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Conserved domains on  [gi|1370473802|ref|XP_024307015|]
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tyrosine-protein kinase Yes isoform X2 [Homo sapiens]

Protein Classification

tyrosine-protein kinase; mitogen-activated protein kinase kinase kinase( domain architecture ID 10186267)

tyrosine-protein kinase is a cytoplasmic (or nonreceptor) kinase that catalyzes the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates; contains Src Homology 3 (SH3) and SH2 domains| mitogen-activated protein kinase kinase kinase (MAP3K) is a serine/threonine-protein kinase that catalyzes the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates; MAP3Ks phosphorylate and activate MAP2Ks, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PKc_like super family cl21453
Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the ...
264-498 2.39e-171

Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the catalytic domains of serine/threonine-specific and tyrosine-specific protein kinases. It also includes RIO kinases, which are atypical serine protein kinases, aminoglycoside phosphotransferases, and choline kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to hydroxyl groups in specific substrates such as serine, threonine, or tyrosine residues of proteins.


The actual alignment was detected with superfamily member cd05069:

Pssm-ID: 473864 [Multi-domain]  Cd Length: 279  Bit Score: 483.80  E-value: 2.39e-171
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 264 GLAKDAWEIPRESLRLEVKLGQGCFGEVWMGTWNGTTKVAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEP 343
Cdd:cd05069     1 GLAKDAWEIPRESLRLDVKLGQGCFGEVWMGTWNGTTKVAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEP 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 344 IYIVTEFMSKGSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIED 423
Cdd:cd05069    81 IYIVTEFMGKGSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGDNLVCKIADFGLARLIED 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 424 NEYTARQ--------------------------------------------GMVNREVLEQVERGYRMPCPQGCPESLHE 459
Cdd:cd05069   161 NEYTARQgakfpikwtapeaalygrftiksdvwsfgilltelvtkgrvpypGMVNREVLEQVERGYRMPCPQGCPESLHE 240
                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 1370473802 460 LMNLCWKKDPDERPTFEYIQSFLEDYFTATEPQYQPGEN 498
Cdd:cd05069   241 LMKLCWKKDPDERPTFEYIQSFLEDYFTATEPQYQPGDN 279
SH2_Src_family cd09933
Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src ...
154-253 1.36e-69

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: 217.06  E-value: 1.36e-69
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 154 QAEEWYFGKMGRKDAERLLLNPGNQRGIFLVRESETTKGAYSLSIRDWDEIRGDNVKHYKIRKLDNGGYYITTRAQFDTL 233
Cdd:cd09933     1 EAEEWFFGKIKRKDAEKLLLAPGNPRGTFLIRESETTPGAYSLSVRDGDDARGDTVKHYRIRKLDNGGYYITTRATFPTL 80
                          90       100
                  ....*....|....*....|
gi 1370473802 234 QKLVKHYTEHADGLCHKLTT 253
Cdd:cd09933    81 QELVQHYSKDADGLCCRLTV 100
SH3_Yes cd12007
Src homology 3 domain of Yes Protein Tyrosine Kinase; Yes (or c-Yes) is a member of the Src ...
94-151 6.19e-39

Src homology 3 domain of Yes Protein Tyrosine Kinase; 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 SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. 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: 212940 [Multi-domain]  Cd Length: 58  Bit Score: 135.55  E-value: 6.19e-39
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1370473802  94 TIFVALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARSIATGKNGYIPSNYVAPAD 151
Cdd:cd12007     1 TIFVALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARSIATGKNGYIPSNYVAPAD 58
 
Name Accession Description Interval E-value
PTKc_Yes cd05069
Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the ...
264-498 2.39e-171

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: 483.80  E-value: 2.39e-171
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 264 GLAKDAWEIPRESLRLEVKLGQGCFGEVWMGTWNGTTKVAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEP 343
Cdd:cd05069     1 GLAKDAWEIPRESLRLDVKLGQGCFGEVWMGTWNGTTKVAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEP 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 344 IYIVTEFMSKGSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIED 423
Cdd:cd05069    81 IYIVTEFMGKGSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGDNLVCKIADFGLARLIED 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 424 NEYTARQ--------------------------------------------GMVNREVLEQVERGYRMPCPQGCPESLHE 459
Cdd:cd05069   161 NEYTARQgakfpikwtapeaalygrftiksdvwsfgilltelvtkgrvpypGMVNREVLEQVERGYRMPCPQGCPESLHE 240
                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 1370473802 460 LMNLCWKKDPDERPTFEYIQSFLEDYFTATEPQYQPGEN 498
Cdd:cd05069   241 LMKLCWKKDPDERPTFEYIQSFLEDYFTATEPQYQPGDN 279
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
277-482 2.56e-100

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: 302.11  E-value: 2.56e-100
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 277 LRLEVKLGQGCFGEVWMGTWNG-----TTKVAIKTLKPGTMMP--EAFLQEAQIMKKLRHDKLVPLYAVVS-EEPIYIVT 348
Cdd:pfam07714   1 LTLGEKLGEGAFGEVYKGTLKGegentKIKVAVKTLKEGADEEerEDFLEEASIMKKLDHPNIVKLLGVCTqGEPLYIVT 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 349 EFMSKGSLLDFLKEGDGKyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNE-YT 427
Cdd:pfam07714  81 EYMPGGDLLDFLRKHKRK-LTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVVKISDFGLSRDIYDDDyYR 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 428 AR--------------------------------------------QGMVNREVLEQVERGYRMPCPQGCPESLHELMNL 463
Cdd:pfam07714 160 KRgggklpikwmapeslkdgkftsksdvwsfgvllweiftlgeqpyPGMSNEEVLEFLEDGYRLPQPENCPDELYDLMKQ 239
                         250
                  ....*....|....*....
gi 1370473802 464 CWKKDPDERPTFEYIQSFL 482
Cdd:pfam07714 240 CWAYDPEDRPTFSELVEDL 258
STYKc smart00221
Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class ...
277-482 7.17e-91

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: 277.89  E-value: 7.17e-91
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802  277 LRLEVKLGQGCFGEVWMGTWNGT-----TKVAIKTLKPGTMM--PEAFLQEAQIMKKLRHDKLVPLYAVVSE-EPIYIVT 348
Cdd:smart00221   1 LTLGKKLGEGAFGEVYKGTLKGKgdgkeVEVAVKTLKEDASEqqIEEFLREARIMRKLDHPNIVKLLGVCTEeEPLMIVM 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802  349 EFMSKGSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYTA 428
Cdd:smart00221  81 EYMPGGDLLDYLRKNRPKELSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRDLYDDDYYK 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802  429 RQ--------------------------------------------GMVNREVLEQVERGYRMPCPQGCPESLHELMNLC 464
Cdd:smart00221 161 VKggklpirwmapeslkegkftsksdvwsfgvllweiftlgeepypGMSNAEVLEYLKKGYRLPKPPNCPPELYKLMLQC 240
                          250
                   ....*....|....*...
gi 1370473802  465 WKKDPDERPTFEYIQSFL 482
Cdd:smart00221 241 WAEDPEDRPTFSELVEIL 258
SH2_Src_family cd09933
Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src ...
154-253 1.36e-69

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: 217.06  E-value: 1.36e-69
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 154 QAEEWYFGKMGRKDAERLLLNPGNQRGIFLVRESETTKGAYSLSIRDWDEIRGDNVKHYKIRKLDNGGYYITTRAQFDTL 233
Cdd:cd09933     1 EAEEWFFGKIKRKDAEKLLLAPGNPRGTFLIRESETTPGAYSLSVRDGDDARGDTVKHYRIRKLDNGGYYITTRATFPTL 80
                          90       100
                  ....*....|....*....|
gi 1370473802 234 QKLVKHYTEHADGLCHKLTT 253
Cdd:cd09933    81 QELVQHYSKDADGLCCRLTV 100
SH3_Yes cd12007
Src homology 3 domain of Yes Protein Tyrosine Kinase; Yes (or c-Yes) is a member of the Src ...
94-151 6.19e-39

Src homology 3 domain of Yes Protein Tyrosine Kinase; 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 SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. 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: 212940 [Multi-domain]  Cd Length: 58  Bit Score: 135.55  E-value: 6.19e-39
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1370473802  94 TIFVALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARSIATGKNGYIPSNYVAPAD 151
Cdd:cd12007     1 TIFVALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARSIATGKNGYIPSNYVAPAD 58
SH2 pfam00017
SH2 domain;
158-240 6.48e-34

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 122.32  E-value: 6.48e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 158 WYFGKMGRKDAERLLLNpGNQRGIFLVRESETTKGAYSLSIRDWDeirgdNVKHYKIRKLDNGGYYITTRAQFDTLQKLV 237
Cdd:pfam00017   1 WYHGKISRQEAERLLLN-GKPDGTFLVRESESTPGGYTLSVRDDG-----KVKHYKIQSTDNGGYYISGGVKFSSLAELV 74

                  ...
gi 1370473802 238 KHY 240
Cdd:pfam00017  75 EHY 77
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
278-433 3.21e-32

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 128.98  E-value: 3.21e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 278 RLEVKLGQGCFGEVWMGTWNGT-TKVAIKTLKPG-TMMPEA---FLQEAQIMKKLRHDKLVPLYAVVSEEPI-YIVTEFM 351
Cdd:COG0515    10 RILRLLGRGGMGVVYLARDLRLgRPVALKVLRPElAADPEArerFRREARALARLNHPNIVRVYDVGEEDGRpYLVMEYV 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 352 SKGSLLDFLKEGdgKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYTaRQG 431
Cdd:COG0515    90 EGESLADLLRRR--GPLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDGRVKLIDFGIARALGGATLT-QTG 166

                  ..
gi 1370473802 432 MV 433
Cdd:COG0515   167 TV 168
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
156-246 6.99e-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: 111.94  E-value: 6.99e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802  156 EEWYFGKMGRKDAERLLLNPGNqrGIFLVRESETTKGAYSLSIRDwdeirGDNVKHYKIRKLDNGGYYITTRAQFDTLQK 235
Cdd:smart00252   1 QPWYHGFISREEAEKLLKNEGD--GDFLVRDSESSPGDYVLSVRV-----KGKVKHYRIRRNEDGKFYLEGGRKFPSLVE 73
                           90
                   ....*....|.
gi 1370473802  236 LVKHYTEHADG 246
Cdd:smart00252  74 LVEHYQKNSLG 84
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
92-148 3.61e-17

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: 75.27  E-value: 3.61e-17
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1370473802   92 GVTIFVALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARsIATGKNGYIPSNYVA 148
Cdd:smart00326   1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGR-LGRGKEGLFPSNYVE 56
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
97-144 1.22e-16

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: 73.39  E-value: 1.22e-16
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1370473802  97 VALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARSIaTGKNGYIPS 144
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIVLEKSEDGWWKGRNK-GGKEGLIPS 47
PknB_PASTA_kin NF033483
Stk1 family PASTA domain-containing Ser/Thr kinase;
302-419 8.92e-16

Stk1 family PASTA domain-containing Ser/Thr kinase;


Pssm-ID: 468045 [Multi-domain]  Cd Length: 563  Bit Score: 79.84  E-value: 8.92e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 302 VAIKTLKPgTMM--PEA---FLQEAQIMKKLRHDKLVPLYAVVSEEPI-YIVTEFMsKGSLL-DFLKEGdGKyLKLPQLV 374
Cdd:NF033483   35 VAVKVLRP-DLArdPEFvarFRREAQSAASLSHPNIVSVYDVGEDGGIpYIVMEYV-DGRTLkDYIREH-GP-LSPEEAV 110
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1370473802 375 DMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR 419
Cdd:NF033483  111 EIMIQILSALEHAHRNGIVHRDIKPQNILITKDGRVKVTDFGIAR 155
PTZ00024 PTZ00024
cyclin-dependent protein kinase; Provisional
283-419 9.19e-14

cyclin-dependent protein kinase; Provisional


Pssm-ID: 240233 [Multi-domain]  Cd Length: 335  Bit Score: 72.49  E-value: 9.19e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVW--MGTWNGTtKVAIKTLKPGTMMPEAF---------------LQEAQIMKKLRHDKLVPLYAV-VSEEPI 344
Cdd:PTZ00024   17 LGEGTYGKVEkaYDTLTGK-IVAIKKVKIIEISNDVTkdrqlvgmcgihfttLRELKIMNEIKHENIMGLVDVyVEGDFI 95
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370473802 345 YIVTEFMSKgsllDFLKEGDGK-YLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR 419
Cdd:PTZ00024   96 NLVMDIMAS----DLKKVVDRKiRLTESQVKCILLQILNGLNVLHKWYFMHRDLSPANIFINSKGICKIADFGLAR 167
 
Name Accession Description Interval E-value
PTKc_Yes cd05069
Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the ...
264-498 2.39e-171

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: 483.80  E-value: 2.39e-171
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 264 GLAKDAWEIPRESLRLEVKLGQGCFGEVWMGTWNGTTKVAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEP 343
Cdd:cd05069     1 GLAKDAWEIPRESLRLDVKLGQGCFGEVWMGTWNGTTKVAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEP 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 344 IYIVTEFMSKGSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIED 423
Cdd:cd05069    81 IYIVTEFMGKGSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGDNLVCKIADFGLARLIED 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 424 NEYTARQ--------------------------------------------GMVNREVLEQVERGYRMPCPQGCPESLHE 459
Cdd:cd05069   161 NEYTARQgakfpikwtapeaalygrftiksdvwsfgilltelvtkgrvpypGMVNREVLEQVERGYRMPCPQGCPESLHE 240
                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 1370473802 460 LMNLCWKKDPDERPTFEYIQSFLEDYFTATEPQYQPGEN 498
Cdd:cd05069   241 LMKLCWKKDPDERPTFEYIQSFLEDYFTATEPQYQPGDN 279
PTKc_Src_Fyn_like cd14203
Catalytic domain of a subset of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
281-484 5.00e-154

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: 438.58  E-value: 5.00e-154
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 281 VKLGQGCFGEVWMGTWNGTTKVAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEPIYIVTEFMSKGSLLDFL 360
Cdd:cd14203     1 VKLGQGCFGEVWMGTWNGTTKVAIKTLKPGTMSPEAFLEEAQIMKKLRHDKLVQLYAVVSEEPIYIVTEFMSKGSLLDFL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 361 KEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYTARQ---------- 430
Cdd:cd14203    81 KDGEGKYLKLPQLVDMAAQIASGMAYIERMNYIHRDLRAANILVGDNLVCKIADFGLARLIEDNEYTARQgakfpikwta 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 431 ----------------------------------GMVNREVLEQVERGYRMPCPQGCPESLHELMNLCWKKDPDERPTFE 476
Cdd:cd14203   161 peaalygrftiksdvwsfgilltelvtkgrvpypGMNNREVLEQVERGYRMPCPPGCPESLHELMCQCWRKDPEERPTFE 240

                  ....*...
gi 1370473802 477 YIQSFLED 484
Cdd:cd14203   241 YLQSFLED 248
PTKc_Src cd05071
Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the ...
267-499 2.95e-149

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: 427.57  E-value: 2.95e-149
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 267 KDAWEIPRESLRLEVKLGQGCFGEVWMGTWNGTTKVAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEPIYI 346
Cdd:cd05071     1 KDAWEIPRESLRLEVKLGQGCFGEVWMGTWNGTTRVAIKTLKPGTMSPEAFLQEAQVMKKLRHEKLVQLYAVVSEEPIYI 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 347 VTEFMSKGSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEY 426
Cdd:cd05071    81 VTEYMSKGSLLDFLKGEMGKYLRLPQLVDMAAQIASGMAYVERMNYVHRDLRAANILVGENLVCKVADFGLARLIEDNEY 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 427 TARQ--------------------------------------------GMVNREVLEQVERGYRMPCPQGCPESLHELMN 462
Cdd:cd05071   161 TARQgakfpikwtapeaalygrftiksdvwsfgilltelttkgrvpypGMVNREVLDQVERGYRMPCPPECPESLHDLMC 240
                         250       260       270
                  ....*....|....*....|....*....|....*..
gi 1370473802 463 LCWKKDPDERPTFEYIQSFLEDYFTATEPQYQPGENL 499
Cdd:cd05071   241 QCWRKEPEERPTFEYLQAFLEDYFTSTEPQYQPGENL 277
PTKc_Src_like cd05034
Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
282-483 2.13e-146

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: 418.99  E-value: 2.13e-146
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGTTKVAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVS-EEPIYIVTEFMSKGSLLDFL 360
Cdd:cd05034     2 KLGAGQFGEVWMGVWNGTTKVAVKTLKPGTMSPEAFLQEAQIMKKLRHDKLVQLYAVCSdEEPIYIVTELMSKGSLLDYL 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 361 KEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYTARQ---------- 430
Cdd:cd05034    82 RTGEGRALRLPQLIDMAAQIASGMAYLESRNYIHRDLAARNILVGENNVCKVADFGLARLIEDDEYTAREgakfpikwta 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 431 ----------------------------------GMVNREVLEQVERGYRMPCPQGCPESLHELMNLCWKKDPDERPTFE 476
Cdd:cd05034   162 peaalygrftiksdvwsfgillyeivtygrvpypGMTNREVLEQVERGYRMPKPPGCPDELYDIMLQCWKKEPEERPTFE 241

                  ....*..
gi 1370473802 477 YIQSFLE 483
Cdd:cd05034   242 YLQSFLE 248
PTKc_Fyn cd05070
Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the ...
267-496 7.77e-144

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: 413.70  E-value: 7.77e-144
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 267 KDAWEIPRESLRLEVKLGQGCFGEVWMGTWNGTTKVAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEPIYI 346
Cdd:cd05070     1 KDVWEIPRESLQLIKRLGNGQFGEVWMGTWNGNTKVAIKTLKPGTMSPESFLEEAQIMKKLKHDKLVQLYAVVSEEPIYI 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 347 VTEFMSKGSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEY 426
Cdd:cd05070    81 VTEYMSKGSLLDFLKDGEGRALKLPNLVDMAAQVAAGMAYIERMNYIHRDLRSANILVGNGLICKIADFGLARLIEDNEY 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 427 TARQ--------------------------------------------GMVNREVLEQVERGYRMPCPQGCPESLHELMN 462
Cdd:cd05070   161 TARQgakfpikwtapeaalygrftiksdvwsfgilltelvtkgrvpypGMNNREVLEQVERGYRMPCPQDCPISLHELMI 240
                         250       260       270
                  ....*....|....*....|....*....|....
gi 1370473802 463 LCWKKDPDERPTFEYIQSFLEDYFTATEPQYQPG 496
Cdd:cd05070   241 HCWKKDPEERPTFEYLQGFLEDYFTATEPQYQPG 274
PTKc_Frk_like cd05068
Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
268-487 2.18e-129

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: 376.75  E-value: 2.18e-129
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 268 DAWEIPRESLRLEVKLGQGCFGEVWMGTWNGTTKVAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVS-EEPIYI 346
Cdd:cd05068     1 DQWEIDRKSLKLLRKLGSGQFGEVWEGLWNNTTPVAVKTLKPGTMDPEDFLREAQIMKKLRHPKLIQLYAVCTlEEPIYI 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 347 VTEFMSKGSLLDFLkEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIE-DNE 425
Cdd:cd05068    81 ITELMKHGSLLEYL-QGKGRSLQLPQLIDMAAQVASGMAYLESQNYIHRDLAARNVLVGENNICKVADFGLARVIKvEDE 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 426 YTARQ--------------------------------------------GMVNREVLEQVERGYRMPCPQGCPESLHELM 461
Cdd:cd05068   160 YEAREgakfpikwtapeaanynrfsiksdvwsfgillteivtygripypGMTNAEVLQQVERGYRMPCPPNCPPQLYDIM 239
                         250       260
                  ....*....|....*....|....*.
gi 1370473802 462 NLCWKKDPDERPTFEYIQSFLEDYFT 487
Cdd:cd05068   240 LECWKADPMERPTFETLQWKLEDFFV 265
PTKc_Lck_Blk cd05067
Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs ...
270-488 1.62e-123

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: 361.51  E-value: 1.62e-123
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 270 WEIPRESLRLEVKLGQGCFGEVWMGTWNGTTKVAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEPIYIVTE 349
Cdd:cd05067     2 WEVPRETLKLVERLGAGQFGEVWMGYYNGHTKVAIKSLKQGSMSPDAFLAEANLMKQLQHQRLVRLYAVVTQEPIYIITE 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 350 FMSKGSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYTAR 429
Cdd:cd05067    82 YMENGSLVDFLKTPSGIKLTINKLLDMAAQIAEGMAFIEERNYIHRDLRAANILVSDTLSCKIADFGLARLIEDNEYTAR 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 430 Q--------------------------------------------GMVNREVLEQVERGYRMPCPQGCPESLHELMNLCW 465
Cdd:cd05067   162 EgakfpikwtapeainygtftiksdvwsfgillteivthgripypGMTNPEVIQNLERGYRMPRPDNCPEELYQLMRLCW 241
                         250       260
                  ....*....|....*....|...
gi 1370473802 466 KKDPDERPTFEYIQSFLEDYFTA 488
Cdd:cd05067   242 KERPEDRPTFEYLRSVLEDFFTA 264
PTKc_Lyn cd05072
Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the ...
269-494 4.52e-121

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: 355.50  E-value: 4.52e-121
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 269 AWEIPRESLRLEVKLGQGCFGEVWMGTWNGTTKVAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVS-EEPIYIV 347
Cdd:cd05072     1 AWEIPRESIKLVKKLGAGQFGEVWMGYYNNSTKVAVKTLKPGTMSVQAFLEEANLMKTLQHDKLVRLYAVVTkEEPIYII 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 348 TEFMSKGSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYT 427
Cdd:cd05072    81 TEYMAKGSLLDFLKSDEGGKVLLPKLIDFSAQIAEGMAYIERKNYIHRDLRAANVLVSESLMCKIADFGLARVIEDNEYT 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 428 ARQ--------------------------------------------GMVNREVLEQVERGYRMPCPQGCPESLHELMNL 463
Cdd:cd05072   161 AREgakfpikwtapeainfgsftiksdvwsfgillyeivtygkipypGMSNSDVMSALQRGYRMPRMENCPDELYDIMKT 240
                         250       260       270
                  ....*....|....*....|....*....|.
gi 1370473802 464 CWKKDPDERPTFEYIQSFLEDYFTATEPQYQ 494
Cdd:cd05072   241 CWKEKAEERPTFDYLQSVLDDFYTATEGQYQ 271
PTKc_Hck cd05073
Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the ...
267-485 4.53e-108

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: 322.36  E-value: 4.53e-108
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 267 KDAWEIPRESLRLEVKLGQGCFGEVWMGTWNGTTKVAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEPIYI 346
Cdd:cd05073     3 KDAWEIPRESLKLEKKLGAGQFGEVWMATYNKHTKVAVKTMKPGSMSVEAFLAEANVMKTLQHDKLVKLHAVVTKEPIYI 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 347 VTEFMSKGSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEY 426
Cdd:cd05073    83 ITEFMAKGSLLDFLKSDEGSKQPLPKLIDFSAQIAEGMAFIEQRNYIHRDLRAANILVSASLVCKIADFGLARVIEDNEY 162
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 427 TARQ--------------------------------------------GMVNREVLEQVERGYRMPCPQGCPESLHELMN 462
Cdd:cd05073   163 TAREgakfpikwtapeainfgsftiksdvwsfgillmeivtygripypGMSNPEVIRALERGYRMPRPENCPEELYNIMM 242
                         250       260
                  ....*....|....*....|...
gi 1370473802 463 LCWKKDPDERPTFEYIQSFLEDY 485
Cdd:cd05073   243 RCWKNRPEERPTFEYIQSVLDDF 265
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
277-482 2.56e-100

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: 302.11  E-value: 2.56e-100
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 277 LRLEVKLGQGCFGEVWMGTWNG-----TTKVAIKTLKPGTMMP--EAFLQEAQIMKKLRHDKLVPLYAVVS-EEPIYIVT 348
Cdd:pfam07714   1 LTLGEKLGEGAFGEVYKGTLKGegentKIKVAVKTLKEGADEEerEDFLEEASIMKKLDHPNIVKLLGVCTqGEPLYIVT 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 349 EFMSKGSLLDFLKEGDGKyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNE-YT 427
Cdd:pfam07714  81 EYMPGGDLLDFLRKHKRK-LTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVVKISDFGLSRDIYDDDyYR 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 428 AR--------------------------------------------QGMVNREVLEQVERGYRMPCPQGCPESLHELMNL 463
Cdd:pfam07714 160 KRgggklpikwmapeslkdgkftsksdvwsfgvllweiftlgeqpyPGMSNEEVLEFLEDGYRLPQPENCPDELYDLMKQ 239
                         250
                  ....*....|....*....
gi 1370473802 464 CWKKDPDERPTFEYIQSFL 482
Cdd:pfam07714 240 CWAYDPEDRPTFSELVEDL 258
STYKc smart00221
Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class ...
277-482 7.17e-91

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: 277.89  E-value: 7.17e-91
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802  277 LRLEVKLGQGCFGEVWMGTWNGT-----TKVAIKTLKPGTMM--PEAFLQEAQIMKKLRHDKLVPLYAVVSE-EPIYIVT 348
Cdd:smart00221   1 LTLGKKLGEGAFGEVYKGTLKGKgdgkeVEVAVKTLKEDASEqqIEEFLREARIMRKLDHPNIVKLLGVCTEeEPLMIVM 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802  349 EFMSKGSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYTA 428
Cdd:smart00221  81 EYMPGGDLLDYLRKNRPKELSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRDLYDDDYYK 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802  429 RQ--------------------------------------------GMVNREVLEQVERGYRMPCPQGCPESLHELMNLC 464
Cdd:smart00221 161 VKggklpirwmapeslkegkftsksdvwsfgvllweiftlgeepypGMSNAEVLEYLKKGYRLPKPPNCPPELYKLMLQC 240
                          250
                   ....*....|....*...
gi 1370473802  465 WKKDPDERPTFEYIQSFL 482
Cdd:smart00221 241 WAEDPEDRPTFSELVEIL 258
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
277-482 4.94e-89

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


Pssm-ID: 197581 [Multi-domain]  Cd Length: 257  Bit Score: 272.87  E-value: 4.94e-89
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802  277 LRLEVKLGQGCFGEVWMGTWNGT-----TKVAIKTLKPGTMMP--EAFLQEAQIMKKLRHDKLVPLYAVVSE-EPIYIVT 348
Cdd:smart00219   1 LTLGKKLGEGAFGEVYKGKLKGKggkkkVEVAVKTLKEDASEQqiEEFLREARIMRKLDHPNVVKLLGVCTEeEPLYIVM 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802  349 EFMSKGSLLDFLKEGDGKyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYTA 428
Cdd:smart00219  81 EYMEGGDLLSYLRKNRPK-LSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRDLYDDDYYR 159
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802  429 RQ--------------------------------------------GMVNREVLEQVERGYRMPCPQGCPESLHELMNLC 464
Cdd:smart00219 160 KRggklpirwmapeslkegkftsksdvwsfgvllweiftlgeqpypGMSNEEVLEYLKNGYRLPQPPNCPPELYDLMLQC 239
                          250
                   ....*....|....*...
gi 1370473802  465 WKKDPDERPTFEYIQSFL 482
Cdd:smart00219 240 WAEDPEDRPTFSELVEIL 257
PTKc_Srm_Brk cd05148
Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal ...
270-485 5.31e-89

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: 273.16  E-value: 5.31e-89
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 270 WEIPRESLRLEVKLGQGCFGEVWMGTWNGTTKVAIKTLKPGTMMP-EAFLQEAQIMKKLRHDKLVPLYAVVSE-EPIYIV 347
Cdd:cd05148     1 WERPREEFTLERKLGSGYFGEVWEGLWKNRVRVAIKILKSDDLLKqQDFQKEVQALKRLRHKHLISLFAVCSVgEPVYII 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 348 TEFMSKGSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYT 427
Cdd:cd05148    81 TELMEKGSLLAFLRSPEGQVLPVASLIDMACQVAEGMAYLEEQNSIHRDLAARNILVGEDLVCKVADFGLARLIKEDVYL 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 428 AR-------------------------------------------QGMVNREVLEQVERGYRMPCPQGCPESLHELMNLC 464
Cdd:cd05148   161 SSdkkipykwtapeaashgtfstksdvwsfgillyemftygqvpyPGMNNHEVYDQITAGYRMPCPAKCPQEIYKIMLEC 240
                         250       260
                  ....*....|....*....|.
gi 1370473802 465 WKKDPDERPTFEYIQSFLEDY 485
Cdd:cd05148   241 WAAEPEDRPSFKALREELDNI 261
PTKc cd00192
Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
282-483 1.31e-85

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: 264.40  E-value: 1.31e-85
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTW----NGTTKVAIKTLKPGTMMPE--AFLQEAQIMKKLRHDKLVPLYAV-VSEEPIYIVTEFMSKG 354
Cdd:cd00192     2 KLGEGAFGEVYKGKLkggdGKTVDVAVKTLKEDASESErkDFLKEARVMKKLGHPNVVRLLGVcTEEEPLYLVMEYMEGG 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 355 SLLDFLKE-------GDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYT 427
Cdd:cd00192    82 DLLDFLRKsrpvfpsPEPSTLSLKDLLSFAIQIAKGMEYLASKKFVHRDLAARNCLVGEDLVVKISDFGLSRDIYDDDYY 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 428 ARQ---------------------------------------------GMVNREVLEQVERGYRMPCPQGCPESLHELMN 462
Cdd:cd00192   162 RKKtggklpirwmapeslkdgiftsksdvwsfgvllweiftlgatpypGLSNEEVLEYLRKGYRLPKPENCPDELYELML 241
                         250       260
                  ....*....|....*....|.
gi 1370473802 463 LCWKKDPDERPTFEYIQSFLE 483
Cdd:cd00192   242 SCWQLDPEDRPTFSELVERLE 262
PTKc_Abl cd05052
Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of ...
270-486 2.97e-70

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: 224.99  E-value: 2.97e-70
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 270 WEIPRESLRLEVKLGQGCFGEVWMGTWNGTTK-VAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEE-PIYIV 347
Cdd:cd05052     1 WEIERTDITMKHKLGGGQYGEVYEGVWKKYNLtVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREpPFYII 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 348 TEFMSKGSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYT 427
Cdd:cd05052    81 TEFMPYGNLLDYLRECNREELNAVVLLYMATQIASAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYT 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 428 ARQGM-------------VNR-------------------------------EVLEQVERGYRMPCPQGCPESLHELMNL 463
Cdd:cd05052   161 AHAGAkfpikwtapeslaYNKfsiksdvwafgvllweiatygmspypgidlsQVYELLEKGYRMERPEGCPPKVYELMRA 240
                         250       260
                  ....*....|....*....|...
gi 1370473802 464 CWKKDPDERPTFEYIQSFLEDYF 486
Cdd:cd05052   241 CWQWNPSDRPSFAEIHQALETMF 263
SH2_Src_family cd09933
Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src ...
154-253 1.36e-69

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: 217.06  E-value: 1.36e-69
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 154 QAEEWYFGKMGRKDAERLLLNPGNQRGIFLVRESETTKGAYSLSIRDWDEIRGDNVKHYKIRKLDNGGYYITTRAQFDTL 233
Cdd:cd09933     1 EAEEWFFGKIKRKDAEKLLLAPGNPRGTFLIRESETTPGAYSLSVRDGDDARGDTVKHYRIRKLDNGGYYITTRATFPTL 80
                          90       100
                  ....*....|....*....|
gi 1370473802 234 QKLVKHYTEHADGLCHKLTT 253
Cdd:cd09933    81 QELVQHYSKDADGLCCRLTV 100
PTKc_Tec_like cd05059
Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
276-475 4.24e-69

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: 221.55  E-value: 4.24e-69
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 276 SLRLEVKLGQGCFGEVWMGTWNGTTKVAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEE-PIYIVTEFMSKG 354
Cdd:cd05059     5 ELTFLKELGSGQFGVVHLGKWRGKIDVAIKMIKEGSMSEDDFIEEAKVMMKLSHPKLVQLYGVCTKQrPIFIVTEYMANG 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 355 SLLDFLKEGDGKyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYTARQG--- 431
Cdd:cd05059    85 CLLNYLRERRGK-FQTEQLLEMCKDVCEAMEYLESNGFIHRDLAARNCLVGEQNVVKVSDFGLARYVLDDEYTSSVGtkf 163
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 432 -----------------------------------------MVNREVLEQVERGYRMPCPQGCPESLHELMNLCWKKDPD 470
Cdd:cd05059   164 pvkwsppevfmyskfssksdvwsfgvlmwevfsegkmpyerFSNSEVVEHISQGYRLYRPHLAPTEVYTIMYSCWHEKPE 243

                  ....*
gi 1370473802 471 ERPTF 475
Cdd:cd05059   244 ERPTF 248
SH2_Src_Yes cd10366
Src homology 2 (SH2) domain found in Yes; Yes is a member of the Src non-receptor type ...
154-254 8.25e-67

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: 210.26  E-value: 8.25e-67
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 154 QAEEWYFGKMGRKDAERLLLNPGNQRGIFLVRESETTKGAYSLSIRDWDEIRGDNVKHYKIRKLDNGGYYITTRAQFDTL 233
Cdd:cd10366     1 QAEEWYFGKMGRKDAERLLLNPGNQRGIFLVRESETTKGAYSLSIRDWDEVRGDNVKHYKIRKLDNGGYYITTRAQFDTL 80
                          90       100
                  ....*....|....*....|.
gi 1370473802 234 QKLVKHYTEHADGLCHKLTTV 254
Cdd:cd10366    81 QKLVKHYTEHADGLCHKLTTV 101
PTKc_Csk_like cd05039
Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
270-483 2.87e-66

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: 214.14  E-value: 2.87e-66
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 270 WEIPRESLRLEVKLGQGCFGEVWMGTWNGTtKVAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEE-PIYIVT 348
Cdd:cd05039     1 WAINKKDLKLGELIGKGEFGDVMLGDYRGQ-KVAVKCLKDDSTAAQAFLAEASVMTTLRHPNLVQLLGVVLEGnGLYIVT 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 349 EFMSKGSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR--------- 419
Cdd:cd05039    80 EYMAKGSLVDYLRSRGRAVITRKDQLGFALDVCEGMEYLESKKFVHRDLAARNVLVSEDNVAKVSDFGLAKeassnqdgg 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 420 ----------LIEDNEYTARQGMVN---------------------REVLEQVERGYRMPCPQGCPESLHELMNLCWKKD 468
Cdd:cd05039   160 klpikwtapeALREKKFSTKSDVWSfgillweiysfgrvpypriplKDVVPHVEKGYRMEAPEGCPPEVYKVMKNCWELD 239
                         250
                  ....*....|....*
gi 1370473802 469 PDERPTFEYIQSFLE 483
Cdd:cd05039   240 PAKRPTFKQLREKLE 254
PTKc_EphR cd05033
Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
272-485 7.70e-66

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: 213.39  E-value: 7.70e-66
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 272 IPRESLRLEVKLGQGCFGEVWMGTWNGTTK----VAIKTLKPG--TMMPEAFLQEAQIMKKLRHDKLVPLYAVVSE-EPI 344
Cdd:cd05033     1 IDASYVTIEKVIGGGEFGEVCSGSLKLPGKkeidVAIKTLKSGysDKQRLDFLTEASIMGQFDHPNVIRLEGVVTKsRPV 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 345 YIVTEFMSKGSLLDFLKEGDGKyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDN 424
Cdd:cd05033    81 MIVTEYMENGSLDKFLRENDGK-FTVTQLVGMLRGIASGMKYLSEMNYVHRDLAARNILVNSDLVCKVSDFGLSRRLEDS 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 425 E--YTARQG-------------------------------------------MVNREVLEQVERGYRMPCPQGCPESLHE 459
Cdd:cd05033   160 EatYTTKGGkipirwtapeaiayrkftsasdvwsfgivmwevmsygerpywdMSNQDVIKAVEDGYRLPPPMDCPSALYQ 239
                         250       260
                  ....*....|....*....|....*.
gi 1370473802 460 LMNLCWKKDPDERPTFEYIQSFLEDY 485
Cdd:cd05033   240 LMLDCWQKDRNERPTFSQIVSTLDKM 265
PTKc_Fes_like cd05041
Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; ...
282-482 1.10e-63

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: 207.30  E-value: 1.10e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGT-TKVAIKTLKPgTMMPE---AFLQEAQIMKKLRHDKLVPLYAV-VSEEPIYIVTEFMSKGSL 356
Cdd:cd05041     2 KIGRGNFGDVYRGVLKPDnTEVAVKTCRE-TLPPDlkrKFLQEARILKQYDHPNIVKLIGVcVQKQPIMIVMELVPGGSL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 357 LDFLKeGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYTA----RQ-- 430
Cdd:cd05041    81 LTFLR-KKGARLTVKQLLQMCLDAAAGMEYLESKNCIHRDLAARNCLVGENNVLKISDFGMSREEEDGEYTVsdglKQip 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 431 ---------------------------------------GMVNREVLEQVERGYRMPCPQGCPESLHELMNLCWKKDPDE 471
Cdd:cd05041   160 ikwtapealnygrytsesdvwsfgillweifslgatpypGMSNQQTREQIESGYRMPAPELCPEAVYRLMLQCWAYDPEN 239
                         250
                  ....*....|.
gi 1370473802 472 RPTFEYIQSFL 482
Cdd:cd05041   240 RPSFSEIYNEL 250
SH2_Src_Fgr cd10367
Src homology 2 (SH2) domain found in Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene ...
154-252 1.20e-63

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: 202.06  E-value: 1.20e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 154 QAEEWYFGKMGRKDAERLLLNPGNQRGIFLVRESETTKGAYSLSIRDWDEIRGDNVKHYKIRKLDNGGYYITTRAQFDTL 233
Cdd:cd10367     1 QAEEWYFGKIGRKDAERQLLSPGNPRGAFLIRESETTKGAYSLSIRDWDQNRGDHVKHYKIRKLDTGGYYITTRAQFDTV 80
                          90
                  ....*....|....*....
gi 1370473802 234 QKLVKHYTEHADGLCHKLT 252
Cdd:cd10367    81 QELVQHYMEVNDGLCYLLT 99
STKc_MAP3K-like cd13999
Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine ...
283-482 9.20e-63

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: 204.69  E-value: 9.20e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTtKVAIKTLKPGTMMP---EAFLQEAQIMKKLRHDKLVPLYAVVSEEP-IYIVTEFMSKGSLLD 358
Cdd:cd13999     1 IGSGSFGEVYKGKWRGT-DVAIKKLKVEDDNDellKEFRREVSILSKLRHPNIVQFIGACLSPPpLCIVTEYMPGGSLYD 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 359 FLKEGDgKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNE-------YTAR-- 429
Cdd:cd13999    80 LLHKKK-IPLSWSLRLKIALDIARGMNYLHSPPIIHRDLKSLNILLDENFTVKIADFGLSRIKNSTTekmtgvvGTPRwm 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 430 ---------------------------------QGMVNREVLEQV-ERGYRMPCPQGCPESLHELMNLCWKKDPDERPTF 475
Cdd:cd13999   159 apevlrgepytekadvysfgivlwelltgevpfKELSPIQIAAAVvQKGLRPPIPPDCPPELSKLIKRCWNEDPEKRPSF 238

                  ....*..
gi 1370473802 476 EYIQSFL 482
Cdd:cd13999   239 SEIVKRL 245
PTKc_Itk cd05112
Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs ...
273-475 3.28e-60

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: 198.64  E-value: 3.28e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 273 PREsLRLEVKLGQGCFGEVWMGTWNGTTKVAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEE-PIYIVTEFM 351
Cdd:cd05112     3 PSE-LTFVQEIGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQaPICLVFEFM 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 352 SKGSLLDFLKEGDGKYLKlPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYTARQG 431
Cdd:cd05112    82 EHGCLSDYLRTQRGLFSA-ETLLGMCLDVCEGMAYLEEASVIHRDLAARNCLVGENQVVKVSDFGMTRFVLDDQYTSSTG 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 432 M--------------------------------------------VNREVLEQVERGYRMPCPQGCPESLHELMNLCWKK 467
Cdd:cd05112   161 TkfpvkwsspevfsfsryssksdvwsfgvlmwevfsegkipyenrSNSEVVEDINAGFRLYKPRLASTHVYEIMNHCWKE 240

                  ....*...
gi 1370473802 468 DPDERPTF 475
Cdd:cd05112   241 RPEDRPSF 248
SH2_Src_Fyn cd10368
Src homology 2 (SH2) domain found in Fyn; Fyn is a member of the Src non-receptor type ...
154-254 7.88e-60

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: 192.17  E-value: 7.88e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 154 QAEEWYFGKMGRKDAERLLLNPGNQRGIFLVRESETTKGAYSLSIRDWDEIRGDNVKHYKIRKLDNGGYYITTRAQFDTL 233
Cdd:cd10368     1 QAEEWYFGKLGRKDAERQLLSFGNPRGTFLIRESETTKGAYSLSIRDWDDMKGDHVKHYKIRKLDNGGYYITTRAQFETL 80
                          90       100
                  ....*....|....*....|.
gi 1370473802 234 QKLVKHYTEHADGLCHKLTTV 254
Cdd:cd10368    81 QQLVQHYSETANGLCKVLIVT 101
PTKc_InsR_like cd05032
Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer ...
270-484 8.51e-60

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: 197.95  E-value: 8.51e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 270 WEIPRESLRLEVKLGQGCFGEVWMGTWNGT------TKVAIKTLKPGTMMPE--AFLQEAQIMKKLRHDKLVPLYAVVS- 340
Cdd:cd05032     1 WELPREKITLIRELGQGSFGMVYEGLAKGVvkgepeTRVAIKTVNENASMREriEFLNEASVMKEFNCHHVVRLLGVVSt 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 341 EEPIYIVTEFMSKGSLLDFLKE--------GDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKI 412
Cdd:cd05032    81 GQPTLVVMELMAKGDLKSYLRSrrpeaennPGLGPPTLQKFIQMAAEIADGMAYLAAKKFVHRDLAARNCMVAEDLTVKI 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 413 ADFGLARLIEDNEY------------------------TAR---------------------QGMVNREVLEQVERGYRM 447
Cdd:cd05032   161 GDFGMTRDIYETDYyrkggkgllpvrwmapeslkdgvfTTKsdvwsfgvvlwematlaeqpyQGLSNEEVLKFVIDGGHL 240
                         250       260       270
                  ....*....|....*....|....*....|....*..
gi 1370473802 448 PCPQGCPESLHELMNLCWKKDPDERPTFEYIQSFLED 484
Cdd:cd05032   241 DLPENCPDKLLELMRMCWQYNPKMRPTFLEIVSSLKD 277
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 ...
154-251 8.84e-60

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: 191.75  E-value: 8.84e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 154 QAEEWYFGKMGRKDAERLLLNPGNQRGIFLVRESETTKGAYSLSIRDWDEIRGDNVKHYKIRKLDNGGYYITTRAQFDTL 233
Cdd:cd10418     1 QAEEWYFGKLGRKDAERQLLSFGNPRGTFLIRESETTKGAYSLSIRDWDDMKGDHVKHYKIRKLDNGGYYITTRAQFETL 80
                          90
                  ....*....|....*...
gi 1370473802 234 QKLVKHYTEHADGLCHKL 251
Cdd:cd10418    81 QQLVQHYSERAAGLCCRL 98
SH2_Src_Src cd10365
Src homology 2 (SH2) domain found in tyrosine kinase sarcoma (Src); Src is a member of the Src ...
154-254 1.04e-56

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: 183.71  E-value: 1.04e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 154 QAEEWYFGKMGRKDAERLLLNPGNQRGIFLVRESETTKGAYSLSIRDWDEIRGDNVKHYKIRKLDNGGYYITTRAQFDTL 233
Cdd:cd10365     1 QAEEWYFGKITRRESERLLLNAENPRGTFLVRESETTKGAYCLSVSDFDNAKGLNVKHYKIRKLDSGGFYITSRTQFNSL 80
                          90       100
                  ....*....|....*....|.
gi 1370473802 234 QKLVKHYTEHADGLCHKLTTV 254
Cdd:cd10365    81 QQLVAYYSKHADGLCHRLTTV 101
PTKc_EphR_A cd05066
Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze ...
277-483 1.45e-55

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: 186.61  E-value: 1.45e-55
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 277 LRLEVKLGQGCFGEVWMGTWNGTTK----VAIKTLKPGTMMPEA--FLQEAQIMKKLRHDKLVPLYAVVSE-EPIYIVTE 349
Cdd:cd05066     6 IKIEKVIGAGEFGEVCSGRLKLPGKreipVAIKTLKAGYTEKQRrdFLSEASIMGQFDHPNIIHLEGVVTRsKPVMIVTE 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 350 FMSKGSLLDFLKEGDGKYLKLpQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDN---EY 426
Cdd:cd05066    86 YMENGSLDAFLRKHDGQFTVI-QLVGMLRGIASGMKYLSDMGYVHRDLAARNILVNSNLVCKVSDFGLSRVLEDDpeaAY 164
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 427 TARQG-------------------------------------------MVNREVLEQVERGYRMPCPQGCPESLHELMNL 463
Cdd:cd05066   165 TTRGGkipirwtapeaiayrkftsasdvwsygivmwevmsygerpyweMSNQDVIKAIEEGYRLPAPMDCPAALHQLMLD 244
                         250       260
                  ....*....|....*....|
gi 1370473802 464 CWKKDPDERPTFEYIQSFLE 483
Cdd:cd05066   245 CWQKDRNERPKFEQIVSILD 264
PTKc_Btk_Bmx cd05113
Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow ...
272-483 7.13e-54

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: 182.00  E-value: 7.13e-54
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 272 IPRESLRLEVKLGQGCFGEVWMGTWNGTTKVAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEE-PIYIVTEF 350
Cdd:cd05113     1 IDPKDLTFLKELGTGQFGVVKYGKWRGQYDVAIKMIKEGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQrPIFIITEY 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 351 MSKGSLLDFLKEGdGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYTARQ 430
Cdd:cd05113    81 MANGCLLNYLREM-RKRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVLDDEYTSSV 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 431 G--------------------------------------------MVNREVLEQVERGYRMPCPQGCPESLHELMNLCWK 466
Cdd:cd05113   160 GskfpvrwsppevlmyskfssksdvwafgvlmwevyslgkmpyerFTNSETVEHVSQGLRLYRPHLASEKVYTIMYSCWH 239
                         250
                  ....*....|....*..
gi 1370473802 467 KDPDERPTFEYIQSFLE 483
Cdd:cd05113   240 EKADERPTFKILLSNIL 256
PTKc_Ack_like cd05040
Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs ...
282-484 1.13e-53

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: 181.39  E-value: 1.13e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTW---NGTT-KVAIKTLKPGTMM----PEAFLQEAQIMKKLRHDKLVPLYAVVSEEPIYIVTEFMSK 353
Cdd:cd05040     2 KLGDGSFGVVRRGEWttpSGKViQVAVKCLKSDVLSqpnaMDDFLKEVNAMHSLDHPNLIRLYGVVLSSPLMMVTELAPL 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 354 GSLLDFLKEGDGKYLkLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNE--YTARQ- 430
Cdd:cd05040    82 GSLLDRLRKDQGHFL-ISTLCDYAVQIANGMAYLESKRFIHRDLAARNILLASKDKVKIGDFGLMRALPQNEdhYVMQEh 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 431 -------------------------------------------GMVNREVLEQVER-GYRMPCPQGCPESLHELMNLCWK 466
Cdd:cd05040   161 rkvpfawcapeslktrkfshasdvwmfgvtlwemftygeepwlGLNGSQILEKIDKeGERLERPDDCPQDIYNVMLQCWA 240
                         250
                  ....*....|....*...
gi 1370473802 467 KDPDERPTFEYIQSFLED 484
Cdd:cd05040   241 HKPADRPTFVALRDFLPE 258
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 ...
155-254 5.18e-53

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: 174.09  E-value: 5.18e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 155 AEEWYFGKMGRKDAERLLLNPGNQRGIFLVRESETTKGAYSLSIRDWDEIRGDNVKHYKIRKLDNGGYYITTRAQFDTLQ 234
Cdd:cd10419     2 AEEWYFGKLGRKDAERQLLSFGNPRGTFLIRESETTKGAYSLSIRDWDDMKGDHVKHYKIRKLDNGGYYITTRAQFETLQ 81
                          90       100
                  ....*....|....*....|
gi 1370473802 235 KLVKHYTEHADGLCHKLTTV 254
Cdd:cd10419    82 QLVQHYSEKADGLCFNLTVI 101
PTKc_c-ros cd05044
Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the ...
283-484 2.76e-52

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: 177.99  E-value: 2.76e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTW-------NGTTKVAIKTLKPGTMMPE--AFLQEAQIMKKLRHDKLVPLYAV-VSEEPIYIVTEFMS 352
Cdd:cd05044     3 LGSGAFGEVFEGTAkdilgdgSGETKVAVKTLRKGATDQEkaEFLKEAHLMSNFKHPNILKLLGVcLDNDPQYIILELME 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 353 KGSLLDFLKE-----GDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGEN----LVCKIADFGLARLIED 423
Cdd:cd05044    83 GGDLLSYLRAarptaFTPPLLTLKDLLSICVDVAKGCVYLEDMHFVHRDLAARNCLVSSKdyreRVVKIGDFGLARDIYK 162
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 424 NEYTARQG---------------------------------------------MVNREVLEQVERGYRMPCPQGCPESLH 458
Cdd:cd05044   163 NDYYRKEGegllpvrwmapeslvdgvfttqsdvwafgvlmweiltlgqqpypaRNNLEVLHFVRAGGRLDQPDNCPDDLY 242
                         250       260
                  ....*....|....*....|....*.
gi 1370473802 459 ELMNLCWKKDPDERPTFEYIQSFLED 484
Cdd:cd05044   243 ELMLRCWSTDPEERPSFARILEQLQN 268
PTKc_Csk cd05082
Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the ...
270-484 3.31e-52

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: 177.48  E-value: 3.31e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 270 WEIPRESLRLEVKLGQGCFGEVWMGTWNGTtKVAIKTLKpGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEP--IYIV 347
Cdd:cd05082     1 WALNMKELKLLQTIGKGEFGDVMLGDYRGN-KVAVKCIK-NDATAQAFLAEASVMTQLRHSNLVQLLGVIVEEKggLYIV 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 348 TEFMSKGSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGL---ARLIEDN 424
Cdd:cd05082    79 TEYMAKGSLVDYLRSRGRSVLGGDCLLKFSLDVCEAMEYLEGNNFVHRDLAARNVLVSEDNVAKVSDFGLtkeASSTQDT 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 425 -----EYTARQGMVN--------------------------------REVLEQVERGYRMPCPQGCPESLHELMNLCWKK 467
Cdd:cd05082   159 gklpvKWTAPEALREkkfstksdvwsfgillweiysfgrvpypriplKDVVPRVEKGYKMDAPDGCPPAVYDVMKNCWHL 238
                         250
                  ....*....|....*..
gi 1370473802 468 DPDERPTFEYIQSFLED 484
Cdd:cd05082   239 DAAMRPSFLQLREQLEH 255
PTKc_FAK cd05056
Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the ...
270-484 1.14e-51

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: 176.46  E-value: 1.14e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 270 WEIPRESLRLEVKLGQGCFGEVWMGTW----NGTTKVAIKTLKPGTM--MPEAFLQEAQIMKKLRHDKLVPLYAVVSEEP 343
Cdd:cd05056     1 YEIQREDITLGRCIGEGQFGDVYQGVYmspeNEKIAVAVKTCKNCTSpsVREKFLQEAYIMRQFDHPHIVKLIGVITENP 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 344 IYIVTEFMSKGSLLDFLKEgDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIED 423
Cdd:cd05056    81 VWIVMELAPLGELRSYLQV-NKYSLDLASLILYAYQLSTALAYLESKRFVHRDIAARNVLVSSPDCVKLGDFGLSRYMED 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 424 NEY------------------------TAR--------------------QGMVNREVLEQVERGYRMPCPQGCPESLHE 459
Cdd:cd05056   160 ESYykaskgklpikwmapesinfrrftSASdvwmfgvcmweilmlgvkpfQGVKNNDVIGRIENGERLPMPPNCPPTLYS 239
                         250       260
                  ....*....|....*....|....*
gi 1370473802 460 LMNLCWKKDPDERPTFEYIQSFLED 484
Cdd:cd05056   240 LMTKCWAYDPSKRPRFTELKAQLSD 264
PTKc_EphR_B cd05065
Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze ...
277-483 3.59e-51

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: 175.06  E-value: 3.59e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 277 LRLEVKLGQGCFGEVWMGTWNGTTK----VAIKTLKPGTMMPEA--FLQEAQIMKKLRHDKLVPLYAVVSEE-PIYIVTE 349
Cdd:cd05065     6 VKIEEVIGAGEFGEVCRGRLKLPGKreifVAIKTLKSGYTEKQRrdFLSEASIMGQFDHPNIIHLEGVVTKSrPVMIITE 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 350 FMSKGSLLDFLKEGDGKYLKLpQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNE---- 425
Cdd:cd05065    86 FMENGALDSFLRQNDGQFTVI-QLVGMLRGIAAGMKYLSEMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTsdpt 164
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 426 YTARQG--------------------------------------------MVNREVLEQVERGYRMPCPQGCPESLHELM 461
Cdd:cd05065   165 YTSSLGgkipirwtapeaiayrkftsasdvwsygivmwevmsygerpywdMSNQDVINAIEQDYRLPPPMDCPTALHQLM 244
                         250       260
                  ....*....|....*....|..
gi 1370473802 462 NLCWKKDPDERPTFEYIQSFLE 483
Cdd:cd05065   245 LDCWQKDRNLRPKFGQIVNTLD 266
PTKc_Fer cd05085
Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; ...
283-482 6.18e-51

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: 174.04  E-value: 6.18e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKVAIKTLKPGtmMPEA----FLQEAQIMKKLRHDKLVPLYAVVSE-EPIYIVTEFMSKGSLL 357
Cdd:cd05085     4 LGKGNFGEVYKGTLKDKTPVAVKTCKED--LPQElkikFLSEARILKQYDHPNIVKLIGVCTQrQPIYIVMELVPGGDFL 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 358 DFLKEGDGKyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYTA---RQ---- 430
Cdd:cd05085    82 SFLRKKKDE-LKTKQLVKFSLDAAAGMAYLESKNCIHRDLAARNCLVGENNALKISDFGMSRQEDDGVYSSsglKQipik 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 431 -------------------------------------GMVNREVLEQVERGYRMPCPQGCPESLHELMNLCWKKDPDERP 473
Cdd:cd05085   161 wtapealnygryssesdvwsfgillwetfslgvcpypGMTNQQAREQVEKGYRMSAPQRCPEDIYKIMQRCWDYNPENRP 240

                  ....*....
gi 1370473802 474 TFEYIQSFL 482
Cdd:cd05085   241 KFSELQKEL 249
PKc cd00180
Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group ...
283-482 7.44e-51

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: 172.45  E-value: 7.44e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGT-TKVAIKTLKPG--TMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEP-IYIVTEFMSKGSLLD 358
Cdd:cd00180     1 LGKGSFGKVYKARDKETgKKVAVKVIPKEklKKLLEELLREIEILKKLNHPNIVKLYDVFETENfLYLVMEYCEGGSLKD 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 359 FLKEGDGKyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYTARQG------- 431
Cdd:cd00180    81 LLKENKGP-LSEEEALSILRQLLSALEYLHSNGIIHRDLKPENILLDSDGTVKLADFGLAKDLDSDDSLLKTTggttppy 159
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370473802 432 MVNREVLEQVERG------------YRMPcpqgcpeSLHELMNLCWKKDPDERPTFEYIQSFL 482
Cdd:cd00180   160 YAPPELLGGRYYGpkvdiwslgvilYELE-------ELKDLIRRMLQYDPKKRPSAKELLEHL 215
PTKc_EphR_A2 cd05063
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the ...
271-483 9.37e-51

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: 174.01  E-value: 9.37e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 271 EIPRESLRLEVKLGQGCFGEVWMGTWNGTTK----VAIKTLKPGTMMPEA--FLQEAQIMKKLRHDKLVPLYAVVSE-EP 343
Cdd:cd05063     1 EIHPSHITKQKVIGAGEFGEVFRGILKMPGRkevaVAIKTLKPGYTEKQRqdFLSEASIMGQFSHHNIIRLEGVVTKfKP 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 344 IYIVTEFMSKGSLLDFLKEGDGKYLKLpQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIED 423
Cdd:cd05063    81 AMIITEYMENGALDKYLRDHDGEFSSY-QLVGMLRGIAAGMKYLSDMNYVHRDLAARNILVNSNLECKVSDFGLSRVLED 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 424 N---EYTARQG-------------------------------------------MVNREVLEQVERGYRMPCPQGCPESL 457
Cdd:cd05063   160 DpegTYTTSGGkipirwtapeaiayrkftsasdvwsfgivmwevmsfgerpywdMSNHEVMKAINDGFRLPAPMDCPSAV 239
                         250       260
                  ....*....|....*....|....*.
gi 1370473802 458 HELMNLCWKKDPDERPTFEYIQSFLE 483
Cdd:cd05063   240 YQLMLQCWQQDRARRPRFVDIVNLLD 265
PTKc_Syk_like cd05060
Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
283-485 1.46e-50

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: 173.30  E-value: 1.46e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTW----NGTTKVAIKTLKPGTMMP--EAFLQEAQIMKKLRHDKLVPLYAVVSEEPIYIVTEFMSKGSL 356
Cdd:cd05060     3 LGHGNFGSVRKGVYlmksGKEVEVAVKTLKQEHEKAgkKEFLREASVMAQLDHPCIVRLIGVCKGEPLMLVMELAPLGPL 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 357 LDFLKegDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLI--EDNEYTARQG--- 431
Cdd:cd05060    83 LKYLK--KRREIPVSDLKELAHQVAMGMAYLESKHFVHRDLAARNVLLVNRHQAKISDFGMSRALgaGSDYYRATTAgrw 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 432 -----------------------------------------MVNREVLEQVERGYRMPCPQGCPESLHELMNLCWKKDPD 470
Cdd:cd05060   161 plkwyapecinygkfssksdvwsygvtlweafsygakpygeMKGPEVIAMLESGERLPRPEECPQEIYSIMLSCWKYRPE 240
                         250
                  ....*....|....*
gi 1370473802 471 ERPTFEYIQSFLEDY 485
Cdd:cd05060   241 DRPTFSELESTFRRD 255
PTKc_Chk cd05083
Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the ...
270-483 1.82e-50

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: 172.75  E-value: 1.82e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 270 WEIPRESLRLEVKLGQGCFGEVWMGTWNGTtKVAIKTLKpGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEPIYIVTE 349
Cdd:cd05083     1 WLLNLQKLTLGEIIGEGEFGAVLQGEYMGQ-KVAVKNIK-CDVTAQAFLEETAVMTKLQHKNLVRLLGVILHNGLYIVME 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 350 FMSKGSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARL--------- 420
Cdd:cd05083    79 LMSKGNLVNFLRSRGRALVPVIQLLQFSLDVAEGMEYLESKKLVHRDLAARNILVSEDGVAKISDFGLAKVgsmgvdnsr 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 421 ----------IEDNEYTARQG---------------------MVNREVLEQVERGYRMPCPQGCPESLHELMNLCWKKDP 469
Cdd:cd05083   159 lpvkwtapeaLKNKKFSSKSDvwsygvllwevfsygrapypkMSVKEVKEAVEKGYRMEPPEGCPPDVYSIMTSCWEAEP 238
                         250
                  ....*....|....
gi 1370473802 470 DERPTFEYIQSFLE 483
Cdd:cd05083   239 GKRPSFKKLREKLE 252
PTKc_Tec_Rlk cd05114
Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular ...
282-476 7.00e-50

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: 171.58  E-value: 7.00e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGTTKVAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEE-PIYIVTEFMSKGSLLDFL 360
Cdd:cd05114    11 ELGSGLFGVVRLGKWRAQYKVAIKAIREGAMSEEDFIEEAKVMMKLTHPKLVQLYGVCTQQkPIYIVTEFMENGCLLNYL 90
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 361 KEGDGKYLKlPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYTARQGM-------- 432
Cdd:cd05114    91 RQRRGKLSR-DMLLSMCQDVCEGMEYLERNNFIHRDLAARNCLVNDTGVVKVSDFGMTRYVLDDQYTSSSGAkfpvkwsp 169
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 433 ------------------------------------VNREVLEQVERGYRMPCPQGCPESLHELMNLCWKKDPDERPTFE 476
Cdd:cd05114   170 pevfnyskfssksdvwsfgvlmwevftegkmpfeskSNYEVVEMVSRGHRLYRPKLASKSVYEVMYSCWHEKPEGRPTFA 249
SH2_Src_HCK cd10363
Src homology 2 (SH2) domain found in HCK; HCK is a member of the Src non-receptor type ...
154-255 4.33e-48

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: 161.29  E-value: 4.33e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 154 QAEEWYFGKMGRKDAERLLLNPGNQRGIFLVRESETTKGAYSLSIRDWDEIRGDNVKHYKIRKLDNGGYYITTRAQFDTL 233
Cdd:cd10363     1 ETEEWFFKGISRKDAERQLLAPGNMLGSFMIRDSETTKGSYSLSVRDYDPQHGDTVKHYKIRTLDNGGFYISPRSTFSTL 80
                          90       100
                  ....*....|....*....|..
gi 1370473802 234 QKLVKHYTEHADGLCHKLTTVC 255
Cdd:cd10363    81 QELVDHYKKGNDGLCQKLSVPC 102
PTKc_FGFR cd05053
Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs ...
269-483 2.29e-47

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: 166.05  E-value: 2.29e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 269 AWEIPRESLRLEVKLGQGCFGEVWMGTW-------NGTTKVAIKTLKPGTMMPEA--FLQEAQIMKKL-RHDKLVPLYAV 338
Cdd:cd05053     6 EWELPRDRLTLGKPLGEGAFGQVVKAEAvgldnkpNEVVTVAVKMLKDDATEKDLsdLVSEMEMMKMIgKHKNIINLLGA 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 339 VSEE-PIYIVTEFMSKGSLLDFLK--------------EGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANIL 403
Cdd:cd05053    86 CTQDgPLYVVVEYASKGNLREFLRarrppgeeaspddpRVPEEQLTQKDLVSFAYQVARGMEYLASKKCIHRDLAARNVL 165
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 404 VGENLVCKIADFGLARLIEDNEY-------------TARQGMVNR--------------------------------EVL 438
Cdd:cd05053   166 VTEDNVMKIADFGLARDIHHIDYyrkttngrlpvkwMAPEALFDRvythqsdvwsfgvllweiftlggspypgipveELF 245
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 1370473802 439 EQVERGYRMPCPQGCPESLHELMNLCWKKDPDERPTFEYIQSFLE 483
Cdd:cd05053   246 KLLKEGHRMEKPQNCTQELYMLMRDCWHEVPSQRPTFKQLVEDLD 290
PTKc_DDR cd05051
Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze ...
271-482 2.23e-46

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: 163.28  E-value: 2.23e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 271 EIPRESLRLEVKLGQGCFGEV---------------WMGTWNGTTK--VAIKTLKPGT--MMPEAFLQEAQIMKKLRHDK 331
Cdd:cd05051     1 EFPREKLEFVEKLGEGQFGEVhlceanglsdltsddFIGNDNKDEPvlVAVKMLRPDAskNAREDFLKEVKIMSQLKDPN 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 332 LVPLYAV-VSEEPIYIVTEFMSKGSLLDFLK--EGDGKYLKLPQ--------LVDMAAQIADGMAYIERMNYIHRDLRAA 400
Cdd:cd05051    81 IVRLLGVcTRDEPLCMIVEYMENGDLNQFLQkhEAETQGASATNsktlsygtLLYMATQIASGMKYLESLNFVHRDLATR 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 401 NILVGENLVCKIADFGLARLIEDNEYTARQG----------------------------------------------MVN 434
Cdd:cd05051   161 NCLVGPNYTIKIADFGMSRNLYSGDYYRIEGravlpirwmawesillgkfttksdvwafgvtlweiltlckeqpyehLTD 240
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1370473802 435 REVLEQVERGYR-------MPCPQGCPESLHELMNLCWKKDPDERPTFEYIQSFL 482
Cdd:cd05051   241 EQVIENAGEFFRddgmevyLSRPPNCPKEIYELMLECWRRDEEDRPTFREIHLFL 295
PTKc_ALK_LTK cd05036
Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte ...
271-478 8.70e-45

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: 158.32  E-value: 8.70e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 271 EIPRESLRLEVKLGQGCFGEVWMGTWNGTT------KVAIKTLkPGTMMPEA---FLQEAQIMKKLRHDKLVPLYAV-VS 340
Cdd:cd05036     2 EVPRKNLTLIRALGQGAFGEVYEGTVSGMPgdpsplQVAVKTL-PELCSEQDemdFLMEALIMSKFNHPNIVRCIGVcFQ 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 341 EEPIYIVTEFMSKGSLLDFLKE-----GDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILV---GENLVCKI 412
Cdd:cd05036    81 RLPRFILLELMAGGDLKSFLREnrprpEQPSSLTMLDLLQLAQDVAKGCRYLEENHFIHRDIAARNCLLtckGPGRVAKI 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 413 ADFGLARLIEDNEY------------------------TARQ---------------------GMVNREVLEQVERGYRM 447
Cdd:cd05036   161 GDFGMARDIYRADYyrkggkamlpvkwmppeafldgifTSKTdvwsfgvllweifslgympypGKSNQEVMEFVTSGGRM 240
                         250       260       270
                  ....*....|....*....|....*....|.
gi 1370473802 448 PCPQGCPESLHELMNLCWKKDPDERPTFEYI 478
Cdd:cd05036   241 DPPKNCPGPVYRIMTQCWQHIPEDRPNFSTI 271
PTKc_Fes cd05084
Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the ...
282-482 1.30e-44

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: 157.40  E-value: 1.30e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNG-TTKVAIKTLKPgTMMPE---AFLQEAQIMKKLRHDKLVPLYAVVSE-EPIYIVTEFMSKGSL 356
Cdd:cd05084     3 RIGRGNFGEVFSGRLRAdNTPVAVKSCRE-TLPPDlkaKFLQEARILKQYSHPNIVRLIGVCTQkQPIYIVMELVQGGDF 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 357 LDFLKEgDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYTARQGM---- 432
Cdd:cd05084    82 LTFLRT-EGPRLKVKELIRMVENAAAGMEYLESKHCIHRDLAARNCLVTEKNVLKISDFGMSREEEDGVYAATGGMkqip 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 433 -----------------------------------------VNREVLEQVERGYRMPCPQGCPESLHELMNLCWKKDPDE 471
Cdd:cd05084   161 vkwtapealnygryssesdvwsfgillwetfslgavpyanlSNQQTREAVEQGVRLPCPENCPDEVYRLMEQCWEYDPRK 240
                         250
                  ....*....|.
gi 1370473802 472 RPTFEYIQSFL 482
Cdd:cd05084   241 RPSFSTVHQDL 251
S_TKc smart00220
Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or ...
282-476 1.59e-44

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


Pssm-ID: 214567 [Multi-domain]  Cd Length: 254  Bit Score: 156.92  E-value: 1.59e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802  282 KLGQGCFGEVWMGTWNGT-TKVAIKTLKPGTM--MPEAFLQEAQIMKKLRHDKLVPLYAV-VSEEPIYIVTEFMSKGSLL 357
Cdd:smart00220   6 KLGEGSFGKVYLARDKKTgKLVAIKVIKKKKIkkDRERILREIKILKKLKHPNIVRLYDVfEDEDKLYLVMEYCEGGDLF 85
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802  358 DFLKEGdgKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDN----------EYT 427
Cdd:smart00220  86 DLLKKR--GRLSEDEARFYLRQILSALEYLHSKGIVHRDLKPENILLDEDGHVKLADFGLARQLDPGeklttfvgtpEYM 163
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802  428 A----RQGMVNREV----------------------------LEQVERGYR--MPCPQGCPESLHELMNLCWKKDPDERP 473
Cdd:smart00220 164 ApevlLGKGYGKAVdiwslgvilyelltgkppfpgddqllelFKKIGKPKPpfPPPEWDISPEAKDLIRKLLVKDPEKRL 243

                   ...
gi 1370473802  474 TFE 476
Cdd:smart00220 244 TAE 246
SH2_Src_Lck cd10362
Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck); Lck is a member of the Src ...
154-251 4.72e-44

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: 150.41  E-value: 4.72e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 154 QAEEWYFGKMGRKDAERLLLNPGNQRGIFLVRESETTKGAYSLSIRDWDEIRGDNVKHYKIRKLDNGGYYITTRAQFDTL 233
Cdd:cd10362     1 EPEPWFFKNLSRNDAERQLLAPGNTHGSFLIRESETTAGSFSLSVRDFDQNQGEVVKHYKIRNLDNGGFYISPRITFPGL 80
                          90
                  ....*....|....*...
gi 1370473802 234 QKLVKHYTEHADGLCHKL 251
Cdd:cd10362    81 HELVRHYTNASDGLCTRL 98
SH2_Src_Lyn cd10364
Src homology 2 (SH2) domain found in Lyn; Lyn is a member of the Src non-receptor type ...
154-251 5.04e-44

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: 150.52  E-value: 5.04e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 154 QAEEWYFGKMGRKDAERLLLNPGNQRGIFLVRESETTKGAYSLSIRDWDEIRGDNVKHYKIRKLDNGGYYITTRAQFDTL 233
Cdd:cd10364     1 ETEEWFFKDITRKDAERQLLAPGNSAGAFLIRESETLKGSYSLSVRDYDPQHGDVIKHYKIRSLDNGGYYISPRITFPCI 80
                          90
                  ....*....|....*...
gi 1370473802 234 QKLVKHYTEHADGLCHKL 251
Cdd:cd10364    81 SDMIKHYQKQSDGLCRRL 98
PTKc_Ror cd05048
Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan ...
271-482 7.65e-43

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: 153.30  E-value: 7.65e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 271 EIPRESLRLEVKLGQGCFGEVWMGTWNG------TTKVAIKTLKPGTMMP--EAFLQEAQIMKKLRHDKLVPLYAVVS-E 341
Cdd:cd05048     1 EIPLSAVRFLEELGEGAFGKVYKGELLGpsseesAISVAIKTLKENASPKtqQDFRREAELMSDLQHPNIVCLLGVCTkE 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 342 EPIYIVTEFMSKGSLLDFL--------------KEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGEN 407
Cdd:cd05048    81 QPQCMLFEYMAHGDLHEFLvrhsphsdvgvssdDDGTASSLDQSDFLHIAIQIAAGMEYLSSHHYVHRDLAARNCLVGDG 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 408 LVCKIADFGLARLIEDNEYTARQ---------------------------------------------GMVNREVLEQVE 442
Cdd:cd05048   161 LTVKISDFGLSRDIYSSDYYRVQsksllpvrwmppeailygkfttesdvwsfgvvlweifsyglqpyyGYSNQEVIEMIR 240
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 1370473802 443 RGYRMPCPQGCPESLHELMNLCWKKDPDERPTFEYIQSFL 482
Cdd:cd05048   241 SRQLLPCPEDCPARVYSLMVECWHEIPSRRPRFKEIHTRL 280
PTKc_Jak_rpt2 cd05038
Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily ...
273-479 2.15e-41

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: 149.45  E-value: 2.15e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 273 PRESLRLEVKLGQGCFGEVWMGTW----NGTTK-VAIKTLKPgtMMPEA----FLQEAQIMKKLRHDKLVPlYAVVSEEP 343
Cdd:cd05038     2 EERHLKFIKQLGEGHFGSVELCRYdplgDNTGEqVAVKSLQP--SGEEQhmsdFKREIEILRTLDHEYIVK-YKGVCESP 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 344 ----IYIVTEFMSKGSLLDFLKEGDGKyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR 419
Cdd:cd05038    79 grrsLRLIMEYLPSGSLRDYLQRHRDQ-IDLKRLLLFASQICKGMEYLGSQRYIHRDLAARNILVESEDLVKISDFGLAK 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 420 LI-EDNEY-----------------------------------------------------------TARQGMVNREVLE 439
Cdd:cd05038   158 VLpEDKEYyyvkepgespifwyapeclresrfssasdvwsfgvtlyelftygdpsqsppalflrmigIAQGQMIVTRLLE 237
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 1370473802 440 QVERGYRMPCPQGCPESLHELMNLCWKKDPDERPTFEYIQ 479
Cdd:cd05038   238 LLKSGERLPRPPSCPDEVYDLMKECWEYEPQDRPSFSDLI 277
PTKc_InsR cd05061
Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer ...
270-484 2.72e-41

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: 149.35  E-value: 2.72e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 270 WEIPRESLRLEVKLGQGCFGEVWMGTWNGT------TKVAIKTLKPGTMMPE--AFLQEAQIMKKLRHDKLVPLYAVVSE 341
Cdd:cd05061     1 WEVSREKITLLRELGQGSFGMVYEGNARDIikgeaeTRVAVKTVNESASLREriEFLNEASVMKGFTCHHVVRLLGVVSK 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 342 -EPIYIVTEFMSKGSLLDFLK-------EGDGKYL-KLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKI 412
Cdd:cd05061    81 gQPTLVVMELMAHGDLKSYLRslrpeaeNNPGRPPpTLQEMIQMAAEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVKI 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 413 ADFGLARLIEDNEYTAR---------------------------------------------QGMVNREVLEQVERGYRM 447
Cdd:cd05061   161 GDFGMTRDIYETDYYRKggkgllpvrwmapeslkdgvfttssdmwsfgvvlweitslaeqpyQGLSNEQVLKFVMDGGYL 240
                         250       260       270
                  ....*....|....*....|....*....|....*..
gi 1370473802 448 PCPQGCPESLHELMNLCWKKDPDERPTFEYIQSFLED 484
Cdd:cd05061   241 DQPDNCPERVTDLMRMCWQFNPKMRPTFLEIVNLLKD 277
PTKc_Musk cd05050
Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the ...
271-483 2.73e-40

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: 146.90  E-value: 2.73e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 271 EIPRESLRLEVKLGQGCFGEVWMGTWNGT------TKVAIKTLKPG--TMMPEAFLQEAQIMKKLRHDKLVPLYAVVSE- 341
Cdd:cd05050     1 EYPRNNIEYVRDIGQGAFGRVFQARAPGLlpyepfTMVAVKMLKEEasADMQADFQREAALMAEFDHPNIVKLLGVCAVg 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 342 EPIYIVTEFMSKGSLLDFLKEG------------------DGKYLKL--PQLVDMAAQIADGMAYIERMNYIHRDLRAAN 401
Cdd:cd05050    81 KPMCLLFEYMAYGDLNEFLRHRspraqcslshstssarkcGLNPLPLscTEQLCIAKQVAAGMAYLSERKFVHRDLATRN 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 402 ILVGENLVCKIADFGLARLIED------------------------NEYTARQ---------------------GMVNRE 436
Cdd:cd05050   161 CLVGENMVVKIADFGLSRNIYSadyykasendaipirwmppesifyNRYTTESdvwaygvvlweifsygmqpyyGMAHEE 240
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*..
gi 1370473802 437 VLEQVERGYRMPCPQGCPESLHELMNLCWKKDPDERPTFEYIQSFLE 483
Cdd:cd05050   241 VIYYVRDGNVLSCPDNCPLELYNLMRLCWSKLPSDRPSFASINRILQ 287
PTKc_EphR_A10 cd05064
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the ...
271-482 3.80e-40

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: 145.84  E-value: 3.80e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 271 EIPRESLRLEVKLGQGCFGEVWMGTWNGTTK----VAIKTLKPGTMMPE--AFLQEAQIMKKLRHDKLVPLYAVVSE-EP 343
Cdd:cd05064     1 ELDNKSIKIERILGTGRFGELCRGCLKLPSKrelpVAIHTLRAGCSDKQrrGFLAEALTLGQFDHSNIVRLEGVITRgNT 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 344 IYIVTEFMSKGSLLDFLKEGDGKyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGlaRLIED 423
Cdd:cd05064    81 MMIVTEYMSNGALDSFLRKHEGQ-LVAGQLMGMLPGLASGMKYLSEMGYVHKGLAAHKVLVNSDLVCKISGFR--RLQED 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 424 NE---YTARQG-------------------------------------------MVNREVLEQVERGYRMPCPQGCPESL 457
Cdd:cd05064   158 KSeaiYTTMSGkspvlwaapeaiqyhhfssasdvwsfgivmwevmsygerpywdMSGQDVIKAVEDGFRLPAPRNCPNLL 237
                         250       260
                  ....*....|....*....|....*
gi 1370473802 458 HELMNLCWKKDPDERPTFEYIQSFL 482
Cdd:cd05064   238 HQLMLDCWQKERGERPRFSQIHSIL 262
PTKc_PDGFR cd05055
Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; ...
269-484 5.08e-40

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: 146.48  E-value: 5.08e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 269 AWEIPRESLRLEVKLGQGCFGEVWMGTWNG------TTKVAIKTLKPGTMMPE--AFLQEAQIMKKL-RHDKLVPLYAVV 339
Cdd:cd05055    29 KWEFPRNNLSFGKTLGAGAFGKVVEATAYGlsksdaVMKVAVKMLKPTAHSSEreALMSELKIMSHLgNHENIVNLLGAC 108
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 340 SEE-PIYIVTEFMSKGSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLA 418
Cdd:cd05055   109 TIGgPILVITEYCCYGDLLNFLRRKRESFLTLEDLLSFSYQVAKGMAFLASKNCIHRDLAARNVLLTHGKIVKICDFGLA 188
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 419 RLI-EDNEYTAR--------------------------------------------QGM-VNREVLEQVERGYRMPCPQG 452
Cdd:cd05055   189 RDImNDSNYVVKgnarlpvkwmapesifncvytfesdvwsygillweifslgsnpyPGMpVDSKFYKLIKEGYRMAQPEH 268
                         250       260       270
                  ....*....|....*....|....*....|..
gi 1370473802 453 CPESLHELMNLCWKKDPDERPTFEYIQSFLED 484
Cdd:cd05055   269 APAEIYDIMKTCWDADPLKRPTFKQIVQLIGK 300
SH2_Src_Blk cd10371
Src homology 2 (SH2) domain found in B lymphoid kinase (Blk); Blk is a member of the Src ...
154-252 1.17e-39

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: 139.00  E-value: 1.17e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 154 QAEEWYFGKMGRKDAERLLLNPGNQRGIFLVRESETTKGAYSLSIRDWdEIRGDNVKHYKIRKLDNGGYYITTRAQFDTL 233
Cdd:cd10371     1 EVEKWFFRTISRKDAERQLLAPMNKAGSFLIRESESNKGAFSLSVKDV-TTQGEVVKHYKIRSLDNGGYYISPRITFPTL 79
                          90
                  ....*....|....*....
gi 1370473802 234 QKLVKHYTEHADGLCHKLT 252
Cdd:cd10371    80 QALVQHYSKKGDGLCQKLT 98
PTKc_EGFR_like cd05057
Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs ...
272-481 2.39e-39

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: 144.09  E-value: 2.39e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 272 IPRES-LRLEVKLGQGCFGEVWMGTW-----NGTTKVAIKTLKPGT--MMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEP 343
Cdd:cd05057     3 IVKETeLEKGKVLGSGAFGTVYKGVWipegeKVKIPVAIKVLREETgpKANEEILDEAYVMASVDHPHLVRLLGICLSSQ 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 344 IYIVTEFMSKGSLLDFLKEGDGKyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILV-GENLVcKIADFGLARLIE 422
Cdd:cd05057    83 VQLITQLMPLGCLLDYVRNHRDN-IGSQLLLNWCVQIAKGMSYLEEKRLVHRDLAARNVLVkTPNHV-KITDFGLAKLLD 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 423 --DNEYTARQGMV-------------------------------------------NREVLEQVERGYRMPCPQGCPESL 457
Cdd:cd05057   161 vdEKEYHAEGGKVpikwmalesiqyriythksdvwsygvtvwelmtfgakpyegipAVEIPDLLEKGERLPQPPICTIDV 240
                         250       260
                  ....*....|....*....|....*
gi 1370473802 458 HELMNLCWKKDPDERPTF-EYIQSF 481
Cdd:cd05057   241 YMVLVKCWMIDAESRPTFkELANEF 265
PTKc_FGFR4 cd05099
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs ...
270-493 5.05e-39

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: 143.95  E-value: 5.05e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 270 WEIPRESLRLEVKLGQGCFGEVWMGTWNGTTK--------VAIKTLKPGTMMPEA--FLQEAQIMKKL-RHDKLVPLYAV 338
Cdd:cd05099     7 WEFPRDRLVLGKPLGEGCFGQVVRAEAYGIDKsrpdqtvtVAVKMLKDNATDKDLadLISEMELMKLIgKHKNIINLLGV 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 339 VSEE-PIYIVTEFMSKGSLLDFLK--------------EGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANIL 403
Cdd:cd05099    87 CTQEgPLYVIVEYAAKGNLREFLRarrppgpdytfditKVPEEQLSFKDLVSCAYQVARGMEYLESRRCIHRDLAARNVL 166
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 404 VGENLVCKIADFGLARLIEDNEY-------------TARQGMVNR--------------------------------EVL 438
Cdd:cd05099   167 VTEDNVMKIADFGLARGVHDIDYykktsngrlpvkwMAPEALFDRvythqsdvwsfgilmweiftlggspypgipveELF 246
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1370473802 439 EQVERGYRMPCPQGCPESLHELMNLCWKKDPDERPTFEYIQSFLEDYFTATEPQY 493
Cdd:cd05099   247 KLLREGHRMDKPSNCTHELYMLMRECWHAVPTQRPTFKQLVEALDKVLAAVSEEY 301
SH2_Src_Src42 cd10370
Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the ...
154-251 5.34e-39

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: 136.87  E-value: 5.34e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 154 QAEEWYFGKMGRKDAERLLLNPGNQRGIFLVRESETTKGAYSLSIRDwdeirGDNVKHYKIRKLDNGGYYITTRAQFDTL 233
Cdd:cd10370     1 EAEPWYFGKIKRIEAEKKLLLPENEHGAFLIRDSESRHNDYSLSVRD-----GDTVKHYRIRQLDEGGFFIARRTTFRTL 75
                          90
                  ....*....|....*...
gi 1370473802 234 QKLVKHYTEHADGLCHKL 251
Cdd:cd10370    76 QELVEHYSKDSDGLCVNL 93
SH3_Yes cd12007
Src homology 3 domain of Yes Protein Tyrosine Kinase; Yes (or c-Yes) is a member of the Src ...
94-151 6.19e-39

Src homology 3 domain of Yes Protein Tyrosine Kinase; 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 SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. 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: 212940 [Multi-domain]  Cd Length: 58  Bit Score: 135.55  E-value: 6.19e-39
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1370473802  94 TIFVALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARSIATGKNGYIPSNYVAPAD 151
Cdd:cd12007     1 TIFVALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARSIATGKNGYIPSNYVAPAD 58
STKc_PknB_like cd14014
Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs ...
278-433 3.31e-38

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: 140.41  E-value: 3.31e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 278 RLEVKLGQGCFGEVWMGTWNGT-TKVAIKTLKPGTMMPEA----FLQEAQIMKKLRHDKLVPLYAVVSEE-PIYIVTEFM 351
Cdd:cd14014     3 RLVRLLGRGGMGEVYRARDTLLgRPVAIKVLRPELAEDEEfrerFLREARALARLSHPNIVRVYDVGEDDgRPYIVMEYV 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 352 SKGSLLDFLKEGdgKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYTaRQG 431
Cdd:cd14014    83 EGGSLADLLRER--GPLPPREALRILAQIADALAAAHRAGIVHRDIKPANILLTEDGRVKLTDFGIARALGDSGLT-QTG 159

                  ..
gi 1370473802 432 MV 433
Cdd:cd14014   160 SV 161
PTKc_Trk cd05049
Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze ...
271-482 1.01e-37

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: 139.52  E-value: 1.01e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 271 EIPRESLRLEVKLGQGCFGEVWMGTW------NGTTKVAIKTLKPGTM--MPEAFLQEAQIMKKLRHDKLVPLYAVVSE- 341
Cdd:cd05049     1 HIKRDTIVLKRELGEGAFGKVFLGECynlepeQDKMLVAVKTLKDASSpdARKDFEREAELLTNLQHENIVKFYGVCTEg 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 342 EPIYIVTEFMSKGSLLDFLK------------EGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLV 409
Cdd:cd05049    81 DPLLMVFEYMEHGDLNKFLRshgpdaaflaseDSAPGELTLSQLLHIAVQIASGMVYLASQHFVHRDLATRNCLVGTNLV 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 410 CKIADFGLARLIEDNEYT------------------------------------------ARQ---GMVNREVLEQVERG 444
Cdd:cd05049   161 VKIGDFGMSRDIYSTDYYrvgghtmlpirwmppesilyrkfttesdvwsfgvvlweiftyGKQpwfQLSNTEVIECITQG 240
                         250       260       270
                  ....*....|....*....|....*....|....*...
gi 1370473802 445 YRMPCPQGCPESLHELMNLCWKKDPDERPTFEYIQSFL 482
Cdd:cd05049   241 RLLQRPRTCPSEVYAVMLGCWKREPQQRLNIKDIHKRL 278
PTKc_IGF-1R cd05062
Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs ...
270-484 2.97e-36

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: 135.55  E-value: 2.97e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 270 WEIPRESLRLEVKLGQGCFGEVWMGTWNGT------TKVAIKTLKPGTMMPE--AFLQEAQIMKKLRHDKLVPLYAVVSE 341
Cdd:cd05062     1 WEVAREKITMSRELGQGSFGMVYEGIAKGVvkdepeTRVAIKTVNEAASMREriEFLNEASVMKEFNCHHVVRLLGVVSQ 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 342 -EPIYIVTEFMSKGSLLDFL-----KEGDGKYLKLPQL---VDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKI 412
Cdd:cd05062    81 gQPTLVIMELMTRGDLKSYLrslrpEMENNPVQAPPSLkkmIQMAGEIADGMAYLNANKFVHRDLAARNCMVAEDFTVKI 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 413 ADFGLARLIEDNEYTAR---------------------------------------------QGMVNREVLEQVERGYRM 447
Cdd:cd05062   161 GDFGMTRDIYETDYYRKggkgllpvrwmspeslkdgvfttysdvwsfgvvlweiatlaeqpyQGMSNEQVLRFVMEGGLL 240
                         250       260       270
                  ....*....|....*....|....*....|....*..
gi 1370473802 448 PCPQGCPESLHELMNLCWKKDPDERPTFEYIQSFLED 484
Cdd:cd05062   241 DKPDNCPDMLFELMRMCWQYNPKMRPSFLEIISSIKE 277
PTKc_RET cd05045
Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs ...
276-483 1.17e-35

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: 134.32  E-value: 1.17e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 276 SLRLEVKLGQGCFGEVWMGT------WNGTTKVAIKTLKPGTMMPE--AFLQEAQIMKKLRHDKLVPLY-AVVSEEPIYI 346
Cdd:cd05045     1 NLVLGKTLGEGEFGKVVKATafrlkgRAGYTTVAVKMLKENASSSElrDLLSEFNLLKQVNHPHVIKLYgACSQDGPLLL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 347 VTEFMSKGSLLDFLKEG----------------------DGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILV 404
Cdd:cd05045    81 IVEYAKYGSLRSFLRESrkvgpsylgsdgnrnssyldnpDERALTMGDLISFAWQISRGMQYLAEMKLVHRDLAARNVLV 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 405 GENLVCKIADFGLAR-LIEDNEYTARQ--------------------------------------------GMVNREVLE 439
Cdd:cd05045   161 AEGRKMKISDFGLSRdVYEEDSYVKRSkgripvkwmaieslfdhiyttqsdvwsfgvllweivtlggnpypGIAPERLFN 240
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 1370473802 440 QVERGYRMPCPQGCPESLHELMNLCWKKDPDERPTFEYIQSFLE 483
Cdd:cd05045   241 LLKTGYRMERPENCSEEMYNLMLTCWKQEPDKRPTFADISKELE 284
SH2_SLAP cd10344
Src homology 2 domain found in Src-like adaptor proteins; SLAP belongs to the subfamily of ...
143-248 4.61e-35

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: 126.45  E-value: 4.61e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 143 PSNYVAPAdsiqAEEWYFGKMGRKDAERLLLNPGNQRGIFLVRESETTKGAYSLSIRDWDEIRGDNVKHYKIRKLDNGGY 222
Cdd:cd10344     1 PSNYVAKV----YHGWLFEGLSREKAEELLMLPGNQVGSFLIRESETRRGCYSLSVRHRGSQSRDSVKHYRIFRLDNGWF 76
                          90       100
                  ....*....|....*....|....*.
gi 1370473802 223 YITTRAQFDTLQKLVKHYTEHADGLC 248
Cdd:cd10344    77 YISPRLTFQCLEDMVNHYSESADGLC 102
SH2_Src_Frk cd10369
Src homology 2 (SH2) domain found in the Fyn-related kinase (Frk); Frk is a member of the Src ...
154-251 1.25e-34

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: 124.99  E-value: 1.25e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 154 QAEEWYFGKMGRKDAERLLLNPGNQRGIFLVRESETTKGAYSLSIRDwdeirGDNVKHYKIRKLDNGGYYITTRAQFDTL 233
Cdd:cd10369     1 QAEPWFFGAIKRADAEKQLLYSENQTGAFLIRESESQKGEFSLSVLD-----GGVVKHYRIRRLDEGGFFLTRRKTFSTL 75
                          90
                  ....*....|....*...
gi 1370473802 234 QKLVKHYTEHADGLCHKL 251
Cdd:cd10369    76 NEFVNYYTTTSDGLCVKL 93
PTKc_DDR_like cd05097
Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the ...
271-482 1.74e-34

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: 131.25  E-value: 1.74e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 271 EIPRESLRLEVKLGQGCFGEVWMGTWNGTTK---------------VAIKTLKP--GTMMPEAFLQEAQIMKKLRHDKLV 333
Cdd:cd05097     1 EFPRQQLRLKEKLGEGQFGEVHLCEAEGLAEflgegapefdgqpvlVAVKMLRAdvTKTARNDFLKEIKIMSRLKNPNII 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 334 PLYAV-VSEEPIYIVTEFMSKGSLLDFL--KEGDGKYLK---LP-----QLVDMAAQIADGMAYIERMNYIHRDLRAANI 402
Cdd:cd05097    81 RLLGVcVSDDPLCMITEYMENGDLNQFLsqREIESTFTHannIPsvsiaNLLYMAVQIASGMKYLASLNFVHRDLATRNC 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 403 LVGENLVCKIADFGLARLIEDNEYTARQG----------------------------------------------MVNRE 436
Cdd:cd05097   161 LVGNHYTIKIADFGMSRNLYSGDYYRIQGravlpirwmawesillgkfttasdvwafgvtlwemftlckeqpyslLSDEQ 240
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1370473802 437 VLEQVERGYR-------MPCPQGCPESLHELMNLCWKKDPDERPTFEYIQSFL 482
Cdd:cd05097   241 VIENTGEFFRnqgrqiyLSQTPLCPSPVFKLMMRCWSRDIKDRPTFNKIHHFL 293
PTKc_TrkA cd05092
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze ...
272-483 1.93e-34

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: 130.86  E-value: 1.93e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 272 IPRESLRLEVKLGQGCFGEVWMGTW------NGTTKVAIKTLKPGTMMP-EAFLQEAQIMKKLRHDKLVPLYAVVSE-EP 343
Cdd:cd05092     2 IKRRDIVLKWELGEGAFGKVFLAEChnllpeQDKMLVAVKALKEATESArQDFQREAELLTVLQHQHIVRFYGVCTEgEP 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 344 IYIVTEFMSKGSLLDFLK----------EGDGK---YLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVC 410
Cdd:cd05092    82 LIMVFEYMRHGDLNRFLRshgpdakildGGEGQapgQLTLGQMLQIASQIASGMVYLASLHFVHRDLATRNCLVGQGLVV 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 411 KIADFGLARLIEDNEYTARQG---------------------------------------------MVNREVLEQVERGY 445
Cdd:cd05092   162 KIGDFGMSRDIYSTDYYRVGGrtmlpirwmppesilyrkfttesdiwsfgvvlweiftygkqpwyqLSNTEAIECITQGR 241
                         250       260       270
                  ....*....|....*....|....*....|....*...
gi 1370473802 446 RMPCPQGCPESLHELMNLCWKKDPDERPTFEYIQSFLE 483
Cdd:cd05092   242 ELERPRTCPPEVYAIMQGCWQREPQQRHSIKDIHSRLQ 279
PTKc_DDR2 cd05095
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2; PTKs catalyze ...
271-484 2.52e-34

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: 130.88  E-value: 2.52e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 271 EIPRESLRLEVKLGQGCFGEVWMGTWNGTTK-----------------VAIKTLKP--GTMMPEAFLQEAQIMKKLRHDK 331
Cdd:cd05095     1 EFPRKLLTFKEKLGEGQFGEVHLCEAEGMEKfmdkdfalevsenqpvlVAVKMLRAdaNKNARNDFLKEIKIMSRLKDPN 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 332 LVPLYAV-VSEEPIYIVTEFMSKGSLLDFL--KEGDGKYLKLP--------QLVDMAAQIADGMAYIERMNYIHRDLRAA 400
Cdd:cd05095    81 IIRLLAVcITDDPLCMITEYMENGDLNQFLsrQQPEGQLALPSnaltvsysDLRFMAAQIASGMKYLSSLNFVHRDLATR 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 401 NILVGENLVCKIADFGLARLIEDNEYTARQG----------------------------------------------MVN 434
Cdd:cd05095   161 NCLVGKNYTIKIADFGMSRNLYSGDYYRIQGravlpirwmswesillgkfttasdvwafgvtlwetltfcreqpysqLSD 240
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1370473802 435 REVLEQVERGYR-------MPCPQGCPESLHELMNLCWKKDPDERPTFEYIQSFLED 484
Cdd:cd05095   241 EQVIENTGEFFRdqgrqtyLPQPALCPDSVYKLMLSCWRRDTKDRPSFQEIHTLLQE 297
SH2 pfam00017
SH2 domain;
158-240 6.48e-34

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 122.32  E-value: 6.48e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 158 WYFGKMGRKDAERLLLNpGNQRGIFLVRESETTKGAYSLSIRDWDeirgdNVKHYKIRKLDNGGYYITTRAQFDTLQKLV 237
Cdd:pfam00017   1 WYHGKISRQEAERLLLN-GKPDGTFLVRESESTPGGYTLSVRDDG-----KVKHYKIQSTDNGGYYISGGVKFSSLAELV 74

                  ...
gi 1370473802 238 KHY 240
Cdd:pfam00017  75 EHY 77
STKc_IRAK cd14066
Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases ...
283-433 1.59e-33

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: 127.77  E-value: 1.59e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKVAIKTLKPGTMM--PEAFLQEAQIMKKLRHDKLVPLYAVVSE--EPIyIVTEFMSKGSLLD 358
Cdd:cd14066     1 IGSGGFGTVYKGVLENGTVVAVKRLNEMNCAasKKEFLTELEMLGRLRHPNLVRLLGYCLEsdEKL-LVYEYMPNGSLED 79
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1370473802 359 FLKEGDGKY-LKLPQLVDMAAQIADGMAYI---ERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYTARQGMV 433
Cdd:cd14066    80 RLHCHKGSPpLPWPQRLKIAKGIARGLEYLheeCPPPIIHGDIKSSNILLDEDFEPKLTDFGLARLIPPSESVSKTSAV 158
PTKc_Syk cd05116
Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the ...
282-486 2.18e-33

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: 127.00  E-value: 2.18e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWN---GTTKVAIKTLKPGTMMP---EAFLQEAQIMKKLRHDKLVPLYAVVSEEPIYIVTEFMSKGS 355
Cdd:cd05116     2 ELGSGNFGTVKKGYYQmkkVVKTVAVKILKNEANDPalkDELLREANVMQQLDNPYIVRMIGICEAESWMLVMEMAELGP 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 356 LLDFLKEGdgKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLI--EDNEYTAR---- 429
Cdd:cd05116    82 LNKFLQKN--RHVTEKNITELVHQVSMGMKYLEESNFVHRDLAARNVLLVTQHYAKISDFGLSKALraDENYYKAQthgk 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 430 ----------------------------------------QGMVNREVLEQVERGYRMPCPQGCPESLHELMNLCWKKDP 469
Cdd:cd05116   160 wpvkwyapecmnyykfssksdvwsfgvlmweafsygqkpyKGMKGNEVTQMIEKGERMECPAGCPPEMYDLMKLCWTYDV 239
                         250
                  ....*....|....*..
gi 1370473802 470 DERPTFEYIQSFLEDYF 486
Cdd:cd05116   240 DERPGFAAVELRLRNYY 256
STKc_Raf cd14062
Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) ...
283-483 8.12e-33

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: 125.58  E-value: 8.12e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTtkVAIKTLK---PGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEPIYIVTEFMSKGSLLDF 359
Cdd:cd14062     1 IGSGSFGTVYKGRWHGD--VAVKKLNvtdPTPSQLQAFKNEVAVLRKTRHVNILLFMGYMTKPQLAIVTQWCEGSSLYKH 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 360 LKEGDGKYlKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLA--------------------- 418
Cdd:cd14062    79 LHVLETKF-EMLQLIDIARQTAQGMDYLHAKNIIHRDLKSNNIFLHEDLTVKIGDFGLAtvktrwsgsqqfeqptgsilw 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 419 ------RLIEDNEYTARQ-----GMV---------------NRE-VLEQVERGYRMP----CPQGCPESLHELMNLCWKK 467
Cdd:cd14062   158 mapeviRMQDENPYSFQSdvyafGIVlyelltgqlpyshinNRDqILFMVGRGYLRPdlskVRSDTPKALRRLMEDCIKF 237
                         250
                  ....*....|....*.
gi 1370473802 468 DPDERPTFEYIQSFLE 483
Cdd:cd14062   238 QRDERPLFPQILASLE 253
STKc_MAPKKK cd06606
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase ...
283-474 8.19e-33

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: 125.33  E-value: 8.19e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTK-VAIKTLKPGTMMPE---AFLQEAQIMKKLRHDKLVP-LYAVVSEEPIYIVTEFMSKGSLL 357
Cdd:cd06606     8 LGKGSFGSVYLALNLDTGElMAVKEVELSGDSEEeleALEREIRILSSLKHPNIVRyLGTERTENTLNIFLEYVPGGSLA 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 358 DFLKegdgKYLKLPQLV--DMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYTARQGMVnR 435
Cdd:cd06606    88 SLLK----KFGKLPEPVvrKYTRQILEGLEYLHSNGIVHRDIKGANILVDSDGVVKLADFGCAKRLAEIATGEGTKSL-R 162
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 436 --------EVLEQVERGYR------------M---------------------------PCPQGCPESLHELMNLCWKKD 468
Cdd:cd06606   163 gtpywmapEVIRGEGYGRAadiwslgctvieMatgkppwselgnpvaalfkigssgeppPIPEHLSEEAKDFLRKCLQRD 242

                  ....*.
gi 1370473802 469 PDERPT 474
Cdd:cd06606   243 PKKRPT 248
PTKc_DDR1 cd05096
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze ...
271-482 9.74e-33

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: 126.59  E-value: 9.74e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 271 EIPRESLRLEVKLGQGCFGEVWMGTWNGTTK-----------------VAIKTLKPGTM--MPEAFLQEAQIMKKLRHDK 331
Cdd:cd05096     1 KFPRGHLLFKEKLGEGQFGEVHLCEVVNPQDlptlqfpfnvrkgrpllVAVKILRPDANknARNDFLKEVKILSRLKDPN 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 332 LVPLYAV-VSEEPIYIVTEFMSKGSLLDFL-------KEGDGKY----------LKLPQLVDMAAQIADGMAYIERMNYI 393
Cdd:cd05096    81 IIRLLGVcVDEDPLCMITEYMENGDLNQFLsshhlddKEENGNDavppahclpaISYSSLLHVALQIASGMKYLSSLNFV 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 394 HRDLRAANILVGENLVCKIADFGLARLIEDNEYTARQG------------------------------------MVNRE- 436
Cdd:cd05096   161 HRDLATRNCLVGENLTIKIADFGMSRNLYAGDYYRIQGravlpirwmawecilmgkfttasdvwafgvtlweilMLCKEq 240
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370473802 437 ---------VLEQVERGYR-------MPCPQGCPESLHELMNLCWKKDPDERPTFEYIQSFL 482
Cdd:cd05096   241 pygeltdeqVIENAGEFFRdqgrqvyLFRPPPCPQGLYELMLQCWSRDCRERPSFSDIHAFL 302
PTKc_Zap-70 cd05115
Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs ...
274-486 2.21e-32

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: 124.67  E-value: 2.21e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 274 RESLRL-EVKLGQGCFGEVWMGTWNGTTK---VAIKTLKPGT--MMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEPIYIV 347
Cdd:cd05115     2 RDNLLIdEVELGSGNFGCVKKGVYKMRKKqidVAIKVLKQGNekAVRDEMMREAQIMHQLDNPYIVRMIGVCEAEALMLV 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 348 TEFMSKGSLLDFLKeGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLI--EDNE 425
Cdd:cd05115    82 MEMASGGPLNKFLS-GKKDEITVSNVVELMHQVSMGMKYLEEKNFVHRDLAARNVLLVNQHYAKISDFGLSKALgaDDSY 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 426 YTARQG--------------------------------------------MVNREVLEQVERGYRMPCPQGCPESLHELM 461
Cdd:cd05115   161 YKARSAgkwplkwyapecinfrkfssrsdvwsygvtmweafsygqkpykkMKGPEVMSFIEQGKRMDCPAECPPEMYALM 240
                         250       260
                  ....*....|....*....|....*
gi 1370473802 462 NLCWKKDPDERPTFEYIQSFLEDYF 486
Cdd:cd05115   241 SDCWIYKWEDRPNFLTVEQRMRTYY 265
PTKc_Ror1 cd05090
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
271-485 2.27e-32

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: 125.12  E-value: 2.27e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 271 EIPRESLRLEVKLGQGCFGEVWMG-----TWNGTTKVAIKTLK--PGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEE- 342
Cdd:cd05090     1 ELPLSAVRFMEELGECAFGKIYKGhlylpGMDHAQLVAIKTLKdyNNPQQWNEFQQEASLMTELHHPNIVCLLGVVTQEq 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 343 PIYIVTEFMSKGSLLDFL------------KEGDGKY---LKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGEN 407
Cdd:cd05090    81 PVCMLFEFMNQGDLHEFLimrsphsdvgcsSDEDGTVkssLDHGDFLHIAIQIAAGMEYLSSHFFVHKDLAARNILVGEQ 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 408 LVCKIADFGLARLIEDNEYTARQ---------------------------------------------GMVNREVLEQVE 442
Cdd:cd05090   161 LHVKISDLGLSREIYSSDYYRVQnksllpirwmppeaimygkfssdsdiwsfgvvlweifsfglqpyyGFSNQEVIEMVR 240
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|...
gi 1370473802 443 RGYRMPCPQGCPESLHELMNLCWKKDPDERPTFEYIQSFLEDY 485
Cdd:cd05090   241 KRQLLPCSEDCPPRMYSLMTECWQEIPSRRPRFKDIHARLRSW 283
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
278-433 3.21e-32

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 128.98  E-value: 3.21e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 278 RLEVKLGQGCFGEVWMGTWNGT-TKVAIKTLKPG-TMMPEA---FLQEAQIMKKLRHDKLVPLYAVVSEEPI-YIVTEFM 351
Cdd:COG0515    10 RILRLLGRGGMGVVYLARDLRLgRPVALKVLRPElAADPEArerFRREARALARLNHPNIVRVYDVGEEDGRpYLVMEYV 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 352 SKGSLLDFLKEGdgKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYTaRQG 431
Cdd:COG0515    90 EGESLADLLRRR--GPLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDGRVKLIDFGIARALGGATLT-QTG 166

                  ..
gi 1370473802 432 MV 433
Cdd:COG0515   167 TV 168
PTKc_FGFR1 cd05098
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs ...
270-492 1.08e-31

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: 123.58  E-value: 1.08e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 270 WEIPRESLRLEVKLGQGCFGEVWMGTW--------NGTTKVAIKTLKPGTMMPEA--FLQEAQIMKKL-RHDKLVPLYAV 338
Cdd:cd05098     8 WELPRDRLVLGKPLGEGCFGQVVLAEAigldkdkpNRVTKVAVKMLKSDATEKDLsdLISEMEMMKMIgKHKNIINLLGA 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 339 VSEE-PIYIVTEFMSKGSLLDFLK--------------EGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANIL 403
Cdd:cd05098    88 CTQDgPLYVIVEYASKGNLREYLQarrppgmeycynpsHNPEEQLSSKDLVSCAYQVARGMEYLASKKCIHRDLAARNVL 167
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 404 VGENLVCKIADFGLARLIEDNEY-------------TARQGMVNR--------------------------------EVL 438
Cdd:cd05098   168 VTEDNVMKIADFGLARDIHHIDYykkttngrlpvkwMAPEALFDRiythqsdvwsfgvllweiftlggspypgvpveELF 247
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1370473802 439 EQVERGYRMPCPQGCPESLHELMNLCWKKDPDERPTFEYIQSFLEDYFTATEPQ 492
Cdd:cd05098   248 KLLKEGHRMDKPSNCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRIVALTSNQ 301
PTK_CCK4 cd05046
Pseudokinase domain of the Protein Tyrosine Kinase, Colon Carcinoma Kinase 4; CCK4, also ...
272-484 2.01e-31

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: 122.19  E-value: 2.01e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 272 IPRESLRLEVKLGQGCFGEVWMGTWNGT------TKVAIKTL--KPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSE-E 342
Cdd:cd05046     2 FPRSNLQEITTLGRGEFGEVFLAKAKGIeeeggeTLVLVKALqkTKDENLQSEFRRELDMFRKLSHKNVVRLLGLCREaE 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 343 PIYIVTEFMSKGSLLDFL---KEGDGKY----LKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADF 415
Cdd:cd05046    82 PHYMILEYTDLGDLKQFLratKSKDEKLkpppLSTKQKVALCTQIALGMDHLSNARFVHRDLAARNCLVSSQREVKVSLL 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 416 GLAR-----------------------LIEDNEYTAR---------------------QGMVNREVLEQVERG-YRMPCP 450
Cdd:cd05046   162 SLSKdvynseyyklrnaliplrwlapeAVQEDDFSTKsdvwsfgvlmwevftqgelpfYGLSDEEVLNRLQAGkLELPVP 241
                         250       260       270
                  ....*....|....*....|....*....|....
gi 1370473802 451 QGCPESLHELMNLCWKKDPDERPTFEYIQSFLED 484
Cdd:cd05046   242 EGCPSRLYKLMTRCWAVNPKDRPSFSELVSALGE 275
SH3_Fyn_Yrk cd12006
Src homology 3 domain of Fyn and Yrk Protein Tyrosine Kinases; Fyn and Yrk (Yes-related kinase) ...
94-149 3.64e-31

Src homology 3 domain of Fyn and Yrk Protein Tyrosine Kinases; Fyn and Yrk (Yes-related kinase) 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. 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 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 SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. 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: 212939 [Multi-domain]  Cd Length: 56  Bit Score: 114.38  E-value: 3.64e-31
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1370473802  94 TIFVALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARSIATGKNGYIPSNYVAP 149
Cdd:cd12006     1 TLFVALYDYEARTEDDLSFHKGEKFQILNSSEGDWWEARSLTTGETGYIPSNYVAP 56
PTK_Ryk cd05043
Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase ...
272-488 6.41e-31

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: 121.02  E-value: 6.41e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 272 IPRESLRLEVKLGQGCFGEVWMGTWN----GTTKVAIKTLKPG------TMMpeafLQEAQIMKKLRHDKLVPLYAVVSE 341
Cdd:cd05043     3 VSRERVTLSDLLQEGTFGRIFHGILRdekgKEEEVLVKTVKDHaseiqvTML----LQESSLLYGLSHQNLLPILHVCIE 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 342 --EPIYIVTEFMSKGSLLDFLK------EGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIA 413
Cdd:cd05043    79 dgEKPMVLYPYMNWGNLKLFLQqcrlseANNPQALSTQQLVHMALQIACGMSYLHRRGVIHKDIAARNCVIDDELQVKIT 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 414 DFGLAR--------LIEDNEY-----TARQGMVNR--------------------------------EVLEQVERGYRMP 448
Cdd:cd05043   159 DNALSRdlfpmdyhCLGDNENrpikwMSLESLVNKeyssasdvwsfgvllwelmtlgqtpyveidpfEMAAYLKDGYRLA 238
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 1370473802 449 CPQGCPESLHELMNLCWKKDPDERPTFEYIQSFLEDYFTA 488
Cdd:cd05043   239 QPINCPDELFAVMACCWALDPEERPSFQQLVQCLTDFHAQ 278
STKc_MLTK cd14060
Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated ...
284-483 1.69e-30

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: 118.91  E-value: 1.69e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 284 GQGCFGEVWMGTWNGTTK-VAIKTLKpgtmmpeAFLQEAQIMKKLRHDKLVPLYAVVSEEPIY-IVTEFMSKGSLLDFLK 361
Cdd:cd14060     2 GGGSFGSVYRAIWVSQDKeVAVKKLL-------KIEKEAEILSVLSHRNIIQFYGAILEAPNYgIVTEYASYGSLFDYLN 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 362 EGDGKYLKLPQLVDMAAQIADGMAYIER---MNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYTARQG------- 431
Cdd:cd14060    75 SNESEEMDMDQIMTWATDIAKGMHYLHMeapVKVIHRDLKSRNVVIAADGVLKICDFGASRFHSHTTHMSLVGtfpwmap 154
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 432 -----------------------MVNREV----LEQ-------VERGYRMPCPQGCPESLHELMNLCWKKDPDERPTFEY 477
Cdd:cd14060   155 eviqslpvsetcdtysygvvlweMLTREVpfkgLEGlqvawlvVEKNERPTIPSSCPRSFAELMRRCWEADVKERPSFKQ 234

                  ....*.
gi 1370473802 478 IQSFLE 483
Cdd:cd14060   235 IIGILE 240
PTKc_Tyk2_rpt2 cd05080
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze ...
277-485 1.76e-30

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: 120.00  E-value: 1.76e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 277 LRLEVKLGQGCFGEVWMGTWNGTTK-----VAIKTLKP--GTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSE---EPIYI 346
Cdd:cd05080     6 LKKIRDLGEGHFGKVSLYCYDPTNDgtgemVAVKALKAdcGPQHRSGWKQEIDILKTLYHENIVKYKGCCSEqggKSLQL 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 347 VTEFMSKGSLLDFLKEGDgkyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEY 426
Cdd:cd05080    86 IMEYVPLGSLRDYLPKHS---IGLAQLLLFAQQICEGMAYLHSQHYIHRDLAARNVLLDNDRLVKIGDFGLAKAVPEGHE 162
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 427 TAR-----------------------------------------------------------QGMVNR-EVLEQVERGYR 446
Cdd:cd05080   163 YYRvredgdspvfwyapeclkeykfyyasdvwsfgvtlyellthcdssqspptkflemigiaQGQMTVvRLIELLERGER 242
                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 1370473802 447 MPCPQGCPESLHELMNLCWKKDPDERPTFEYIQSFLEDY 485
Cdd:cd05080   243 LPCPDKCPQEVYHLMKNCWETEASFRPTFENLIPILKTV 281
PTKc_FGFR2 cd05101
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2; PTKs ...
270-489 4.96e-30

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: 119.35  E-value: 4.96e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 270 WEIPRESLRLEVKLGQGCFGEVWMGTWNGTTK--------VAIKTLKPGTMMPEA--FLQEAQIMKKL-RHDKLVPLYAV 338
Cdd:cd05101    19 WEFPRDKLTLGKPLGEGCFGQVVMAEAVGIDKdkpkeavtVAVKMLKDDATEKDLsdLVSEMEMMKMIgKHKNIINLLGA 98
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 339 VSEE-PIYIVTEFMSKGSLLDFLK-----EGDGKY---------LKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANIL 403
Cdd:cd05101    99 CTQDgPLYVIVEYASKGNLREYLRarrppGMEYSYdinrvpeeqMTFKDLVSCTYQLARGMEYLASQKCIHRDLAARNVL 178
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 404 VGENLVCKIADFGLARLIEDNEY-------------TARQGMVNR--------------------------------EVL 438
Cdd:cd05101   179 VTENNVMKIADFGLARDINNIDYykkttngrlpvkwMAPEALFDRvythqsdvwsfgvlmweiftlggspypgipveELF 258
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1370473802 439 EQVERGYRMPCPQGCPESLHELMNLCWKKDPDERPTFEYIQSFLEDYFTAT 489
Cdd:cd05101   259 KLLKEGHRMDKPANCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRILTLT 309
STKc_TAK1 cd14058
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated ...
283-484 6.10e-30

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: 117.54  E-value: 6.10e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTkVAIKTLKPGTMMpEAFLQEAQIMKKLRHDKLVPLY-AVVSEEPIYIVTEFMSKGSLLDFLK 361
Cdd:cd14058     1 VGRGSFGVVCKARWRNQI-VAVKIIESESEK-KAFEVEVRQLSRVDHPNIIKLYgACSNQKPVCLVMEYAEGGSLYNVLH 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 362 EGDGK-YLKLPQLVDMAAQIADGMAYIERMN---YIHRDLRAANILV---GENLvcKIADFGLA---------------- 418
Cdd:cd14058    79 GKEPKpIYTAAHAMSWALQCAKGVAYLHSMKpkaLIHRDLKPPNLLLtngGTVL--KICDFGTAcdisthmtnnkgsaaw 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 419 ---RLIEDNEYTAR-----QGMVNREVLEQ-----------------VERGYRMPCPQGCPESLHELMNLCWKKDPDERP 473
Cdd:cd14058   157 mapEVFEGSKYSEKcdvfsWGIILWEVITRrkpfdhiggpafrimwaVHNGERPPLIKNCPKPIESLMTRCWSKDPEKRP 236
                         250
                  ....*....|.
gi 1370473802 474 TFEYIQSFLED 484
Cdd:cd14058   237 SMKEIVKIMSH 247
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
156-246 6.99e-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: 111.94  E-value: 6.99e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802  156 EEWYFGKMGRKDAERLLLNPGNqrGIFLVRESETTKGAYSLSIRDwdeirGDNVKHYKIRKLDNGGYYITTRAQFDTLQK 235
Cdd:smart00252   1 QPWYHGFISREEAEKLLKNEGD--GDFLVRDSESSPGDYVLSVRV-----KGKVKHYRIRRNEDGKFYLEGGRKFPSLVE 73
                           90
                   ....*....|.
gi 1370473802  236 LVKHYTEHADG 246
Cdd:smart00252  74 LVEHYQKNSLG 84
SH3_Src_like cd11845
Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members ...
95-146 8.79e-30

Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. 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). However, Brk lacks the N-terminal myristoylation sites. 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, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. 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: 212779 [Multi-domain]  Cd Length: 52  Bit Score: 110.36  E-value: 8.79e-30
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1370473802  95 IFVALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARSIATGKNGYIPSNY 146
Cdd:cd11845     1 IYVALYDYEARTDDDLSFKKGDRLQILDDSDGDWWLARHLSTGKEGYIPSNY 52
PTKc_VEGFR cd05054
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
270-475 2.16e-29

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: 117.21  E-value: 2.16e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 270 WEIPRESLRLEVKLGQGCFGEVWMGTWNGTTK------VAIKTLKPGTMMPE--AFLQEAQIMKKL-RHDKLVPLYAVV- 339
Cdd:cd05054     2 WEFPRDRLKLGKPLGRGAFGKVIQASAFGIDKsatcrtVAVKMLKEGATASEhkALMTELKILIHIgHHLNVVNLLGACt 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 340 -SEEPIYIVTEFMSKGSLLDFLK---------------------EGDGKY---LKLPQLVDMAAQIADGMAYIERMNYIH 394
Cdd:cd05054    82 kPGGPLMVIVEFCKFGNLSNYLRskreefvpyrdkgardveeeeDDDELYkepLTLEDLICYSFQVARGMEFLASRKCIH 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 395 RDLRAANILVGENLVCKIADFGLARLIEDNEYTARQG------------------------------------------- 431
Cdd:cd05054   162 RDLAARNILLSENNVVKICDFGLARDIYKDPDYVRKGdarlplkwmapesifdkvyttqsdvwsfgvllweifslgaspy 241
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*..
gi 1370473802 432 ---MVNREVLEQVERGYRMPCPQGCPESLHELMNLCWKKDPDERPTF 475
Cdd:cd05054   242 pgvQMDEEFCRRLKEGTRMRAPEYTTPEIYQIMLDCWHGEPKERPTF 288
PTKc_TrkB cd05093
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze ...
272-493 5.32e-29

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: 115.91  E-value: 5.32e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 272 IPRESLRLEVKLGQGCFGEVWMGTWNGTTK------VAIKTLKPGTMMPEA-FLQEAQIMKKLRHDKLVPLYAV-VSEEP 343
Cdd:cd05093     2 IKRHNIVLKRELGEGAFGKVFLAECYNLCPeqdkilVAVKTLKDASDNARKdFHREAELLTNLQHEHIVKFYGVcVEGDP 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 344 IYIVTEFMSKGSLLDFLKE--------GDGK---YLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKI 412
Cdd:cd05093    82 LIMVFEYMKHGDLNKFLRAhgpdavlmAEGNrpaELTQSQMLHIAQQIAAGMVYLASQHFVHRDLATRNCLVGENLLVKI 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 413 ADFGLARLIEDNEYTARQG---------------------------------------------MVNREVLEQVERGYRM 447
Cdd:cd05093   162 GDFGMSRDVYSTDYYRVGGhtmlpirwmppesimyrkfttesdvwslgvvlweiftygkqpwyqLSNNEVIECITQGRVL 241
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*.
gi 1370473802 448 PCPQGCPESLHELMNLCWKKDPDERPTFEYIQSFLEDYFTATePQY 493
Cdd:cd05093   242 QRPRTCPKEVYDLMLGCWQREPHMRLNIKEIHSLLQNLAKAS-PVY 286
PTKc_Jak1_rpt2 cd05079
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the ...
283-481 5.61e-29

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: 115.80  E-value: 5.61e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTW-----NGTTKVAIKTLKPGTMMPEA--FLQEAQIMKKLRHDKLVPLYAVVSEEP---IYIVTEFMS 352
Cdd:cd05079    12 LGEGHFGKVELCRYdpegdNTGEQVAVKSLKPESGGNHIadLKKEIEILRNLYHENIVKYKGICTEDGgngIKLIMEFLP 91
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 353 KGSLLDFLKEGDGKyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNE--YTAR- 429
Cdd:cd05079    92 SGSLKEYLPRNKNK-INLKQQLKYAVQICKGMDYLGSRQYVHRDLAARNVLVESEHQVKIGDFGLTKAIETDKeyYTVKd 170
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 430 --------------------------------------------------------QG-MVNREVLEQVERGYRMPCPQG 452
Cdd:cd05079   171 dldspvfwyapecliqskfyiasdvwsfgvtlyelltycdsesspmtlflkmigptHGqMTVTRLVRVLEEGKRLPRPPN 250
                         250       260       270
                  ....*....|....*....|....*....|
gi 1370473802 453 CPESLHELMNLCWKKDPDERPTFE-YIQSF 481
Cdd:cd05079   251 CPEEVYQLMRKCWEFQPSKRTTFQnLIEGF 280
PTKc_HER2 cd05109
Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the ...
283-476 6.67e-29

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: 115.51  E-value: 6.67e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTW-----NGTTKVAIKTLKPGTMmPEA---FLQEAQIMKKLRHDKLVPLYAVVSEEPIYIVTEFMSKG 354
Cdd:cd05109    15 LGSGAFGTVYKGIWipdgeNVKIPVAIKVLRENTS-PKAnkeILDEAYVMAGVGSPYVCRLLGICLTSTVQLVTQLMPYG 93
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 355 SLLDFLKEGDGKyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARL--IEDNEYTARQGM 432
Cdd:cd05109    94 CLLDYVRENKDR-IGSQDLLNWCVQIAKGMSYLEEVRLVHRDLAARNVLVKSPNHVKITDFGLARLldIDETEYHADGGK 172
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 433 V-------------------------------------------NREVLEQVERGYRMPCPQGCPESLHELMNLCWKKDP 469
Cdd:cd05109   173 VpikwmalesilhrrfthqsdvwsygvtvwelmtfgakpydgipAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDS 252

                  ....*..
gi 1370473802 470 DERPTFE 476
Cdd:cd05109   253 ECRPRFR 259
PTKc_FGFR3 cd05100
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs ...
266-496 9.38e-29

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: 116.27  E-value: 9.38e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 266 AKDAWEIPRESLRLEVKLGQGCFGEVWMGTWNGTTK--------VAIKTLKPGTMMPEA--FLQEAQIMKKL-RHDKLVP 334
Cdd:cd05100     3 ADPKWELSRTRLTLGKPLGEGCFGQVVMAEAIGIDKdkpnkpvtVAVKMLKDDATDKDLsdLVSEMEMMKMIgKHKNIIN 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 335 LYAVVSEE-PIYIVTEFMSKGSLLDFLK-------EGDGKYLKLPQ-------LVDMAAQIADGMAYIERMNYIHRDLRA 399
Cdd:cd05100    83 LLGACTQDgPLYVLVEYASKGNLREYLRarrppgmDYSFDTCKLPEeqltfkdLVSCAYQVARGMEYLASQKCIHRDLAA 162
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 400 ANILVGENLVCKIADFGLARLIEDNEY-------------TARQGMVNR------------------------------- 435
Cdd:cd05100   163 RNVLVTEDNVMKIADFGLARDVHNIDYykkttngrlpvkwMAPEALFDRvythqsdvwsfgvllweiftlggspypgipv 242
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370473802 436 -EVLEQVERGYRMPCPQGCPESLHELMNLCWKKDPDERPTFEYIQSFLEDYFTATEP-----------QYQPG 496
Cdd:cd05100   243 eELFKLLKEGHRMDKPANCTHELYMIMRECWHAVPSQRPTFKQLVEDLDRVLTVTSTdeyldlsvpfeQYSPG 315
PTKc_CSF-1R cd05106
Catalytic domain of the Protein Tyrosine Kinase, Colony-Stimulating Factor-1 Receptor; PTKs ...
262-483 1.79e-28

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: 116.10  E-value: 1.79e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 262 TQGLAKDAWEIPRESLRLEVKLGQGCFGEV------WMGTWNGTTKVAIKTLKPG--TMMPEAFLQEAQIMKKL-RHDKL 332
Cdd:cd05106    25 TQLPYNEKWEFPRDNLQFGKTLGAGAFGKVveatafGLGKEDNVLRVAVKMLKASahTDEREALMSELKILSHLgQHKNI 104
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 333 VPLY-AVVSEEPIYIVTEFMSKGSLLDFLK-----------------EGDGKY--------------------------- 367
Cdd:cd05106   105 VNLLgACTHGGPVLVITEYCCYGDLLNFLRkkaetflnfvmalpeisETSSDYknitlekkyirsdsgfssqgsdtyvem 184
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 368 ------------------------LKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIED 423
Cdd:cd05106   185 rpvsssssqssdskdeedtedswpLDLDDLLRFSSQVAQGMDFLASKNCIHRDVAARNVLLTDGRVAKICDFGLARDIMN 264
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 424 NE------------------------YTARQG----------------------MVNREVLEQVERGYRMPCPQGCPESL 457
Cdd:cd05106   265 DSnyvvkgnarlpvkwmapesifdcvYTVQSDvwsygillweifslgkspypgiLVNSKFYKMVKRGYQMSRPDFAPPEI 344
                         330       340
                  ....*....|....*....|....*.
gi 1370473802 458 HELMNLCWKKDPDERPTFEYIQSFLE 483
Cdd:cd05106   345 YSIMKMCWNLEPTERPTFSQISQLIQ 370
STKc_B-Raf cd14151
Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) ...
268-483 2.69e-28

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: 113.62  E-value: 2.69e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 268 DAWEIPRESLRLEVKLGQGCFGEVWMGTWNGttKVAIKTLK---PGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEPI 344
Cdd:cd14151     1 DDWEIPDGQITVGQRIGSGSFGTVYKGKWHG--DVAVKMLNvtaPTPQQLQAFKNEVGVLRKTRHVNILLFMGYSTKPQL 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 345 YIVTEFMSKGSLLDFLKEGDGKYlKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLA------ 418
Cdd:cd14151    79 AIVTQWCEGSSLYHHLHIIETKF-EMIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGLAtvksrw 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 419 ---------------------RLIEDNEYTARQ-----GMV---------------NR-EVLEQVERGYRMP----CPQG 452
Cdd:cd14151   158 sgshqfeqlsgsilwmapeviRMQDKNPYSFQSdvyafGIVlyelmtgqlpysninNRdQIIFMVGRGYLSPdlskVRSN 237
                         250       260       270
                  ....*....|....*....|....*....|.
gi 1370473802 453 CPESLHELMNLCWKKDPDERPTFEYIQSFLE 483
Cdd:cd14151   238 CPKAMKRLMAECLKKKRDERPLFPQILASIE 268
PTKc_Axl cd05075
Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the ...
283-483 3.45e-28

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: 113.18  E-value: 3.45e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWN---GTTKVAIKTLKPG----TMMpEAFLQEAQIMKKLRHDKLVPLYAVV---SEEPIY----IVT 348
Cdd:cd05075     8 LGEGEFGSVMEGQLNqddSVLKVAVKTMKIAictrSEM-EDFLSEAVCMKEFDHPNVMRLIGVClqnTESEGYpspvVIL 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 349 EFMSKGSLLDFL---KEGDGK-YLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDN 424
Cdd:cd05075    87 PFMKHGDLHSFLlysRLGDCPvYLPTQMLVKFMTDIASGMEYLSSKNFIHRDLAARNCMLNENMNVCVADFGLSKKIYNG 166
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 425 EYTaRQGMV----------------------------------------------NREVLEQVERGYRMPCPQGCPESLH 458
Cdd:cd05075   167 DYY-RQGRIskmpvkwiaiesladrvyttksdvwsfgvtmweiatrgqtpypgveNSEIYDYLRQGNRLKQPPDCLDGLY 245
                         250       260
                  ....*....|....*....|....*
gi 1370473802 459 ELMNLCWKKDPDERPTFEYIQSFLE 483
Cdd:cd05075   246 ELMSSCWLLNPKDRPSFETLRCELE 270
PTKc_Met_Ron cd05058
Catalytic domain of the Protein Tyrosine Kinases, Met and Ron; PTKs catalyze the transfer of ...
283-488 4.08e-28

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: 112.57  E-value: 4.08e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGT----TKVAIKTLKPGTMMPE--AFLQEAQIMKKLRHDKLVPLYAVV--SEEPIYIVTEFMSKG 354
Cdd:cd05058     3 IGKGHFGCVYHGTLIDSdgqkIHCAVKSLNRITDIEEveQFLKEGIIMKDFSHPNVLSLLGIClpSEGSPLVVLPYMKHG 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 355 SLLDFL-KEGDGKYLKlpQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYTARQ--- 430
Cdd:cd05058    83 DLRNFIrSETHNPTVK--DLIGFGLQVAKGMEYLASKKFVHRDLAARNCMLDESFTVKVADFGLARDIYDKEYYSVHnht 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 431 ----------------------------GMVNREVLEQ----------------VERGYRMPCPQGCPESLHELMNLCWK 466
Cdd:cd05058   161 gaklpvkwmaleslqtqkfttksdvwsfGVLLWELMTRgappypdvdsfditvyLLQGRRLLQPEYCPDPLYEVMLSCWH 240
                         250       260
                  ....*....|....*....|..
gi 1370473802 467 KDPDERPTFEYIQSFLEDYFTA 488
Cdd:cd05058   241 PKPEMRPTFSELVSRISQIFST 262
STKc_RIP cd13978
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze ...
283-475 5.81e-28

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: 112.16  E-value: 5.81e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEV---WMGTWNGttKVAIKTLKPGT---MMPEAFLQEAQIMKKLRHDKLVPLYAV-VSEEPIYIVTEFMSKGS 355
Cdd:cd13978     1 LGSGGFGTVskaRHVSWFG--MVAIKCLHSSPnciEERKALLKEAEKMERARHSYVLPLLGVcVERRSLGLVMEYMENGS 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 356 LLDFLKEGDGKyLKLPQLVDMAAQIADGMAYIERMN--YIHRDLRAANILVGENLVCKIADFGLARL----IEDNE---- 425
Cdd:cd13978    79 LKSLLEREIQD-VPWSLRFRIIHEIALGMNFLHNMDppLLHHDLKPENILLDNHFHVKISDFGLSKLgmksISANRrrgt 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 426 --------YTARQ------------------GMVNREVLEQ----------------VERGYR-------MPCPQGCPES 456
Cdd:cd13978   158 enlggtpiYMAPEafddfnkkptsksdvysfAIVIWAVLTRkepfenainpllimqiVSKGDRpslddigRLKQIENVQE 237
                         250
                  ....*....|....*....
gi 1370473802 457 LHELMNLCWKKDPDERPTF 475
Cdd:cd13978   238 LISLMIRCWDGNPDARPTF 256
STKc_MAP3K12_13 cd14059
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase ...
283-483 1.94e-27

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: 109.89  E-value: 1.94e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTtKVAIKTLKPgtmmpeafLQEAQI--MKKLRHDKLVPLYAVVSEEPIY-IVTEFMSKGSLLDF 359
Cdd:cd14059     1 LGSGAQGAVFLGKFRGE-EVAVKKVRD--------EKETDIkhLRKLNHPNIIKFKGVCTQAPCYcILMEYCPYGQLYEV 71
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 360 LKegDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNE----------YTAR 429
Cdd:cd14059    72 LR--AGREITPSLLVDWSKQIASGMNYLHLHKIIHRDLKSPNVLVTYNDVLKISDFGTSKELSEKStkmsfagtvaWMAP 149
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 430 QGMVNREVLEQV---------------ERGY-----------------RMPCPQGCPESLHELMNLCWKKDPDERPTFEY 477
Cdd:cd14059   150 EVIRNEPCSEKVdiwsfgvvlwelltgEIPYkdvdssaiiwgvgsnslQLPVPSTCPDGFKLLMKQCWNSKPRNRPSFRQ 229

                  ....*.
gi 1370473802 478 IQSFLE 483
Cdd:cd14059   230 ILMHLD 235
STKc_Cdc7_like cd06627
Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs ...
278-474 2.25e-27

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: 110.39  E-value: 2.25e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 278 RLEVKLGQGCFGEVWMG-TWNGTTKVAIKTLKPgTMMPEAFLQ----EAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFM 351
Cdd:cd06627     3 QLGDLIGRGAFGSVYKGlNLNTGEFVAIKQISL-EKIPKSDLKsvmgEIDLLKKLNHPNIVKYIGSVkTKDSLYIILEYV 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 352 SKGSLLDFLKegdgKYLKLPQ-LVDM-AAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLA-RLIE-DNEYT 427
Cdd:cd06627    82 ENGSLASIIK----KFGKFPEsLVAVyIYQVLEGLAYLHEQGVIHRDIKGANILTTKDGLVKLADFGVAtKLNEvEKDEN 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 428 ARQGMVN---REVLEQVERG-------------------------------YR------MPCPQGCPESLHELMNLCWKK 467
Cdd:cd06627   158 SVVGTPYwmaPEVIEMSGVTtasdiwsvgctvielltgnppyydlqpmaalFRivqddhPPLPENISPELRDFLLQCFQK 237

                  ....*..
gi 1370473802 468 DPDERPT 474
Cdd:cd06627   238 DPTLRPS 244
STKc_MLK cd14061
Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the ...
283-483 2.30e-27

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: 110.56  E-value: 2.30e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTkVAIKTLKPG-----TMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEP-IYIVTEFMSKGSL 356
Cdd:cd14061     2 IGVGGFGKVYRGIWRGEE-VAVKAARQDpdediSVTLENVRQEARLFWMLRHPNIIALRGVCLQPPnLCLVMEYARGGAL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 357 LDFLKegdGKYLKLPQLVDMAAQIADGMAYIER---MNYIHRDLRAANILVGE--------NLVCKIADFGLAR------ 419
Cdd:cd14061    81 NRVLA---GRKIPPHVLVDWAIQIARGMNYLHNeapVPIIHRDLKSSNILILEaienedleNKTLKITDFGLARewhktt 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 420 --------------LIEDNEYTARQ-----GMVNREVL--EQVERG-------YR-------MPCPQGCPESLHELMNLC 464
Cdd:cd14061   158 rmsaagtyawmapeVIKSSTFSKASdvwsyGVLLWELLtgEVPYKGidglavaYGvavnkltLPIPSTCPEPFAQLMKDC 237
                         250
                  ....*....|....*....
gi 1370473802 465 WKKDPDERPTFEYIQSFLE 483
Cdd:cd14061   238 WQPDPHDRPSFADILKQLE 256
PTKc_TAM cd05035
Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer ...
283-484 2.39e-27

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: 110.70  E-value: 2.39e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNG----TTKVAIKTLKPGTMMP---EAFLQEAQIMKKLRHDKLVPLYAVVSE--------EPIyIV 347
Cdd:cd05035     7 LGEGEFGSVMEAQLKQddgsQLKVAVKTMKVDIHTYseiEEFLSEAACMKDFDHPNVMRLIGVCFTasdlnkppSPM-VI 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 348 TEFMSKGSLLDFL----KEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLI-- 421
Cdd:cd05035    86 LPFMKHGDLHSYLlysrLGGLPEKLPLQTLLKFMVDIAKGMEYLSNRNFIHRDLAARNCMLDENMTVCVADFGLSRKIys 165
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 422 ----------------------EDNEYTARQ---------------------GMVNREVLEQVERGYRMPCPQGCPESLH 458
Cdd:cd05035   166 gdyyrqgriskmpvkwialeslADNVYTSKSdvwsfgvtmweiatrgqtpypGVENHEIYDYLRNGNRLKQPEDCLDEVY 245
                         250       260
                  ....*....|....*....|....*.
gi 1370473802 459 ELMNLCWKKDPDERPTFEYIQSFLED 484
Cdd:cd05035   246 FLMYFCWTVDPKDRPTFTKLREVLEN 271
STKc_AMPK-like cd14003
Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze ...
278-426 2.94e-27

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: 109.91  E-value: 2.94e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 278 RLEVKLGQGCFGEVWMGTWNGT-TKVAIKTL---KPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFMS 352
Cdd:cd14003     3 ELGKTLGEGSFGKVKLARHKLTgEKVAIKIIdksKLKEEIEEKIKREIEIMKLLNHPNIIKLYEVIeTENKIYLVMEYAS 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 353 KGSLLDF------LKEGDGKYLklpqlvdmAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEY 426
Cdd:cd14003    83 GGELFDYivnngrLSEDEARRF--------FQQLISAVDYCHSNGIVHRDLKLENILLDKNGNLKIIDFGLSNEFRGGSL 154
PTKc_Tie cd05047
Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
283-478 2.99e-27

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: 110.52  E-value: 2.99e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVW--MGTWNGT-TKVAIKTLKPGTMMPEA--FLQEAQIMKKL-RHDKLVPLYAVVSEEP-IYIVTEFMSKGS 355
Cdd:cd05047     3 IGEGNFGQVLkaRIKKDGLrMDAAIKRMKEYASKDDHrdFAGELEVLCKLgHHPNIINLLGACEHRGyLYLAIEYAPHGN 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 356 LLDFLKE--------------GDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR-- 419
Cdd:cd05047    83 LLDFLRKsrvletdpafaianSTASTLSSQQLLHFAADVARGMDYLSQKQFIHRDLAARNILVGENYVAKIADFGLSRgq 162
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 420 ----------------LIEDNEY------------------------TARQGMVNREVLEQVERGYRMPCPQGCPESLHE 459
Cdd:cd05047   163 evyvkktmgrlpvrwmAIESLNYsvyttnsdvwsygvllweivslggTPYCGMTCAELYEKLPQGYRLEKPLNCDDEVYD 242
                         250
                  ....*....|....*....
gi 1370473802 460 LMNLCWKKDPDERPTFEYI 478
Cdd:cd05047   243 LMRQCWREKPYERPSFAQI 261
PKc_STE cd05122
Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the ...
278-474 3.01e-27

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: 109.99  E-value: 3.01e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 278 RLEVKLGQGCFGEVWMGTWNGTTK-VAIKTLKPGTMMP-EAFLQEAQIMKKLRHDKLVPLY-AVVSEEPIYIVTEFMSKG 354
Cdd:cd05122     3 EILEKIGKGGFGVVYKARHKKTGQiVAIKKINLESKEKkESILNEIAILKKCKHPNIVKYYgSYLKKDELWIVMEFCSGG 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 355 SLLDFLKEGDGKyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLA-RLIEDNEYTARQG-- 431
Cdd:cd05122    83 SLKDLLKNTNKT-LTEQQIAYVCKEVLKGLEYLHSHGIIHRDIKAANILLTSDGEVKLIDFGLSaQLSDGKTRNTFVGtp 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 432 ------MVNRE--------------VLEQVERGY--------------------RMPCPQGCPESLHELMNLCWKKDPDE 471
Cdd:cd05122   162 ywmapeVIQGKpygfkadiwslgitAIEMAEGKPpyselppmkalfliatngppGLRNPKKWSKEFKDFLKKCLQKDPEK 241

                  ...
gi 1370473802 472 RPT 474
Cdd:cd05122   242 RPT 244
STKc_A-Raf cd14150
Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) ...
282-483 3.10e-27

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: 110.49  E-value: 3.10e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGttKVAIKTLK---PGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEPIYIVTEFMSKGSLLD 358
Cdd:cd14150     7 RIGTGSFGTVFRGKWHG--DVAVKILKvtePTPEQLQAFKNEMQVLRKTRHVNILLFMGFMTRPNFAIITQWCEGSSLYR 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 359 FLKEGDGKYlKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLA-------------------- 418
Cdd:cd14150    85 HLHVTETRF-DTMQLIDVARQTAQGMDYLHAKNIIHRDLKSNNIFLHEGLTVKIGDFGLAtvktrwsgsqqveqpsgsil 163
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 419 -------RLIEDNEYTARQ-----GMV---------------NR-EVLEQVERGYRMP----CPQGCPESLHELMNLCWK 466
Cdd:cd14150   164 wmapeviRMQDTNPYSFQSdvyayGVVlyelmsgtlpysninNRdQIIFMVGRGYLSPdlskLSSNCPKAMKRLLIDCLK 243
                         250
                  ....*....|....*..
gi 1370473802 467 KDPDERPTFEYIQSFLE 483
Cdd:cd14150   244 FKREERPLFPQILVSIE 260
STKc_C-Raf cd14149
Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) ...
270-483 3.24e-27

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: 110.89  E-value: 3.24e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 270 WEIPRESLRLEVKLGQGCFGEVWMGTWNGttKVAIKTLKPGTMMPE---AFLQEAQIMKKLRHDKLVPLYAVVSEEPIYI 346
Cdd:cd14149     7 WEIEASEVMLSTRIGSGSFGTVYKGKWHG--DVAVKILKVVDPTPEqfqAFRNEVAVLRKTRHVNILLFMGYMTKDNLAI 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 347 VTEFMSKGSLLDFLKEGDGKYlKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLA-------- 418
Cdd:cd14149    85 VTQWCEGSSLYKHLHVQETKF-QMFQLIDIARQTAQGMDYLHAKNIIHRDMKSNNIFLHEGLTVKIGDFGLAtvksrwsg 163
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 419 -------------------RLIEDNEYTARQ-----GMV---------------NR-EVLEQVERGYRMP----CPQGCP 454
Cdd:cd14149   164 sqqveqptgsilwmapeviRMQDNNPFSFQSdvysyGIVlyelmtgelpyshinNRdQIIFMVGRGYASPdlskLYKNCP 243
                         250       260
                  ....*....|....*....|....*....
gi 1370473802 455 ESLHELMNLCWKKDPDERPTFEYIQSFLE 483
Cdd:cd14149   244 KAMKRLVADCIKKVKEERPLFPQILSSIE 272
STKc_MAK_like cd07830
Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs ...
282-428 3.39e-27

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: 110.70  E-value: 3.39e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGT-TKVAIKTLKpgtmmpEAF--------LQEAQIMKKL-RHDKLVPLYAVVSE-EPIYIVTEF 350
Cdd:cd07830     6 QLGDGTFGSVYLARNKETgELVAIKKMK------KKFysweecmnLREVKSLRKLnEHPNIVKLKEVFREnDELYFVFEY 79
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1370473802 351 MsKGSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNE-YTA 428
Cdd:cd07830    80 M-EGNLYQLMKDRKGKPFSESVIRSIIYQILQGLAHIHKHGFFHRDLKPENLLVSGPEVVKIADFGLAREIRSRPpYTD 157
PTKc_Tyro3 cd05074
Catalytic domain of the Protein Tyrosine Kinase, Tyro3; PTKs catalyze the transfer of the ...
272-483 3.98e-27

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: 110.39  E-value: 3.98e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 272 IPRESLRLEVKLGQGCFG---EVWMGTWNGT-TKVAIKTLKPGTMMP---EAFLQEAQIMKKLRHDKLVPLYAVVSEE-- 342
Cdd:cd05074     6 IQEQQFTLGRMLGKGEFGsvrEAQLKSEDGSfQKVAVKMLKADIFSSsdiEEFLREAACMKEFDHPNVIKLIGVSLRSra 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 343 ----PI-YIVTEFMSKGSLLDFL---KEGDGKY-LKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIA 413
Cdd:cd05074    86 kgrlPIpMVILPFMKHGDLHTFLlmsRIGEEPFtLPLQTLVRFMIDIASGMEYLSSKNFIHRDLAARNCMLNENMTVCVA 165
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 414 DFGLARLI------------------------EDNEYTARQ---------------------GMVNREVLEQVERGYRMP 448
Cdd:cd05074   166 DFGLSKKIysgdyyrqgcasklpvkwlaleslADNVYTTHSdvwafgvtmweimtrgqtpyaGVENSEIYNYLIKGNRLK 245
                         250       260       270
                  ....*....|....*....|....*....|....*
gi 1370473802 449 CPQGCPESLHELMNLCWKKDPDERPTFEYIQSFLE 483
Cdd:cd05074   246 QPPDCLEDVYELMCQCWSPEPKCRPSFQHLRDQLE 280
PTKc_Mer cd14204
Catalytic Domain of the Protein Tyrosine Kinase, Mer; PTKs catalyze the transfer of the ...
272-483 6.07e-27

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: 110.02  E-value: 6.07e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 272 IPRESLRLEVKLGQGCFGEVWMGTW---NGTT-KVAIKTLKPGTMMP---EAFLQEAQIMKKLRHDKLVPLYAVVSE--- 341
Cdd:cd14204     4 IDRNLLSLGKVLGEGEFGSVMEGELqqpDGTNhKVAVKTMKLDNFSQreiEEFLSEAACMKDFNHPNVIRLLGVCLEvgs 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 342 ----EPIyIVTEFMSKGSLLDFL----KEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIA 413
Cdd:cd14204    84 qripKPM-VILPFMKYGDLHSFLlrsrLGSGPQHVPLQTLLKFMIDIALGMEYLSSRNFLHRDLAARNCMLRDDMTVCVA 162
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 414 DFGLARLIEDNEYTaRQGMV----------------------------------------------NREVLEQVERGYRM 447
Cdd:cd14204   163 DFGLSKKIYSGDYY-RQGRIakmpvkwiavesladrvytvksdvwafgvtmweiatrgmtpypgvqNHEIYDYLLHGHRL 241
                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 1370473802 448 PCPQGCPESLHELMNLCWKKDPDERPTFEYIQSFLE 483
Cdd:cd14204   242 KQPEDCLDELYDIMYSCWRSDPTDRPTFTQLRENLE 277
PTKc_TrkC cd05094
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze ...
272-489 7.82e-27

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: 109.71  E-value: 7.82e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 272 IPRESLRLEVKLGQGCFGEVWMGT-WN-GTTK----VAIKTLK-PGTMMPEAFLQEAQIMKKLRHDKLVPLYAV-VSEEP 343
Cdd:cd05094     2 IKRRDIVLKRELGEGAFGKVFLAEcYNlSPTKdkmlVAVKTLKdPTLAARKDFQREAELLTNLQHDHIVKFYGVcGDGDP 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 344 IYIVTEFMSKGSLLDFLKEG--------DGKYLK------LPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLV 409
Cdd:cd05094    82 LIMVFEYMKHGDLNKFLRAHgpdamilvDGQPRQakgelgLSQMLHIATQIASGMVYLASQHFVHRDLATRNCLVGANLL 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 410 CKIADFGLARLIEDNEYTARQG---------------------------------------------MVNREVLEQVERG 444
Cdd:cd05094   162 VKIGDFGMSRDVYSTDYYRVGGhtmlpirwmppesimyrkfttesdvwsfgvilweiftygkqpwfqLSNTEVIECITQG 241
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 1370473802 445 YRMPCPQGCPESLHELMNLCWKKDPDERPTFEYIQSFLEDYFTAT 489
Cdd:cd05094   242 RVLERPRVCPKEVYDIMLGCWQREPQQRLNIKEIYKILHALGKAT 286
SH3_Src cd12008
Src homology 3 domain of Src Protein Tyrosine Kinase; Src (or c-Src) is a cytoplasmic (or ...
96-150 1.34e-26

Src homology 3 domain of Src Protein Tyrosine Kinase; Src (or c-Src) is a cytoplasmic (or non-receptor) PTK and 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. 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 SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. 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: 212941 [Multi-domain]  Cd Length: 56  Bit Score: 101.73  E-value: 1.34e-26
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1370473802  96 FVALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARSIATGKNGYIPSNYVAPA 150
Cdd:cd12008     2 FVALYDYESRTETDLSFKKGERLQIVNNTEGDWWLAHSLTTGQTGYIPSNYVAPS 56
PTKc_Tie1 cd05089
Catalytic domain of the Protein Tyrosine Kinase, Tie1; Protein Tyrosine Kinase (PTK) family; ...
275-478 1.41e-26

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: 109.32  E-value: 1.41e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 275 ESLRLEVKLGQGCFGEV--WMGTWNGTT-KVAIKTLKPGTMMPEA--FLQEAQIMKKL-RHDKLVPLYAVVSEEP-IYIV 347
Cdd:cd05089     2 EDIKFEDVIGEGNFGQVikAMIKKDGLKmNAAIKMLKEFASENDHrdFAGELEVLCKLgHHPNIINLLGACENRGyLYIA 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 348 TEFMSKGSLLDFLKE--------------GDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIA 413
Cdd:cd05089    82 IEYAPYGNLLDFLRKsrvletdpafakehGTASTLTSQQLLQFASDVAKGMQYLSEKQFIHRDLAARNVLVGENLVSKIA 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 414 DFGLAR------------------LIEDNEY------------------------TARQGMVNREVLEQVERGYRMPCPQ 451
Cdd:cd05089   162 DFGLSRgeevyvkktmgrlpvrwmAIESLNYsvyttksdvwsfgvllweivslggTPYCGMTCAELYEKLPQGYRMEKPR 241
                         250       260
                  ....*....|....*....|....*..
gi 1370473802 452 GCPESLHELMNLCWKKDPDERPTFEYI 478
Cdd:cd05089   242 NCDDEVYELMRQCWRDRPYERPPFSQI 268
PTKc_Ror2 cd05091
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
271-485 1.59e-26

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: 108.95  E-value: 1.59e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 271 EIPRESLRLEVKLGQGCFGEVWMGTWNGTTK------VAIKTLKPGTMMP--EAFLQEAQIMKKLRHDKLVPLYAVVS-E 341
Cdd:cd05091     2 EINLSAVRFMEELGEDRFGKVYKGHLFGTAPgeqtqaVAIKTLKDKAEGPlrEEFRHEAMLRSRLQHPNIVCLLGVVTkE 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 342 EPIYIVTEFMSKGSLLDFL----------KEGDGKYLKL----PQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGEN 407
Cdd:cd05091    82 QPMSMIFSYCSHGDLHEFLvmrsphsdvgSTDDDKTVKStlepADFLHIVTQIAAGMEYLSSHHVVHKDLATRNVLVFDK 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 408 LVCKIADFGLARLIEDNEYTARQ---------------------------------------------GMVNREVLEQVE 442
Cdd:cd05091   162 LNVKISDLGLFREVYAADYYKLMgnsllpirwmspeaimygkfsidsdiwsygvvlwevfsyglqpycGYSNQDVIEMIR 241
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|...
gi 1370473802 443 RGYRMPCPQGCPESLHELMNLCWKKDPDERPTFEYIQSFLEDY 485
Cdd:cd05091   242 NRQVLPCPDDCPAWVYTLMLECWNEFPSRRPRFKDIHSRLRTW 284
PTKc_Jak2_rpt2 cd14205
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the ...
282-484 4.55e-26

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: 107.41  E-value: 4.55e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTW-----NGTTKVAIKTLKPGTM-MPEAFLQEAQIMKKLRHDKLVPLYAV---VSEEPIYIVTEFMS 352
Cdd:cd14205    11 QLGKGNFGSVEMCRYdplqdNTGEVVAVKKLQHSTEeHLRDFEREIEILKSLQHDNIVKYKGVcysAGRRNLRLIMEYLP 90
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 353 KGSLLDFLKEGDGKyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLI-EDNEYTA--- 428
Cdd:cd14205    91 YGSLRDYLQKHKER-IDHIKLLQYTSQICKGMEYLGTKRYIHRDLATRNILVENENRVKIGDFGLTKVLpQDKEYYKvke 169
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 429 --------------------------------------------------------RQG-MVNREVLEQVERGYRMPCPQ 451
Cdd:cd14205   170 pgespifwyapeslteskfsvasdvwsfgvvlyelftyieksksppaefmrmigndKQGqMIVFHLIELLKNNGRLPRPD 249
                         250       260       270
                  ....*....|....*....|....*....|...
gi 1370473802 452 GCPESLHELMNLCWKKDPDERPTFEYIQSFLED 484
Cdd:cd14205   250 GCPDEIYMIMTECWNNNVNQRPSFRDLALRVDQ 282
PTKc_HER4 cd05110
Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the ...
283-492 8.88e-26

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: 107.07  E-value: 8.88e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTW--NGTT---KVAIKTLKPgTMMPEA---FLQEAQIMKKLRHDKLVPLYAVVSEEPIYIVTEFMSKG 354
Cdd:cd05110    15 LGSGAFGTVYKGIWvpEGETvkiPVAIKILNE-TTGPKAnveFMDEALIMASMDHPHLVRLLGVCLSPTIQLVTQLMPHG 93
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 355 SLLDFL---KEGDGKYLklpqLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIE--DNEYTAR 429
Cdd:cd05110    94 CLLDYVhehKDNIGSQL----LLNWCVQIAKGMMYLEERRLVHRDLAARNVLVKSPNHVKITDFGLARLLEgdEKEYNAD 169
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 430 -------------------------------------------QGMVNREVLEQVERGYRMPCPQGCPESLHELMNLCWK 466
Cdd:cd05110   170 ggkmpikwmalecihyrkfthqsdvwsygvtiwelmtfggkpyDGIPTREIPDLLEKGERLPQPPICTIDVYMVMVKCWM 249
                         250       260
                  ....*....|....*....|....*.
gi 1370473802 467 KDPDERPTFEYIQSflEDYFTATEPQ 492
Cdd:cd05110   250 IDADSRPKFKELAA--EFSRMARDPQ 273
PTKc_EGFR cd05108
Catalytic domain of the Protein Tyrosine Kinase, Epidermal Growth Factor Receptor; PTKs ...
283-492 9.40e-26

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: 107.42  E-value: 9.40e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTK-----VAIKTLKPGTMmPEA---FLQEAQIMKKLRHDKLVPLYAVVSEEPIYIVTEFMSKG 354
Cdd:cd05108    15 LGSGAFGTVYKGLWIPEGEkvkipVAIKELREATS-PKAnkeILDEAYVMASVDNPHVCRLLGICLTSTVQLITQLMPFG 93
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 355 SLLDFLKEGDGKyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLI--EDNEYTARQGM 432
Cdd:cd05108    94 CLLDYVREHKDN-IGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAARNVLVKTPQHVKITDFGLAKLLgaEEKEYHAEGGK 172
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 433 V-------------------------------------------NREVLEQVERGYRMPCPQGCPESLHELMNLCWKKDP 469
Cdd:cd05108   173 VpikwmalesilhriythqsdvwsygvtvwelmtfgskpydgipASEISSILEKGERLPQPPICTIDVYMIMVKCWMIDA 252
                         250       260
                  ....*....|....*....|....
gi 1370473802 470 DERPTF-EYIQSFLEdyfTATEPQ 492
Cdd:cd05108   253 DSRPKFrELIIEFSK---MARDPQ 273
STKc_LIMK cd14154
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer ...
283-483 1.28e-25

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: 106.05  E-value: 1.28e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKVAI-KTL-KPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFMSKGSLLDF 359
Cdd:cd14154     1 LGKGFFGQAIKVTHRETGEVMVmKELiRFDEEAQRNFLKEVKVMRSLDHPNVLKFIGVLyKDKKLNLITEYIPGGTLKDV 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 360 LKEGDgKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYTARQ--------- 430
Cdd:cd14154    81 LKDMA-RPLPWAQRVRFAKDIASGMAYLHSMNIIHRDLNSHNCLVREDKTVVVADFGLARLIVEERLPSGNmspsetlrh 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 431 --------------------------------------GMVNREVLEQVE----------------RGYRMPCPQGCPES 456
Cdd:cd14154   160 lkspdrkkrytvvgnpywmapemlngrsydekvdifsfGIVLCEIIGRVEadpdylprtkdfglnvDSFREKFCAGCPPP 239
                         250       260
                  ....*....|....*....|....*..
gi 1370473802 457 LHELMNLCWKKDPDERPTFEYIQSFLE 483
Cdd:cd14154   240 FFKLAFLCCDLDPEKRPPFETLEEWLE 266
STKc_CDK9_like cd07840
Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs ...
282-429 1.02e-24

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: 103.80  E-value: 1.02e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGT-TKVAIKTLKPGTM---MPEAFLQEAQIMKKLRHDKLVPLYAVVSEEP-------IYIVTEF 350
Cdd:cd07840     6 QIGEGTYGQVYKARNKKTgELVALKKIRMENEkegFPITAIREIKLLQKLDHPNVVRLKEIVTSKGsakykgsIYMVFEY 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 351 MSKgsllDF--LKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNE--- 425
Cdd:cd07840    86 MDH----DLtgLLDNPEVKFTESQIKCYMKQLLEGLQYLHSNGILHRDIKGSNILINNDGVLKLADFGLARPYTKENnad 161

                  ....
gi 1370473802 426 YTAR 429
Cdd:cd07840   162 YTNR 165
STKc_BUR1 cd07866
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), ...
278-448 1.08e-24

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: 104.32  E-value: 1.08e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 278 RLEVKLGQGCFGEVWMGTWNGT-TKVAIKTL-----KPGtmMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEP-------- 343
Cdd:cd07866    11 EILGKLGEGTFGEVYKARQIKTgRVVALKKIlmhneKDG--FPITALREIKILKKLKHPNVVPLIDMAVERPdkskrkrg 88
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 344 -IYIVTEFMSkgSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIE 422
Cdd:cd07866    89 sVYMVTPYMD--HDLSGLLENPSVKLTESQIKCYMLQLLEGINYLHENHILHRDIKAANILIDNQGILKIADFGLARPYD 166
                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 1370473802 423 DN-------------EYTarqGMVnrevleqVERGYRMP 448
Cdd:cd07866   167 GPppnpkggggggtrKYT---NLV-------VTRWYRPP 195
STKc_PAK cd06614
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the ...
281-478 1.26e-24

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: 102.67  E-value: 1.26e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 281 VKLGQGCFGEVWMGTWNGTTK-VAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLY-AVVSEEPIYIVTEFMSKGSLLD 358
Cdd:cd06614     6 EKIGEGASGEVYKATDRATGKeVAIKKMRLRKQNKELIINEILIMKECKHPNIVDYYdSYLVGDELWVVMEYMDGGSLTD 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 359 FLkEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLA-------------------- 418
Cdd:cd06614    86 II-TQNPVRMNESQIAYVCREVLQGLEYLHSQNVIHRDIKSDNILLSKDGSVKLADFGFAaqltkekskrnsvvgtpywm 164
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 419 --RLIEDNEYTAR-----QGMVNREVLEQVERGYRMPcP---------QGCPE---------SLHELMNLCWKKDPDERP 473
Cdd:cd06614   165 apEVIKRKDYGPKvdiwsLGIMCIEMAEGEPPYLEEP-PlralflittKGIPPlknpekwspEFKDFLNKCLVKDPEKRP 243

                  ....*
gi 1370473802 474 TFEYI 478
Cdd:cd06614   244 SAEEL 248
STKc_CAMK cd05117
The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of ...
282-449 1.71e-24

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: 102.17  E-value: 1.71e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGT-TKVAIKTL---KPGTMMPEAFLQEAQIMKKLRHDKLVPLYAV-VSEEPIYIVTEFMSKGSL 356
Cdd:cd05117     7 VLGRGSFGVVRLAVHKKTgEEYAVKIIdkkKLKSEDEEMLRREIEILKRLDHPNIVKLYEVfEDDKNLYLVMELCTGGEL 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 357 LDFLKEGdgKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILV---GENLVCKIADFGLARLIEDNE-------- 425
Cdd:cd05117    87 FDRIVKK--GSFSEREAAKIMKQILSAVAYLHSQGIVHRDLKPENILLaskDPDSPIKIIDFGLAKIFEEGEklktvcgt 164
                         170       180
                  ....*....|....*....|....*.
gi 1370473802 426 --YTArqgmvnREVLEQveRGYRMPC 449
Cdd:cd05117   165 pyYVA------PEVLKG--KGYGKKC 182
STKc_MLK3 cd14147
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the ...
275-483 1.88e-24

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: 102.41  E-value: 1.88e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 275 ESLRLEVKLGQGCFGEVWMGTWNGTTkVAIKTLKPG-----TMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEP-IYIVT 348
Cdd:cd14147     3 QELRLEEVIGIGGFGKVYRGSWRGEL-VAVKAARQDpdediSVTAESVRQEARLFAMLAHPNIIALKAVCLEEPnLCLVM 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 349 EFMSKGSLLDFLKegdGKYLKLPQLVDMAAQIADGMAYIER---MNYIHRDLRAANILVG--------ENLVCKIADFGL 417
Cdd:cd14147    82 EYAAGGPLSRALA---GRRVPPHVLVNWAVQIARGMHYLHCealVPVIHRDLKSNNILLLqpienddmEHKTLKITDFGL 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 418 AR--------------------LIEDNEYT-----ARQGMVNREVLEQvERGYR-----------------MPCPQGCPE 455
Cdd:cd14147   159 ARewhkttqmsaagtyawmapeVIKASTFSkgsdvWSFGVLLWELLTG-EVPYRgidclavaygvavnkltLPIPSTCPE 237
                         250       260
                  ....*....|....*....|....*...
gi 1370473802 456 SLHELMNLCWKKDPDERPTFEYIQSFLE 483
Cdd:cd14147   238 PFAQLMADCWAQDPHRRPDFASILQQLE 265
STKc_Nek cd08215
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; ...
282-478 2.65e-24

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: 101.77  E-value: 2.65e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGTTK-VAIKTLKPGTMMP---EAFLQEAQIMKKLRHDKLVPLYAVVSEEP-IYIVTEFMSKGSL 356
Cdd:cd08215     7 VIGKGSFGSAYLVRRKSDGKlYVLKEIDLSNMSEkerEEALNEVKLLSKLKHPNIVKYYESFEENGkLCIVMEYADGGDL 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 357 LDFLKE--GDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR--------------- 419
Cdd:cd08215    87 AQKIKKqkKKGQPFPEEQILDWFVQICLALKYLHSRKILHRDLKTQNIFLTKDGVVKLGDFGISKvlesttdlaktvvgt 166
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 420 -------LIEDNEYT--------------------ARQGMVNREVLEQVERGYRMPCPQGCPESLHELMNLCWKKDPDER 472
Cdd:cd08215   167 pyylspeLCENKPYNyksdiwalgcvlyelctlkhPFEANNLPALVYKIVKGQYPPIPSQYSSELRDLVNSMLQKDPEKR 246

                  ....*.
gi 1370473802 473 PTFEYI 478
Cdd:cd08215   247 PSANEI 252
STKc_LIMK1 cd14221
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the ...
283-484 2.87e-24

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: 101.96  E-value: 2.87e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKVAI--KTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFMSKGSLLDF 359
Cdd:cd14221     1 LGKGCFGQAIKVTHRETGEVMVmkELIRFDEETQRTFLKEVKVMRCLEHPNVLKFIGVLyKDKRLNFITEYIKGGTLRGI 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 360 LKEGDGKYlKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIED---------------- 423
Cdd:cd14221    81 IKSMDSHY-PWSQRVSFAKDIASGMAYLHSMNIIHRDLNSHNCLVRENKSVVVADFGLARLMVDektqpeglrslkkpdr 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 424 --------NEYTARQGMVN-REVLEQVE--------------------------------RGY-RMPCPQGCPESLHELM 461
Cdd:cd14221   160 kkrytvvgNPYWMAPEMINgRSYDEKVDvfsfgivlceiigrvnadpdylprtmdfglnvRGFlDRYCPPNCPPSFFPIA 239
                         250       260
                  ....*....|....*....|...
gi 1370473802 462 NLCWKKDPDERPTFEYIQSFLED 484
Cdd:cd14221   240 VLCCDLDPEKRPSFSKLEHWLET 262
STKc_MLK4 cd14146
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the ...
283-478 4.29e-24

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: 101.65  E-value: 4.29e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTtKVAIKTLKPG-----TMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEP-IYIVTEFMSKGSL 356
Cdd:cd14146     2 IGVGGFGKVYRATWKGQ-EVAVKAARQDpdediKATAESVRQEAKLFSMLRHPNIIKLEGVCLEEPnLCLVMEFARGGTL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 357 LDFLKEGDG-----KYLKLPQ--LVDMAAQIADGMAYIER---MNYIHRDLRAANILVGENL----VC----KIADFGLA 418
Cdd:cd14146    81 NRALAAANAapgprRARRIPPhiLVNWAVQIARGMLYLHEeavVPILHRDLKSSNILLLEKIehddICnktlKITDFGLA 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 419 R--------------------LIEDNEYTA-----RQGMVNREVLEQvERGYR-----------------MPCPQGCPES 456
Cdd:cd14146   161 RewhrttkmsaagtyawmapeVIKSSLFSKgsdiwSYGVLLWELLTG-EVPYRgidglavaygvavnkltLPIPSTCPEP 239
                         250       260
                  ....*....|....*....|..
gi 1370473802 457 LHELMNLCWKKDPDERPTFEYI 478
Cdd:cd14146   240 FAKLMKECWEQDPHIRPSFALI 261
PTKc_Jak3_rpt2 cd05081
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the ...
283-483 4.38e-24

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: 101.89  E-value: 4.38e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTW-----NGTTKVAIKTLKPGTM-MPEAFLQEAQIMKKLRHDKLVPlYAVVSEEP----IYIVTEFMS 352
Cdd:cd05081    12 LGKGNFGSVELCRYdplgdNTGALVAVKQLQHSGPdQQRDFQREIQILKALHSDFIVK-YRGVSYGPgrrsLRLVMEYLP 90
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 353 KGSLLDFLKEGDGKyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLI-EDNEYT---- 427
Cdd:cd05081    91 SGCLRDFLQRHRAR-LDASRLLLYSSQICKGMEYLGSRRCVHRDLAARNILVESEAHVKIADFGLAKLLpLDKDYYvvre 169
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 428 -------------------ARQ------GMVNRE------------------------------VLEQVERGYRMPCPQG 452
Cdd:cd05081   170 pgqspifwyapeslsdnifSRQsdvwsfGVVLYElftycdkscspsaeflrmmgcerdvpalcrLLELLEEGQRLPAPPA 249
                         250       260       270
                  ....*....|....*....|....*....|.
gi 1370473802 453 CPESLHELMNLCWKKDPDERPTFEYIQSFLE 483
Cdd:cd05081   250 CPAEVHELMKLCWAPSPQDRPSFSALGPQLD 280
STKc_CDK_like cd07829
Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs ...
278-427 1.02e-23

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: 100.63  E-value: 1.02e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 278 RLEvKLGQGCFGEVWMGTWNGTTK-VAIKTLKPGTM---MPEAFLQEAQIMKKLRHDKLVPLYAV-VSEEPIYIVTEFMS 352
Cdd:cd07829     3 KLE-KLGEGTYGVVYKAKDKKTGEiVALKKIRLDNEeegIPSTALREISLLKELKHPNIVKLLDViHTENKLYLVFEYCD 81
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370473802 353 KgSLLDFLKEGDGKyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARL--IEDNEYT 427
Cdd:cd07829    82 Q-DLKKYLDKRPGP-LPPNLIKSIMYQLLRGLAYCHSHRILHRDLKPQNLLINRDGVLKLADFGLARAfgIPLRTYT 156
STKc_MEKK1_plant cd06632
Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP) ...
283-474 2.91e-23

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: 99.01  E-value: 2.91e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGtWNGTTK--VAIKTL------KPGTMMPEAFLQEAQIMKKLRHDKLVPLYAV-VSEEPIYIVTEFMSK 353
Cdd:cd06632     8 LGSGSFGSVYEG-FNGDTGdfFAVKEVslvdddKKSRESVKQLEQEIALLSKLRHPNIVQYYGTeREEDNLYIFLEYVPG 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 354 GSLLDFLKEGDGkyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYTAR-QG- 431
Cdd:cd06632    87 GSIHKLLQRYGA--FEEPVIRLYTRQILSGLAYLHSRNTVHRDIKGANILVDTNGVVKLADFGMAKHVEAFSFAKSfKGs 164
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 432 ---MVNrEVLEQVERGYRMPC---PQGC---------------------------------PESL----HELMNLCWKKD 468
Cdd:cd06632   165 pywMAP-EVIMQKNSGYGLAVdiwSLGCtvlematgkppwsqyegvaaifkignsgelppiPDHLspdaKDFIRLCLQRD 243

                  ....*.
gi 1370473802 469 PDERPT 474
Cdd:cd06632   244 PEDRPT 249
STKc_CMGC cd05118
Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
282-427 3.78e-23

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: 98.08  E-value: 3.78e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGT-TKVAIKTLKPGTMMPEAFLQEAQIMKKLR----HDKLVPLYAVVSEEP---IYIVTEFMSK 353
Cdd:cd05118     6 KIGEGAFGTVWLARDKVTgEKVAIKKIKNDFRHPKAALREIKLLKHLNdvegHPNIVKLLDVFEHRGgnhLCLVFELMGM 85
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370473802 354 gSLLDFLKEgDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILV-GENLVCKIADFGLARLIEDNEYT 427
Cdd:cd05118    86 -NLYELIKD-YPRGLPLDLIKSYLYQLLQALDFLHSNGIIHRDLKPENILInLELGQLKLADFGLARSFTSPPYT 158
STKc_IRAK4 cd14158
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; ...
282-419 4.68e-23

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: 99.11  E-value: 4.68e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGTTkVAIKTLKP--GTMMPE---AFLQEAQIMKKLRHDKLVPLYAVVSEEPIY-IVTEFMSKGS 355
Cdd:cd14158    22 KLGEGGFGVVFKGYINDKN-VAVKKLAAmvDISTEDltkQFEQEIQVMAKCQHENLVELLGYSCDGPQLcLVYTYMPNGS 100
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370473802 356 LLDFLKEGDGKY-LKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR 419
Cdd:cd14158   101 LLDRLACLNDTPpLSWHMRCKIAQGTANGINYLHENNHIHRDIKSANILLDETFVPKISDFGLAR 165
SH2_ABL cd09935
Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ...
158-251 5.27e-23

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: 93.22  E-value: 5.27e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 158 WYFGKMGRKDAERLLLNPGNqrGIFLVRESETTKGAYSLSIRdWDEirgdNVKHYKIRKLDNGGYYITTRAQFDTLQKLV 237
Cdd:cd09935     5 WYHGPISRNAAEYLLSSGIN--GSFLVRESESSPGQYSISLR-YDG----RVYHYRISEDSDGKVYVTQEHRFNTLAELV 77
                          90
                  ....*....|....
gi 1370473802 238 KHYTEHADGLCHKL 251
Cdd:cd09935    78 HHHSKNADGLITTL 91
PTKc_PDGFR_beta cd05107
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta; ...
269-487 6.14e-23

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: 100.86  E-value: 6.14e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 269 AWEIPRESLRLEVKLGQGCFGEVWMGTWNG------TTKVAIKTLKPGTMMPE--AFLQEAQIMKKL-RHDKLVPLYAVV 339
Cdd:cd05107    31 AWEMPRDNLVLGRTLGSGAFGRVVEATAHGlshsqsTMKVAVKMLKSTARSSEkqALMSELKIMSHLgPHLNIVNLLGAC 110
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 340 SEE-PIYIVTEFMSKGSLLDFLK---------------------------------------EGDGKYLK---------- 369
Cdd:cd05107   111 TKGgPIYIITEYCRYGDLVDYLHrnkhtflqyyldknrddgslisggstplsqrkshvslgsESDGGYMDmskdesadyv 190
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 370 --------------------------LPQ---------------------LVDMAAQIADGMAYIERMNYIHRDLRAANI 402
Cdd:cd05107   191 pmqdmkgtvkyadiessnyespydqyLPSapertrrdtlinespalsymdLVGFSYQVANGMEFLASKNCVHRDLAARNV 270
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 403 LVGENLVCKIADFGLAR-LIEDNEYTARQGM---------------------------------------------VNRE 436
Cdd:cd05107   271 LICEGKLVKICDFGLARdIMRDSNYISKGSTflplkwmapesifnnlyttlsdvwsfgillweiftlggtpypelpMNEQ 350
                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1370473802 437 VLEQVERGYRMPCPQGCPESLHELMNLCWKKDPDERPTFEYIQSFLEDYFT 487
Cdd:cd05107   351 FYNAIKRGYRMAKPAHASDEIYEIMQKCWEEKFEIRPDFSQLVHLVGDLLT 401
PTKc_VEGFR1 cd14207
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
270-475 9.26e-23

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: 99.31  E-value: 9.26e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 270 WEIPRESLRLEVKLGQGCFGEVWMGTWNGTTK------VAIKTLKPGTMMPE--AFLQEAQIMKKLRHD-KLVPLYAVVS 340
Cdd:cd14207     2 WEFARERLKLGKSLGRGAFGKVVQASAFGIKKsptcrvVAVKMLKEGATASEykALMTELKILIHIGHHlNVVNLLGACT 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 341 EE--PIYIVTEFMSKGSLLDFLK--------------------------------------------------------- 361
Cdd:cd14207    82 KSggPLMVIVEYCKYGNLSNYLKskrdffvtnkdtslqeelikekkeaeptggkkkrlesvtssesfassgfqedkslsd 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 362 -----EGDGKYLKLP----QLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYTARQG- 431
Cdd:cd14207   162 veeeeEDSGDFYKRPltmeDLISYSFQVARGMEFLSSRKCIHRDLAARNILLSENNVVKICDFGLARDIYKNPDYVRKGd 241
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 432 ---------------------------------------------MVNREVLEQVERGYRMPCPQGCPESLHELMNLCWK 466
Cdd:cd14207   242 arlplkwmapesifdkiystksdvwsygvllweifslgaspypgvQIDEDFCSKLKEGIRMRAPEFATSEIYQIMLDCWQ 321

                  ....*....
gi 1370473802 467 KDPDERPTF 475
Cdd:cd14207   322 GDPNERPRF 330
PTKc_PDGFR_alpha cd05105
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor alpha; ...
270-483 9.26e-23

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: 100.10  E-value: 9.26e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 270 WEIPRESLRLEVKLGQGCFGEVWMGTWNGTT------KVAIKTLKPGTMMPE--AFLQEAQIMKKL-RHDKLVPLYAVVS 340
Cdd:cd05105    32 WEFPRDGLVLGRILGSGAFGKVVEGTAYGLSrsqpvmKVAVKMLKPTARSSEkqALMSELKIMTHLgPHLNIVNLLGACT 111
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 341 EE-PIYIVTEFMSKGSLLDFLK--------------------------------------EGDGKYLKLPQ--------- 372
Cdd:cd05105   112 KSgPIYIITEYCFYGDLVNYLHknrdnflsrhpekpkkdldifginpadestrsyvilsfENKGDYMDMKQadttqyvpm 191
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 373 -----------------------------------------------LVDMAAQIADGMAYIERMNYIHRDLRAANILVG 405
Cdd:cd05105   192 leikeaskysdiqrsnydrpasykgsndsevknllsddgseglttldLLSFTYQVARGMEFLASKNCVHRDLAARNVLLA 271
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 406 ENLVCKIADFGLAR-LIEDNEYTARQG---------------------------------------------MVNREVLE 439
Cdd:cd05105   272 QGKIVKICDFGLARdIMHDSNYVSKGStflpvkwmapesifdnlyttlsdvwsygillweifslggtpypgmIVDSTFYN 351
                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....
gi 1370473802 440 QVERGYRMPCPQGCPESLHELMNLCWKKDPDERPTFEYIQSFLE 483
Cdd:cd05105   352 KIKSGYRMAKPDHATQEVYDIMVKCWNSEPEKRPSFLHLSDIVE 395
STKc_MLK1 cd14145
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the ...
271-478 2.02e-22

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: 96.65  E-value: 2.02e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 271 EIPRESLRLEVKLGQGCFGEVWMGTWNGtTKVAIKTLKPG-----TMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEP-I 344
Cdd:cd14145     2 EIDFSELVLEEIIGIGGFGKVYRAIWIG-DEVAVKAARHDpdediSQTIENVRQEAKLFAMLKHPNIIALRGVCLKEPnL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 345 YIVTEFMSKGSLLDFLKegdGKYLKLPQLVDMAAQIADGMAYIER---MNYIHRDLRAANILVGE--------NLVCKIA 413
Cdd:cd14145    81 CLVMEFARGGPLNRVLS---GKRIPPDILVNWAVQIARGMNYLHCeaiVPVIHRDLKSSNILILEkvengdlsNKILKIT 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 414 DFGLAR--------------------LIEDNEYTA-----RQGMVNREVLE-----------QVERGYRM-----PCPQG 452
Cdd:cd14145   158 DFGLARewhrttkmsaagtyawmapeVIRSSMFSKgsdvwSYGVLLWELLTgevpfrgidglAVAYGVAMnklslPIPST 237
                         250       260
                  ....*....|....*....|....*.
gi 1370473802 453 CPESLHELMNLCWKKDPDERPTFEYI 478
Cdd:cd14145   238 CPEPFARLMEDCWNPDPHSRPPFTNI 263
PKc_LIMK_like cd14065
Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of ...
283-475 4.75e-22

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: 95.25  E-value: 4.75e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKVAIktLKPGTMMPE--AFLQEAQIMKKLRHDKLVPLYAV-VSEEPIYIVTEFMSKGSLLDF 359
Cdd:cd14065     1 LGKGFFGEVYKVTHRETGKVMV--MKELKRFDEqrSFLKEVKLMRRLSHPNILRFIGVcVKDNKLNFITEYVNGGTLEEL 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 360 LKEGDGKYlKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILV-----GENLVckIADFGLARLIEDNEYT--ARQ-- 430
Cdd:cd14065    79 LKSMDEQL-PWSQRVSLAKDIASGMAYLHSKNIIHRDLNSKNCLVreanrGRNAV--VADFGLAREMPDEKTKkpDRKkr 155
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 431 -----------------------------GMVNREVLEQVE----------------RGYRMPCPQGCPESLHELMNLCW 465
Cdd:cd14065   156 ltvvgspywmapemlrgesydekvdvfsfGIVLCEIIGRVPadpdylprtmdfgldvRAFRTLYVPDCPPSFLPLAIRCC 235
                         250
                  ....*....|
gi 1370473802 466 KKDPDERPTF 475
Cdd:cd14065   236 QLDPEKRPSF 245
PTKc_Tie2 cd05088
Catalytic domain of the Protein Tyrosine Kinase, Tie2; PTKs catalyze the transfer of the ...
283-478 4.83e-22

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: 96.22  E-value: 4.83e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGT---TKVAIKTLKPGTMMPEA--FLQEAQIMKKLRHDKLVP--LYAVVSEEPIYIVTEFMSKGS 355
Cdd:cd05088    15 IGEGNFGQVLKARIKKDglrMDAAIKRMKEYASKDDHrdFAGELEVLCKLGHHPNIInlLGACEHRGYLYLAIEYAPHGN 94
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 356 LLDFLK-----EGDGKY---------LKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR-- 419
Cdd:cd05088    95 LLDFLRksrvlETDPAFaianstastLSSQQLLHFAADVARGMDYLSQKQFIHRDLAARNILVGENYVAKIADFGLSRgq 174
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 420 ----------------LIEDNEY------------------------TARQGMVNREVLEQVERGYRMPCPQGCPESLHE 459
Cdd:cd05088   175 evyvkktmgrlpvrwmAIESLNYsvyttnsdvwsygvllweivslggTPYCGMTCAELYEKLPQGYRLEKPLNCDDEVYD 254
                         250
                  ....*....|....*....
gi 1370473802 460 LMNLCWKKDPDERPTFEYI 478
Cdd:cd05088   255 LMRQCWREKPYERPSFAQI 273
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
157-240 6.85e-22

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: 89.44  E-value: 6.85e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 157 EWYFGKMGRKDAERLLLnpGNQRGIFLVRESETTKGAYSLSIRDwdeiRGDNVKHYKIRKLDNGGYYI-TTRAQFDTLQK 235
Cdd:cd00173     1 PWFHGSISREEAERLLR--GKPDGTFLVRESSSEPGDYVLSVRS----GDGKVKHYLIERNEGGYYLLgGSGRTFPSLPE 74

                  ....*
gi 1370473802 236 LVKHY 240
Cdd:cd00173    75 LVEHY 79
PTKc_Kit cd05104
Catalytic domain of the Protein Tyrosine Kinase, Kit; PTKs catalyze the transfer of the ...
270-483 1.00e-21

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: 96.90  E-value: 1.00e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 270 WEIPRESLRLEVKLGQGCFGEVWMGTWNGTTK------VAIKTLKPGTMMPE--AFLQEAQIMKKL-RHDKLVPLY-AVV 339
Cdd:cd05104    30 WEFPRDRLRFGKTLGAGAFGKVVEATAYGLAKadsamtVAVKMLKPSAHSTEreALMSELKVLSYLgNHINIVNLLgACT 109
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 340 SEEPIYIVTEFMSKGSLLDFLK---------------------------------------------------------- 361
Cdd:cd05104   110 VGGPTLVITEYCCYGDLLNFLRrkrdsficpkfedlaeaalyrnllhqremacdslneymdmkpsvsyvvptkadkrrgv 189
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 362 ---------------EGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIE-DNE 425
Cdd:cd05104   190 rsgsyvdqdvtseilEEDELALDTEDLLSFSYQVAKGMEFLASKNCIHRDLAARNILLTHGRITKICDFGLARDIRnDSN 269
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 426 YTAR--------------------------------------------QGM-VNREVLEQVERGYRMPCPQGCPESLHEL 460
Cdd:cd05104   270 YVVKgnarlpvkwmapesifecvytfesdvwsygillweifslgsspyPGMpVDSKFYKMIKEGYRMDSPEFAPSEMYDI 349
                         330       340
                  ....*....|....*....|...
gi 1370473802 461 MNLCWKKDPDERPTFEYIQSFLE 483
Cdd:cd05104   350 MRSCWDADPLKRPTFKQIVQLIE 372
STKc_NUAK cd14073
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze ...
278-425 1.48e-21

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: 93.99  E-value: 1.48e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 278 RLEV--KLGQGCFGEVWMGTWNGTTK-VAIKTLKPGTMMPEAFL----QEAQIMKKLRHDKLVPLYAVV-SEEPIYIVTE 349
Cdd:cd14073     2 RYELleTLGKGTYGKVKLAIERATGReVAIKSIKKDKIEDEQDMvrirREIEIMSSLNHPHIIRIYEVFeNKDKIVIVME 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 350 FMSKGSLLDFLKEGDgkylklpQLVDMAA-----QIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDN 424
Cdd:cd14073    82 YASGGELYDYISERR-------RLPEREArrifrQIVSAVHYCHKNGVVHRDLKLENILLDQNGNAKIADFGLSNLYSKD 154

                  .
gi 1370473802 425 E 425
Cdd:cd14073   155 K 155
STKc_MLK2 cd14148
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the ...
283-484 1.66e-21

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: 93.90  E-value: 1.66e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTtKVAIKTLKPG-----TMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEP-IYIVTEFMSKGSL 356
Cdd:cd14148     2 IGVGGFGKVYKGLWRGE-EVAVKAARQDpdediAVTAENVRQEARLFWMLQHPNIIALRGVCLNPPhLCLVMEYARGGAL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 357 LDFLKegdGKYLKLPQLVDMAAQIADGMAYIERMNY---IHRDLRAANILVGE--------NLVCKIADFGLAR------ 419
Cdd:cd14148    81 NRALA---GKKVPPHVLVNWAVQIARGMNYLHNEAIvpiIHRDLKSSNILILEpienddlsGKTLKITDFGLARewhktt 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 420 -------------------LIEDNEYTARQGMVNREVLEQvERGYR-----------------MPCPQGCPESLHELMNL 463
Cdd:cd14148   158 kmsaagtyawmapevirlsLFSKSSDVWSFGVLLWELLTG-EVPYReidalavaygvamnkltLPIPSTCPEPFARLLEE 236
                         250       260
                  ....*....|....*....|.
gi 1370473802 464 CWKKDPDERPTFEYIQSFLED 484
Cdd:cd14148   237 CWDPDPHGRPDFGSILKRLED 257
PTK_HER3 cd05111
Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR ...
273-476 2.08e-21

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: 93.87  E-value: 2.08e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 273 PRESLRLEVkLGQGCFGEVWMGTW--NGTT---KVAIKTL--KPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEPIY 345
Cdd:cd05111     6 ETELRKLKV-LGSGVFGTVHKGIWipEGDSikiPVAIKVIqdRSGRQSFQAVTDHMLAIGSLDHAYIVRLLGICPGASLQ 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 346 IVTEFMSKGSLLDFLKEGDGKyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLI--ED 423
Cdd:cd05111    85 LVTQLLPLGSLLDHVRQHRGS-LGPQLLLNWCVQIAKGMYYLEEHRMVHRNLAARNVLLKSPSQVQVADFGVADLLypDD 163
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 424 NEYTARQ-------------------------------------------GMVNREVLEQVERGYRMPCPQGCPESLHEL 460
Cdd:cd05111   164 KKYFYSEaktpikwmalesihfgkythqsdvwsygvtvwemmtfgaepyaGMRLAEVPDLLEKGERLAQPQICTIDVYMV 243
                         250
                  ....*....|....*.
gi 1370473802 461 MNLCWKKDPDERPTFE 476
Cdd:cd05111   244 MVKCWMIDENIRPTFK 259
STKc_EIF2AK cd13996
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
282-428 2.28e-21

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: 93.90  E-value: 2.28e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMgTWNGTTKV--AIKT--LKPGTMMPEAFLQEAQIMKKLRHDKLVPLY-AVVSEEPIYIVTEFMSKGSL 356
Cdd:cd13996    13 LLGSGGFGSVYK-VRNKVDGVtyAIKKirLTEKSSASEKVLREVKALAKLNHPNIVRYYtAWVEEPPLYIQMELCEGGTL 91
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370473802 357 LDFLKEGDG-KYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILV-GENLVCKIADFGLARLIEDNEYTA 428
Cdd:cd13996    92 RDWIDRRNSsSKNDRKLALELFKQILKGVSYIHSKGIVHRDLKPSNIFLdNDDLQVKIGDFGLATSIGNQKREL 165
STKc_MST1_2 cd06612
Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; ...
273-423 2.37e-21

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: 93.48  E-value: 2.37e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 273 PRESLRLEVKLGQGCFGEVWMGTWNGTTK-VAIKTLkPGTMMPEAFLQEAQIMKKLRHDKLVPLYA-VVSEEPIYIVTEF 350
Cdd:cd06612     1 PEEVFDILEKLGEGSYGSVYKAIHKETGQvVAIKVV-PVEEDLQEIIKEISILKQCDSPYIVKYYGsYFKNTDLWIVMEY 79
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370473802 351 MSKGSLLDFLKEgDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIED 423
Cdd:cd06612    80 CGAGSVSDIMKI-TNKTLTEEEIAAILYQTLKGLEYLHSNKKIHRDIKAGNILLNEEGQAKLADFGVSGQLTD 151
STKc_ATG1_ULK_like cd14009
Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like ...
283-476 2.93e-21

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: 93.06  E-value: 2.93e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGT-TKVAIKTLKPGTMMP---EAFLQEAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFMSKGSLL 357
Cdd:cd14009     1 IGRGSFATVWKGRHKQTgEVVAIKEISRKKLNKklqENLESEIAILKSIKHPNIVRLYDVQkTEDFIYLVLEYCAGGDLS 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 358 DFLKegdgKYLKLPQLV--DMAAQIADGMAYIERMNYIHRDLRAANILV---GENLVCKIADFGLARLIEDN-------- 424
Cdd:cd14009    81 QYIR----KRGRLPEAVarHFMQQLASGLKFLRSKNIIHRDLKPQNLLLstsGDDPVLKIADFGFARSLQPAsmaetlcg 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 425 -------------EYTAR--------------------QGMVNREVLEQVERGYRMPCPQGCPESLHELMNLCW---KKD 468
Cdd:cd14009   157 splymapeilqfqKYDAKadlwsvgailfemlvgkppfRGSNHVQLLRNIERSDAVIPFPIAAQLSPDCKDLLRrllRRD 236

                  ....*...
gi 1370473802 469 PDERPTFE 476
Cdd:cd14009   237 PAERISFE 244
PK_KSR cd14063
Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to ...
282-483 3.99e-21

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: 93.18  E-value: 3.99e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGttKVAIKTLKPGTMMPE---AFLQEAQIMKKLRHDKLVPLYAVVSEEPIY-IVTEFMSKGSLL 357
Cdd:cd14063     7 VIGKGRFGRVHRGRWHG--DVAIKLLNIDYLNEEqleAFKEEVAAYKNTRHDNLVLFMGACMDPPHLaIVTSLCKGRTLY 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 358 DFLKEGDGKyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCkIADFGLARLIEDNEYTARQG------ 431
Cdd:cd14063    85 SLIHERKEK-FDFNKTVQIAQQICQGMGYLHAKGIIHKDLKSKNIFLENGRVV-ITDFGLFSLSGLLQPGRREDtlvipn 162
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 432 -----------------------------------------MVNRE----------VLEQVERGYRMPCPQ-GCPESLHE 459
Cdd:cd14063   163 gwlcylapeiiralspdldfeeslpftkasdvyafgtvwyeLLAGRwpfkeqpaesIIWQVGCGKKQSLSQlDIGREVKD 242
                         250       260
                  ....*....|....*....|....
gi 1370473802 460 LMNLCWKKDPDERPTFEYIQSFLE 483
Cdd:cd14063   243 ILMQCWAYDPEKRPTFSDLLRMLE 266
PTKc_VEGFR3 cd05102
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; ...
270-484 4.26e-21

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: 94.28  E-value: 4.26e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 270 WEIPRESLRLEVKLGQGCFGEVWMGTWNGTTK------VAIKTLKPGTMMPE--AFLQEAQIMKKL-RHDKLVPLYAVVS 340
Cdd:cd05102     2 WEFPRDRLRLGKVLGHGAFGKVVEASAFGIDKssscetVAVKMLKEGATASEhkALMSELKILIHIgNHLNVVNLLGACT 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 341 EE--PIYIVTEFMSKGSLLDFLK---EGDGKY------------------------------------------------ 367
Cdd:cd05102    82 KPngPLMVIVEFCKYGNLSNFLRakrEGFSPYrersprtrsqvrsmveavradrrsrqgsdrvasftestsstnqprqev 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 368 -------LKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLI-EDNEYTaRQG-------- 431
Cdd:cd05102   162 ddlwqspLTMEDLICYSFQVARGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLARDIyKDPDYV-RKGsarlplkw 240
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 432 --------------------------------------MVNREVLEQVERGYRMPCPQGCPESLHELMNLCWKKDPDERP 473
Cdd:cd05102   241 mapesifdkvyttqsdvwsfgvllweifslgaspypgvQINEEFCQRLKDGTRMRAPEYATPEIYRIMLSCWHGDPKERP 320
                         330
                  ....*....|.
gi 1370473802 474 TFEYIQSFLED 484
Cdd:cd05102   321 TFSDLVEILGD 331
STKc_LKB1_CaMKK cd14008
Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent ...
283-429 6.73e-21

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: 92.23  E-value: 6.73e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGT-TKVAIKTL----------------KPGTMMpEAFLQEAQIMKKLRHDKLVPLYAVV---SEE 342
Cdd:cd14008     1 LGRGSFGKVKLALDTETgQLYAIKIFnksrlrkrregkndrgKIKNAL-DDVRREIAIMKKLDHPNIVRLYEVIddpESD 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 343 PIYIVTEFMSKGSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIE 422
Cdd:cd14008    80 KLYLVLEYCEGGPVMELDSGDRVPPLPEETARKYFRDLVLGLEYLHENGIVHRDIKPENLLLTADGTVKISDFGVSEMFE 159

                  ....*...
gi 1370473802 423 -DNEYTAR 429
Cdd:cd14008   160 dGNDTLQK 167
STKc_RIP1 cd14027
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze ...
283-475 7.20e-21

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: 92.18  E-value: 7.20e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKVAIKTLKPGTMMPE---AFLQEAQIMKKLRHDKLVPLYAVVSEEPIY-IVTEFMSKGSLLD 358
Cdd:cd14027     1 LDSGGFGKVSLCFHRTQGLVVLKTVYTGPNCIEhneALLEEGKMMNRLRHSRVVKLLGVILEEGKYsLVMEYMEKGNLMH 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 359 FLKEgdgkyLKLPQLVD--MAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLA------RLieDNEYTARQ 430
Cdd:cd14027    81 VLKK-----VSVPLSVKgrIILEIIEGMAYLHGKGVIHKDLKPENILVDNDFHIKIADLGLAsfkmwsKL--TKEEHNEQ 153
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 431 --------------------------------------GMV------NREVLE-------------QVERGYRMPCPQGC 453
Cdd:cd14027   154 revdgtakknagtlyymapehlndvnakpteksdvysfAIVlwaifaNKEPYEnainedqiimcikSGNRPDVDDITEYC 233
                         250       260
                  ....*....|....*....|..
gi 1370473802 454 PESLHELMNLCWKKDPDERPTF 475
Cdd:cd14027   234 PREIIDLMKLCWEANPEARPTF 255
PKc_MAPKK_plant_like cd06623
Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and ...
275-424 1.63e-20

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: 91.11  E-value: 1.63e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 275 ESLRLEVKLGQGCFGEVWMGTWNGTTK-VAIKTLKPG--TMMPEAFLQEAQIMKKLRHDKLVPLY-AVVSEEPIYIVTEF 350
Cdd:cd06623     1 SDLERVKVLGQGSSGVVYKVRHKPTGKiYALKKIHVDgdEEFRKQLLRELKTLRSCESPYVVKCYgAFYKEGEISIVLEY 80
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370473802 351 MSKGSLLDFLKegdgKYLKLP--QLVDMAAQIADGMAYIERM-NYIHRDLRAANILVGENLVCKIADFGLARLIEDN 424
Cdd:cd06623    81 MDGGSLADLLK----KVGKIPepVLAYIARQILKGLDYLHTKrHIIHRDIKPSNLLINSKGEVKIADFGISKVLENT 153
Pkinase pfam00069
Protein kinase domain;
277-476 1.70e-20

Protein kinase domain;


Pssm-ID: 459660 [Multi-domain]  Cd Length: 217  Bit Score: 90.00  E-value: 1.70e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 277 LRLEVKLGQGCFGEVWMGTWNGTTK-VAIKTLK---PGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEP-IYIVTEFM 351
Cdd:pfam00069   1 YEVLRKLGSGSFGTVYKAKHRDTGKiVAIKKIKkekIKKKKDKNILREIKILKKLNHPNIVRLYDAFEDKDnLYLVLEYV 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 352 SKGSLLDFLKEgdGKYLKLPQLVDMAAQIADGMAYIERMN-------YI------------HRDLRAANILVGEnLVCKI 412
Cdd:pfam00069  81 EGGSLFDLLSE--KGAFSEREAKFIMKQILEGLESGSSLTtfvgtpwYMapevlggnpygpKVDVWSLGCILYE-LLTGK 157
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370473802 413 ADFGLARLIEDNEYTARQgmvnrevleqveRGYRMPCPQGCPESLHELMNLCWKKDPDERPTFE 476
Cdd:pfam00069 158 PPFPGINGNEIYELIIDQ------------PYAFPELPSNLSEEAKDLLKKLLKKDPSKRLTAT 209
STKc_Aurora cd14007
Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of ...
282-418 1.93e-20

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: 90.61  E-value: 1.93e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGT-TKVAIKTLKPGTM----MPEAFLQEAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFMSKGS 355
Cdd:cd14007     7 PLGKGKFGNVYLAREKKSgFIVALKVISKSQLqksgLEHQLRREIEIQSHLRHPNILRLYGYFeDKKRIYLILEYAPNGE 86
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370473802 356 LLDFLKegdgKYLKLPQlvDMAA----QIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLA 418
Cdd:cd14007    87 LYKELK----KQKRFDE--KEAAkyiyQLALALDYLHSKNIIHRDIKPENILLGSNGELKLADFGWS 147
STKc_CDK9 cd07865
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs ...
281-437 1.96e-20

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: 91.66  E-value: 1.96e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 281 VKLGQGCFGEVWMGTWNGTTK-VAIKTL-----KPGtmMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEP---------IY 345
Cdd:cd07865    18 AKIGQGTFGEVFKARHRKTGQiVALKKVlmeneKEG--FPITALREIKILQLLKHENVVNLIEICRTKAtpynrykgsIY 95
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 346 IVTEFMSKgSLLDFLKEGDGKYlKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNE 425
Cdd:cd07865    96 LVFEFCEH-DLAGLLSNKNVKF-TLSEIKKVMKMLLNGLYYIHRNKILHRDMKAANILITKDGVLKLADFGLARAFSLAK 173
                         170
                  ....*....|..
gi 1370473802 426 YTARQGMVNREV 437
Cdd:cd07865   174 NSQPNRYTNRVV 185
SH2_csk_like cd09937
Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal ...
158-259 3.22e-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: 85.42  E-value: 3.22e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 158 WYFGKMGRKDAERLLLNPGNqrGIFLVRESETTKGAYSLSIRdwdeiRGDNVKHYKIRKLdNGGYYITTRAQFDTLQKLV 237
Cdd:cd09937     5 WFHGKISREEAERLLQPPED--GLFLVRESTNYPGDYTLCVS-----FEGKVEHYRVIYR-NGKLTIDEEEYFENLIQLV 76
                          90       100
                  ....*....|....*....|..
gi 1370473802 238 KHYTEHADGLCHKLTTvcPTVK 259
Cdd:cd09937    77 EHYTKDADGLCTRLVK--PKVK 96
STKc_TSSK4-like cd14162
Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs ...
283-419 6.19e-20

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: 89.28  E-value: 6.19e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNG-TTKVAIKTLKPgTMMPEAFLQ-----EAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFMSKGS 355
Cdd:cd14162     8 LGHGSYAVVKKAYSTKhKCKVAIKIVSK-KKAPEDYLQkflprEIEVIKGLKHPNLICFYEAIeTTSRVYIIMELAENGD 86
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370473802 356 LLDFLKEGdgKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR 419
Cdd:cd14162    87 LLDYIRKN--GALPEPQARRWFRQLVAGVEYCHSKGVVHRDLKCENLLLDKNNNLKITDFGFAR 148
STKc_AMPK_alpha cd14079
Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein ...
278-426 6.70e-20

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: 89.25  E-value: 6.70e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 278 RLEVKLGQGCFGEVWMGTWNGT-TKVAIKTLKPGTM----MPEAFLQEAQIMKKLRHDKLVPLYAVVsEEP--IYIVTEF 350
Cdd:cd14079     5 ILGKTLGVGSFGKVKLAEHELTgHKVAVKILNRQKIksldMEEKIRREIQILKLFRHPHIIRLYEVI-ETPtdIFMVMEY 83
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370473802 351 MSKGSLLDFLKEgDGKyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEY 426
Cdd:cd14079    84 VSGGELFDYIVQ-KGR-LSEDEARRFFQQIISGVEYCHRHMVVHRDLKPENLLLDSNMNVKIADFGLSNIMRDGEF 157
PTKc_Aatyk1 cd05087
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 1; PTKs ...
282-482 7.31e-20

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: 89.28  E-value: 7.31e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWN---GTTKVAIKTLKPGTMMPEA--FLQEAQIMKKLRHDKLVPLYAVVSE-EPIYIVTEFMSKGS 355
Cdd:cd05087     4 EIGHGWFGKVFLGEVNsglSSTQVVVKELKASASVQDQmqFLEEAQPYRALQHTNLLQCLAQCAEvTPYLLVMEFCPLGD 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 356 LLDFLKEGDGKYLKLPQ---LVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEY--TARQ 430
Cdd:cd05087    84 LKGYLRSCRAAESMAPDpltLQRMACEVACGLLHLHRNNFVHSDLALRNCLLTADLTVKIGDYGLSHCKYKEDYfvTADQ 163
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 431 GMV--------------------------------------------------NREVLEQV--ERGYRMPCPQ---GCPE 455
Cdd:cd05087   164 LWVplrwiapelvdevhgnllvvdqtkqsnvwslgvtiwelfelgnqpyrhysDRQVLTYTvrEQQLKLPKPQlklSLAE 243
                         250       260
                  ....*....|....*....|....*..
gi 1370473802 456 SLHELMNLCWKKdPDERPTFEYIQSFL 482
Cdd:cd05087   244 RWYEVMQFCWLQ-PEQRPTAEEVHLLL 269
PK_GC cd13992
Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows ...
302-482 1.01e-19

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: 88.99  E-value: 1.01e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 302 VAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEP-IYIVTEFMSKGSLLDFLKEGDGKylklpqlVD----- 375
Cdd:cd13992    28 VAIKHITFSRTEKRTILQELNQLKELVHDNLNKFIGICINPPnIAVVTEYCTRGSLQDVLLNREIK-------MDwmfks 100
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 376 -MAAQIADGMAYIERMNYI-HRDLRAANILVGENLVCKIADFGLARLIEDNE--------------YTA----RQ----- 430
Cdd:cd13992   101 sFIKDIVKGMNYLHSSSIGyHGRLKSSNCLVDSRWVVKLTDFGLRNLLEEQTnhqldedaqhkkllWTApellRGsllev 180
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 431 -----------GMVNREVLEQVERGY----------------RMPCPQ------GCPESLHELMNLCWKKDPDERPTFEY 477
Cdd:cd13992   181 rgtqkgdvysfAIILYEILFRSDPFAlerevaivekvisggnKPFRPElavlldEFPPRLVLLVKQCWAENPEKRPSFKQ 260

                  ....*
gi 1370473802 478 IQSFL 482
Cdd:cd13992   261 IKKTL 265
STKc_PLK cd14099
Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the ...
283-425 1.06e-19

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: 88.38  E-value: 1.06e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKV-AIKTLKPGTM----MPEAFLQEAQIMKKLRHDKLVPLYAV-VSEEPIYIVTEFMSKGSL 356
Cdd:cd14099     9 LGKGGFAKCYEVTDMSTGKVyAGKVVPKSSLtkpkQREKLKSEIKIHRSLKHPNIVKFHDCfEDEENVYILLELCSNGSL 88
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1370473802 357 LDFLKEGdgKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNE 425
Cdd:cd14099    89 MELLKRR--KALTEPEVRYFMRQILSGVKYLHSNRIIHRDLKLGNLFLDENMNVKIGDFGLAARLEYDG 155
STKc_TSSK-like cd14080
Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs ...
278-425 1.08e-19

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: 88.78  E-value: 1.08e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 278 RLEVKLGQGCFGEVWMGTWNGTT---KVAIKTLKPgTMMPEAFLQ-----EAQIMKKLRHDKLVPLYAVVSEEP-IYIVT 348
Cdd:cd14080     3 RLGKTIGEGSYSKVKLAEYTKSGlkeKVACKIIDK-KKAPKDFLEkflprELEILRKLRHPNIIQVYSIFERGSkVFIFM 81
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370473802 349 EFMSKGSLLDFLKEGdGKyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNE 425
Cdd:cd14080    82 EYAEHGDLLEYIQKR-GA-LSESQARIWFRQLALAVQYLHSLDIAHRDLKCENILLDSNNNVKLSDFGFARLCPDDD 156
STKc_SIK cd14071
Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the ...
279-426 1.11e-19

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: 88.60  E-value: 1.11e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 279 LEVKLGQGCFGEVWMGTWNGT-TKVAIKTLKPgTMMPEAFLQ----EAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFMS 352
Cdd:cd14071     4 IERTIGKGNFAVVKLARHRITkTEVAIKIIDK-SQLDEENLKkiyrEVQIMKMLNHPHIIKLYQVMeTKDMLYLVTEYAS 82
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370473802 353 KGSLLDFLKEgDGKyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEY 426
Cdd:cd14071    83 NGEIFDYLAQ-HGR-MSEKEARKKFWQILSAVEYCHKRHIVHRDLKAENLLLDANMNIKIADFGFSNFFKPGEL 154
PTKc_VEGFR2 cd05103
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; ...
270-489 1.69e-19

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: 89.65  E-value: 1.69e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 270 WEIPRESLRLEVKLGQGCFGEVWMGTWNGTTK------VAIKTLKPGTMMPE--AFLQEAQIMKKLRHD-KLVPLYAVVS 340
Cdd:cd05103     2 WEFPRDRLKLGKPLGRGAFGQVIEADAFGIDKtatcrtVAVKMLKEGATHSEhrALMSELKILIHIGHHlNVVNLLGACT 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 341 EE--PIYIVTEFMSKGSLLDFL----------KEGDGKY----------------------------------------- 367
Cdd:cd05103    82 KPggPLMVIVEFCKFGNLSAYLrskrsefvpyKTKGARFrqgkdyvgdisvdlkrrldsitssqssassgfveekslsdv 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 368 --------------LKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR-------------- 419
Cdd:cd05103   162 eeeeagqedlykdfLTLEDLICYSFQVAKGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLARdiykdpdyvrkgda 241
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 420 ----------LIEDNEYTARQGM----------------------VNREVLEQVERGYRMPCPQGCPESLHELMNLCWKK 467
Cdd:cd05103   242 rlplkwmapeTIFDRVYTIQSDVwsfgvllweifslgaspypgvkIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHG 321
                         330       340
                  ....*....|....*....|..
gi 1370473802 468 DPDERPTFEYIQSFLEDYFTAT 489
Cdd:cd05103   322 EPSQRPTFSELVEHLGNLLQAN 343
PK_GC-A_B cd14042
Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The ...
293-482 1.73e-19

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: 88.42  E-value: 1.73e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 293 MGTWNGTtKVAIK-TLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEP-IYIVTEFMSKGSLLDFLkEGDGkyLKL 370
Cdd:cd14042    25 TGYYKGN-LVAIKkVNKKRIDLTREVLKELKHMRDLQHDNLTRFIGACVDPPnICILTEYCPKGSLQDIL-ENED--IKL 100
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 371 PQL--VDMAAQIADGMAYIE----RMnyiHRDLRAANILVGENLVCKIADFGLARL-------IEDNEYTAR-------- 429
Cdd:cd14042   101 DWMfrYSLIHDIVKGMHYLHdseiKS---HGNLKSSNCVVDSRFVLKITDFGLHSFrsgqeppDDSHAYYAKllwtapel 177
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 430 -----------------------QGMVNRE---------------VLEQVERGYRMP-----CPQGCPESLHELMNLCWK 466
Cdd:cd14042   178 lrdpnppppgtqkgdvysfgiilQEIATRQgpfyeegpdlspkeiIKKKVRNGEKPPfrpslDELECPDEVLSLMQRCWA 257
                         250
                  ....*....|....*.
gi 1370473802 467 KDPDERPTFEYIQSFL 482
Cdd:cd14042   258 EDPEERPDFSTLRNKL 273
SH3_Blk cd12009
Src homology 3 domain of Blk Protein Tyrosine Kinase; Blk is a member of the Src subfamily of ...
97-149 2.47e-19

Src homology 3 domain of Blk Protein Tyrosine Kinase; Blk is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. It is expressed specifically in B-cells and 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 SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. 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: 212942 [Multi-domain]  Cd Length: 54  Bit Score: 81.40  E-value: 2.47e-19
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1370473802  97 VALYDYEARTTEDLSFKKGERFQIINNTeGDWWEARSIATGKNGYIPSNYVAP 149
Cdd:cd12009     3 IAQYDFVPSNERDLQLKKGEKLQVLKSD-GEWWLAKSLTTGKEGYIPSNYVAR 54
STKc_MAPK cd07834
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs ...
279-467 3.40e-19

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: 88.35  E-value: 3.40e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 279 LEVKLGQGCFGEVWMGTWNGT-TKVAIKtlkpgtMMPEAF---------LQEAQIMKKLRHDKLVPLYAVV------SEE 342
Cdd:cd07834     4 LLKPIGSGAYGVVCSAYDKRTgRKVAIK------KISNVFddlidakriLREIKILRHLKHENIIGLLDILrppspeEFN 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 343 PIYIVTEFMskgslldflkEGD-GKYLKLPQ-LVD-----MAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADF 415
Cdd:cd07834    78 DVYIVTELM----------ETDlHKVIKSPQpLTDdhiqyFLYQILRGLKYLHSAGVIHRDLKPSNILVNSNCDLKICDF 147
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1370473802 416 GLARLIEDNEytaRQGMVNREVleqVERGYRMPcpqgcpeslhELMnLCWKK 467
Cdd:cd07834   148 GLARGVDPDE---DKGFLTEYV---VTRWYRAP----------ELL-LSSKK 182
SH2_N-SH2_PLC_gamma_like cd10341
N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
154-243 4.10e-19

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: 82.40  E-value: 4.10e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 154 QAEEWYFGKM--GRKDAERLLL--NPGNQrGIFLVRESETTKGAYSLSIrdWdeiRGDNVKHYKIRKLDNGG---YYITT 226
Cdd:cd10341     2 FTEPWFHGKLgdGRDEAEKLLLeyCEGGD-GTFLVRESETFVGDYTLSF--W---RNGKVQHCRIRSRQENGekkYYLTD 75
                          90
                  ....*....|....*..
gi 1370473802 227 RAQFDTLQKLVKHYTEH 243
Cdd:cd10341    76 NLVFDSLYELIDYYRQN 92
STKc_ACVR2 cd14053
Catalytic domain of the Serine/Threonine Kinase, Activin Type II Receptor; STKs catalyze the ...
280-425 4.82e-19

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: 87.38  E-value: 4.82e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 280 EVKLGqGCFGEVWMGTWNGTTkVAIKtlkpgtMMPE----AFLQEAQIMK--KLRHDKLVPLYAV----VSEEPIY-IVT 348
Cdd:cd14053     1 EIKAR-GRFGAVWKAQYLNRL-VAVK------IFPLqekqSWLTEREIYSlpGMKHENILQFIGAekhgESLEAEYwLIT 72
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 349 EFMSKGSLLDFLKegdGKYLKLPQLVDMAAQIADGMAYI--ERMNY--------IHRDLRAANILVGENLVCKIADFGLA 418
Cdd:cd14053    73 EFHERGSLCDYLK---GNVISWNELCKIAESMARGLAYLheDIPATngghkpsiAHRDFKSKNVLLKSDLTACIADFGLA 149

                  ....*..
gi 1370473802 419 RLIEDNE 425
Cdd:cd14053   150 LKFEPGK 156
STKc_LIMK2 cd14222
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the ...
283-488 6.41e-19

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: 86.54  E-value: 6.41e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKVAI--KTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFMSKGSLLDF 359
Cdd:cd14222     1 LGKGFFGQAIKVTHKATGKVMVmkELIRCDEETQKTFLTEVKVMRSLDHPNVLKFIGVLyKDKRLNLLTEFIEGGTLKDF 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 360 LKEGDgkYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLI-ED--------------- 423
Cdd:cd14222    81 LRADD--PFPWQQKVSFAKGIASGMAYLHSMSIIHRDLNSHNCLIKLDKTVVVADFGLSRLIvEEkkkpppdkpttkkrt 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 424 --------------NEYTARQGMVNR-----------------EVLEQVergYRMP-C-------------------PQG 452
Cdd:cd14222   159 lrkndrkkrytvvgNPYWMAPEMLNGksydekvdifsfgivlcEIIGQV---YADPdClprtldfglnvrlfwekfvPKD 235
                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 1370473802 453 CPESLHELMNLCWKKDPDERPTFEYiqsfLEDYFTA 488
Cdd:cd14222   236 CPPAFFPLAAICCRLEPDSRPAFSK----LEDSFEA 267
STKc_OSR1_SPAK cd06610
Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and ...
301-474 2.03e-18

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: 85.10  E-value: 2.03e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 301 KVAIKTL---KPGTMMPEAfLQEAQIMKKLRHDKLVPLY-AVVSEEPIYIVTEFMSKGSLLDFLKEgdgkylKLPQLVDM 376
Cdd:cd06610    28 KVAIKRIdleKCQTSMDEL-RKEIQAMSQCNHPNVVSYYtSFVVGDELWLVMPLLSGGSLLDIMKS------SYPRGGLD 100
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 377 AAQIA-------DGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDN---EYTARQGMVNR------EVLEQ 440
Cdd:cd06610   101 EAIIAtvlkevlKGLEYLHSNGQIHRDVKAGNILLGEDGSVKIADFGVSASLATGgdrTRKVRKTFVGTpcwmapEVMEQ 180
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1370473802 441 VeRGYR-------------------------------MPCPQGCPESLH-------------ELMNLCWKKDPDERPT 474
Cdd:cd06610   181 V-RGYDfkadiwsfgitaielatgaapyskyppmkvlMLTLQNDPPSLEtgadykkysksfrKMISLCLQKDPSKRPT 257
STKc_CDK7 cd07841
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs ...
282-419 2.16e-18

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: 85.70  E-value: 2.16e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGT-TKVAIKTLKPGTMmPEAF-------LQEAQIMKKLRHDKLVPLYAVVSEEP-IYIVTEFMS 352
Cdd:cd07841     7 KLGEGTYAVVYKARDKETgRIVAIKKIKLGER-KEAKdginftaLREIKLLQELKHPNIIGLLDVFGHKSnINLVFEFME 85
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370473802 353 ---KGSLLD---FLKEGDGKYLKLpqlvdmaaQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR 419
Cdd:cd07841    86 tdlEKVIKDksiVLTPADIKSYML--------MTLRGLEYLHSNWILHRDLKPNNLLIASDGVLKLADFGLAR 150
STKc_FA2-like cd08529
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar ...
279-480 2.20e-18

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: 84.77  E-value: 2.20e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 279 LEVKLGQGCFGEVWMGTWNGTTKV-AIKTLKPGTM---MPEAFLQEAQIMKKLRHDKLVPLY-AVVSEEPIYIVTEFMSK 353
Cdd:cd08529     4 ILNKLGKGSFGVVYKVVRKVDGRVyALKQIDISRMsrkMREEAIDEARVLSKLNSPYVIKYYdSFVDKGKLNIVMEYAEN 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 354 GSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR-------------- 419
Cdd:cd08529    84 GDLHSLIKSQRGRPLPEDQIWKFFIQTLLGLSHLHSKKILHRDIKSMNIFLDKGDNVKIGDLGVAKilsdttnfaqtivg 163
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 420 --------LIEDNEYTARQ-----GMVNRE---------------VLEQVERGYRMPCPQGCPESLHELMNLCWKKDPDE 471
Cdd:cd08529   164 tpyylspeLCEDKPYNEKSdvwalGCVLYElctgkhpfeaqnqgaLILKIVRGKYPPISASYSQDLSQLIDSCLTKDYRQ 243
                         250
                  ....*....|
gi 1370473802 472 RP-TFEYIQS 480
Cdd:cd08529   244 RPdTTELLRN 253
STKc_MEKK3_like cd06625
Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) ...
283-422 2.88e-18

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: 84.33  E-value: 2.88e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTK-VAIKTLKPGTMMPE------AFLQEAQIMKKLRHDKLVPLYAVVSEE-PIYIVTEFMSKG 354
Cdd:cd06625     8 LGQGAFGQVYLCYDADTGReLAVKQVEIDPINTEaskevkALECEIQLLKNLQHERIVQYYGCLQDEkSLSIFMEYMPGG 87
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 355 SLLDFLKegdgKYLKLPQLV--DMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIE 422
Cdd:cd06625    88 SVKDEIK----AYGALTENVtrKYTRQILEGLAYLHSNMIVHRDIKGANILRDSNGNVKLGDFGASKRLQ 153
STKc_TGFbR_I cd14056
Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta family Type ...
283-418 4.37e-18

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: 84.63  E-value: 4.37e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTtKVAIKTLKpgTMMPEAFLQEAQI--MKKLRHDKLVPLYA--VVSEEPI---YIVTEFMSKGS 355
Cdd:cd14056     3 IGKGRYGEVWLGKYRGE-KVAVKIFS--SRDEDSWFRETEIyqTVMLRHENILGFIAadIKSTGSWtqlWLITEYHEHGS 79
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370473802 356 LLDFLKEGDgkyLKLPQLVDMAAQIADGMAYI--ERMNY------IHRDLRAANILVGENLVCKIADFGLA 418
Cdd:cd14056    80 LYDYLQRNT---LDTEEALRLAYSAASGLAHLhtEIVGTqgkpaiAHRDLKSKNILVKRDGTCCIADLGLA 147
STKc_MEKK4 cd06626
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
282-434 6.63e-18

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: 83.51  E-value: 6.63e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGTTKV-AIKTLKPGTMMPEAFLQ---EAQIMKKLRHDKLVPLYAV-VSEEPIYIVTEFMSKGSL 356
Cdd:cd06626     7 KIGEGTFGKVYTAVNLDTGELmAMKEIRFQDNDPKTIKEiadEMKVLEGLDHPNLVRYYGVeVHREEVYIFMEYCQEGTL 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 357 LDFLKEGDGkylkLPQLV--DMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYTARQGMVN 434
Cdd:cd06626    87 EELLRHGRI----LDEAVirVYTLQLLEGLAYLHENGIVHRDIKPANIFLDSNGLIKLGDFGSAVKLKNNTTTMAPGEVN 162
SH3_Lyn cd12004
Src homology 3 domain of Lyn Protein Tyrosine Kinase; Lyn is a member of the Src subfamily of ...
95-151 8.11e-18

Src homology 3 domain of Lyn Protein Tyrosine Kinase; 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 SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. 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: 212937 [Multi-domain]  Cd Length: 56  Bit Score: 77.34  E-value: 8.11e-18
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1370473802  95 IFVALYDYEARTTEDLSFKKGERFQIINNtEGDWWEARSIATGKNGYIPSNYVAPAD 151
Cdd:cd12004     1 IVVALYPYDGIHEDDLSFKKGEKLKVIEE-HGEWWKARSLTTKKEGFIPSNYVAKVN 56
SH2_Grb2_like cd09941
Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar ...
158-243 8.38e-18

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: 78.47  E-value: 8.38e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 158 WYFGKMGRKDAERLLLNPGNqRGIFLVRESETTKGAYSLSIRDwdeirGDNVKHYKIRKLDNGGYYITTrAQFDTLQKLV 237
Cdd:cd09941     5 WFHGKISRAEAEEILMNQRP-DGAFLIRESESSPGDFSLSVKF-----GNDVQHFKVLRDGAGKYFLWV-VKFNSLNELV 77

                  ....*.
gi 1370473802 238 KHYTEH 243
Cdd:cd09941    78 DYHRTT 83
PTKc_Wee1_fungi cd14052
Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the ...
283-428 1.23e-17

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: 82.85  E-value: 1.23e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTW-NGTTKV-AIKTLKPGTMMP---EAFLQEAQIMKKLR---HDKLVPLYAVVSEEP-IYIVTEFMSK 353
Cdd:cd14052     8 IGSGEFSQVYKVSErVPTGKVyAVKKLKPNYAGAkdrLRRLEEVSILRELTldgHDNIVQLIDSWEYHGhLYIQTELCEN 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 354 GSLLDFLKE-GDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLA------RLIE---D 423
Cdd:cd14052    88 GSLDVFLSElGLLGRLDEFRVWKILVELSLGLRFIHDHHFVHLDLKPANVLITFEGTLKIGDFGMAtvwpliRGIEregD 167

                  ....*
gi 1370473802 424 NEYTA 428
Cdd:cd14052   168 REYIA 172
SH2_Srm cd10360
Src homology 2 (SH2) domain found in Src-related kinase lacking C-terminal regulatory tyrosine ...
158-240 1.50e-17

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: 77.30  E-value: 1.50e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 158 WYFGKMGRKDAERLLLNPGNQRGIFLVRESETTKGAYSLSIRDWDEirgdnVKHYKIRKLDNGGYYITTRAQFDTLQKLV 237
Cdd:cd10360     2 WYFSGISRTQAQQLLLSPPNEPGAFLIRPSESSLGGYSLSVRAQAK-----VCHYRICMAPSGSLYLQKGRLFPGLEELL 76

                  ...
gi 1370473802 238 KHY 240
Cdd:cd10360    77 AYY 79
STKc_Rad53_Cds1 cd14098
Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the ...
283-457 1.65e-17

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: 82.52  E-value: 1.65e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWM------GTWNGTTKVAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSE-EPIYIVTEFMSKGS 355
Cdd:cd14098     8 LGSGTFAEVKKavevetGKMRAIKQIVKRKVAGNDKNLQLFQREINILKSLEHPGIVRLIDWYEDdQHIYLVMEYVEGGD 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 356 LLDFLKEGDGkylkLPQLV--DMAAQIADGMAYIERMNYIHRDLRAANILVGEN--LVCKIADFGLARLIEDNE----YT 427
Cdd:cd14098    88 LMDFIMAWGA----IPEQHarELTKQILEAMAYTHSMGITHRDLKPENILITQDdpVIVKISDFGLAKVIHTGTflvtFC 163
                         170       180       190
                  ....*....|....*....|....*....|
gi 1370473802 428 ARQGMVNREVLEQVERGyrmpcPQGCPESL 457
Cdd:cd14098   164 GTMAYLAPEILMSKEQN-----LQGGYSNL 188
STKc_AGC cd05123
Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
283-427 1.76e-17

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: 81.79  E-value: 1.76e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKV-AIKTLKPGTM----MPEAFLQEAQIMKKLRHDKLVPL-YAVVSEEPIYIVTEFMSKGSL 356
Cdd:cd05123     1 LGKGSFGKVLLVRKKDTGKLyAMKVLRKKEIikrkEVEHTLNERNILERVNHPFIVKLhYAFQTEEKLYLVLDYVPGGEL 80
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370473802 357 LDFLKegdgKYLKLPQlvDM----AAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR-LIEDNEYT 427
Cdd:cd05123    81 FSHLS----KEGRFPE--ERarfyAAEIVLALEYLHSLGIIYRDLKPENILLDSDGHIKLTDFGLAKeLSSDGDRT 150
PKc_Wee1_like cd13997
Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the ...
276-478 3.36e-17

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: 81.28  E-value: 3.36e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 276 SLRLEVKLGQGCFGEVWMGT--WNGTTKVAIKTLKP--GTMMPEAFLQEAQIMKKL-RHDKLVPLYAVVSE-EPIYIVTE 349
Cdd:cd13997     1 HFHELEQIGSGSFSEVFKVRskVDGCLYAVKKSKKPfrGPKERARALREVEAHAALgQHPNIVRYYSSWEEgGHLYIQME 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 350 FMSKGSLLDFLKE-GDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIE------ 422
Cdd:cd13997    81 LCENGSLQDALEElSPISKLSEAEVWDLLLQVALGLAFIHSKGIVHLDIKPDNIFISNKGTCKIGDFGLATRLEtsgdve 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 423 --DNEYTARQ--------------------------GMV---NREVLEQVERGYRMPCPQ-GCPESLHELMNLCWKKDPD 470
Cdd:cd13997   161 egDSRYLAPEllnenythlpkadifslgvtvyeaatGEPlprNGQQWQQLRQGKLPLPPGlVLSQELTRLLKVMLDPDPT 240

                  ....*...
gi 1370473802 471 ERPTFEYI 478
Cdd:cd13997   241 RRPTADQL 248
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
92-148 3.61e-17

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: 75.27  E-value: 3.61e-17
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1370473802   92 GVTIFVALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARsIATGKNGYIPSNYVA 148
Cdd:smart00326   1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGR-LGRGKEGLFPSNYVE 56
SH2_Fps_family cd10361
Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related ...
151-243 4.86e-17

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: 76.03  E-value: 4.86e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 151 DSIQAEEWYFGKMGRKDAERLLLNPGNqrgiFLVRESE---TTKGAYSLSIRdWDEirgdNVKHYKIRKLDNGGYYITTR 227
Cdd:cd10361     1 KDLENEPYYHGLLPREDAEELLKNDGD----FLVRKTEpkgGGKRKLVLSVR-WDG----KIRHFVINRDDGGKYYIEGK 71
                          90
                  ....*....|....*.
gi 1370473802 228 AqFDTLQKLVKHYTEH 243
Cdd:cd10361    72 S-FKSISELINYYQKT 86
STKc_BMPR1 cd14144
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type I Receptor; ...
282-441 5.75e-17

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: 5.75e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGTtKVAIKTLKpgTMMPEAFLQEAQIMKK--LRHDKLVPLYAVV-----SEEPIYIVTEFMSKG 354
Cdd:cd14144     2 SVGKGRYGEVWKGKWRGE-KVAVKIFF--TTEEASWFRETEIYQTvlMRHENILGFIAADikgtgSWTQLYLITDYHENG 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 355 SLLDFLKegdGKYLKLPQLVDMAAQIADGMAYIERMNY--------IHRDLRAANILVGENLVCKIADFGLA-RLI-EDN 424
Cdd:cd14144    79 SLYDFLR---GNTLDTQSMLKLAYSAACGLAHLHTEIFgtqgkpaiAHRDIKSKNILVKKNGTCCIADLGLAvKFIsETN 155
                         170       180
                  ....*....|....*....|....*
gi 1370473802 425 EY----TARQGmVNR----EVLEQV 441
Cdd:cd14144   156 EVdlppNTRVG-TKRymapEVLDES 179
STKc_Nek11 cd08222
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
278-474 6.66e-17

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: 80.55  E-value: 6.66e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 278 RLEVKLGQGCFGEVWM-----GTWNGTTKVaIKTLKPGTMMPEAFLQ---EAQIMKKLRHDKLVPLYA-VVSEEPIYIVT 348
Cdd:cd08222     3 RVVRKLGSGNFGTVYLvsdlkATADEELKV-LKEISVGELQPDETVDanrEAKLLSKLDHPAIVKFHDsFVEKESFCIVT 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 349 EFMSKGSLLDFLKE--GDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVcKIADFGLARLI----- 421
Cdd:cd08222    82 EYCEGGDLDDKISEykKSGTTIDENQILDWFIQLLLAVQYMHERRILHRDLKAKNIFLKNNVI-KVGDFGISRILmgtsd 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 422 EDNEYTARQGMVNREVLEQVERG------------YRMPC-------------------------PQGCPESLHELMNLC 464
Cdd:cd08222   161 LATTFTGTPYYMSPEVLKHEGYNsksdiwslgcilYEMCClkhafdgqnllsvmykivegetpslPDKYSKELNAIYSRM 240
                         250
                  ....*....|
gi 1370473802 465 WKKDPDERPT 474
Cdd:cd08222   241 LNKDPALRPS 250
STKc_STK36 cd14002
Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the ...
284-424 7.01e-17

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: 80.37  E-value: 7.01e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 284 GQGCFGEVWMGTWNGTTK-VAIK-TLKPGTMMPE--AFLQEAQIMKKLRHDKLVPLY-AVVSEEPIYIVTEFmSKGSLLD 358
Cdd:cd14002    10 GEGSFGKVYKGRRKYTGQvVALKfIPKRGKSEKElrNLRQEIEILRKLNHPNIIEMLdSFETKKEFVVVTEY-AQGELFQ 88
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1370473802 359 FLkEGDGKylkLP--QLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDN 424
Cdd:cd14002    89 IL-EDDGT---LPeeEVRSIAKQLVSALHYLHSNRIIHRDMKPQNILIGKGGVVKLCDFGFARAMSCN 152
STKc_MARK cd14072
Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; ...
278-427 8.50e-17

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: 79.87  E-value: 8.50e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 278 RLEVKLGQGCFGEVWMGTWNGTTK-VAIKTLKPGTMMP---EAFLQEAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFMS 352
Cdd:cd14072     3 RLLKTIGKGNFAKVKLARHVLTGReVAIKIIDKTQLNPsslQKLFREVRIMKILNHPNIVKLFEVIeTEKTLYLVMEYAS 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 353 KGSLLDFL--------KEGDGKYlklpqlvdmaAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLArliedN 424
Cdd:cd14072    83 GGEVFDYLvahgrmkeKEARAKF----------RQIVSAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFGFS-----N 147

                  ...
gi 1370473802 425 EYT 427
Cdd:cd14072   148 EFT 150
SH2_C-SH2_SHP_like cd09931
C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
158-243 1.09e-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: 75.39  E-value: 1.09e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 158 WYFGKMGRKDAERLLLNPGnQRGIFLVRESETTKGAYSLSIRDWDeirgDNVKHYKIRkLDNGGYYITTRAQFDTLQKLV 237
Cdd:cd09931     2 WFHGHLSGKEAEKLLLEKG-KPGSFLVRESQSKPGDFVLSVRTDD----DKVTHIMIR-CQGGKYDVGGGEEFDSLTDLV 75

                  ....*.
gi 1370473802 238 KHYTEH 243
Cdd:cd09931    76 EHYKKN 81
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
97-144 1.22e-16

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: 73.39  E-value: 1.22e-16
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1370473802  97 VALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARSIaTGKNGYIPS 144
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIVLEKSEDGWWKGRNK-GGKEGLIPS 47
STKc_Mos cd13979
Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze ...
275-423 1.22e-16

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: 79.74  E-value: 1.22e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 275 ESLRLEVKLGQGCFGEVWMGTWNGTTkVAIKTLKP---GTMMPEAFLQEAQIMKkLRHDKLVPLYAVVS----EEPIYIV 347
Cdd:cd13979     3 EPLRLQEPLGSGGFGSVYKATYKGET-VAVKIVRRrrkNRASRQSFWAELNAAR-LRHENIVRVLAAETgtdfASLGLII 80
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370473802 348 TEFMSKGSLLDFLKEGDGKyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIED 423
Cdd:cd13979    81 MEYCGNGTLQQLIYEGSEP-LPLAHRILISLDIARALRFCHSHGIVHLDVKPANILISEQGVCKLCDFGCSVKLGE 155
STKc_RIP4_like cd14025
Catalytic domain of the Serine/Threonine kinases, Receptor Interacting Protein 4 and similar ...
282-480 1.52e-16

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: 79.46  E-value: 1.52e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVW---MGTWNgtTKVAIKTlkPGTMMPEA-----FLQEAQIMKKLRHDKLVPLYAVVSEePIYIVTEFMSK 353
Cdd:cd14025     3 KVGSGGFGQVYkvrHKHWK--TWLAIKC--PPSLHVDDsermeLLEEAKKMEMAKFRHILPVYGICSE-PVGLVMEYMET 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 354 GSLLDFLKEgdgKYLKLPQLVDMAAQIADGMAYIERMN--YIHRDLRAANILVGENLVCKIADFGLARLIE-----DNEY 426
Cdd:cd14025    78 GSLEKLLAS---EPLPWELRFRIIHETAVGMNFLHCMKppLLHLDLKPANILLDAHYHVKISDFGLAKWNGlshshDLSR 154
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 427 TARQGMV-----------NR----------------EVLEQ----------------VERGYR---MPCPQGCPES---L 457
Cdd:cd14025   155 DGLRGTIaylpperfkekNRcpdtkhdvysfaiviwGILTQkkpfagennilhimvkVVKGHRpslSPIPRQRPSEcqqM 234
                         250       260
                  ....*....|....*....|...
gi 1370473802 458 HELMNLCWKKDPDERPTFEYIQS 480
Cdd:cd14025   235 ICLMKRCWDQDPRKRPTFQDITS 257
STKc_Bck1_like cd06629
Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein ...
283-474 1.52e-16

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: 79.73  E-value: 1.52e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTwNGTTK--VAIKTLK-PGTM----------MPEAFLQEAQIMKKLRHDKLVP-LYAVVSEEPIYIVT 348
Cdd:cd06629     9 IGKGTYGRVYLAM-NATTGemLAVKQVElPKTSsdradsrqktVVDALKSEIDTLKDLDHPNIVQyLGFEETEDYFSIFL 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 349 EFMSKGSLLDFLKegdgKYLKL-PQLV-DMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIED--- 423
Cdd:cd06629    88 EYVPGGSIGSCLR----KYGKFeEDLVrFFTRQILDGLAYLHSKGILHRDLKADNILVDLEGICKISDFGISKKSDDiyg 163
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 424 -NEYTARQGMV---NREVLEQVERGYRMPC---PQGC---------------------------------PESLH----- 458
Cdd:cd06629   164 nNGATSMQGSVfwmAPEVIHSQGQGYSAKVdiwSLGCvvlemlagrrpwsddeaiaamfklgnkrsappvPEDVNlspea 243
                         250
                  ....*....|....*..
gi 1370473802 459 -ELMNLCWKKDPDERPT 474
Cdd:cd06629   244 lDFLNACFAIDPRDRPT 260
STKc_NIM1 cd14075
Catalytic domain of the Serine/Threonine Kinase, NIM1; STKs catalyze the transfer of the ...
278-416 1.66e-16

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: 79.30  E-value: 1.66e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 278 RLEVKLGQGCFGEVWMGTWNGTT-KVAIKTLKPGTM---MPEAFLQEAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFMS 352
Cdd:cd14075     5 RIRGELGSGNFSQVKLGIHQLTKeKVAIKILDKTKLdqkTQRLLSREISSMEKLHHPNIIRLYEVVeTLSKLHLVMEYAS 84
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 353 KGSLLDF------LKEGDGKYLklpqlvdmAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFG 416
Cdd:cd14075    85 GGELYTKistegkLSESEAKPL--------FAQIVSAVKHMHENNIIHRDLKAENVFYASNNCVKVGDFG 146
STKc_Chk2 cd14084
Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze ...
282-423 1.88e-16

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: 79.36  E-value: 1.88e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGT-TKVAIKTLKPGTMM---------PEAFLQEAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEF 350
Cdd:cd14084    13 TLGSGACGEVKLAYDKSTcKKVAIKIINKRKFTigsrreinkPRNIETEIEILKKLSHPCIIKIEDFFdAEDDYYIVLEL 92
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 351 MSKGSLLD------FLKEGDGKYLklpqlvdmAAQIADGMAYIERMNYIHRDLRAANILVG---ENLVCKIADFGLARLI 421
Cdd:cd14084    93 MEGGELFDrvvsnkRLKEAICKLY--------FYQMLLAVKYLHSNGIIHRDLKPENVLLSsqeEECLIKITDFGLSKIL 164

                  ..
gi 1370473802 422 ED 423
Cdd:cd14084   165 GE 166
STKc_BRSK1_2 cd14081
Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the ...
278-424 3.97e-16

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: 78.06  E-value: 3.97e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 278 RLEVKLGQGCFGEVWMGTWNGT-TKVAIKTLKPGTMMPEAFLQ----EAQIMKKLRHDKLVPLYAVVS-EEPIYIVTEFM 351
Cdd:cd14081     4 RLGKTLGKGQTGLVKLAKHCVTgQKVAIKIVNKEKLSKESVLMkverEIAIMKLIEHPNVLKLYDVYEnKKYLYLVLEYV 83
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370473802 352 SKGSLLDFL-KEGdgkylKLP--QLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDN 424
Cdd:cd14081    84 SGGELFDYLvKKG-----RLTekEARKFFRQIISALDYCHSHSICHRDLKPENLLLDEKNNIKIADFGMASLQPEG 154
STKc_CDKL cd07833
Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs ...
282-421 4.33e-16

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: 78.51  E-value: 4.33e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGTTK-VAIKTLK---PGTMMPEAFLQEAQIMKKLRHDKLVPLY-AVVSEEPIYIVTEFMSKgSL 356
Cdd:cd07833     8 VVGEGAYGVVLKCRNKATGEiVAIKKFKeseDDEDVKKTALREVKVLRQLRHENIVNLKeAFRRKGRLYLVFEYVER-TL 86
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370473802 357 LDFLKEgdgkylkLPQLVDMAA------QIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLI 421
Cdd:cd07833    87 LELLEA-------SPGGLPPDAvrsyiwQLLQAIAYCHSHNIIHRDIKPENILVSESGVLKLCDFGFARAL 150
STKc_PDK1 cd05581
Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs ...
283-425 4.61e-16

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: 78.41  E-value: 4.61e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTK-VAIKTLKPGTMMPE----AFLQEAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFMSKGSL 356
Cdd:cd05581     9 LGEGSYSTVVLAKEKETGKeYAIKVLDKRHIIKEkkvkYVTIEKEVLSRLAHPGIVKLYYTFqDESKLYFVLEYAPNGDL 88
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370473802 357 LDFLKegdgKYLKLpqlvDM------AAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNE 425
Cdd:cd05581    89 LEYIR----KYGSL----DEkctrfyTAEIVLALEYLHSKGIIHRDLKPENILLDEDMHIKITDFGTAKVLGPDS 155
STKc_SnRK3 cd14663
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
283-445 4.73e-16

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: 77.83  E-value: 4.73e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMG--TWNGTtKVAIKTLKPGTM----MPEAFLQEAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFMSKGS 355
Cdd:cd14663     8 LGEGTFAKVKFArnTKTGE-SVAIKIIDKEQVaregMVEQIKREIAIMKLLRHPNIVELHEVMaTKTKIFFVMELVTGGE 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 356 LldFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNeytARQGM--- 432
Cdd:cd14663    87 L--FSKIAKNGRLKEDKARKYFQQLIDAVDYCHSRGVFHRDLKPENLLLDEDGNLKISDFGLSALSEQF---RQDGLlht 161
                         170       180
                  ....*....|....*....|
gi 1370473802 433 -------VNREVLEQveRGY 445
Cdd:cd14663   162 tcgtpnyVAPEVLAR--RGY 179
SH3 cd00174
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ...
95-146 5.73e-16

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: 71.73  E-value: 5.73e-16
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1370473802  95 IFVALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARsIATGKNGYIPSNY 146
Cdd:cd00174     1 YARALYDYEAQDDDELSFKKGDIITVLEKDDDGWWEGE-LNGGREGLFPANY 51
SH2_Cterm_RasGAP cd10354
C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP ...
157-240 6.40e-16

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: 72.46  E-value: 6.40e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 157 EWYFGKMGRKDAERLLLNPGnQRGIFLVRESETTKGAYSLSIRdwdeiRGDNVKHYKIRKLDNGGYYITTRAqFDTLQKL 236
Cdd:cd10354     1 IWFHGKISREEAYNMLVKVG-GPGSFLVRESDNTPGDYSLSFR-----VNEGIKHFKIIPTGNNQFMMGGRY-FSSLDDV 73

                  ....
gi 1370473802 237 VKHY 240
Cdd:cd10354    74 IDRY 77
STKc_NUAK2 cd14161
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs ...
283-426 8.46e-16

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: 77.30  E-value: 8.46e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKVAIKTLKPGTMMPEAFL----QEAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFMSKGSLL 357
Cdd:cd14161    11 LGKGTYGRVKKARDSSGRLVAIKSIRKDRIKDEQDLlhirREIEIMSSLNHPHIISVYEVFeNSSKIVIVMEYASRGDLY 90
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370473802 358 DFLKEGDgkylklpQLVDMAA-----QIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEY 426
Cdd:cd14161    91 DYISERQ-------RLSELEArhffrQIVSAVHYCHANGIVHRDLKLENILLDANGNIKIADFGLSNLYNQDKF 157
PknB_PASTA_kin NF033483
Stk1 family PASTA domain-containing Ser/Thr kinase;
302-419 8.92e-16

Stk1 family PASTA domain-containing Ser/Thr kinase;


Pssm-ID: 468045 [Multi-domain]  Cd Length: 563  Bit Score: 79.84  E-value: 8.92e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 302 VAIKTLKPgTMM--PEA---FLQEAQIMKKLRHDKLVPLYAVVSEEPI-YIVTEFMsKGSLL-DFLKEGdGKyLKLPQLV 374
Cdd:NF033483   35 VAVKVLRP-DLArdPEFvarFRREAQSAASLSHPNIVSVYDVGEDGGIpYIVMEYV-DGRTLkDYIREH-GP-LSPEEAV 110
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1370473802 375 DMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR 419
Cdd:NF033483  111 EIMIQILSALEHAHRNGIVHRDIKPQNILITKDGRVKVTDFGIAR 155
STKc_TGFbR-like cd13998
Catalytic domain of Transforming Growth Factor beta Receptor-like Serine/Threonine Kinases; ...
284-418 9.44e-16

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: 77.48  E-value: 9.44e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 284 GQGCFGEVWMGTWNGTTkVAIKTLKPGTMmpEAFLQEAQIMKK--LRHDKLVPLyaVVSEE-------PIYIVTEFMSKG 354
Cdd:cd13998     4 GKGRFGEVWKASLKNEP-VAVKIFSSRDK--QSWFREKEIYRTpmLKHENILQF--IAADErdtalrtELWLVTAFHPNG 78
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370473802 355 SLLDFLKegdGKYLKLPQLVDMAAQIADGMAYIE---------RMNYIHRDLRAANILVGENLVCKIADFGLA 418
Cdd:cd13998    79 SL*DYLS---LHTIDWVSLCRLALSVARGLAHLHseipgctqgKPAIAHRDLKSKNILVKNDGTCCIADFGLA 148
STKc_MLCK-like cd14006
Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs ...
283-427 1.15e-15

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: 76.54  E-value: 1.15e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTK-VAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEPIYI-VTEFMSKGSLLDFL 360
Cdd:cd14006     1 LGRGRFGVVKRCIEKATGReFAAKFIPKRDKKKEAVLREISILNQLQHPRIIQLHEAYESPTELVlILELCSGGELLDRL 80
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 361 KEgDGKYLKlPQLVDMAAQIADGMAYIERMNYIHRDLRAANILV---GENLVcKIADFGLARLIEDNEYT 427
Cdd:cd14006    81 AE-RGSLSE-EEVRTYMRQLLEGLQYLHNHHILHLDLKPENILLadrPSPQI-KIIDFGLARKLNPGEEL 147
STKc_MST3_like cd06609
Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs ...
275-424 1.32e-15

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: 76.90  E-value: 1.32e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 275 ESLRLEVKLGQGCFGEVWMGTWNGTTK-VAIKT--LKPGTMMPEAFLQEAQIMKKLRHDKLVPLYA-VVSEEPIYIVTEF 350
Cdd:cd06609     1 ELFTLLERIGKGSFGEVYKGIDKRTNQvVAIKVidLEEAEDEIEDIQQEIQFLSQCDSPYITKYYGsFLKGSKLWIIMEY 80
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370473802 351 MSKGSLLDFLKEG--DGKYLKLpqlvdMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDN 424
Cdd:cd06609    81 CGGGSVLDLLKPGplDETYIAF-----ILREVLLGLEYLHSEGKIHRDIKAANILLSEEGDVKLADFGVSGQLTST 151
STKc_BMPR1a cd14220
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IA Receptor; ...
282-418 1.38e-15

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: 77.00  E-value: 1.38e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGTtKVAIKTLKpgTMMPEAFLQEAQIMKK--LRHDKLVPLYA-----VVSEEPIYIVTEFMSKG 354
Cdd:cd14220     2 QIGKGRYGEVWMGKWRGE-KVAVKVFF--TTEEASWFRETEIYQTvlMRHENILGFIAadikgTGSWTQLYLITDYHENG 78
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370473802 355 SLLDFLKegdGKYLKLPQLVDMAAQIADGMAYIERMNY--------IHRDLRAANILVGENLVCKIADFGLA 418
Cdd:cd14220    79 SLYDFLK---CTTLDTRALLKLAYSAACGLCHLHTEIYgtqgkpaiAHRDLKSKNILIKKNGTCCIADLGLA 147
SH2_N-SH2_Zap70_Syk_like cd09938
N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
158-261 1.42e-15

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: 72.43  E-value: 1.42e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 158 WYFGKMGRKDAERLLLNPGNQRGIFLVRESETTKGAYSLSIrdwdeIRGDNVKHYKIRKLDNGGYYITTRAQFDTLQKLV 237
Cdd:cd09938     3 FFYGSITREEAEEYLKLAGMSDGLFLLRQSLRSLGGYVLSV-----CHGRKFHHYTIERQLNGTYAIAGGKAHCGPAELC 77
                          90       100
                  ....*....|....*....|....*..
gi 1370473802 238 KHYTEHADGLCHKLTTVC---PTVKPQ 261
Cdd:cd09938    78 EYHSTDLDGLVCLLRKPCnrpPGVEPK 104
STKc_EIF2AK4_GCN2_rpt2 cd14046
Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation ...
283-418 1.71e-15

Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GCN2 (or EIF2AK4) 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-kB 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. Its kinase domain is activated via conformational changes as a result of the binding of uncharged tRNA to the HisRS-like domain. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. The GCN2 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: 270948 [Multi-domain]  Cd Length: 278  Bit Score: 76.64  E-value: 1.71e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVwmgtwngtTKV---------AIK--TLKPGTMMPEAFLQEAQIMKKLRHDKLVPLY-AVVSEEPIYIVTEF 350
Cdd:cd14046    14 LGKGAFGQV--------VKVrnkldgryyAIKkiKLRSESKNNSRILREVMLLSRLNHQHVVRYYqAWIERANLYIQMEY 85
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1370473802 351 MSKGSLLDFLKegDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLA 418
Cdd:cd14046    86 CEKSTLRDLID--SGLFQDTDRLWRLFRQILEGLAYIHSQGIIHRDLKPVNIFLDSNGNVKIGDFGLA 151
STKc_p38 cd07851
Catalytic domain of the Serine/Threonine Kinase, p38 Mitogen-Activated Protein Kinase; STKs ...
263-465 1.84e-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: 77.72  E-value: 1.84e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 263 QGLAKDAWEIPRESLRLEVkLGQGCFGEVWMGTWNGT-TKVAIKTL-KP--GTMMPEAFLQEAQIMKKLRHDKLVPLYAV 338
Cdd:cd07851     4 QELNKTVWEVPDRYQNLSP-VGSGAYGQVCSAFDTKTgRKVAIKKLsRPfqSAIHAKRTYRELRLLKHMKHENVIGLLDV 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 339 VSE-------EPIYIVTEFMskGSLLdflkegdGKYLKLPQLVD-----MAAQIADGMAYIERMNYIHRDLRAANILVGE 406
Cdd:cd07851    83 FTPassledfQDVYLVTHLM--GADL-------NNIVKCQKLSDdhiqfLVYQILRGLKYIHSAGIIHRDLKPSNLAVNE 153
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1370473802 407 NLVCKIADFGLARLIEDnEYTarqGMVnrevleqVERGYRMPcpqgcpeslhELMnLCW 465
Cdd:cd07851   154 DCELKILDFGLARHTDD-EMT---GYV-------ATRWYRAP----------EIM-LNW 190
STKc_PKA_like cd05580
Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs ...
283-427 2.41e-15

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: 76.46  E-value: 2.41e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTK-VAIKTLKPGTMMP----EAFLQEAQIMKKLRHDKLVPLYAVVSEEP-IYIVTEFMSKGSL 356
Cdd:cd05580     9 LGTGSFGRVRLVKHKDSGKyYALKILKKAKIIKlkqvEHVLNEKRILSEVRHPFIVNLLGSFQDDRnLYMVMEYVPGGEL 88
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370473802 357 LDFLKegdgKYLKLPQLVDM--AAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYT 427
Cdd:cd05580    89 FSLLR----RSGRFPNDVAKfyAAEVVLALEYLHSLDIVYRDLKPENLLLDSDGHIKITDFGFAKRVKDRTYT 157
STKc_LRRK cd14000
Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the ...
283-484 2.87e-15

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: 76.11  E-value: 2.87e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTtKVAIKTLKPGTMMPEA----------------------FLQEAQIMKKLRHDKLVPLYAVvS 340
Cdd:cd14000     2 LGDGGFGSVYRASYKGE-PVAVKIFNKHTSSNFAnvpadtmlrhlratdamknfrlLRQELTVLSHLHHPSIVYLLGI-G 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 341 EEPIYIVTEFMSKGSLLDFLKEGDGKYLKLPQLV--DMAAQIADGMAYIERMNYIHRDLRAANILV-----GENLVCKIA 413
Cdd:cd14000    80 IHPLMLVLELAPLGSLDHLLQQDSRSFASLGRTLqqRIALQVADGLRYLHSAMIIYRDLKSHNVLVwtlypNSAIIIKIA 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 414 DFGLAR--------------------LIEDNEYTARQ------GMVNREVL-------------EQVERGYRMPCPQGCP 454
Cdd:cd14000   160 DYGISRqccrmgakgsegtpgfrapeIARGNVIYNEKvdvfsfGMLLYEILsggapmvghlkfpNEFDIHGGLRPPLKQY 239
                         250       260       270
                  ....*....|....*....|....*....|....*
gi 1370473802 455 ES-----LHELMNLCWKKDPDERPTFEYIQSFLED 484
Cdd:cd14000   240 ECapwpeVEVLMKKCWKENPQQRPTAVTVVSILNS 274
PTK_Jak_rpt1 cd05037
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak ...
283-478 2.87e-15

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: 75.59  E-value: 2.87e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMG-------TWNGTTKVAIKTLKP-GTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEPIYIVTEFMSKG 354
Cdd:cd05037     7 LGQGTFTNIYDGilrevgdGRVQEVEVLLKVLDSdHRDISESFFETASLMSQISHKHLVKLYGVCVADENIMVQEYVRYG 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 355 SLLDFLKEgDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILV------GENLVCKIADFGLARLIEDNEYTA 428
Cdd:cd05037    87 PLDKYLRR-MGNNVPLSWKLQVAKQLASALHYLEDKKLIHGNVRGRNILLaregldGYPPFIKLSDPGVPITVLSREERV 165
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 429 -----------RQGMVN------------------------------REVLEQVERGYRMPCPQgCPEsLHELMNLCWKK 467
Cdd:cd05037   166 dripwiapeclRNLQANltiaadkwsfgttlweicsggeeplsalssQEKLQFYEDQHQLPAPD-CAE-LAELIMQCWTY 243
                         250
                  ....*....|.
gi 1370473802 468 DPDERPTFEYI 478
Cdd:cd05037   244 EPTKRPSFRAI 254
STKc_TSSK1_2-like cd14165
Catalytic domain of testis-specific serine/threonine kinase 1, TSSK2, and similar proteins; ...
279-425 2.95e-15

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: 75.59  E-value: 2.95e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 279 LEVKLGQGCFGEVWMGTWNGTT-KVAIKTL---KPGTMMPEAFL-QEAQIMKKLRHDKLVPLYAV--VSEEPIYIVTEFM 351
Cdd:cd14165     5 LGINLGEGSYAKVKSAYSERLKcNVAIKIIdkkKAPDDFVEKFLpRELEILARLNHKSIIKTYEIfeTSDGKVYIVMELG 84
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370473802 352 SKGSLLDFLKEGdgkyLKLPQLV--DMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNE 425
Cdd:cd14165    85 VQGDLLEFIKLR----GALPEDVarKMFHQLSSAIKYCHELDIVHRDLKCENLLLDKDFNIKLTDFGFSKRCLRDE 156
STKc_GSK3 cd14137
The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze ...
276-425 3.04e-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: 76.00  E-value: 3.04e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 276 SLRLEVKLGQGCFGEVWMGTWNGTTK-VAIKTLkpgtmmpeafLQ-------EAQIMKKLRHDKLVPL-YAVVSEEP--- 343
Cdd:cd14137     5 SYTIEKVIGSGSFGVVYQAKLLETGEvVAIKKV----------LQdkryknrELQIMRRLKHPNIVKLkYFFYSSGEkkd 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 344 ---IYIVTEFMSKgSLLDFLKegdgKYLKLPQLVDM------AAQIADGMAYIERMNYIHRDLRAANILV-GENLVCKIA 413
Cdd:cd14137    75 evyLNLVMEYMPE-TLYRVIR----HYSKNKQTIPIiyvklySYQLFRGLAYLHSLGICHRDIKPQNLLVdPETGVLKLC 149
                         170
                  ....*....|..
gi 1370473802 414 DFGLARLIEDNE 425
Cdd:cd14137   150 DFGSAKRLVPGE 161
STKc_MELK cd14078
Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; ...
283-418 3.07e-15

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: 75.50  E-value: 3.07e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTT-KVAIKTL---KPGTMMPEAFLqEAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFMSKGSLL 357
Cdd:cd14078    11 IGSGGFAKVKLATHILTGeKVAIKIMdkkALGDDLPRVKT-EIEALKNLSHQHICRLYHVIeTDNKIFMVLEYCPGGELF 89
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370473802 358 DFLKEGDgkYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLA 418
Cdd:cd14078    90 DYIVAKD--RLSEDEARVFFRQIVSAVAYVHSQGYAHRDLKPENLLLDEDQNLKLIDFGLC 148
SH2_Vav_family cd09940
Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several ...
157-243 3.12e-15

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: 71.17  E-value: 3.12e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 157 EWYFGKMGRKDAERLLLNPGNqrGIFLVRESETTKGAYSLSIRdwdeiRGDNVKHYKIRKLDNGGYYITTRAQFDTLQKL 236
Cdd:cd09940     6 LWFVGEMERDTAENRLENRPD--GTYLVRVRPQGETQYALSIK-----YNGDVKHMKIEQRSDGLYYLSESRHFKSLVEL 78

                  ....*..
gi 1370473802 237 VKHYTEH 243
Cdd:cd09940    79 VNYYERN 85
STKc_GAK_like cd13985
Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of ...
276-469 3.28e-15

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: 75.83  E-value: 3.28e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 276 SLRLEVKLGQGCFGEVWMGTWNGTTK-VAIKTLKPGTMMP-EAFLQEAQIMKKL-RHDKLVPLY--AVVSEEP---IYIV 347
Cdd:cd13985     1 RYQVTKQLGEGGFSYVYLAHDVNTGRrYALKRMYFNDEEQlRVAIKEIEIMKRLcGHPNIVQYYdsAILSSEGrkeVLLL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 348 TEFmSKGSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMN--YIHRDLRAANILVGENLVCKIADFGLArLIEDNE 425
Cdd:cd13985    81 MEY-CPGSLVDILEKSPPSPLSEEEVLRIFYQICQAVGHLHSQSppIIHRDIKIENILFSNTGRFKLCDFGSA-TTEHYP 158
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 1370473802 426 YTARQGMVNREvlEQVER----GYRMPcpqgcpeslhELMNLcWKKDP 469
Cdd:cd13985   159 LERAEEVNIIE--EEIQKnttpMYRAP----------EMIDL-YSKKP 193
STKc_CDK2_3 cd07860
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase 2 and 3; ...
282-419 3.59e-15

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: 76.00  E-value: 3.59e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGTTK-VAIKTLKPGTMM---PEAFLQEAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFMSKgSL 356
Cdd:cd07860     7 KIGEGTYGVVYKARNKLTGEvVALKKIRLDTETegvPSTAIREISLLKELNHPNIVKLLDVIhTENKLYLVFEFLHQ-DL 85
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370473802 357 LDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR 419
Cdd:cd07860    86 KKFMDASALTGIPLPLIKSYLFQLLQGLAFCHSHRVLHRDLKPQNLLINTEGAIKLADFGLAR 148
STKc_WNK cd13983
Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze ...
277-486 4.12e-15

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: 75.34  E-value: 4.12e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 277 LRLEVKLGQGCFGEVWMG---------TWNgttkvAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAV---VSEEPI 344
Cdd:cd13983     3 LKFNEVLGRGSFKTVYRAfdteegievAWN-----EIKLRKLPKAERQRFKQEIEILKSLKHPNIIKFYDSwesKSKKEV 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 345 YIVTEFMSKGSLLDFLKegDGKYLKLPQLVDMAAQIADGMAYIERMNY--IHRDLRAANILV-GENLVCKIADFGLARLI 421
Cdd:cd13983    78 IFITELMTSGTLKQYLK--RFKRLKLKVIKSWCRQILEGLNYLHTRDPpiIHRDLKCDNIFInGNTGEVKIGDLGLATLL 155
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 422 EDN---------EYTARQ---------------GMVnreVLEQVERGY-RMPCP----------QGC-PESLH------- 458
Cdd:cd13983   156 RQSfaksvigtpEFMAPEmyeehydekvdiyafGMC---LLEMATGEYpYSECTnaaqiykkvtSGIkPESLSkvkdpel 232
                         250       260
                  ....*....|....*....|....*....
gi 1370473802 459 -ELMNLCWKKdPDERPTfeyIQSFLEDYF 486
Cdd:cd13983   233 kDFIEKCLKP-PDERPS---ARELLEHPF 257
STKc_Nek5 cd08225
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
282-429 4.20e-15

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: 74.99  E-value: 4.20e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGTTKVAIKTLKPGTMMP----EAFLQEAQIMKKLRHDKLVPLYAVVSEE-PIYIVTEFMSKGSL 356
Cdd:cd08225     7 KIGEGSFGKIYLAKAKSDSEHCVIKEIDLTKMPvkekEASKKEVILLAKMKHPNIVTFFASFQENgRLFIVMEYCDGGDL 86
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370473802 357 LDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGEN-LVCKIADFGLARLIEDNEYTAR 429
Cdd:cd08225    87 MKRINRQRGVLFSEDQILSWFVQISLGLKHIHDRKILHRDIKSQNIFLSKNgMVAKLGDFGIARQLNDSMELAY 160
STK_BAK1_like cd14664
Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; ...
283-423 5.14e-15

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: 75.22  E-value: 5.14e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKVAIKTLK-PGTMMPE-AFLQEAQIMKKLRHDKLVPLYAVVS-EEPIYIVTEFMSKGSLLDF 359
Cdd:cd14664     1 IGRGGAGTVYKGVMPNGTLVAVKRLKgEGTQGGDhGFQAEIQTLGMIRHRNIVRLRGYCSnPTTNLLVYEYMPNGSLGEL 80
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1370473802 360 L--KEGDGKYLKLPQLVDMAAQIADGMAYIER---MNYIHRDLRAANILVGENLVCKIADFGLARLIED 423
Cdd:cd14664    81 LhsRPESQPPLDWETRQRIALGSARGLAYLHHdcsPLIIHRDVKSNNILLDEEFEAHVADFGLAKLMDD 149
STKc_TGFbR1_ACVR1b_ACVR1c cd14143
Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta Type I ...
283-418 6.06e-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: 75.17  E-value: 6.06e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTkVAIKTLKpgTMMPEAFLQEAQIMKK--LRHDKLVPLYAVVSEE-----PIYIVTEFMSKGS 355
Cdd:cd14143     3 IGKGRFGEVWRGRWRGED-VAVKIFS--SREERSWFREAEIYQTvmLRHENILGFIAADNKDngtwtQLWLVSDYHEHGS 79
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370473802 356 LLDFLKEgdgKYLKLPQLVDMAAQIADGMAYIErMNYI---------HRDLRAANILVGENLVCKIADFGLA 418
Cdd:cd14143    80 LFDYLNR---YTVTVEGMIKLALSIASGLAHLH-MEIVgtqgkpaiaHRDLKSKNILVKKNGTCCIADLGLA 147
SH2_Tec_family cd09934
Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the ...
151-256 7.48e-15

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: 70.51  E-value: 7.48e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 151 DSIQAEEWYFGKMGRKDAERLLLNPGNQrGIFLVRESeTTKGAYSLSIrdWDEIRGD-NVKHYKIRKLDNGGYYITTRAQ 229
Cdd:cd09934     1 LNLEKYEWYVGDMSRQRAESLLKQEDKE-GCFVVRNS-STKGLYTVSL--FTKVPGSpHVKHYHIKQNARSEFYLAEKHC 76
                          90       100
                  ....*....|....*....|....*...
gi 1370473802 230 FDTLQKLVKHYTEHADGLCHKL-TTVCP 256
Cdd:cd09934    77 FETIPELINYHQHNSGGLATRLkYPVCD 104
PKc_TNNI3K cd14064
Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting kinase; ...
283-484 7.67e-15

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: 74.49  E-value: 7.67e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTkVAIKTLKPGTMMPEA----FLQEAQIMKKLRHDKLVPLYAVVSEEP--IYIVTEFMSKGSL 356
Cdd:cd14064     1 IGSGSFGKVYKGRCRNKI-VAIKRYRANTYCSKSdvdmFCREVSILCRLNHPCVIQFVGACLDDPsqFAIVTQYVSGGSL 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 357 LDFLKEgDGKYLKLPQLVDMAAQIADGMAYIERMNY--IHRDLRAANILVGENLVCKIADFGLARLI----EDN------ 424
Cdd:cd14064    80 FSLLHE-QKRVIDLQSKLIIAVDVAKGMEYLHNLTQpiIHRDLNSHNILLYEDGHAVVADFGESRFLqsldEDNmtkqpg 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 425 --------------EYTARQGMVNR-----EVL----------------EQVERGYRMPCPQGCPESLHELMNLCWKKDP 469
Cdd:cd14064   159 nlrwmapevftqctRYSIKADVFSYalclwELLtgeipfahlkpaaaaaDMAYHHIRPPIGYSIPKPISSLLMRGWNAEP 238
                         250
                  ....*....|....*
gi 1370473802 470 DERPTFEYIQSFLED 484
Cdd:cd14064   239 ESRPSFVEIVALLEP 253
STKc_CCRK cd07832
Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the ...
282-448 8.25e-15

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: 74.67  E-value: 8.25e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGTTK-VAIKTLKPGTM---MPEAFLQEAQIMKKLR-HDKLVPLYAVVSE-EPIYIVTEFMSkGS 355
Cdd:cd07832     7 RIGEGAHGIVFKAKDRETGEtVALKKVALRKLeggIPNQALREIKALQACQgHPYVVKLRDVFPHgTGFVLVFEYML-SS 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 356 LLDFLKEGDgKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEytarqgmvNR 435
Cdd:cd07832    86 LSEVLRDEE-RPLTEAQVKRYMRMLLKGVAYMHANRIMHRDLKPANLLISSTGVLKIADFGLARLFSEED--------PR 156
                         170
                  ....*....|....
gi 1370473802 436 EVLEQV-ERGYRMP 448
Cdd:cd07832   157 LYSHQVaTRWYRAP 170
STKc_CDK1_euk cd07861
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher ...
282-419 8.68e-15

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: 74.76  E-value: 8.68e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGTTK-VAIKTLKPGTM---MPEAFLQEAQIMKKLRHDKLVPLYAVVSEEP-IYIVTEFMSkgsl 356
Cdd:cd07861     7 KIGEGTYGVVYKGRNKKTGQiVAMKKIRLESEeegVPSTAIREISLLKELQHPNIVCLEDVLMQENrLYLVFEFLS---- 82
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370473802 357 LDFLKEGD----GKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR 419
Cdd:cd07861    83 MDLKKYLDslpkGKYMDAELVKSYLYQILQGILFCHSRRVLHRDLKPQNLLIDNKGVIKLADFGLAR 149
PK_GC_unk cd14045
Pseudokinase domain of the unknown subfamily of membrane Guanylate Cyclase receptors; The ...
294-482 9.22e-15

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: 74.51  E-value: 9.22e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 294 GTWNGTTkVAIKTLKPGTM-MPEAFLQEAQIMKKLRHDKLVPLYAVVSEEP-IYIVTEFMSKGSLLDFLKEGDGKyLKLP 371
Cdd:cd14045    26 GIYDGRT-VAIKKIAKKSFtLSKRIRKEVKQVRELDHPNLCKFIGGCIEVPnVAIITEYCPKGSLNDVLLNEDIP-LNWG 103
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 372 QLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGL---------------------------ARLIEDN 424
Cdd:cd14045   104 FRFSFATDIARGMAYLHQHKIYHGRLKSSNCVIDDRWVCKIADYGLttyrkedgsenasgyqqrlmqvylppeNHSNTDT 183
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 425 EYTA----------------RQGMVNREVlEQVERGYRMP------------CPqgCPESLHELMNLCWKKDPDERPTFE 476
Cdd:cd14045   184 EPTQatdvysyaiilleiatRNDPVPEDD-YSLDEAWCPPlpelisgktensCP--CPADYVELIRRCRKNNPAQRPTFE 260

                  ....*.
gi 1370473802 477 YIQSFL 482
Cdd:cd14045   261 QIKKTL 266
STKc_ACVR1_ALK1 cd14142
Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin ...
283-418 1.02e-14

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: 74.78  E-value: 1.02e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTkVAIKTLKpgTMMPEAFLQEAQIMKK--LRHDKLVPLYAV-----VSEEPIYIVTEFMSKGS 355
Cdd:cd14142    13 IGKGRYGEVWRGQWQGES-VAVKIFS--SRDEKSWFRETEIYNTvlLRHENILGFIASdmtsrNSCTQLWLITHYHENGS 89
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370473802 356 LLDFLKEGDgkyLKLPQLVDMAAQIADGMAYIE--------RMNYIHRDLRAANILVGENLVCKIADFGLA 418
Cdd:cd14142    90 LYDYLQRTT---LDHQEMLRLALSAASGLVHLHteifgtqgKPAIAHRDLKSKNILVKSNGQCCIADLGLA 157
STKc_MLCK cd14103
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the ...
283-425 1.09e-14

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: 73.80  E-value: 1.09e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKVA----IKTLKPGTMmpEAFLQEAQIMKKLRHDKLVPLY-AVVSEEPIYIVTEFMSKGSLL 357
Cdd:cd14103     1 LGRGKFGTVYRCVEKATGKELaakfIKCRKAKDR--EDVRNEIEIMNQLRHPRLLQLYdAFETPREMVLVMEYVAGGELF 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 358 D-------FLKEGDG-KYLKlpqlvdmaaQIADGMAYIERMNYIHRDLRAANILvgenlvC--------KIADFGLARLI 421
Cdd:cd14103    79 ErvvdddfELTERDCiLFMR---------QICEGVQYMHKQGILHLDLKPENIL------CvsrtgnqiKIIDFGLARKY 143

                  ....
gi 1370473802 422 EDNE 425
Cdd:cd14103   144 DPDK 147
STKc_LKB1 cd14119
Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer ...
283-480 1.31e-14

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: 73.45  E-value: 1.31e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEV--WMGTWNgTTKVAIKTLK-------PGTmmPEAFLQEAQIMKKLRHDKLVPLYAVVSEE---PIYIVTEF 350
Cdd:cd14119     1 LGEGSYGKVkeVLDTET-LCRRAVKILKkrklrriPNG--EANVKREIQILRRLNHRNVIKLVDVLYNEekqKLYMVMEY 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 351 mSKGSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLI----EDNEY 426
Cdd:cd14119    78 -CVGGLQEMLDSAPDKRLPIWQAHGYFVQLIDGLEYLHSQGIIHKDIKPGNLLLTTDGTLKISDFGVAEALdlfaEDDTC 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 427 TARQG--------------------------------MVNRE----------VLEQVERG-YRMpcPQGCPESLHELMNL 463
Cdd:cd14119   157 TTSQGspafqppeiangqdsfsgfkvdiwsagvtlynMTTGKypfegdniykLFENIGKGeYTI--PDDVDPDLQDLLRG 234
                         250
                  ....*....|....*..
gi 1370473802 464 CWKKDPDERPTFEYIQS 480
Cdd:cd14119   235 MLEKDPEKRFTIEQIRQ 251
STKc_Nek4 cd08223
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
283-422 1.46e-14

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: 73.63  E-value: 1.46e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTW-NGTTKVAIKTL---KPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEP--IYIVTEFMSKGSL 356
Cdd:cd08223     8 IGKGSYGEVWLVRHkRDRKQYVIKKLnlkNASKRERKAAEQEAKLLSKLKHPNIVSYKESFEGEDgfLYIVMGFCEGGDL 87
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370473802 357 LDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIE 422
Cdd:cd08223    88 YTRLKEQKGVLLEERQVVEWFVQIAMALQYMHERNILHRDLKTQNIFLTKSNIIKVGDLGIARVLE 153
SH2_C-SH2_Syk_like cd10401
C-terminal Src homology 2 (SH2) domain found in Spleen tyrosine kinase (Syk) proteins; ZAP-70 ...
158-256 1.59e-14

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: 69.15  E-value: 1.59e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 158 WYFGKMGRKDAERLLLNPGNQRGIFLVRESETtKGAYSLSIrdwdeIRGDNVKHYKIRKLDNGGYYITTRAQFDTLQKLV 237
Cdd:cd10401     5 WFHGKISREESEQILLIGSKTNGKFLIRERDN-NGSYALCL-----LHDGKVLHYRIDKDKTGKLSIPDGKKFDTLWQLV 78
                          90
                  ....*....|....*....
gi 1370473802 238 KHYTEHADGLCHKLTTVCP 256
Cdd:cd10401    79 EHYSYKPDGLLRVLTEPCP 97
STKc_IRAK1 cd14159
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 1; ...
283-419 1.70e-14

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: 74.09  E-value: 1.70e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNgTTKVAIKTLKPG-----TMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEPIY-IVTEFMSKGSL 356
Cdd:cd14159     1 IGEGGFGCVYQAVMR-NTEYAVKRLKEDseldwSVVKNSFLTEVEKLSRFRHPNIVDLAGYSAQQGNYcLIYVYLPNGSL 79
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370473802 357 LDFLK-EGDGKYLKLPQLVDMAAQIADGMAYIERMN--YIHRDLRAANILVGENLVCKIADFGLAR 419
Cdd:cd14159    80 EDRLHcQVSCPCLSWSQRLHVLLGTARAIQYLHSDSpsLIHGDVKSSNILLDAALNPKLGDFGLAR 145
STKc_p38gamma cd07880
Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase ...
262-448 1.74e-14

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: 74.60  E-value: 1.74e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 262 TQGLAKDAWEIPrESLRLEVKLGQGCFGEVWMGTWNGT-TKVAIKTL-KP--GTMMPEAFLQEAQIMKKLRHDKLVPLYA 337
Cdd:cd07880     3 RQEVNKTIWEVP-DRYRDLKQVGSGAYGTVCSALDRRTgAKVAIKKLyRPfqSELFAKRAYRELRLLKHMKHENVIGLLD 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 338 VVSEE-------PIYIVTEFMskGSLLdflkegdGKYLKLPQLVD-----MAAQIADGMAYIERMNYIHRDLRAANILVG 405
Cdd:cd07880    82 VFTPDlsldrfhDFYLVMPFM--GTDL-------GKLMKHEKLSEdriqfLVYQMLKGLKYIHAAGIIHRDLKPGNLAVN 152
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 1370473802 406 ENLVCKIADFGLARLiEDNEYTarqGMVnrevleqVERGYRMP 448
Cdd:cd07880   153 EDCELKILDFGLARQ-TDSEMT---GYV-------VTRWYRAP 184
PK_ILK cd14057
Pseudokinase domain of Integrin Linked Kinase; The pseudokinase domain shows similarity to ...
282-483 1.93e-14

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: 72.91  E-value: 1.93e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGTTKVAiKTLKPGTMMPEA---FLQEAQIMKKLRHDKLVPLYAVVSEEP-IYIVTEFMSKGSLL 357
Cdd:cd14057     2 KINETHSGELWKGRWQGNDIVA-KILKVRDVTTRIsrdFNEEYPRLRIFSHPNVLPVLGACNSPPnLVVISQYMPYGSLY 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 358 DFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYI--HRDLRAANILVGENLVCKI--ADF------------------ 415
Cdd:cd14057    81 NVLHEGTGVVVDQSQAVKFALDIARGMAFLHTLEPLipRHHLNSKHVMIDEDMTARInmADVkfsfqepgkmynpawmap 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 416 -GLARLIED-NEYTARQ--------GMVNREV----LEQVE-------RGYRMPCPQGCPESLHELMNLCWKKDPDERPT 474
Cdd:cd14057   161 eALQKKPEDiNRRSADMwsfaillwELVTREVpfadLSNMEigmkialEGLRVTIPPGISPHMCKLMKICMNEDPGKRPK 240

                  ....*....
gi 1370473802 475 FEYIQSFLE 483
Cdd:cd14057   241 FDMIVPILE 249
STKc_CDC2L1 cd07843
Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze ...
282-427 2.31e-14

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: 73.41  E-value: 2.31e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGTTK-VAIKTLKpgtMMPEA--F----LQEAQIMKKLRHDKLVPLYAVV---SEEPIYIVTEFM 351
Cdd:cd07843    12 RIEEGTYGVVYRARDKKTGEiVALKKLK---MEKEKegFpitsLREINILLKLQHPNIVTVKEVVvgsNLDKIYMVMEYV 88
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1370473802 352 SKgSLLDFLKEGDGKYLkLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDN--EYT 427
Cdd:cd07843    89 EH-DLKSLMETMKQPFL-QSEVKCLMLQLLSGVAHLHDNWILHRDLKTSNLLLNNRGILKICDFGLAREYGSPlkPYT 164
STKc_CDK12 cd07864
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs ...
283-429 2.35e-14

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: 73.68  E-value: 2.35e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTK-VAIKTL-----KPGtmMPEAFLQEAQIMKKLRHDKLVPLYAVVSE-----------EPIY 345
Cdd:cd07864    15 IGEGTYGQVYKAKDKDTGElVALKKVrldneKEG--FPITAIREIKILRQLNHRSVVNLKEIVTDkqdaldfkkdkGAFY 92
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 346 IVTEFMS-------KGSLLDFLKEGDGKYLKlpqlvdmaaQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLA 418
Cdd:cd07864    93 LVFEYMDhdlmgllESGLVHFSEDHIKSFMK---------QLLEGLNYCHKKNFLHRDIKCSNILLNNKGQIKLADFGLA 163
                         170
                  ....*....|....
gi 1370473802 419 RLIEDNE---YTAR 429
Cdd:cd07864   164 RLYNSEEsrpYTNK 177
STKc_CDK1_CdkB_like cd07835
Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of ...
278-419 2.53e-14

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: 73.09  E-value: 2.53e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 278 RLEvKLGQGCFGEVWMGTWNGTTK-VAIKTLKPGTM---MPEAFLQEAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFMS 352
Cdd:cd07835     3 KLE-KIGEGTYGVVYKARDKLTGEiVALKKIRLETEdegVPSTAIREISLLKELNHPNIVRLLDVVhSENKLYLVFEFLD 81
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 353 kgslLDFLKEGDGKYL--KLPQLVDM-AAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR 419
Cdd:cd07835    82 ----LDLKKYMDSSPLtgLDPPLIKSyLYQLLQGIAFCHSHRVLHRDLKPQNLLIDTEGALKLADFGLAR 147
STKc_RIP2 cd14026
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2; STKs catalyze ...
283-419 2.79e-14

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: 73.03  E-value: 2.79e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGT---WNgtTKVAIKTLKPGTMMPEA----FLQEAQIMKKLRHDKLVPLYAVVSE-EPIYIVTEFMSKG 354
Cdd:cd14026     5 LSRGAFGTVSRARhadWR--VTVAIKCLKLDSPVGDSerncLLKEAEILHKARFSYILPILGICNEpEFLGIVTEYMTNG 82
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1370473802 355 SLLDFLKEGDgKY--LKLPQLVDMAAQIADGMAYIERMN--YIHRDLRAANILVGENLVCKIADFGLAR 419
Cdd:cd14026    83 SLNELLHEKD-IYpdVAWPLRLRILYEIALGVNYLHNMSppLLHHDLKTQNILLDGEFHVKIADFGLSK 150
STKc_MST3 cd06641
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs ...
273-425 3.04e-14

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: 73.18  E-value: 3.04e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 273 PRESLRLEVKLGQGCFGEVWMGTWNGTTKV-AIKT--LKPGTMMPEAFLQEAQIMKKLRHDKLVPLY-AVVSEEPIYIVT 348
Cdd:cd06641     2 PEELFTKLEKIGKGSFGEVFKGIDNRTQKVvAIKIidLEEAEDEIEDIQQEITVLSQCDSPYVTKYYgSYLKDTKLWIIM 81
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370473802 349 EFMSKGSLLDFLKEGDgkyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNE 425
Cdd:cd06641    82 EYLGGGSALDLLEPGP---LDETQIATILREILKGLDYLHSEKKIHRDIKAANVLLSEHGEVKLADFGVAGQLTDTQ 155
PTKc_Aatyk cd05042
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs ...
282-482 3.52e-14

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: 72.62  E-value: 3.52e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMG-TWNGTT--KVAIKTLKPGTMMPE--AFLQEAQIMKKLRHDKLVPLYAVVSEE-PIYIVTEFMSKGS 355
Cdd:cd05042     2 EIGNGWFGKVLLGeIYSGTSvaQVVVKELKASANPKEqdTFLKEGQPYRILQHPNILQCLGQCVEAiPYLLVMEFCDLGD 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 356 LLDFLKEGDGKYLKLPQ---LVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLA--RLIEDNEYTARQ 430
Cdd:cd05042    82 LKAYLRSEREHERGDSDtrtLQRMACEVAAGLAHLHKLNFVHSDLALRNCLLTSDLTVKIGDYGLAhsRYKEDYIETDDK 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 431 GMV--------------------------------------------------NREVLEQV--ERGYRMPCPQ---GCPE 455
Cdd:cd05042   162 LWFplrwtapelvtefhdrllvvdqtkysniwslgvtlwelfengaqpysnlsDLDVLAQVvrEQDTKLPKPQlelPYSD 241
                         250       260
                  ....*....|....*....|....*..
gi 1370473802 456 SLHELMNLCWKKdPDERPTFEYIQSFL 482
Cdd:cd05042   242 RWYEVLQFCWLS-PEQRPAAEDVHLLL 267
SH2_Cterm_shark_like cd10348
C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
157-247 3.70e-14

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: 67.83  E-value: 3.70e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 157 EWYFGKMGRKDAERLLLNPGNQRGIFLVRESETTKGAYSLSIrdwdeIRGDNVKHYKIRKLDNGGYYITTRAQFDTLQKL 236
Cdd:cd10348     1 QWLHGALDRNEAVEILKQKADADGSFLVRYSRRRPGGYVLTL-----VYENHVYHFEIQNRDDKWFYIDDGPYFESLEHL 75
                          90
                  ....*....|.
gi 1370473802 237 VKHYTEHADGL 247
Cdd:cd10348    76 IEHYTQFADGL 86
SH3_Abl cd11850
Src homology 3 domain of the Protein Tyrosine Kinase, Abelson kinase; Abl (or c-Abl) is a ...
95-149 4.00e-14

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: 66.67  E-value: 4.00e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1370473802  95 IFVALYDYEARTTEDLSFKKGERFQIIN-NTEGDWWEARSIATGKNGYIPSNYVAP 149
Cdd:cd11850     1 LFVALYDFVASGENQLSIKKGEQLRVLGyNKNGEWCEAESKSTGGQGWVPSNYITP 56
STKc_ULK3 cd14121
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the ...
282-425 4.23e-14

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: 71.94  E-value: 4.23e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVW--MGTWNGTTKVAIK-----TLKPGTMmpEAFLQEAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFMSK 353
Cdd:cd14121     2 KLGSGTYATVYkaYRKSGAREVVAVKcvsksSLNKAST--ENLLTEIELLKKLKHPHIVELKDFQwDEEHIYLIMEYCSG 79
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370473802 354 GSLLDFLKegdgKYLKLPQLV--DMAAQIADGMAYIERMNYIHRDLRAANILV--GENLVCKIADFGLARLIEDNE 425
Cdd:cd14121    80 GDLSRFIR----SRRTLPESTvrRFLQQLASALQFLREHNISHMDLKPQNLLLssRYNPVLKLADFGFAQHLKPND 151
STKc_Kin4 cd14076
Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the ...
283-418 4.29e-14

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: 72.52  E-value: 4.29e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMG------TWNGTTKVAIKTLKPGTMMPEA----FLQEAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFM 351
Cdd:cd14076     9 LGEGEFGKVKLGwplpkaNHRSGVQVAIKLIRRDTQQENCqtskIMREINILKGLTHPNIVRLLDVLkTKKYIGIVLEFV 88
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370473802 352 SKGSLLDFLKEGdgKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLA 418
Cdd:cd14076    89 SGGELFDYILAR--RRLKDSVACRLFAQLISGVAYLHKKGVVHRDLKLENLLLDKNRNLVITDFGFA 153
STKc_TGFbR2_like cd14055
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Type II ...
283-418 4.43e-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: 72.79  E-value: 4.43e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTK-----VAIKTLKPGTMmpEAFLQEAQI--MKKLRHDKLVPLYAvvSEEPI-------YIVT 348
Cdd:cd14055     3 VGKGRFAEVWKAKLKQNASgqyetVAVKIFPYEEY--ASWKNEKDIftDASLKHENILQFLT--AEERGvgldrqyWLIT 78
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1370473802 349 EFMSKGSLLDFLKegdGKYLKLPQLVDMAAQIADGMAY---------IERMNYIHRDLRAANILVGENLVCKIADFGLA 418
Cdd:cd14055    79 AYHENGSLQDYLT---RHILSWEDLCKMAGSLARGLAHlhsdrtpcgRPKIPIAHRDLKSSNILVKNDGTCVLADFGLA 154
STKc_TBK1 cd13988
Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1; STKs catalyze the ...
283-425 4.62e-14

Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TBK1 is also called T2K and NF-kB-activating kinase. It is widely expressed in most cell types and acts as an IkappaB kinase (IKK)-activating kinase responsible for NF-kB activation in response to growth factors. It plays a role in modulating inflammatory responses through the NF-kB pathway. TKB1 is also a major player in innate immune responses since it functions as a virus-activated kinase necessary for establishing an antiviral state. It phosphorylates IRF-3 and IRF-7, which are important transcription factors for inducing type I interferon during viral infection. In addition, TBK1 may also play roles in cell transformation and oncogenesis. The TBK1 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: 270890 [Multi-domain]  Cd Length: 316  Bit Score: 72.91  E-value: 4.62e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTK-VAIKTLKPGTMM--PEAFLQEAQIMKKLRHDKLVPLYAVVSEEPI---YIVTEFMSKGSL 356
Cdd:cd13988     1 LGQGATANVFRGRHKKTGDlYAVKVFNNLSFMrpLDVQMREFEVLKKLNHKNIVKLFAIEEELTTrhkVLVMELCPCGSL 80
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370473802 357 LDFLKEGDGKYlKLPQ--LVDMAAQIADGMAYIERMNYIHRDLRAANIL--VGEN--LVCKIADFGLARLIEDNE 425
Cdd:cd13988    81 YTVLEEPSNAY-GLPEseFLIVLRDVVAGMNHLRENGIVHRDIKPGNIMrvIGEDgqSVYKLTDFGAARELEDDE 154
PKc_LIMK_like_unk cd14156
Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs ...
283-484 4.88e-14

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: 72.17  E-value: 4.88e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKVAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVP-LYAVVSEEPIYIVTEFMSKGSLLDFLK 361
Cdd:cd14156     1 IGSGFFSKVYKVTHGATGKVMVVKIYKNDVDQHKIVREISLLQKLSHPNIVRyLGICVKDEKLHPILEYVSGGCLEELLA 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 362 EGDGKyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILV---GENLVCKIADFGLARLIED--------------- 423
Cdd:cd14156    81 REELP-LSWREKVELACDISRGMVYLHSKNIYHRDLNSKNCLIrvtPRGREAVVTDFGLAREVGEmpandperklslvgs 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 424 -----------NEYTaRQ------GMVNREVLEQVE----------------RGYRMPCPqGCPESLHELMNLCWKKDPD 470
Cdd:cd14156   160 afwmapemlrgEPYD-RKvdvfsfGIVLCEILARIPadpevlprtgdfgldvQAFKEMVP-GCPEPFLDLAASCCRMDAF 237
                         250
                  ....*....|....
gi 1370473802 471 ERPTFEYIQSFLED 484
Cdd:cd14156   238 KRPSFAELLDELED 251
SH3_Lck cd12005
Src homology 3 domain of Lck Protein Tyrosine Kinase; Lck is a member of the Src subfamily of ...
97-148 4.98e-14

Src homology 3 domain of Lck Protein Tyrosine Kinase; Lck is a member 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. 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 SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. 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: 212938 [Multi-domain]  Cd Length: 54  Bit Score: 66.39  E-value: 4.98e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1370473802  97 VALYDYEARTTEDLSFKKGERFQIINNtEGDWWEARSIATGKNGYIPSNYVA 148
Cdd:cd12005     3 VALYSYEPSHDGDLGFEKGEKLRILEQ-SGEWWKAQSLTTGQEGFIPFNFVA 53
STKc_ERK1_2_like cd07849
Catalytic domain of Extracellular signal-Regulated Kinase 1 and 2-like Serine/Threonine ...
282-448 5.04e-14

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: 73.11  E-value: 5.04e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGT-TKVAIKTLKP--GTMMPEAFLQEAQIMKKLRHDKLVPLYAVV------SEEPIYIVTEFMs 352
Cdd:cd07849    12 YIGEGAYGMVCSAVHKPTgQKVAIKKISPfeHQTYCLRTLREIKILLRFKHENIIGILDIQrpptfeSFKDVYIVQELM- 90
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 353 kgslldflkEGD-GKYLKLPQLVD-----MAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLI---ED 423
Cdd:cd07849    91 ---------ETDlYKLIKTQHLSNdhiqyFLYQILRGLKYIHSANVLHRDLKPSNLLLNTNCDLKICDFGLARIAdpeHD 161
                         170       180       190
                  ....*....|....*....|....*....|
gi 1370473802 424 N-----EYTArqgmvnrevleqvERGYRMP 448
Cdd:cd07849   162 HtgfltEYVA-------------TRWYRAP 178
SH3_SLAP-like cd11848
Src homology 3 domain of Src-Like Adaptor Proteins; SLAPs are adaptor proteins with limited ...
97-148 5.20e-14

Src homology 3 domain of Src-Like Adaptor Proteins; SLAPs are adaptor proteins with limited similarity to Src family tyrosine kinases. They contain an N-terminal SH3 domain followed by an SH2 domain, and a unique C-terminal sequence. They function in regulating the signaling, ubiquitination, and trafficking of T-cell receptor (TCR) and B-cell receptor (BCR) components. Vertebrates contain two SLAPs, named SLAP (or SLA1) and SLAP2 (or SLA2). SLAP has been shown to interact with the EphA receptor, EpoR, Lck, PDGFR, Syk, CD79a, among others, while SLAP2 interacts with CSF1R. Both SLAPs interact with c-Cbl, LAT, CD247, and Zap70. SLAP modulates TCR surface expression levels as well as surface and total BCR levels. As an adaptor to c-Cbl, SLAP increases the ubiquitination, intracellular retention, and targeted degradation of the BCR complex components. SLAP2 plays a role in c-Cbl-dependent regulation of CSF1R, a tyrosine kinase important for myeloid cell growth and differentiation. The SH3 domain of SLAP forms a complex with v-Abl. 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: 212782  Cd Length: 55  Bit Score: 66.44  E-value: 5.20e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1370473802  97 VALYDYEARTTEDLSFKKGERFQIINNtEGDWWEARSIATGKNGYIPSNYVA 148
Cdd:cd11848     3 VALGDYPSGGPAELSLRLGEPLTIVSD-EGDWWKVLSEVTGRESYIPSVHVA 53
STKc_BMPR2_AMHR2 cd14054
Catalytic domain of the Serine/Threonine Kinases, Bone Morphogenetic Protein and ...
283-430 5.85e-14

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: 72.39  E-value: 5.85e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTkVAIKTLKPGTMmpEAFLQEAQIMK--KLRHDKLVPLYAvvSEEPIY--------IVTEFMS 352
Cdd:cd14054     3 IGQGRYGTVWKGSLDERP-VAVKVFPARHR--QNFQNEKDIYElpLMEHSNILRFIG--ADERPTadgrmeylLVLEYAP 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 353 KGSLLDFLKEGDgkyLKLPQLVDMAAQIADGMAYI---ERMNYI------HRDLRAANILVGENLVCKIADFGLARLIED 423
Cdd:cd14054    78 KGSLCSYLRENT---LDWMSSCRMALSLTRGLAYLhtdLRRGDQykpaiaHRDLNSRNVLVKADGSCVICDFGLAMVLRG 154

                  ....*..
gi 1370473802 424 NEYTARQ 430
Cdd:cd14054   155 SSLVRGR 161
STKc_Pho85 cd07836
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; ...
278-419 6.37e-14

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: 72.13  E-value: 6.37e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 278 RLEvKLGQGCFGEVWMGTwNGTTK--VAIKTLK----PGTmmPEAFLQEAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEF 350
Cdd:cd07836     4 QLE-KLGEGTYATVYKGR-NRTTGeiVALKEIHldaeEGT--PSTAIREISLMKELKHENIVRLHDVIhTENKLMLVFEY 79
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370473802 351 MSKgsllDFLK----EGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR 419
Cdd:cd07836    80 MDK----DLKKymdtHGVRGALDPNTVKSFTYQLLKGIAFCHENRVLHRDLKPQNLLINKRGELKLADFGLAR 148
SH2_Nck_family cd09943
Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate ...
156-241 7.44e-14

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: 67.15  E-value: 7.44e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 156 EEWYFGKMGRKDAERLLLNPGNQrGIFLVRESETTKGAYSLSIRDwdeiRGDNvKHYKIrKLDNGGYYITTRaQFDTLQK 235
Cdd:cd09943     1 QPWYYGRITRHQAETLLNEHGHE-GDFLIRDSESNPGDYSVSLKA----PGRN-KHFKV-QVVDNVYCIGQR-KFHTMDE 72

                  ....*.
gi 1370473802 236 LVKHYT 241
Cdd:cd09943    73 LVEHYK 78
PTZ00024 PTZ00024
cyclin-dependent protein kinase; Provisional
283-419 9.19e-14

cyclin-dependent protein kinase; Provisional


Pssm-ID: 240233 [Multi-domain]  Cd Length: 335  Bit Score: 72.49  E-value: 9.19e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVW--MGTWNGTtKVAIKTLKPGTMMPEAF---------------LQEAQIMKKLRHDKLVPLYAV-VSEEPI 344
Cdd:PTZ00024   17 LGEGTYGKVEkaYDTLTGK-IVAIKKVKIIEISNDVTkdrqlvgmcgihfttLRELKIMNEIKHENIMGLVDVyVEGDFI 95
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370473802 345 YIVTEFMSKgsllDFLKEGDGK-YLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR 419
Cdd:PTZ00024   96 NLVMDIMAS----DLKKVVDRKiRLTESQVKCILLQILNGLNVLHKWYFMHRDLSPANIFINSKGICKIADFGLAR 167
PKc_MAPKK cd06605
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase ...
283-476 1.06e-13

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: 71.22  E-value: 1.06e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKV-AIKT--LKPGTMMPEAFLQEAQIMKKLRHDKLVPLY-AVVSEEPIYIVTEFMSKGSLLD 358
Cdd:cd06605     9 LGEGNGGVVSKVRHRPSGQImAVKVirLEIDEALQKQILRELDVLHKCNSPYIVGFYgAFYSEGDISICMEYMDGGSLDK 88
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 359 FLKEGDGkyLKLPQLVDMAAQIADGMAYI-ERMNYIHRDLRAANILVGENLVCKIADFGLA-RLIED------------- 423
Cdd:cd06605    89 ILKEVGR--IPERILGKIAVAVVKGLIYLhEKHKIIHRDVKPSNILVNSRGQVKLCDFGVSgQLVDSlaktfvgtrsyma 166
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 424 ------NEYTARQ-----GMVNRE------------------VLEQVERGYRMPCPQ----GCPESLHELMNLCWKKDPD 470
Cdd:cd06605   167 perisgGKYTVKSdiwslGLSLVElatgrfpypppnakpsmmIFELLSYIVDEPPPLlpsgKFSPDFQDFVSQCLQKDPT 246

                  ....*.
gi 1370473802 471 ERPTFE 476
Cdd:cd06605   247 ERPSYK 252
SH3_SLAP2 cd12011
Src homology 3 domain of Src-Like Adaptor Protein 2; SLAP2 plays a role in c-Cbl-dependent ...
95-148 1.31e-13

Src homology 3 domain of Src-Like Adaptor Protein 2; SLAP2 plays a role in c-Cbl-dependent regulation of CSF1R, a tyrosine kinase important for myeloid cell growth and differentiation. It has been shown to interact with CSF1R, c-Cbl, LAT, CD247, and Zap70. SLAPs are adaptor proteins with limited similarity to Src family tyrosine kinases. They contain an N-terminal SH3 domain followed by an SH2 domain, and a unique C-terminal sequence. They function in regulating the signaling, ubiquitination, and trafficking of T-cell receptor (TCR) and B-cell receptor (BCR) components. The SH3 domain of SLAP forms a complex with v-Abl. 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: 212944  Cd Length: 55  Bit Score: 65.15  E-value: 1.31e-13
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1370473802  95 IFVALYDYEARTTEDLSFKKGERFQIINNtEGDWWEARSIATGKNGYIPSNYVA 148
Cdd:cd12011     1 VAVALCNFPSGGPTELSIRMGEQLTILSE-DGDWWKVSSAVTGRECYIPSNYVA 53
STKc_Chk1 cd14069
Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the ...
283-418 1.39e-13

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: 70.82  E-value: 1.39e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMG-TWNGTTKVAIK--TLKPGTMM-PEAFLQEAQIMKKLRHDKLVPLYAVVSEEPI-YIVTEFMSKGSLL 357
Cdd:cd14069     9 LGEGAFGEVFLAvNRNTEEAVAVKfvDMKRAPGDcPENIKKEVCIQKMLSHKNVVRFYGHRREGEFqYLFLEYASGGELF 88
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370473802 358 DFLKEGDGkylkLPQlvDMA----AQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLA 418
Cdd:cd14069    89 DKIEPDVG----MPE--DVAqfyfQQLMAGLKYLHSCGITHRDIKPENLLLDENDNLKISDFGLA 147
SH2_Nterm_shark_like cd10347
N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
158-240 1.41e-13

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: 65.86  E-value: 1.41e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 158 WYFGKMGRKDAERLLLNPGNQRGIFLVRESETTKGAYSLSIRDWDEIRgdnvkHYKIRKL-------DNGGYYittraqF 230
Cdd:cd10347     3 WYHGKISREVAEALLLREGGRDGLFLVRESTSAPGDYVLSLLAQGEVL-----HYQIRRHgedaffsDDGPLI------F 71
                          90
                  ....*....|
gi 1370473802 231 DTLQKLVKHY 240
Cdd:cd10347    72 HGLDTLIEHY 81
STKc_MST4 cd06640
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs ...
273-425 1.42e-13

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: 70.85  E-value: 1.42e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 273 PRESLRLEVKLGQGCFGEVWMGTWNGTTKV-AIKT--LKPGTMMPEAFLQEAQIMKKLRHDKLVPLY-AVVSEEPIYIVT 348
Cdd:cd06640     2 PEELFTKLERIGKGSFGEVFKGIDNRTQQVvAIKIidLEEAEDEIEDIQQEITVLSQCDSPYVTKYYgSYLKGTKLWIIM 81
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370473802 349 EFMSKGSLLDFLKEGDGKYLklpQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNE 425
Cdd:cd06640    82 EYLGGGSALDLLRAGPFDEF---QIATMLKEILKGLDYLHSEKKIHRDIKAANVLLSEQGDVKLADFGVAGQLTDTQ 155
STKc_SLK_like cd06611
Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the ...
268-418 1.47e-13

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: 70.93  E-value: 1.47e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 268 DAWEIPREslrlevkLGQGCFGEVWMgTWNGTTKV--AIKTLKPGTMMP-EAFLQEAQIMKKLRHDKLVPLYAVVSEEP- 343
Cdd:cd06611     5 DIWEIIGE-------LGDGAFGKVYK-AQHKETGLfaAAKIIQIESEEElEDFMVEIDILSECKHPNIVGLYEAYFYENk 76
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370473802 344 IYIVTEFMSKGSLlDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLA 418
Cdd:cd06611    77 LWILIEFCDGGAL-DSIMLELERGLTEPQIRYVCRQMLEALNFLHSHKVIHRDLKAGNILLTLDGDVKLADFGVS 150
STKc_MAPK4_6 cd07854
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also ...
301-435 1.60e-13

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: 71.73  E-value: 1.60e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 301 KVAIK--TLKPGTMMPEAfLQEAQIMKKLRHDKLVPLYAV---------------VSEEPIYIVTEFMSKgSLLDFLKEG 363
Cdd:cd07854    32 RVAVKkiVLTDPQSVKHA-LREIKIIRRLDHDNIVKVYEVlgpsgsdltedvgslTELNSVYIVQEYMET-DLANVLEQG 109
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1370473802 364 --DGKYLKLpqlvdMAAQIADGMAYIERMNYIHRDLRAANILVG-ENLVCKIADFGLARlIEDNEYTAR----QGMVNR 435
Cdd:cd07854   110 plSEEHARL-----FMYQLLRGLKYIHSANVLHRDLKPANVFINtEDLVLKIGDFGLAR-IVDPHYSHKgylsEGLVTK 182
PK_eIF2AK_GCN2_rpt1 cd14012
Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or ...
325-474 1.63e-13

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: 70.47  E-value: 1.63e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 325 KKLRHDKLVPLYAVVSEEP-------IYIVTEFMSKGSLLDFLKEGDgkYLKLPQLVDMAAQIADGMAYIERMNYIHRDL 397
Cdd:cd14012    53 KKLRHPNLVSYLAFSIERRgrsdgwkVYLLTEYAPGGSLSELLDSVG--SVPLDTARRWTLQLLEALEYLHRNGVVHKSL 130
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 398 RAANILVGENL---VCKIADFGLARLIED------------------------NEYTAR-----------QGMVNREVLE 439
Cdd:cd14012   131 HAGNVLLDRDAgtgIVKLTDYSLGKTLLDmcsrgsldefkqtywlppelaqgsKSPTRKtdvwdlgllflQMLFGLDVLE 210
                         170       180       190
                  ....*....|....*....|....*....|....*
gi 1370473802 440 QVERGYRMPCPQGCPESLHELMNLCWKKDPDERPT 474
Cdd:cd14012   211 KYTSPNPVLVSLDLSASLQDFLSKCLSLDPKKRPT 245
STKc_BMPR1b cd14219
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IB; STKs ...
275-423 2.08e-13

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: 70.85  E-value: 2.08e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 275 ESLRLEVKLGQGCFGEVWMGTWNGTtKVAIKTLKpgTMMPEAFLQEAQIMKK--LRHDKLVPLYA-----VVSEEPIYIV 347
Cdd:cd14219     5 KQIQMVKQIGKGRYGEVWMGKWRGE-KVAVKVFF--TTEEASWFRETEIYQTvlMRHENILGFIAadikgTGSWTQLYLI 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 348 TEFMSKGSLLDFLKegdGKYLKLPQLVDMAAQIADGMAYIE--------RMNYIHRDLRAANILVGENLVCKIADFGLA- 418
Cdd:cd14219    82 TDYHENGSLYDYLK---STTLDTKAMLKLAYSSVSGLCHLHteifstqgKPAIAHRDLKSKNILVKKNGTCCIADLGLAv 158

                  ....*
gi 1370473802 419 RLIED 423
Cdd:cd14219   159 KFISD 163
SH2_C-SH2_Zap70 cd10402
C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
158-256 2.14e-13

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: 66.10  E-value: 2.14e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 158 WYFGKMGRKDAERLLLNPGNQRGIFLVRESETTkGAYSLSIrdwdeIRGDNVKHYKIRKLDNGGYYITTRAQFDTLQKLV 237
Cdd:cd10402    12 WYHGSIARDEAERRLYSGAQPDGKFLLRERKES-GTYALSL-----VYGKTVYHYRIDQDKSGKYSIPEGTKFDTLWQLV 85
                          90
                  ....*....|....*....
gi 1370473802 238 KHYTEHADGLCHKLTTVCP 256
Cdd:cd10402    86 EYLKLKPDGLIFVLRESCP 104
SH3_Tec_like cd11768
Src Homology 3 domain of Tec-like Protein Tyrosine Kinases; The Tec (Tyrosine kinase expressed ...
95-149 2.50e-13

Src Homology 3 domain of Tec-like Protein Tyrosine Kinases; The Tec (Tyrosine kinase expressed in hepatocellular carcinoma) subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) tyr kinases containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. 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 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. The function of Tec kinases in lymphoid cells have been studied extensively. They play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. 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: 212702 [Multi-domain]  Cd Length: 54  Bit Score: 64.22  E-value: 2.50e-13
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1370473802  95 IFVALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARSiATGKNGYIPSNYVAP 149
Cdd:cd11768     1 IVVALYDFQPIEPGDLPLEKGEEYVVLDDSNEHWWRARD-KNGNEGYIPSNYVTE 54
STKc_TNIK cd06637
Catalytic domain of the Serine/Threonine Kinase, Traf2- and Nck-Interacting Kinase; STKs ...
283-418 2.58e-13

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: 70.52  E-value: 2.58e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKVA-IKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLY--AVVSEEP------IYIVTEFMSK 353
Cdd:cd06637    14 VGNGTYGQVYKGRHVKTGQLAaIKVMDVTGDEEEEIKQEINMLKKYSHHRNIATYygAFIKKNPpgmddqLWLVMEFCGA 93
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370473802 354 GSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLA 418
Cdd:cd06637    94 GSVTDLIKNTKGNTLKEEWIAYICREILRGLSHLHQHKVIHRDIKGQNVLLTENAEVKLVDFGVS 158
STKc_ROCK_NDR_like cd05573
Catalytic domain of Rho-associated coiled-coil containing protein kinase (ROCK)- and Nuclear ...
283-418 2.60e-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: 2.60e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKV-AIKTLKPGTM--MPE--AFLQEAQIMKKLRHDKLVPL-YAVVSEEPIYIVTEFMSKGSL 356
Cdd:cd05573     9 IGRGAFGEVWLVRDKDTGQVyAMKILRKSDMlkREQiaHVRAERDILADADSPWIVRLhYAFQDEDHLYLVMEYMPGGDL 88
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370473802 357 LDFLKegdgKYLKLPQlvDMA----AQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLA 418
Cdd:cd05573    89 MNLLI----KYDVFPE--ETArfyiAELVLALDSLHKLGFIHRDIKPDNILLDADGHIKLADFGLC 148
SH3_OSTF1 cd11772
Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or ...
95-149 2.62e-13

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. 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: 212706 [Multi-domain]  Cd Length: 53  Bit Score: 64.24  E-value: 2.62e-13
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1370473802  95 IFVALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARSiaTGKNGYIPSNYVAP 149
Cdd:cd11772     1 VFRALYDYEAQHPDELSFEEGDLLYISDKSDPNWWKATC--GGKTGLIPSNYVEE 53
STKc_MAP4K4_6_N cd06636
N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase ...
283-418 2.79e-13

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: 70.04  E-value: 2.79e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKVA-IKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLY--AVVSEEP------IYIVTEFMSK 353
Cdd:cd06636    24 VGNGTYGQVYKGRHVKTGQLAaIKVMDVTEDEEEEIKLEINMLKKYSHHRNIATYygAFIKKSPpghddqLWLVMEFCGA 103
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370473802 354 GSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLA 418
Cdd:cd06636   104 GSVTDLVKNTKGNALKEDWIAYICREILRGLAHLHAHKVIHRDIKGQNVLLTENAEVKLVDFGVS 168
STKc_CK1 cd14016
Catalytic domain of the Serine/Threonine protein kinase, Casein Kinase 1; STKs catalyze the ...
278-419 2.94e-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: 69.79  E-value: 2.94e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 278 RLEVKLGQGCFGEVWMGTWNGT-TKVAIKtLKPGTMMPEAFLQEAQIMKKLRHDKLVP-LYAVVSEEPI-YIVTEFMSKg 354
Cdd:cd14016     3 KLVKKIGSGSFGEVYLGIDLKTgEEVAIK-IEKKDSKHPQLEYEAKVYKLLQGGPGIPrLYWFGQEGDYnVMVMDLLGP- 80
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370473802 355 SLLDFLKEGDGKY-LKlpqlvdMAAQIADGMA----YIERMNYIHRDLRAANILVGENLVCK---IADFGLAR 419
Cdd:cd14016    81 SLEDLFNKCGRKFsLK------TVLMLADQMIsrleYLHSKGYIHRDIKPENFLMGLGKNSNkvyLIDFGLAK 147
STKc_Nek6_7 cd08224
Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related ...
279-478 3.15e-13

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: 69.61  E-value: 3.15e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 279 LEVKLGQGCFGEVWMG--TWNGTTkVAIKTLKPGTMMP----EAFLQEAQIMKKLRHDKLVPLYA-VVSEEPIYIVTEFM 351
Cdd:cd08224     4 IEKKIGKGQFSVVYRArcLLDGRL-VALKKVQIFEMMDakarQDCLKEIDLLQQLNHPNIIKYLAsFIENNELNIVLELA 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 352 SKGSLLDFLKE--GDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEdNEYTAR 429
Cdd:cd08224    83 DAGDLSRLIKHfkKQKRLIPERTIWKYFVQLCSALEHMHSKRIMHRDIKPANVFITANGVVKLGDLGLGRFFS-SKTTAA 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 430 QGMV------NREVLEqvERGYRM-----------------------------------------PCPQGC-PESLHELM 461
Cdd:cd08224   162 HSLVgtpyymSPERIR--EQGYDFksdiwslgcllyemaalqspfygekmnlyslckkiekceypPLPADLySQELRDLV 239
                         250
                  ....*....|....*..
gi 1370473802 462 NLCWKKDPDERPTFEYI 478
Cdd:cd08224   240 AACIQPDPEKRPDISYV 256
STKc_Sty1_Hog1 cd07856
Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases ...
283-467 3.17e-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: 70.68  E-value: 3.17e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGT-TKVAIKTL-KPGT--MMPEAFLQEAQIMKKLRHDKLVPLYAVVSE--EPIYIVTEFMskGSL 356
Cdd:cd07856    18 VGMGAFGLVCSARDQLTgQNVAVKKImKPFStpVLAKRTYRELKLLKHLRHENIISLSDIFISplEDIYFVTELL--GTD 95
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 357 LDFLkegdgkyLKLPQLVDMAAQ-----IADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARlIEDNEYTarqG 431
Cdd:cd07856    96 LHRL-------LTSRPLEKQFIQyflyqILRGLKYVHSAGVIHRDLKPSNILVNENCDLKICDFGLAR-IQDPQMT---G 164
                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 1370473802 432 MVNrevleqvERGYRMPcpqgcpeslhELMnLCWKK 467
Cdd:cd07856   165 YVS-------TRYYRAP----------EIM-LTWQK 182
STKc_LRRK2 cd14068
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze ...
283-448 4.01e-13

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: 69.21  E-value: 4.01e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTtKVAIKTLKPGTMMpEAFLQEAQIMKKLRHDKLVPLYAVvSEEPIYIVTEFMSKGSLLDFLKE 362
Cdd:cd14068     2 LGDGGFGSVYRAVYRGE-DVAVKIFNKHTSF-RLLRQELVVLSHLHHPSLVALLAA-GTAPRMLVMELAPKGSLDALLQQ 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 363 GDGKYLKLPQLvDMAAQIADGMAYIERMNYIHRDLRAANILV-----GENLVCKIADFGLArliednEYTARQGMVNREv 437
Cdd:cd14068    79 DNASLTRTLQH-RIALHVADGLRYLHSAMIIYRDLKPHNVLLftlypNCAIIAKIADYGIA------QYCCRMGIKTSE- 150
                         170
                  ....*....|.
gi 1370473802 438 leqVERGYRMP 448
Cdd:cd14068   151 ---GTPGFRAP 158
STKc_p38alpha cd07877
Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase ...
263-423 4.98e-13

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: 70.07  E-value: 4.98e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 263 QGLAKDAWEIPRESLRLEvKLGQGCFGEVwMGTWNGTT--KVAIKTL-KPGTMMPEA--FLQEAQIMKKLRHDKLVPLYA 337
Cdd:cd07877     6 QELNKTIWEVPERYQNLS-PVGSGAYGSV-CAAFDTKTglRVAVKKLsRPFQSIIHAkrTYRELRLLKHMKHENVIGLLD 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 338 VVS-----EE--PIYIVTEFMskGSLLDFLkegdgkyLKLPQLVD-----MAAQIADGMAYIERMNYIHRDLRAANILVG 405
Cdd:cd07877    84 VFTparslEEfnDVYLVTHLM--GADLNNI-------VKCQKLTDdhvqfLIYQILRGLKYIHSADIIHRDLKPSNLAVN 154
                         170
                  ....*....|....*...
gi 1370473802 406 ENLVCKIADFGLARLIED 423
Cdd:cd07877   155 EDCELKILDFGLARHTDD 172
STKc_ULK2 cd14201
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the ...
283-428 6.48e-13

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: 68.88  E-value: 6.48e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTT--KVAIKTLKPGTMMPEAFL--QEAQIMKKLRHDKLVPLYAVvSEEP--IYIVTEFMSKGSL 356
Cdd:cd14201    14 VGHGAFAVVFKGRHRKKTdwEVAIKSINKKNLSKSQILlgKEIKILKELQHENIVALYDV-QEMPnsVFLVMEYCNGGDL 92
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 357 LDFLkEGDGKyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVG---------ENLVCKIADFGLARLIEDNEYT 427
Cdd:cd14201    93 ADYL-QAKGT-LSEDTIRVFLQQIAAAMRILHSKGIIHRDLKPQNILLSyasrkkssvSGIRIKIADFGFARYLQSNMMA 170

                  .
gi 1370473802 428 A 428
Cdd:cd14201   171 A 171
STKc_YSK4 cd06631
Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs ...
283-419 8.03e-13

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: 68.62  E-value: 8.03e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKVAIKTLKPGTMMPEAF------LQ-EAQIMKKLRHDKLVP-LYAVVSEEPIYIVTEFMSKG 354
Cdd:cd06631     9 LGKGAYGTVYCGLTSTGQLIAVKQVELDTSDKEKAekeyekLQeEVDLLKTLKHVNIVGyLGTCLEDNVVSIFMEFVPGG 88
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370473802 355 SLLDFLKegdgKYLKLPQLV--DMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR 419
Cdd:cd06631    89 SIASILA----RFGALEEPVfcRYTKQILEGVAYLHNNNVIHRDIKGNNIMLMPNGVIKLIDFGCAK 151
STKc_STK33 cd14097
Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the ...
282-418 8.78e-13

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: 68.34  E-value: 8.78e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGT-TKVAIKTL---KPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVsEEP--IYIVTEFMSKGS 355
Cdd:cd14097     8 KLGQGSFGVVIEATHKETqTKWAIKKInreKAGSSAVKLLEREVDILKHVNHAHIIHLEEVF-ETPkrMYLVMELCEDGE 86
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370473802 356 LLDFL------KEGDGKYLklpqlvdmAAQIADGMAYIERMNYIHRDLRAANILVGENLV-------CKIADFGLA 418
Cdd:cd14097    87 LKELLlrkgffSENETRHI--------IQSLASAVAYLHKNDIVHRDLKLENILVKSSIIdnndklnIKVTDFGLS 154
STKc_Nek2 cd08217
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
282-476 9.19e-13

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: 68.34  E-value: 9.19e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVwmgtwngtTKV---------AIKTLKPGTMMP---EAFLQEAQIMKKLRHDKLVPLY---AVVSEEPIYI 346
Cdd:cd08217     7 TIGKGSFGTV--------RKVrrksdgkilVWKEIDYGKMSEkekQQLVSEVNILRELKHPNIVRYYdriVDRANTTLYI 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 347 VTEFMSKGSLLDFLKEG--DGKYLKLPQLVDMAAQIADGMAYIERMNY-----IHRDLRAANILVGENLVCKIADFGLAR 419
Cdd:cd08217    79 VMEYCEGGDLAQLIKKCkkENQYIPEEFIWKIFTQLLLALYECHNRSVgggkiLHRDLKPANIFLDSDNNVKLGDFGLAR 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 420 ----------------------LIEDNEYTAR--------------------QGMVNREVLEQVERGYRMPCPQGCPESL 457
Cdd:cd08217   159 vlshdssfaktyvgtpyymspeLLNEQSYDEKsdiwslgcliyelcalhppfQAANQLELAKKIKEGKFPRIPSRYSSEL 238
                         250
                  ....*....|....*....
gi 1370473802 458 HELMNLCWKKDPDERPTFE 476
Cdd:cd08217   239 NEVIKSMLNVDPDKRPSVE 257
STKc_ULK1_2-like cd14120
Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar ...
283-424 9.33e-13

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: 68.16  E-value: 9.33e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTK--VAIKTL-KPGTMMPEAFL-QEAQIMKKLRHDKLVPLYAV-VSEEPIYIVTEFMSKGSLL 357
Cdd:cd14120     1 IGHGAFAVVFKGRHRKKPDlpVAIKCItKKNLSKSQNLLgKEIKILKELSHENVVALLDCqETSSSVYLVMEYCNGGDLA 80
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370473802 358 DFL-KEGDgkyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILV---------GENLVCKIADFGLARLIEDN 424
Cdd:cd14120    81 DYLqAKGT---LSEDTIRVFLQQIAAAMKALHSKGIVHRDLKPQNILLshnsgrkpsPNDIRLKIADFGFARFLQDG 154
STKc_GAK cd14036
Catalytic domain of the Serine/Threonine protein kinase, cyclin G-Associated Kinase; STKs ...
277-448 1.08e-12

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: 68.31  E-value: 1.08e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 277 LRLEVKLGQGCFGEVWMGTWNGT-TKVAIKTLKPGTMMP-EAFLQEAQIMKKLR-HDKLVPLYAVVS---EEPIYIVTEF 350
Cdd:cd14036     2 LRIKRVIAEGGFAFVYEAQDVGTgKEYALKRLLSNEEEKnKAIIQEINFMKKLSgHPNIVQFCSAASigkEESDQGQAEY 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 351 M-----SKGSLLDFLKE-GDGKYLKLPQLVDMAAQIADGMAYIERMN--YIHRDLRAANILVGENLVCKIADFGLAR--- 419
Cdd:cd14036    82 LlltelCKGQLVDFVKKvEAPGPFSPDTVLKIFYQTCRAVQHMHKQSppIIHRDLKIENLLIGNQGQIKLCDFGSATtea 161
                         170       180       190
                  ....*....|....*....|....*....|
gi 1370473802 420 LIEDNEYTA-RQGMVNREVLEQVERGYRMP 448
Cdd:cd14036   162 HYPDYSWSAqKRSLVEDEITRNTTPMYRTP 191
PKc_DYRK_like cd14133
Catalytic domain of Dual-specificity tYrosine-phosphorylated and -Regulated Kinase-like ...
283-448 1.14e-12

Catalytic domain of Dual-specificity tYrosine-phosphorylated and -Regulated Kinase-like protein kinases; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity DYRKs and YAK1, as well as the S/T kinases (STKs), HIPKs. DYRKs and YAK1 autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. Proteins in this subfamily play important roles in cell proliferation, differentiation, survival, growth, and development. The DYRK-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: 271035 [Multi-domain]  Cd Length: 262  Bit Score: 68.06  E-value: 1.14e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTK-VAIKTLKPgtmMPEAFLQ---EAQIMKKLR------HDKLVPLY-AVVSEEPIYIVTEFM 351
Cdd:cd14133     7 LGKGTFGQVVKCYDLLTGEeVALKIIKN---NKDYLDQsldEIRLLELLNkkdkadKYHIVRLKdVFYFKNHLCIVFELL 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 352 SKgSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVC--KIADFGLARLIEDNEYTAR 429
Cdd:cd14133    84 SQ-NLYEFLKQNKFQYLSLPRIRKIAQQILEALVFLHSLGLIHCDLKPENILLASYSRCqiKIIDFGSSCFLTQRLYSYI 162
                         170
                  ....*....|....*....
gi 1370473802 430 QgmvnrevleqvERGYRMP 448
Cdd:cd14133   163 Q-----------SRYYRAP 170
STKc_TSSK6-like cd14164
Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs ...
283-423 1.15e-12

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: 67.96  E-value: 1.15e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNG-TTKVAIKTLKPGTMMPEaFLQ-----EAQIMKKLRHDKLVPLYAV--VSEEPIYIVTEFMSKg 354
Cdd:cd14164     8 IGEGSFSKVKLATSQKyCCKVAIKIVDRRRASPD-FVQkflprELSILRRVNHPNIVQMFECieVANGRLYIVMEAAAT- 85
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 355 SLLDFLKEGdgKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILV-GENLVCKIADFGLARLIED 423
Cdd:cd14164    86 DLLQKIQEV--HHIPKDLARDMFAQMVGAVNYLHDMNIVHRDLKCENILLsADDRKIKIADFGFARFVED 153
STKc_MAP4K3_like cd06613
Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like ...
282-421 1.16e-12

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: 68.10  E-value: 1.16e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGTTK-VAIKTLK--PGTMMpEAFLQEAQIMKKLRHDKLVPLY-AVVSEEPIYIVTEFMSKGSLL 357
Cdd:cd06613     7 RIGSGTYGDVYKARNIATGElAAVKVIKlePGDDF-EIIQQEISMLKECRHPNIVAYFgSYLRRDKLWIVMEYCGGGSLQ 85
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370473802 358 DFLKEGDGkyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLI 421
Cdd:cd06613    86 DIYQVTGP--LSELQIAYVCRETLKGLAYLHSTGKIHRDIKGANILLTEDGDVKLADFGVSAQL 147
STKc_p38beta cd07878
Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase ...
263-448 1.16e-12

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: 68.92  E-value: 1.16e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 263 QGLAKDAWEIPRESLRLeVKLGQGCFGEVwMGTWNGTT--KVAIKTL-KPGTMMPEA--FLQEAQIMKKLRHDKLVPLYA 337
Cdd:cd07878     4 QELNKTVWEVPERYQNL-TPVGSGAYGSV-CSAYDTRLrqKVAVKKLsRPFQSLIHArrTYRELRLLKHMKHENVIGLLD 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 338 VVSE-------EPIYIVTEFMskGSLLDFLkegdgkyLKLPQLVD-----MAAQIADGMAYIERMNYIHRDLRAANILVG 405
Cdd:cd07878    82 VFTPatsienfNEVYLVTNLM--GADLNNI-------VKCQKLSDehvqfLIYQLLRGLKYIHSAGIIHRDLKPSNVAVN 152
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 1370473802 406 ENLVCKIADFGLARLiEDNEYTarqGMVnrevleqVERGYRMP 448
Cdd:cd07878   153 EDCELRILDFGLARQ-ADDEMT---GYV-------ATRWYRAP 184
STKc_Yank1 cd05578
Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the ...
284-427 1.16e-12

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: 68.05  E-value: 1.16e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 284 GQGCFGEVWMGTWNGTTKV-AIKTlkpgtMMPEA---------FLQEAQIMKKLRHDKLVPL-YAVVSEEPIYIVtefms 352
Cdd:cd05578     9 GKGSFGKVCIVQKKDTKKMfAMKY-----MNKQKciekdsvrnVLNELEILQELEHPFLVNLwYSFQDEEDMYMV----- 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 353 kgslLDFLKEGDGKYlKLPQLVDM--------AAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDN 424
Cdd:cd05578    79 ----VDLLLGGDLRY-HLQQKVKFseetvkfyICEIVLALDYLHSKNIIHRDIKPDNILLDEQGHVHITDFNIATKLTDG 153

                  ...
gi 1370473802 425 EYT 427
Cdd:cd05578   154 TLA 156
STKc_CDKL2_3 cd07846
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; ...
282-421 1.37e-12

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: 68.22  E-value: 1.37e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVwMGTWNGTTK--VAIKTLKPG---TMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEP-IYIVTEFMSKGS 355
Cdd:cd07846     8 LVGEGSYGMV-MKCRHKETGqiVAIKKFLESeddKMVKKIAMREIKMLKQLRHENLVNLIEVFRRKKrWYLVFEFVDHTV 86
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370473802 356 LLDFLKEGDGkyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLI 421
Cdd:cd07846    87 LDDLEKYPNG--LDESRVRKYLFQILRGIDFCHSHNIIHRDIKPENILVSQSGVVKLCDFGFARTL 150
SH3_Bem1p_1 cd11878
First Src Homology 3 domain of Bud emergence protein 1 and similar domains; Members of this ...
98-146 1.40e-12

First Src Homology 3 domain of Bud emergence protein 1 and similar domains; Members of this subfamily bear similarity to Saccharomyces cerevisiae Bem1p, containing two Src Homology 3 (SH3) domains at the N-terminus, a central PX domain, and a C-terminal PB1 domain. Bem1p is a scaffolding protein that is critical for proper Cdc42p activation during bud formation in yeast. During budding and mating, Bem1p migrates to the plasma membrane where it can serve as an adaptor for Cdc42p and some other proteins. Bem1p also functions as an effector of the G1 cyclin Cln3p and the cyclin-dependent kinase Cdc28p in promoting vacuolar fusion. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212811 [Multi-domain]  Cd Length: 54  Bit Score: 62.31  E-value: 1.40e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1370473802  98 ALYDYEARTTEDLSFKKGERFQIIN-NTEGDWWEARSIATGKNGYIPSNY 146
Cdd:cd11878     4 ALYDYRAQTPGELSFSKGDFFHVIGeEDQGEWYEATNPVTGKRGLVPKSY 53
SH3_Nck_3 cd11767
Third Src Homology 3 domain of Nck adaptor proteins; This group contains the third SH3 domain ...
97-148 1.46e-12

Third Src Homology 3 domain of Nck adaptor proteins; This group contains the third SH3 domain of Nck, the first SH3 domain of Caenorhabditis elegans Ced-2 (Cell death abnormality protein 2), and similar domains. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. Ced-2 is a cell corpse engulfment protein that interacts with Ced-5 in a pathway that regulates the activation of Ced-10, a Rac small GTPase.


Pssm-ID: 212701 [Multi-domain]  Cd Length: 56  Bit Score: 62.33  E-value: 1.46e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1370473802  97 VALYDYEARTTEDLSFKKGERFQIINNTEGD--WWEARSiATGKNGYIPSNYVA 148
Cdd:cd11767     3 VALYPFTGENDEELSFEKGERLEIIEKPEDDpdWWKARN-ALGTTGLVPRNYVE 55
STKc_MEKK3_like_u1 cd06653
Catalytic domain of an Uncharacterized subfamily of Mitogen-Activated Protein (MAP) ...
275-422 1.79e-12

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: 67.36  E-value: 1.79e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 275 ESLRLEVKLGQGCFGEVWMgTWNGTT--KVAIKTL--KPGTMMPE----AFLQEAQIMKKLRHDKLVPLYAVV---SEEP 343
Cdd:cd06653     2 VNWRLGKLLGRGAFGEVYL-CYDADTgrELAVKQVpfDPDSQETSkevnALECEIQLLKNLRHDRIVQYYGCLrdpEEKK 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 344 IYIVTEFMSKGSLLDFLKegdgKYLKLPQLVD--MAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLI 421
Cdd:cd06653    81 LSIFVEYMPGGSVKDQLK----AYGALTENVTrrYTRQILQGVSYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASKRI 156

                  .
gi 1370473802 422 E 422
Cdd:cd06653   157 Q 157
STKc_PLK2 cd14188
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the ...
283-429 1.86e-12

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: 67.34  E-value: 1.86e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKVAIKTLKPGTMMP-----EAFLQEAQIMKKLRHDKLVPLYAVVSE-EPIYIVTEFMSKGSL 356
Cdd:cd14188     9 LGKGGFAKCYEMTDLTTNKVYAAKIIPHSRVSkphqrEKIDKEIELHRILHHKHVVQFYHYFEDkENIYILLEYCSRRSM 88
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370473802 357 LDFLKEGdgKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYTAR 429
Cdd:cd14188    89 AHILKAR--KVLTEPEVRYYLRQIVSGLKYLHEQEILHRDLKLGNFFINENMELKVGDFGLAARLEPLEHRRR 159
STKc_DCKL cd14095
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called ...
320-427 1.97e-12

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: 67.35  E-value: 1.97e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 320 EAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFMSKGSLLDFLKEGdGKYLKlPQLVDMAAQIADGMAYIERMNYIHRDLR 398
Cdd:cd14095    48 EVAILRRVKHPNIVQLIEEYdTDTELYLVMELVKGGDLFDAITSS-TKFTE-RDASRMVTDLAQALKYLHSLSIVHRDIK 125
                          90       100       110
                  ....*....|....*....|....*....|...
gi 1370473802 399 AANILVGEN----LVCKIADFGLARLIEDNEYT 427
Cdd:cd14095   126 PENLLVVEHedgsKSLKLADFGLATEVKEPLFT 158
STKc_STK25 cd06642
Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); ...
282-425 2.25e-12

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: 67.39  E-value: 2.25e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGTTKV-AIKT--LKPGTMMPEAFLQEAQIMKKLRHDKLVPLY-AVVSEEPIYIVTEFMSKGSLL 357
Cdd:cd06642    11 RIGKGSFGEVYKGIDNRTKEVvAIKIidLEEAEDEIEDIQQEITVLSQCDSPYITRYYgSYLKGTKLWIIMEYLGGGSAL 90
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1370473802 358 DFLKEGDgkyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNE 425
Cdd:cd06642    91 DLLKPGP---LEETYIATILREILKGLDYLHSERKIHRDIKAANVLLSEQGDVKLADFGVAGQLTDTQ 155
STKc_NLK cd07853
Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer ...
283-448 2.40e-12

Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NLK is an atypical mitogen-activated protein kinase (MAPK) that is not regulated by a MAPK kinase. It functions downstream of the MAPK kinase kinase Tak1, which also plays a role in activating the JNK and p38 MAPKs. The Tak1/NLK pathways are regulated by Wnts, a family of secreted proteins that is critical in the control of asymmetric division and cell polarity. NLK can phosphorylate transcription factors from the TCF/LEF family, inhibiting their ability to activate the transcription of target genes. In prostate cancer cells, NLK is involved in regulating androgen receptor-mediated transcription and its expression is altered during cancer progression. MAPKs are important mediators of cellular responses to extracellular signals. The NLK 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: 173748 [Multi-domain]  Cd Length: 372  Bit Score: 68.23  E-value: 2.40e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGT--WNGTtKVAIKTlkpgtmMPEAF---------LQEAQIMKKLRHDKLVPLYAVVSE------EPIY 345
Cdd:cd07853     8 IGYGAFGVVWSVTdpRDGK-RVALKK------MPNVFqnlvsckrvFRELKMLCFFKHDNVLSALDILQPphidpfEEIY 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 346 IVTEFM---------SKGSLLDflkegdgKYLKLpqlvdMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFG 416
Cdd:cd07853    81 VVTELMqsdlhkiivSPQPLSS-------DHVKV-----FLYQILRGLKYLHSAGILHRDIKPGNLLVNSNCVLKICDFG 148
                         170       180       190
                  ....*....|....*....|....*....|..
gi 1370473802 417 LARLIEDNEytaRQGMvNREVLEQVergYRMP 448
Cdd:cd07853   149 LARVEEPDE---SKHM-TQEVVTQY---YRAP 173
STKc_PCTAIRE1 cd07873
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer ...
282-419 2.53e-12

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: 67.72  E-value: 2.53e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGTTK-VAIKT--LKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFMSKgSLL 357
Cdd:cd07873     9 KLGEGTYATVYKGRSKLTDNlVALKEirLEHEEGAPCTAIREVSLLKDLKHANIVTLHDIIhTEKSLTLVFEYLDK-DLK 87
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370473802 358 DFLKEGdGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR 419
Cdd:cd07873    88 QYLDDC-GNSINMHNVKLFLFQLLRGLAYCHRRKVLHRDLKPQNLLINERGELKLADFGLAR 148
SH3_Brk cd11847
Src homology 3 domain of Brk (Breast tumor kinase) Protein Tyrosine Kinase (PTK), also called ...
95-148 2.63e-12

Src homology 3 domain of Brk (Breast tumor kinase) Protein Tyrosine Kinase (PTK), also called PTK6; Brk is a cytoplasmic (or non-receptor) PTK with limited homology to Src kinases. It has been found to be overexpressed in a majority of breast tumors. It plays roles in normal cell differentiation, proliferation, survival, migration, and cell cycle progression. Brk substrates include RNA-binding proteins (SLM-1/2, Sam68), transcription factors (STAT3/5), and signaling molecules (Akt, paxillin, IRS-4). 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). However, Brk lacks the N-terminal myristoylation site. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. 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: 212781 [Multi-domain]  Cd Length: 58  Bit Score: 61.81  E-value: 2.63e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1370473802  95 IFVALYDYEARTTEDLSFKKGERFQIINNtEGDWWEARSI-----ATGKnGYIPSNYVA 148
Cdd:cd11847     1 IYKALWDFKARGDEELSFQAGDQFRIAER-SGDWWTALKLdraggVVAQ-GFVPNNYLA 57
STKc_MLCK2 cd14190
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze ...
283-425 2.85e-12

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: 66.87  E-value: 2.85e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGT-TKVAIKTL-KPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVsEEP--IYIVTEFMSKGSLLD 358
Cdd:cd14190    12 LGGGKFGKVHTCTEKRTgLKLAAKVInKQNSKDKEMVLLEIQVMNQLNHRNLIQLYEAI-ETPneIVLFMEYVEGGELFE 90
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1370473802 359 FLKEGDGKYLKLPQLVdMAAQIADGMAYIERMNYIHRDLRAANILV--GENLVCKIADFGLARLIEDNE 425
Cdd:cd14190    91 RIVDEDYHLTEVDAMV-FVRQICEGIQFMHQMRVLHLDLKPENILCvnRTGHQVKIIDFGLARRYNPRE 158
SH2_N-SH2_SHP_like cd10340
N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
158-243 2.86e-12

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: 62.80  E-value: 2.86e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 158 WYFGKMGRKDAERLLLNPGNQrGIFLVRESETTKGAYSLSIRdwdeiRGDNVKHYKIRKldNGGYY-ITTRAQFDTLQKL 236
Cdd:cd10340     2 WFHPVISGIEAENLLKTRGVD-GSFLARPSKSNPGDFTLSVR-----RGDEVTHIKIQN--TGDYYdLYGGEKFATLSEL 73

                  ....*..
gi 1370473802 237 VKHYTEH 243
Cdd:cd10340    74 VQYYMEQ 80
STKc_MAST_like cd05579
Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs ...
285-436 3.10e-12

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: 66.86  E-value: 3.10e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 285 QGCFGEVWMGTWNGTTKV-AIKTLKP----GTMMPEAFLQEAQIMKKLRHDKLVPL-YAVVSEEPIYIVTEFMSKG---S 355
Cdd:cd05579     3 RGAYGRVYLAKKKSTGDLyAIKVIKKrdmiRKNQVDSVLAERNILSQAQNPFVVKLyYSFQGKKNLYLVMEYLPGGdlyS 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 356 LLDflkegdgKYLKLPQlvDMA----AQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLiedneytarqG 431
Cdd:cd05579    83 LLE-------NVGALDE--DVAriyiAEIVLALEYLHSHGIIHRDLKPDNILIDANGHLKLTDFGLSKV----------G 143

                  ....*
gi 1370473802 432 MVNRE 436
Cdd:cd05579   144 LVRRQ 148
PTKc_Aatyk2 cd05086
Catalytic domain of the Protein Tyrosine Kinase, Apoptosis-associated tyrosine kinase 2; PTKs ...
282-482 3.53e-12

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: 66.81  E-value: 3.53e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMG---TWNGTTKVAIKTLKPGTMMPEA--FLQEAQIMKKLRHDKLVP-LYAVVSEEPIYIVTEFMSKGS 355
Cdd:cd05086     4 EIGNGWFGKVLLGeiyTGTSVARVVVKELKASANPKEQddFLQQGEPYYILQHPNILQcVGQCVEAIPYLLVFEFCDLGD 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 356 LLDFLKEGDGKYLKLPQLVD---MAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGL--ARLIED------- 423
Cdd:cd05086    84 LKTYLANQQEKLRGDSQIMLlqrMACEIAAGLAHMHKHNFLHSDLALRNCYLTSDLTVKVGDYGIgfSRYKEDyietddk 163
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 424 ----------NEYTARQGMV---------------------------------NREVLEQV--ERGYRMPCP---QGCPE 455
Cdd:cd05086   164 kyaplrwtapELVTSFQDGLlaaeqtkysniwslgvtlwelfenaaqpysdlsDREVLNHVikERQVKLFKPhleQPYSD 243
                         250       260
                  ....*....|....*....|....*..
gi 1370473802 456 SLHELMNLCWKKdPDERPTFEYIQSFL 482
Cdd:cd05086   244 RWYEVLQFCWLS-PEKRPTAEEVHRLL 269
STKc_Nek8 cd08220
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
283-421 4.14e-12

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: 66.29  E-value: 4.14e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTK-VAIKTLKPGTMMPE---AFLQEAQIMKKLRHDKLVPLY-AVVSEEPIYIVTEFMSKGSLL 357
Cdd:cd08220     8 VGRGAYGTVYLCRRKDDNKlVIIKQIPVEQMTKEerqAALNEVKVLSMLHHPNIIEYYeSFLEDKALMIVMEYAPGGTLF 87
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370473802 358 DFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGEN-LVCKIADFGLARLI 421
Cdd:cd08220    88 EYIQQRKGSLLSEEEILHFFVQILLALHHVHSKQILHRDLKTQNILLNKKrTVVKIGDFGISKIL 152
STKc_PhKG cd14093
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs ...
310-426 4.16e-12

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: 66.61  E-value: 4.16e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 310 GTMMPEAFLQEAQIMKKL-RHDKLVPLYAVV-SEEPIYIVTEFMSKGSLLDFL------KEGDGKYLKLpqlvdmaaQIA 381
Cdd:cd14093    48 AEELREATRREIEILRQVsGHPNIIELHDVFeSPTFIFLVFELCRKGELFDYLtevvtlSEKKTRRIMR--------QLF 119
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1370473802 382 DGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEY 426
Cdd:cd14093   120 EAVEFLHSLNIVHRDLKPENILLDDNLNVKISDFGFATRLDEGEK 164
STKc_Byr2_like cd06628
Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein ...
283-424 4.70e-12

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: 66.40  E-value: 4.70e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMG--TWNG---------TTKVAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVP-LYAVVSEEPIYIVTEF 350
Cdd:cd06628     8 IGSGSFGSVYLGmnASSGelmavkqveLPSVSAENKDRKKSMLDALQREIALLRELQHENIVQyLGSSSDANHLNIFLEY 87
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370473802 351 MSKGSLLDFLKEgdgkYLKLPQ-LV-DMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDN 424
Cdd:cd06628    88 VPGGSVATLLNN----YGAFEEsLVrNFVRQILKGLNYLHNRGIIHRDIKGANILVDNKGGIKISDFGISKKLEAN 159
PTKc_Aatyk3 cd14206
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 3; PTKs ...
282-418 5.01e-12

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: 66.51  E-value: 5.01e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMG---TWNGTTKVAIKTLK--PGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEE-PIYIVTEFMSKGS 355
Cdd:cd14206     4 EIGNGWFGKVILGeifSDYTPAQVVVKELRvsAGPLEQRKFISEAQPYRSLQHPNILQCLGLCTETiPFLLIMEFCQLGD 83
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370473802 356 LLDFLK---EGDGKYLKLP-----QLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLA 418
Cdd:cd14206    84 LKRYLRaqrKADGMTPDLPtrdlrTLQRMAYEITLGLLHLHKNNYIHSDLALRNCLLTSDLTVRIGDYGLS 154
PLN00009 PLN00009
cyclin-dependent kinase A; Provisional
282-419 5.42e-12

cyclin-dependent kinase A; Provisional


Pssm-ID: 177649 [Multi-domain]  Cd Length: 294  Bit Score: 66.38  E-value: 5.42e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGTTK-VAIKTLK---PGTMMPEAFLQEAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFMSkgsl 356
Cdd:PLN00009    9 KIGEGTYGVVYKARDRVTNEtIALKKIRleqEDEGVPSTAIREISLLKEMQHGNIVRLQDVVhSEKRLYLVFEYLD---- 84
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370473802 357 LDFLKEGDG--KYLKLPQLVDMAA-QIADGMAYIERMNYIHRDLRAANILVGE-NLVCKIADFGLAR 419
Cdd:PLN00009   85 LDLKKHMDSspDFAKNPRLIKTYLyQILRGIAYCHSHRVLHRDLKPQNLLIDRrTNALKLADFGLAR 151
STKc_IRE1 cd13982
Catalytic domain of the Serine/Threonine kinase, Inositol-requiring protein 1; STKs catalyze ...
282-427 5.72e-12

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: 66.14  E-value: 5.72e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGE-VWMGTWNGTtKVAIKTlkpgtMMPEAFLQEAQIMKKLR----HDKLVPLYAV-VSEEPIYIVTEFmSKGS 355
Cdd:cd13982     8 VLGYGSEGTiVFRGTFDGR-PVAVKR-----LLPEFFDFADREVQLLResdeHPNVIRYFCTeKDRQFLYIALEL-CAAS 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 356 LLDFLKEGDGKYLKL---PQLVDMAAQIADGMAYIERMNYIHRDLRAANILV-----GENLVCKIADFGLARLIEDNEYT 427
Cdd:cd13982    81 LQDLVESPRESKLFLrpgLEPVRLLRQIASGLAHLHSLNIVHRDLKPQNILIstpnaHGNVRAMISDFGLCKKLDVGRSS 160
STKc_ULK1 cd14202
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the ...
270-428 5.95e-12

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: 66.19  E-value: 5.95e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 270 WEIPRESLrlevkLGQGCFGEVWMG--TWNGTTKVAIKTLKPGTMMPEAFL--QEAQIMKKLRHDKLVPLYAVVS-EEPI 344
Cdd:cd14202     2 FEFSRKDL-----IGHGAFAVVFKGrhKEKHDLEVAVKCINKKNLAKSQTLlgKEIKILKELKHENIVALYDFQEiANSV 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 345 YIVTEFMSKGSLLDFLKEGdgKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVG---------ENLVCKIADF 415
Cdd:cd14202    77 YLVMEYCNGGDLADYLHTM--RTLSEDTIRLFLQQIAGAMKMLHSKGIIHRDLKPQNILLSysggrksnpNNIRIKIADF 154
                         170
                  ....*....|...
gi 1370473802 416 GLARLIEDNEYTA 428
Cdd:cd14202   155 GFARYLQNNMMAA 167
SH2_Tec_Txk cd10398
Src homology 2 (SH2) domain found in Tec protein, Txk; A member of the Tec protein tyrosine ...
157-251 5.96e-12

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: 62.27  E-value: 5.96e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 157 EWYFGKMGRKDAERLLLNPGNQrGIFLVRESeTTKGAYSLSI--RDWDEIRGDnVKHYKIRKLDNGGYYITTRAQFDTLQ 234
Cdd:cd10398     7 EWYHKNITRNQAERLLRQESKE-GAFIVRDS-RHLGSYTISVftRARRSTEAS-IKHYQIKKNDSGQWYVAERHLFQSIP 83
                          90
                  ....*....|....*..
gi 1370473802 235 KLVKHYTEHADGLCHKL 251
Cdd:cd10398    84 ELIQYHQHNAAGLMSRL 100
STKc_CDK10 cd07845
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs ...
282-423 6.17e-12

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: 66.62  E-value: 6.17e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTwNGTTK--VAIKTLKpgtM------MPEAFLQEAQIMKKLRHDKLVPLYAVV---SEEPIYIVTEF 350
Cdd:cd07845    14 RIGEGTYGIVYRAR-DTTSGeiVALKKVR---MdnerdgIPISSLREITLLLNLRHPNIVELKEVVvgkHLDSIFLVMEY 89
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370473802 351 MSK--GSLLDFLKEGdgkyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIED 423
Cdd:cd07845    90 CEQdlASLLDNMPTP----FSESQVKCLMLQLLRGLQYLHENFIIHRDLKVSNLLLTDKGCLKIADFGLARTYGL 160
STKc_MEKK2 cd06652
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular ...
278-422 6.45e-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: 65.84  E-value: 6.45e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 278 RLEVKLGQGCFGEVWMgTWNGTT--KVAIKTLKPGTMMPE------AFLQEAQIMKKLRHDKLVPLYAVV---SEEPIYI 346
Cdd:cd06652     5 RLGKLLGQGAFGRVYL-CYDADTgrELAVKQVQFDPESPEtskevnALECEIQLLKNLLHERIVQYYGCLrdpQERTLSI 83
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1370473802 347 VTEFMSKGSLLDFLKEgdgkYLKLPQLV--DMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIE 422
Cdd:cd06652    84 FMEYMPGGSIKDQLKS----YGALTENVtrKYTRQILEGVHYLHSNMIVHRDIKGANILRDSVGNVKLGDFGASKRLQ 157
STKc_p38delta cd07879
Catalytic domain of the Serine/Threonine Kinase, p38delta Mitogen-Activated Protein Kinase ...
263-448 6.50e-12

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: 66.85  E-value: 6.50e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 263 QGLAKDAWEIPRESLRLEvKLGQGCFGEVWMGTWNGT-TKVAIKTL-KPgtMMPEAF----LQEAQIMKKLRHDKLVPLY 336
Cdd:cd07879     4 EEVNKTVWELPERYTSLK-QVGSGAYGSVCSAIDKRTgEKVAIKKLsRP--FQSEIFakraYRELTLLKHMQHENVIGLL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 337 AVVSEEPI-------YIVTEFMSKGslldfLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLV 409
Cdd:cd07879    81 DVFTSAVSgdefqdfYLVMPYMQTD-----LQKIMGHPLSEDKVQYLVYQMLCGLKYIHSAGIIHRDLKPGNLAVNEDCE 155
                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 1370473802 410 CKIADFGLARLiEDNEYTarqGMVnrevleqVERGYRMP 448
Cdd:cd07879   156 LKILDFGLARH-ADAEMT---GYV-------VTRWYRAP 183
STKc_myosinIII_N_like cd06608
N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze ...
268-419 7.02e-12

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: 65.79  E-value: 7.02e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 268 DAWEIpreslrLEVkLGQGCFGEVWMGTWNGTTK-VAIKTLKPGTMMPEAFLQEAQIMKKL-RHDKLVPLYAV------- 338
Cdd:cd06608     6 GIFEL------VEV-IGEGTYGKVYKARHKKTGQlAAIKIMDIIEDEEEEIKLEINILRKFsNHPNIATFYGAfikkdpp 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 339 VSEEPIYIVTEFMSKGSLLDFLKE--GDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFG 416
Cdd:cd06608    79 GGDDQLWLVMEYCGGGSVTDLVKGlrKKGKRLKEEWIAYILRETLRGLAYLHENKVIHRDIKGQNILLTEEAEVKLVDFG 158

                  ...
gi 1370473802 417 LAR 419
Cdd:cd06608   159 VSA 161
STKc_Pat1_like cd13993
Catalytic domain of Fungal Pat1-like Serine/Threonine kinases; STKs catalyze the transfer of ...
276-418 7.19e-12

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: 65.83  E-value: 7.19e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 276 SLRLEVKLGQGCFGEVWMGTWNGT-TKVAIKTL-KPGTMMPEA-------FLQEAQIMKKL-RHDKLVPLYAVV-SEEPI 344
Cdd:cd13993     1 RYQLISPIGEGAYGVVYLAVDLRTgRKYAIKCLyKSGPNSKDGndfqklpQLREIDLHRRVsRHPNIITLHDVFeTEVAI 80
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370473802 345 YIVTEFMSKGSLLDFLKEgDGKYLKLPQLV-DMAAQIADGMAYIERMNYIHRDLRAANILVGEN-LVCKIADFGLA 418
Cdd:cd13993    81 YIVLEYCPNGDLFEAITE-NRIYVGKTELIkNVFLQLIDAVKHCHSLGIYHRDIKPENILLSQDeGTVKLCDFGLA 155
PKc_like cd13968
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ...
283-416 7.57e-12

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: 62.84  E-value: 7.57e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEV-WMGTWNGTTKVAIKTLK-PGTMMPEAFLQEAQIMKKLR-HDKLVPLYAVVSE--EPIYIVTEFMSKGSLL 357
Cdd:cd13968     1 MGEGASAKVfWAEGECTTIGVAVKIGDdVNNEEGEDLESEMDILRRLKgLELNIPKVLVTEDvdGPNILLMELVKGGTLI 80
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1370473802 358 DFLKEGdgkYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFG 416
Cdd:cd13968    81 AYTQEE---ELDEKDVESIMYQLAECMRLLHSFHLIHRDLNNDNILLSEDGNVKLIDFG 136
STKc_CDK4_6_like cd07838
Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; ...
283-424 8.28e-12

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: 65.76  E-value: 8.28e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTK-VAIKTLK-PGTM--MPEAFLQEAQIMKKLR---HDKLVPLYAVV------SEEPIYIVTE 349
Cdd:cd07838     7 IGEGAYGTVYKARDLQDGRfVALKKVRvPLSEegIPLSTIREIALLKQLEsfeHPNVVRLLDVChgprtdRELKLTLVFE 86
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370473802 350 FMSKgSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDN 424
Cdd:cd07838    87 HVDQ-DLATYLDKCPKPGLPPETIKDLMRQLLRGLDFLHSHRIVHRDLKPQNILVTSDGQVKLADFGLARIYSFE 160
SH3_BTK cd11906
Src Homology 3 domain of Bruton's tyrosine kinase; BTK is a cytoplasmic (or nonreceptor) tyr ...
97-147 8.45e-12

Src Homology 3 domain of Bruton's tyrosine kinase; BTK is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and 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 (BCR), 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. 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: 212839 [Multi-domain]  Cd Length: 55  Bit Score: 60.22  E-value: 8.45e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1370473802  97 VALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARSiATGKNGYIPSNYV 147
Cdd:cd11906     4 VALYDYTPMNAQDLQLRKGEEYVILEESNLPWWRARD-KNGREGYIPSNYV 53
SH3_Tec cd11905
Src Homology 3 domain of Tec (Tyrosine kinase expressed in hepatocellular carcinoma); Tec is a ...
95-147 8.81e-12

Src Homology 3 domain of Tec (Tyrosine kinase expressed in hepatocellular carcinoma); Tec is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. It is more widely-expressed than other Tec subfamily kinases. Tec 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. Tec is a key component of T-cell receptor (TCR) signaling, and is important in TCR-stimulated proliferation, IL-2 production and phospholipase C-gamma1 activation. 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: 212838 [Multi-domain]  Cd Length: 56  Bit Score: 60.21  E-value: 8.81e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1370473802  95 IFVALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARSiATGKNGYIPSNYV 147
Cdd:cd11905     2 IVVAMYDFQPTEPHDLRLETGEEYVILEKNDVHWWKARD-KYGKEGYIPSNYV 53
SH2_C-SH2_PLC_gamma_like cd09932
C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
156-243 1.12e-11

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: 61.13  E-value: 1.12e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 156 EEWYFGKMGRKDAERLLlNPGNQRGIFLVRESETTKGAYSLSIRDWDEIrgdnvKHYKIRKldNGGYYITTRAQFDTLQK 235
Cdd:cd09932     4 KEWFHANLTREQAEEML-MRVPRDGAFLVRPSETDPNSFAISFRAEGKI-----KHCRIKQ--EGRLFVIGTSQFESLVE 75

                  ....*...
gi 1370473802 236 LVKHYTEH 243
Cdd:cd09932    76 LVSYYEKH 83
STKc_MAPK15-like cd07852
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15 and ...
278-448 1.17e-11

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: 66.04  E-value: 1.17e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 278 RLEV--KLGQGCFGEVWMGTwNGTTK--VAIKTLKpgtmmpEAF--LQEAQ-----IM--KKLR-HDKLVPLYAVVSEE- 342
Cdd:cd07852     8 RYEIlkKLGKGAYGIVWKAI-DKKTGevVALKKIF------DAFrnATDAQrtfreIMflQELNdHPNIIKLLNVIRAEn 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 343 --PIYIVTEFMS--------KGSLLDFLKegdgKYLklpqlvdmAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKI 412
Cdd:cd07852    81 dkDIYLVFEYMEtdlhavirANILEDIHK----QYI--------MYQLLKALKYLHSGGVIHRDLKPSNILLNSDCRVKL 148
                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 1370473802 413 ADFGLARLIedneyTARQGMVNREVL-EQVE-RGYRMP 448
Cdd:cd07852   149 ADFGLARSL-----SQLEEDDENPVLtDYVAtRWYRAP 181
STKc_STK10 cd06644
Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase ...
268-418 1.36e-11

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: 65.44  E-value: 1.36e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 268 DAWEIPREslrlevkLGQGCFGEVWMGTWNGTTKVA----IKTLKPGTMmpEAFLQEAQIMKKLRHDKLVPLY-AVVSEE 342
Cdd:cd06644    12 EVWEIIGE-------LGDGAFGKVYKAKNKETGALAaakvIETKSEEEL--EDYMVEIEILATCNHPYIVKLLgAFYWDG 82
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370473802 343 PIYIVTEFMSKGSLLDFLKEGDgKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLA 418
Cdd:cd06644    83 KLWIMIEFCPGGAVDAIMLELD-RGLTEPQIQVICRQMLEALQYLHSMKIIHRDLKAGNVLLTLDGDIKLADFGVS 157
SH3_Eve1_4 cd11817
Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
97-146 1.38e-11

Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. 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: 212751 [Multi-domain]  Cd Length: 50  Bit Score: 59.41  E-value: 1.38e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1370473802  97 VALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARsiATGKNGYIPSNY 146
Cdd:cd11817     3 VALYDFTGETEEDLSFQRGDRILVTEHLDAEWSRGR--LNGREGIFPRAF 50
STKc_PLK4 cd14186
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the ...
275-418 1.42e-11

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: 64.50  E-value: 1.42e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 275 ESLRLEVKLGQGCFGEVWMG-TWNGTTKVAIKTLKPGTM----MPEAFLQEAQIMKKLRHDKLVPLYAVVSEEP-IYIVT 348
Cdd:cd14186     1 EDFKVLNLLGKGSFACVYRArSLHTGLEVAIKMIDKKAMqkagMVQRVRNEVEIHCQLKHPSILELYNYFEDSNyVYLVL 80
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370473802 349 EFMSKGSLLDFLKEgdgkyLKLPQLVDMAA----QIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLA 418
Cdd:cd14186    81 EMCHNGEMSRYLKN-----RKKPFTEDEARhfmhQIVTGMLYLHSHGILHRDLTLSNLLLTRNMNIKIADFGLA 149
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, ...
158-243 1.59e-11

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: 60.52  E-value: 1.59e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 158 WYFGKMGRKDAERLLlnPGNQRGIFLVRESETTKGAYSLSIRDwdeirGDNVKHYKIRKLDNGGYYI-TTRAQFDTLQKL 236
Cdd:cd09945     3 WYHGAITRIEAESLL--RPCKEGSYLVRNSESTKQDYSLSLKS-----AKGFMHMRIQRNETGQYILgQFSRPFETIPEM 75

                  ....*..
gi 1370473802 237 VKHYTEH 243
Cdd:cd09945    76 IRHYCLN 82
PKc_TESK cd14155
Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; ...
283-458 1.90e-11

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: 64.42  E-value: 1.90e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKVAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAV-VSEEPIYIVTEFMSKGSLLDFLK 361
Cdd:cd14155     1 IGSGFFSEVYKVRHRTSGQVMALKMNTLSSNRANMLREVQLMNRLSHPNILRFMGVcVHQGQLHALTEYINGGNLEQLLD 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 362 egDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILV---GENLVCKIADFGLARLIEDNEYtarqgmvNREVL 438
Cdd:cd14155    81 --SNEPLSWTVRVKLALDIARGLSYLHSKGIFHRDLTSKNCLIkrdENGYTAVVGDFGLAEKIPDYSD-------GKEKL 151
                         170       180
                  ....*....|....*....|
gi 1370473802 439 EQVERGYRMpcpqgCPESLH 458
Cdd:cd14155   152 AVVGSPYWM-----APEVLR 166
STKc_HAL4_like cd13994
Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs ...
283-418 1.93e-11

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: 64.25  E-value: 1.93e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGT-WNGTTKV--AIKTL--KPGTMMPEAF----LQEAQIMKKLRHDKLVP-LYAVVSEEP-IYIVTEFM 351
Cdd:cd13994     1 IGKGATSVVRIVTkKNPRSGVlyAVKEYrrRDDESKRKDYvkrlTSEYIISSKLHHPNIVKvLDLCQDLHGkWCLVMEYC 80
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 352 SKGSLLDFLKEGDGkylklPQLVDMAA---QIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLA 418
Cdd:cd13994    81 PGGDLFTLIEKADS-----LSLEEKDCffkQILRGVAYLHSHGIAHRDLKPENILLDEDGVLKLTDFGTA 145
STKc_CDK8_like cd07842
Catalytic domain of Cyclin-Dependent protein Kinase 8-like Serine/Threonine Kinases; STKs ...
282-421 1.98e-11

Catalytic domain of Cyclin-Dependent protein Kinase 8-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 CDK8, CDC2L6, and similar proteins. CDK8 functions as a negative or positive regulator of transcription, depending on the scenario. Together with its regulator, cyclin C, it reversibly associates with the multi-subunit core Mediator complex, a cofactor that is involved in regulating RNA polymerase II-dependent transcription. CDC2L6 also associates with Mediator in complexes lacking CDK8. In VP16-dependent transcriptional activation, CDK8 and CDC2L6 exerts opposing effects by positive and negative regulation, respectively, in similar conditions. 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 CDK8-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: 270834 [Multi-domain]  Cd Length: 316  Bit Score: 65.00  E-value: 1.98e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEV---WMGTWNGTTKVAIKTLKP----GTMMPEAFLQEAQIMKKLRHDKLVPLYAVV---SEEPIYIVTEFM 351
Cdd:cd07842     7 CIGRGTYGRVykaKRKNGKDGKEYAIKKFKGdkeqYTGISQSACREIALLRELKHENVVSLVEVFlehADKSVYLLFDYA 86
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370473802 352 SK--GSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILV-GENLVC---KIADFGLARLI 421
Cdd:cd07842    87 EHdlWQIIKFHRQAKRVSIPPSMVKSLLWQILNGIHYLHSNWVLHRDLKPANILVmGEGPERgvvKIGDLGLARLF 162
SH2_DAPP1_BAM32_like cd10355
Src homology 2 domain found in dual adaptor for phosphotyrosine and 3-phosphoinositides ( ...
151-240 2.29e-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: 60.18  E-value: 2.29e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 151 DSIQAEEWYFGKMGRKDAERLLLNPGnQRGIFLVRESETTKGAYSLSIRDwdeirGDNVKHYKIRKldNGGYYITTRAQF 230
Cdd:cd10355     1 ELLQSLGWYHGNLTRHAAEALLLSNG-VDGSYLLRNSNEGTGLFSLSVRA-----KDSVKHFHVEY--TGYSFKFGFNEF 72
                          90
                  ....*....|
gi 1370473802 231 DTLQKLVKHY 240
Cdd:cd10355    73 SSLQDFVKHF 82
SH2_Nck1 cd10408
Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin ...
157-240 2.40e-11

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: 60.04  E-value: 2.40e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 157 EWYFGKMGRKDAERLLLNPGNQrGIFLVRESETTKGAYSLSIRdwdeIRGDNvKHYKIRKLDNggYYITTRAQFDTLQKL 236
Cdd:cd10408     2 PWYYGKVTRHQAEMALNERGNE-GDFLIRDSESSPNDFSVSLK----AQGKN-KHFKVQLKEC--VYCIGQRKFSSMEEL 73

                  ....
gi 1370473802 237 VKHY 240
Cdd:cd10408    74 VEHY 77
STKc_PFTAIRE2 cd07870
Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-2 kinase; STKs catalyze the transfer ...
277-419 2.49e-11

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: 64.21  E-value: 2.49e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 277 LRLEvKLGQGCFGEVWMGT--WNGTTkVAIK--TLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFM 351
Cdd:cd07870     3 LNLE-KLGEGSYATVYKGIsrINGQL-VALKviSMKTEEGVPFTAIREASLLKGLKHANIVLLHDIIhTKETLTFVFEYM 80
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1370473802 352 SKgSLLDFLKEGDGKyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR 419
Cdd:cd07870    81 HT-DLAQYMIQHPGG-LHPYNVRLFMFQLLRGLAYIHGQHILHRDLKPQNLLISYLGELKLADFGLAR 146
STKc_PCTAIRE2 cd07872
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-2 kinase; STKs catalyze the transfer ...
277-419 2.61e-11

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: 64.63  E-value: 2.61e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 277 LRLEvKLGQGCFGEVWMGTWNGTTK-VAIKT--LKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFMS 352
Cdd:cd07872     9 IKLE-KLGEGTYATVFKGRSKLTENlVALKEirLEHEEGAPCTAIREVSLLKDLKHANIVTLHDIVhTDKSLTLVFEYLD 87
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370473802 353 KgSLLDFLKEGdGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR 419
Cdd:cd07872    88 K-DLKQYMDDC-GNIMSMHNVKIFLYQILRGLAYCHRRKVLHRDLKPQNLLINERGELKLADFGLAR 152
STKc_PRP4 cd14135
Catalytic domain of the Serine/Threonine Kinase, Pre-mRNA-Processing factor 4; STKs catalyze ...
282-448 2.66e-11

Catalytic domain of the Serine/Threonine Kinase, Pre-mRNA-Processing factor 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PRP4 phosphorylates a number of factors involved in the formation of active spliceosomes, which catalyze pre-mRNA splicing. It phosphorylates PRP6 and PRP31, components of the U4/U6-U5 tri-small nuclear ribonucleoprotein (snRNP), during spliceosomal complex formation. In fission yeast, PRP4 phosphorylates the splicing factor PRP1 (U5-102 kD in mammals). Thus, PRP4 plays a key role in regulating spliceosome assembly and pre-mRNA splicing. It also plays an important role in mitosis by acting as a spindle assembly checkpoint kinase that is required for chromosome alignment and the recruitment of the checkpoint proteins MPS1, MAD1, and MAD2 at kinetochores. The PRP4 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: 271037 [Multi-domain]  Cd Length: 318  Bit Score: 64.55  E-value: 2.66e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMG--TWNGTTKVAIKTLKPGTMMPEAFLQEAQIMKKL----RHDK--LVPLYAVVS-EEPIYIVTEFMS 352
Cdd:cd14135     7 YLGKGVFSNVVRArdLARGNQEVAIKIIRNNELMHKAGLKELEILKKLndadPDDKkhCIRLLRHFEhKNHLCLVFESLS 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 353 kGSLLDFLKE-GDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGEN-LVCKIADFGLARLIEDNEYTarq 430
Cdd:cd14135    87 -MNLREVLKKyGKNVGLNIKAVRSYAQQLFLALKHLKKCNILHADIKPDNILVNEKkNTLKLCDFGSASDIGENEIT--- 162
                         170
                  ....*....|....*...
gi 1370473802 431 gmvnrEVLeqVERGYRMP 448
Cdd:cd14135   163 -----PYL--VSRFYRAP 173
PK_GC-C cd14044
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-C; The pseudokinase domain ...
319-487 2.70e-11

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: 64.14  E-value: 2.70e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 319 QEAQIMKKLRHD--KLVPLYAVVS-EEPIYIVTEFMSKGSLLDFLKEG----DGKYLKLPQLVDMAAQIADGMAYIERMN 391
Cdd:cd14044    50 QKIELNKLLQIDyyNLTKFYGTVKlDTMIFGVIEYCERGSLRDVLNDKisypDGTFMDWEFKISVMYDIAKGMSYLHSSK 129
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 392 Y-IHRDLRAANILVGENLVCKIADFGLARLI--EDNEYTA----RQ------------GMVNREVL------------EQ 440
Cdd:cd14044   130 TeVHGRLKSTNCVVDSRMVVKITDFGCNSILppSKDLWTApehlRQagtsqkgdvysyGIIAQEIIlrketfytaacsDR 209
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370473802 441 VERGYRMPCPQGCP--------ESLHE-------LMNLCWKKDPDERPTFEYIQSFLEDYFT 487
Cdd:cd14044   210 KEKIYRVQNPKGMKpfrpdlnlESAGErerevygLVKNCWEEDPEKRPDFKKIENTLAKIFS 271
STKc_CDK5 cd07839
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 5; STKs ...
281-419 3.06e-11

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: 63.99  E-value: 3.06e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 281 VKLGQGCFGEVWMGTWNGTTK-VAIKTLK---PGTMMPEAFLQEAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFMSKgS 355
Cdd:cd07839     6 EKIGEGTYGTVFKAKNRETHEiVALKRVRlddDDEGVPSSALREICLLKELKHKNIVRLYDVLhSDKKLTLVFEYCDQ-D 84
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370473802 356 LLDFLKEGDGkYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR 419
Cdd:cd07839    85 LKKYFDSCNG-DIDPEIVKSFMFQLLKGLAFCHSHNVLHRDLKPQNLLINKNGELKLADFGLAR 147
STKc_ERK5 cd07855
Catalytic domain of the Serine/Threonine Kinase, Extracellular signal-Regulated Kinase 5; ...
282-421 3.35e-11

Catalytic domain of the Serine/Threonine Kinase, Extracellular signal-Regulated Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ERK5 (also called Big MAPK1 (BMK1) or MAPK7) has a unique C-terminal extension, making it approximately twice as big as other MAPKs. This extension contains transcriptional activation capability which is inhibited by the N-terminal half. ERK5 is activated in response to growth factors and stress by a cascade that leads to its phosphorylation by the MAP2K MEK5, which in turn is regulated by the MAP3Ks MEKK2 and MEKK3. Activated ERK5 phosphorylates its targets including myocyte enhancer factor 2 (MEF2), Sap1a, c-Myc, and RSK. It plays a role in EGF-induced cell proliferation during the G1/S phase transition. Studies on knockout mice revealed that ERK5 is essential for cardiovascular development and plays an important role in angiogenesis. It is also critical for neural differentiation and survival. The ERK5 pathway has been implicated in the pathogenesis of many diseases including cancer, cardiac hypertrophy, and atherosclerosis. MAPKs are important mediators of cellular responses to extracellular signals. The ERK5 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: 270842 [Multi-domain]  Cd Length: 336  Bit Score: 64.69  E-value: 3.35e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGT-TKVAIKTLkpgtmmPEAF---------LQEAQIMKKLRHDKLVPlyavvseepiyIVTEFM 351
Cdd:cd07855    12 TIGSGAYGVVCSAIDTKSgQKVAIKKI------PNAFdvvttakrtLRELKILRHFKHDNIIA-----------IRDILR 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 352 SKGSLLDF--------LKEGD-------GKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFG 416
Cdd:cd07855    75 PKVPYADFkdvyvvldLMESDlhhiihsDQPLTLEHIRYFLYQLLRGLKYIHSANVIHRDLKPSNLLVNENCELKIGDFG 154

                  ....*
gi 1370473802 417 LARLI 421
Cdd:cd07855   155 MARGL 159
STKc_CaMKK2 cd14199
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2; ...
305-425 3.49e-11

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: 63.83  E-value: 3.49e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 305 KTLKPGTMMP----EAFLQEAQIMKKLRHDKLVPLYAVV---SEEPIYIVTEFMSKGSLLDFLKEgdgKYLKLPQLVDMA 377
Cdd:cd14199    56 RAAPEGCTQPrgpiERVYQEIAILKKLDHPNVVKLVEVLddpSEDHLYMVFELVKQGPVMEVPTL---KPLSEDQARFYF 132
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1370473802 378 AQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNE 425
Cdd:cd14199   133 QDLIKGIEYLHYQKIIHRDVKPSNLLVGEDGHIKIADFGVSNEFEGSD 180
PLN00034 PLN00034
mitogen-activated protein kinase kinase; Provisional
282-421 3.74e-11

mitogen-activated protein kinase kinase; Provisional


Pssm-ID: 215036 [Multi-domain]  Cd Length: 353  Bit Score: 64.46  E-value: 3.74e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGTTKV-AIKTLKpGTMMPEAFLQ---EAQIMKKLRHDKLVPLYAVVSEE-PIYIVTEFMSKGSL 356
Cdd:PLN00034   81 RIGSGAGGTVYKVIHRPTGRLyALKVIY-GNHEDTVRRQicrEIEILRDVNHPNVVKCHDMFDHNgEIQVLLEFMDGGSL 159
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370473802 357 ldflkegDGKYL-KLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLI 421
Cdd:PLN00034  160 -------EGTHIaDEQFLADVARQILSGIAYLHRRHIVHRDIKPSNLLINSAKNVKIADFGVSRIL 218
PK_GC-2D cd14043
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain ...
291-478 4.41e-11

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: 63.19  E-value: 4.41e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 291 VWMGTWNGTTKVAIKtlkPGTMmpEAFLQeaqiMKKLRHDKLVPLYAVVSEEPIY-IVTEFMSKGSLLDFLKEGDGKY-- 367
Cdd:cd14043    26 VWLKKFPGGSHTELR---PSTK--NVFSK----LRELRHENVNLFLGLFVDCGILaIVSEHCSRGSLEDLLRNDDMKLdw 96
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 368 -LKLPQLVDMAAqiadGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLI------------EDNEYTA----RQ 430
Cdd:cd14043    97 mFKSSLLLDLIK----GMRYLHHRGIVHGRLKSRNCVVDGRFVLKITDYGYNEILeaqnlplpepapEELLWTApellRD 172
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 431 GMVNR----------------EVL-------------EQVERGYRMPCP---------QGCPESLHeLMNLCWKKDPDER 472
Cdd:cd14043   173 PRLERrgtfpgdvfsfaiimqEVIvrgapycmlglspEEIIEKVRSPPPlcrpsvsmdQAPLECIQ-LMKQCWSEAPERR 251

                  ....*.
gi 1370473802 473 PTFEYI 478
Cdd:cd14043   252 PTFDQI 257
STKc_TLK cd13990
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase; STKs catalyze the ...
283-432 4.68e-11

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: 63.49  E-value: 4.68e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVW----MGTWNgttKVAIKTLKPGTMMPEA--------FLQEAQIMKKLRHDKLVPLYAVVSEEPIYIVT-- 348
Cdd:cd13990     8 LGKGGFSEVYkafdLVEQR---YVACKIHQLNKDWSEEkkqnyikhALREYEIHKSLDHPRIVKLYDVFEIDTDSFCTvl 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 349 EFmSKGSLLDF-LKEGDGKYLKLPQLVDMaaQIADGMAYIE--RMNYIHRDLRAANILVGENLVC---KIADFGLARLIE 422
Cdd:cd13990    85 EY-CDGNDLDFyLKQHKSIPEREARSIIM--QVVSALKYLNeiKPPIIHYDLKPGNILLHSGNVSgeiKITDFGLSKIMD 161
                         170
                  ....*....|
gi 1370473802 423 DNEYTArQGM 432
Cdd:cd13990   162 DESYNS-DGM 170
STKc_TAO cd06607
Catalytic domain of the Serine/Threonine Kinases, Thousand-and-One Amino acids proteins; STKs ...
283-421 4.78e-11

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: 63.24  E-value: 4.78e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTK-VAIKTL----KPGTMMPEAFLQEAQIMKKLRHDKLVPLYAV-VSEEPIYIVTEFM--SKG 354
Cdd:cd06607     9 IGHGSFGAVYYARNKRTSEvVAIKKMsysgKQSTEKWQDIIKEVKFLRQLRHPNTIEYKGCyLREHTAWLVMEYClgSAS 88
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 355 SLLDFLKegdgkylKLPQLVDMAA---QIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLI 421
Cdd:cd06607    89 DIVEVHK-------KPLQEVEIAAichGALQGLAYLHSHNRIHRDVKAGNILLTEPGTVKLADFGSASLV 151
SH3_CRK_N cd11758
N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor ...
98-147 5.26e-11

N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor proteins consists of SH2 and SH3 domains, which bind tyrosine-phosphorylated peptides and proline-rich motifs, respectively. They function downstream of protein tyrosine kinases in many signaling pathways started by various extracellular signals, including growth and differentiation factors. Cellular CRK (c-CRK) contains a single SH2 domain, followed by N-terminal and C-terminal SH3 domains. It is involved in the regulation of many cellular processes including cell growth, motility, adhesion, and apoptosis. CRK has been implicated in the malignancy of various human cancers. The N-terminal SH3 domain of CRK binds a number of target proteins including DOCK180, C3G, SOS, and cABL. The CRK family includes two alternatively spliced protein forms, CRKI and CRKII, that are expressed by the CRK gene, and the CRK-like (CRKL) protein, which is expressed by a distinct gene (CRKL). 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: 212692 [Multi-domain]  Cd Length: 55  Bit Score: 57.76  E-value: 5.26e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1370473802  98 ALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARSiATGKNGYIPSNYV 147
Cdd:cd11758     5 ALFDFPGNDDEDLPFKKGEILTVIRKPEEQWWNARN-SEGKTGMIPVPYV 53
STKc_CaMKI_gamma cd14166
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
274-440 5.52e-11

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: 63.47  E-value: 5.52e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 274 RESLRLEVKLGQGCFGEVWMGTWNGTTKV-AIKTLKPGTMMPEAFLQ-EAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEF 350
Cdd:cd14166     2 RETFIFMEVLGSGAFSEVYLVKQRSTGKLyALKCIKKSPLSRDSSLEnEIAVLKRIKHENIVTLEDIYeSTTHYYLVMQL 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 351 MSKGSLLDFLKEgDGKYLKlPQLVDMAAQIADGMAYIERMNYIHRDLRAANILV---GENLVCKIADFGLARLiEDNEYT 427
Cdd:cd14166    82 VSGGELFDRILE-RGVYTE-KDASRVINQVLSAVKYLHENGIVHRDLKPENLLYltpDENSKIMITDFGLSKM-EQNGIM 158
                         170
                  ....*....|....*..
gi 1370473802 428 ARQ----GMVNREVLEQ 440
Cdd:cd14166   159 STAcgtpGYVAPEVLAQ 175
SH2_C-SH2_Zap70_Syk_like cd10345
C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
158-256 5.71e-11

C-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 C-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: 198208  Cd Length: 95  Bit Score: 58.93  E-value: 5.71e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 158 WYFGKMGRKDAERLLLNPGNQRGIFLVRESETtKGAYSLSIrdwdeIRGDNVKHYKIRKLDNGGYYITTRAQFDTLQKLV 237
Cdd:cd10345     2 WFHGKISREESEQIVLIGSKTNGKFLIRARDN-NGSYALCL-----LHEGKVLHYRIDKDKTGKLSIPEGKKFDTLWQLV 75
                          90
                  ....*....|....*....
gi 1370473802 238 KHYTEHADGLCHKLTTVCP 256
Cdd:cd10345    76 EHYSYKADGLLRVLTVPCQ 94
STKc_WNK3 cd14031
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3; STKs catalyze ...
277-421 6.37e-11

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: 63.20  E-value: 6.37e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 277 LRLEVKLGQGCFGEVWMG----TWNGTTKVAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLY-----AVVSEEPIYIV 347
Cdd:cd14031    12 LKFDIELGRGAFKTVYKGldteTWVEVAWCELQDRKLTKAEQQRFKEEAEMLKGLQHPNIVRFYdswesVLKGKKCIVLV 91
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370473802 348 TEFMSKGSLLDFLKEgdGKYLKLPQLVDMAAQIADGMAYIERMN--YIHRDLRAANILV-GENLVCKIADFGLARLI 421
Cdd:cd14031    92 TELMTSGTLKTYLKR--FKVMKPKVLRSWCRQILKGLQFLHTRTppIIHRDLKCDNIFItGPTGSVKIGDLGLATLM 166
STKc_CaMKI_beta cd14169
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
279-440 6.52e-11

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: 62.99  E-value: 6.52e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 279 LEVKLGQGCFGEVWMGTWNGTTK-VAIKTL-KPGTMMPEAFLQ-EAQIMKKLRHDKLVPLYAVVsEEP--IYIVTEFMSK 353
Cdd:cd14169     7 LKEKLGEGAFSEVVLAQERGSQRlVALKCIpKKALRGKEAMVEnEIAVLRRINHENIVSLEDIY-ESPthLYLAMELVTG 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 354 GSLLDFLKEgDGKYLK--LPQLVdmaAQIADGMAYIERMNYIHRDLRAANILVG---ENLVCKIADFGLARLIEDNEYT- 427
Cdd:cd14169    86 GELFDRIIE-RGSYTEkdASQLI---GQVLQAVKYLHQLGIVHRDLKPENLLYAtpfEDSKIMISDFGLSKIEAQGMLSt 161
                         170
                  ....*....|....*
gi 1370473802 428 --ARQGMVNREVLEQ 440
Cdd:cd14169   162 acGTPGYVAPELLEQ 176
STKc_ASK cd06624
Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase; STKs ...
281-448 7.01e-11

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: 62.81  E-value: 7.01e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 281 VKLGQGCFGEVWMG-TWNGTTKVAIKTLkpgtmmPEAFLQEAQ-------IMKKLRHDKLVPLYAVVSEEPIY-IVTEFM 351
Cdd:cd06624    14 VVLGKGTFGVVYAArDLSTQVRIAIKEI------PERDSREVQplheeiaLHSRLSHKNIVQYLGSVSEDGFFkIFMEQV 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 352 SKGSLLDFLKEGDGkylklPQLVDMAA------QIADGMAYIERMNYIHRDLRAANILVGE-NLVCKIADFGLA-RLIED 423
Cdd:cd06624    88 PGGSLSALLRSKWG-----PLKDNENTigyytkQILEGLKYLHDNKIVHRDIKGDNVLVNTySGVVKISDFGTSkRLAGI 162
                         170       180       190
                  ....*....|....*....|....*....|
gi 1370473802 424 NEYTAR-----QGMVNrEVLEQVERGYRMP 448
Cdd:cd06624   163 NPCTETftgtlQYMAP-EVIDKGQRGYGPP 191
STKc_CaMKK1 cd14200
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 1; ...
308-425 7.28e-11

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: 63.04  E-value: 7.28e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 308 KPGTMMP-EAFLQEAQIMKKLRHDKLVPLYAVV---SEEPIYIVTEFMSKGSLLD------FLKEGDGKYLKlpqlvdma 377
Cdd:cd14200    60 QAKPLAPlERVYQEIAILKKLDHVNIVKLIEVLddpAEDNLYMVFDLLRKGPVMEvpsdkpFSEDQARLYFR-------- 131
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1370473802 378 aQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNE 425
Cdd:cd14200   132 -DIVLGIEYLHYQKIVHRDIKPSNLLLGDDGHVKIADFGVSNQFEGND 178
SH2_CRK_like cd09926
Src homology 2 domain found in cancer-related signaling adaptor protein CRK; SH2 domain in the ...
151-243 7.90e-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: 59.02  E-value: 7.90e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 151 DSIQAEEWYFGKMGRKDAERLLLnpGNQRGIFLVRESETTKGAYSLSIRDwdeirGDNVKHYKIRKLDNGGY----YITT 226
Cdd:cd09926     2 DSSDRSSWYFGPMSRQEAQELLQ--GQRHGVFLVRDSSTIPGDYVLSVSE-----NSRVSHYIINSLGQPAPnqsrYRIG 74
                          90
                  ....*....|....*..
gi 1370473802 227 RAQFDTLQKLVKHYTEH 243
Cdd:cd09926    75 DQEFDDLPALLEFYKLH 91
STKc_PCTAIRE3 cd07871
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-3 kinase; STKs catalyze the transfer ...
282-419 8.17e-11

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: 62.72  E-value: 8.17e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGTTK-VAIKT--LKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFMSKgSLL 357
Cdd:cd07871    12 KLGEGTYATVFKGRSKLTENlVALKEirLEHEEGAPCTAIREVSLLKNLKHANIVTLHDIIhTERCLTLVFEYLDS-DLK 90
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370473802 358 DFLkEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR 419
Cdd:cd07871    91 QYL-DNCGNLMSMHNVKIFMFQLLRGLSYCHKRKILHRDLKPQNLLINEKGELKLADFGLAR 151
PTZ00426 PTZ00426
cAMP-dependent protein kinase catalytic subunit; Provisional
283-427 8.44e-11

cAMP-dependent protein kinase catalytic subunit; Provisional


Pssm-ID: 173616 [Multi-domain]  Cd Length: 340  Bit Score: 63.46  E-value: 8.44e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTT--KVAIKTLKPGTMMPEA----FLQEAQIMKKLRHDKLVPLYAVVSEEP-IYIVTEFMSKGS 355
Cdd:PTZ00426   38 LGTGSFGRVILATYKNEDfpPVAIKRFEKSKIIKQKqvdhVFSERKILNYINHPFCVNLYGSFKDESyLYLVLEFVIGGE 117
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370473802 356 LLDFLKEGDgkylKLPQLVD--MAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYT 427
Cdd:PTZ00426  118 FFTFLRRNK----RFPNDVGcfYAAQIVLIFEYLQSLNIVYRDLKPENLLLDKDGFIKMTDFGFAKVVDTRTYT 187
STKc_DAPK cd14105
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase; STKs ...
319-426 8.53e-11

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: 62.50  E-value: 8.53e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 319 QEAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFMSKGSLLDFLKEGDGkyLKLPQLVDMAAQIADGMAYIERMNYIHRDL 397
Cdd:cd14105    57 REVSILRQVLHPNIITLHDVFeNKTDVVLILELVAGGELFDFLAEKES--LSEEEATEFLKQILDGVNYLHTKNIAHFDL 134
                          90       100       110
                  ....*....|....*....|....*....|....
gi 1370473802 398 RAANILVGENLV----CKIADFGLARLIED-NEY 426
Cdd:cd14105   135 KPENIMLLDKNVpiprIKLIDFGLAHKIEDgNEF 168
PTZ00263 PTZ00263
protein kinase A catalytic subunit; Provisional
259-427 8.57e-11

protein kinase A catalytic subunit; Provisional


Pssm-ID: 140289 [Multi-domain]  Cd Length: 329  Bit Score: 63.30  E-value: 8.57e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 259 KPQTQGlakdaWEIprESLRLEVKLGQGCFGEVWMGTWNGTTK-VAIKTLKPGTMMP----EAFLQEAQIMKKLRHDKLV 333
Cdd:PTZ00263    9 KPDTSS-----WKL--SDFEMGETLGTGSFGRVRIAKHKGTGEyYAIKCLKKREILKmkqvQHVAQEKSILMELSHPFIV 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 334 PLY-AVVSEEPIYIVTEFMSKGSLLDFLKEGdGKYlklPQlvDMA----AQIADGMAYIERMNYIHRDLRAANILVGENL 408
Cdd:PTZ00263   82 NMMcSFQDENRVYFLLEFVVGGELFTHLRKA-GRF---PN--DVAkfyhAELVLAFEYLHSKDIIYRDLKPENLLLDNKG 155
                         170
                  ....*....|....*....
gi 1370473802 409 VCKIADFGLARLIEDNEYT 427
Cdd:PTZ00263  156 HVKVTDFGFAKKVPDRTFT 174
SH3_Nephrocystin cd11770
Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain ...
95-149 9.36e-11

Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain involved in signaling pathways that regulate cell adhesion and cytoskeletal organization. It is a protein that in humans is associated with juvenile nephronophthisis, an inherited kidney disease characterized by renal fibrosis that lead to chronic renal failure in children. It is localized in cell-cell junctions in renal duct cells, and is known to interact with Ack1, an activated Cdc42-associated kinase. 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: 212704 [Multi-domain]  Cd Length: 54  Bit Score: 56.94  E-value: 9.36e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1370473802  95 IFVALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARSiATGKNGYIPSNYVAP 149
Cdd:cd11770     1 LYEALSDFQAEQEGDLSFKKGEVLRIISKRADGWWLAEN-SKGNRGLVPKTYLKV 54
STKc_IKK_alpha cd14039
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
283-419 9.55e-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: 62.63  E-value: 9.55e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTT-KVAIKT--LKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEPIYI------VTEFMSK 353
Cdd:cd14039     1 LGTGGFGNVCLYQNQETGeKIAIKScrLELSVKNKDRWCHEIQIMKKLNHPNVVKACDVPEEMNFLVndvpllAMEYCSG 80
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 354 GSLLDFL-KEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANIL---VGENLVCKIADFGLAR 419
Cdd:cd14039    81 GDLRKLLnKPENCCGLKESQVLSLLSDIGSGIQYLHENKIIHRDLKPENIVlqeINGKIVHKIIDLGYAK 150
SH2_Nck2 cd10409
Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin ...
156-247 1.02e-10

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: 58.51  E-value: 1.02e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 156 EEWYFGKMGRKDAERLLlnpgNQRGI---FLVRESETTKGAYSLSIRdwdeIRGDNvKHYKIrKLDNGGYYITTRaQFDT 232
Cdd:cd10409     1 KEWYYGNVTRHQAECAL----NERGVegdFLIRDSESSPSDFSVSLK----AVGKN-KHFKV-QLVDNVYCIGQR-RFNS 69
                          90       100
                  ....*....|....*....|..
gi 1370473802 233 LQKLVKHY-------TEHADGL 247
Cdd:cd10409    70 MDELVEHYkkapiftSEHGEKL 91
STKc_MLCK1 cd14191
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze ...
279-423 1.04e-10

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: 62.33  E-value: 1.04e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 279 LEVKLGQGCFGEVWMGTWNGTTKV-AIKTLKP-GTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEP-IYIVTEFMSKGS 355
Cdd:cd14191     6 IEERLGSGKFGQVFRLVEKKTKKVwAGKFFKAySAKEKENIRQEISIMNCLHHPKLVQCVDAFEEKAnIVMVLEMVSGGE 85
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370473802 356 LLDFLKEGDGKyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANIL----VGENLvcKIADFGLARLIED 423
Cdd:cd14191    86 LFERIIDEDFE-LTERECIKYMRQISEGVEYIHKQGIVHLDLKPENIMcvnkTGTKI--KLIDFGLARRLEN 154
SH2_a2chimerin_b2chimerin cd10352
Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins ...
159-249 1.04e-10

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: 58.14  E-value: 1.04e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 159 YFGKMGRKDAERLLLNPGNqrGIFLVRESETTKGAYSLSIRdwdeiRGDNVKHYKIRKLDNGGYYITTRAQFDTLQKLVk 238
Cdd:cd10352     9 YHGLISREEAEQLLSGASD--GSYLIRESSRDDGYYTLSLR-----FNGKVKNYKLYYDGKNHYHYVGEKRFDTIHDLV- 80
                          90
                  ....*....|.
gi 1370473802 239 hytehADGLCH 249
Cdd:cd10352    81 -----ADGLIT 86
SH3_PIX cd11877
Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine ...
98-147 1.05e-10

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. 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: 212810 [Multi-domain]  Cd Length: 53  Bit Score: 56.94  E-value: 1.05e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1370473802  98 ALYDYEARTTEDLSFKKGERFQIINNTEGDWWEArsIATGKNGYIPSNYV 147
Cdd:cd11877     4 AKFNFEGTNEDELSFDKGDIITVTQVVEGGWWEG--TLNGKTGWFPSNYV 51
STKc_WNK4 cd14033
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze ...
277-420 1.09e-10

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: 61.94  E-value: 1.09e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 277 LRLEVKLGQGCFGEVWMGTWNGTT-KVA---IKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLY-----AVVSEEPIYIV 347
Cdd:cd14033     3 LKFNIEIGRGSFKTVYRGLDTETTvEVAwceLQTRKLSKGERQRFSEEVEMLKGLQHPNIVRFYdswksTVRGHKCIILV 82
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370473802 348 TEFMSKGSLLDFLKEgdGKYLKLPQLVDMAAQIADGMAYIERMN--YIHRDLRAANILV-GENLVCKIADFGLARL 420
Cdd:cd14033    83 TELMTSGTLKTYLKR--FREMKLKLLQRWSRQILKGLHFLHSRCppILHRDLKCDNIFItGPTGSVKIGDLGLATL 156
STKc_CaMKI_alpha cd14167
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
274-440 1.11e-10

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: 61.97  E-value: 1.11e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 274 RESLRLEVKLGQGCFGEVWMGTWNGTTK-VAIKTLKPGTMMPE--AFLQEAQIMKKLRHDKLVPLYAVV-SEEPIYIVTE 349
Cdd:cd14167     2 RDIYDFREVLGTGAFSEVVLAEEKRTQKlVAIKCIAKKALEGKetSIENEIAVLHKIKHPNIVALDDIYeSGGHLYLIMQ 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 350 FMSKGSLLD------FLKEGDGKYLklpqlvdmAAQIADGMAYIERMNYIHRDLRAANIL---VGENLVCKIADFGLARl 420
Cdd:cd14167    82 LVSGGELFDrivekgFYTERDASKL--------IFQILDAVKYLHDMGIVHRDLKPENLLyysLDEDSKIMISDFGLSK- 152
                         170       180
                  ....*....|....*....|....*
gi 1370473802 421 IED-----NEYTARQGMVNREVLEQ 440
Cdd:cd14167   153 IEGsgsvmSTACGTPGYVAPEVLAQ 177
STKc_MAP4K5 cd06646
Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase ...
273-421 1.21e-10

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: 61.97  E-value: 1.21e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 273 PRESLRLEVKLGQGCFGEVWMGTWNGTTKVA---IKTLKPGTMMpEAFLQEAQIMKKLRHDKLVPLY-AVVSEEPIYIVT 348
Cdd:cd06646     7 PQHDYELIQRVGSGTYGDVYKARNLHTGELAavkIIKLEPGDDF-SLIQQEIFMVKECKHCNIVAYFgSYLSREKLWICM 85
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370473802 349 EFMSKGSLLDfLKEGDGKYLKLpQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLI 421
Cdd:cd06646    86 EYCGGGSLQD-IYHVTGPLSEL-QIAYVCRETLQGLAYLHSKGKMHRDIKGANILLTDNGDVKLADFGVAAKI 156
STKc_HUNK cd14070
Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase ...
282-418 1.22e-10

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: 62.14  E-value: 1.22e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGT-TKVAIKTLKPGTMMPEAFL-----QEAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFMSKG 354
Cdd:cd14070     9 KLGEGSFAKVREGLHAVTgEKVAIKVIDKKKAKKDSYVtknlrREGRIQQMIRHPNITQLLDILeTENSYYLVMELCPGG 88
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370473802 355 SLLDflKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLA 418
Cdd:cd14070    89 NLMH--RIYDKKRLEEREARRYIRQLVSAVEHLHRAGVVHRDLKIENLLLDENDNIKLIDFGLS 150
STKc_WNK2_like cd14032
Catalytic domain of With No Lysine (WNK) 2-like Serine/Threonine kinases; STKs catalyze the ...
277-420 1.25e-10

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: 62.02  E-value: 1.25e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 277 LRLEVKLGQGCFGEVWMG----TWNGTTKVAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLY-----AVVSEEPIYIV 347
Cdd:cd14032     3 LKFDIELGRGSFKTVYKGldteTWVEVAWCELQDRKLTKVERQRFKEEAEMLKGLQHPNIVRFYdfwesCAKGKRCIVLV 82
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370473802 348 TEFMSKGSLLDFLKEgdGKYLKLPQLVDMAAQIADGMAYIERMN--YIHRDLRAANILV-GENLVCKIADFGLARL 420
Cdd:cd14032    83 TELMTSGTLKTYLKR--FKVMKPKVLRSWCRQILKGLLFLHTRTppIIHRDLKCDNIFItGPTGSVKIGDLGLATL 156
STKc_CaMKI cd14083
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
283-440 1.25e-10

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: 62.00  E-value: 1.25e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTK-VAIKTL-KPGTMMPEAFLQ-EAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFMSKGSLLD 358
Cdd:cd14083    11 LGTGAFSEVVLAEDKATGKlVAIKCIdKKALKGKEDSLEnEIAVLRKIKHPNIVQLLDIYeSKSHLYLVMELVTGGELFD 90
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 359 FLKEgDGKYLKlPQLVDMAAQIADGMAYIERMNYIHRDLRAANILV---GENLVCKIADFGLARlIEDNEYTARQ----G 431
Cdd:cd14083    91 RIVE-KGSYTE-KDASHLIRQVLEAVDYLHSLGIVHRDLKPENLLYyspDEDSKIMISDFGLSK-MEDSGVMSTAcgtpG 167

                  ....*....
gi 1370473802 432 MVNREVLEQ 440
Cdd:cd14083   168 YVAPEVLAQ 176
STKc_PAK_II cd06648
Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze ...
273-416 1.37e-10

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: 61.69  E-value: 1.37e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 273 PRESLRLEVKLGQGCFGEVWMGTWNGT-TKVAIKtlkpgtMMP-------EAFLQEAQIMKKLRHDKLVPLYA--VVSEE 342
Cdd:cd06648     5 PRSDLDNFVKIGEGSTGIVCIATDKSTgRQVAVK------KMDlrkqqrrELLFNEVVIMRDYQHPNIVEMYSsyLVGDE 78
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370473802 343 pIYIVTEFMSKGSLLDFLKEGDgkyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFG 416
Cdd:cd06648    79 -LWVVMEFLEGGALTDIVTHTR---MNEEQIATVCRAVLKALSFLHSQGVIHRDIKSDSILLTSDGRVKLSDFG 148
STKc_SLK cd06643
Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer ...
267-418 1.44e-10

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: 61.97  E-value: 1.44e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 267 KDAWEIPREslrlevkLGQGCFGEVWMGTwNGTTKV--AIKTLKPGTMMP-EAFLQEAQIMKKLRHDKLVPLY-AVVSEE 342
Cdd:cd06643     4 EDFWEIVGE-------LGDGAFGKVYKAQ-NKETGIlaAAKVIDTKSEEElEDYMVEIDILASCDHPNIVKLLdAFYYEN 75
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370473802 343 PIYIVTEFMSKGSLLDFLKEGDgKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLA 418
Cdd:cd06643    76 NLWILIEFCAGGAVDAVMLELE-RPLTEPQIRVVCKQTLEALVYLHENKIIHRDLKAGNILFTLDGDIKLADFGVS 150
STKc_Nek6 cd08228
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
276-481 1.46e-10

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: 61.97  E-value: 1.46e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 276 SLRLEVKLGQGCFGEVWMGTWN-GTTKVAIKTLKPGTMMP----EAFLQEAQIMKKLRHDKLVP-LYAVVSEEPIYIVTE 349
Cdd:cd08228     3 NFQIEKKIGRGQFSEVYRATCLlDRKPVALKKVQIFEMMDakarQDCVKEIDLLKQLNHPNVIKyLDSFIEDNELNIVLE 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 350 FMSKGSLLDFLKEGDGKYLKLPQ--LVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEdNEYT 427
Cdd:cd08228    83 LADAGDLSQMIKYFKKQKRLIPErtVWKYFVQLCSAVEHMHSRRVMHRDIKPANVFITATGVVKLGDLGLGRFFS-SKTT 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 428 ARQGMVNREVLEQVER----GYRM-----------------------------------------PCP-QGCPESLHELM 461
Cdd:cd08228   162 AAHSLVGTPYYMSPERihenGYNFksdiwslgcllyemaalqspfygdkmnlfslcqkieqcdypPLPtEHYSEKLRELV 241
                         250       260
                  ....*....|....*....|
gi 1370473802 462 NLCWKKDPDERPTFEYIQSF 481
Cdd:cd08228   242 SMCIYPDPDQRPDIGYVHQI 261
STKc_EIF2AK2_PKR cd14047
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
283-442 1.49e-10

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: 61.74  E-value: 1.49e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKV-AIKTLKpgtMMPEAFLQEAQIMKKLRHDKLVPLY-----------------AVVSEEPI 344
Cdd:cd14047    14 IGSGGFGQVFKAKHRIDGKTyAIKRVK---LNNEKAEREVKALAKLDHPNIVRYNgcwdgfdydpetsssnsSRSKTKCL 90
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 345 YIVTEFMSKGSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGL-ARLIED 423
Cdd:cd14047    91 FIQMEFCEKGTLESWIEKRNGEKLDKVLALEIFEQITKGVEYIHSKKLIHRDLKPSNIFLVDTGKVKIGDFGLvTSLKND 170
                         170
                  ....*....|....*....
gi 1370473802 424 NEYTARQGMVNREVLEQVE 442
Cdd:cd14047   171 GKRTKSKGTLSYMSPEQIS 189
PKc_Myt1 cd14050
Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze ...
282-476 1.51e-10

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: 61.56  E-value: 1.51e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGTTKV-AIKTlkpgtmMPEAFLQEAQIMKKLR----------HDKLVPLYAVVSEEPI-YIVTE 349
Cdd:cd14050     8 KLGEGSFGEVFKVRSREDGKLyAVKR------SRSRFRGEKDRKRKLEeverheklgeHPNCVRFIKAWEEKGIlYIQTE 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 350 fMSKGSLLDFLKEGDgkylKLPQ------LVDMAAqiadGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLarLIE- 422
Cdd:cd14050    82 -LCDTSLQQYCEETH----SLPEsevwniLLDLLK----GLKHLHDHGLIHLDIKPANIFLSKDGVCKLGDFGL--VVEl 150
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 423 -----------DNEYTARQ---------------GMVNREV------------LEQVERGYrMP--CPQGCPESLHELMN 462
Cdd:cd14050   151 dkedihdaqegDPRYMAPEllqgsftkaadifslGITILELacnlelpsggdgWHQLRQGY-LPeeFTAGLSPELRSIIK 229
                         250
                  ....*....|....
gi 1370473802 463 LCWKKDPDERPTFE 476
Cdd:cd14050   230 LMMDPDPERRPTAE 243
STKc_Nek3 cd08219
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
283-421 1.74e-10

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: 61.53  E-value: 1.74e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTW-NGTTKVAIKTLKpgtmMPEAF------LQEAQIMKKLRHDKLVPLY-AVVSEEPIYIVTEFMSKG 354
Cdd:cd08219     8 VGEGSFGRALLVQHvNSDQKYAMKEIR----LPKSSsavedsRKEAVLLAKMKHPNIVAFKeSFEADGHLYIVMEYCDGG 83
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370473802 355 SLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLI 421
Cdd:cd08219    84 DLMQKIKLQRGKLFPEDTILQWFVQMCLGVQHIHEKRVLHRDIKSKNIFLTQNGKVKLGDFGSARLL 150
SH3_Sho1p cd11855
Src homology 3 domain of High osmolarity signaling protein Sho1p; Sho1p (or Sho1), also called ...
98-148 1.75e-10

Src homology 3 domain of High osmolarity signaling protein Sho1p; Sho1p (or Sho1), also called SSU81 (Suppressor of SUA8-1 mutation), is a yeast membrane protein that regulates adaptation to high salt conditions by activating the HOG (high-osmolarity glycerol) pathway. High salt concentrations lead to the localization to the membrane of the MAPKK Pbs2, which is then activated by the MAPKK Ste11 and in turn, activates the MAPK Hog1. Pbs2 is localized to the membrane though the interaction of its PxxP motif with the SH3 domain of Sho1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. 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: 212789 [Multi-domain]  Cd Length: 55  Bit Score: 56.27  E-value: 1.75e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1370473802  98 ALYDYEARTTE--DLSFKKGERFQIInNTEGDWWEARSiATGKNGYIPSNYVA 148
Cdd:cd11855     4 ALYPYDASPDDpnELSFEKGEILEVS-DTSGKWWQARK-SNGETGICPSNYLQ 54
SH3_CSK cd11769
Src Homology 3 domain of C-terminal Src kinase; CSK is a cytoplasmic (or nonreceptor) tyr ...
97-147 1.75e-10

Src Homology 3 domain of C-terminal Src kinase; CSK is a cytoplasmic (or nonreceptor) tyr kinase 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 is 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. It is expressed in a wide variety of tissues and plays a role, as a regulator of Src, in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. 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. 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: 212703 [Multi-domain]  Cd Length: 57  Bit Score: 56.54  E-value: 1.75e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1370473802  97 VALYDYEARTTEDLSFKKGERFQIINNTEG-DWWEARSiATGKNGYIPSNYV 147
Cdd:cd11769     5 IAKYNFNGASEEDLPFKKGDILTIVAVTKDpNWYKAKN-KDGREGMIPANYV 55
STKc_TAO3 cd06633
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze ...
282-418 1.82e-10

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: 61.98  E-value: 1.82e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTwNGTTK--VAIKTLK-PGTMMPEAF---LQEAQIMKKLRHDKLVPLYAV-VSEEPIYIVTEFmSKG 354
Cdd:cd06633    28 EIGHGSFGAVYFAT-NSHTNevVAIKKMSySGKQTNEKWqdiIKEVKFLQQLKHPNTIEYKGCyLKDHTAWLVMEY-CLG 105
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370473802 355 SLLDFLkEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLA 418
Cdd:cd06633   106 SASDLL-EVHKKPLQEVEIAAITHGALQGLAYLHSHNMIHRDIKAGNILLTEPGQVKLADFGSA 168
SH3_PRMT2 cd11806
Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, ...
95-149 2.05e-10

Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, belongs to the arginine methyltransferase protein family. It functions as a coactivator to both estrogen receptor alpha (ER-alpha) and androgen receptor (AR), presumably through arginine methylation. The ER-alpha transcription factor is involved in cell proliferation, differentiation, morphogenesis, and apoptosis, and is also implicated in the development and progression of breast cancer. PRMT2 and its variants are upregulated in breast cancer cells and may be involved in modulating the ER-alpha signaling pathway during formation of breast cancer. PRMT2 also plays a role in regulating the function of E2F transcription factors, which are critical cell cycle regulators, by binding to the retinoblastoma gene product (RB). It contains an N-terminal SH3 domain and an AdoMet binding domain. 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: 212740 [Multi-domain]  Cd Length: 53  Bit Score: 56.25  E-value: 2.05e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1370473802  95 IFVALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARSiaTGKNGYIPSNYVAP 149
Cdd:cd11806     1 EYVAIADFVATDDSQLSFESGDKLLVLRKPSVDWWWAEH--NGCCGYIPASHLHQ 53
SH3_ARHGAP9_like cd11888
Src Homology 3 domain of Rho GTPase-activating protein 9 and similar proteins; This subfamily ...
97-146 2.05e-10

Src Homology 3 domain of Rho GTPase-activating protein 9 and similar proteins; This subfamily is composed of Rho GTPase-activating proteins including mammalian ARHGAP9, and vertebrate ARHGAPs 12 and 27. RhoGAPs (or ARHGAPs) bind to Rho proteins and enhance the hydrolysis rates of bound GTP. ARHGAP9 functions as a GAP for Rac and Cdc42, but not for RhoA. It negatively regulates cell migration and adhesion. It also acts as a docking protein for the MAP kinases Erk2 and p38alpha, and may facilitate cross-talk between the Rho GTPase and MAPK pathways to control actin remodeling. ARHGAP27, also called CAMGAP1, shows GAP activity towards Rac1 and Cdc42. It binds the adaptor protein CIN85 and may play a role in clathrin-mediated endocytosis. ARHGAP12 has been shown to display GAP activity towards Rac1. It plays a role in regulating HFG-driven cell growth and invasiveness. ARHGAPs in this subfamily contain SH3, WW, Pleckstin homology (PH), and RhoGAP domains. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212821 [Multi-domain]  Cd Length: 54  Bit Score: 56.22  E-value: 2.05e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1370473802  97 VALYDYEARTTED--LSFKKGERFQIINNTEGDWWEARSIATGKNGYIPSNY 146
Cdd:cd11888     3 VVLYPFEYTGKDGrkVSIKEGERFLLLKKSNDDWWQVRRPGDSKPFYVPAQY 54
STKc_GRK cd05577
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase; STKs ...
283-418 2.08e-10

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. GRKs play important roles in the cardiovascular, immune, respiratory, skeletal, and nervous systems. They contain a central catalytic domain, flanked by N- and C-terminal extensions. The N-terminus contains an RGS (regulator of G protein signaling) homology (RH) domain and several motifs. The C-terminus diverges among different groups of GRKs. There are seven types of GRKs, named GRK1 to GRK7, which are subdivided into three main groups: visual (GRK1/7); beta-adrenergic receptor kinases (GRK2/3); and GRK4-like (GRK4/5/6). Expression of GRK2/3/5/6 is widespread while GRK1/4/7 show a limited tissue distribution. The substrate spectrum of the widely expressed GRKs partially overlaps. The GRK 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: 270729 [Multi-domain]  Cd Length: 278  Bit Score: 61.39  E-value: 2.08e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKV-AIKTL-------KPGTMMPeafLQEAQIMKKLRHDKLVPL-YAVVSEEPIYIVTEFMSK 353
Cdd:cd05577     1 LGRGGFGEVCACQVKATGKMyACKKLdkkrikkKKGETMA---LNEKIILEKVSSPFIVSLaYAFETKDKLCLVLTLMNG 77
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370473802 354 GSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLA 418
Cdd:cd05577    78 GDLKYHIYNVGTRGFSEARAIFYAAEIICGLEHLHNRFIVYRDLKPENILLDDHGHVRISDLGLA 142
STKc_GRK7 cd05607
Catalytic domain of the Protein Serine/Threonine Kinase, G protein-coupled Receptor Kinase 7; ...
283-461 2.10e-10

Catalytic domain of the Protein Serine/Threonine Kinase, G protein-coupled Receptor Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK7 (also called iodopsin kinase) belongs to the visual group of GRKs. It is primarily found in the retina and plays a role in the regulation of opsin light receptors. GRK7 is located in retinal cone outer segments and plays an important role in regulating photoresponse of the cones. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK7 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: 270758 [Multi-domain]  Cd Length: 286  Bit Score: 61.46  E-value: 2.10e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVW------MGTWNGTTKVAIKTLKPGTMMPEAFLqEAQIMKKLRHDKLVPL-YAVVSEEPIYIVTEFMSKGS 355
Cdd:cd05607    10 LGKGGFGEVCavqvknTGQMYACKKLDKKRLKKKSGEKMALL-EKEILEKVNSPFIVSLaYAFETKTHLCLVMSLMNGGD 88
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 356 LLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYTARQ----G 431
Cdd:cd05607    89 LKYHIYNVGERGIEMERVIFYSAQITCGILHLHSLKIVYRDMKPENVLLDDNGNCRLSDLGLAVEVKEGKPITQRagtnG 168
                         170       180       190
                  ....*....|....*....|....*....|...
gi 1370473802 432 MVNREVLEQVErgYRMPC---PQGCpeSLHELM 461
Cdd:cd05607   169 YMAPEILKEES--YSYPVdwfAMGC--SIYEMV 197
STKc_Twitchin_like cd14114
The catalytic domain of the Giant Serine/Threonine Kinases, Twitchin and Projectin; STKs ...
282-425 2.13e-10

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: 61.06  E-value: 2.13e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGTTKV--AIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLY-AVVSEEPIYIVTEFMSKGSLLD 358
Cdd:cd14114     9 ELGTGAFGVVHRCTERATGNNfaAKFIMTPHESDKETVRKEIQIMNQLHHPKLINLHdAFEDDNEMVLILEFLSGGELFE 88
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1370473802 359 FLKEGDGKyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANIL--VGENLVCKIADFGLARLIEDNE 425
Cdd:cd14114    89 RIAAEHYK-MSEAEVINYMRQVCEGLCHMHENNIVHLDIKPENIMctTKRSNEVKLIDFGLATHLDPKE 156
SH3_srGAP4 cd11956
Src homology 3 domain of Slit-Robo GTPase Activating Protein 4; srGAP4, also called ARHGAP4, ...
97-148 2.19e-10

Src homology 3 domain of Slit-Robo GTPase Activating Protein 4; srGAP4, also called ARHGAP4, is highly expressed in hematopoietic cells and may play a role in lymphocyte differentiation. It is able to stimulate the GTPase activity of Rac1, Cdc42, and RhoA. In the nervous system, srGAP4 has been detected in differentiating neurites and may be involved in axon and dendritic growth. srGAPs are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. 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: 212889 [Multi-domain]  Cd Length: 55  Bit Score: 56.00  E-value: 2.19e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1370473802  97 VALYDYEARTTEDLSFKKGERFQIINNTEGDWWeaRSIATGKNGYIPSNYVA 148
Cdd:cd11956     5 VACFDYTGRTAQELSFKRGDVLLLHSKASSDWW--RGEHNGMRGLIPHKYIS 54
STKc_PCTAIRE_like cd07844
Catalytic domain of PCTAIRE-like Serine/Threonine Kinases; STKs catalyze the transfer of the ...
282-419 2.25e-10

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: 61.63  E-value: 2.25e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGTTK-VAIK--TLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFMSKGsll 357
Cdd:cd07844     7 KLGEGSYATVYKGRSKLTGQlVALKeiRLEHEEGAPFTAIREASLLKDLKHANIVTLHDIIhTKKTLTLVFEYLDTD--- 83
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1370473802 358 dfLKegdgKYL-KLPQLVDMAA------QIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR 419
Cdd:cd07844    84 --LK----QYMdDCGGGLSMHNvrlflfQLLRGLAYCHQRRVLHRDLKPQNLLISERGELKLADFGLAR 146
SH3_SPIN90 cd11849
Src homology 3 domain of SH3 protein interacting with Nck, 90 kDa (SPIN90); SPIN90 is also ...
98-147 2.33e-10

Src homology 3 domain of SH3 protein interacting with Nck, 90 kDa (SPIN90); SPIN90 is also called NCK interacting protein with SH3 domain (NCKIPSD), Dia-interacting protein (DIP), 54 kDa vimentin-interacting protein (VIP54), or WASP-interacting SH3-domain protein (WISH). It is an F-actin binding protein that regulates actin polymerization and endocytosis. It associates with the Arp2/3 complex near actin filaments and determines filament localization at the leading edge of lamellipodia. SPIN90 is expressed in the early stages of neuronal differentiation and plays a role in regulating growth cone dynamics and neurite outgrowth. It also interacts with IRSp53 and regulates cell motility by playing a role in the formation of membrane protrusions. SPIN90 contains an N-terminal SH3 domain, a proline-rich domain, and a C-terminal VCA (verprolin-homology and cofilin-like acidic) domain. 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: 212783 [Multi-domain]  Cd Length: 53  Bit Score: 55.78  E-value: 2.33e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1370473802  98 ALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARSIaTGKNGYIPSNYV 147
Cdd:cd11849     4 ALYDFKSAEPNTLSFSEGETFLLLERSNAHWWLVTNH-SGETGYVPANYV 52
STKc_DCKL3 cd14185
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called ...
320-421 2.35e-10

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: 61.12  E-value: 2.35e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 320 EAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFMSKGSLLDFLKEGdgkyLKLPQLvDMAAQIAD---GMAYIERMNYIHR 395
Cdd:cd14185    48 EILIIKSLSHPNIVKLFEVYeTEKEIYLILEYVRGGDLFDAIIES----VKFTEH-DAALMIIDlceALVYIHSKHIVHR 122
                          90       100       110
                  ....*....|....*....|....*....|
gi 1370473802 396 DLRAANILVGEN----LVCKIADFGLARLI 421
Cdd:cd14185   123 DLKPENLLVQHNpdksTTLKLADFGLAKYV 152
PKc_Byr1_like cd06620
Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; ...
275-474 2.36e-10

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: 61.30  E-value: 2.36e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 275 ESLRLEVKLGQGcfgevwmgtwNGTTKVAIKTLKPGTMMPEA-------------FLQEAQIMKKLRHDKLVPLY-AVVS 340
Cdd:cd06620     5 QDLETLKDLGAG----------NGGSVSKVLHIPTGTIMAKKvihidakssvrkqILRELQILHECHSPYIVSFYgAFLN 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 341 EEP-IYIVTEFMSKGSLLDFLKEGdgKYLKLPQLVDMAAQIADGMAYIERMNYI-HRDLRAANILVGENLVCKIADFGLA 418
Cdd:cd06620    75 ENNnIIICMEYMDCGSLDKILKKK--GPFPEEVLGKIAVAVLEGLTYLYNVHRIiHRDIKPSNILVNSKGQIKLCDFGVS 152
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 419 R---------------------------------------LIE--------------DNEYTARQGMVnrEVLEQV--ER 443
Cdd:cd06620   153 GelinsiadtfvgtstymsperiqggkysvksdvwslglsIIElalgefpfagsnddDDGYNGPMGIL--DLLQRIvnEP 230
                         250       260       270
                  ....*....|....*....|....*....|.
gi 1370473802 444 GYRMPCPQGCPESLHELMNLCWKKDPDERPT 474
Cdd:cd06620   231 PPRLPKDRIFPKDLRDFVDRCLLKDPRERPS 261
SH2_SHC cd09925
Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC); SHC is involved in a wide ...
150-197 2.37e-10

Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC); SHC is involved in a wide variety of pathways including regulating proliferation, angiogenesis, invasion and metastasis, and bone metabolism. An adapter protein, SHC has been implicated in Ras activation following the stimulation of a number of different receptors, including growth factors [insulin, epidermal growth factor (EGF), nerve growth factor, and platelet derived growth factor (PDGF)], cytokines [interleukins 2, 3, and 5], erythropoietin, and granulocyte/macrophage colony-stimulating factor, and antigens [T-cell and B-cell receptors]. SHC has been shown to bind to tyrosine-phosphorylated receptors, and receptor stimulation leads to tyrosine phosphorylation of SHC. Upon phosphorylation, SHC interacts with another adapter protein, Grb2, which binds to the Ras GTP/GDP exchange factor mSOS which leads to Ras activation. SHC is composed of an N-terminal domain that interacts with proteins containing phosphorylated tyrosines, a (glycine/proline)-rich collagen-homology domain that contains the phosphorylated binding site, and a C-terminal SH2 domain. SH2 has been shown to interact with the tyrosine-phosphorylated receptors of EGF and PDGF and with the tyrosine-phosphorylated C chain of the T-cell receptor, providing one of the mechanisms of T-cell-mediated Ras activation. 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: 198179  Cd Length: 104  Bit Score: 57.36  E-value: 2.37e-10
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1370473802 150 ADSIQAEEWYFGKMGRKDAERLLLNPGNqrgiFLVRESETTKGAYSLS 197
Cdd:cd09925     1 AEQLRGEPWYHGKMSRRDAESLLQTDGD----FLVRESTTTPGQYVLT 44
STKc_MEKK3 cd06651
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular ...
283-422 2.46e-10

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK3 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. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. In addition, MEKK3 is involved in interleukin-1 receptor and Toll-like receptor 4 signaling. It is also a specific regulator of the proinflammatory cytokines IL-6 and GM-CSF in some immune cells. MEKK3 also regulates calcineurin, which plays a critical role in T cell activation, apoptosis, skeletal myocyte differentiation, and cardiac hypertrophy. The MEKK3 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: 270817 [Multi-domain]  Cd Length: 271  Bit Score: 61.25  E-value: 2.46e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWM------GTWNGTTKVAIKTLKPGTMMPEAFLQ-EAQIMKKLRHDKLVPLYAVV---SEEPIYIVTEFMS 352
Cdd:cd06651    15 LGQGAFGRVYLcydvdtGRELAAKQVQFDPESPETSKEVSALEcEIQLLKNLQHERIVQYYGCLrdrAEKTLTIFMEYMP 94
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370473802 353 KGSLLDFLKegdgKYLKLPQLV--DMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIE 422
Cdd:cd06651    95 GGSVKDQLK----AYGALTESVtrKYTRQILEGMSYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASKRLQ 162
PKc_Pek1_like cd06621
Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ...
282-418 2.72e-10

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: 61.28  E-value: 2.72e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGTTKV-AIKTL--KPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEP---IYIVTEFMSKGS 355
Cdd:cd06621     8 SLGEGAGGSVTKCRLRNTKTIfALKTIttDPNPDVQKQILRELEINKSCASPYIVKYYGAFLDEQdssIGIAMEYCEGGS 87
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370473802 356 LLDFLKEGDGKYLKLPQLV--DMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLA 418
Cdd:cd06621    88 LDSIYKKVKKKGGRIGEKVlgKIAESVLKGLSYLHSRKIIHRDIKPSNILLTRKGQVKLCDFGVS 152
STKc_DMPK_like cd05597
Catalytic domain of Myotonic Dystrophy protein kinase (DMPK)-like Serine/Threonine Kinases; ...
283-416 3.23e-10

Catalytic domain of Myotonic Dystrophy protein kinase (DMPK)-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The DMPK-like subfamily is composed of DMPK and DMPK-related cell division control protein 42 (Cdc42) binding kinase (MRCK). DMPK is expressed in skeletal and cardiac muscles, and in central nervous tissues. The functional role of DMPK is not fully understood. It may play a role in the signal transduction and homeostasis of calcium. The DMPK gene is implicated in myotonic dystrophy 1 (DM1), an inherited multisystemic disorder with symptoms that include muscle hyperexcitability, progressive muscle weakness and wasting, cataract development, testicular atrophy, and cardiac conduction defects. The genetic basis for DM1 is the mutational expansion of a CTG repeat in the 3'-UTR of DMPK. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. Three isoforms of MRCK are known, named alpha, beta and gamma. MRCKgamma is expressed in heart and skeletal muscles, unlike MRCKalpha and MRCKbeta, which are expressed ubiquitously. The DMPK-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: 270748 [Multi-domain]  Cd Length: 331  Bit Score: 61.59  E-value: 3.23e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKV-AIKTLKPGTMMPEA----FLQEAQIMKKLRHDKLVPL-YAVVSEEPIYIVTEFMSKGSL 356
Cdd:cd05597     9 IGRGAFGEVAVVKLKSTEKVyAMKILNKWEMLKRAetacFREERDVLVNGDRRWITKLhYAFQDENYLYLVMDYYCGGDL 88
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370473802 357 LDFL-KEGDgkylKLPQlvDMA----AQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFG 416
Cdd:cd05597    89 LTLLsKFED----RLPE--EMArfylAEMVLAIDSIHQLGYVHRDIKPDNVLLDRNGHIRLADFG 147
STKc_PLK1 cd14187
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; STKs catalyze the ...
283-422 4.54e-10

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: 60.33  E-value: 4.54e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKVAIKTLKPGTMM-----PEAFLQEAQIMKKLRHDKLVPLYAVVSEEP-IYIVTEFMSKGSL 356
Cdd:cd14187    15 LGKGGFAKCYEITDADTKEVFAGKIVPKSLLlkphqKEKMSMEIAIHRSLAHQHVVGFHGFFEDNDfVYVVLELCRRRSL 94
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370473802 357 LDFLKEGdgKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIE 422
Cdd:cd14187    95 LELHKRR--KALTEPEARYYLRQIILGCQYLHRNRVIHRDLKLGNLFLNDDMEVKIGDFGLATKVE 158
SH3_9 pfam14604
Variant SH3 domain;
98-148 4.77e-10

Variant SH3 domain;


Pssm-ID: 434066 [Multi-domain]  Cd Length: 49  Bit Score: 54.93  E-value: 4.77e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1370473802  98 ALYDYEARTTEDLSFKKGERFQIINNTEGDWWEArsIATGKNGYIPSNYVA 148
Cdd:pfam14604   1 ALYPYEPKDDDELSLQRGDVITVIEESEDGWWEG--INTGRTGLVPANYVE 49
STKc_CaMKII cd14086
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
319-445 5.39e-10

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: 60.51  E-value: 5.39e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 319 QEAQIMKKLRHDKLVPLYAVVSEEPI-YIVTEFMSKGSLLD------FLKEGDGKYLklpqlvdmAAQIADGMAYIERMN 391
Cdd:cd14086    49 REARICRLLKHPNIVRLHDSISEEGFhYLVFDLVTGGELFEdivareFYSEADASHC--------IQQILESVNHCHQNG 120
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370473802 392 YIHRDLRAANILVG---ENLVCKIADFGLARLIEDNE-----YTARQGMVNREVLEQVERGY 445
Cdd:cd14086   121 IVHRDLKPENLLLAsksKGAAVKLADFGLAIEVQGDQqawfgFAGTPGYLSPEVLRKDPYGK 182
SH2_BCAR3 cd10337
Src homology 2 (SH2) domain in the Breast Cancer Anti-estrogen Resistance protein 3; BCAR3 is ...
153-240 5.41e-10

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: 57.34  E-value: 5.41e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 153 IQAEEWYFGKMGRKDAERLLLNPGNqrgiFLVRESETTKGAYSLSIRdWdeiRGdNVKHYKIRKLDNGGYYITTRAQ--- 229
Cdd:cd10337     3 LRSHAWYHGRIPRQVAESLVQREGD----FLVRDSLSSPGDYVLTCR-W---KG-QPLHFKINRVVLRPSEAYTRVQyqf 73
                          90
                  ....*....|....*
gi 1370473802 230 ----FDTLQKLVKHY 240
Cdd:cd10337    74 edeqFDSIPALVHFY 88
STKc_IKK cd13989
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
283-425 5.50e-10

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: 60.54  E-value: 5.50e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEV--WMGTWNGTtKVAIKT----LKPGTMMPEAFLQEAQIMKKLRHDKLV-------PLYAVVSEEPIYIVTE 349
Cdd:cd13989     1 LGSGGFGYVtlWKHQDTGE-YVAIKKcrqeLSPSDKNRERWCLEVQIMKKLNHPNVVsardvppELEKLSPNDLPLLAME 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 350 FMSKGSL---LDFLKEGDGkyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANIL---VGENLVCKIADFGLARLIED 423
Cdd:cd13989    80 YCSGGDLrkvLNQPENCCG--LKESEVRTLLSDISSAISYLHENRIIHRDLKPENIVlqqGGGRVIYKLIDLGYAKELDQ 157

                  ..
gi 1370473802 424 NE 425
Cdd:cd13989   158 GS 159
SH3_Intersectin_5 cd11840
Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor ...
97-149 5.67e-10

Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. 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: 212774 [Multi-domain]  Cd Length: 53  Bit Score: 54.73  E-value: 5.67e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1370473802  97 VALYDYEARTTEDLSFKKGERFQIINNTEGDWWeaRSIATGKNGYIPSNYVAP 149
Cdd:cd11840     3 IALFPYTAQNEDELSFQKGDIINVLSKDDPDWW--RGELNGQTGLFPSNYVEP 53
STKc_IRAK2 cd14157
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 2; ...
285-432 5.75e-10

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 2; 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. IRAK2 plays a role in mediating NFkB activation by TLR3, TLR4, and TLR8. It is specifically targeted by the viral protein A52, which is important for virulence, to inhibit all IL-1/TLR pathways, indicating that IRAK2 has a predominant role in NFkB activation. It is redundant with IRAK1 in early signaling but is critical for late and sustained activation. The IRAK2 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: 271059 [Multi-domain]  Cd Length: 289  Bit Score: 60.24  E-value: 5.75e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 285 QGCFGEVWMGtWNGTTKVAIKTLK------PGTMmpEAFLQ-EAQIMKKLRHDKLVPL--YAVVSEEPIYIvTEFMSKGS 355
Cdd:cd14157     3 EGTFADIYKG-YRHGKQYVIKRLKetecesPKST--ERFFQtEVQICFRCCHPNILPLlgFCVESDCHCLI-YPYMPNGS 78
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1370473802 356 LLDFLK-EGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLaRLIEDNEYTARQGM 432
Cdd:cd14157    79 LQDRLQqQGGSHPLPWEQRLSISLGLLKAVQHLHNFGILHGNIKSSNVLLDGNLLPKLGHSGL-RLCPVDKKSVYTMM 155
STKc_PAK5 cd06658
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the ...
273-448 5.93e-10

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: 60.44  E-value: 5.93e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 273 PRESLRLEVKLGQGCFGEVWMGTWNGTTK-VAIKTLK-PGTMMPEAFLQEAQIMKKLRHDKLVPLYA--VVSEEpIYIVT 348
Cdd:cd06658    20 PREYLDSFIKIGEGSTGIVCIATEKHTGKqVAVKKMDlRKQQRRELLFNEVVIMRDYHHENVVDMYNsyLVGDE-LWVVM 98
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 349 EFMSKGSLLDFLKEgdgKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEdNEYTA 428
Cdd:cd06658    99 EFLEGGALTDIVTH---TRMNEEQIATVCLSVLRALSYLHNQGVIHRDIKSDSILLTSDGRIKLSDFGFCAQVS-KEVPK 174
                         170       180
                  ....*....|....*....|
gi 1370473802 429 RQGMVNREVLEQVERGYRMP 448
Cdd:cd06658   175 RKSLVGTPYWMAPEVISRLP 194
STKc_MAP4K3 cd06645
Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase ...
273-421 6.69e-10

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: 60.06  E-value: 6.69e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 273 PRESLRLEVKLGQGCFGEVWMGTWNGTTKVA-IKTLK--PGTMMpEAFLQEAQIMKKLRHDKLVPLY-AVVSEEPIYIVT 348
Cdd:cd06645     9 PQEDFELIQRIGSGTYGDVYKARNVNTGELAaIKVIKlePGEDF-AVVQQEIIMMKDCKHSNIVAYFgSYLRRDKLWICM 87
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370473802 349 EFMSKGSLLDFLKEGDGkyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLI 421
Cdd:cd06645    88 EFCGGGSLQDIYHVTGP--LSESQIAYVSRETLQGLYYLHSKGKMHRDIKGANILLTDNGHVKLADFGVSAQI 158
SH2_PTK6_Brk cd10358
Src homology 2 domain found in protein-tyrosine kinase-6 (PTK6) which is also known as breast ...
155-259 7.31e-10

Src homology 2 domain found in protein-tyrosine kinase-6 (PTK6) which is also known as breast tumor kinase (Brk); Human protein-tyrosine kinase-6 (PTK6, also known as breast tumor kinase (Brk)) is a member of the non-receptor protein-tyrosine kinase family and is expressed in two-thirds of all breast tumors. PTK6 (9). PTK6 contains a SH3 domain, a SH2 domain, and catalytic domains. For the case of the non-receptor protein-tyrosine kinases, the SH2 domain is typically involved in negative regulation of kinase activity by binding to a phosphorylated tyrosine residue near to the C terminus. The C-terminal sequence of PTK6 (PTSpYENPT where pY is phosphotyrosine) is thought to be a self-ligand for the SH2 domain. The structure of the SH2 domain resembles other SH2 domains except for a centrally located four-stranded antiparallel beta-sheet (strands betaA, betaB, betaC, and betaD). There are also differences in the loop length which might be responsible for PTK6 ligand specificity. There are two possible means of regulation of PTK6: autoinhibitory with the phosphorylation of Tyr playing a role in its negative regulation and autophosphorylation at this site, though it has been shown that PTK6 might phosphorylate signal transduction-associated proteins Sam68 and signal transducing adaptor family member 2 (STAP/BKS) in vivo. 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: 198221  Cd Length: 100  Bit Score: 55.91  E-value: 7.31e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 155 AEEWYFGKMGRKDAERLLLNPGNQRGIFLVRESETTKGAYSLSIRDWDEIRgdnvkHYKIRKLDNGGYYITTRAQFDTLQ 234
Cdd:cd10358     1 SEPWFFGCISRSEAVRRLQAEGNATGAFLIRVSEKPSADYVLSVRDTQAVR-----HYKIWRRAGGRLHLNEAVSFLSLP 75
                          90       100
                  ....*....|....*....|....*
gi 1370473802 235 KLVKHYTEHAdgLCHKLTTVCPTVK 259
Cdd:cd10358    76 ELVNYHRAQS--LSHGLRLAAPCRK 98
STKc_TEY_MAPK cd07858
Catalytic domain of the Serine/Threonine Kinases, Plant TEY Mitogen-Activated Protein Kinases; ...
283-448 7.42e-10

Catalytic domain of the Serine/Threonine Kinases, Plant TEY 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 TEY subtype of plant MAPKs and is further subdivided into three groups (A, B, and C). Group A is represented by AtMPK3, AtMPK6, Nicotiana tabacum BTF4 (NtNTF4), among others. They are mostly involved in environmental and hormonal responses. AtMPK3 and AtMPK6 are also key regulators for stomatal development and patterning. Group B is represented by AtMPK4, AtMPK13, and NtNTF6, among others. They may be involved in both cell division and environmental stress response. AtMPK4 also participates in regulating innate immunity. Group C is represented by AtMPK1, AtMPK2, NtNTF3, Oryza sativa MAPK4 (OsMAPK4), among others. They may also be involved in stress responses. AtMPK1 and AtMPK2 are activated following mechanical injury and in the presence of stress chemicals such as jasmonic acid, hydrogen peroxide and abscisic acid. OsMAPK4 is also called OsMSRMK3 for Multiple Stress-Responsive MAPK3. 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. The TEY MAPK 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: 143363 [Multi-domain]  Cd Length: 337  Bit Score: 60.46  E-value: 7.42e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTT-KVAIKTLKpgtmmpEAF---------LQEAQIMKKLRHDKLVPLYAVV------SEEPIYI 346
Cdd:cd07858    13 IGRGAYGIVCSAKNSETNeKVAIKKIA------NAFdnridakrtLREIKLLRHLDHENVIAIKDIMppphreAFNDVYI 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 347 VTEFM---------SKGSLLD-----FLkegdgkYlklpqlvdmaaQIADGMAYIERMNYIHRDLRAANILVGENLVCKI 412
Cdd:cd07858    87 VYELMdtdlhqiirSSQTLSDdhcqyFL------Y-----------QLLRGLKYIHSANVLHRDLKPSNLLLNANCDLKI 149
                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 1370473802 413 ADFGLARLIEDNEytarqGMVNREVleqVERGYRMP 448
Cdd:cd07858   150 CDFGLARTTSEKG-----DFMTEYV---VTRWYRAP 177
STKc_SNRK cd14074
Catalytic domain of the Serine/Threonine Kinase, SNF1-related kinase; STKs catalyze the ...
279-425 7.54e-10

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: 59.73  E-value: 7.54e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 279 LEVKLGQGCFGEVWMGTWNGT-TKVAIKTL---KPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFMSK 353
Cdd:cd14074     7 LEETLGRGHFAVVKLARHVFTgEKVAVKVIdktKLDDVSKAHLFQEVRCMKLVQHPNVVRLYEVIdTQTKLYLILELGDG 86
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370473802 354 GSLLDFLKEGDGKylkLPQlvDMA----AQIADGMAYIERMNYIHRDLRAANILVGENLVC-KIADFGLARLIEDNE 425
Cdd:cd14074    87 GDMYDYIMKHENG---LNE--DLArkyfRQIVSAISYCHKLHVVHRDLKPENVVFFEKQGLvKLTDFGFSNKFQPGE 158
STKc_CAMKK cd14118
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; ...
319-425 8.62e-10

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: 59.68  E-value: 8.62e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 319 QEAQIMKKLRHDKLVPLYAVV---SEEPIYIVTEFMSKGSLLD------FLKEGDGKYLKlpqlvdmaaQIADGMAYIER 389
Cdd:cd14118    63 REIAILKKLDHPNVVKLVEVLddpNEDNLYMVFELVDKGAVMEvptdnpLSEETARSYFR---------DIVLGIEYLHY 133
                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1370473802 390 MNYIHRDLRAANILVGENLVCKIADFGLARLIEDNE 425
Cdd:cd14118   134 QKIIHRDIKPSNLLLGDDGHVKIADFGVSNEFEGDD 169
STKc_16 cd13986
Catalytic domain of Serine/Threonine Kinase 16; STKs catalyze the transfer of the ...
318-484 9.09e-10

Catalytic domain of Serine/Threonine Kinase 16; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK16 is associated with many names including Myristylated and Palmitylated Serine/threonine Kinase 1 (MPSK1), Kinase related to cerevisiae and thaliana (Krct), and Protein Kinase expressed in day 12 fetal liver (PKL12). It is widely expressed in mammals with highest levels found in liver, testis, and kidney. It is localized in the Golgi but is translocated to the nucleus upon disorganization of the Golgi. STK16 is constitutively active and is capable of phosphorylating itself and other substrates. It may be involved in regulating stromal-epithelial interactions during mammary gland ductal morphogenesis. It may also function as a transcriptional co-activator of type-C natriuretic peptide and VEGF. The STK16 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: 270888 [Multi-domain]  Cd Length: 282  Bit Score: 59.62  E-value: 9.09e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 318 LQEAQIMKKLRHDKLVPL--YAVVSEEP----IYIVTEFMSKGSLLDFLKEGD--GKYLKLPQLVDMAAQIADGMAYI-- 387
Cdd:cd13986    45 MREIENYRLFNHPNILRLldSQIVKEAGgkkeVYLLLPYYKRGSLQDEIERRLvkGTFFPEDRILHIFLGICRGLKAMhe 124
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 388 -ERMNYIHRDLRAANILVGENLVCKIADFG---LARL-IEDN-EYTARQGMV------------------NREVLEQV-- 441
Cdd:cd13986   125 pELVPYAHRDIKPGNVLLSEDDEPILMDLGsmnPARIeIEGRrEALALQDWAaehctmpyrapelfdvksHCTIDEKTdi 204
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370473802 442 ---------------------ERG-----------YRMPCPQGCPESLHELMNLCWKKDPDERPTFEYIQSFLED 484
Cdd:cd13986   205 wslgctlyalmygespferifQKGdslalavlsgnYSFPDNSRYSEELHQLVKSMLVVNPAERPSIDDLLSRVHD 279
SH3_Sla1p_3 cd11775
Third Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates ...
97-149 9.34e-10

Third Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. The third SH3 domain of Sla1p can bind ubiquitin while retaining the ability to bind proline-rich ligands; monoubiquitination of target proteins signals internalization and sorting through the endocytic pathway. 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: 212709 [Multi-domain]  Cd Length: 57  Bit Score: 54.25  E-value: 9.34e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1370473802  97 VALYDYEARTTEDLSFKKGERFQIINNTEG-DWWEARSIATGKNGYIPSNYVAP 149
Cdd:cd11775     4 KVLYDFDAQSDDELTVKEGDVVYILDDKKSkDWWMVENVSTGKEGVVPASYIEI 57
STKc_cPKC_alpha cd05615
Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha; STKs ...
283-419 9.70e-10

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: 60.01  E-value: 9.70e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKV-AIKTLKPGTMMPEAFLQEAQIMKKL--RHDK---LVPLYAVVSE-EPIYIVTEFMSKGS 355
Cdd:cd05615    18 LGKGSFGKVMLAERKGSDELyAIKILKKDVVIQDDDVECTMVEKRVlaLQDKppfLTQLHSCFQTvDRLYFVMEYVNGGD 97
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370473802 356 LLDFLKEGdGKYlKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR 419
Cdd:cd05615    98 LMYHIQQV-GKF-KEPQAVFYAAEISVGLFFLHKKGIIYRDLKLDNVMLDSEGHIKIADFGMCK 159
STKc_ULK4 cd14010
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the ...
282-424 9.87e-10

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: 59.23  E-value: 9.87e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGTTK-VAIKTLKPGTMmPEaFLQEAQIMKKLRHDKLVPLYA-VVSEEPIYIVTEFMSKGSLLDF 359
Cdd:cd14010     7 EIGRGKHSVVYKGRRKGTIEfVAIKCVDKSKR-PE-VLNEVRLTHELKHPNVLKFYEwYETSNHLWLVVEYCTGGDLETL 84
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370473802 360 LKEgDGKylkLPQLV--DMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDN 424
Cdd:cd14010    85 LRQ-DGN---LPESSvrKFGRDLVRGLHYIHSKGIIYCDLKPSNILLDGNGTLKLSDFGLARREGEI 147
SH3_SH3RF2_3 cd11784
Third Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called ...
95-149 1.01e-09

Third Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF2. 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: 212718  Cd Length: 55  Bit Score: 54.01  E-value: 1.01e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1370473802  95 IFVALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARSIATGKNGYIPSNYVAP 149
Cdd:cd11784     1 MCVALHSYSAHRPEELELQKGEGVRVLGKFQEGWLRGLSLVTGRVGIFPSNYVSP 55
STKc_cPKC cd05587
Catalytic domain of the Serine/Threonine Kinase, Classical (or Conventional) Protein Kinase C; ...
283-419 1.07e-09

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: 59.71  E-value: 1.07e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKV-AIKTLKPGTMMPEAFLQEAQIMKKL-----RHDKLVPLYAVV-SEEPIYIVTEFMSKGS 355
Cdd:cd05587     4 LGKGSFGKVMLAERKGTDELyAIKILKKDVIIQDDDVECTMVEKRVlalsgKPPFLTQLHSCFqTMDRLYFVMEYVNGGD 83
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370473802 356 LLdFLKEGDGKYlKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR 419
Cdd:cd05587    84 LM-YHIQQVGKF-KEPVAVFYAAEIAVGLFFLHSKGIIYRDLKLDNVMLDAEGHIKIADFGMCK 145
SH3_Ysc84p_like cd11842
Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the ...
97-147 1.16e-09

Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the Saccharomyces cerevisiae proteins, Ysc84p (also called LAS17-binding protein 4, Lsb4p) and Lsb3p, and similar fungal proteins. They contain an N-terminal SYLF domain (also called DUF500) and a C-terminal SH3 domain. Ysc84p localizes to actin patches and plays an important in actin polymerization during endocytosis. The N-terminal domain of both Ysc84p and Lsb3p can bind and bundle actin filaments. A study of the yeast SH3 domain interactome predicts that the SH3 domains of Lsb3p and Lsb4p may function as molecular hubs for the assembly of endocytic complexes. 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: 212776 [Multi-domain]  Cd Length: 55  Bit Score: 53.97  E-value: 1.16e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1370473802  97 VALYDYEARTTEDLSFKKGERFQIIN--NTEGDWWEARsiATGKNGYIPSNYV 147
Cdd:cd11842     3 VALYDFAGEQPGDLAFQKGDIITILKksDSQNDWWTGR--IGGREGIFPANYV 53
STKc_PFTAIRE1 cd07869
Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-1 kinase; STKs catalyze the transfer ...
282-419 1.21e-09

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: 59.32  E-value: 1.21e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGTTK-VAIKTLK----PGTmmPEAFLQEAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFMSKgS 355
Cdd:cd07869    12 KLGEGSYATVYKGKSKVNGKlVALKVIRlqeeEGT--PFTAIREASLLKGLKHANIVLLHDIIhTKETLTLVFEYVHT-D 88
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370473802 356 LLDFLKEGDGKyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR 419
Cdd:cd07869    89 LCQYMDKHPGG-LHPENVKLFLFQLLRGLSYIHQRYILHRDLKPQNLLISDTGELKLADFGLAR 151
SH2_Grb7_family cd09944
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) ...
158-258 1.21e-09

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: 55.50  E-value: 1.21e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 158 WYFGKMGRKDAERLLLNPGNQRGIFLVRESETTKGAYSLSIRdwdeiRGDNVKHYKIRKLDNGGYYITT----RAQFDTL 233
Cdd:cd09944     7 WFHGGISRDEAARLIRQQGLVDGVFLVRESQSNPGAFVLSLK-----HGQKIKHYQIIPIEDEGQWYFTlddgVTKFYDL 81
                          90       100
                  ....*....|....*....|....*
gi 1370473802 234 QKLVKHYTEHADGLCHKLTTVCPTV 258
Cdd:cd09944    82 LQLVEFYQLNAGSLPTRLKHYCTRV 106
SH3_ITK cd11908
Src Homology 3 domain of Interleukin-2-inducible T-cell Kinase; ITK (also known as Tsk or Emt) ...
94-148 1.33e-09

Src Homology 3 domain of Interleukin-2-inducible T-cell Kinase; ITK (also known as Tsk or Emt) is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. 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. 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: 212841 [Multi-domain]  Cd Length: 56  Bit Score: 53.86  E-value: 1.33e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1370473802  94 TIFVALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARSiATGKNGYIPSNYVA 148
Cdd:cd11908     1 TLVIALYDYQTNDPQELALRYNEEYHLLDSSEIHWWRVQD-KNGHEGYVPSSYLV 54
STKc_CRIK cd05601
Catalytic domain of the Serine/Threonine Kinase, Citron Rho-interacting kinase; STKs catalyze ...
280-432 1.37e-09

Catalytic domain of the Serine/Threonine Kinase, Citron Rho-interacting kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CRIK (also called citron kinase) is an effector of the small GTPase Rho. It plays an important function during cytokinesis and affects its contractile process. CRIK-deficient mice show severe ataxia and epilepsy as a result of abnormal cytokinesis and massive apoptosis in neuronal precursors. A Down syndrome critical region protein TTC3 interacts with CRIK and inhibits CRIK-dependent neuronal differentiation and neurite extension. CRIK contains a catalytic domain, a central coiled-coil domain, and a C-terminal region containing a Rho-binding domain (RBD), a zinc finger, and a pleckstrin homology (PH) domain, in addition to other motifs. The CRIK 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: 270752 [Multi-domain]  Cd Length: 328  Bit Score: 59.63  E-value: 1.37e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 280 EVK--LGQGCFGEVWMGTWNGTTKV-AIKTLKPGTMMPEA----FLQEAQIMKKLRHDKLVPL-YAVVSEEPIYIVTEFM 351
Cdd:cd05601     4 EVKnvIGRGHFGEVQVVKEKATGDIyAMKVLKKSETLAQEevsfFEEERDIMAKANSPWITKLqYAFQDSENLYLVMEYH 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 352 SKGSLLDFLKEGDGKYLKlpqlvDMA----AQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFG-LARLIEDNey 426
Cdd:cd05601    84 PGGDLLSLLSRYDDIFEE-----SMArfylAELVLAIHSLHSMGYVHRDIKPENILIDRTGHIKLADFGsAAKLSSDK-- 156

                  ....*.
gi 1370473802 427 TARQGM 432
Cdd:cd05601   157 TVTSKM 162
STKc_MLCK4 cd14193
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze ...
283-419 1.53e-09

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: 58.77  E-value: 1.53e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGT-TKVAIKTLKPGTMM-PEAFLQEAQIMKKLRHDKLVPLY-AVVSEEPIYIVTEFMSKGSLLDF 359
Cdd:cd14193    12 LGGGRFGQVHKCEEKSSgLKLAAKIIKARSQKeKEEVKNEIEVMNQLNHANLIQLYdAFESRNDIVLVMEYVDGGELFDR 91
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370473802 360 LKEGDGKYLKLPQLVDMAaQIADGMAYIERMNYIHRDLRAANILV--GENLVCKIADFGLAR 419
Cdd:cd14193    92 IIDENYNLTELDTILFIK-QICEGIQYMHQMYILHLDLKPENILCvsREANQVKIIDFGLAR 152
STKc_cGK cd05572
Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); ...
283-427 1.71e-09

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: 58.39  E-value: 1.71e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKV-AIKTLKP----GTMMPEAFLQEAQIMKKLRHDKLVPLYAVVS-EEPIYIVTEFMSKGSL 356
Cdd:cd05572     1 LGVGGFGRVELVQLKSKGRTfALKCVKKrhivQTRQQEHIFSEKEILEECNSPFIVKLYRTFKdKKYLYMLMEYCLGGEL 80
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370473802 357 LDFLK------EGDGKYLklpqlvdmAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYT 427
Cdd:cd05572    81 WTILRdrglfdEYTARFY--------TACVVLAFEYLHSRGIIYRDLKPENLLLDSNGYVKLVDFGFAKKLGSGRKT 149
SH2_cSH2_p85_like cd09930
C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
158-247 1.73e-09

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: 55.11  E-value: 1.73e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 158 WYFGKMGRKDAERLLLnpGNQRGIFLVRESeTTKGAYSLSIrdwdeIRGDNVKHYKIRKLDNGGYYITTRAQFDTLQKLV 237
Cdd:cd09930     8 WLVGDINRTQAEELLR--GKPDGTFLIRES-STQGCYACSV-----VCNGEVKHCVIYKTETGYGFAEPYNLYESLKELV 79
                          90
                  ....*....|....*
gi 1370473802 238 KHYT-----EHADGL 247
Cdd:cd09930    80 LHYAhnsleQHNDSL 94
STKc_MRCK_beta cd05624
Catalytic domain of the Protein Serine/Threonine Kinase, DMPK-related cell division control ...
258-444 1.91e-09

Catalytic domain of the Protein Serine/Threonine Kinase, DMPK-related cell division control protein 42 binding kinase (MRCK) beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MRCK-beta is expressed ubiquitously in many tissues. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. The MRCK-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. This alignment model includes the dimerization domain.


Pssm-ID: 270774 [Multi-domain]  Cd Length: 409  Bit Score: 59.64  E-value: 1.91e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 258 VKPQTQgLAKDAwEIPRESLRLEVKLGQGCFGEVWMGTWNGTTKV-AIKTLKPGTMMPEA----FLQEAQIMKKLRHDKL 332
Cdd:cd05624    57 AKPFTQ-LVKEM-QLHRDDFEIIKVIGRGAFGEVAVVKMKNTERIyAMKILNKWEMLKRAetacFREERNVLVNGDCQWI 134
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 333 VPL-YAVVSEEPIYIVTEFMSKGSLLDFLKEGDGKylkLPQlvDMA----AQIADGMAYIERMNYIHRDLRAANILVGEN 407
Cdd:cd05624   135 TTLhYAFQDENYLYLVMDYYVGGDLLTLLSKFEDK---LPE--DMArfyiGEMVLAIHSIHQLHYVHRDIKPDNVLLDMN 209
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 1370473802 408 LVCKIADFG-LARLIEDNEYTARQGM-----VNREVLEQVERG 444
Cdd:cd05624   210 GHIRLADFGsCLKMNDDGTVQSSVAVgtpdyISPEILQAMEDG 252
SH3_Nck_1 cd11765
First Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin ...
97-147 1.92e-09

First Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The first SH3 domain of Nck proteins preferentially binds the PxxDY sequence, which is present in the CD3e cytoplasmic tail. This binding inhibits phosphorylation by Src kinases, resulting in the downregulation of TCR surface expression. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. 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: 212699 [Multi-domain]  Cd Length: 51  Bit Score: 53.19  E-value: 1.92e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1370473802  97 VALYDYEARTTEDLSFKKGERFQIINNTEgDWWEARSiATGKNGYIPSNYV 147
Cdd:cd11765     3 VAKYDYTAQGDQELSIKKNEKLTLLDDSK-HWWKVQN-SSNQTGYVPSNYV 51
STKc_CDK6 cd07862
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 6; STKs ...
282-420 1.97e-09

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: 58.89  E-value: 1.97e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGT--WNGTTKVAIKTLKPGTM---MPEAFLQEAQIMKKLR---HDKLVPLYAVVS------EEPIYIV 347
Cdd:cd07862     8 EIGEGAYGKVFKARdlKNGGRFVALKRVRVQTGeegMPLSTIREVAVLRHLEtfeHPNVVRLFDVCTvsrtdrETKLTLV 87
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370473802 348 TEFMSKgSLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARL 420
Cdd:cd07862    88 FEHVDQ-DLTTYLDKVPEPGVPTETIKDMMFQLLRGLDFLHSHRVVHRDLKPQNILVTSSGQIKLADFGLARI 159
STKc_Kin1_2 cd14077
Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the ...
283-420 2.03e-09

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: 58.23  E-value: 2.03e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGT-TKVAIKTLK---PGTMMPEAFLQ-------------EAQIMKKLRHDKLVPLYAVV-SEEPI 344
Cdd:cd14077     9 IGAGSMGKVKLAKHIRTgEKCAIKIIPrasNAGLKKEREKRlekeisrdirtirEAALSSLLNHPHICRLRDFLrTPNHY 88
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370473802 345 YIVTEFMSKGSLLDFLKEgDGKyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARL 420
Cdd:cd14077    89 YMLFEYVDGGQLLDYIIS-HGK-LKEKQARKFARQIASALDYLHRNSIVHRDLKIENILISKSGNIKIIDFGLSNL 162
STKc_LRRK1 cd14067
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 1; STKs catalyze ...
317-419 2.09e-09

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: 58.44  E-value: 2.09e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 317 FLQEAQIMKKLRHDKLVPLYAVvSEEPIYIVTEFMSKGSLLDFLKEG--DGKYLKLPQLV--DMAAQIADGMAYIERMNY 392
Cdd:cd14067    57 FRQEASMLHSLQHPCIVYLIGI-SIHPLCFALELAPLGSLNTVLEENhkGSSFMPLGHMLtfKIAYQIAAGLAYLHKKNI 135
                          90       100       110
                  ....*....|....*....|....*....|..
gi 1370473802 393 IHRDLRAANILV-----GENLVCKIADFGLAR 419
Cdd:cd14067   136 IFCDLKSDNILVwsldvQEHINIKLSDYGISR 167
SH2_Tec_Bmx cd10399
Src homology 2 (SH2) domain found in Tec protein, Bmx; A member of the Tec protein tyrosine ...
156-257 2.13e-09

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: 54.96  E-value: 2.13e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 156 EEWYFGKMGRKDAERLLLNPGNQrGIFLVRESETTkGAYSLSI-RDWDEIRGDNVKHYKIRKLDNGGYYITTRAQFDTLQ 234
Cdd:cd10399     6 YDWFAGNISRSQSEQLLRQKGKE-GAFMVRNSSQV-GMYTVSLfSKAVNDKKGTVKHYHVHTNAENKLYLAENYCFDSIP 83
                          90       100
                  ....*....|....*....|...
gi 1370473802 235 KLVKHYTEHADGLCHKLTTVCPT 257
Cdd:cd10399    84 KLIHYHQHNSAGMITRLRHPVST 106
STKc_PKN cd05589
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N; STKs catalyze the transfer ...
283-417 2.19e-09

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: 58.85  E-value: 2.19e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKV-AIKTLKPGTMMP----EAFLQEAQIMK---KLRHDKLVPLYAVV-SEEPIYIVTEFMSK 353
Cdd:cd05589     7 LGRGHFGKVLLAEYKPTGELfAIKALKKGDIIArdevESLMCEKRIFEtvnSARHPFLVNLFACFqTPEHVCFVMEYAAG 86
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1370473802 354 GSLL-----DFLKEgdgkylklPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGL 417
Cdd:cd05589    87 GDLMmhiheDVFSE--------PRAVFYAACVVLGLQFLHEHKIVYRDLKLDNLLLDTEGYVKIADFGL 147
STKc_Aurora-A cd14116
Catalytic domain of the Serine/Threonine kinase, Aurora-A kinase; STKs catalyze the transfer ...
283-416 2.56e-09

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: 58.04  E-value: 2.56e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTT-----KVAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEP-IYIVTEFMSKGSL 356
Cdd:cd14116    13 LGKGKFGNVYLAREKQSKfilalKVLFKAQLEKAGVEHQLRREVEIQSHLRHPNILRLYGYFHDATrVYLILEYAPLGTV 92
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370473802 357 LDFLKegdgkylKLPQLVDMAA-----QIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFG 416
Cdd:cd14116    93 YRELQ-------KLSKFDEQRTatyitELANALSYCHSKRVIHRDIKPENLLLGSAGELKIADFG 150
SH3_SH3RF1_3 cd11926
Third Src Homology 3 domain of SH3 domain containing ring finger 1, an E3 ubiquitin-protein ...
95-149 2.57e-09

Third Src Homology 3 domain of SH3 domain containing ring finger 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF1. 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: 212859 [Multi-domain]  Cd Length: 55  Bit Score: 53.05  E-value: 2.57e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1370473802  95 IFVALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARSIATGKNGYIPSNYVAP 149
Cdd:cd11926     1 VYVAIYPYTPRKEDELELRKGEMFLVFERCQDGWFKGTSMHTSKIGVFPGNYVAP 55
SH3_2 pfam07653
Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in ...
96-149 2.82e-09

Variant 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: 429575 [Multi-domain]  Cd Length: 54  Bit Score: 52.98  E-value: 2.82e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1370473802  96 FVALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARSIatGKNGYIPSNYVAP 149
Cdd:pfam07653   2 GRVIFDYVGTDKNGLTLKKGDVVKVLGKDNDGWWEGETG--GRVGLVPSTAVEE 53
STKc_MPK1 cd07857
Catalytic domain of the Serine/Threonine Kinase, Fungal Mitogen-Activated Protein Kinase MPK1; ...
282-448 2.89e-09

Catalytic domain of the Serine/Threonine Kinase, Fungal Mitogen-Activated Protein Kinase MPK1; 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 MPK1 from Saccharomyces cerevisiae, Pmk1 from Schizosaccharomyces pombe, and similar proteins. MPK1 (also called Slt2) and Pmk1 (also called Spm1) are stress-activated MAPKs that regulate the cell wall integrity pathway, and are therefore important in the maintainance of cell shape, cell wall construction, morphogenesis, and ion homeostasis. MPK1 is activated in response to cell wall stress including heat stimulation, osmotic shock, UV irradiation, and any agents that interfere with cell wall biogenesis such as chitin antagonists, caffeine, or zymolase. MPK1 is regulated by the MAP2Ks Mkk1/2, which are regulated by the MAP3K Bck1. Pmk1 is also activated by multiple stresses including elevated temperatures, hyper- or hypotonic stress, glucose deprivation, exposure to cell-wall damaging compounds, and oxidative stress. It is regulated by the MAP2K Pek1, which is regulated by the MAP3K Mkh1. MAPKs are important mediators of cellular responses to extracellular signals. The MPK1 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: 173750 [Multi-domain]  Cd Length: 332  Bit Score: 58.57  E-value: 2.89e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGT---TKVAIKTLK---PGTMMPEAFLQEAQIMKKLR-HDKLVPLY--AVVSEEP---IYIVTE 349
Cdd:cd07857     7 ELGQGAYGIVCSARNAETseeETVAIKKITnvfSKKILAKRALRELKLLRHFRgHKNITCLYdmDIVFPGNfneLYLYEE 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 350 FMsKGSLLDFLKEGDgkylklpQLVD-----MAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDN 424
Cdd:cd07857    87 LM-EADLHQIIRSGQ-------PLTDahfqsFIYQILCGLKYIHSANVLHRDLKPGNLLVNADCELKICDFGLARGFSEN 158
                         170       180
                  ....*....|....*....|....*
gi 1370473802 425 eytarQGMVNREVLEQV-ERGYRMP 448
Cdd:cd07857   159 -----PGENAGFMTEYVaTRWYRAP 178
STKc_CK2_alpha cd14132
Catalytic subunit (alpha) of the Serine/Threonine Kinase, Casein Kinase 2; STKs catalyze the ...
268-418 2.90e-09

Catalytic subunit (alpha) of the Serine/Threonine Kinase, Casein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK2 is a tetrameric protein with two catalytic (alpha) and two regulatory (beta) subunits. It is constitutively active and ubiquitously expressed, and is found in the cytoplasm, nucleus, as well as in the plasma membrane. It phosphorylates a wide variety of substrates including gylcogen synthase, cell cycle proteins, nuclear proteins (e.g. DNA topoisomerase II), and ion channels (e.g. ENaC), among others. It may be considered a master kinase controlling the activity or lifespan of many other kinases and exerting its effect over cell fate, gene expression, protein synthesis and degradation, and viral infection. CK2 is implicated in every stage of the cell cycle and is required for cell cycle progression. It plays crucial roles in cell differentiation, proliferation, and survival, and is thus implicated in cancer. CK2 is not an oncogene by itself but elevated CK2 levels create an environment that enhances the survival of tumor cells. The CK2 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: 271034 [Multi-domain]  Cd Length: 306  Bit Score: 58.32  E-value: 2.90e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 268 DAWEIPRESL-RLEV--KLGQGCFGEVWMGtWNGTT--KVAIKTLKPgtMMPEAFLQEAQIMKKLR-HDKLVPLYAVV-- 339
Cdd:cd14132     8 ENLNVEWGSQdDYEIirKIGRGKYSEVFEG-INIGNneKVVIKVLKP--VKKKKIKREIKILQNLRgGPNIVKLLDVVkd 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 340 -SEEPIYIVTEFMSKgslLDFlkegdgKYLkLPQLVDMAA-----QIADGMAYIERMNYIHRDLRAANILVG-ENLVCKI 412
Cdd:cd14132    85 pQSKTPSLIFEYVNN---TDF------KTL-YPTLTDYDIryymyELLKALDYCHSKGIMHRDVKPHNIMIDhEKRKLRL 154

                  ....*.
gi 1370473802 413 ADFGLA 418
Cdd:cd14132   155 IDWGLA 160
STKc_myosinIIIA_N cd06638
N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIA myosin; STKs catalyze ...
268-418 2.95e-09

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: 58.10  E-value: 2.95e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 268 DAWEIPReslrlevKLGQGCFGEVW--MGTWNGTtKVAIKTLKPGTMMPEAFLQEAQIMKKLR-HDKLVPLYA------V 338
Cdd:cd06638    18 DTWEIIE-------TIGKGTYGKVFkvLNKKNGS-KAAVKILDPIHDIDEEIEAEYNILKALSdHPNVVKFYGmyykkdV 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 339 VSEEPIYIVTEFMSKGSLLD----FLKEGDgkYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIAD 414
Cdd:cd06638    90 KNGDQLWLVLELCNGGSVTDlvkgFLKRGE--RMEEPIIAYILHEALMGLQHLHVNKTIHRDVKGNNILLTTEGGVKLVD 167

                  ....
gi 1370473802 415 FGLA 418
Cdd:cd06638   168 FGVS 171
STKc_RSK_C cd14091
C-terminal catalytic domain of the Serine/Threonine Kinases, Ribosomal S6 kinases; STKs ...
282-449 3.00e-09

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: 58.03  E-value: 3.00e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGTTKV-AIKTLKPGTMMPEaflQEAQIMkkLR---HDKLVPLYAVVSEEP-IYIVTEFMSKGSL 356
Cdd:cd14091     7 EIGKGSYSVCKRCIHKATGKEyAVKIIDKSKRDPS---EEIEIL--LRygqHPNIITLRDVYDDGNsVYLVTELLRGGEL 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 357 LDflkegdgKYLKLPQLVDMAAQ-----IADGMAYIERMNYIHRDLRAANILVG------ENLvcKIADFGLAR-LIEDN 424
Cdd:cd14091    82 LD-------RILRQKFFSEREASavmktLTKTVEYLHSQGVVHRDLKPSNILYAdesgdpESL--RICDFGFAKqLRAEN 152
                         170       180       190
                  ....*....|....*....|....*....|.
gi 1370473802 425 E------YTARqgMVNREVLEQveRGYRMPC 449
Cdd:cd14091   153 GllmtpcYTAN--FVAPEVLKK--QGYDAAC 179
STKc_MEKK1 cd06630
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
315-418 3.14e-09

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: 57.82  E-value: 3.14e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 315 EAFLQEAQIMKKLRHDKLVPLYAVVSEEPIY-IVTEFMSKGSLLDFLKegdgKYLKLPQLVDMA--AQIADGMAYIERMN 391
Cdd:cd06630    48 EAIREEIRMMARLNHPNIVRMLGATQHKSHFnIFVEWMAGGSVASLLS----KYGAFSENVIINytLQILRGLAYLHDNQ 123
                          90       100       110
                  ....*....|....*....|....*....|
gi 1370473802 392 YIHRDLRAANILV---GENLvcKIADFGLA 418
Cdd:cd06630   124 IIHRDLKGANLLVdstGQRL--RIADFGAA 151
SH3_MyoIe_If_like cd11827
Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If ...
98-147 3.27e-09

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (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: 212761 [Multi-domain]  Cd Length: 53  Bit Score: 52.80  E-value: 3.27e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1370473802  98 ALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARsiATGKNGYIPSNYV 147
Cdd:cd11827     4 ALYAYDAQDTDELSFNEGDIIEILKEDPSGWWTGR--LRGKEGLFPGNYV 51
STKc_MRCK_alpha cd05623
Catalytic domain of the Serine/Threonine Kinase, DMPK-related cell division control protein 42 ...
274-444 3.28e-09

Catalytic domain of the Serine/Threonine Kinase, DMPK-related cell division control protein 42 binding kinase (MRCK) alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MRCK-alpha is expressed ubiquitously in many tissues. It plays a role in the regulation of peripheral actin reorganization and neurite outgrowth. It may also play a role in the transferrin iron uptake pathway. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. The MRCK-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. This alignment model includes the dimerization domain.


Pssm-ID: 270773 [Multi-domain]  Cd Length: 409  Bit Score: 58.87  E-value: 3.28e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 274 RESLRLEVKLGQGCFGEVWMGTWNGTTKV-AIKTLKPGTMMPEA----FLQEAQIMKKLRHDKLVPL-YAVVSEEPIYIV 347
Cdd:cd05623    71 KEDFEILKVIGRGAFGEVAVVKLKNADKVfAMKILNKWEMLKRAetacFREERDVLVNGDSQWITTLhYAFQDDNNLYLV 150
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 348 TEFMSKGSLLDFLKEGDGKylkLPQlvDMA----AQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFG-LARLIE 422
Cdd:cd05623   151 MDYYVGGDLLTLLSKFEDR---LPE--DMArfylAEMVLAIDSVHQLHYVHRDIKPDNILMDMNGHIRLADFGsCLKLME 225
                         170       180
                  ....*....|....*....|....*..
gi 1370473802 423 DNEYTARQGM-----VNREVLEQVERG 444
Cdd:cd05623   226 DGTVQSSVAVgtpdyISPEILQAMEDG 252
STKc_CdkB_plant cd07837
Catalytic domain of the Serine/Threonine Kinase, Plant B-type Cyclin-Dependent protein Kinase; ...
268-419 3.36e-09

Catalytic domain of the Serine/Threonine Kinase, 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. 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 CdkB 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: 270830 [Multi-domain]  Cd Length: 294  Bit Score: 57.92  E-value: 3.36e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 268 DAWEipreslRLEvKLGQGCFGEVWMGTWNGTTK-VAIKTLK---PGTMMPEAFLQEAQIMKKLRHD-KLVPLYAV--VS 340
Cdd:cd07837     1 DAYE------KLE-KIGEGTYGKVYKARDKNTGKlVALKKTRlemEEEGVPSTALREVSLLQMLSQSiYIVRLLDVehVE 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 341 EEP---IYIVTEFMSKG--SLLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVG-ENLVCKIAD 414
Cdd:cd07837    74 ENGkplLYLVFEYLDTDlkKFIDSYGRGPHNPLPAKTIQSFMYQLCKGVAHCHSHGVMHRDLKPQNLLVDkQKGLLKIAD 153

                  ....*
gi 1370473802 415 FGLAR 419
Cdd:cd07837   154 LGLGR 158
STKc_Sid2p_like cd05600
Catalytic domain of Fungal Sid2p-like Protein Serine/Threonine Kinases; STKs catalyze the ...
281-419 3.36e-09

Catalytic domain of Fungal Sid2p-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This group contains fungal kinases including Schizosaccharomyces pombe Sid2p and Saccharomyces cerevisiae Dbf2p. Group members show similarity to NDR kinases in that they contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Sid2p plays a crucial role in the septum initiation network (SIN) and in the initiation of cytokinesis. Dbf2p is important in regulating the mitotic exit network (MEN) and in cytokinesis. The Sid2p-like group 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: 270751 [Multi-domain]  Cd Length: 386  Bit Score: 58.50  E-value: 3.36e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 281 VKLGQGCFGEVWMGTWNGTTK-VAIKTLKPGTM--MPEA--FLQEAQIMKKLRHDKLVPL-YAVVSEEPIYIVTEFMSKG 354
Cdd:cd05600    17 TQVGQGGYGSVFLARKKDTGEiCALKIMKKKVLfkLNEVnhVLTERDILTTTNSPWLVKLlYAFQDPENVYLAMEYVPGG 96
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370473802 355 sllDF---------LKEGDGKYLklpqLVDMAAQIADgmayIERMNYIHRDLRAANILVGENLVCKIADFGLAR 419
Cdd:cd05600    97 ---DFrtllnnsgiLSEEHARFY----IAEMFAAISS----LHQLGYIHRDLKPENFLIDSSGHIKLTDFGLAS 159
STKc_CNK2-like cd08530
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar ...
282-424 3.54e-09

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: 57.40  E-value: 3.54e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGTTKV-AIKTLKPGTMMP---EAFLQEAQIMKKLRHDKLVPLY-AVVSEEPIYIVTEFMSKGSL 356
Cdd:cd08530     7 KLGKGSYGSVYKVKRLSDNQVyALKEVNLGSLSQkerEDSVNEIRLLASVNHPNIIRYKeAFLDGNRLCIVMEYAPFGDL 86
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370473802 357 LDFLKEGDGKYLKLPQlvDM----AAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDN 424
Cdd:cd08530    87 SKLISKRKKKRRLFPE--DDiwriFIQMLRGLKALHDQKILHRDLKSANILLSAGDLVKIGDLGISKVLKKN 156
STKc_MSK_C cd14092
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
319-425 3.59e-09

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: 58.08  E-value: 3.59e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 319 QEAQIMKKLR-HDKLVPLYAVVSEE-PIYIVTEFMSKGSLLDFLKegdgkylKLPQLVDMAA-----QIADGMAYIERMN 391
Cdd:cd14092    47 REVQLLRLCQgHPNIVKLHEVFQDElHTYLVMELLRGGELLERIR-------KKKRFTESEAsrimrQLVSAVSFMHSKG 119
                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1370473802 392 YIHRDLRAANILV---GENLVCKIADFGLARLIEDNE 425
Cdd:cd14092   120 VVHRDLKPENLLFtdeDDDAEIKIVDFGFARLKPENQ 156
STKc_PAK_I cd06647
Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze ...
273-433 3.61e-09

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: 57.63  E-value: 3.61e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 273 PRESLRLEVKLGQGCFGEVWMGTWNGT-TKVAIKTL----KPGTmmpEAFLQEAQIMKKLRHDKLVPLYA--VVSEEpIY 345
Cdd:cd06647     5 PKKKYTRFEKIGQGASGTVYTAIDVATgQEVAIKQMnlqqQPKK---ELIINEILVMRENKNPNIVNYLDsyLVGDE-LW 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 346 IVTEFMSKGSLLDFLKEgdgKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDnE 425
Cdd:cd06647    81 VVMEYLAGGSLTDVVTE---TCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITP-E 156

                  ....*...
gi 1370473802 426 YTARQGMV 433
Cdd:cd06647   157 QSKRSTMV 164
STKc_PLK3 cd14189
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the ...
283-425 3.63e-09

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: 57.63  E-value: 3.63e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKV-AIKTL------KPgtMMPEAFLQEAQIMKKLRHDKLVPL-YAVVSEEPIYIVTEFMSKG 354
Cdd:cd14189     9 LGKGGFARCYEMTDLATNKTyAVKVIphsrvaKP--HQREKIVNEIELHRDLHHKHVVKFsHHFEDAENIYIFLELCSRK 86
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370473802 355 SLLDFLKEGdgKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNE 425
Cdd:cd14189    87 SLAHIWKAR--HTLLEPEVRYYLKQIISGLKYLHLKGILHRDLKLGNFFINENMELKVGDFGLAARLEPPE 155
STKc_PKA cd14209
Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze ...
283-427 3.78e-09

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: 57.80  E-value: 3.78e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTK-VAIKTLKPGTMMP----EAFLQEAQIMKKLRHDKLVPL-YAVVSEEPIYIVTEFMSKGSL 356
Cdd:cd14209     9 LGTGSFGRVMLVRHKETGNyYAMKILDKQKVVKlkqvEHTLNEKRILQAINFPFLVKLeYSFKDNSNLYMVMEYVPGGEM 88
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370473802 357 LDFLKEgDGKYLKlPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYT 427
Cdd:cd14209    89 FSHLRR-IGRFSE-PHARFYAAQIVLAFEYLHSLDLIYRDLKPENLLIDQQGYIKVTDFGFAKRVKGRTWT 157
SH3_SH3YL1_like cd11841
Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes ...
98-148 3.79e-09

Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes to the plasma membrane and is required for dorsal ruffle formation. It binds phosphoinositides (PIs) with high affinity through its N-terminal SYLF domain (also called DUF500). In addition, SH3YL1 contains a C-terminal SH3 domain which has been reported to bind to N-WASP, dynamin 2, and SHIP2 (a PI 5-phosphatase). 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: 212775  Cd Length: 54  Bit Score: 52.39  E-value: 3.79e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1370473802  98 ALYDYEARTTEDLSFKKGERFQIINNT--EGDWWEARsiATGKNGYIPSNYVA 148
Cdd:cd11841     4 ALYSFEGQQPCDLSFQAGDRITVLTRTdsQFDWWEGR--LRGRVGIFPANYVS 54
SH2_SH2D7 cd10417
Src homology 2 domain found in the SH2 domain containing protein 7 (SH2D7); SH2D7 contains a ...
158-256 3.91e-09

Src homology 2 domain found in the SH2 domain containing protein 7 (SH2D7); SH2D7 contains a single 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: 199832  Cd Length: 102  Bit Score: 54.13  E-value: 3.91e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 158 WYFGKMGRKDAERLLLNpgNQRGIFLVRESETTKGaYSLSIRDWDEIRgdnvkHYKIRKLDNGGYYITTRAQ-FDTLQKL 236
Cdd:cd10417     9 WFHGFITRKQTEQLLRD--KALGSFLIRLSDRATG-YILSYRGSDRCR-----HFVINQLRNRRYLISGDTSsHSTLAEL 80
                          90       100
                  ....*....|....*....|.
gi 1370473802 237 VKHYTEHADG-LCHKLTTVCP 256
Cdd:cd10417    81 VRHYQEVQLEpFGETLTAACP 101
STKc_CaMKIV cd14085
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
279-423 3.94e-09

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: 57.91  E-value: 3.94e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 279 LEVKLGQGCFGEVWMGTWNGTTK-VAIKTLKPgTMMPEAFLQEAQIMKKLRHD---KLVPLYAVVSEepIYIVTEFMSKG 354
Cdd:cd14085     7 IESELGRGATSVVYRCRQKGTQKpYAVKKLKK-TVDKKIVRTEIGVLLRLSHPniiKLKEIFETPTE--ISLVLELVTGG 83
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370473802 355 SLLDFLKEGDgkYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILV---GENLVCKIADFGLARLIED 423
Cdd:cd14085    84 ELFDRIVEKG--YYSERDAADAVKQILEAVAYLHENGIVHRDLKPENLLYatpAPDAPLKIADFGLSKIVDQ 153
SH3_Intersectin2_5 cd11996
Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
97-147 3.95e-09

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. 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: 212929 [Multi-domain]  Cd Length: 54  Bit Score: 52.68  E-value: 3.95e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1370473802  97 VALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARsiATGKNGYIPSNYV 147
Cdd:cd11996     4 IAMYDYTANNEDELSFSKGQLINVLNKDDPDWWQGE--INGVTGLFPSNYV 52
STKc_cPKC_beta cd05616
Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C beta; STKs ...
283-419 3.97e-09

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: 58.09  E-value: 3.97e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKV-AIKTLKPGTMMPEAFLQEAQIMKKL-----RHDKLVPLYAVV-SEEPIYIVTEFMSKGS 355
Cdd:cd05616     8 LGKGSFGKVMLAERKGTDELyAVKILKKDVVIQDDDVECTMVEKRVlalsgKPPFLTQLHSCFqTMDRLYFVMEYVNGGD 87
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370473802 356 LLDFLKEGdGKYlKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR 419
Cdd:cd05616    88 LMYHIQQV-GRF-KEPHAVFYAAEIAIGLFFLQSKGIIYRDLKLDNVMLDSEGHIKIADFGMCK 149
SH3_p47phox_like cd11856
Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This ...
95-149 4.37e-09

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: 52.25  E-value: 4.37e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1370473802  95 IFVALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARsiATGKNGYIPSNYVAP 149
Cdd:cd11856     1 SYVAIADYEAQGDDEISLQEGEVVEVLEKNDSGWWYVR--KGDKEGWVPASYLEP 53
STKc_nPKC_theta cd05619
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze ...
275-419 4.50e-09

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: 58.01  E-value: 4.50e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 275 ESLRLEVKLGQGCFGEVWMGTWNGTTK-VAIKTLKPGTMMPEAFLQEAQIMKKL-----RHDKLVPLYAVV-SEEPIYIV 347
Cdd:cd05619     5 EDFVLHKMLGKGSFGKVFLAELKGTNQfFAIKALKKDVVLMDDDVECTMVEKRVlslawEHPFLTHLFCTFqTKENLFFV 84
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370473802 348 TEFMSKGSLLdFLKEGDGKYlKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR 419
Cdd:cd05619    85 MEYLNGGDLM-FHIQSCHKF-DLPRATFYAAEIICGLQFLHSKGIVYRDLKLDNILLDKDGHIKIADFGMCK 154
STKc_Nek1 cd08218
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
282-486 4.65e-09

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: 57.13  E-value: 4.65e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGE-VWMGTWNGTTKVAIKTLKPGTMMP---EAFLQEAQIMKKLRHDKLVPlYAVVSEE--PIYIVTEFMSKGS 355
Cdd:cd08218     7 KIGEGSFGKaLLVKSKEDGKQYVIKEINISKMSPkerEESRKEVAVLSKMKHPNIVQ-YQESFEEngNLYIVMDYCDGGD 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 356 LLDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEYTARQ----- 430
Cdd:cd08218    86 LYKRINAQRGVLFPEDQILDWFVQLCLALKHVHDRKILHRDIKSQNIFLTKDGIIKLGDFGIARVLNSTVELARTcigtp 165
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 431 ----------------------GMVNREVLE---------------QVERGYRMPCPQGCPESLHELMNLCWKKDPDERP 473
Cdd:cd08218   166 yylspeicenkpynnksdiwalGCVLYEMCTlkhafeagnmknlvlKIIRGSYPPVPSRYSYDLRSLVSQLFKRNPRDRP 245
                         250
                  ....*....|...
gi 1370473802 474 TfeyIQSFLEDYF 486
Cdd:cd08218   246 S---INSILEKPF 255
SH3_SLAP cd12010
Src homology 3 domain of Src-Like Adaptor Protein; SLAP (or SLA1) modulates TCR surface ...
97-148 4.73e-09

Src homology 3 domain of Src-Like Adaptor Protein; SLAP (or SLA1) modulates TCR surface expression levels as well as surface and total BCR levels. As an adaptor to c-Cbl, SLAP increases the ubiquitination, intracellular retention, and targeted degradation of the BCR complex components. SLAP has been shown to interact with the EphA receptor, EpoR, Lck, PDGFR, Syk, CD79a, c-Cbl, LAT, CD247, and Zap70, among others. SLAPs are adaptor proteins with limited similarity to Src family tyrosine kinases. They contain an N-terminal SH3 domain followed by an SH2 domain, and a unique C-terminal sequence. The SH3 domain of SLAP forms a complex with v-Abl. 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: 212943  Cd Length: 55  Bit Score: 52.12  E-value: 4.73e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1370473802  97 VALYDYEARTTEDLSFKKGERFQIINNtEGDWWEARSIATGKNGYIPSNYVA 148
Cdd:cd12010     3 AVLADYPSPDISEPIFHMGEKLRVLSD-EGGWWKVRSLQTGRENYIPGKCVA 53
SH3_SH3RF_3 cd11783
Third Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and ...
95-149 4.77e-09

Third Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. 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: 212717 [Multi-domain]  Cd Length: 55  Bit Score: 52.40  E-value: 4.77e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1370473802  95 IFVALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARSIATGKNGYIPSNYVAP 149
Cdd:cd11783     1 IYVALYPYKPQKPDELELRKGEMYTVTEKCQDGWFKGTSLRTGQSGVFPGNYVQP 55
STKc_KSR1 cd14152
Catalytic domain of the Serine/Threonine Kinase, Kinase Suppressor of Ras 1; STKs catalyze the ...
283-417 5.43e-09

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: 57.29  E-value: 5.43e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGttKVAIKTLK-PGTMMPEAFLQEAQIM--KKLRHDKLVPLYAVVSEEP-IYIVTEFMSKGSLLD 358
Cdd:cd14152     8 IGQGRWGKVHRGRWHG--EVAIRLLEiDGNNQDHLKLFKKEVMnyRQTRHENVVLFMGACMHPPhLAIITSFCKGRTLYS 85
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1370473802 359 FLKEGDGKyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCkIADFGL 417
Cdd:cd14152    86 FVRDPKTS-LDINKTRQIAQEIIKGMGYLHAKGIVHKDLKSKNVFYDNGKVV-ITDFGL 142
pknD PRK13184
serine/threonine-protein kinase PknD;
282-425 5.56e-09

serine/threonine-protein kinase PknD;


Pssm-ID: 183880 [Multi-domain]  Cd Length: 932  Bit Score: 58.63  E-value: 5.56e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMG-TWNGTTKVAIKT----LKPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSE-EPIYIVTEFMSKGS 355
Cdd:PRK13184    9 LIGKGGMGEVYLAyDPVCSRRVALKKiredLSENPLLKKRFLREAKIAADLIHPGIVPVYSICSDgDPVYYTMPYIEGYT 88
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1370473802 356 LLDFLK-----EGDGKYL----KLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNE 425
Cdd:PRK13184   89 LKSLLKsvwqkESLSKELaektSVGAFLSIFHKICATIEYVHSKGVLHRDLKPDNILLGLFGEVVILDWGAAIFKKLEE 167
STKc_WNK1 cd14030
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 1; STKs catalyze ...
277-420 6.67e-09

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: 56.98  E-value: 6.67e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 277 LRLEVKLGQGCFGEVWMGTWNGTT-KVA---IKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPLY-----AVVSEEPIYIV 347
Cdd:cd14030    27 LKFDIEIGRGSFKTVYKGLDTETTvEVAwceLQDRKLSKSERQRFKEEAGMLKGLQHPNIVRFYdswesTVKGKKCIVLV 106
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370473802 348 TEFMSKGSLLDFLKEgdGKYLKLPQLVDMAAQIADGMAYIERMN--YIHRDLRAANILV-GENLVCKIADFGLARL 420
Cdd:cd14030   107 TELMTSGTLKTYLKR--FKVMKIKVLRSWCRQILKGLQFLHTRTppIIHRDLKCDNIFItGPTGSVKIGDLGLATL 180
STKc_DAPK1 cd14194
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 1; STKs ...
319-426 6.94e-09

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: 56.95  E-value: 6.94e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 319 QEAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFMSKGSLLDFLKEGDGkyLKLPQLVDMAAQIADGMAYIERMNYIHRDL 397
Cdd:cd14194    57 REVSILKEIQHPNVITLHEVYeNKTDVILILELVAGGELFDFLAEKES--LTEEEATEFLKQILNGVYYLHSLQIAHFDL 134
                          90       100       110
                  ....*....|....*....|....*....|....
gi 1370473802 398 RAANILVGENLV----CKIADFGLARLIE-DNEY 426
Cdd:cd14194   135 KPENIMLLDRNVpkprIKIIDFGLAHKIDfGNEF 168
PK_STRAD cd08216
Pseudokinase domain of STE20-related kinase adapter protein; The pseudokinase domain shows ...
317-465 7.35e-09

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: 57.30  E-value: 7.35e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 317 FLQEAQIMKKLRHDKLVPLYAV-VSEEPIYIVTEFMSKGSLLDFLKE--GDGkylkLPQLVdmAAQI----ADGMAYIER 389
Cdd:cd08216    46 LQQEILTSRQLQHPNILPYVTSfVVDNDLYVVTPLMAYGSCRDLLKThfPEG----LPELA--IAFIlrdvLNALEYIHS 119
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370473802 390 MNYIHRDLRAANILV-GENLVCkIADFglarliedneytarqgmvnREVLEQVERGYRMPCPQGCPEslHELMNLCW 465
Cdd:cd08216   120 KGYIHRSVKASHILIsGDGKVV-LSGL-------------------RYAYSMVKHGKRQRVVHDFPK--SSEKNLPW 174
STKc_PKC cd05570
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer ...
283-419 7.36e-09

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: 57.22  E-value: 7.36e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKV-AIKTLKPGTMMP----EAFLQEAQIMKK-LRHDKLVPLYAVV-SEEPIYIVTEFMSKGS 355
Cdd:cd05570     3 LGKGSFGKVMLAERKKTDELyAIKVLKKEVIIEdddvECTMTEKRVLALaNRHPFLTGLHACFqTEDRLYFVMEYVNGGD 82
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370473802 356 LLdFLKEGDGKYlKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR 419
Cdd:cd05570    83 LM-FHIQRARRF-TEERARFYAAEICLALQFLHERGIIYRDLKLDNVLLDAEGHIKIADFGMCK 144
SH3_p67phox_C cd12046
C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, ...
97-149 8.82e-09

C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, also called Neutrophil cytosol factor 2 (NCF-2), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox plays a regulatory role and contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. It binds, via its C-terminal SH3 domain, to a proline-rich region of p47phox and upon activation, this complex assembles with flavocytochrome b558, the Nox2-p22phox heterodimer. Concurrently, RacGTP translocates to the membrane and interacts with the TPR domain of p67phox, which leads to the activation of NADPH oxidase. The PB1 domain of p67phox binds to its partner PB1 domain in p40phox, and this facilitates the assembly of p47phox-p67phox at the membrane. 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: 212979 [Multi-domain]  Cd Length: 53  Bit Score: 51.34  E-value: 8.82e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1370473802  97 VALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARSiaTGKNGYIPSNYVAP 149
Cdd:cd12046     3 VALFSYEASQPEDLEFQKGDVILVLSKVNEDWLEGQC--KGKIGIFPSAFVED 53
SH3_Eps8 cd11764
Src Homology 3 domain of Epidermal growth factor receptor kinase substrate 8 and similar ...
99-149 9.09e-09

Src Homology 3 domain of Epidermal growth factor receptor kinase substrate 8 and similar proteins; This group is composed of Eps8 and Eps8-like proteins including Eps8-like 1-3, among others. These proteins contain N-terminal Phosphotyrosine-binding (PTB), central SH3, and C-terminal effector domains. Eps8 binds either Abi1 (also called E3b1) or Rab5 GTPase activating protein RN-tre through its SH3 domain. With Abi1 and Sos1, it becomes part of a trimeric complex that is required to activate Rac. Together with RN-tre, it inhibits the internalization of EGFR. The SH3 domains of Eps8 and similar proteins recognize peptides containing a PxxDY motif, instead of the classical PxxP motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity. 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: 212698 [Multi-domain]  Cd Length: 54  Bit Score: 51.49  E-value: 9.09e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1370473802  99 LYDYEARTTEDLSFKKGERFQIINNTeGDWWEARSIAtGKNGYIPSNYVAP 149
Cdd:cd11764     5 LYDFTARNSKELSVLKGEYLEVLDDS-RQWWKVRNSR-GQVGYVPHNILEP 53
STKc_SBK1 cd13987
Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the ...
283-427 9.77e-09

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: 56.18  E-value: 9.77e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGT-TKVAIKTLKPGTMMPEAFLQEAQIMKKLR-HDKLVPLYAVVSEEPIYIV--TEFMSKGSLLD 358
Cdd:cd13987     1 LGEGTYGKVLLAVHKGSgTKMALKFVPKPSTKLKDFLREYNISLELSvHPHIIKTYDVAFETEDYYVfaQEYAPYGDLFS 80
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370473802 359 FLKEGDGkylkLPQLV--DMAAQIADGMAYIERMNYIHRDLRAANILV--GENLVCKIADFGLAR----LIEDNEYT 427
Cdd:cd13987    81 IIPPQVG----LPEERvkRCAAQLASALDFMHSKNLVHRDIKPENVLLfdKDCRRVKLCDFGLTRrvgsTVKRVSGT 153
STKc_TSSK3-like cd14163
Catalytic domain of testis-specific serine/threonine kinase 3 and similar proteins; STKs ...
301-424 1.09e-08

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: 56.15  E-value: 1.09e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 301 KVAIKTL-KPGTmmPEAFLQ-----EAQIMKKLRHDKLVPLYAVV--SEEPIYIVTEFMSKGSLLDF------LKEGDGK 366
Cdd:cd14163    27 KVAIKIIdKSGG--PEEFIQrflprELQIVERLDHKNIIHVYEMLesADGKIYLVMELAEDGDVFDCvlhggpLPEHRAK 104
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1370473802 367 YLKLpqlvdmaaQIADGMAYIERMNYIHRDLRAANILV-GENLvcKIADFGLARLIEDN 424
Cdd:cd14163   105 ALFR--------QLVEAIRYCHGCGVAHRDLKCENALLqGFTL--KLTDFGFAKQLPKG 153
SH3_Nebulin_family_C cd11789
C-terminal Src Homology 3 domain of the Nebulin family of proteins; Nebulin family proteins ...
96-149 1.09e-08

C-terminal Src Homology 3 domain of the Nebulin family of proteins; Nebulin family proteins contain multiple nebulin repeats, and may contain an N-terminal LIM domain and/or a C-terminal SH3 domain. They have molecular weights ranging from 34 to 900 kD, depending on the number of nebulin repeats, and they all bind actin. They are involved in the regulation of actin filament architecture and function as stabilizers and scaffolds for cytoskeletal structures with which they associate, such as long actin filaments or focal adhesions. Nebulin family proteins that contain a C-terminal SH3 domain include the giant filamentous protein nebulin, nebulette, Lasp1, and Lasp2. Lasp2, also called LIM-nebulette, is an alternatively spliced variant of nebulette. 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: 212723 [Multi-domain]  Cd Length: 55  Bit Score: 51.16  E-value: 1.09e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1370473802  96 FVALYDYEARTTEDLSFKKGErfQIINNTEGD--WWEARSIATGKNGYIPSNYVAP 149
Cdd:cd11789     2 YRAMYDYAAADDDEVSFQEGD--VIINVEIIDdgWMEGTVQRTGQSGMLPANYVEL 55
STKc_Nek7 cd08229
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
256-480 1.14e-08

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: 56.58  E-value: 1.14e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 256 PTVKPQtQGLAKDAWEIPRESLRLEVKLGQGCFGEVWMGTWN-GTTKVAIKTLKPGTMMP----EAFLQEAQIMKKLRHD 330
Cdd:cd08229     6 PQFQPQ-KALRPDMGYNTLANFRIEKKIGRGQFSEVYRATCLlDGVPVALKKVQIFDLMDakarADCIKEIDLLKQLNHP 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 331 KLVPLYA-VVSEEPIYIVTEFMSKGSLLDFLKEGDGKYLKLPQ--LVDMAAQIADGMAYIERMNYIHRDLRAANILVGEN 407
Cdd:cd08229    85 NVIKYYAsFIEDNELNIVLELADAGDLSRMIKHFKKQKRLIPEktVWKYFVQLCSALEHMHSRRVMHRDIKPANVFITAT 164
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 408 LVCKIADFGLARLIEdNEYTARQGMVNREVLEQVER----GYRM------------------------------------ 447
Cdd:cd08229   165 GVVKLGDLGLGRFFS-SKTTAAHSLVGTPYYMSPERihenGYNFksdiwslgcllyemaalqspfygdkmnlyslckkie 243
                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 1370473802 448 -----PCPQG-CPESLHELMNLCWKKDPDERPTFEYIQS 480
Cdd:cd08229   244 qcdypPLPSDhYSEELRQLVNMCINPDPEKRPDITYVYD 282
SH3_DNMBP_C2 cd12141
Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and ...
95-147 1.20e-08

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. 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: 213017 [Multi-domain]  Cd Length: 57  Bit Score: 51.35  E-value: 1.20e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1370473802  95 IFVALYDYEARTTEDLSFKKGERFQIIN----NTEGDWWEARsiATGKNGYIPSNYV 147
Cdd:cd12141     1 VYYAVYTFKARSPNELSVSANQRVRILEfsdlTGNKEWWLAE--ANGQKGYVPSNYI 55
SH3_Sla1p_2 cd11774
Second Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates ...
98-147 1.24e-08

Second Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. 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: 212708 [Multi-domain]  Cd Length: 52  Bit Score: 50.93  E-value: 1.24e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1370473802  98 ALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARSIATgKNGYIPSNYV 147
Cdd:cd11774     4 ALYDYDKQTEEELSFNEGDTLDVYDDSDSDWILVGFNGT-QFGFVPANYI 52
STKc_NAK1_like cd06917
Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of ...
278-433 1.30e-08

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: 55.94  E-value: 1.30e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 278 RLEVkLGQGCFGEVWMGTWNGTTK-VAIKTLKPGTMMPEA--FLQEAQIMKKLRHDK---LVPLYAVVSEEP-IYIVTEF 350
Cdd:cd06917     5 RLEL-VGRGSYGAVYRGYHVKTGRvVALKVLNLDTDDDDVsdIQKEVALLSQLKLGQpknIIKYYGSYLKGPsLWIIMDY 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 351 MSKGSLLDFLKEG--DGKYLKLpqlvdMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNEyTA 428
Cdd:cd06917    84 CEGGSIRTLMRAGpiAERYIAV-----IMREVLVALKFIHKDGIIHRDIKAANILVTNTGNVKLCDFGVAASLNQNS-SK 157

                  ....*
gi 1370473802 429 RQGMV 433
Cdd:cd06917   158 RSTFV 162
STKc_SGK2 cd05603
Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 2; ...
283-419 1.30e-08

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: 56.52  E-value: 1.30e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKV-AIKTLKPGTMMPEAflQEAQIM-------KKLRHDKLVPL-YAVVSEEPIYIVTEFMSK 353
Cdd:cd05603     3 IGKGSFGKVLLAKRKCDGKFyAVKVLQKKTILKKK--EQNHIMaernvllKNLKHPFLVGLhYSFQTSEKLYFVLDYVNG 80
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370473802 354 GSLldFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR 419
Cdd:cd05603    81 GEL--FFHLQRERCFLEPRARFYAAEVASAIGYLHSLNIIYRDLKPENILLDCQGHVVLTDFGLCK 144
PK_KSR2 cd14153
Pseudokinase domain of Kinase Suppressor of Ras 2; The pseudokinase domain shows similarity to ...
283-417 1.42e-08

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: 55.78  E-value: 1.42e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGttKVAIKTL---KPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEPIYIVTEFMSKGSLLDF 359
Cdd:cd14153     8 IGKGRFGQVYHGRWHG--EVAIRLIdieRDNEEQLKAFKREVMAYRQTRHENVVLFMGACMSPPHLAIITSLCKGRTLYS 85
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1370473802 360 LKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCkIADFGL 417
Cdd:cd14153    86 VVRDAKVVLDVNKTRQIAQEIVKGMGYLHAKGILHKDLKSKNVFYDNGKVV-ITDFGL 142
STKc_ACVR2b cd14140
Catalytic domain of the Serine/Threonine Kinase, Activin Type IIB Receptor; STKs catalyze the ...
280-418 1.53e-08

Catalytic domain of the Serine/Threonine Kinase, Activin Type IIB Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR2b (or ActRIIB) 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. ACVR2b is one of two ACVR2 receptors found in vertebrates. Type II receptors 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. The ACVR2b 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: 271042 [Multi-domain]  Cd Length: 291  Bit Score: 56.19  E-value: 1.53e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 280 EVKlGQGCFGEVWMGTW-NGTTKVAIKTLKPgtmmPEAFLQEAQIMKK--LRHDKLVPLYAVVS-----EEPIYIVTEFM 351
Cdd:cd14140     1 EIK-ARGRFGCVWKAQLmNEYVAVKIFPIQD----KQSWQSEREIFSTpgMKHENLLQFIAAEKrgsnlEMELWLITAFH 75
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1370473802 352 SKGSLLDFLKegdGKYLKLPQLVDMAAQIADGMAYIE-----------RMNYIHRDLRAANILVGENLVCKIADFGLA 418
Cdd:cd14140    76 DKGSLTDYLK---GNIVSWNELCHIAETMARGLSYLHedvprckgeghKPAIAHRDFKSKNVLLKNDLTAVLADFGLA 150
SH2_Vav2 cd10406
Src homology 2 (SH2) domain found in the Vav2 proteins; Proto-oncogene vav is a member of the ...
158-244 1.54e-08

Src homology 2 (SH2) domain found in the Vav2 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. Vav2 is a GEF for RhoA, RhoB and RhoG and may activate Rac1 and Cdc42. Vav2 has been shown to interact with CD19 and Grb2. Alternatively spliced transcript variants encoding different isoforms have been found for Vav2. 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: 198269  Cd Length: 103  Bit Score: 52.38  E-value: 1.54e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 158 WYFGKMGRKDAERLLlnPGNQRGIFLVRESETTKGAYSLSIRDWDEirgdnVKHYKIRKLDNGgYYITTRAQFDTLQKLV 237
Cdd:cd10406     7 WFAGNMERQQTDNLL--KSHASGTYLIRERPAEAERFAISIKFNDE-----VKHIKVVEKDNW-IHITEAKKFESLLELV 78

                  ....*..
gi 1370473802 238 KHYTEHA 244
Cdd:cd10406    79 EYYQCHS 85
SH3_TXK cd11907
Src Homology 3 domain of TXK, also called Resting lymphocyte kinase (Rlk); TXK is a ...
97-147 1.58e-08

Src Homology 3 domain of TXK, also called Resting lymphocyte kinase (Rlk); TXK is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal cysteine-rich region. Rlk is expressed in T-cells and mast cell lines, and is a key component of T-cell receptor (TCR) signaling. It is important in TCR-stimulated proliferation, IL-2 production and phospholipase C-gamma1 activation. 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: 212840 [Multi-domain]  Cd Length: 55  Bit Score: 50.72  E-value: 1.58e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1370473802  97 VALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARSiATGKNGYIPSNYV 147
Cdd:cd11907     4 KALYDFLPREPSNLALKRAEEYLILEQYDPHWWKARD-RYGNEGLIPSNYV 53
STKc_RSK_N cd05582
N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase; ...
283-425 1.58e-08

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: 56.25  E-value: 1.58e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWM-----GTWNGTTkVAIKTLKPGTMMPEAFLQ---EAQIMKKLRHDKLVPL-YAVVSEEPIYIVTEFMSK 353
Cdd:cd05582     3 LGQGSFGKVFLvrkitGPDAGTL-YAMKVLKKATLKVRDRVRtkmERDILADVNHPFIVKLhYAFQTEGKLYLILDFLRG 81
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1370473802 354 GSLLDFLK------EGDGK-YLklpqlvdmaAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNE 425
Cdd:cd05582    82 GDLFTRLSkevmftEEDVKfYL---------AELALALDHLHSLGIIYRDLKPENILLDEDGHIKLTDFGLSKESIDHE 151
STKc_MLCK3 cd14192
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze ...
283-419 1.59e-08

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: 55.74  E-value: 1.59e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGT-TKVAIKTLK-PGTMMPEAFLQEAQIMKKLRHDKLVPLY-AVVSEEPIYIVTEFMSKGSLLDF 359
Cdd:cd14192    12 LGGGRFGQVHKCTELSTgLTLAAKIIKvKGAKEREEVKNEINIMNQLNHVNLIQLYdAFESKTNLTLIMEYVDGGELFDR 91
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370473802 360 LKEGDGKYLKLPQLVdMAAQIADGMAYIERMNYIHRDLRAANIL----VGENLvcKIADFGLAR 419
Cdd:cd14192    92 ITDESYQLTELDAIL-FTRQICEGVHYLHQHYILHLDLKPENILcvnsTGNQI--KIIDFGLAR 152
STKc_RCK1-like cd14096
Catalytic domain of RCK1-like Serine/Threonine Kinases; STKs catalyze the transfer of the ...
275-425 1.61e-08

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: 55.91  E-value: 1.61e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 275 ESLRLEVKLGQGCFGEVWMGTWNGTT--KVAIKTLKPGTMMPEAF--------LQEAQIMKKLRHDKLVPLYA-VVSEEP 343
Cdd:cd14096     1 ENYRLINKIGEGAFSNVYKAVPLRNTgkPVAIKVVRKADLSSDNLkgssraniLKEVQIMKRLSHPNIVKLLDfQESDEY 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 344 IYIVTEFMSKGSLLDflkegdgKYLKLPQLV-DMA----AQIADGMAYIERMNYIHRDLRAANILV-------------- 404
Cdd:cd14096    81 YYIVLELADGGEIFH-------QIVRLTYFSeDLSrhviTQVASAVKYLHEIGVVHRDIKPENLLFepipfipsivklrk 153
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 1370473802 405 -------------------GENLVCKIADFGLARLIEDNE 425
Cdd:cd14096   154 adddetkvdegefipgvggGGIGIVKLADFGLSKQVWDSN 193
SH3_Vinexin_2 cd11924
Second Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 ...
97-147 1.62e-08

Second Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. 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: 212857  Cd Length: 56  Bit Score: 50.73  E-value: 1.62e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1370473802  97 VALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARSIATGKNGYIPSNYV 147
Cdd:cd11924     4 VAQYTFKGDLEVELSFRKGEHICLIRKVNENWYEGRITGTGRQGIFPASYV 54
SH2_Tec_Btk cd10397
Src homology 2 (SH2) domain found in Tec protein, Bruton's tyrosine kinase (Btk); A member of ...
151-251 1.64e-08

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: 52.53  E-value: 1.64e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 151 DSIQAEEWYFGKMGRKDAERLLLNPGNQRGiFLVRESeTTKGAYSLSI--RDWDEIRGdNVKHYKIRKLDNGGYYITTRA 228
Cdd:cd10397     1 DSLEMYEWYSKNMTRSQAEQLLKQEGKEGG-FIVRDS-SKAGKYTVSVfaKSAGDPQG-VIRHYVVCSTPQSQYYLAEKH 77
                          90       100
                  ....*....|....*....|...
gi 1370473802 229 QFDTLQKLVKHYTEHADGLCHKL 251
Cdd:cd10397    78 LFSTIPELINYHQHNAAGLISRL 100
SH3_GRB2_C cd11949
C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical ...
98-149 1.72e-08

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRB2 binds to Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, as well as to the proline-rich C-terminus of FGRF2. SH3 domains are protein interaction domains that typically 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: 212882 [Multi-domain]  Cd Length: 53  Bit Score: 50.61  E-value: 1.72e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1370473802  98 ALYDYEARTTEDLSFKKGERFQIINNTEGDWWeaRSIATGKNGYIPSNYVAP 149
Cdd:cd11949     4 ALFDFDPQEDGELGFRRGDFIEVMDNSDPNWW--KGACHGQTGMFPRNYVTP 53
PK_IRAK3 cd14160
Pseudokinase domain of Interleukin-1 Receptor Associated Kinase 3; The pseudokinase domain ...
283-420 1.81e-08

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: 55.66  E-value: 1.81e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWnGTTKVAIKTLKPGTMMP-----EAFLQEAQIMKKLRHDKLVPLYAVVSE-EPIYIVTEFMSKGSL 356
Cdd:cd14160     1 IGEGEIFEVYRVRI-GNRSYAVKLFKQEKKMQwkkhwKRFLSELEVLLLFQHPNILELAAYFTEtEKFCLVYPYMQNGTL 79
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1370473802 357 LDFL-KEGDGKYLKLPQLVDMAAQIADGMAYIERMN---YIHRDLRAANILVGENLVCKIADFGLARL 420
Cdd:cd14160    80 FDRLqCHGVTKPLSWHERINILIGIAKAIHYLHNSQpctVICGNISSANILLDDQMQPKLTDFALAHF 147
STKc_DCKL2 cd14184
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 2 (also called ...
320-427 1.82e-08

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: 55.42  E-value: 1.82e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 320 EAQIMKKLRHDKLVPLYAVV-SEEPIYIVTEFMSKGSLLDFLKEGDgKYLKLPQLVdMAAQIADGMAYIERMNYIHRDLR 398
Cdd:cd14184    49 EVSILRRVKHPNIIMLIEEMdTPAELYLVMELVKGGDLFDAITSST-KYTERDASA-MVYNLASALKYLHGLCIVHRDIK 126
                          90       100       110
                  ....*....|....*....|....*....|...
gi 1370473802 399 AANILVGE----NLVCKIADFGLARLIEDNEYT 427
Cdd:cd14184   127 PENLLVCEypdgTKSLKLGDFGLATVVEGPLYT 159
SH3_SH3RF3_3 cd11925
Third Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ...
95-149 1.83e-08

Third Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF3. 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: 212858  Cd Length: 57  Bit Score: 50.77  E-value: 1.83e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1370473802  95 IFVALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARSIATGKNGYIPSNYVAP 149
Cdd:cd11925     2 IYLALYAYKPQKNDELELRKGEMYRVIEKCQDGWFKGTSLRTGVSGVFPGNYVTP 56
SH3_GRB2_like_N cd11804
N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related ...
97-147 1.94e-08

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The N-terminal SH3 domain of GRB2 binds to Sos and Sos-derived proline-rich peptides. 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: 212738 [Multi-domain]  Cd Length: 52  Bit Score: 50.43  E-value: 1.94e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1370473802  97 VALYDYEARTTEDLSFKKGERFQIINNTEG-DWWEARSiaTGKNGYIPSNYV 147
Cdd:cd11804     3 VAKHDFKATAEDELSFKKGSILKVLNMEDDpNWYKAEL--DGKEGLIPKNYI 52
SH2_nSH2_p85_like cd09942
N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
151-242 2.09e-08

N-terminal Src homology 2 (nSH2) 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, an internal 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: 198195  Cd Length: 110  Bit Score: 52.33  E-value: 2.09e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 151 DSIQAEEWYFGKMGRKDAERLLLNPGNqrGIFLVRESETTKGAYSLSIRdwdeiRGDNVKHYKIRKLDnGGYYITTRAQF 230
Cdd:cd09942     2 HSLQEAEWYWGDISREEVNEKMRDTPD--GTFLVRDASTMKGDYTLTLR-----KGGNNKLIKIFHRD-GKYGFSDPLTF 73
                          90
                  ....*....|..
gi 1370473802 231 DTLQKLVKHYTE 242
Cdd:cd09942    74 NSVVELINYYRN 85
STKc_MASTL cd05610
Catalytic domain of the Serine/Threonine Kinase, Microtubule-associated serine/threonine-like ...
283-425 2.29e-08

Catalytic domain of the Serine/Threonine Kinase, Microtubule-associated serine/threonine-like kinase (also called greatwall kinase); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MASTL kinases in this group carry only a catalytic domain, which contains a long insertion relative to MAST kinases. MASTL, also called greatwall kinase (Gwl), is involved in the regulation of mitotic entry, which is controlled by the coordinated activities of protein kinases and opposing protein phosphatases (PPs). The cyclin B/CDK1 complex induces entry into M-phase while PP2A-B55 shows anti-mitotic activity. MASTL/Gwl is activated downstream of cyclin B/CDK1 and indirectly inhibits PP2A-B55 by phosphorylating the small protein alpha-endosulfine (Ensa) or the cAMP-regulated phosphoprotein 19 (Arpp19), resulting in M-phase progression. Gwl kinase may also play roles in mRNA stabilization and DNA checkpoint recovery. The human MASTL gene has also been named FLJ14813; a missense mutation in FLJ14813 is associated with autosomal dominant thrombocytopenia. The MASTL 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: 270761 [Multi-domain]  Cd Length: 349  Bit Score: 56.04  E-value: 2.29e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKV-AIKTLKPGTMMPEAFLQEAQIMKKL----RHDKLVPL-YAVVSEEPIYIVTEFMSKG-- 354
Cdd:cd05610    12 ISRGAFGKVYLGRKKNNSKLyAVKVVKKADMINKNMVHQVQAERDAlalsKSPFIVHLyYSLQSANNVYLVMEYLIGGdv 91
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370473802 355 -SLLDFLKegdgkYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNE 425
Cdd:cd05610    92 kSLLHIYG-----YFDEEMAVKYISEVALALDYLHRHGIIHRDLKPDNMLISNEGHIKLTDFGLSKVTLNRE 158
SH3_SNX9_like cd11763
Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox ...
98-147 2.30e-08

Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. This subfamily consists of SH3 domain containing SNXs including SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. 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: 212697 [Multi-domain]  Cd Length: 55  Bit Score: 50.40  E-value: 2.30e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1370473802  98 ALYDYEARTTEDLSFKKGERFQIINNTEGD-WWEARSiATGKNGYIPSNYV 147
Cdd:cd11763     4 ALYDFDSQPSGELSLRAGEVLTITRQDVGDgWLEGRN-SRGEVGLFPSSYV 53
SH3_GRB2_like_C cd11805
C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related ...
98-149 2.32e-08

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The C-terminal SH3 domains (SH3c) of GRB2 and GRAP2 have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically 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: 212739 [Multi-domain]  Cd Length: 53  Bit Score: 50.32  E-value: 2.32e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1370473802  98 ALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARSiaTGKNGYIPSNYVAP 149
Cdd:cd11805     4 ALYDFNPQEPGELEFRRGDIITVLDSSDPDWWKGEL--RGRVGIFPANYVQP 53
STKc_ROCK1 cd05622
Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein ...
283-416 2.36e-08

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK1 is preferentially expressed in the liver, lung, spleen, testes, and kidney. It mediates signaling from Rho to the actin cytoskeleton. It is implicated in the development of cardiac fibrosis, cardiomyocyte apoptosis, and hyperglycemia. Mice deficient with ROCK1 display eyelids open at birth (EOB) and omphalocele phenotypes due to the disorganization of actin filaments in the eyelids and the umbilical ring. ROCK contains an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain, and is activated via interaction with Rho GTPases. The ROCK1 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: 270772 [Multi-domain]  Cd Length: 405  Bit Score: 56.17  E-value: 2.36e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKV-AIKTLKPGTMMPEA----FLQEAQIMKKLRHDKLVPL-YAVVSEEPIYIVTEFMSKGSL 356
Cdd:cd05622    81 IGRGAFGEVQLVRHKSTRKVyAMKLLSKFEMIKRSdsafFWEERDIMAFANSPWVVQLfYAFQDDRYLYMVMEYMPGGDL 160
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370473802 357 LDFLKEGD--GKYLKLpqlvdMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFG 416
Cdd:cd05622   161 VNLMSNYDvpEKWARF-----YTAEVVLALDAIHSMGFIHRDVKPDNMLLDKSGHLKLADFG 217
STKc_PAK6 cd06659
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the ...
273-421 2.38e-08

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: 55.38  E-value: 2.38e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 273 PRESLRLEVKLGQGCFGEVWMGTWNGTTK-VAIKtlkpgtMMP-------EAFLQEAQIMKKLRHDKLVPLY--AVVSEE 342
Cdd:cd06659    19 PRQLLENYVKIGEGSTGVVCIAREKHSGRqVAVK------MMDlrkqqrrELLFNEVVIMRDYQHPNVVEMYksYLVGEE 92
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1370473802 343 pIYIVTEFMSKGSLLDFLKEgdgKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLI 421
Cdd:cd06659    93 -LWVLMEYLQGGALTDIVSQ---TRLNEEQIATVCEAVLQALAYLHSQGVIHRDIKSDSILLTLDGRVKLSDFGFCAQI 167
SH3_ASPP1 cd11954
Src Homology 3 domain of Apoptosis Stimulating of p53 protein 1; ASPP1, like ASPP2, activates ...
98-145 2.66e-08

Src Homology 3 domain of Apoptosis Stimulating of p53 protein 1; ASPP1, like ASPP2, activates the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73). In addition, it functions in the cytoplasm to regulate the nuclear localization of the transcriptional cofactors YAP and TAZ by inihibiting their phosphorylation; YAP and TAZ are important regulators of cell expansion, differentiation, migration, and invasion. ASPP1 is downregulated in breast tumors expressing wild-type p53. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of ASPP1 contribute to the p53 binding site; they bind to the DNA binding domain of p53. 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: 212887 [Multi-domain]  Cd Length: 57  Bit Score: 50.40  E-value: 2.66e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1370473802  98 ALYDYEARTTEDLSFKKGERFQII---NNTEGDWWEARsiATGKNGYIPSN 145
Cdd:cd11954     5 ALWDYEAQNADELSFQEGDAITILrrkDDSETEWWWAR--LNDKEGYVPKN 53
SH3_srGAP1-3 cd11955
Src homology 3 domain of Slit-Robo GTPase Activating Proteins 1, 2, and 3; srGAP1, also called ...
97-147 2.67e-08

Src homology 3 domain of Slit-Robo GTPase Activating Proteins 1, 2, and 3; srGAP1, also called Rho GTPase-Activating Protein 13 (ARHGAP13), is a Cdc42- and RhoA-specific GAP and is expressed later in the development of central nervous system tissues. srGAP2 is expressed in zones of neuronal differentiation. It plays a role in the regeneration of neurons and axons. srGAP3, also called MEGAP (MEntal disorder associated GTPase-Activating Protein), is a Rho GAP with activity towards Rac1 and Cdc42. It impacts cell migration by regulating actin and microtubule cytoskeletal dynamics. The association between srGAP3 haploinsufficiency and mental retardation is under debate. srGAPs are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. 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: 212888 [Multi-domain]  Cd Length: 53  Bit Score: 50.33  E-value: 2.67e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1370473802  97 VALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARSiaTGKNGYIPSNYV 147
Cdd:cd11955     3 IAKFDYVGRSARELSFKKGASLLLYHRASDDWWEGRH--NGIDGLVPHQYI 51
STKc_SGK3 cd05604
Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced ...
283-419 2.76e-08

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: 55.35  E-value: 2.76e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKV-AIKTLKPGTMMPEAflQEAQIM-------KKLRHDKLVPL-YAVVSEEPIYIVTEFMSK 353
Cdd:cd05604     4 IGKGSFGKVLLAKRKRDGKYyAVKVLQKKVILNRK--EQKHIMaernvllKNVKHPFLVGLhYSFQTTDKLYFVLDFVNG 81
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370473802 354 GSLLDFLKEGdgKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLAR 419
Cdd:cd05604    82 GELFFHLQRE--RSFPEPRARFYAAEIASALGYLHSINIVYRDLKPENILLDSQGHIVLTDFGLCK 145
STKc_PhKG2 cd14181
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 2 subunit; STKs ...
302-425 2.96e-08

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 2 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). The gamma 2 subunit (PhKG2) is also referred to as the testis/liver gamma isoform. Mutations in its gene cause autosomal-recessive glycogenosis of the liver. 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 PhKG2 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: 271083 [Multi-domain]  Cd Length: 279  Bit Score: 54.98  E-value: 2.96e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 302 VAIKTLKPGTMMPE-------AFLQEAQIMKKLR-HDKLVPLY-AVVSEEPIYIVTEFMSKGSLLDFLKEGdgKYLKLPQ 372
Cdd:cd14181    40 VKIIEVTAERLSPEqleevrsSTLKEIHILRQVSgHPSIITLIdSYESSTFIFLVFDLMRRGELFDYLTEK--VTLSEKE 117
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1370473802 373 LVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDNE 425
Cdd:cd14181   118 TRSIMRSLLEAVSYLHANNIVHRDLKPENILLDDQLHIKLSDFGFSCHLEPGE 170
STKc_PASK cd14004
Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs ...
282-422 3.01e-08

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: 54.70  E-value: 3.01e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMGTWNGTTK-VAIKTLKPGTMMPEAFLQ---------EAQIMKKLRHD------KLVPLYAvvSEEPIY 345
Cdd:cd14004     7 EMGEGAYGQVNLAIYKSKGKeVVIKFIFKERILVDTWVRdrklgtvplEIHILDTLNKRshpnivKLLDFFE--DDEFYY 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 346 IVTEFMSKG-SLLDF------LKEGDGKYLklpqlvdmAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLA 418
Cdd:cd14004    85 LVMEKHGSGmDLFDFierkpnMDEKEAKYI--------FRQVADAVKHLHDQGIVHRDIKDENVILDGNGTIKLIDFGSA 156

                  ....
gi 1370473802 419 RLIE 422
Cdd:cd14004   157 AYIK 160
STKc_TAO2 cd06634
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze ...
282-421 3.23e-08

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: 55.03  E-value: 3.23e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 282 KLGQGCFGEVWMG-TWNGTTKVAIKTL----KPGTMMPEAFLQEAQIMKKLRHDKLVPLYAV-VSEEPIYIVTEFmSKGS 355
Cdd:cd06634    22 EIGHGSFGAVYFArDVRNNEVVAIKKMsysgKQSNEKWQDIIKEVKFLQKLRHPNTIEYRGCyLREHTAWLVMEY-CLGS 100
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370473802 356 LLDFLkEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLI 421
Cdd:cd06634   101 ASDLL-EVHKKPLQEVEIAAITHGALQGLAYLHSHNMIHRDVKAGNILLTEPGLVKLGDFGSASIM 165
STKc_ROCK cd05596
Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein ...
283-416 3.32e-08

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK is also referred to as Rho-associated kinase or simply as Rho kinase. It contains an N-terminal extension, a catalytic kinase domain, and a long C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain. It is activated via interaction with Rho GTPases and is involved in many cellular functions including contraction, adhesion, migration, motility, proliferation, and apoptosis. The ROCK subfamily consists of two isoforms, ROCK1 and ROCK2, which may be functionally redundant in some systems, but exhibit different tissue distributions. Both isoforms are ubiquitously expressed in most tissues, but ROCK2 is more prominent in brain and skeletal muscle while ROCK1 is more pronounced in the liver, testes, and kidney. Studies in knockout mice result in different phenotypes, suggesting that the two isoforms do not compensate for each other during embryonic development. The ROCK 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: 270747 [Multi-domain]  Cd Length: 352  Bit Score: 55.46  E-value: 3.32e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKV-AIKTLKPGTMM----PEAFLQEAQIMKKLRHDKLVPL-YAVVSEEPIYIVTEFMSKGSL 356
Cdd:cd05596    34 IGRGAFGEVQLVRHKSTKKVyAMKLLSKFEMIkrsdSAFFWEERDIMAHANSEWIVQLhYAFQDDKYLYMVMDYMPGGDL 113
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370473802 357 LDFLKEGDgkylkLPQlvDMA----AQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFG 416
Cdd:cd05596   114 VNLMSNYD-----VPE--KWArfytAEVVLALDAIHSMGFVHRDVKPDNMLLDASGHLKLADFG 170
STKc_GRK6 cd05630
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6; STKs ...
283-433 3.42e-08

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK6 is widely expressed in many tissues and is expressed as multiple splice variants with different domain architectures. It is post-translationally palmitoylated and localized in the membrane. GRK6 plays important roles in the regulation of dopamine, M3 muscarinic, opioid, and chemokine receptor signaling. It also plays maladaptive roles in addiction and Parkinson's disease. GRK6-deficient mice exhibit altered dopamine receptor regulation, decreased lymphocyte chemotaxis, and increased acute inflammation and neutrophil chemotaxis. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK6 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: 270779 [Multi-domain]  Cd Length: 285  Bit Score: 55.03  E-value: 3.42e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKV-AIKTL-------KPGTMMPeafLQEAQIMKKLRHDKLVPL-YAVVSEEPIYIVTEFMSK 353
Cdd:cd05630     8 LGKGGFGEVCACQVRATGKMyACKKLekkrikkRKGEAMA---LNEKQILEKVNSRFVVSLaYAYETKDALCLVLTLMNG 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 354 GSL-LDFLKEGDGKYLKlPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLA-RLIEDNEYTARQG 431
Cdd:cd05630    85 GDLkFHIYHMGQAGFPE-ARAVFYAAEICCGLEDLHRERIVYRDLKPENILLDDHGHIRISDLGLAvHVPEGQTIKGRVG 163

                  ..
gi 1370473802 432 MV 433
Cdd:cd05630   164 TV 165
SH3_MLK cd11876
Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), ...
95-149 3.42e-08

Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T 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. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. 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. 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: 212809 [Multi-domain]  Cd Length: 58  Bit Score: 49.82  E-value: 3.42e-08
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802  95 IFVALYDYEARTTEDLSFKKGERFQIINN---TEGD--WWEARsIATgKNGYIPSNYVAP 149
Cdd:cd11876     1 LWTALFDYDARGEDELTLRRGQPVEVLSKdaaVSGDegWWTGK-IGD-KVGIFPSNYVAP 58
SH3_AHI-1 cd11812
Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called ...
97-147 3.49e-08

Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called Jouberin, is expressed in high levels in the brain, gonad tissues, and skeletal muscle. It is an adaptor protein that interacts with the small GTPase Rab8a and regulates it distribution and function, affecting cilium formation and vesicle transport. Mutations in the AHI-1 gene can cause Joubert syndrome, a disorder characterized by brainstem malformations, cerebellar aplasia/hypoplasia, and retinal dystrophy. AHI-1 variation is also associated with susceptibility to schizophrenia and type 2 diabetes mellitus progression. AHI-1 contains WD40 and SH3 domains. 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: 212746 [Multi-domain]  Cd Length: 52  Bit Score: 49.82  E-value: 3.49e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1370473802  97 VALYDYEARTTEDLSFKKGERFQIINNTEGDWWEArSIATGKNGYIPSNYV 147
Cdd:cd11812     3 VALYDYTANRSDELTIHRGDIIRVLYKDNDNWWFG-SLVNGQQGYFPANYV 52
SH3_Srms cd11846
Src homology 3 domain of Srms Protein Tyrosine Kinase; Src-related kinase lacking C-terminal ...
95-148 3.79e-08

Src homology 3 domain of Srms Protein Tyrosine Kinase; Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristoylation sites (Srms) is a cytoplasmic (or non-receptor) PTK with limited homology to Src kinases. 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). However, Srms lacks the N-terminal myristoylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. 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: 212780  Cd Length: 55  Bit Score: 49.77  E-value: 3.79e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1370473802  95 IFVALYDYEARTTEDLSFKKGERFQIINNtEGDWWEARSIaTGK--NGYIPSNYVA 148
Cdd:cd11846     1 LFTALYDFTARSTHELSVEQGDKLCVIEE-EGDYIFARKL-TGNpeSGLVPASYVA 54
STKc_phototropin_like cd05574
Catalytic domain of Phototropin-like Serine/Threonine Kinases; STKs catalyze the transfer of ...
283-418 3.82e-08

Catalytic domain of Phototropin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phototropins are blue-light receptors that control responses such as phototropism, stromatal opening, and chloroplast movement in order to optimize the photosynthetic efficiency of plants. They are light-activated STKs that contain an N-terminal photosensory domain and a C-terminal catalytic domain. The N-terminal domain contains two LOV (Light, Oxygen or Voltage) domains that binds FMN. Photoexcitation of the LOV domains results in autophosphorylation at multiple sites and activation of the catalytic domain. In addition to plant phototropins, included in this subfamily are predominantly uncharacterized fungal STKs whose catalytic domains resemble the phototropin kinase domain. One protein from Neurospora crassa is called nrc-2, which plays a role in growth and development by controlling entry into the conidiation program. The phototropin-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: 270726 [Multi-domain]  Cd Length: 316  Bit Score: 54.94  E-value: 3.82e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 283 LGQGCFGEVWMGTWNGTTKV-AIKTLKPGTMMPEAFLQ----EAQIMKKLRHDKLVPLYAV-VSEEPIYIVTEFMSKGSL 356
Cdd:cd05574     9 LGKGDVGRVYLVRLKGTGKLfAMKVLDKEEMIKRNKVKrvltEREILATLDHPFLPTLYASfQTSTHLCFVMDYCPGGEL 88
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370473802 357 LDFLKEGDGKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLA 418
Cdd:cd05574    89 FRLLQKQPGKRLPEEVARFYAAEVLLALEYLHLLGFVYRDLKPENILLHESGHIMLTDFDLS 150
SH2_Vav3 cd10407
Src homology 2 (SH2) domain found in the Vav3 proteins; Proto-oncogene vav is a member of the ...
158-244 4.02e-08

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: 51.16  E-value: 4.02e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370473802 158 WYFGKMGRKDAERLLLNPGNQrgIFLVRESETTKGAYSLSIRdwdeiRGDNVKHYKIRKLDnGGYYITTRAQFDTLQKLV 237
Cdd:cd10407     7 WYAGAMERLQAETELINRVNS--TYLVRHRTKESGEYAISIK-----YNNEVKHIKILTRD-GFFHIAENRKFKSLMELV 78

                  ....*..
gi 1370473802 238 KHYTEHA 244
Cdd:cd10407    79 EYYKHHS 85
SH3_Nck1_1 cd11900
First Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a ...
95-152 4.09e-08

First Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The first SH3 domain of Nck1 binds the PxxDY sequence in the CD3e cytoplasmic tail; this binding inhibits phosphorylation by Src kinases, resulting in the downregulation of TCR surface expression. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. 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: 212833 [Multi-domain]  Cd Length: 59  Bit Score: 49.72  E-value: 4.09e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1370473802  95 IFVALYDYEARTTEDLSFKKGERFQIINNTEgDWWEARSiATGKNGYIPSNYVAPADS 152
Cdd:cd11900     4 VVVAKFDYVAQQDQELDIKKNERLWLLDDSK-SWWRVRN-AMNKTGFVPSNYVERKNS 59
SH3_ASPP cd11807
Src homology 3 domain of Apoptosis Stimulating of p53 proteins (ASPP); The ASPP family of ...
98-148 4.54e-08

Src homology 3 domain of Apoptosis Stimulating of p53 proteins (ASPP); The ASPP family of proteins bind to important regulators of apoptosis (p53, Bcl-2, and RelA) and cell growth (APCL, PP1). They share similarity at their C-termini, where they harbor a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain. Vertebrates contain three members of the family: ASPP1, ASPP2, and iASPP. ASPP1 and ASPP2 activate the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73), while iASPP is an oncoprotein that specifically inhibits p53-induced apoptosis. The expression of ASPP proteins is altered in tumors; ASPP1 and ASPP2 are downregulated whereas iASPP is upregulated is some cancer types. ASPP proteins also bind and regulate protein phosphatase 1 (PP1), and this binding is competitive with p53 binding. The SH3 domain and the ANK repeats of ASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. 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: 212741 [Multi-domain]  Cd Length: 57  Bit Score: 49.68  E-value: 4.54e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1370473802  98 ALYDYEARTTEDLSFKKGERFQII---NNTEGDWWEARsiATGKNGYIPSNYVA 148
Cdd:cd11807     5 ALFDYEAENGDELSFREGDELTVLrkgDDDETEWWWAR--LNDKEGYVPRNLLG 56
 
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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