-domain]  Cd Length: 261  Bit Score: 75.17  E-value: 1.45e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  239 RTDITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFL-KEAAVMKEIKHPNLVQLLGVCTREPPFYIITEF 317
Cdd:cd06648    6 RSDLDNFVKIGEGSTGIVCIATDKSTGRQVAVKKMDLRKQQRRELLfNEVVIMRDYQHPNIVEMYSSYLVGDELWVVMEF 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  318 MTYGNLLDYLRECNRQEVNavvLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHA 397
Cdd:cd06648   86 LEGGALTDIVTHTRMNEEQ---IATVCRAVLKALSFLHSQGVIHRDIKSDSILLTSDGRVKLSDFGFCAQVSKEVPRRKS 162
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 62362414  398 GAKFPIkWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPY 440
Cdd:cd06648  163 LVGTPY-WMAPEVISRLPYGTEVDIWSLGIMVIEMVD-GEPPY 203
STKc_PKB_gamma cd05593
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); ...
248-460 1.56e-14

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-gamma is predominantly expressed in neuronal tissues. Mice deficient in PKB-gamma show a reduction in brain weight due to the decreases in cell size and cell number. PKB-gamma has also been shown to be upregulated in estrogen-deficient breast cancer cells, androgen-independent prostate cancer cells, and primary ovarian tumors. It acts as a key mediator in the genesis of ovarian cancer. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270745 [Multi-domain]  Cd Length: 348  Bit Score: 76.27  E-value: 1.56e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM----EVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNL 323
Cdd:cd05593   23 LGKGTFGKVILVREKASGKYYAMKILKKEVIiakdEVAHTLTESRVLKNTRHPFLTSLKYSFQTKDRLCFVMEYVNGGEL 102
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  324 LDYLrecNRQEV-NAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFP 402
Cdd:cd05593  103 FFHL---SRERVfSEDRTRFYGAEIVSALDYLHSGKIVYRDLKLENLMLDKDGHIKITDFGLCKEGITDAATMKTFCGTP 179
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 62362414  403 iKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYEL-LEKDYRMER 460
Cdd:cd05593  180 -EYLAPEVLEDNDYGRAVDWWGLGVVMYEMMC-GRLPFYNQDHEKLFELiLMEDIKFPR 236
STKc_MOK cd07831
Catalytic domain of the Serine/Threonine Kinase, MAPK/MAK/MRK Overlapping Kinase; STKs ...
246-434 1.72e-14

Catalytic domain of the Serine/Threonine Kinase, MAPK/MAK/MRK Overlapping Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MOK, also called Renal tumor antigen 1 (RAGE-1), is widely expressed and is enriched in testis, kidney, lung, and brain. It is expressed in approximately 50% of renal cell carcinomas (RCC) and is a potential target for immunotherapy. MOK is stabilized by its association with the HSP90 molecular chaperone. It is induced by the transcription factor Cdx2 and may be involved in regulating intestinal epithelial development and differentiation. The MOK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270825 [Multi-domain]  Cd Length: 282  Bit Score: 75.39  E-value: 1.72e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  246 HKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEF--LKEAAVMKEIK-HPNLVQLLGVCTREPP--FYIITEFMTy 320
Cdd:cd07831    5 GKIGEGTFSEVLKAQSRKTGKYYAIKCMKKHFKSLEQVnnLREIQALRRLSpHPNILRLIEVLFDRKTgrLALVFELMD- 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  321 GNLLDYLRECNRQEVNAVVLLYMaTQISSAMEYLEKKNFIHRDLAARNCLVGENHLvKVADFGLSR-LMTGDTYTAHAGA 399
Cdd:cd07831   84 MNLYELIKGRKRPLPEKRVKNYM-YQLLKSLDHMHRNGIFHRDIKPENILIKDDIL-KLADFGSCRgIYSKPPYTEYIST 161
                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 62362414  400 KFpikWTAPESLAYNKF-SIKSDVWAFGVLLWEIAT 434
Cdd:cd07831  162 RW---YRAPECLLTDGYyGPKMDIWAVGCVFFEILS 194
SH2_Src_Src cd10365
Src homology 2 (SH2) domain found in tyrosine kinase sarcoma (Src); Src is a member of the Src ...
123-213 1.86e-14

Src homology 2 (SH2) domain found in tyrosine kinase sarcoma (Src); Src is a member of the Src non-receptor type tyrosine kinase family of proteins. Src is thought to play a role in the regulation of embryonic development and cell growth. Members here include v-Src and c-Src. v-Src lacks the C-terminal inhibitory phosphorylation site and is therefore constitutively active as opposed to normal cellular src (c-Src) which is only activated under certain circumstances where it is required (e.g. growth factor signaling). v-Src is an oncogene whereas c-Src is a proto-oncogene. c-Src consists of three domains, an N-terminal SH3 domain, a central SH2 domain and a tyrosine kinase domain. The SH2 and SH3 domains work together in the auto-inhibition of the kinase domain. The phosphorylation of an inhibitory tyrosine near the c-terminus of the protein produces a binding site for the SH2 domain which then facilitates binding of the SH3 domain to a polyproline site within the linker between the SH2 domain and the kinase domain. Binding of the SH3 domain inactivates the enzyme. This allows for multiple mechanisms for c-Src activation: dephosphorylation of the C-terminal tyrosine by a protein tyrosine phosphatase, binding of the SH2 domain by a competitive phospho-tyrosine residue, or competitive binding of a polyproline binding site to the SH3 domain. Unlike most other Src members Src lacks cysteine residues in the SH4 domain that undergo palmitylation. Serine and threonine phosphorylation sites have also been identified in the unique domains of Src and are believed to modulate protein-protein interactions or regulate catalytic activity. Alternatively spliced forms of Src, which contain 6- or 11-amino acid insertions in the SH3 domain, are expressed in CNS neurons. c-Src has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198228  Cd Length: 101  Bit Score: 70.08  E-value: 1.86e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  123 EKHSWYHGPVSRNAAEYLLSSGIN--GSFLVRESESSPGQRSIS-LRYEG----RVYHYRINTASDGKLYVSSESRFNTL 195
Cdd:cd10365    1 QAEEWYFGKITRRESERLLLNAENprGTFLVRESETTKGAYCLSvSDFDNakglNVKHYKIRKLDSGGFYITSRTQFNSL 80
                         90
                 ....*....|....*...
gi 62362414  196 AELVHHHSTVADGLITTL 213
Cdd:cd10365   81 QQLVAYYSKHADGLCHRL 98
SH2_Nck2 cd10409
Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin ...
127-202 2.00e-14

Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198272  Cd Length: 98  Bit Score: 70.06  E-value: 2.00e-14
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 62362414  127 WYHGPVSRNAAEYLLSS-GINGSFLVRESESSPGQRSISLRYEGRVYHYRINTASDgkLYVSSESRFNTLAELVHHH 202
Cdd:cd10409    3 WYYGNVTRHQAECALNErGVEGDFLIRDSESSPSDFSVSLKAVGKNKHFKVQLVDN--VYCIGQRRFNSMDELVEHY 77
STKc_RSK3_C cd14178
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called ...
244-440 2.03e-14

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called Ribosomal protein S6 kinase alpha-2 or 90kDa ribosomal protein S6 kinase 2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK3 is also called S6K-alpha-2, RPS6KA2, p90RSK2 or MAPK-activated protein kinase 1c (MAPKAPK-1c). RSK3 binds muscle A-kinase anchoring protein (mAKAP)-b directly and regulates concentric cardiac myocyte growth. The RSK3 gene, RPS6KA2, is a putative tumor suppressor gene in sporadic epithelial ovarian cancer and variations to the gene may be associated with rectal cancer risk. RSK3 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271080 [Multi-domain]  Cd Length: 293  Bit Score: 75.05  E-value: 2.03e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  244 MKHKLGGGQYGEVYEGVWKKYSLTVAVKTL---KEDTMEVEEFLkeaavMKEIKHPNLVQLLGVCTREPPFYIITEFMTY 320
Cdd:cd14178    7 IKEDIGIGSYSVCKRCVHKATSTEYAVKIIdksKRDPSEEIEIL-----LRYGQHPNIITLKDVYDDGKFVYLVMELMRG 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  321 GNLLDYL--REC-NRQEVNAVVLLymatqISSAMEYLEKKNFIHRDLAARNCL----VGENHLVKVADFGLSR------- 386
Cdd:cd14178   82 GELLDRIlrQKCfSEREASAVLCT-----ITKTVEYLHSQGVVHRDLKPSNILymdeSGNPESIRICDFGFAKqlraeng 156
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 62362414  387 -LMTgDTYTAHagakfpikWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPY 440
Cdd:cd14178  157 lLMT-PCYTAN--------FVAPEVLKRQGYDAACDIWSLGILLYTMLA-GFTPF 201
STKc_CDK6 cd07862
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 6; STKs ...
247-432 2.04e-14

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK6 is regulated by D-type cyclins and INK4 inhibitors. It is active towards the retinoblastoma (pRb) protein, implicating it to function in regulating the early G1 phase of the cell cycle. It is expressed ubiquitously and is localized in the cytoplasm. It is also present in the ruffling edge of spreading fibroblasts and may play a role in cell spreading. It binds to the p21 inhibitor without any effect on its own activity and it is overexpressed in squamous cell carcinomas and neuroblastomas. CDK6 has also been shown to inhibit cell differentiation in many cell types. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270846 [Multi-domain]  Cd Length: 290  Bit Score: 75.07  E-value: 2.04e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGV-WKKYSLTVAVKTLKEDTMEVE---EFLKEAAVMKEIK---HPNLVQLLGVCT-----REPPFYII 314
Cdd:cd07862    8 EIGEGAYGKVFKARdLKNGGRFVALKRVRVQTGEEGmplSTIREVAVLRHLEtfeHPNVVRLFDVCTvsrtdRETKLTLV 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  315 TEFMTYgNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDtyT 394
Cdd:cd07862   88 FEHVDQ-DLTTYLDKVPEPGVPTETIKDMMFQLLRGLDFLHSHRVVHRDLKPQNILVTSSGQIKLADFGLARIYSFQ--M 164
                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 62362414  395 AHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEI 432
Cdd:cd07862  165 ALTSVVVTLWYRAPEVLLQSSYATPVDLWSVGCIFAEM 202
STKc_Kalirin_C cd14115
C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide ...
248-440 2.28e-14

C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide Exchange Factor, Kalirin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Kalirin, also called Duo or Duet, is a large multidomain protein containing a series of spectrin-like repeats, two each of RhoGEF and SH3 domains, an immunoglobulin-like (Ig) domain and a C-terminal kinase. As a GEF, it activates Rac1, RhoA, and RhoG. It is highly expressed in neurons and is required for spine formation. The kalirin gene produces at least 10 isoforms from alternative promoter use and splicing. Of the major isoforms (Kalirin-7, -9, and -12), only kalirin-12 contains the C-terminal kinase domain. Kalirin-12 is highly expressed during embryonic development and it plays an important role in axon outgrowth. The Kalirin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271017 [Multi-domain]  Cd Length: 248  Bit Score: 74.23  E-value: 2.28e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGvcTREPP--FYIITEFMTYGNLLD 325
Cdd:cd14115    1 IGRGRFSIVKKCLHKATRKDVAVKFVSKKMKKKEQAAHEAALLQHLQHPQYITLHD--TYESPtsYILVLELMDDGRLLD 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  326 YLreCNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVG---ENHLVKVADFGLSRLMTGDtYTAHAGAKFP 402
Cdd:cd14115   79 YL--MNHDELMEEKVAFYIRDIMEALQYLHNCRVAHLDIKPENLLIDlriPVPRVKLIDLEDAVQISGH-RHVHHLLGNP 155
                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 62362414  403 iKWTAPESLAYNKFSIKSDVWAFGVLLWeIATYGMSPY 440
Cdd:cd14115  156 -EFAAPEVIQGTPVSLATDIWSIGVLTY-VMLSGVSPF 191
STKc_YPK1_like cd05585
Catalytic domain of Yeast Protein Kinase 1-like Serine/Threonine Kinases; STKs catalyze the ...
248-483 2.40e-14

Catalytic domain of Yeast Protein Kinase 1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of fungal proteins with similarity to the AGC STKs, Saccharomyces cerevisiae YPK1 and Schizosaccharomyces pombe Gad8p. YPK1 is required for cell growth and acts as a downstream kinase in the sphingolipid-mediated signaling pathway of yeast. It also plays a role in efficient endocytosis and in the maintenance of cell wall integrity. Gad8p is a downstream target of Tor1p, the fission yeast homolog of mTOR. It plays a role in cell growth and sexual development. The YPK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270737 [Multi-domain]  Cd Length: 313  Bit Score: 75.30  E-value: 2.40e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM----EVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNL 323
Cdd:cd05585    2 IGKGSFGKVMQVRKKDTSRIYALKTIRKAHIvsrsEVTHTLAERTVLAQVDCPFIVPLKFSFQSPEKLYLVLAFINGGEL 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  324 LDYLRECNRQEVNAVvLLYMAtQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPi 403
Cdd:cd05585   82 FHHLQREGRFDLSRA-RFYTA-ELLCALECLHKFNVIYRDLKPENILLDYTGHIALCDFGLCKLNMKDDDKTNTFCGTP- 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  404 KWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVY-ELLEKDYRMerPEGCPEKVYELMRACWQWNPSD 482
Cdd:cd05585  159 EYLAPELLLGHGYTKAVDWWTLGVLLYEMLT-GLPPFYDENTNEMYrKILQEPLRF--PDGFDRDAKDLLIGLLNRDPTK 235

                 .
gi 62362414  483 R 483
Cdd:cd05585  236 R 236
STKc_ULK4 cd14010
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the ...
247-456 2.60e-14

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ULK4 is a functionally uncharacterized kinase that shows similarity to ATG1/ULKs. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. The ULK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270912 [Multi-domain]  Cd Length: 269  Bit Score: 74.25  E-value: 2.60e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLkeDTMEVEEFLKEAAVMKEIKHPNLVQllgvctreppFY----------IITE 316
Cdd:cd14010    7 EIGRGKHSVVYKGRRKGTIEFVAIKCV--DKSKRPEVLNEVRLTHELKHPNVLK----------FYewyetsnhlwLVVE 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  317 FMTYGNLLDYLRE-CNRQEvNAVvlLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMT------ 389
Cdd:cd14010   75 YCTGGDLETLLRQdGNLPE-SSV--RKFGRDLVRGLHYIHSKGIIYCDLKPSNILLDGNGTLKLSDFGLARREGeilkel 151
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 62362414  390 -GDTYTAHAGAKFPIK--------WTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYEL-LEKDY 456
Cdd:cd14010  152 fGQFSDEGNVNKVSKKqakrgtpyYMAPELFQGGVHSFASDLWALGCVLYEMFT-GKPPFVAESFTELVEKiLNEDP 227
STKc_RSK_C cd14091
C-terminal catalytic domain of the Serine/Threonine Kinases, Ribosomal S6 kinases; STKs ...
241-441 2.79e-14

C-terminal catalytic domain of the Serine/Threonine Kinases, Ribosomal S6 kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), 90 kDa ribosomal protein S6 kinases (p90-RSKs), or p90S6Ks. The RSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270993 [Multi-domain]  Cd Length: 291  Bit Score: 74.59  E-value: 2.79e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  241 DITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTL---KED-TMEVEEFLKEAavmkeiKHPNLVQLLGVCTREPPFYIITE 316
Cdd:cd14091    1 EYEIKEEIGKGSYSVCKRCIHKATGKEYAVKIIdksKRDpSEEIEILLRYG------QHPNIITLRDVYDDGNSVYLVTE 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  317 FMTYGNLLDYL---RECNRQEVNAVvllyMATqISSAMEYLEKKNFIHRDLAARNCLV----GENHLVKVADFGLSR--- 386
Cdd:cd14091   75 LLRGGELLDRIlrqKFFSEREASAV----MKT-LTKTVEYLHSQGVVHRDLKPSNILYadesGDPESLRICDFGFAKqlr 149
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  387 -----LMTgDTYTAHagakfpikWTAPESLAYNKFSIKSDVWAFGVLLWeIATYGMSPYP 441
Cdd:cd14091  150 aenglLMT-PCYTAN--------FVAPEVLKKQGYDAACDIWSLGVLLY-TMLAGYTPFA 199
STKc_EIF2AK2_PKR cd14047
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
239-432 2.80e-14

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Protein Kinase regulated by RNA; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKR (or EIF2AK2) contains an N-terminal double-stranded RNA (dsRNA) binding domain and a C-terminal catalytic kinase domain. It is activated by dsRNA, which is produced as a replication intermediate in virally infected cells. It plays a key role in mediating innate immune responses to viral infection. PKR is also directly activated by PACT (protein activator of PKR) and heparin, and is inhibited by viral proteins and RNAs. PKR also regulates transcription and signal transduction in diseased cells, playing roles in tumorigenesis and neurodegenerative diseases. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The PKR subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270949 [Multi-domain]  Cd Length: 267  Bit Score: 74.45  E-value: 2.80e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  239 RTDITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAvmkEIKHPNLVQLLGVCT------------ 306
Cdd:cd14047    5 RQDFKEIELIGSGGFGQVFKAKHRIDGKTYAIKRVKLNNEKAEREVKALA---KLDHPNIVRYNGCWDgfdydpetsssn 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  307 ----REPPFYIITEFMTYGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADF 382
Cdd:cd14047   82 ssrsKTKCLFIQMEFCEKGTLESWIEKRNGEKLDKVLALEIFEQITKGVEYIHSKKLIHRDLKPSNIFLVDTGKVKIGDF 161
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 62362414  383 GLSRLMTGdtYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEI 432
Cdd:cd14047  162 GLVTSLKN--DGKRTKSKGTLSYMSPEQISSQDYGKEVDIYALGLILFEL 209
STKc_PKN cd05589
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N; STKs catalyze the transfer ...
248-450 2.88e-14

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKN has a C-terminal catalytic domain that is highly homologous to PKCs. Its unique N-terminal regulatory region contains antiparallel coiled-coil (ACC) domains. In mammals, there are three PKN isoforms from different genes (designated PKN-alpha, beta, and gamma), which show different enzymatic properties, tissue distribution, and varied functions. PKN can be activated by the small GTPase Rho, and by fatty acids such as arachidonic and linoleic acids. It is involved in many biological processes including cytokeletal regulation, cell adhesion, vesicle transport, glucose transport, regulation of meiotic maturation and embryonic cell cycles, signaling to the nucleus, and tumorigenesis. The PKN subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270741 [Multi-domain]  Cd Length: 326  Bit Score: 75.41  E-value: 2.88e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM----EVEEFLKEA---AVMKEIKHPNLVQLLGvC--TREPPFYIiTEFM 318
Cdd:cd05589    7 LGRGHFGKVLLAEYKPTGELFAIKALKKGDIiardEVESLMCEKrifETVNSARHPFLVNLFA-CfqTPEHVCFV-MEYA 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  319 TYGNLLDYLRECNRQEVNAVvllYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR--LMTGDTYTAH 396
Cdd:cd05589   85 AGGDLMMHIHEDVFSEPRAV---FYAACVVLGLQFLHEHKIVYRDLKLDNLLLDTEGYVKIADFGLCKegMGFGDRTSTF 161
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 62362414  397 AGAKfpiKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYE 450
Cdd:cd05589  162 CGTP---EFLAPEVLTDTSYTRAVDWWGLGVLIYEMLV-GESPFPGDDEEEVFD 211
SH2_Nterm_shark_like cd10347
N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
126-202 3.26e-14

N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) proteins; These non-receptor protein-tyrosine kinases contain two SH2 domains, five ankyrin (ANK)-like repeats, and a potential tyrosine phosphorylation site in the carboxyl-terminal tail which resembles the phosphorylation site in members of the src family. Like, mammalian non-receptor protein-tyrosine kinases, ZAP-70 and syk proteins, they do not have SH3 domains. However, the presence of ANK makes these unique among protein-tyrosine kinases. Both tyrosine kinases and ANK repeats have been shown to transduce developmental signals, and SH2 domains are known to participate intimately in tyrosine kinase signaling. These tyrosine kinases are believed to be involved in epithelial cell polarity. The members of this family include the shark (SH2 domains, ANK, and kinase domain) gene in Drosophila and yellow fever mosquitos, as well as the hydra protein HTK16. Drosophila Shark is proposed to transduce intracellularly the Crumbs, a protein necessary for proper organization of ectodermal epithelia, intercellular signal. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198210  Cd Length: 81  Bit Score: 68.94  E-value: 3.26e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  126 SWYHGPVSRNAAEYLLS--SGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTASDGKLYVSSES-RFNTLAELVHHH 202
Cdd:cd10347    2 RWYHGKISREVAEALLLreGGRDGLFLVRESTSAPGDYVLSLLAQGEVLHYQIRRHGEDAFFSDDGPlIFHGLDTLIEHY 81
STKc_HAL4_like cd13994
Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs ...
248-434 3.89e-14

Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of HAL4, Saccharomyces cerevisiae Ptk2/Stk2, and similar fungal proteins. Proteins in this subfamily are involved in regulating ion transporters. In budding and fission yeast, HAL4 promotes potassium ion uptake, which increases cellular resistance to other cations such as sodium, lithium, and calcium ions. HAL4 stabilizes the major high-affinity K+ transporter Trk1 at the plasma membrane under low K+ conditions, which prevents endocytosis and vacuolar degradation. Budding yeast Ptk2 phosphorylates and regulates the plasma membrane H+ ATPase, Pma1. The HAL4-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270896 [Multi-domain]  Cd Length: 265  Bit Score: 73.88  E-value: 3.89e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVyEGVWKKYSLT---VAVKTL-KEDTMEVEE-----FLKEAAVMKEIKHPNLVQLLGVCTREPPFY-IITEF 317
Cdd:cd13994    1 IGKGATSVV-RIVTKKNPRSgvlYAVKEYrRRDDESKRKdyvkrLTSEYIISSKLHHPNIVKVLDLCQDLHGKWcLVMEY 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  318 MTYGNLLDYLRECNRQEVNAVVLLYmaTQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLS--RLMTGDtYTA 395
Cdd:cd13994   80 CPGGDLFTLIEKADSLSLEEKDCFF--KQILRGVAYLHSHGIAHRDLKPENILLDEDGVLKLTDFGTAevFGMPAE-KES 156
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 62362414  396 H--AGAKFPIKWTAPE---SLAYNKFSikSDVWAFGVLLWEIAT 434
Cdd:cd13994  157 PmsAGLCGSEPYMAPEvftSGSYDGRA--VDVWSCGIVLFALFT 198
STKc_p38beta cd07878
Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase ...
248-453 4.48e-14

Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase (also called MAPK11); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38beta/MAPK11 is widely expressed in tissues and shows more similarity with p38alpha than with the other isoforms. Both are sensitive to pyridinylimidazoles and share some common substrates such as MAPK activated protein kinase 2 (MK2) and the transcription factors ATF2, c-Fos and, ELK-1. p38beta is involved in regulating the activation of the cyclooxygenase-2 promoter and the expression of TGFbeta-induced alpha-smooth muscle cell actin. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143383 [Multi-domain]  Cd Length: 343  Bit Score: 75.09  E-value: 4.48e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLK---EDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPF------YIITEFM 318
Cdd:cd07878   23 VGSGAYGSVCSAYDTRLRQKVAVKKLSrpfQSLIHARRTYRELRLLKHMKHENVIGLLDVFTPATSIenfnevYLVTNLM 102
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  319 tyGNLLDYLRECNRQEVNAV-VLLYmatQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRlMTGDTYTAHA 397
Cdd:cd07878  103 --GADLNNIVKCQKLSDEHVqFLIY---QLLRGLKYIHSAGIIHRDLKPSNVAVNEDCELRILDFGLAR-QADDEMTGYV 176
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 62362414  398 GAKFpikWTAPE-SLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGID-LSQVYELLE 453
Cdd:cd07878  177 ATRW---YRAPEiMLNWMHYNQTVDIWSVGCIMAELLK-GKALFPGNDyIDQLKRIME 230
STKc_TGFbR2_like cd14055
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Type II ...
248-483 4.88e-14

Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Type II Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TGFbR2 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors, such as TGFbR2, are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. TGFbR2 acts as the receptor for TGFbeta, which is crucial in growth control and homeostasis in many different tissues. It plays roles in regulating apoptosis and in maintaining the balance between self renewal and cell loss. It also plays a key role in maintaining vascular integrity and in regulating responses to genotoxic stress. Mutations in TGFbR2 can cause aortic aneurysm disorders such as Loeys-Dietz and Marfan syndromes. The TGFbR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270957 [Multi-domain]  Cd Length: 295  Bit Score: 73.95  E-value: 4.88e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSL----TVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTR----EPPFYIITEFMT 319
Cdd:cd14055    3 VGKGRFAEVWKAKLKQNASgqyeTVAVKIFPYEEYASWKNEKDIFTDASLKHENILQFLTAEERgvglDRQYWLITAYHE 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  320 YGNLLDYLRecnRQEVNAVVLLYMATQISSAMEYLE---------KKNFIHRDLAARNCLVGENHLVKVADFGLS-RL-- 387
Cdd:cd14055   83 NGSLQDYLT---RHILSWEDLCKMAGSLARGLAHLHsdrtpcgrpKIPIAHRDLKSSNILVKNDGTCVLADFGLAlRLdp 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  388 -MTGDTYtAHAGAKFPIKWTAPESLA--YNKFSIKS----DVWAFGVLLWEIA-----TYGMSPY-----------PGID 444
Cdd:cd14055  160 sLSVDEL-ANSGQVGTARYMAPEALEsrVNLEDLESfkqiDVYSMALVLWEMAsrceaSGEVKPYelpfgskvrerPCVE 238
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*..
gi 62362414  445 LSQVYELLEKdyrmERPEGCPE-KVYELMRA-------CWQWNPSDR 483
Cdd:cd14055  239 SMKDLVLRDR----GRPEIPDSwLTHQGMCVlcdtiteCWDHDPEAR 281
SH2_C-SH2_PLC_gamma_like cd09932
C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
123-204 7.37e-14

C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198186  Cd Length: 104  Bit Score: 68.45  E-value: 7.37e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  123 EKHSWYHGPVSRNAAEYLLSS-GINGSFLVRESESSPGQRSISLRYEGRVYHYRINTasDGKLYVSSESRFNTLAELVHH 201
Cdd:cd09932    2 ESKEWFHANLTREQAEEMLMRvPRDGAFLVRPSETDPNSFAISFRAEGKIKHCRIKQ--EGRLFVIGTSQFESLVELVSY 79

                 ...
gi 62362414  202 HST 204
Cdd:cd09932   80 YEK 82
STKc_PKB_alpha cd05594
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B alpha (also called Akt1); ...
230-466 8.15e-14

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B alpha (also called Akt1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-alpha is predominantly expressed in endothelial cells. It is critical for the regulation of angiogenesis and the maintenance of vascular integrity. It also plays a role in adipocyte differentiation. Mice deficient in PKB-alpha exhibit perinatal morbidity, growth retardation, reduction in body weight accompanied by reduced sizes of multiple organs, and enhanced apoptosis in some cell types. PKB-alpha activity has been reported to be frequently elevated in breast and prostate cancers. In some cancer cells, PKB-alpha may act as a suppressor of metastasis. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270746 [Multi-domain]  Cd Length: 356  Bit Score: 74.30  E-value: 8.15e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  230 PNYDKWEMERTDITMKHK-----------LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM----EVEEFLKEAAVMKEIK 294
Cdd:cd05594    4 DNSGAEEMEVSLTKPKHKvtmndfeylklLGKGTFGKVILVKEKATGRYYAMKILKKEVIvakdEVAHTLTENRVLQNSR 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  295 HPNLVQLLGVCTREPPFYIITEFMTYGNLLDYL-RECNRQEVNAvvlLYMATQISSAMEYLE-KKNFIHRDLAARNCLVG 372
Cdd:cd05594   84 HPFLTALKYSFQTHDRLCFVMEYANGGELFFHLsRERVFSEDRA---RFYGAEIVSALDYLHsEKNVVYRDLKLENLMLD 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  373 ENHLVKVADFGLSRLMTGDTYTAHAGAKFPiKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYEL- 451
Cdd:cd05594  161 KDGHIKITDFGLCKEGIKDGATMKTFCGTP-EYLAPEVLEDNDYGRAVDWWGLGVVMYEMMC-GRLPFYNQDHEKLFELi 238
                        250
                 ....*....|....*
gi 62362414  452 LEKDYRMERPEGcPE 466
Cdd:cd05594  239 LMEEIRFPRTLS-PE 252
SH2_Src_Fyn_isoform_b_like cd10419
Src homology 2 (SH2) domain found in Fyn isoform b like proteins; Fyn is a member of the Src ...
127-213 9.21e-14

Src homology 2 (SH2) domain found in Fyn isoform b like proteins; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. This cd contains the SH2 domain found in Fyn isoform b type proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198282  Cd Length: 101  Bit Score: 68.16  E-value: 9.21e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  127 WYHGPVSRNAAEYLLSSGIN--GSFLVRESESSPGQRSISLR----YEG-RVYHYRINTASDGKLYVSSESRFNTLAELV 199
Cdd:cd10419    5 WYFGKLGRKDAERQLLSFGNprGTFLIRESETTKGAYSLSIRdwddMKGdHVKHYKIRKLDNGGYYITTRAQFETLQQLV 84
                         90
                 ....*....|....
gi 62362414  200 HHHSTVADGLITTL 213
Cdd:cd10419   85 QHYSEKADGLCFNL 98
SH2_Tec_Btk cd10397
Src homology 2 (SH2) domain found in Tec protein, Bruton's tyrosine kinase (Btk); A member of ...
120-216 9.22e-14

Src homology 2 (SH2) domain found in Tec protein, Bruton's tyrosine kinase (Btk); A member of the Tec protein tyrosine kinase Btk is expressed in bone marrow, spleen, all hematopoietic cells except T lymphocytes and plasma cells where it plays a crucial role in B cell maturation and mast cell activation. Btk has been shown to interact with GNAQ, PLCG2, protein kinase D1, B-cell linker, SH3BP5, caveolin 1, ARID3A, and GTF2I. Most of the Tec family members have a PH domain (Txk and the short (type 1) splice variant of Drosophila Btk29A are exceptions), a Tec homology (TH) domain, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. Btk is implicated in the primary immunodeficiency disease X-linked agammaglobulinemia (Bruton's agammaglobulinemia). The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP. It is crucial for the function of Tec PH domains and it's lack of presence in Txk is not surprising since it lacks a PH domain. The type 1 splice form of the Drosophila homolog also lacks both the PH domain and the Btk motif. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. Two tyrosine phosphorylation (pY) sites have been identified in Btk: one located in the activation loop of the catalytic domain which regulates the transition between open (active) and closed (inactive) states and the other in its SH3 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198260 [Multi-domain]  Cd Length: 106  Bit Score: 68.32  E-value: 9.22e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  120 NSLEKHSWYHGPVSRNAAEYLL-SSGINGSFLVRESeSSPGQRSISL------RYEGRVYHYRINTASDGKLYVSSESRF 192
Cdd:cd10397    1 DSLEMYEWYSKNMTRSQAEQLLkQEGKEGGFIVRDS-SKAGKYTVSVfaksagDPQGVIRHYVVCSTPQSQYYLAEKHLF 79
                         90       100
                 ....*....|....*....|....
gi 62362414  193 NTLAELVHHHSTVADGLITTLHYP 216
Cdd:cd10397   80 STIPELINYHQHNAAGLISRLKYP 103
STKc_GAK cd14036
Catalytic domain of the Serine/Threonine protein kinase, cyclin G-Associated Kinase; STKs ...
251-489 9.59e-14

Catalytic domain of the Serine/Threonine protein kinase, cyclin G-Associated Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GAK, also called auxilin-2, contains an N-terminal kinase domain that phosphorylates the mu subunits of adaptor protein (AP) 1 and AP2. In addition, it contains an auxilin-1-like domain structure consisting of PTEN-like, clathrin-binding, and J domains. Like auxilin-1, GAK facilitates Hsc70-mediated dissociation of clathrin from clathrin-coated vesicles. GAK is expressed ubiquitously and is enriched in the Golgi, unlike auxilin-1 which is nerve-specific. GAK also plays regulatory roles outside of clathrin-mediated membrane traffic including the maintenance of centrosome integrity and chromosome congression, neural patterning, survival of neurons, and immune responses through interaction with the interleukin 12 receptor. It also interacts with the androgen receptor, acting as a transcriptional coactivator, and its expression is significantly increased with the progression of prostate cancer. The GAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270938 [Multi-domain]  Cd Length: 282  Bit Score: 72.93  E-value: 9.59e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  251 GQYGEVYE----GVWKKYSLTvavKTLKEDTMEVEEFLKEAAVMKEIK-HPNLVQLLGVCTREPP--------FYIITEF 317
Cdd:cd14036   11 GGFAFVYEaqdvGTGKEYALK---RLLSNEEEKNKAIIQEINFMKKLSgHPNIVQFCSAASIGKEesdqgqaeYLLLTEL 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  318 MTyGNLLDYLRECN-RQEVNAVVLLYMATQISSAMEYLEKKN--FIHRDLAARNCLVGENHLVKVADFGLSR---LMTGD 391
Cdd:cd14036   88 CK-GQLVDFVKKVEaPGPFSPDTVLKIFYQTCRAVQHMHKQSppIIHRDLKIENLLIGNQGQIKLCDFGSATteaHYPDY 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  392 TYTAHAGAKF---------PIkWTAPESL-AYNKFSI--KSDVWAFGVLLWeIATYGMSPYP-GIDLSQV---YELLEKD 455
Cdd:cd14036  167 SWSAQKRSLVedeitrnttPM-YRTPEMIdLYSNYPIgeKQDIWALGCILY-LLCFRKHPFEdGAKLRIInakYTIPPND 244
                        250       260       270
                 ....*....|....*....|....*....|....*.
gi 62362414  456 --YRMerpegcpekVYELMRACWQWNPSDRPSFAEI 489
Cdd:cd14036  245 tqYTV---------FHDLIRSTLKVNPEERLSITEI 271
STKc_PFTAIRE1 cd07869
Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-1 kinase; STKs catalyze the transfer ...
226-443 9.78e-14

Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-1 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PFTAIRE-1 is widely expressed except in the spleen and thymus. It is highly expressed in the brain, heart, pancreas, testis, and ovary, and is localized in the cytoplasm. It is regulated by cyclin D3 and is inhibited by the p21 cell cycle inhibitor. It has also been shown to interact with the membrane-associated cyclin Y, which recruits the protein to the plasma membrane. PFTAIRE-1 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PFTAIRE-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143374 [Multi-domain]  Cd Length: 303  Bit Score: 73.19  E-value: 9.78e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  226 YGVSPNYDKWEmertditmkhKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEF--LKEAAVMKEIKHPNLVQLLG 303
Cdd:cd07869    1 FGKADSYEKLE----------KLGEGSYATVYKGKSKVNGKLVALKVIRLQEEEGTPFtaIREASLLKGLKHANIVLLHD 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  304 VCTREPPFYIITEFMtYGNLLDYLRE--CNRQEVNAVVLLYmatQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVAD 381
Cdd:cd07869   71 IIHTKETLTLVFEYV-HTDLCQYMDKhpGGLHPENVKLFLF---QLLRGLSYIHQRYILHRDLKPQNLLISDTGELKLAD 146
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 62362414  382 FGLSRLMTGDTYTaHAGAKFPIKWTAPES-LAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGI 443
Cdd:cd07869  147 FGLARAKSVPSHT-YSNEVVTLWYRPPDVlLGSTEYSTCLDMWGVGCIFVEMIQ-GVAAFPGM 207
STKc_IRAK1 cd14159
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 1; ...
248-434 1.12e-13

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain, and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK1 plays a role in the activation of IRF3/7, STAT, and NFkB. It mediates IL-6 and IFN-gamma responses following IL-1 and IL-18 stimulation, respectively. It also plays an essential role in IFN-alpha induction downstream of TLR7 and TLR9. The IRAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271061 [Multi-domain]  Cd Length: 296  Bit Score: 72.94  E-value: 1.12e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKkySLTVAVKTLKED-----TMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGN 322
Cdd:cd14159    1 IGEGGFGCVYQAVMR--NTEYAVKRLKEDseldwSVVKNSFLTEVEKLSRFRHPNIVDLAGYSAQQGNYCLIYVYLPNGS 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLrecnRQEVNAVVL-----LYMATQISSAMEYL--EKKNFIHRDLAARNCLVGENHLVKVADFGLSRLmtgDTYTA 395
Cdd:cd14159   79 LEDRL----HCQVSCPCLswsqrLHVLLGTARAIQYLhsDSPSLIHGDVKSSNILLDAALNPKLGDFGLARF---SRRPK 151
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 62362414  396 HAGAKFPIKWTA----------PESLAYNKFSIKSDVWAFGVLLWEIAT 434
Cdd:cd14159  152 QPGMSSTLARTQtvrgtlaylpEEYVKTGTLSVEIDVYSFGVVLLELLT 200
PK_IRAK3 cd14160
Pseudokinase domain of Interleukin-1 Receptor Associated Kinase 3; The pseudokinase domain ...
248-434 1.15e-13

Pseudokinase domain of Interleukin-1 Receptor Associated Kinase 3; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain (a pseudokinase in the case of IRAK3), and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK3 (or IRAK-M) is the only IRAK that does not show kinase activity. It is found only in monocytes and macrophages in humans, and functions as a negative regulator of TLR signaling including TLR-2 induced p38 activation. It also negatively regulates the alternative NFkB pathway in a TLR-2 specific manner. IRAK3 is downregulated in the monocytes of obese people, and is associated with high SOD2, a marker of mitochondrial oxidative stress. It is an important inhibitor of inflammation in association with obesity and metabolic syndrome. The IRAK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271062 [Multi-domain]  Cd Length: 276  Bit Score: 72.61  E-value: 1.15e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKkySLTVAVKTLK-EDTMEV----EEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGN 322
Cdd:cd14160    1 IGEGEIFEVYRVRIG--NRSYAVKLFKqEKKMQWkkhwKRFLSELEVLLLFQHPNILELAAYFTETEKFCLVYPYMQNGT 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLRECN-RQEVNAVVLLYMATQISSAMEYLEKKN---FIHRDLAARNCLVGENHLVKVADFGLSRLMT-----GDTY 393
Cdd:cd14160   79 LFDRLQCHGvTKPLSWHERINILIGIAKAIHYLHNSQpctVICGNISSANILLDDQMQPKLTDFALAHFRPhledqSCTI 158
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 62362414  394 TAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIAT 434
Cdd:cd14160  159 NMTTALHKHLWYMPEEYIRQGKLSVKTDVYSFGIVIMEVLT 199
SH2_Tec_Txk cd10398
Src homology 2 (SH2) domain found in Tec protein, Txk; A member of the Tec protein tyrosine ...
121-216 1.15e-13

Src homology 2 (SH2) domain found in Tec protein, Txk; A member of the Tec protein tyrosine kinase Txk is expressed in thymus, spleen, lymph node, T lymphocytes, NK cells, mast cell lines, and myeloid cell line. Txk plays a role in TCR signal transduction, T cell development, and selection which is analogous to the function of Itk. Txk has been shown to interact with IFN-gamma. Unlike most of the Tec family members Txk lacks a PH domain. Instead Txk has a unique region containing a palmitoylated cysteine string which has a similar membrane tethering function as the PH domain. Txk also has a zinc-binding motif, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP and crucial to the function of the PH domain. It is not present in Txk which is not surprising since it lacks a PH domain. The type 1 splice form of the Drosophila homolog also lacks both the PH domain and the Btk motif. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198261  Cd Length: 106  Bit Score: 68.05  E-value: 1.15e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  121 SLEKHSWYHGPVSRNAAEYLL-SSGINGSFLVRESeSSPGQRSISL------RYEGRVYHYRINTASDGKLYVSSESRFN 193
Cdd:cd10398    2 NLEIYEWYHKNITRNQAERLLrQESKEGAFIVRDS-RHLGSYTISVftrarrSTEASIKHYQIKKNDSGQWYVAERHLFQ 80
                         90       100
                 ....*....|....*....|...
gi 62362414  194 TLAELVHHHSTVADGLITTLHYP 216
Cdd:cd10398   81 SIPELIQYHQHNAAGLMSRLRYP 103
STKc_DAPK2 cd14196
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 2; STKs ...
247-442 1.16e-13

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK2, also called DAPK-related protein 1 (DRP-1), is a Ca2+/calmodulin (CaM)-regulated protein containing an N-terminal kinase domain, a CaM autoinhibitory site and a dimerization module. It lacks the cytoskeletal binding regions of DAPK1 and the exogenous protein has been shown to be soluble and cytoplasmic. FLAG-tagged DAPK2, however, accumulated within membrane-enclosed autophagic vesicles. It is unclear where endogenous DAPK2 is localized. DAPK2 participates in TNF-alpha and FAS-receptor induced cell death and enhances neutrophilic maturation in myeloid leukemic cells. It contributes to the induction of anoikis and its down-regulation is implicated in the beta-catenin induced resistance of malignant epithelial cells to anoikis. The DAPK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271098 [Multi-domain]  Cd Length: 269  Bit Score: 72.68  E-value: 1.16e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEV-------EEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMT 319
Cdd:cd14196   12 ELGSGQFAIVKKCREKSTGLEYAAKFIKKRQSRAsrrgvsrEEIEREVSILRQVLHPNIITLHDVYENRTDVVLILELVS 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  320 YGNLLDYLREcnRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHL----VKVADFGLSrlmtgdtYTA 395
Cdd:cd14196   92 GGELFDFLAQ--KESLSEEEATSFIKQILDGVNYLHTKKIAHFDLKPENIMLLDKNIpiphIKLIDFGLA-------HEI 162
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 62362414  396 HAGAKFP-----IKWTAPESLAYNKFSIKSDVWAFGVLLWeIATYGMSPYPG 442
Cdd:cd14196  163 EDGVEFKnifgtPEFVAPEIVNYEPLGLEADMWSIGVITY-ILLSGASPFLG 213
STKc_myosinIIIB_N cd06639
N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIB myosin; STKs catalyze ...
233-433 1.19e-13

N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIB myosin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class IIIB myosin is expressed highly in retina. It is also present in the brain and testis. The human class IIIB myosin gene maps to a region that overlaps the locus for Bardet-Biedl syndrome, which is characterized by dysmorphic extremities, retinal dystrophy, obesity, male hypogenitalism, and renal abnormalities. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain. They may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. They may also function as cargo carriers during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The class III myosin subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270808 [Multi-domain]  Cd Length: 291  Bit Score: 72.72  E-value: 1.19e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  233 DKWEMERTditmkhkLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEI-KHPNLVQLLGVCTREPPF 311
Cdd:cd06639   22 DTWDIIET-------IGKGTYGKVYKVTNKKDGSLAAVKILDPISDVDEEIEAEYNILRSLpNHPNVVKFYGMFYKADQY 94
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  312 -----YIITEFMTYGNLLDYLRECNR--QEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGL 384
Cdd:cd06639   95 vggqlWLVLELCNGGSVTELVKGLLKcgQRLDEAMISYILYGALLGLQHLHNNRIIHRDVKGNNILLTTEGGVKLVDFGV 174
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 62362414  385 SRLMTGDTYTAHAGAKFPIkWTAPESLAYNK-----FSIKSDVWAFGVLLWEIA 433
Cdd:cd06639  175 SAQLTSARLRRNTSVGTPF-WMAPEVIACEQqydysYDARCDVWSLGITAIELA 227
STKc_aPKC_iota cd05618
Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C iota; STKs catalyze ...
241-496 1.21e-13

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C iota; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-iota is directly implicated in carcinogenesis. It is critical to oncogenic signaling mediated by Ras and Bcr-Abl. The PKC-iota gene is the target of tumor-specific gene amplification in many human cancers, and has been identified as a human oncogene. In addition to its role in transformed growth, PKC-iota also promotes invasion, chemoresistance, and tumor cell survival. Expression profiling of PKC-iota is a prognostic marker of poor clinical outcome in several human cancers. PKC-iota also plays a role in establishing cell polarity, and has critical embryonic functions. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. The aPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270769 [Multi-domain]  Cd Length: 364  Bit Score: 73.91  E-value: 1.21e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  241 DITMKHKLGGGQYGEVYEGVWKK----YSLTVAVKTLKEDTMEVEEFLKEAAVMKEIK-HPNLVQLLGVCTREPPFYIIT 315
Cdd:cd05618   21 DFDLLRVIGRGSYAKVLLVRLKKteriYAMKVVKKELVNDDEDIDWVQTEKHVFEQASnHPFLVGLHSCFQTESRLFFVI 100
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  316 EFMTYGNLLDYL-RECNRQEVNAvvlLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR--LMTGDT 392
Cdd:cd05618  101 EYVNGGDLMFHMqRQRKLPEEHA---RFYSAEISLALNYLHERGIIYRDLKLDNVLLDSEGHIKLTDYGMCKegLRPGDT 177
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  393 YTAHAGAKfpiKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLS----QVYE------LLEKDYRMerPE 462
Cdd:cd05618  178 TSTFCGTP---NYIAPEILRGEDYGFSVDWWALGVLMFEMMA-GRSPFDIVGSSdnpdQNTEdylfqvILEKQIRI--PR 251
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 62362414  463 GCPEKVYELMRACWQWNPSDR------PSFAEI--HQAFETM 496
Cdd:cd05618  252 SLSVKAASVLKSFLNKDPKERlgchpqTGFADIqgHPFFRNV 293
STKc_MAP3K8 cd13995
Catalytic domain of the Serine/Threonine kinase, Mitogen-Activated Protein Kinase (MAPK) ...
251-493 1.90e-13

Catalytic domain of the Serine/Threonine kinase, Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K8 is also called Tumor progression locus 2 (Tpl2) or Cancer Osaka thyroid (Cot), and was first identified as a proto-oncogene in T-cell lymphoma induced by MoMuL virus and in breast carcinoma induced by MMTV. Activated MAP3K8 induces various MAPK pathways including Extracellular Regulated Kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), and p38. It plays a pivotal role in innate immunity, linking Toll-like receptors to the production of TNF and the activation of ERK in macrophages. It is also required in interleukin-1beta production and is critical in host defense against Gram-positive bacteria. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The MAP3K8 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270897 [Multi-domain]  Cd Length: 256  Bit Score: 71.58  E-value: 1.90e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  251 GQYGEVYEGVWKKYSLTVAVKTLKedtmeVEEFL-KEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDYLRE 329
Cdd:cd13995   15 GAFGKVYLAQDTKTKKRMACKLIP-----VEQFKpSDVEIQACFRHENIAELYGALLWEETVHLFMEAGEGGSVLEKLES 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  330 CNrqEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVaDFGLSRLMTGDTYTAHAGAKFPIkWTAPE 409
Cdd:cd13995   90 CG--PMREFEIIWVTKHVLKGLDFLHSKNIIHHDIKPSNIVFMSTKAVLV-DFGLSVQMTEDVYVPKDLRGTEI-YMSPE 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  410 SLAYNKFSIKSDVWAFGVLLWEIAT--------YGMSPYPgidlSQVYELLEKDYRMER-PEGCPEKVYELMRACWQWNP 480
Cdd:cd13995  166 VILCRGHNTKADIYSLGATIIHMQTgsppwvrrYPRSAYP----SYLYIIHKQAPPLEDiAQDCSPAMRELLEAALERNP 241
                        250
                 ....*....|....*
gi 62362414  481 SDRPSFAEI--HQAF 493
Cdd:cd13995  242 NHRSSAAELlkHEAL 256
STKc_PIM cd14005
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
246-493 2.05e-13

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are two PIM1 and three PIM2 isoforms as a result of alternative translation initiation sites, while there is only one PIM3 protein. Compound knockout mice deficient of all three PIM kinases that survive the perinatal period show a profound reduction in body size, indicating that PIMs are important for body growth. The PIM subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270907 [Multi-domain]  Cd Length: 255  Bit Score: 71.50  E-value: 2.05e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  246 HKLGGGQYGEVYEGVWKKYSLTVAVK-TLKEDTME------VEEFLKEAAVMKEI---KHPNLVQLLGVCTREPPFYIIT 315
Cdd:cd14005    6 DLLGKGGFGTVYSGVRIRDGLPVAVKfVPKSRVTEwamingPVPVPLEIALLLKAskpGVPGVIRLLDWYERPDGFLLIM 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  316 EF----MtygNLLDYLRECNRQEVNAVVLLYmaTQISSAMEYLEKKNFIHRDLAARNCLVG-ENHLVKVADFGLSRLMTG 390
Cdd:cd14005   86 ERpepcQ---DLFDFITERGALSENLARIIF--RQVVEAVRHCHQRGVLHRDIKDENLLINlRTGEVKLIDFGCGALLKD 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  391 DTYTAHAGAKFpikWTAPESLAYNKFSIKS-DVWAFGVLLWEIATyGMSPYPGiDLSQVYELLEKDYRMErPEGCpekvy 469
Cdd:cd14005  161 SVYTDFDGTRV---YSPPEWIRHGRYHGRPaTVWSLGILLYDMLC-GDIPFEN-DEQILRGNVLFRPRLS-KECC----- 229
                        250       260
                 ....*....|....*....|....*.
gi 62362414  470 ELMRACWQWNPSDRPSFAEI--HQAF 493
Cdd:cd14005  230 DLISRCLQFDPSKRPSLEQIlsHPWF 255
STKc_Sty1_Hog1 cd07856
Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases ...
224-452 2.67e-13

Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases Sty1 and Hog1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs Sty1 from Schizosaccharomyces pombe, Hog1 from Saccharomyces cerevisiae, and similar proteins. Sty1 and Hog1 are stress-activated MAPKs that partipate in transcriptional regulation in response to stress. Sty1 is activated in response to oxidative stress, osmotic stress, and UV radiation. It is regulated by the MAP2K Wis1, which is activated by the MAP3Ks Wis4 and Win1, which receive signals of the stress condition from membrane-spanning histidine kinases Mak1-3. Activated Sty1 stabilizes the Atf1 transcription factor and induces transcription of Atf1-dependent genes of the core environmetal stress response. Hog1 is the key element in the high osmolarity glycerol (HOG) pathway and is activated upon hyperosmotic stress. Activated Hog1 accumulates in the nucleus and regulates stress-induced transcription. The HOG pathway is mediated by two transmembrane osmosensors, Sln1 and Sho1. MAPKs are important mediators of cellular responses to extracellular signals. The Sty1/Hog1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270843 [Multi-domain]  Cd Length: 328  Bit Score: 72.22  E-value: 2.67e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  224 TVYGVSPNYDKWEmertditmkhKLGGGQYGEVYEGVWKKYSLTVAVKTLKE---DTMEVEEFLKEAAVMKEIKHPNLVQ 300
Cdd:cd07856    4 TVFEITTRYSDLQ----------PVGMGAFGLVCSARDQLTGQNVAVKKIMKpfsTPVLAKRTYRELKLLKHLRHENIIS 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  301 LLGVCTRepPF---YIITEFMtyGNLLDYLRECNRQEVNAVvlLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLV 377
Cdd:cd07856   74 LSDIFIS--PLediYFVTELL--GTDLHRLLTSRPLEKQFI--QYFLYQILRGLKYVHSAGVIHRDLKPSNILVNENCDL 147
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  378 KVADFGLSRL----MTGDTYTAHagakfpikWTAPE-SLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGID----LSQV 448
Cdd:cd07856  148 KICDFGLARIqdpqMTGYVSTRY--------YRAPEiMLTWQKYDVEVDIWSAGCIFAEMLE-GKPLFPGKDhvnqFSII 218

                 ....
gi 62362414  449 YELL 452
Cdd:cd07856  219 TELL 222
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
62-117 2.96e-13

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.


Pssm-ID: 214620 [Multi-domain]  Cd Length: 56  Bit Score: 65.25  E-value: 2.96e-13
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*..
gi 62362414      62 DPNLFVALYDFVASGDNTLSITKGEKLRVLGyNHNGEWCEAQTKNGQ-GWVPSNYIT 117
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLE-KSDDGWWKGRLGRGKeGLFPSNYVE 56
STKc_CK1 cd14016
Catalytic domain of the Serine/Threonine protein kinase, Casein Kinase 1; STKs catalyze the ...
245-386 3.18e-13

Catalytic domain of the Serine/Threonine protein kinase, Casein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK1 phosphorylates a variety of substrates including enzymes, transcription and splice factors, cytoskeletal proteins, viral oncogenes, receptors, and membrane-associated proteins. There are mutliple isoforms of CK1 and in mammals, seven isoforms (alpha, beta, gamma1-3, delta, and epsilon) have been characterized. These isoforms differ mainly in the length and structure of their C-terminal non-catalytic region. Some isoforms have several splice variants such as the long (L) and short (S) variants of CK1alpha. CK1 proteins are involved in the regulation of many cellular processes including membrane transport processes, circadian rhythm, cell division, apoptosis, and the development of cancer and neurodegenerative diseases. The CK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270918 [Multi-domain]  Cd Length: 266  Bit Score: 70.95  E-value: 3.18e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  245 KHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTmEVEEFLKEAAVMKEIKH----PNLVQllgvCTREPPFYIITefMTY 320
Cdd:cd14016    5 VKKIGSGSFGEVYLGIDLKTGEEVAIKIEKKDS-KHPQLEYEAKVYKLLQGgpgiPRLYW----FGQEGDYNVMV--MDL 77
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 62362414  321 -G-NLLDYLRECNRQEVNAVVLLyMATQISSAMEYLEKKNFIHRDLAARNCLVG---ENHLVKVADFGLSR 386
Cdd:cd14016   78 lGpSLEDLFNKCGRKFSLKTVLM-LADQMISRLEYLHSKGYIHRDIKPENFLMGlgkNSNKVYLIDFGLAK 147
STKc_DRAK2 cd14198
The catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
245-489 3.33e-13

The catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2 (also called STK17B). Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. DRAK2 has been implicated in inducing or enhancing apoptosis in beta cells, fibroblasts, and lymphoid cells, where it is highly expressed. It is involved in regulating many immune processes including the germinal center (GC) reaction, responses to thymus-dependent antigens, activated T cell survival, memory T cell responses. It may be involved in the development of autoimmunity. The DRAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271100 [Multi-domain]  Cd Length: 270  Bit Score: 71.11  E-value: 3.33e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  245 KHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVE---EFLKEAAVMKEIK-HPNLVQLLGVCTREPPFYIITEFMTY 320
Cdd:cd14198   13 SKELGRGKFAVVRQCISKSTGQEYAAKFLKKRRRGQDcraEILHEIAVLELAKsNPRVVNLHEVYETTSEIILILEYAAG 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  321 GNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGE-NHL--VKVADFGLSRLMtgdtytAHA 397
Cdd:cd14198   93 GEIFNLCVPDLAEMVSENDIIRLIRQILEGVYYLHQNNIVHLDLKPQNILLSSiYPLgdIKIVDFGMSRKI------GHA 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  398 GAKFPI----KWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEK---DYRMERPEGCPEKVYE 470
Cdd:cd14198  167 CELREImgtpEYLAPEILNYDPITTATDMWNIGVIAYMLLT-HESPFVGEDNQETFLNISQvnvDYSEETFSSVSQLATD 245
                        250
                 ....*....|....*....
gi 62362414  471 LMRACWQWNPSDRPSfAEI 489
Cdd:cd14198  246 FIQKLLVKNPEKRPT-AEI 263
STKc_IKK cd13989
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
248-440 3.37e-13

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The IKK complex functions as a master regulator of Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. It is composed of two kinases, IKKalpha and IKKbeta, and the regulatory subunit IKKgamma or NEMO (NF-kB Essential MOdulator). IKKs facilitate the release of NF-kB dimers from an inactive state, allowing them to migrate to the nucleus where they regulate gene transcription. There are two IKK pathways that regulate NF-kB signaling, called the classical (involving IKKbeta and NEMO) and non-canonical (involving IKKalpha) pathways. The classical pathway regulates the majority of genes activated by NF-kB. The IKK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270891 [Multi-domain]  Cd Length: 289  Bit Score: 71.33  E-value: 3.37e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYegVWK--KYSLTVAVKTLKEDTMEV----EEFLKEAAVMKEIKHPNLVQLLGVctrEPPFYIIT------ 315
Cdd:cd13989    1 LGSGGFGYVT--LWKhqDTGEYVAIKKCRQELSPSdknrERWCLEVQIMKKLNHPNVVSARDV---PPELEKLSpndlpl 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  316 ---EFMTYGNLLDYLRE----CNRQEVNAVVLLymaTQISSAMEYLEKKNFIHRDLAARNCLV--GENHLV-KVADFGLS 385
Cdd:cd13989   76 lamEYCSGGDLRKVLNQpencCGLKESEVRTLL---SDISSAISYLHENRIIHRDLKPENIVLqqGGGRVIyKLIDLGYA 152
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 62362414  386 R-LMTGDTYTAHAGAkfpIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPY 440
Cdd:cd13989  153 KeLDQGSLCTSFVGT---LQYLAPELFESKKYTCTVDYWSFGTLAFECIT-GYRPF 204
STKc_PLK1 cd14187
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; STKs catalyze the ...
248-489 4.29e-13

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. Its localization changes during mitotic progression; associating first with centrosomes in prophase, with kinetochores in prometaphase and metaphase, at the central spindle in anaphase, and in the midbody during telophase. It carries multiple functions throughout the cell cycle through interactions with differrent substrates at these specific subcellular locations. PLK1 is overexpressed in many human cancers and is associated with poor prognosis. The PLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271089 [Multi-domain]  Cd Length: 265  Bit Score: 70.73  E-value: 4.29e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYE----GVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNL 323
Cdd:cd14187   15 LGKGGFAKCYEitdaDTKEVFAGKIVPKSLLLKPHQKEKMSMEIAIHRSLAHQHVVGFHGFFEDNDFVYVVLELCRRRSL 94
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  324 LDYLREcnRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPi 403
Cdd:cd14187   95 LELHKR--RKALTEPEARYYLRQIILGCQYLHRNRVIHRDLKLGNLFLNDDMEVKIGDFGLATKVEYDGERKKTLCGTP- 171
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  404 KWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEK-DYRMerPEGCPEKVYELMRACWQWNPSD 482
Cdd:cd14187  172 NYIAPEVLSKKGHSFEVDIWSIGCIMYTLLV-GKPPFETSCLKETYLRIKKnEYSI--PKHINPVAASLIQKMLQTDPTA 248

                 ....*..
gi 62362414  483 RPSFAEI 489
Cdd:cd14187  249 RPTINEL 255
STKc_DRAK1 cd14197
Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
238-488 4.63e-13

Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 (also called STK17A) and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. Rabbit DRAK1 has been shown to induce apoptosis in osteoclasts and overexpressio of human DRAK1 induces apoptosis in cultured fibroblast cells. DRAK1 may be involved in apoptotic signaling. The DRAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271099 [Multi-domain]  Cd Length: 271  Bit Score: 70.73  E-value: 4.63e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  238 ERTDITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVE---EFLKEAAVMKEIK-HPNLVQLLGVCTREPPFYI 313
Cdd:cd14197    7 ERYSLSPGRELGRGKFAVVRKCVEKDSGKEFAAKFMRKRRKGQDcrmEIIHEIAVLELAQaNPWVINLHEVYETASEMIL 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  314 ITEFMTYGNLLDYL---RECNRQEVNAVVLLymaTQISSAMEYLEKKNFIHRDLAARNCLV-GENHL--VKVADFGLSRL 387
Cdd:cd14197   87 VLEYAAGGEIFNQCvadREEAFKEKDVKRLM---KQILEGVSFLHNNNVVHLDLKPQNILLtSESPLgdIKIVDFGLSRI 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  388 MTgDTYTAHAGAKFPiKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVY---ELLEKDYRMERPEGC 464
Cdd:cd14197  164 LK-NSEELREIMGTP-EYVAPEILSYEPISTATDMWSIGVLAYVMLT-GISPFLGDDKQETFlniSQMNVSYSEEEFEHL 240
                        250       260
                 ....*....|....*....|....
gi 62362414  465 PEKVYELMRACWQWNPSDRPSFAE 488
Cdd:cd14197  241 SESAIDFIKTLLIKKPENRATAED 264
SH2_Src_Lyn cd10364
Src homology 2 (SH2) domain found in Lyn; Lyn is a member of the Src non-receptor type ...
123-216 4.74e-13

Src homology 2 (SH2) domain found in Lyn; Lyn is a member of the Src non-receptor type tyrosine kinase family of proteins and is expressed in the hematopoietic cells, in neural tissues, liver, and adipose tissue. There are two alternatively spliced forms of Lyn. Lyn plays an inhibitory role in myeloid lineage proliferation. Following engagement of the B cell receptors, Lyn undergoes rapid phosphorylation and activation, triggering a cascade of signaling events mediated by Lyn phosphorylation of tyrosine residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the receptor proteins, and subsequent recruitment and activation of other kinases including Syk, phospholipase C2 (PLC2) and phosphatidyl inositol-3 kinase. These kinases play critical roles in proliferation, Ca2+ mobilization and cell differentiation. Lyn plays an essential role in the transmission of inhibitory signals through phosphorylation of tyrosine residues within the immunoreceptor tyrosine-based inhibitory motifs (ITIM) in regulatory proteins such as CD22, PIR-B and FC RIIb1. Their ITIM phosphorylation subsequently leads to recruitment and activation of phosphatases such as SHIP-1 and SHP-1 which further down modulate signaling pathways, attenuate cell activation and can mediate tolerance. Lyn also plays a role in the insulin signaling pathway. Activated Lyn phosphorylates insulin receptor substrate 1 (IRS1) leading to an increase in translocation of Glut-4 to the cell membrane and increased glucose utilization. It is the primary Src family member involved in signaling downstream of the B cell receptor. Lyn plays an unusual, 2-fold role in B cell receptor signaling; it is essential for initiation of signaling but is also later involved in negative regulation of the signal. Lyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198227  Cd Length: 101  Bit Score: 66.16  E-value: 4.74e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  123 EKHSWYHGPVSRNAAE-YLLSSGIN-GSFLVRESESSPGQRSISLR-----YEGRVYHYRINTASDGKLYVSSESRFNTL 195
Cdd:cd10364    1 ETEEWFFKDITRKDAErQLLAPGNSaGAFLIRESETLKGSYSLSVRdydpqHGDVIKHYKIRSLDNGGYYISPRITFPCI 80
                         90       100
                 ....*....|....*....|.
gi 62362414  196 AELVHHHSTVADGLITTLHYP 216
Cdd:cd10364   81 SDMIKHYQKQSDGLCRRLEKA 101
SH2_SOCS_family cd09923
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) family; SH2 ...
126-201 4.98e-13

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) family; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198178  Cd Length: 81  Bit Score: 65.30  E-value: 4.98e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  126 SWYHGPVSRNAAEYLLSSGINGSFLVRESESSPGQRSISLRYEGRVYHYRInTASDGKLYVSSES----RFNTLAELVHH 201
Cdd:cd09923    1 GWYWGGITRYEAEELLAGKPEGTFLVRDSSDSRYLFSVSFRTYGRTLHARI-EYSNGRFSFDSSDpsvpRFPCVVELIEH 79
SH2_Tec_Bmx cd10399
Src homology 2 (SH2) domain found in Tec protein, Bmx; A member of the Tec protein tyrosine ...
121-216 5.28e-13

Src homology 2 (SH2) domain found in Tec protein, Bmx; A member of the Tec protein tyrosine kinase Bmx is expressed in the endothelium of large arteries, fetal endocardium, adult endocardium of the left ventricle, bone marrow, lung, testis, granulocytes, myeloid cell lines, and prostate cell lines. Bmx is involved in the regulation of Rho and serum response factor (SRF). Bmx has been shown to interact with PAK1, PTK2, PTPN21, and RUFY1. Most of the Tec family members have a PH domain (Txk and the short (type 1) splice variant of Drosophila Btk29A are exceptions), a Tec homology (TH) domain, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP. It is crucial for the function of Tec PH domains. It is not present in Txk and the type 1 splice form of the Drosophila homolog. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198262  Cd Length: 106  Bit Score: 66.13  E-value: 5.28e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  121 SLEKHSWYHGPVSRNAAEYLL-SSGINGSFLVRESeSSPGQRSISL------RYEGRVYHYRINTASDGKLYVSSESRFN 193
Cdd:cd10399    2 NLDAYDWFAGNISRSQSEQLLrQKGKEGAFMVRNS-SQVGMYTVSLfskavnDKKGTVKHYHVHTNAENKLYLAENYCFD 80
                         90       100
                 ....*....|....*....|...
gi 62362414  194 TLAELVHHHSTVADGLITTLHYP 216
Cdd:cd10399   81 SIPKLIHYHQHNSAGMITRLRHP 103
STKc_p38gamma cd07880
Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase ...
248-453 5.45e-13

Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase (also called MAPK12); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38gamma/MAPK12 is predominantly expressed in skeletal muscle. Unlike p38alpha and p38beta, p38gamma is insensitive to pyridinylimidazoles. It displays an antagonizing function compared to p38alpha. p38gamma inhibits, while p38alpha stimulates, c-Jun phosphorylation and AP-1 mediated transcription. p38gamma also plays a role in the signaling between Ras and the estrogen receptor and has been implicated to increase cell invasion and breast cancer progression. In Xenopus, p38gamma is critical in the meiotic maturation of oocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143385 [Multi-domain]  Cd Length: 343  Bit Score: 71.52  E-value: 5.45e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEdTMEVEEFLKEA----AVMKEIKHPNLVQLLGVCT------REPPFYIITEF 317
Cdd:cd07880   23 VGSGAYGTVCSALDRRTGAKVAIKKLYR-PFQSELFAKRAyrelRLLKHMKHENVIGLLDVFTpdlsldRFHDFYLVMPF 101
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  318 MtyGNLLDYLRECNRQEVNAVvlLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRL----MTGDTY 393
Cdd:cd07880  102 M--GTDLGKLMKHEKLSEDRI--QFLVYQMLKGLKYIHAAGIIHRDLKPGNLAVNEDCELKILDFGLARQtdseMTGYVV 177
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 62362414  394 TahagakfpiKW-TAPES-LAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGID-LSQVYELLE 453
Cdd:cd07880  178 T---------RWyRAPEViLNWMHYTQTVDIWSVGCIMAEMLT-GKPLFKGHDhLDQLMEIMK 230
STKc_MSK2_C cd14180
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
248-489 5.62e-13

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271082 [Multi-domain]  Cd Length: 309  Bit Score: 71.06  E-value: 5.62e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEdTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDYL 327
Cdd:cd14180   14 LGEGSFSVCRKCRHRQSGQEYAVKIISR-RMEANTQREVAALRLCQSHPNIVALHEVLHDQYHTYLVMELLRGGELLDRI 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  328 RECNR-QEVNAVVLLymaTQISSAMEYLEKKNFIHRDLAARNCLV---GENHLVKVADFGLSRLMTGDTYTAHAGAkFPI 403
Cdd:cd14180   93 KKKARfSESEASQLM---RSLVSAVSFMHEAGVVHRDLKPENILYadeSDGAVLKVIDFGFARLRPQGSRPLQTPC-FTL 168
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  404 KWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPG----IDLSQVYELLEK----DYRMERP--EGCPEKVYELMR 473
Cdd:cd14180  169 QYAAPELFSNQGYDESCDLWSLGVILYTMLS-GQVPFQSkrgkMFHNHAADIMHKikegDFSLEGEawKGVSEEAKDLVR 247
                        250
                 ....*....|....*.
gi 62362414  474 ACWQWNPSDRPSFAEI 489
Cdd:cd14180  248 GLLTVDPAKRLKLSEL 263
STKc_CaMKIV cd14085
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
243-440 5.84e-13

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type IV; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKIV is found predominantly in neurons and immune cells. It is activated by the binding of calcium/CaM and phosphorylation by CaMKK (alpha or beta). The CaMKK-CaMKIV cascade participates in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors. It also is implicated in T-cell development and signaling, cytokine secretion, and signaling through Toll-like receptors, and is thus, pivotal in immune response and inflammation. The CaMKIV subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270987 [Multi-domain]  Cd Length: 294  Bit Score: 71.01  E-value: 5.84e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  243 TMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEdTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGN 322
Cdd:cd14085    6 EIESELGRGATSVVYRCRQKGTQKPYAVKKLKK-TVDKKIVRTEIGVLLRLSHPNIIKLKEIFETPTEISLVLELVTGGE 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLRE----CNRQEVNAVvllymaTQISSAMEYLEKKNFIHRDLAARNCLV---GENHLVKVADFGLSRLMTgDTYTA 395
Cdd:cd14085   85 LFDRIVEkgyySERDAADAV------KQILEAVAYLHENGIVHRDLKPENLLYatpAPDAPLKIADFGLSKIVD-QQVTM 157
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 62362414  396 HAGAKFPiKWTAPESLAYNKFSIKSDVWAFGVLLWeIATYGMSPY 440
Cdd:cd14085  158 KTVCGTP-GYCAPEILRGCAYGPEVDMWSVGVITY-ILLCGFEPF 200
PKc_Myt1 cd14050
Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze ...
247-489 5.86e-13

Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Myt1 is a cytoplasmic cell cycle checkpoint kinase that can keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of N-terminal thr (T14) and tyr (Y15) residues, leading to the delay of meiosis I entry. Meiotic progression is ensured by a two-step inhibition and downregulation of Myt1 by CDK1/XRINGO and p90Rsk during oocyte maturation. In addition, Myt1 targets cyclin B1/B2 and is essential for Golgi and ER assembly during telophase. In Drosophila, Myt1 may be a downstream target of Notch during eye development. The Myt1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270952 [Multi-domain]  Cd Length: 249  Bit Score: 70.03  E-value: 5.86e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLKE---DTMEVEEFLKEAAVMKEIK-HPNLVQLLGVCTREPPFYIITEfMTYGN 322
Cdd:cd14050    8 KLGEGSFGEVFKVRSREDGKLYAVKRSRSrfrGEKDRKRKLEEVERHEKLGeHPNCVRFIKAWEEKGILYIQTE-LCDTS 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLRECNRQEVNAV--VLLYMAtqisSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGL-SRLMTGDTYTAHAGA 399
Cdd:cd14050   87 LQQYCEETHSLPESEVwnILLDLL----KGLKHLHDHGLIHLDIKPANIFLSKDGVCKLGDFGLvVELDKEDIHDAQEGD 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  400 KfpiKWTAPESLAyNKFSIKSDVWAFGVLLWEIATYGMSPYPGidlsQVYELLEKDYrmeRPEGCPEKVYELMRACWQW- 478
Cdd:cd14050  163 P---RYMAPELLQ-GSFTKAADIFSLGITILELACNLELPSGG----DGWHQLRQGY---LPEEFTAGLSPELRSIIKLm 231
                        250
                 ....*....|....
gi 62362414  479 ---NPSDRPSFAEI 489
Cdd:cd14050  232 mdpDPERRPTAEDL 245
STKc_IRE1 cd13982
Catalytic domain of the Serine/Threonine kinase, Inositol-requiring protein 1; STKs catalyze ...
242-489 6.09e-13

Catalytic domain of the Serine/Threonine kinase, Inositol-requiring protein 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRE1, also called Endoplasmic reticulum (ER)-to-nucleus signaling protein (or ERN), is an ER-localized type I transmembrane protein with kinase and endoribonuclease domains in the cytoplasmic side. It acts as an ER stress sensor and is the oldest and most conserved component of the unfolded protein response (UPR) in eukaryotes. The UPR is activated when protein misfolding is detected in the ER in order to decrease the synthesis of new proteins and increase the capacity of the ER to cope with the stress. During ER stress, IRE1 dimerizes and forms oligomers, allowing the kinase domain to undergo trans-autophosphorylation. This leads to a conformational change that stimulates its endoribonuclease activity and results in the cleavage of its mRNA substrate, HAC1 in yeast and XBP1 in metazoans, promoting a splicing event that enables translation into a transcription factor which activates the UPR. Mammals contain two IRE1 proteins, IRE1alpha (or ERN1) and IRE1beta (or ERN2). The Ire1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270884 [Multi-domain]  Cd Length: 269  Bit Score: 70.38  E-value: 6.09e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  242 ITMKHK-LGGGQYGE-VYEGVWKKYSltVAVKTLkedtmeVEEFLKEAAvmKEIK-------HPNLVQLLgvCTREPP-F 311
Cdd:cd13982    2 LTFSPKvLGYGSEGTiVFRGTFDGRP--VAVKRL------LPEFFDFAD--REVQllresdeHPNVIRYF--CTEKDRqF 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  312 -YIITEFMTyGNLLDYL---RECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLV-----GENHLVKVADF 382
Cdd:cd13982   70 lYIALELCA-ASLQDLVespRESKLFLRPGLEPVRLLRQIASGLAHLHSLNIVHRDLKPQNILIstpnaHGNVRAMISDF 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  383 GLSRLMTGDTYTAH--AGAKFPIKWTAPESL---AYNKFSIKSDVWAFGVLLWEIATYGMSPYpGIDLSQVYELLEKDYR 457
Cdd:cd13982  149 GLCKKLDVGRSSFSrrSGVAGTSGWIAPEMLsgsTKRRQTRAVDIFSLGCVFYYVLSGGSHPF-GDKLEREANILKGKYS 227
                        250       260       270
                 ....*....|....*....|....*....|....*
gi 62362414  458 MERPEG---CPEKVYELMRACWQWNPSDRPSFAEI 489
Cdd:cd13982  228 LDKLLSlgeHGPEAQDLIERMIDFDPEKRPSAEEV 262
STKc_CDK9 cd07865
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs ...
247-386 6.74e-13

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK9, together with a cyclin partner (cyclin T1, T2a, T2b, or K), is the main component of distinct positive transcription elongation factors (P-TEFb), which function as Ser2 C-terminal domain kinases of RNA polymerase II. P-TEFb participates in multiple steps of gene expression including transcription elongation, mRNA synthesis, processing, export, and translation. It also plays a role in mediating cytokine induced transcription networks such as IL6-induced STAT3 signaling. In addition, the CDK9/cyclin T2a complex promotes muscle differentiation and enhances the function of some myogenic regulatory factors. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270848 [Multi-domain]  Cd Length: 310  Bit Score: 70.86  E-value: 6.74e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTmEVEEF----LKEAAVMKEIKHPNLVQLLGVCTREP--------PFYII 314
Cdd:cd07865   19 KIGQGTFGEVFKARHRKTGQIVALKKVLMEN-EKEGFpitaLREIKILQLLKHENVVNLIEICRTKAtpynrykgSIYLV 97
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 62362414  315 TEFMTYgNLLDYLRECNRQeVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR 386
Cdd:cd07865   98 FEFCEH-DLAGLLSNKNVK-FTLSEIKKVMKMLLNGLYYIHRNKILHRDMKAANILITKDGVLKLADFGLAR 167
STKc_CDC2L1 cd07843
Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze ...
251-434 6.87e-13

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDC2L1, also called PITSLRE, exists in different isoforms which are named using the alias CDK11(p). The CDC2L1 gene produces two protein products, CDK11(p110) and CDK11(p58). CDC2L1 is also represented by the caspase-processed CDK11(p46). CDK11(p110), the major isoform, associates with cyclin L and is expressed throughout the cell cycle. It is involved in RNA processing and the regulation of transcription. CDK11(p58) associates with cyclin D3 and is expressed during the G2/M phase of the cell cycle. It plays roles in spindle morphogenesis, centrosome maturation, sister chromatid cohesion, and the completion of mitosis. CDK11(p46) is formed from the larger isoforms by caspases during TNFalpha- and Fas-induced apoptosis. It functions as a downstream effector kinase in apoptotic signaling pathways and interacts with eukaryotic initiation factor 3f (eIF3f), p21-activated kinase (PAK1), and Ran-binding protein (RanBPM). CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDC2L1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173741 [Multi-domain]  Cd Length: 293  Bit Score: 70.72  E-value: 6.87e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  251 GQYGEVYEGVWKKYSLTVAVKTLKEDTmEVEEF----LKEAAVMKEIKHPNLVQL--LGVCTREPPFYIITEFMTYG--N 322
Cdd:cd07843   16 GTYGVVYRARDKKTGEIVALKKLKMEK-EKEGFpitsLREINILLKLQHPNIVTVkeVVVGSNLDKIYMVMEYVEHDlkS 94
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLRECNRQ-EVNAVVLlymatQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRlmtgdtytahagaKF 401
Cdd:cd07843   95 LMETMKQPFLQsEVKCLML-----QLLSGVAHLHDNWILHRDLKTSNLLLNNRGILKICDFGLAR-------------EY 156
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 62362414  402 --PIK---------W-TAPESL-AYNKFSIKSDVWAFGVLLWEIAT 434
Cdd:cd07843  157 gsPLKpytqlvvtlWyRAPELLlGAKEYSTAIDMWSVGCIFAELLT 202
SH2_cSH2_p85_like cd09930
C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
126-217 7.07e-13

C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. p110, the catalytic subunit, is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. The regulatory unit is called p85 and is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, a inter SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are 2 inhibitory interactions between p110alpha and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and 2) p85 iSH2 domain with C2 domain of p110alpha. There are 3 inhibitory interactions between p110beta and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, 2) p85 iSH2 domain with C2 domain of p110alpha, and 3) p85 cSH2 domain with the kinase domain of p110alpha. It is interesting to note that p110beta is oncogenic as a wild type protein while p110alpha lacks this ability. One explanation is the idea that the regulation of p110beta by p85 is unique because of the addition of inhibitory contacts from the cSH2 domain and the loss of contacts in the iSH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198184  Cd Length: 104  Bit Score: 65.90  E-value: 7.07e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  126 SWYHGPVSRNAAEYLLSSGINGSFLVRESeSSPGQRSISLRYEGRVYHYRINTASDGKLYVSSESRFNTLAELVHHHSTV 205
Cdd:cd09930    7 TWLVGDINRTQAEELLRGKPDGTFLIRES-STQGCYACSVVCNGEVKHCVIYKTETGYGFAEPYNLYESLKELVLHYAHN 85
                         90
                 ....*....|....*..
gi 62362414  206 A-----DGLITTLHYPA 217
Cdd:cd09930   86 SleqhnDSLTVTLAYPV 102
STKc_ROCK_NDR_like cd05573
Catalytic domain of Rho-associated coiled-coil containing protein kinase (ROCK)- and Nuclear ...
248-449 7.18e-13

Catalytic domain of Rho-associated coiled-coil containing protein kinase (ROCK)- and Nuclear Dbf2-Related (NDR)-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include ROCK and ROCK-like proteins such as DMPK, MRCK, and CRIK, as well as NDR and NDR-like proteins such as LATS, CBK1 and Sid2p. ROCK and CRIK are effectors of the small GTPase Rho, while MRCK is an effector of the small GTPase Cdc42. NDR and NDR-like kinases contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Proteins in this subfamily are involved in regulating many cellular functions including contraction, motility, division, proliferation, apoptosis, morphogenesis, and cytokinesis. The ROCK/NDR-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270725 [Multi-domain]  Cd Length: 350  Bit Score: 71.16  E-value: 7.18e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEgVWKKYSLTV-AVKTLKEDTM----EVEEFLKEAAVMKEIKHPNLVQLlgVCTREPP--FYIITEFMTY 320
Cdd:cd05573    9 IGRGAFGEVWL-VRDKDTGQVyAMKILRKSDMlkreQIAHVRAERDILADADSPWIVRL--HYAFQDEdhLYLVMEYMPG 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  321 GNLLDYLreCNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLM--TGDTYT---- 394
Cdd:cd05573   86 GDLMNLL--IKYDVFPEETARFYIAELVLALDSLHKLGFIHRDIKPDNILLDADGHIKLADFGLCTKMnkSGDRESylnd 163
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 62362414  395 -------AHAGAKFPIK---------------WTAPESLAYNKFSIKSDVWAFGVLLWEiATYGMSPYPGIDLSQVY 449
Cdd:cd05573  164 svntlfqDNVLARRRPHkqrrvraysavgtpdYIAPEVLRGTGYGPECDWWSLGVILYE-MLYGFPPFYSDSLVETY 239
SH2_N-SH2_PLC_gamma_like cd10341
N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
127-202 7.53e-13

N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199829  Cd Length: 99  Bit Score: 65.45  E-value: 7.53e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  127 WYHGPVS--RNAAEYLLS---SGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTASDG---KLYVSSESRFNTLAEL 198
Cdd:cd10341    6 WFHGKLGdgRDEAEKLLLeycEGGDGTFLVRESETFVGDYTLSFWRNGKVQHCRIRSRQENgekKYYLTDNLVFDSLYEL 85

                 ....
gi 62362414  199 VHHH 202
Cdd:cd10341   86 IDYY 89
STKc_aPKC_zeta cd05617
Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C zeta; STKs catalyze ...
241-483 7.61e-13

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C zeta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-zeta plays a critical role in activating the glucose transport response. It is activated by glucose, insulin, and exercise through diverse pathways. PKC-zeta also plays a central role in maintaining cell polarity in yeast and mammalian cells. In addition, it affects actin remodeling in muscle cells. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. The aPKC-zeta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270768 [Multi-domain]  Cd Length: 357  Bit Score: 71.21  E-value: 7.61e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  241 DITMKHKLGGGQYGEVYEGVWKK----YSLTVAVKTLKEDTMEVEEFLKEAAVMKEIK-HPNLVQLLGVCTREPPFYIIT 315
Cdd:cd05617   16 DFDLIRVIGRGSYAKVLLVRLKKndqiYAMKVVKKELVHDDEDIDWVQTEKHVFEQASsNPFLVGLHSCFQTTSRLFLVI 95
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  316 EFMTYGNLLDYL-RECNRQEVNAvvlLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR--LMTGDT 392
Cdd:cd05617   96 EYVNGGDLMFHMqRQRKLPEEHA---RFYAAEICIALNFLHERGIIYRDLKLDNVLLDADGHIKLTDYGMCKegLGPGDT 172
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  393 YTAHAGAKfpiKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPY------PGID----LSQVyeLLEKDYRMerPE 462
Cdd:cd05617  173 TSTFCGTP---NYIAPEILRGEEYGFSVDWWALGVLMFEMMA-GRSPFdiitdnPDMNtedyLFQV--ILEKPIRI--PR 244
                        250       260
                 ....*....|....*....|.
gi 62362414  463 GCPEKVYELMRACWQWNPSDR 483
Cdd:cd05617  245 FLSVKASHVLKGFLNKDPKER 265
STKc_obscurin_rpt2 cd14110
Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs ...
251-428 1.06e-12

Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Obscurin, approximately 800 kDa in size, is one of three giant proteins expressed in vetebrate striated muscle, together with titin and nebulin. It is a multidomain protein composed of tandem adhesion and signaling domains, including 49 immunoglobulin (Ig) and 2 fibronectin type III (FN3) domains at the N-terminus followed by a more complex region containing more Ig domains, a conserved SH3 domain near a RhoGEF and PH domains, non-modular regions, as well as IQ and phosphorylation motifs. The obscurin gene also encode two kinase domains, which are not expressed as part of the 800 kDa protein, but as a smaller, alternatively spliced product present mainly in the heart muscle, also called obscurin-MLCK. Obscurin is localized at the peripheries of Z-disks and M-lines, where it is able to communicate with the surrounding myoplasm. It interacts with diverse proteins including sAnk1, myosin, titin, and MyBP-C. It may act as a scaffold for the assembly of elements of the contractile apparatus. The obscurin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271012 [Multi-domain]  Cd Length: 257  Bit Score: 69.56  E-value: 1.06e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  251 GQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDYLREC 330
Cdd:cd14110   14 GRFSVVRQCEEKRSGQMLAAKIIPYKPEDKQLVLREYQVLRRLSHPRIAQLHSAYLSPRHLVLIEELCSGPELLYNLAER 93
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  331 NR-QEVNAVVLLYmatQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPIKWTAPE 409
Cdd:cd14110   94 NSySEAEVTDYLW---QILSAVDYLHSRRILHLDLRSENMIITEKNLLKIVDLGNAQPFNQGKVLMTDKKGDYVETMAPE 170
                        170
                 ....*....|....*....
gi 62362414  410 SLAYNKFSIKSDVWAFGVL 428
Cdd:cd14110  171 LLEGQGAGPQTDIWAIGVT 189
SH2_BCAR3 cd10337
Src homology 2 (SH2) domain in the Breast Cancer Anti-estrogen Resistance protein 3; BCAR3 is ...
122-202 1.44e-12

Src homology 2 (SH2) domain in the Breast Cancer Anti-estrogen Resistance protein 3; BCAR3 is part of a growing family of guanine nucleotide exchange factors is responsible for activation of Ras-family GTPases, including Sos1 and 2, GRF1 and 2, CalDAG-GEF/GRP1-4, C3G, cAMP-GEF/Epac 1 and 2, PDZ-GEFs, MR-GEF, RalGDS family members, RalGPS, RasGEF, Smg GDS, and phospholipase C(epsilon). 12102558 21262352 BCAR3 binds to the carboxy-terminus of BCAR1/p130Cas, a focal adhesion adapter protein. Over expression of BCAR1 (p130Cas) and BCAR3 induces estrogen independent growth in normally estrogen-dependent cell lines. They have been linked to resistance to anti-estrogens in breast cancer, Rac activation, and cell motility, though the BCAR3/p130Cas complex is not required for this activity in BCAR3. Many BCAR3-mediated signaling events in epithelial and mesenchymal cells are independent of p130Cas association. Structurally these proteins contain a single SH2 domain upstream of their RasGEF domain, which is responsible for the ability of BCAR3 to enhance p130Cas over-expression-induced migration. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198200 [Multi-domain]  Cd Length: 136  Bit Score: 65.82  E-value: 1.44e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  122 LEKHSWYHGPVSRNAAEYLLSSgiNGSFLVRESESSPGQRSISLRYEGRVYHYRIN-------TASDGKLYVSSESRFNT 194
Cdd:cd10337    3 LRSHAWYHGRIPRQVAESLVQR--EGDFLVRDSLSSPGDYVLTCRWKGQPLHFKINrvvlrpsEAYTRVQYQFEDEQFDS 80

                 ....*...
gi 62362414  195 LAELVHHH 202
Cdd:cd10337   81 IPALVHFY 88
PLN00034 PLN00034
mitogen-activated protein kinase kinase; Provisional
236-491 1.49e-12

mitogen-activated protein kinase kinase; Provisional


Pssm-ID: 215036 [Multi-domain]  Cd Length: 353  Bit Score: 70.24  E-value: 1.49e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   236 EMERTDitmkhKLGGGQYGEVYEGVWKKYSLTVAVKTL---KEDTMEvEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFY 312
Cdd:PLN00034   75 ELERVN-----RIGSGAGGTVYKVIHRPTGRLYALKVIygnHEDTVR-RQICREIEILRDVNHPNVVKCHDMFDHNGEIQ 148
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   313 IITEFMTYGNLLdylrecNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLM--TG 390
Cdd:PLN00034  149 VLLEFMDGGSLE------GTHIADEQFLADVARQILSGIAYLHRRHIVHRDIKPSNLLINSAKNVKIADFGVSRILaqTM 222
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   391 DTYTAHAGAkfpIKWTAPESL-------AYNKFSikSDVWAFGVLLWEiatYGMSPYP-GIDLSQVYELLEKDYRMERPE 462
Cdd:PLN00034  223 DPCNSSVGT---IAYMSPERIntdlnhgAYDGYA--GDIWSLGVSILE---FYLGRFPfGVGRQGDWASLMCAICMSQPP 294
                         250       260       270
                  ....*....|....*....|....*....|...
gi 62362414   463 GCPEKVYELMRA----CWQWNPSDRPSFAEIHQ 491
Cdd:PLN00034  295 EAPATASREFRHfiscCLQREPAKRWSAMQLLQ 327
STKc_MAPK15-like cd07852
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15 and ...
245-494 1.69e-12

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15 and similar MAPKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human MAPK15 is also called Extracellular signal Regulated Kinase 8 (ERK8) while the rat protein is called ERK7. ERK7 and ERK8 display both similar and different biochemical properties. They autophosphorylate and activate themselves and do not require upstream activating kinases. ERK7 is constitutively active and is not affected by extracellular stimuli whereas ERK8 shows low basal activity and is activated by DNA-damaging agents. ERK7 and ERK8 also have different substrate profiles. Genome analysis shows that they are orthologs with similar gene structures. ERK7 and ERK 8 may be involved in the signaling of some nuclear receptor transcription factors. ERK7 regulates hormone-dependent degradation of estrogen receptor alpha while ERK8 down-regulates the transcriptional co-activation androgen and glucocorticoid receptors. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK15 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270841 [Multi-domain]  Cd Length: 337  Bit Score: 69.89  E-value: 1.69e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  245 KHKLGGGQYGEVYEGVWKKYSLTVAVK--------------TLKEDTmeveeFLKEAAvmkeiKHPNLVQLLGVCTRE-- 308
Cdd:cd07852   12 LKKLGKGAYGIVWKAIDKKTGEVVALKkifdafrnatdaqrTFREIM-----FLQELN-----DHPNIIKLLNVIRAEnd 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  309 PPFYIITEFM-------TYGNLLdylrecnrQEVNAVVLLYmatQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVAD 381
Cdd:cd07852   82 KDIYLVFEYMetdlhavIRANIL--------EDIHKQYIMY---QLLKALKYLHSGGVIHRDLKPSNILLNSDCRVKLAD 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  382 FGLSRLMTGDTytahAGAKFPI-------KW-TAPESL-AYNKFSIKSDVWAFGVLLWE--------------------I 432
Cdd:cd07852  151 FGLARSLSQLE----EDDENPVltdyvatRWyRAPEILlGSTRYTKGVDMWSVGCILGEmllgkplfpgtstlnqlekiI 226
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 62362414  433 ATYGM----------SPYPGIDLSQVYELLEKDYRmERPEGCPEKVYELMRACWQWNPSDRPSfAEihQAFE 494
Cdd:cd07852  227 EVIGRpsaediesiqSPFAATMLESLPPSRPKSLD-ELFPKASPDALDLLKKLLVFNPNKRLT-AE--EALR 294
STKc_Twitchin_like cd14114
The catalytic domain of the Giant Serine/Threonine Kinases, Twitchin and Projectin; STKs ...
247-494 1.76e-12

The catalytic domain of the Giant Serine/Threonine Kinases, Twitchin and Projectin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. Twitchin and Projectin are both associated with thick filaments. Twitchin is localized in the outer parts of A-bands and is involved in regulating muscle contraction. It interacts with the myofibrillar proteins myosin and actin in a phosphorylation-dependent manner, and may be involved in regulating the myosin cross-bridge cycle. The kinase activity of Twitchen is activated by Ca2+ and the Ca2+ binding protein S100A1. Projectin is associated with the end of thick filaments and is a component of flight muscle connecting filaments. The kinase domain of Projectin may play roles in autophosphorylation and transphosphorylation, which impact the formation of myosin filaments. The Twitchin-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271016 [Multi-domain]  Cd Length: 259  Bit Score: 68.76  E-value: 1.76e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLKED-TMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLD 325
Cdd:cd14114    9 ELGTGAFGVVHRCTERATGNNFAAKFIMTPhESDKETVRKEIQIMNQLHHPKLINLHDAFEDDNEMVLILEFLSGGELFE 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  326 YLRECNRQEVNAVVLLYMaTQISSAMEYLEKKNFIHRDLAARN--CLVGENHLVKVADFGLsrlmtgdtyTAHAGAKFPI 403
Cdd:cd14114   89 RIAAEHYKMSEAEVINYM-RQVCEGLCHMHENNIVHLDIKPENimCTTKRSNEVKLIDFGL---------ATHLDPKESV 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  404 KWT-------APESLAYNKFSIKSDVWAFGVLLWeIATYGMSPYPGIDLSQVYELLEK---DYRMERPEGCPEKVYELMR 473
Cdd:cd14114  159 KVTtgtaefaAPEIVEREPVGFYTDMWAVGVLSY-VLLSGLSPFAGENDDETLRNVKScdwNFDDSAFSGISEEAKDFIR 237
                        250       260
                 ....*....|....*....|.
gi 62362414  474 ACWQWNPSDRPSfaeIHQAFE 494
Cdd:cd14114  238 KLLLADPNKRMT---IHQALE 255
PKc_MEK cd06615
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
240-504 1.87e-12

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 and MEK2 are MAPK kinases (MAPKKs or MKKs), and are dual-specificity PKs that phosphorylate and activate the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1/2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. This cascade has also been implicated in synaptic plasticity, migration, morphological determination, and stress response immunological reactions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1/2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132946 [Multi-domain]  Cd Length: 308  Bit Score: 69.39  E-value: 1.87e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  240 TDITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKedtMEVE-----EFLKEAAVMKEIKHPNLVQLLGVCTREPPFYII 314
Cdd:cd06615    1 DDFEKLGELGAGNGGVVTKVLHRPSGLIMARKLIH---LEIKpairnQIIRELKVLHECNSPYIVGFYGAFYSDGEISIC 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  315 TEFMTYGNLLDYLRECNRqeVNAVVLLYMATQISSAMEYL-EKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTY 393
Cdd:cd06615   78 MEHMDGGSLDQVLKKAGR--IPENILGKISIAVLRGLTYLrEKHKIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMA 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  394 TAHAGAKfpiKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQ-------------------------- 447
Cdd:cd06615  156 NSFVGTR---SYMSPERLQGTHYTVQSDIWSLGLSLVEMAI-GRYPIPPPDAKEleamfgrpvsegeakeshrpvsghpp 231
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  448 -------VYELLekDYRM-ERPEGCPEKVY-----ELMRACWQWNPSDRPSFAEIHQAfeTMFQESSISD 504
Cdd:cd06615  232 dsprpmaIFELL--DYIVnEPPPKLPSGAFsdefqDFVDKCLKKNPKERADLKELTKH--PFIKRAELEE 297
STKc_WNK1 cd14030
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 1; STKs catalyze ...
247-501 1.92e-12

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK1 is widely expressed and is most abundant in the testis. In hyperosmotic or hypotonic low-chloride stress conditions, WNK1 is activated and it phosphorylates its substrates including SPAK and OSR1 kinases, which regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. Mutations in WNK1 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension and hyperkalemia. WNK1 negates WNK4-mediated inhibition of the sodium-chloride cotransporter NCC and activates the epithelial sodium channel ENaC by activating SGK1. WNK1 also decreases the surface expression of renal outer medullary potassium channel (ROMK) by stimulating their endocytosis. Hypertension and hyperkalemia in PHAII patients with WNK1 mutations may be due partly to increased activity of NCC and ENaC, and impaired renal potassium secretion by ROMK, respectively. In addition, WNK1 interacts with MEKK2/3 and acts as an activator of extracellular signal-regulated kinase (ERK) 5. It also negatively regulates TGFbeta signaling. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. The WNK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270932 [Multi-domain]  Cd Length: 289  Bit Score: 69.31  E-value: 1.92e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM---EVEEFLKEAAVMKEIKHPNLVQLLGvcTREPP------FYIITEF 317
Cdd:cd14030   32 EIGRGSFKTVYKGLDTETTVEVAWCELQDRKLsksERQRFKEEAGMLKGLQHPNIVRFYD--SWESTvkgkkcIVLVTEL 109
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  318 MTYGNLLDYLRECNRQEVNavVLLYMATQISSAMEYLEKKN--FIHRDLAARNCLV-GENHLVKVADFGLSRLMTGDTYT 394
Cdd:cd14030  110 MTSGTLKTYLKRFKVMKIK--VLRSWCRQILKGLQFLHTRTppIIHRDLKCDNIFItGPTGSVKIGDLGLATLKRASFAK 187
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  395 AHAGAKfpiKWTAPEsLAYNKFSIKSDVWAFGVLLWEIATygmSPYPGIDLSQVYELLEKDYRMERPE-----GCPEkVY 469
Cdd:cd14030  188 SVIGTP---EFMAPE-MYEEKYDESVDVYAFGMCMLEMAT---SEYPYSECQNAAQIYRRVTSGVKPAsfdkvAIPE-VK 259
                        250       260       270
                 ....*....|....*....|....*....|...
gi 62362414  470 ELMRACWQWNPSDRPSFAE-IHQAFetmFQESS 501
Cdd:cd14030  260 EIIEGCIRQNKDERYAIKDlLNHAF---FQEET 289
STKc_MEKK2 cd06652
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular ...
248-434 2.00e-12

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK2 is a MAPK kinase kinase (MAPKKK or MKKK), that phosphorylates and activates the MAPK kinase MEK5 (or MKK5), which in turn phosphorylates and activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK2 also activates ERK1/2, c-Jun N-terminal kinase (JNK) and p38 through their respective MAPKKs MEK1/2, JNK-activating kinase 2 (JNKK2), and MKK3/6. MEKK2 plays roles in T cell receptor signaling, immune synapse formation, cytokine gene expression, as well as in EGF and FGF receptor signaling. The MEKK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270818 [Multi-domain]  Cd Length: 264  Bit Score: 68.92  E-value: 2.00e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLK------EDTMEVEEFLKEAAVMKEIKHPNLVQLLGvCTREPP---FYIITEFM 318
Cdd:cd06652   10 LGQGAFGRVYLCYDADTGRELAVKQVQfdpespETSKEVNALECEIQLLKNLLHERIVQYYG-CLRDPQertLSIFMEYM 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  319 TYGNLLDYLRECNRQEVNavVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR-----LMTGDTY 393
Cdd:cd06652   89 PGGSIKDQLKSYGALTEN--VTRKYTRQILEGVHYLHSNMIVHRDIKGANILRDSVGNVKLGDFGASKrlqtiCLSGTGM 166
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 62362414  394 TAHAGAKFpikWTAPESLAYNKFSIKSDVWAFGVLLWEIAT 434
Cdd:cd06652  167 KSVTGTPY---WMSPEVISGEGYGRKADIWSVGCTVVEMLT 204
STKc_Mnk cd14090
Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase ...
248-442 2.28e-12

Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase signal-integrating kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270992 [Multi-domain]  Cd Length: 289  Bit Score: 68.98  E-value: 2.28e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTlkedtMEVEEFLKEAAVMKEIK-------HPNLVQLLGVCTREPPFYIITEFMTY 320
Cdd:cd14090   10 LGEGAYASVQTCINLYTGKEYAVKI-----IEKHPGHSRSRVFREVEtlhqcqgHPNILQLIEYFEDDERFYLVFEKMRG 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  321 GNLLDYLREC---NRQEVNAVVllymaTQISSAMEYLEKKNFIHRDLAARNCLVGENHL---VKVADFGLSRLMtGDTYT 394
Cdd:cd14090   85 GPLLSHIEKRvhfTEQEASLVV-----RDIASALDFLHDKGIAHRDLKPENILCESMDKvspVKICDFDLGSGI-KLSST 158
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 62362414  395 AHAGAKFP--------IKWTAPE--------SLAYNKfsiKSDVWAFGVLLWeIATYGMSPYPG 442
Cdd:cd14090  159 SMTPVTTPelltpvgsAEYMAPEvvdafvgeALSYDK---RCDLWSLGVILY-IMLCGYPPFYG 218
SH2_Src_Yes cd10366
Src homology 2 (SH2) domain found in Yes; Yes is a member of the Src non-receptor type ...
123-209 2.62e-12

Src homology 2 (SH2) domain found in Yes; Yes is a member of the Src non-receptor type tyrosine kinase family of proteins. Yes is the cellular homolog of the Yamaguchi sarcoma virus oncogene. In humans it is encoded by the YES1 gene which maps to chromosome 18 and is in close proximity to thymidylate synthase. A corresponding Yes pseudogene has been found on chromosome 22. YES1 has been shown to interact with Janus kinase 2, CTNND1,RPL10, and Occludin. Yes1 has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198229  Cd Length: 101  Bit Score: 64.27  E-value: 2.62e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  123 EKHSWYHGPVSRNAAEYLLSSGIN--GSFLVRESESSPGQRSISLR-----YEGRVYHYRINTASDGKLYVSSESRFNTL 195
Cdd:cd10366    1 QAEEWYFGKMGRKDAERLLLNPGNqrGIFLVRESETTKGAYSLSIRdwdevRGDNVKHYKIRKLDNGGYYITTRAQFDTL 80
                         90
                 ....*....|....
gi 62362414  196 AELVHHHSTVADGL 209
Cdd:cd10366   81 QKLVKHYTEHADGL 94
SH2_Cterm_RasGAP cd10354
C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP ...
127-202 2.85e-12

C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP is part of the GAP1 family of GTPase-activating proteins. The protein is located in the cytoplasm and stimulates the GTPase activity of normal RAS p21, but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in RAS inactivation, thereby allowing control of cellular proliferation and differentiation. Mutations leading to changes in the binding sites of either protein are associated with basal cell carcinomas. Alternative splicing results in two isoforms. The shorter isoform which lacks the N-terminal hydrophobic region, has the same activity, and is expressed in placental tissues. In general longer isoform contains 2 SH2 domains, a SH3 domain, a pleckstrin homology (PH) domain, and a calcium-dependent phospholipid-binding C2 domain. The C-terminus contains the catalytic domain of RasGap which catalyzes the activation of Ras by hydrolyzing GTP-bound active Ras into an inactive GDP-bound form of Ras. This model contains the C-terminal SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198217  Cd Length: 77  Bit Score: 63.21  E-value: 2.85e-12
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 62362414  127 WYHGPVSRNAAE-YLLSSGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTASDGKLYVSSEsRFNTLAELVHHH 202
Cdd:cd10354    2 WFHGKISREEAYnMLVKVGGPGSFLVRESDNTPGDYSLSFRVNEGIKHFKIIPTGNNQFMMGGR-YFSSLDDVIDRY 77
STKc_SGK1 cd05602
Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced ...
248-450 3.45e-12

Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK1 is ubiquitously expressed and is under transcriptional control of numerous stimuli including cell stress (cell shrinkage), serum, hormones (gluco- and mineralocorticoids), gonadotropins, growth factors, interleukin-6, and other cytokines. It plays roles in sodium retention and potassium elimination in the kidney, nutrient transport, salt sensitivity, memory consolidation, and cardiac repolarization. A common SGK1 variant is associated with increased blood pressure and body weight. SGK1 may also contribute to tumor growth, neurodegeneration, fibrosing disease, and ischemia. The SGK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270753 [Multi-domain]  Cd Length: 339  Bit Score: 69.28  E-value: 3.45e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM----EVEEFLKEAAVM-KEIKHPNLVQLLGVCTREPPFYIITEFMTYGN 322
Cdd:cd05602   15 IGKGSFGKVLLARHKSDEKFYAVKVLQKKAIlkkkEEKHIMSERNVLlKNVKHPFLVGLHFSFQTTDKLYFVLDYINGGE 94
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYL-RECNRQEVNAvvlLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKF 401
Cdd:cd05602   95 LFYHLqRERCFLEPRA---RFYAAEIASALGYLHSLNIVYRDLKPENILLDSQGHIVLTDFGLCKENIEPNGTTSTFCGT 171
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 62362414  402 PiKWTAPESLAYNKFSIKSDVWAFGVLLWEIaTYGMSPYPGIDLSQVYE 450
Cdd:cd05602  172 P-EYLAPEVLHKQPYDRTVDWWCLGAVLYEM-LYGLPPFYSRNTAEMYD 218
PKc_MEK2 cd06649
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
236-448 4.64e-12

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 2; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK2 is a dual-specificity PK and a MAPK kinase (MAPKK or MKK) that phosphorylates and activates the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132980 [Multi-domain]  Cd Length: 331  Bit Score: 68.54  E-value: 4.64e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  236 EMERTDITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEV--EEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYI 313
Cdd:cd06649    1 ELKDDDFERISELGAGNGGVVTKVQHKPSGLIMARKLIHLEIKPAirNQIIRELQVLHECNSPYIVGFYGAFYSDGEISI 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  314 ITEFMTYGNLLDYLRECNRqeVNAVVLLYMATQISSAMEYL-EKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDT 392
Cdd:cd06649   81 CMEHMDGGSLDQVLKEAKR--IPEEILGKVSIAVLRGLAYLrEKHQIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSM 158
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 62362414  393 YTAHAGAKfpiKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQV 448
Cdd:cd06649  159 ANSFVGTR---SYMSPERLQGTHYSVQSDIWSMGLSLVELAI-GRYPIPPPDAKEL 210
PKc_Mps1 cd14131
Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle ...
247-489 5.02e-12

Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle 1 (also called TTK); Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TTK/Mps1 is a spindle checkpoint kinase that was first discovered due to its necessity in centrosome duplication in budding yeast. It was later found to function in the spindle assembly checkpoint, which monitors the proper attachment of chromosomes to the mitotic spindle. In yeast, substrates of Mps1 include the spindle pole body components Spc98p, Spc110p, and Spc42p. The TTK/Mps1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271033 [Multi-domain]  Cd Length: 271  Bit Score: 67.62  E-value: 5.02e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLtVAVK--TLKE-DTMEVEEFLKEAAVMKEIKH-PNLVQLLG--VCTREPPFYIItefMTY 320
Cdd:cd14131    8 QLGKGGSSKVYKVLNPKKKI-YALKrvDLEGaDEQTLQSYKNEIELLKKLKGsDRIIQLYDyeVTDEDDYLYMV---MEC 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  321 GN--LLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLvKVADFGLSRLMTGDTYT---- 394
Cdd:cd14131   84 GEidLATILKKKRPKPIDPNFIRYYWKQMLEAVHTIHEEGIVHSDLKPANFLLVKGRL-KLIDFGIAKAIQNDTTSivrd 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  395 AHAGAkfpIKWTAPESLAYN----------KFSIKSDVWAFGVLLWEIaTYGMSPYPGID--LSQVYELLEKDYRMERPE 462
Cdd:cd14131  163 SQVGT---LNYMSPEAIKDTsasgegkpksKIGRPSDVWSLGCILYQM-VYGKTPFQHITnpIAKLQAIIDPNHEIEFPD 238
                        250       260
                 ....*....|....*....|....*..
gi 62362414  463 GCPEKVYELMRACWQWNPSDRPSFAEI 489
Cdd:cd14131  239 IPNPDLIDVMKRCLQRDPKKRPSIPEL 265
PK_STRAD cd08216
Pseudokinase domain of STE20-related kinase adapter protein; The pseudokinase domain shows ...
262-454 5.24e-12

Pseudokinase domain of STE20-related kinase adapter protein; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. STRAD forms a complex with the scaffolding protein MO25, and the serine/threonine kinase (STK), LKB1, resulting in the activation of the kinase. In the complex, LKB1 phosphorylates and activates adenosine monophosphate-activated protein kinases (AMPKs), which regulate cell energy metabolism and cell polarity. LKB1 is a tumor suppressor linked to the rare inherited disease, Peutz-Jeghers syndrome, which is characterized by a predisposition to benign polyps and hyperpigmentation of the buccal mucosa. There are two forms of STRAD, alpha and beta, that complex with LKB1 and MO25. The structure of STRAD-alpha is available and shows that this protein binds ATP, has an ordered activation loop, and adopts a closed conformation typical of fully active protein kinases. It does not possess activity due to nonconservative substitutions of essential catalytic residues. ATP binding enhances the affinity of STRAD for MO25. The conformation of STRAD-alpha stabilized through ATP and MO25 may be needed to activate LKB1. The STRAD subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270856 [Multi-domain]  Cd Length: 315  Bit Score: 68.09  E-value: 5.24e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  262 KKYSLTVAVKTlkedtmEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDYLRECNRQEVNAVVLL 341
Cdd:cd08216   31 KKINLESDSKE------DLKFLQQEILTSRQLQHPNILPYVTSFVVDNDLYVVTPLMAYGSCRDLLKTHFPEGLPELAIA 104
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  342 YMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTG--------DTYTAHAGAKFPikWTAPESLAY 413
Cdd:cd08216  105 FILRDVLNALEYIHSKGYIHRSVKASHILISGDGKVVLSGLRYAYSMVKhgkrqrvvHDFPKSSEKNLP--WLSPEVLQQ 182
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 62362414  414 N--KFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVyeLLEK 454
Cdd:cd08216  183 NllGYNEKSDIYSVGITACELAN-GVVPFSDMPATQM--LLEK 222
STKc_PIM2 cd14101
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
243-491 5.29e-12

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are three PIM2 isoforms resulting from alternative translation initiation sites. PIM2 is highly expressed in leukemia and lymphomas and has been shown to promote the survival and proliferation of tumor cells. The PIM2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271003 [Multi-domain]  Cd Length: 257  Bit Score: 67.18  E-value: 5.29e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  243 TMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDtmEVEEFLK---------EAAVMKEI----KHPNLVQLLGVCTREP 309
Cdd:cd14101    3 TMGNLLGKGGFGTVYAGHRISDGLQVAIKQISRN--RVQQWSKlpgvnpvpnEVALLQSVgggpGHRGVIRLLDWFEIPE 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  310 PFYIITEFMTYG-NLLDYLREcnRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVG-ENHLVKVADFGLSRL 387
Cdd:cd14101   81 GFLLVLERPQHCqDLFDYITE--RGALDESLARRFFKQVVEAVQHCHSKGVVHRDIKDENILVDlRTGDIKLIDFGSGAT 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  388 MTGDTYTAHAGAKFpikWTAPESLAYNKF-SIKSDVWAFGVLLWEIATyGMSPYpgidlSQVYELLEKdyRMERPEGCPE 466
Cdd:cd14101  159 LKDSMYTDFDGTRV---YSPPEWILYHQYhALPATVWSLGILLYDMVC-GDIPF-----ERDTDILKA--KPSFNKRVSN 227
                        250       260
                 ....*....|....*....|....*
gi 62362414  467 KVYELMRACWQWNPSDRPSFAEIHQ 491
Cdd:cd14101  228 DCRSLIRSCLAYNPSDRPSLEQILL 252
STKc_PAK6 cd06659
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the ...
247-440 5.53e-12

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK6 may play a role in stress responses through its activation by the mitogen-activated protein kinase (MAPK) p38 and MAPK kinase 6 (MKK6) pathway. PAK6 is highly expressed in the brain. It is not required for viability, but together with PAK5, it is required for normal levels of locomotion and activity, and for learning and memory. Increased expression of PAK6 is found in primary and metastatic prostate cancer. PAK6 may play a role in the regulation of motility. PAK6 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270821 [Multi-domain]  Cd Length: 297  Bit Score: 68.09  E-value: 5.53e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFL-KEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLD 325
Cdd:cd06659   28 KIGEGSTGVVCIAREKHSGRQVAVKMMDLRKQQRRELLfNEVVIMRDYQHPNVVEMYKSYLVGEELWVLMEYLQGGALTD 107
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  326 YLRECNRQEVnavvllYMATQISS---AMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFP 402
Cdd:cd06659  108 IVSQTRLNEE------QIATVCEAvlqALAYLHSQGVIHRDIKSDSILLTLDGRVKLSDFGFCAQISKDVPKRKSLVGTP 181
                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 62362414  403 IkWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPY 440
Cdd:cd06659  182 Y-WMAPEVISRCPYGTEVDIWSLGIMVIEMVD-GEPPY 217
STKc_CaMK_like cd14088
Catalytic domain of an Uncharacterized group of Serine/Threonine kinases with similarity to ...
271-461 5.91e-12

Catalytic domain of an Uncharacterized group of Serine/Threonine kinases with similarity to Calcium/calmodulin-dependent protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of uncharacterized STKs with similarity to CaMKs, which are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). CaMKs contain an N-terminal catalytic domain followed by a regulatory domain that harbors a CaM binding site. This uncharacterized subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270990 [Multi-domain]  Cd Length: 265  Bit Score: 67.36  E-value: 5.91e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  271 KTLKEDTMEVEEFLK-EAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDYLRE----CNRQEVNAVvllymaT 345
Cdd:cd14088   33 KFLKRDGRKVRKAAKnEINILKMVKHPNILQLVDVFETRKEYFIFLELATGREVFDWILDqgyySERDTSNVI------R 106
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  346 QISSAMEYLEKKNFIHRDLAARNcLVGENHL----VKVADFGLSRLMTGDTytahagaKFPI---KWTAPESLAYNKFSI 418
Cdd:cd14088  107 QVLEAVAYLHSLKIVHRNLKLEN-LVYYNRLknskIVISDFHLAKLENGLI-------KEPCgtpEYLAPEVVGRQRYGR 178
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 62362414  419 KSDVWAFGVLLWeIATYGMSP---------YPGIDLSQVYELLEKDYRMERP 461
Cdd:cd14088  179 PVDCWAIGVIMY-ILLSGNPPfydeaeeddYENHDKNLFRKILAGDYEFDSP 229
STKc_DRAK cd14106
Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
248-488 6.90e-12

Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs, also called STK17, were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. They may play a role in apoptotic signaling. The DRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271008 [Multi-domain]  Cd Length: 268  Bit Score: 67.38  E-value: 6.90e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLK-----EDTMEveEFLKEAAVMKEIK-HPNLVQLLGVCTREPPFYIITEFMTYG 321
Cdd:cd14106   16 LGRGKFAVVRKCIHKETGKEYAAKFLRkrrrgQDCRN--EILHEIAVLELCKdCPRVVNLHEVYETRSELILILELAAGG 93
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  322 NLLdylRECNRQEV----NAVVLLymaTQISSAMEYLEKKNFIHRDLAARNCLV-GENHL--VKVADFGLSRLM-TGDTY 393
Cdd:cd14106   94 ELQ---TLLDEEEClteaDVRRLM---RQILEGVQYLHERNIVHLDLKPQNILLtSEFPLgdIKLCDFGISRVIgEGEEI 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  394 TAHAGAKfpiKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELLEK---DYRMERPEGCPEKVYE 470
Cdd:cd14106  168 REILGTP---DYVAPEILSYEPISLATDMWSIGVLTYVLLT-GHSPFGGDDKQETFLNISQcnlDFPEELFKDVSPLAID 243
                        250
                 ....*....|....*...
gi 62362414  471 LMRACWQWNPSDRPSFAE 488
Cdd:cd14106  244 FIKRLLVKDPEKRLTAKE 261
STKc_p70S6K cd05584
Catalytic domain of the Serine/Threonine Kinase, 70 kDa ribosomal protein S6 kinase; STKs ...
248-442 6.96e-12

Catalytic domain of the Serine/Threonine Kinase, 70 kDa ribosomal protein S6 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p70S6K (or S6K) contains only one catalytic kinase domain, unlike p90 ribosomal S6 kinases (RSKs). It acts as a downstream effector of the STK mTOR (mammalian Target of Rapamycin) and plays a role in the regulation of the translation machinery during protein synthesis. p70S6K also plays a pivotal role in regulating cell size and glucose homeostasis. Its targets include S6, the translation initiation factor eIF3, and the insulin receptor substrate IRS-1, among others. Mammals contain two isoforms of p70S6K, named S6K1 and S6K2 (or S6K-beta). The p70S6K subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270736 [Multi-domain]  Cd Length: 323  Bit Score: 67.81  E-value: 6.96e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEgVWKKYSL----TVAVKTLKE--------DTMEVEeflKEAAVMKEIKHPNLVQLLGVCTREPPFYIIT 315
Cdd:cd05584    4 LGKGGYGKVFQ-VRKTTGSdkgkIFAMKVLKKasivrnqkDTAHTK---AERNILEAVKHPFIVDLHYAFQTGGKLYLIL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  316 EFMTYGNLLDYL-RECNRQEVNAVvlLYMAtQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYT 394
Cdd:cd05584   80 EYLSGGELFMHLeREGIFMEDTAC--FYLA-EITLALGHLHSLGIIYRDLKPENILLDAQGHVKLTDFGLCKESIHDGTV 156
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 62362414  395 AHA--GAkfpIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPG 442
Cdd:cd05584  157 THTfcGT---IEYMAPEILTRSGHGKAVDWWSLGALMYDMLT-GAPPFTA 202
STKc_PKB cd05571
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B; STKs catalyze the transfer ...
248-432 7.13e-12

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. There are three PKB isoforms from different genes, PKB-alpha (or Akt1), PKB-beta (or Akt2), and PKB-gamma (or Akt3). PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. It is activated downstream of phosphoinositide 3-kinase (PI3K) and plays important roles in diverse cellular functions including cell survival, growth, proliferation, angiogenesis, motility, and migration. PKB also has a central role in a variety of human cancers, having been implicated in tumor initiation, progression, and metastasis. The PKB subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and PI3K.


Pssm-ID: 270723 [Multi-domain]  Cd Length: 322  Bit Score: 67.77  E-value: 7.13e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM----EVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNL 323
Cdd:cd05571    3 LGKGTFGKVILCREKATGELYAIKILKKEVIiakdEVAHTLTENRVLQNTRHPFLTSLKYSFQTNDRLCFVMEYVNGGEL 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  324 LDYLRECnRQEVNAVVLLYMAtQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR--LMTGDTYTAHAGAKf 401
Cdd:cd05571   83 FFHLSRE-RVFSEDRTRFYGA-EIVLALGYLHSQGIVYRDLKLENLLLDKDGHIKITDFGLCKeeISYGATTKTFCGTP- 159
                        170       180       190
                 ....*....|....*....|....*....|.
gi 62362414  402 piKWTAPESLAYNKFSIKSDVWAFGVLLWEI 432
Cdd:cd05571  160 --EYLAPEVLEDNDYGRAVDWWGLGVVMYEM 188
STKc_ERK1_2_like cd07849
Catalytic domain of Extracellular signal-Regulated Kinase 1 and 2-like Serine/Threonine ...
226-457 8.85e-12

Catalytic domain of Extracellular signal-Regulated Kinase 1 and 2-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the mitogen-activated protein kinases (MAPKs) ERK1, ERK2, baker's yeast Fus3, and similar proteins. MAPK pathways are important mediators of cellular responses to extracellular signals. ERK1/2 activation is preferentially by mitogenic factors, differentiation stimuli, and cytokines, through a kinase cascade involving the MAPK kinases MEK1/2 and a MAPK kinase kinase from the Raf family. ERK1/2 have numerous substrates, many of which are nuclear and participate in transcriptional regulation of many cellular processes. They regulate cell growth, cell proliferation, and cell cycle progression from G1 to S phase. Although the distinct roles of ERK1 and ERK2 have not been fully determined, it is known that ERK2 can maintain most functions in the absence of ERK1, and that the deletion of ERK2 is embryonically lethal. The MAPK, Fus3, regulates yeast mating processes including mating-specific gene expression, G1 arrest, mating projection, and cell fusion. This ERK1/2-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270839 [Multi-domain]  Cd Length: 336  Bit Score: 67.71  E-value: 8.85e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  226 YGVSPNYdkwemertdiTMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLK--EDTMEVEEFLKEAAVMKEIKHPNLVQLLG 303
Cdd:cd07849    1 FDVGPRY----------QNLSYIGEGAYGMVCSAVHKPTGQKVAIKKISpfEHQTYCLRTLREIKILLRFKHENIIGILD 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  304 VcTREPPF------YIITEFMTygnlLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLV 377
Cdd:cd07849   71 I-QRPPTFesfkdvYIVQELME----TDLYKLIKTQHLSNDHIQYFLYQILRGLKYIHSANVLHRDLKPSNLLLNTNCDL 145
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  378 KVADFGLSRLMTGDT--------YTAhagakfpIKW-TAPE----SLAYNKfSIksDVWAFGVLLWEIATyGMSPYPGid 444
Cdd:cd07849  146 KICDFGLARIADPEHdhtgflteYVA-------TRWyRAPEimlnSKGYTK-AI--DIWSVGCILAEMLS-NRPLFPG-- 212
                        250
                 ....*....|...
gi 62362414  445 lsqvyelleKDYR 457
Cdd:cd07849  213 ---------KDYL 216
PKc_Wee1_like cd13997
Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the ...
247-489 9.43e-12

Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity kinase Myt1, the protein tyrosine kinase Wee1, and similar proteins. These proteins are cell cycle checkpoint kinases that are involved in the regulation of cyclin-dependent kinase CDK1, the master engine for mitosis. CDK1 is kept inactivated through phosphorylation of N-terminal thr (T14 by Myt1) and tyr (Y15 by Myt1 and Wee1) residues. Mitosis progression is ensured through activation of CDK1 by dephoshorylation and inactivation of Myt1/Wee1. The Wee1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270899 [Multi-domain]  Cd Length: 252  Bit Score: 66.64  E-value: 9.43e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLKED---TMEVEEFLKE---AAVMKEikHPNLVQLLGVCTREPPFYIITEFMTY 320
Cdd:cd13997    7 QIGSGSFSEVFKVRSKVDGCLYAVKKSKKPfrgPKERARALREveaHAALGQ--HPNIVRYYSSWEEGGHLYIQMELCEN 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  321 GNLLDYLRECNRQEV--NAVVLLYMaTQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMT-------GD 391
Cdd:cd13997   85 GSLQDALEELSPISKlsEAEVWDLL-LQVALGLAFIHSKGIVHLDIKPDNIFISNKGTCKIGDFGLATRLEtsgdveeGD 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  392 TytahagakfpiKWTAPESLAYNK-FSIKSDVWAFGVLLWEIATygmspypGIDLSQVYELLEKdYRMERPEGCPEKVY- 469
Cdd:cd13997  164 S-----------RYLAPELLNENYtHLPKADIFSLGVTVYEAAT-------GEPLPRNGQQWQQ-LRQGKLPLPPGLVLs 224
                        250       260
                 ....*....|....*....|....
gi 62362414  470 ----ELMRACWQWNPSDRPSFAEI 489
Cdd:cd13997  225 qeltRLLKVMLDPDPTRRPTADQL 248
SH3 cd00174
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ...
66-115 1.15e-11

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.


Pssm-ID: 212690 [Multi-domain]  Cd Length: 51  Bit Score: 60.55  E-value: 1.15e-11
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 62362414   66 FVALYDFVASGDNTLSITKGEKLRVLGyNHNGEWCEAQTKNGQ-GWVPSNY 115
Cdd:cd00174    2 ARALYDYEAQDDDELSFKKGDIITVLE-KDDDGWWEGELNGGReGLFPANY 51
PTZ00266 PTZ00266
NIMA-related protein kinase; Provisional
232-440 1.23e-11

NIMA-related protein kinase; Provisional


Pssm-ID: 173502 [Multi-domain]  Cd Length: 1021  Bit Score: 69.38  E-value: 1.23e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   232 YDKWEMERTDITMKHKLGGGQYGEVYEGVWKKYS-----LTVAVKTLKEdtMEVEEFLKEAAVMKEIKHPNLVQLLG--V 304
Cdd:PTZ00266    5 YDDGESRLNEYEVIKKIGNGRFGEVFLVKHKRTQeffcwKAISYRGLKE--REKSQLVIEVNVMRELKHKNIVRYIDrfL 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   305 CTREPPFYIITEFMTYGNLLDYLRECNRQ--EVNAVVLLYMATQISSAMEYLEK-------KNFIHRDLAARNCLV--GE 373
Cdd:PTZ00266   83 NKANQKLYILMEFCDAGDLSRNIQKCYKMfgKIEEHAIVDITRQLLHALAYCHNlkdgpngERVLHRDLKPQNIFLstGI 162
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   374 NHL---------------VKVADFGLSRLMtGDTYTAHAGAKFPIKWTaPESLAY--NKFSIKSDVWAFGVLLWEIATyG 436
Cdd:PTZ00266  163 RHIgkitaqannlngrpiAKIGDFGLSKNI-GIESMAHSCVGTPYYWS-PELLLHetKSYDDKSDMWALGCIIYELCS-G 239

                  ....
gi 62362414   437 MSPY 440
Cdd:PTZ00266  240 KTPF 243
STKc_PIM1 cd14100
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
248-489 1.36e-11

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are two PIM1 isoforms resulting from alternative translation initiation sites. PIM1 is the founding member of the PIM subfamily. It is involved in regulating cell growth, differentiation, and apoptosis. It promotes cancer development when overexpressed by inhibiting apoptosis, promoting cell proliferation, and promoting genomic instability. The PIM1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271002 [Multi-domain]  Cd Length: 254  Bit Score: 66.15  E-value: 1.36e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM-EVEEFLKEAAVMKEI--------KHPNLVQLLGVCTREPPFYIITEF- 317
Cdd:cd14100    8 LGSGGFGSVYSGIRVADGAPVAIKHVEKDRVsEWGELPNGTRVPMEIvllkkvgsGFRGVIRLLDWFERPDSFVLVLERp 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  318 MTYGNLLDYLREcnRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLV----GEnhlVKVADFGLSRLMTGDTY 393
Cdd:cd14100   88 EPVQDLFDFITE--RGALPEELARSFFRQVLEAVRHCHNCGVLHRDIKDENILIdlntGE---LKLIDFGSGALLKDTVY 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  394 TAHAGAKFpikWTAPESLAYNKFSIKS-DVWAFGVLLWEIATyGMSPYPG---IDLSQVYellekdYRMERPEGCPEkvy 469
Cdd:cd14100  163 TDFDGTRV---YSPPEWIRFHRYHGRSaAVWSLGILLYDMVC-GDIPFEHdeeIIRGQVF------FRQRVSSECQH--- 229
                        250       260
                 ....*....|....*....|
gi 62362414  470 eLMRACWQWNPSDRPSFAEI 489
Cdd:cd14100  230 -LIKWCLALRPSDRPSFEDI 248
PTZ00036 PTZ00036
glycogen synthase kinase; Provisional
248-432 1.59e-11

glycogen synthase kinase; Provisional


Pssm-ID: 173333 [Multi-domain]  Cd Length: 440  Bit Score: 67.75  E-value: 1.59e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEeflKEAAVMKEIKHPNLVQLLGV----CTREPP----FYIITEFM- 318
Cdd:PTZ00036   74 IGNGSFGVVYEAICIDTSEKVAIKKVLQDPQYKN---RELLIMKNLNHINIIFLKDYyyteCFKKNEknifLNVVMEFIp 150
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   319 -TYGNLLDYLRECNRQEVNAVVLLYmATQISSAMEYLEKKNFIHRDLAARNCLVGEN-HLVKVADFGLSR-LMTGDTYTA 395
Cdd:PTZ00036  151 qTVHKYMKHYARNNHALPLFLVKLY-SYQLCRALAYIHSKFICHRDLKPQNLLIDPNtHTLKLCDFGSAKnLLAGQRSVS 229
                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 62362414   396 HAGAKFpikWTAPE-SLAYNKFSIKSDVWAFGVLLWEI 432
Cdd:PTZ00036  230 YICSRF---YRAPElMLGATNYTTHIDLWSLGCIIAEM 264
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
67-113 1.60e-11

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 394975 [Multi-domain]  Cd Length: 47  Bit Score: 59.91  E-value: 1.60e-11
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 62362414     67 VALYDFVASGDNTLSITKGEKLRVLGYNhNGEWCEAQTKNGQ-GWVPS 113
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLEKS-EDGWWKGRNKGGKeGLIPS 47
PLN00009 PLN00009
cyclin-dependent kinase A; Provisional
247-434 1.63e-11

cyclin-dependent kinase A; Provisional


Pssm-ID: 177649 [Multi-domain]  Cd Length: 294  Bit Score: 66.38  E-value: 1.63e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   247 KLGGGQYGEVYEGVWKKYSLTVAVKTLK---EDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYgNL 323
Cdd:PLN00009    9 KIGEGTYGVVYKARDRVTNETIALKKIRleqEDEGVPSTAIREISLLKEMQHGNIVRLQDVVHSEKRLYLVFEYLDL-DL 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   324 LDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGE-NHLVKVADFGLSRLMtGDTYTAHAGAKFP 402
Cdd:PLN00009   88 KKHMDSSPDFAKNPRLIKTYLYQILRGIAYCHSHRVLHRDLKPQNLLIDRrTNALKLADFGLARAF-GIPVRTFTHEVVT 166
                         170       180       190
                  ....*....|....*....|....*....|...
gi 62362414   403 IKWTAPESLAYNK-FSIKSDVWAFGVLLWEIAT 434
Cdd:PLN00009  167 LWYRAPEILLGSRhYSTPVDIWSVGCIFAEMVN 199
SH2_Tec_Itk cd10396
Src homology 2 (SH2) domain found in Tec protein, IL2-inducible T-cell kinase (Itk); A member ...
120-216 1.69e-11

Src homology 2 (SH2) domain found in Tec protein, IL2-inducible T-cell kinase (Itk); A member of the Tec protein tyrosine kinase Itk is expressed thymus, spleen, lymph node, T lymphocytes, NK and mast cells. It plays a role in T-cell proliferation and differentiation, analogous to Tec family kinases Txk. Itk has been shown to interact with Fyn, Wiskott-Aldrich syndrome protein, KHDRBS1, PLCG1, Lymphocyte cytosolic protein 2, Linker of activated T cells, Karyopherin alpha 2, Grb2, and Peptidylprolyl isomerase A. Most of the Tec family members have a PH domain (Txk and the short (type 1) splice variant of Drosophila Btk29A are exceptions), a Tec homology (TH) domain, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP. It is crucial for the function of Tec PH domains and it's lack of presence in Txk is not surprising since it lacks a PH domain. The type 1 splice form of the Drosophila homolog also lacks both the PH domain and the Btk motif. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198259  Cd Length: 108  Bit Score: 62.12  E-value: 1.69e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  120 NSLEKHSWYHGPVSRNAAEYLL-SSGINGSFLVRESeSSPGQRSISL--RYEG------RVYHYRINTASDGKLYVSSES 190
Cdd:cd10396    1 NNLDQYEWYNKNINRSKAEKLLrDEGKEGGFMVRDS-SQPGLYTVSLytKAGGegnpciRHYHIKETNDSPKKYYLAEKH 79
                         90       100
                 ....*....|....*....|....*.
gi 62362414  191 RFNTLAELVHHHSTVADGLITTLHYP 216
Cdd:cd10396   80 VFNSIPELIEYHKHNAAGLVTRLRYP 105
STKc_PAK5 cd06658
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the ...
247-440 1.77e-11

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK5 is mainly expressed in the brain. It is not required for viability, but together with PAK6, it is required for normal levels of locomotion and activity, and for learning and memory. PAK5 cooperates with Inca (induced in neural crest by AP2) in the regulation of cell adhesion and cytoskeletal organization in the embryo and in neural crest cells during craniofacial development. PAK5 may also play a role in controlling the signaling of Raf-1, an effector of Ras, at the mitochondria. PAK5 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132989 [Multi-domain]  Cd Length: 292  Bit Score: 66.22  E-value: 1.77e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFL-KEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLD 325
Cdd:cd06658   29 KIGEGSTGIVCIATEKHTGKQVAVKKMDLRKQQRRELLfNEVVIMRDYHHENVVDMYNSYLVGDELWVVMEFLEGGALTD 108
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  326 YLREC--NRQEVNAVVLlymatQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPI 403
Cdd:cd06658  109 IVTHTrmNEEQIATVCL-----SVLRALSYLHNQGVIHRDIKSDSILLTSDGRIKLSDFGFCAQVSKEVPKRKSLVGTPY 183
                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 62362414  404 kWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPY 440
Cdd:cd06658  184 -WMAPEVISRLPYGTEVDIWSLGIMVIEMID-GEPPY 218
STKc_MSK_N cd05583
N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
247-440 1.89e-11

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2. The MSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270735 [Multi-domain]  Cd Length: 268  Bit Score: 65.88  E-value: 1.89e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYE-GVWKKYSLTVAVKTLkEDTMeveeflKEAAVMKEIKH-PNLVQLLGVCTREPPFYIITEFMTYGNLL 324
Cdd:cd05583   15 KVGGHDAGKLYAmKVLKKATIVQKAKTA-EHTM------TERQVLEAVRQsPFLVTLHYAFQTDAKLHLILDYVNGGELF 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  325 DYLreCNRQEVN-AVVLLYMAtQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLM-TGDTYTAHA--GAk 400
Cdd:cd05583   88 THL--YQREHFTeSEVRIYIG-EIVLALEHLHKLGIIYRDIKLENILLDSEGHVVLTDFGLSKEFlPGENDRAYSfcGT- 163
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 62362414  401 fpIKWTAPE-----SLAYNKfsiKSDVWAFGVLLWEIATyGMSPY 440
Cdd:cd05583  164 --IEYMAPEvvrggSDGHDK---AVDWWSLGVLTYELLT-GASPF 202
PHA03212 PHA03212
serine/threonine kinase US3; Provisional
286-434 2.30e-11

serine/threonine kinase US3; Provisional


Pssm-ID: 165478 [Multi-domain]  Cd Length: 391  Bit Score: 66.94  E-value: 2.30e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   286 EAAVMKEIKHPNLVQLLGVCTREP-PFYIITEFMTygNLLDYLreCNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDL 364
Cdd:PHA03212  133 EAHILRAINHPSIIQLKGTFTYNKfTCLILPRYKT--DLYCYL--AAKRNIAICDILAIERSVLRAIQYLHENRIIHRDI 208
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 62362414   365 AARNCLVGENHLVKVADFGLSRL---MTGDTYTAHAGAkfpIKWTAPESLAYNKFSIKSDVWAFGVLLWEIAT 434
Cdd:PHA03212  209 KAENIFINHPGDVCLGDFGAACFpvdINANKYYGWAGT---IATNAPELLARDPYGPAVDIWSAGIVLFEMAT 278
STKc_MAPK4_6 cd07854
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also ...
248-453 2.34e-11

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also called ERK4) and 6 (also called ERK3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK4 (also called ERK4 or p63MAPK) and MAPK6 (also called ERK3 or p97MAPK) are atypical MAPKs that are not regulated by MAPK kinases. MAPK6 is expressed ubiquitously with highest amounts in brain and skeletal muscle. It may be involved in the control of cell differentiation by negatively regulating cell cycle progression in certain conditions. It may also play a role in glucose-induced insulin secretion. MAPK6 and MAPK4 cooperate to regulate the activity of MAPK-activated protein kinase 5 (MK5), leading to its relocation to the cytoplasm and exclusion from the nucleus. The MAPK6/MK5 and MAPK4/MK5 pathways may play critical roles in embryonic and post-natal development. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK4/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143359 [Multi-domain]  Cd Length: 342  Bit Score: 66.73  E-value: 2.34e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLK-EDTMEVEEFLKEAAVMKEIKHPNLVQL--------------LGVCTREPPFY 312
Cdd:cd07854   13 LGCGSNGLVFSAVDSDCDKRVAVKKIVlTDPQSVKHALREIKIIRRLDHDNIVKVyevlgpsgsdltedVGSLTELNSVY 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  313 IITEFMTyGNLLDYLRECNRQEVNAVVLLYmatQISSAMEYLEKKNFIHRDLAARNCLVGENHLV-KVADFGLSRLMtgD 391
Cdd:cd07854   93 IVQEYME-TDLANVLEQGPLSEEHARLFMY---QLLRGLKYIHSANVLHRDLKPANVFINTEDLVlKIGDFGLARIV--D 166
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 62362414  392 TYTAHAG---AKFPIKW-TAPE-SLAYNKFSIKSDVWAFGVLLWEIATyGMSPYPGI-DLSQVYELLE 453
Cdd:cd07854  167 PHYSHKGylsEGLVTKWyRSPRlLLSPNNYTKAIDMWAAGCIFAEMLT-GKPLFAGAhELEQMQLILE 233
PTZ00267 PTZ00267
NIMA-related protein kinase; Provisional
333-525 2.37e-11

NIMA-related protein kinase; Provisional


Pssm-ID: 140293 [Multi-domain]  Cd Length: 478  Bit Score: 67.35  E-value: 2.37e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   333 QEVNAVVLLYmatQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTgDTYTAHAGAKF---PIkWTAPE 409
Cdd:PTZ00267  167 QEYEVGLLFY---QIVLALDEVHSRKMMHRDLKSANIFLMPTGIIKLGDFGFSKQYS-DSVSLDVASSFcgtPY-YLAPE 241
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   410 SLAYNKFSIKSDVWAFGVLLWEIATYgMSPYPGIdlSQVYELLEKDYRMERPEGCP--EKVYELMRACWQWNPSDRPSFA 487
Cdd:PTZ00267  242 LWERKRYSKKADMWSLGVILYELLTL-HRPFKGP--SQREIMQQVLYGKYDPFPCPvsSGMKALLDPLLSKNPALRPTTQ 318
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 62362414   488 E-IHQAF----ETMFQE-----SSIS----DEVEKELGKQGVRGAVSTLLQA 525
Cdd:PTZ00267  319 QlLHTEFlkyvANLFQDivrhsETISphdrEEILRQLQESGERAPPPSSIRY 370
PTZ00283 PTZ00283
serine/threonine protein kinase; Provisional
340-485 2.42e-11

serine/threonine protein kinase; Provisional


Pssm-ID: 240344 [Multi-domain]  Cd Length: 496  Bit Score: 67.59  E-value: 2.42e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   340 LLYMatQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRlMTGDTYTAHAGAKF---PIkWTAPESLAYNKF 416
Cdd:PTZ00283  147 LLFI--QVLLAVHHVHSKHMIHRDIKSANILLCSNGLVKLGDFGFSK-MYAATVSDDVGRTFcgtPY-YVAPEIWRRKPY 222
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414   417 SIKSDVWAFGVLLWEIATYgMSPYPGIDLSQV-YELLEKDYRMERPEGCPEkVYELMRACWQWNPSDRPS 485
Cdd:PTZ00283  223 SKKADMFSLGVLLYELLTL-KRPFDGENMEEVmHKTLAGRYDPLPPSISPE-MQEIVTALLSSDPKRRPS 290
STKc_PSKH1 cd14087
Catalytic domain of the Protein Serine/Threonine kinase H1; STKs catalyze the transfer of the ...
269-452 2.44e-11

Catalytic domain of the Protein Serine/Threonine kinase H1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PSKH1 is an autophosphorylating STK that is expressed ubiquitously and exhibits multiple intracellular localizations including the centrosome, Golgi apparatus, and splice factor compartments. It contains a catalytic kinase domain and an N-terminal SH4-like motif that is acylated to facilitate membrane attachment. PSKH1 plays a rile in the maintenance of the Golgi apparatus, an important organelle within the secretory pathway. It may also function as a novel splice factor and a regulator of prostate cancer cell growth. The PSKH1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270989 [Multi-domain]  Cd Length: 259  Bit Score: 65.25  E-value: 2.44e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  269 AVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLD-YLRECNRQEVNAVVLLYMatqI 347
Cdd:cd14087   30 AIKMIETKCRGREVCESELNVLRRVRHTNIIQLIEVFETKERVYMVMELATGGELFDrIIAKGSFTERDATRVLQM---V 106
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  348 SSAMEYLEKKNFIHRDLAARNCLV---GENHLVKVADFGL-SRLMTGDTYTAHAGAKFPiKWTAPESLAYNKFSIKSDVW 423
Cdd:cd14087  107 LDGVKYLHGLGITHRDLKPENLLYyhpGPDSKIMITDFGLaSTRKKGPNCLMKTTCGTP-EYIAPEILLRKPYTQSVDMW 185
                        170       180
                 ....*....|....*....|....*....
gi 62362414  424 AFGVLLWeIATYGMSPYPGIDLSQVYELL 452
Cdd:cd14087  186 AVGVIAY-ILLSGTMPFDDDNRTRLYRQI 213
STKc_IKK_alpha cd14039
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
248-440 2.50e-11

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKalpha is involved in the non-canonical or alternative pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The non-canonical pathway functions in cells lacking NEMO (NF-kB Essential MOdulator) and IKKbeta. It is induced by a subset of TNFR family members including CD40, RANK, and B cell-activating factor receptor. IKKalpha processes the Inhibitor of NF-kB (IkB)-like C-terminus of NF-kB2/p100 to produce p52, allowing the p52/RelB dimer to migrate to the nucleus. This pathway is dependent on NIK (NF-kB Inducing Kinase) which phosphorylates and activates IKKalpha. The IKKalpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270941 [Multi-domain]  Cd Length: 289  Bit Score: 65.71  E-value: 2.50e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKT--LKEDTMEVEEFLKEAAVMKEIKHPNLVQL------LGVCTREPPFyIITEFMT 319
Cdd:cd14039    1 LGTGGFGNVCLYQNQETGEKIAIKScrLELSVKNKDRWCHEIQIMKKLNHPNVVKAcdvpeeMNFLVNDVPL-LAMEYCS 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  320 YGNLLDYLRE----CNRQEVNAVVLLymaTQISSAMEYLEKKNFIHRDLAARNCL---VGENHLVKVADFGLSR-LMTGD 391
Cdd:cd14039   80 GGDLRKLLNKpencCGLKESQVLSLL---SDIGSGIQYLHENKIIHRDLKPENIVlqeINGKIVHKIIDLGYAKdLDQGS 156
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 62362414  392 TYTAHAGAkfpIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPY 440
Cdd:cd14039  157 LCTSFVGT---LQYLAPELFENKSYTVTVDYWSFGTMVFECIA-GFRPF 201
STKc_MSK1_N cd05613
N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
248-440 2.57e-11

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK1 plays a role in the regulation of translational control and transcriptional activation. It phosphorylates the transcription factors, CREB and NFkB. It also phosphorylates the nucleosomal proteins H3 and HMG-14. Increased phosphorylation of MSK1 is associated with the development of cerebral ischemic/hypoxic preconditioning. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270764 [Multi-domain]  Cd Length: 290  Bit Score: 65.79  E-value: 2.57e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVY-------EGVWKKYSLTVAVK-TLKEDTMEVEEFLKEAAVMKEIKH-PNLVQLLGVCTREPPFYIITEFM 318
Cdd:cd05613    8 LGTGAYGKVFlvrkvsgHDAGKLYAMKVLKKaTIVQKAKTAEHTRTERQVLEHIRQsPFLVTLHYAFQTDTKLHLILDYI 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  319 TYGNLLDYLRECNRQEVNAVvLLYMAtQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAG 398
Cdd:cd05613   88 NGGELFTHLSQRERFTENEV-QIYIG-EIVLALEHLHKLGIIYRDIKLENILLDSSGHVVLTDFGLSKEFLLDENERAYS 165
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 62362414  399 AKFPIKWTAPESL-----AYNKfsiKSDVWAFGVLLWEIATyGMSPY 440
Cdd:cd05613  166 FCGTIEYMAPEIVrggdsGHDK---AVDWWSLGVLMYELLT-GASPF 208
STKc_JNK3 cd07874
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 3; STKs catalyze the ...
248-523 2.74e-11

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK3 is expressed primarily in the brain, and to a lesser extent in the heart and testis. Mice deficient in JNK3 are protected against kainic acid-induced seizures, stroke, sciatic axotomy neural death, and neuronal death due to NGF deprivation, oxidative stress, or exposure to beta-amyloid peptide. This suggests that JNK3 may play roles in the pathogenesis of these diseases. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143379 [Multi-domain]  Cd Length: 355  Bit Score: 66.65  E-value: 2.74e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEV---YEGVWKKyslTVAVKTLK---EDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPF------YIIT 315
Cdd:cd07874   25 IGSGAQGIVcaaYDAVLDR---NVAIKKLSrpfQNQTHAKRAYRELVLMKCVNHKNIISLLNVFTPQKSLeefqdvYLVM 101
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  316 EFMTyGNLLDYLRecnrQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLM-TGDTYT 394
Cdd:cd07874  102 ELMD-ANLCQVIQ----MELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTAgTSFMMT 176
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  395 AHAGAKFpikWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSpYPGID-LSQVYELLEKdyrMERPegCPEKVYELMR 473
Cdd:cd07874  177 PYVVTRY---YRAPEVILGMGYKENVDIWSVGCIMGEMVRHKIL-FPGRDyIDQWNKVIEQ---LGTP--CPEFMKKLQP 247
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|.
gi 62362414  474 ACWQWnPSDRPSFAEIhqAFETMFQESSI-SDEVEKELGKQGVRGAVSTLL 523
Cdd:cd07874  248 TVRNY-VENRPKYAGL--TFPKLFPDSLFpADSEHNKLKASQARDLLSKML 295
STKc_MSK_C cd14092
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
295-430 2.75e-11

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2. The MSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270994 [Multi-domain]  Cd Length: 311  Bit Score: 66.17  E-value: 2.75e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  295 HPNLVQLLGVCTREPPFYIITEFMTYGNLLDYLRECNR-QEVNAVVLLymaTQISSAMEYLEKKNFIHRDLAARNCLV-- 371
Cdd:cd14092   58 HPNIVKLHEVFQDELHTYLVMELLRGGELLERIRKKKRfTESEASRIM---RQLVSAVSFMHSKGVVHRDLKPENLLFtd 134
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 62362414  372 -GENHLVKVADFGLSRL------MTGDTYTAHagakfpikWTAPESLA-------YNKfsiKSDVWAFGVLLW 430
Cdd:cd14092  135 eDDDAEIKIVDFGFARLkpenqpLKTPCFTLP--------YAAPEVLKqalstqgYDE---SCDLWSLGVILY 196
STKc_SGK cd05575
Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase; ...
248-458 2.80e-11

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGKs are activated by insulin and growth factors via phosphoinositide 3-kinase and PDK1. They activate ion channels, ion carriers, and the Na-K-ATPase, as well as regulate the activity of enzymes and transcription factors. SGKs play important roles in transport, hormone release, neuroexcitability, cell proliferation, and apoptosis. There are three isoforms of SGK, named SGK1, SGK2, and SGK3 (also called cytokine-independent survival kinase CISK). The SGK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270727 [Multi-domain]  Cd Length: 323  Bit Score: 66.19  E-value: 2.80e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTL-KEDTM---EVEEFLKEAAV-MKEIKHPNLVQL-LGVCTREPpFYIITEFMTYG 321
Cdd:cd05575    3 IGKGSFGKVLLARHKAEGKLYAVKVLqKKAILkrnEVKHIMAERNVlLKNVKHPFLVGLhYSFQTKDK-LYFVLDYVNGG 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  322 NLLDYL-RECNRQEVNAvvlLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR--LMTGDTYTAHAG 398
Cdd:cd05575   82 ELFFHLqRERHFPEPRA---RFYAAEIASALGYLHSLNIIYRDLKPENILLDSQGHVVLTDFGLCKegIEPSDTTSTFCG 158
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 62362414  399 AkfPiKWTAPESLAYNKFSIKSDVWAFGVLLWEIaTYGMSPYPGIDLSQVYE-LLEKDYRM 458
Cdd:cd05575  159 T--P-EYLAPEVLRKQPYDRTVDWWCLGAVLYEM-LYGLPPFYSRDTAEMYDnILHKPLRL 215
STKc_nPKC_epsilon cd05591
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C epsilon; STKs catalyze ...
248-440 2.98e-11

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C epsilon; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-epsilon has been shown to behave as an oncoprotein. Its overexpression contributes to neoplastic transformation depending on the cell type. It contributes to oncogenesis by inducing disordered cell growth and inhibiting cell death. It also plays a role in tumor invasion and metastasis. PKC-epsilon has also been found to confer cardioprotection against ischemia and reperfusion-mediated damage. Other cellular functions include the regulation of gene expression, cell adhesion, and cell motility. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-epsilon subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270743 [Multi-domain]  Cd Length: 321  Bit Score: 65.98  E-value: 2.98e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEDTM----EVEEFLKEAAVMK-EIKHPNLVQLLGVCTREPPFYIITEFMTYGN 322
Cdd:cd05591    3 LGKGSFGKVMLAERKGTDEVYAIKVLKKDVIlqddDVDCTMTEKRILAlAAKHPFLTALHSCFQTKDRLFFVMEYVNGGD 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDYLRECNR-QEVNAvvlLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR--LMTGDTYTAHAGA 399
Cdd:cd05591   83 LMFQIQRARKfDEPRA---RFYAAEVTLALMFLHRHGVIYRDLKLDNILLDAEGHCKLADFGMCKegILNGKTTTTFCGT 159
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 62362414  400 KfpiKWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPY 440
Cdd:cd05591  160 P---DYIAPEILQELEYGPSVDWWALGVLMYEMMA-GQPPF 196
STKc_WNK2_like cd14032
Catalytic domain of With No Lysine (WNK) 2-like Serine/Threonine kinases; STKs catalyze the ...
247-441 3.12e-11

Catalytic domain of With No Lysine (WNK) 2-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK2 is widely expressed and has been shown to be epigenetically silenced in gliomas. It inhibits cell growth by acting as a negative regulator of MEK1-ERK1/2 signaling. WNK2 modulates growth factor-induced cancer cell proliferation, suggesting that it may be a tumor suppressor gene. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. They are critical in regulating ion balance and are thus, important components in the control of blood pressure. The WNK2-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270934 [Multi-domain]  Cd Length: 266  Bit Score: 65.10  E-value: 3.12e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVA---VKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPP----FYIITEFMT 319
Cdd:cd14032    8 ELGRGSFKTVYKGLDTETWVEVAwceLQDRKLTKVERQRFKEEAEMLKGLQHPNIVRFYDFWESCAKgkrcIVLVTELMT 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  320 YGNLLDYLRECnrQEVNAVVLLYMATQISSAMEYLEKKN--FIHRDLAARNCLV-GENHLVKVADFGLSRLMTGDTYTAH 396
Cdd:cd14032   88 SGTLKTYLKRF--KVMKPKVLRSWCRQILKGLLFLHTRTppIIHRDLKCDNIFItGPTGSVKIGDLGLATLKRASFAKSV 165
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 62362414  397 AGAKfpiKWTAPEsLAYNKFSIKSDVWAFGVLLWEIATygmSPYP 441
Cdd:cd14032  166 IGTP---EFMAPE-MYEEHYDESVDVYAFGMCMLEMAT---SEYP 203
SH2_Vav3 cd10407
Src homology 2 (SH2) domain found in the Vav3 proteins; Proto-oncogene vav is a member of the ...
127-216 3.18e-11

Src homology 2 (SH2) domain found in the Vav3 proteins; Proto-oncogene vav is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. All vavs are activated by tyrosine phosphorylation leading to their activation. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, and Vav2 and Vav3 are more ubiquitously expressed. Vav3 preferentially activates RhoA, RhoG and, to a lesser extent, Rac1. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. VAV3 has been shown to interact with Grb2. Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198270  Cd Length: 103  Bit Score: 61.17  E-value: 3.18e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  127 WYHGPVSRNAAEYLLSSGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTaSDGKLYVSSESRFNTLAELVHH--HST 204
Cdd:cd10407    7 WYAGAMERLQAETELINRVNSTYLVRHRTKESGEYAISIKYNNEVKHIKILT-RDGFFHIAENRKFKSLMELVEYykHHS 85
                         90
                 ....*....|....*
gi 62362414  205 VADG---LITTLHYP 216
Cdd:cd10407   86 LKEGfrsLDTTLQFP 100
SH3_p47phox_like cd11856
Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This ...
66-118 3.53e-11

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212790 [Multi-domain]  Cd Length: 53  Bit Score: 59.19  E-value: 3.53e-11
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 62362414   66 FVALYDFVASGDNTLSITKGEKLRVLGYNHNGEWCeAQTKNGQGWVPSNYITP 118
Cdd:cd11856    2 YVAIADYEAQGDDEISLQEGEVVEVLEKNDSGWWY-VRKGDKEGWVPASYLEP 53
SH2_CRK_like cd09926
Src homology 2 domain found in cancer-related signaling adaptor protein CRK; SH2 domain in the ...
120-220 3.83e-11

Src homology 2 domain found in cancer-related signaling adaptor protein CRK; SH2 domain in the CRK proteins. CRKI (SH2-SH3) and CRKII (SH2-SH3-SH3) are splicing isoforms of the oncoprotein CRK. CRKs regulate transcription and cytoskeletal reorganization for cell growth and motility by linking tyrosine kinases to small G proteins. The SH2 domain of CRK associates with tyrosine-phosphorylated receptors or components of focal adhesions, such as p130Cas and paxillin. CRK transmits signals to small G proteins through effectors that bind its SH3 domain, such as C3G, the guanine-nucleotide exchange factor (GEF) for Rap1 and R-Ras, and DOCK180, the GEF for Rac6. The binding of p130Cas to the CRK-C3G complex activates Rap1, leading to regulation of cell adhesion, and activates R-Ras, leading to JNK-mediated activation of cell proliferation, whereas the binding of CRK DOCK180 induces Rac1-mediated activation of cellular migration. The activity of the different splicing isoforms varies greatly with CRKI displaying substantial transforming activity, CRKII less so, and phosphorylated CRKII with no biological activity whatsoever. CRKII has a linker region with a phosphorylated Tyr and an additional C-terminal SH3 domain. The phosphorylated Tyr creates a binding site for its SH2 domain which disrupts the association between CRK and its SH2 target proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198180 [Multi-domain]  Cd Length: 106  Bit Score: 60.95  E-value: 3.83e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  120 NSLEKHSWYHGPVSRNAAEYLLSSGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTASDGKLYVSS----ESRFNTL 195
Cdd:cd09926    2 DSSDRSSWYFGPMSRQEAQELLQGQRHGVFLVRDSSTIPGDYVLSVSENSRVSHYIINSLGQPAPNQSRyrigDQEFDDL 81
                         90       100       110
                 ....*....|....*....|....*....|
gi 62362414  196 AEL-----VHHHSTvadgliTTLHYPAPKR 220
Cdd:cd09926   82 PALlefykLHYLDT------TTLIEPASRG 105
SH2_Vav1 cd10405
Src homology 2 (SH2) domain found in the Vav1 proteins; Proto-oncogene vav is a member of the ...
122-216 3.95e-11

Src homology 2 (SH2) domain found in the Vav1 proteins; Proto-oncogene vav is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. All vavs are activated by tyrosine phosphorylation leading to their activation. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, and Vav2 and Vav3 are more ubiquitously expressed. Vav1 plays a role in T-cell and B-cell development and activation. It has been identified as the specific binding partner of Nef proteins from HIV-1, resulting in morphological changes, cytoskeletal rearrangements, and the JNK/SAPK signaling cascade, leading to increased levels of viral transcription and replication. Vav1 has been shown to interact with Ku70, PLCG1, Lymphocyte cytosolic protein 2, Janus kinase 2, SIAH2, S100B, Abl gene, ARHGDIB, SHB, PIK3R1, PRKCQ, Grb2, MAPK1, Syk, Linker of activated T cells, Cbl gene and EZH2. Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198268  Cd Length: 103  Bit Score: 60.80  E-value: 3.95e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  122 LEKHSWYHGPVSRNAAEYLLSSGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTAsdGKLYVSSESR-FNTLAELV- 199
Cdd:cd10405    2 LSVHLWYAGPMERAGAESILANRSDGTYLVRQRVKDAAEFAISIKYNVEVKHIKIMTA--EGLYRITEKKaFRGLTELVe 79
                         90       100
                 ....*....|....*....|.
gi 62362414  200 -HHHSTVAD---GLITTLHYP 216
Cdd:cd10405   80 fYQQNSLKDcfkSLDTTLQFP 100
SH2_N-SH2_SHP_like cd10340
N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
127-216 4.26e-11

N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The SH2 domain phosphatases (SHP-1, SHP-2/Syp, Drosophila corkscrew (csw), and Caenorhabditis elegans Protein Tyrosine Phosphatase (Ptp-2)) are cytoplasmic signaling enzymes. They are both targeted and regulated by interactions of their SH2 domains with phosphotyrosine docking sites. These proteins contain two SH2 domains (N-SH2, C-SH2) followed by a tyrosine phosphatase (PTP) domain, and a C-terminal extension. Shp1 and Shp2 have two tyrosyl phosphorylation sites in their C-tails, which are phosphorylated differentially by receptor and nonreceptor PTKs. Csw retains the proximal tyrosine and Ptp-2 lacks both sites. Shp-binding proteins include receptors, scaffolding adapters, and inhibitory receptors. Some of these bind both Shp1 and Shp2 while others bind only one. Most proteins that bind a Shp SH2 domain contain one or more immuno-receptor tyrosine-based inhibitory motifs (ITIMs): [IVL]xpYxx[IVL]. Shp1 N-SH2 domain blocks the catalytic domain and keeps the enzyme in the inactive conformation, and is thus believed to regulate the phosphatase activity of SHP-1. Its C-SH2 domain is thought to be involved in searching for phosphotyrosine activators. The SHP2 N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. The C-SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation. Csw SH2 domain function is essential, but either SH2 domain can fulfill this requirement. The role of the csw SH2 domains during Sevenless receptor tyrosine kinase (SEV) signaling is to bind Daughter of Sevenless rather than activated SEV. Ptp-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote major sperm protein (MSP)-induced MAP Kinase (MPK-1) phosphorylation. Ptp-2 functions in the oocyte cytoplasm, not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation. It is thought that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation and that secreted MSP domains and Cu/Zn superoxide dismutases function antagonistically to control ROS and MAPK signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198203  Cd Length: 99  Bit Score: 60.49  E-value: 4.26e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  127 WYHGPVSRNAAEYLLSS-GINGSFLVRESESSPGQRSISLRYEGRVYHYRI-NTASDGKLYvsSESRFNTLAELV----H 200
Cdd:cd10340    2 WFHPVISGIEAENLLKTrGVDGSFLARPSKSNPGDFTLSVRRGDEVTHIKIqNTGDYYDLY--GGEKFATLSELVqyymE 79
                         90
                 ....*....|....*...
gi 62362414  201 HHSTV--ADGLITTLHYP 216
Cdd:cd10340   80 QHGQLreKNGDVIELKYP 97
SH2_SHF cd10392
Src homology 2 domain found in SH2 domain-containing adapter protein F (SHF); SHF is thought ...
127-204 4.63e-11

Src homology 2 domain found in SH2 domain-containing adapter protein F (SHF); SHF is thought to play a role in PDGF-receptor signaling and regulation of apoptosis. SHF is mainly expressed in skeletal muscle, brain, liver, prostate, testis, ovary, small intestine, and colon. SHF contains four putative tyrosine phosphorylation sites and an SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198255  Cd Length: 98  Bit Score: 60.47  E-value: 4.63e-11
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 62362414  127 WYHGPVSRNAAEYLLSSGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTASDGKLYVSSES-RFNTLAELVHHHST 204
Cdd:cd10392    3 WYHGAISRTDAENLLRLCKEASYLVRNSETSKNDFSLSLKSSQGFMHMKLSRTKEHKYVLGQNSpPFSSVPEIIHHYAS 81
STKc_TTBK cd14017
Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase; STKs catalyze the ...
247-386 4.73e-11

Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TTBK is a neuron-specific kinase that phosphorylates the microtubule-associated protein tau and promotes its aggregation. Higher vertebrates contain two TTBK proteins, TTBK1 and TTBK2, both of which have been implicated in neurodegeneration. TTBK1 has been linked to Alzheimer's disease (AD) while TTBK2 is associated with spinocerebellar ataxia type 11 (SCA11). Both AD and SCA11 patients show the presence of neurofibrillary tangles in the brain. The Drosophila TTBK homolog, Asator, is an essential protein that localizes to the mitotic spindle during mitosis and may be involved in regulating microtubule dynamics and function. The TTBK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270919 [Multi-domain]  Cd Length: 263  Bit Score: 64.59  E-value: 4.73e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEG---VWKKYsltVAVKTlkEDTMEVEEFLK-EAAVMKEI---KH-PNLVQllgvCTREPPF-YIItef 317
Cdd:cd14017    7 KIGGGGFGEIYKVrdvVDGEE---VAMKV--ESKSQPKQVLKmEVAVLKKLqgkPHfCRLIG----CGRTERYnYIV--- 74
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 62362414  318 MT-YG-NLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGEN----HLVKVADFGLSR 386
Cdd:cd14017   75 MTlLGpNLAELRRSQPRGKFSVSTTLRLGIQILKAIEDIHEVGFLHRDVKPSNFAIGRGpsdeRTVYILDFGLAR 149
STKc_PAK4 cd06657
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the ...
247-440 4.81e-11

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK4 regulates cell morphology and cytoskeletal organization. It is essential for embryonic viability and proper neural development. Mice lacking PAK4 die due to defects in the fetal heart. In addition, their spinal cord motor neurons showed failure to differentiate and migrate. PAK4 also plays a role in cell survival and tumorigenesis. It is overexpressed in many primary tumors including colon, esophageal, and mammary tumors. PAK4 has also been implicated in viral and bacterial infection pathways. PAK4 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132988 [Multi-domain]  Cd Length: 292  Bit Score: 65.04  E-value: 4.81e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  247 KLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFL-KEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLD 325
Cdd:cd06657   27 KIGEGSTGIVCIATVKSSGKLVAVKKMDLRKQQRRELLfNEVVIMRDYQHENVVEMYNSYLVGDELWVVMEFLEGGALTD 106
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  326 YLREC--NRQEVNAVVLlymatQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPI 403
Cdd:cd06657  107 IVTHTrmNEEQIAAVCL-----AVLKALSVLHAQGVIHRDIKSDSILLTHDGRVKLSDFGFCAQVSKEVPRRKSLVGTPY 181
                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 62362414  404 kWTAPESLAYNKFSIKSDVWAFGVLLWEIATyGMSPY 440
Cdd:cd06657  182 -WMAPELISRLPYGPEVDIWSLGIMVIEMVD-GEPPY 216
STKc_TDY_MAPK cd07859
Catalytic domain of the Serine/Threonine Kinases, Plant TDY Mitogen-Activated Protein Kinases; ...
248-452 5.56e-11

Catalytic domain of the Serine/Threonine Kinases, Plant TDY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TDY subtype and is composed of Group D plant MAPKs including Arabidopsis thaliana MPK18 (AtMPK18), Oryza sativa Blast- and Wound-induced MAPK1 (OsBWMK1), OsWJUMK1 (Wound- and JA-Uninducible MAPK1), Zea mays MPK6, and the Medicago sativa TDY1 gene product. OsBWMK1 enhances resistance to pathogenic infections. It mediates stress-activated defense responses by activating a transcription factor that affects the expression of stress-related genes. AtMPK18 is involved in microtubule-related functions. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20 while Oryza sativa contains at least 17 MAPKs. Arabidopsis thaliana contains more TEY-type MAPKs than TDY-type, whereas the reverse is true for Oryza sativa. The TDY MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143364 [Multi-domain]  Cd Length: 338  Bit Score: 65.57  E-value: 5.56e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLK---EDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTrePP-------FYIITEF 317
Cdd:cd07859    8 IGKGSYGVVCSAIDTHTGEKVAIKKINdvfEHVSDATRILREIKLLRLLRHPDIVEIKHIML--PPsrrefkdIYVVFEL 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  318 MTY-------GNllDYLRECNRQevnavVLLYmatQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTG 390
Cdd:cd07859   86 MESdlhqvikAN--DDLTPEHHQ-----FFLY---QLLRALKYIHTANVFHRDLKPKNILANADCKLKICDFGLARVAFN 155
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 62362414  391 DTYTAhagakfpIKWT---------APESLA--YNKFSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELL 452
Cdd:cd07859  156 DTPTA-------IFWTdyvatrwyrAPELCGsfFSKYTPAIDIWSIGCIFAEVLT-GKPLFPGKNVVHQLDLI 220
PKc_Dusty cd13975
Catalytic domain of the Dual-specificity Protein Kinase, Dusty; Dual-specificity PKs catalyze ...
341-498 5.65e-11

Catalytic domain of the Dual-specificity Protein Kinase, Dusty; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Dusty protein kinase is also called Receptor-interacting protein kinase 5 (RIPK5 or RIP5) or RIP-homologous kinase. It is widely distributed in the central nervous system, and may be involved in inducing both caspase-dependent and caspase-independent cell death. The Dusty subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270877 [Multi-domain]  Cd Length: 262  Bit Score: 64.43  E-value: 5.65e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  341 LYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR---LMTGDTYTAhagakfPIKwTAPEsLAYNKFS 417
Cdd:cd13975  105 LQIALDVVEGIRFLHSQGLVHRDIKLKNVLLDKKNRAKITDLGFCKpeaMMSGSIVGT------PIH-MAPE-LFSGKYD 176
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  418 IKSDVWAFGVLLWEIATygmspyPGIDLSQVYE-LLEKDY------RMERPEGCP---EKVYELMRACWQWNPSDRPSFA 487
Cdd:cd13975  177 NSVDVYAFGILFWYLCA------GHVKLPEAFEqCASKDHlwnnvrKGVRPERLPvfdEECWNLMEACWSGDPSQRPLLG 250
                        170
                 ....*....|.
gi 62362414  488 EIHQAFETMFQ 498
Cdd:cd13975  251 IVQPKLQGIMD 261
SH2_SH2B3 cd10412
Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B3 (Lnk), ...
122-201 6.06e-11

Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B3 (Lnk), like other members of the SH2B adapter protein family, contains a pleckstrin homology domain, at least one dimerization domain, and a C-terminal SH2 domain which binds to phosphorylated tyrosines in a variety of tyrosine kinases. SH2B3 negatively regulates lymphopoiesis and early hematopoiesis. The lnk-deficiency results in enhanced production of B cells, and expansion as well as enhanced function of hematopoietic stem cells (HSCs), demonstrating negative regulatory functions of Sh2b3/Lnk in cytokine signaling. Sh2b3/Lnk also functions in responses controlled by cell adhesion and in crosstalk between integrin- and cytokine-mediated signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198275  Cd Length: 97  Bit Score: 59.91  E-value: 6.06e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  122 LEKHSWYHGPVSRNAAEYLL-SSGIN--GSFLVRESESSPGQRSISLRYEGRVYHYRINTASDGKLYVsSESRFNTLAEL 198
Cdd:cd10412    5 LSCYPWFHGPISRVKAAQLVqLQGPDahGVFLVRQSETRRGEYVLTFNFQGRAKHLRLSLTERGQCRV-QHLHFPSVVDM 83

                 ...
gi 62362414  199 VHH 201
Cdd:cd10412   84 LHH 86
STKc_Sck1_like cd05586
Catalytic domain of Suppressor of loss of cAMP-dependent protein kinase-like Serine/Threonine ...
248-452 6.17e-11

Catalytic domain of Suppressor of loss of cAMP-dependent protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Sck1 and similar fungal proteins. Sck1 plays a role in trehalase activation triggered by glucose and a nitrogen source. Trehalase catalyzes the cleavage of the disaccharide trehalose to glucose. Trehalose, as a carbohydrate reserve and stress metabolite, plays an important role in the response of yeast to environmental changes. The Sck1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270738 [Multi-domain]  Cd Length: 330  Bit Score: 65.28  E-value: 6.17e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTLKEdtmeveeflKEAAVMKEIKHPNLVQLLGVCT--REPPF-------------- 311
Cdd:cd05586    1 IGKGTFGQVYQVRKKDTRRIYAMKVLSK---------KVIVAKKEVAHTIGERNILVRTalDESPFivglkfsfqtptdl 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  312 YIITEFMTYGNLLDYLRECNR-QEVNAVvlLYMAtQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSR--LM 388
Cdd:cd05586   72 YLVTDYMSGGELFWHLQKEGRfSEDRAK--FYIA-ELVLALEHLHKNDIVYRDLKPENILLDANGHIALCDFGLSKadLT 148
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 62362414  389 TGDTYTAHAGAKfpiKWTAPESLAYNK-FSIKSDVWAFGVLLWEIATyGMSPYPGIDLSQVYELL 452
Cdd:cd05586  149 DNKTTNTFCGTT---EYLAPEVLLDEKgYTKMVDFWSLGVLVFEMCC-GWSPFYAEDTQQMYRNI 209
SH2_Grb7_family cd09944
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) ...
127-215 6.36e-11

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. There are 3 members of the Grb7 family of proteins: Grb7, Grb10, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb7 binds strongly to the erbB2 receptor, unlike Grb10 and Grb14 which bind weakly to it. Grb14 binds to Fibroblast Growth Factor Receptor (FGFR). Grb10 has been shown to interact with many different proteins, including the insulin and IGF1 receptors, platelet-derived growth factor (PDGF) receptor-beta, Ret, Kit, Raf1 and MEK1, and Nedd4. Grb7 family proteins are phosphorylated on serine/threonine as well as tyrosine residues. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198197 [Multi-domain]  Cd Length: 108  Bit Score: 60.51  E-value: 6.36e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  127 WYHGPVSRNAAEYLLSS--GINGSFLVRESESSPGQRSISLRYEGRVYHYRINTASD-GKLYVSSE---SRFNTLAELVH 200
Cdd:cd09944    7 WFHGGISRDEAARLIRQqgLVDGVFLVRESQSNPGAFVLSLKHGQKIKHYQIIPIEDeGQWYFTLDdgvTKFYDLLQLVE 86
                         90
                 ....*....|....*.
gi 62362414  201 HHSTVADGLITTL-HY 215
Cdd:cd09944   87 FYQLNAGSLPTRLkHY 102
STKc_Titin cd14104
Catalytic domain of the Giant Serine/Threonine Kinase Titin; STKs catalyze the transfer of the ...
244-459 7.41e-11

Catalytic domain of the Giant Serine/Threonine Kinase Titin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Titin, also called connectin, is a muscle-specific elastic protein and is the largest known protein to date. It contains multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains, and a single kinase domain near the C-terminus. It spans half of the sarcomere, the repeating contractile unit of striated muscle, and performs mechanical and catalytic functions. Titin contributes to the passive force generated when muscle is stretched during relaxation. Its kinase domain phosphorylates and regulates the muscle protein telethonin, which is required for sarcomere formation in differentiating myocytes. In addition, titin binds many sarcomere proteins and acts as a molecular scaffold for filament formation during myofibrillogenesis. The Titin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271006 [Multi-domain]  Cd Length: 277  Bit Score: 64.11  E-value: 7.41e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  244 MKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGNL 323
Cdd:cd14104    4 IAEELGRGQFGIVHRCVETSSKKTYMAKFVKVKGADQVLVKKEISILNIARHRNILRLHESFESHEELVMIFEFISGVDI 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  324 LDYLREcNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARN--CLVGENHLVKVADFGLSRLMTgdtytahAGAKF 401
Cdd:cd14104   84 FERITT-ARFELNEREIVSYVRQVCEALEFLHSKNIGHFDIRPENiiYCTRRGSYIKIIEFGQSRQLK-------PGDKF 155
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 62362414  402 PIKWT-----APESLAYNKFSIKSDVWAFGVLLWeIATYGMSPYPGIDLSQVYE-LLEKDYRME 459
Cdd:cd14104  156 RLQYTsaefyAPEVHQHESVSTATDMWSLGCLVY-VLLSGINPFEAETNQQTIEnIRNAEYAFD 218
SH2_SHE cd10391
Src homology 2 domain found in SH2 domain-containing adapter protein E (SHE); SHE is expressed ...
125-204 7.61e-11

Src homology 2 domain found in SH2 domain-containing adapter protein E (SHE); SHE is expressed in heart, lung, brain, and skeletal muscle. SHE contains two pTry protein binding domains, protein interaction domain (PID) and a SH2 domain, followed by a glycine-proline rich region, all of which are N-terminal to the phosphotyrosine binding (PTB) domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198254  Cd Length: 98  Bit Score: 59.97  E-value: 7.61e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  125 HSWYHGPVSRNAAEYLLSSGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTASDGKLYVSSESR-FNTLAELVHHHS 203
Cdd:cd10391    1 QPWYHGSISRAEAESRLQPCKEASYLVRNSESGNSKYSIALKTSQGCVHIIVAQTKDNKYTLNQTSAvFDSIPEVVHYYS 80

                 .
gi 62362414  204 T 204
Cdd:cd10391   81 N 81
SH2_DAPP1_BAM32_like cd10355
Src homology 2 domain found in dual adaptor for phosphotyrosine and 3-phosphoinositides ( ...
122-201 8.77e-11

Src homology 2 domain found in dual adaptor for phosphotyrosine and 3-phosphoinositides ( DAPP1)/B lymphocyte adaptor molecule of 32 kDa (Bam32)-like proteins; DAPP1/Bam32 contains a putative myristoylation site at its N-terminus, followed by a SH2 domain, and a pleckstrin homology (PH) domain at its C-terminus. DAPP1 could potentially be recruited to the cell membrane by any of these domains. Its putative myristoylation site could facilitate the interaction of DAPP1 with the lipid bilayer. Its SH2 domain may also interact with phosphotyrosine residues on membrane-associated proteins such as activated tyrosine kinase receptors. And finally its PH domain exhibits a high-affinity interaction with the PtdIns(3,4,5)P(3) PtdIns(3,4)P(2) second messengers produced at the cell membrane following the activation of PI 3-kinases. DAPP1 is thought to interact with both tyrosine phosphorylated proteins and 3-phosphoinositides and therefore may play a role in regulating the location and/or activity of such proteins(s) in response to agonists that elevate PtdIns(3,4,5)P(3) and PtdIns(3,4)P(2). This protein is likely to play an important role in triggering signal transduction pathways that lie downstream from receptor tyrosine kinases and PI 3-kinase. It is likely that DAPP1 functions as an adaptor to recruit other proteins to the plasma membrane in response to extracellular signals. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198218  Cd Length: 92  Bit Score: 59.41  E-value: 8.77e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  122 LEKHSWYHGPVSRNAAE-YLLSSGINGSFLVRESESSPGQRSISLRYEGRVYHYRIntASDGKLYVSSESRFNTLAELVH 200
Cdd:cd10355    3 LQSLGWYHGNLTRHAAEaLLLSNGVDGSYLLRNSNEGTGLFSLSVRAKDSVKHFHV--EYTGYSFKFGFNEFSSLQDFVK 80

                 .
gi 62362414  201 H 201
Cdd:cd10355   81 H 81
STKc_TSSK3-like cd14163
Catalytic domain of testis-specific serine/threonine kinase 3 and similar proteins; STKs ...
248-489 9.11e-11

Catalytic domain of testis-specific serine/threonine kinase 3 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. Its mRNA levels is low at birth, increases at puberty, and remains high throughout adulthood. The TSSK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271065 [Multi-domain]  Cd Length: 257  Bit Score: 63.86  E-value: 9.11e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  248 LGGGQYGEVYEGVWKKYSLTVAVKTL-KEDTME--VEEFL-KEAAVMKEIKHPNLVQLLGVC-TREPPFYIITEFMTYGN 322
Cdd:cd14163    8 IGEGTYSKVKEAFSKKHQRKVAIKIIdKSGGPEefIQRFLpRELQIVERLDHKNIIHVYEMLeSADGKIYLVMELAEDGD 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  323 LLDY-LRECNRQEVNAVVLLymaTQISSAMEYLEKKNFIHRDLAARNCLVgENHLVKVADFGLSRLMTGDTYTAHAGAKF 401
Cdd:cd14163   88 VFDCvLHGGPLPEHRAKALF---RQLVEAIRYCHGCGVAHRDLKCENALL-QGFTLKLTDFGFAKQLPKGGRELSQTFCG 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62362414  402 PIKWTAPESL-AYNKFSIKSDVWAFGVLLWEIATYGMsPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQWNP 480
Cdd:cd14163  164 STAYAAPEVLqGVPHDSRKGDIWSMGVVLYVMLCAQL-PFDDTDIPKMLCQQQKGVSLPGHLGVSRTCQDLLKRLLEPDM 242

                 ....*....
gi 62362414  481 SDRPSFAEI 489
Cdd:cd14163  243 VLRPSIEEV 251
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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