NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|111118978|ref|NP_059145|]
View 

ephrin type-B receptor 2 isoform 1 precursor [Homo sapiens]

Protein Classification

ephrin type-B receptor 2( domain architecture ID 10875642)

ephrin type-B receptor 2 is a receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

Name Accession Description Interval E-value
PTKc_EphR_B cd05065
Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze ...
616-884 0e+00

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: 614.57  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 616 IDISCVKIEQVIGAGEFGEVCSGHLKLPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPV 695
Cdd:cd05065    1 IDVSCVKIEEVIGAGEFGEVCRGRLKLPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNIIHLEGVVTKSRPV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 696 MIITEFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDT 775
Cdd:cd05065   81 MIITEFMENGALDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLSEMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDT 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 776 SDPTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSAL 855
Cdd:cd05065  161 SDPTYTSSLGGKIPIRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSYGERPYWDMSNQDVINAIEQDYRLPPPMDCPTAL 240
                        250       260
                 ....*....|....*....|....*....
gi 111118978 856 HQLMLDCWQKDRNHRPKFGQIVNTLDKMI 884
Cdd:cd05065  241 HQLMLDCWQKDRNLRPKFGQIVNTLDKMI 269
EphR_LBD_B2 cd10477
Ligand Binding Domain of Ephrin type-B Receptor 2; Ephrin receptors (EphRs) comprise the ...
19-196 2.55e-134

Ligand Binding Domain of Ephrin type-B Receptor 2; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EhpB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. EphB2 plays a role in cell positioning in the gastrointestinal tract by being expressed in proliferating progenitor cells. It also has been implicated in colorectal cancer. A loss of EphB2, as well as EphA4, also precedes memory decline in a murine model of Alzheimers disease. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine 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).


:

Pssm-ID: 198445  Cd Length: 178  Bit Score: 400.97  E-value: 2.55e-134
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  19 VEETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCS 98
Cdd:cd10477    1 AEETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIRTYQVCNVFESSQNNWLRTKYIRRRGAHRIHVEMKFSVRDCS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  99 SIPSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGFYLAF 178
Cdd:cd10477   81 SIPSVPGSCKETFNLYYYESDFDSATKTFPNWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRNGFYLAF 160
                        170
                 ....*....|....*...
gi 111118978 179 QDYGGCMSLIAVRVFYRK 196
Cdd:cd10477  161 QDYGGCMSLIAVRVFYRK 178
SAM_EPH-B2 cd09552
SAM domain of EPH-B2 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
910-980 1.69e-46

SAM domain of EPH-B2 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B2 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B2 receptors and appears to mediate cell-cell initiated signal transduction. SAM domains of this subfamily form homodimers/oligomers (in head-to-head/tail-to-tail orientation); apparently such clustering is necessary for signaling. EPH-B2 receptor is involved in regulation of synaptic function; it is needed for normal vestibular function, proper formation of anterior commissure, control of cell positioning, and ordered migration in the intestinal epithelium. EPH-B2 plays a tumor suppressor role in colorectal cancer. It was found to be downregulated in gastric cancer and thus may be a negative biomarker for it.


:

Pssm-ID: 188951  Cd Length: 71  Bit Score: 160.17  E-value: 1.69e-46
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 111118978 910 PDYTSFNTVDEWLEAIKMGQYKESFANAGFTSFDVVSQMMMEDILRVGVTLAGHQKKILNSIQVMRAQMNQ 980
Cdd:cd09552    1 PDYTSFSTVDEWLDAIKMGQYKESFANAGFTSFDVVSQMTMEDILRVGVTLAGHQKKILNSIQVMRAQMNQ 71
EphA2_TM pfam14575
Ephrin type-A receptor 2 transmembrane domain; Epha2_TM represents the left-handed dimer ...
544-617 1.62e-25

Ephrin type-A receptor 2 transmembrane domain; Epha2_TM represents the left-handed dimer transmembrane domain of of EphA2 receptor. This domain oligomerises and is important for the active signalling process.


:

Pssm-ID: 464211  Cd Length: 72  Bit Score: 100.37  E-value: 1.62e-25
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 111118978  544 IIGSSAAGLVFLIAVVVIAIVCNRR-GFERADSEYTDKLQHYtsghMTPGMKIYIDPFTYEDPNEAVREFAKEID 617
Cdd:pfam14575   1 VVASVAGGLVLLLVVGVVLIRRRRCcGRKKSQDDDEEEFHQY----KPPGRKTYIDPHTYEDPNQAVLEFAKEID 71
fn3 pfam00041
Fibronectin type III domain;
437-520 4.34e-19

Fibronectin type III domain;


:

Pssm-ID: 394996 [Multi-domain]  Cd Length: 85  Bit Score: 82.85  E-value: 4.34e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  437 SAVSIMHQVSRTVDSITLSWSQPDQPNGVILDYELQYYEKELSEYNATA-IKSPTNTVTVQGLKAGAIYVFQVRARTVAG 515
Cdd:pfam00041   1 SAPSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEPWNEItVPGTTTSVTLTGLKPGTEYEVRVQAVNGGG 80

                  ....*
gi 111118978  516 YGRYS 520
Cdd:pfam00041  81 EGPPS 85
fn3 pfam00041
Fibronectin type III domain;
326-421 1.95e-12

Fibronectin type III domain;


:

Pssm-ID: 394996 [Multi-domain]  Cd Length: 85  Bit Score: 63.59  E-value: 1.95e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  326 SAPQAV-ISSVNETSLMLEWTPPRDSGGrEDLVYNIICKSCGSGRGActrcgdnvqyAPRQLGLTEPRIYISDLLAHTQY 404
Cdd:pfam00041   1 SAPSNLtVTDVTSTSLTVSWTPPPDGNG-PITGYEVEYRPKNSGEPW----------NEITVPGTTTSVTLTGLKPGTEY 69
                          90
                  ....*....|....*..
gi 111118978  405 TFEIQAVNGVTdQSPFS 421
Cdd:pfam00041  70 EVRVQAVNGGG-EGPPS 85
 
Name Accession Description Interval E-value
PTKc_EphR_B cd05065
Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze ...
616-884 0e+00

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: 614.57  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 616 IDISCVKIEQVIGAGEFGEVCSGHLKLPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPV 695
Cdd:cd05065    1 IDVSCVKIEEVIGAGEFGEVCRGRLKLPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNIIHLEGVVTKSRPV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 696 MIITEFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDT 775
Cdd:cd05065   81 MIITEFMENGALDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLSEMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDT 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 776 SDPTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSAL 855
Cdd:cd05065  161 SDPTYTSSLGGKIPIRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSYGERPYWDMSNQDVINAIEQDYRLPPPMDCPTAL 240
                        250       260
                 ....*....|....*....|....*....
gi 111118978 856 HQLMLDCWQKDRNHRPKFGQIVNTLDKMI 884
Cdd:cd05065  241 HQLMLDCWQKDRNLRPKFGQIVNTLDKMI 269
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
621-880 4.46e-143

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


Pssm-ID: 462242 [Multi-domain]  Cd Length: 258  Bit Score: 426.91  E-value: 4.46e-143
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  621 VKIEQVIGAGEFGEVCSGHLK-LPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIIT 699
Cdd:pfam07714   1 LTLGEKLGEGAFGEVYKGTLKgEGENTKIKVAVKTLKEGADEEEREDFLEEASIMKKLDHPNIVKLLGVCTQGEPLYIVT 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  700 EFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDdtsDPT 779
Cdd:pfam07714  81 EYMPGGDLLDFLRKHKRKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVVKISDFGLSRDIYD---DDY 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  780 YTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSALHQLM 859
Cdd:pfam07714 158 YRKRGGGKLPIKWMAPESLKDGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEFLEDGYRLPQPENCPDELYDLM 237
                         250       260
                  ....*....|....*....|.
gi 111118978  860 LDCWQKDRNHRPKFGQIVNTL 880
Cdd:pfam07714 238 KQCWAYDPEDRPTFSELVEDL 258
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
621-880 2.01e-137

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


Pssm-ID: 197581 [Multi-domain]  Cd Length: 257  Bit Score: 412.31  E-value: 2.01e-137
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978   621 VKIEQVIGAGEFGEVCSGHLK-LPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIIT 699
Cdd:smart00219   1 LTLGKKLGEGAFGEVYKGKLKgKGGKKKVEVAVKTLKEDASEQQIEEFLREARIMRKLDHPNVVKLLGVCTEEEPLYIVM 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978   700 EFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDtsdpT 779
Cdd:smart00219  81 EYMEGGDLLSYLRKNRPKLSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRDLYDD----D 156
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978   780 YTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSALHQLM 859
Cdd:smart00219 157 YYRKRGGKLPIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEYLKNGYRLPQPPNCPPELYDLM 236
                          250       260
                   ....*....|....*....|.
gi 111118978   860 LDCWQKDRNHRPKFGQIVNTL 880
Cdd:smart00219 237 LQCWAEDPEDRPTFSELVEIL 257
EphR_LBD_B2 cd10477
Ligand Binding Domain of Ephrin type-B Receptor 2; Ephrin receptors (EphRs) comprise the ...
19-196 2.55e-134

Ligand Binding Domain of Ephrin type-B Receptor 2; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EhpB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. EphB2 plays a role in cell positioning in the gastrointestinal tract by being expressed in proliferating progenitor cells. It also has been implicated in colorectal cancer. A loss of EphB2, as well as EphA4, also precedes memory decline in a murine model of Alzheimers disease. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine 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).


Pssm-ID: 198445  Cd Length: 178  Bit Score: 400.97  E-value: 2.55e-134
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  19 VEETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCS 98
Cdd:cd10477    1 AEETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIRTYQVCNVFESSQNNWLRTKYIRRRGAHRIHVEMKFSVRDCS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  99 SIPSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGFYLAF 178
Cdd:cd10477   81 SIPSVPGSCKETFNLYYYESDFDSATKTFPNWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRNGFYLAF 160
                        170
                 ....*....|....*...
gi 111118978 179 QDYGGCMSLIAVRVFYRK 196
Cdd:cd10477  161 QDYGGCMSLIAVRVFYRK 178
EPH_lbd smart00615
Ephrin receptor ligand binding domain;
20-196 3.28e-112

Ephrin receptor ligand binding domain;


Pssm-ID: 128877  Cd Length: 177  Bit Score: 343.11  E-value: 3.28e-112
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978    20 EETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSS 99
Cdd:smart00615   1 EVVLLDTKTETGELGWTTYPPEGWEEVSGMDENGTPIRTYQVCNVQEGNQNNWLRTNFIRRRGAQRIYVELKFTVRDCSS 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978   100 IPSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGFYLAFQ 179
Cdd:smart00615  81 LPGVGGSCKETFNLYYYESDTDTATNTLPNWMENPYTKVDTIAADESFTGGDVGKRNVKLNTEVRSLGPLSKKGFYLAFQ 160
                          170
                   ....*....|....*..
gi 111118978   180 DYGGCMSLIAVRVFYRK 196
Cdd:smart00615 161 DQGACVALVSVRVFYKK 177
Ephrin_lbd pfam01404
Ephrin receptor ligand binding domain; The Eph receptors, which bind to ephrins pfam00812 are ...
21-197 1.66e-103

Ephrin receptor ligand binding domain; The Eph receptors, which bind to ephrins pfam00812 are a large family of receptor tyrosine kinases. This family represents the amino terminal domain which binds the ephrin ligand.


Pssm-ID: 460198  Cd Length: 177  Bit Score: 320.38  E-value: 1.66e-103
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978   21 ETLMDSTTATAELGWMVHPPS-GWEEVSGYDENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSS 99
Cdd:pfam01404   1 EVLLDTTSATSDLGWTTYPYDgGWEEVSGLDENGRTIRTYQVCNVEEPNQNNWLRTPFIPRGGASRVYVELKFTVRDCSS 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  100 IPSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADESFSQVDlGGRVMKINTEVRSFGPVSRSGFYLAFQ 179
Cdd:pfam01404  81 IPGVSGTCKETFNLYYYESDADAATATPPAWRENPYKKIDTIAADESFTDTG-KGRVMKLNTETRSIGPLSKRGFYLAFQ 159
                         170
                  ....*....|....*...
gi 111118978  180 DYGGCMSLIAVRVFYRKC 197
Cdd:pfam01404 160 DQGACIALLSVRVFYKKC 177
SAM_EPH-B2 cd09552
SAM domain of EPH-B2 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
910-980 1.69e-46

SAM domain of EPH-B2 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B2 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B2 receptors and appears to mediate cell-cell initiated signal transduction. SAM domains of this subfamily form homodimers/oligomers (in head-to-head/tail-to-tail orientation); apparently such clustering is necessary for signaling. EPH-B2 receptor is involved in regulation of synaptic function; it is needed for normal vestibular function, proper formation of anterior commissure, control of cell positioning, and ordered migration in the intestinal epithelium. EPH-B2 plays a tumor suppressor role in colorectal cancer. It was found to be downregulated in gastric cancer and thus may be a negative biomarker for it.


Pssm-ID: 188951  Cd Length: 71  Bit Score: 160.17  E-value: 1.69e-46
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 111118978 910 PDYTSFNTVDEWLEAIKMGQYKESFANAGFTSFDVVSQMMMEDILRVGVTLAGHQKKILNSIQVMRAQMNQ 980
Cdd:cd09552    1 PDYTSFSTVDEWLDAIKMGQYKESFANAGFTSFDVVSQMTMEDILRVGVTLAGHQKKILNSIQVMRAQMNQ 71
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
623-871 4.74e-40

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 155.17  E-value: 4.74e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 623 IEQVIGAGEFGEVCSGHLKLPGKReifVAIKTLKSGYT--EKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITE 700
Cdd:COG0515   11 ILRLLGRGGMGVVYLARDLRLGRP---VALKVLRPELAadPEARERFRREARALARLNHPNIVRVYDVGEEDGRPYLVME 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMENGSLDSFLRQNdGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLedDTSDPTY 780
Cdd:COG0515   88 YVEGESLADLLRRR-GPLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDGRVKLIDFGIARAL--GGATLTQ 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 781 TSALGGKIPirWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVINAIEQDYRLPPP---MDCPSALHQ 857
Cdd:COG0515  165 TGTVVGTPG--YMAPEQARGEPVDPRSDVYSLGVTLYE-LLTGRPPFDGDSPAELLRAHLREPPPPPSelrPDLPPALDA 241
                        250
                 ....*....|....
gi 111118978 858 LMLDCWQKDRNHRP 871
Cdd:COG0515  242 IVLRALAKDPEERY 255
EphA2_TM pfam14575
Ephrin type-A receptor 2 transmembrane domain; Epha2_TM represents the left-handed dimer ...
544-617 1.62e-25

Ephrin type-A receptor 2 transmembrane domain; Epha2_TM represents the left-handed dimer transmembrane domain of of EphA2 receptor. This domain oligomerises and is important for the active signalling process.


Pssm-ID: 464211  Cd Length: 72  Bit Score: 100.37  E-value: 1.62e-25
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 111118978  544 IIGSSAAGLVFLIAVVVIAIVCNRR-GFERADSEYTDKLQHYtsghMTPGMKIYIDPFTYEDPNEAVREFAKEID 617
Cdd:pfam14575   1 VVASVAGGLVLLLVVGVVLIRRRRCcGRKKSQDDDEEEFHQY----KPPGRKTYIDPHTYEDPNQAVLEFAKEID 71
SAM_1 pfam00536
SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily ...
911-975 1.10e-21

SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily conserved protein binding domain that is involved in the regulation of numerous developmental processes in diverse eukaryotes. The SAM domain can potentially function as a protein interaction module through its ability to homo- and heterooligomerise with other SAM domains.


Pssm-ID: 425739  Cd Length: 64  Bit Score: 89.25  E-value: 1.10e-21
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 111118978  911 DYTSFNTVDEWLEAIKMGQYKESFAnAGFTSFDVVSQMMMEDILRVGVTLAGHQKKILNSIQVMR 975
Cdd:pfam00536   1 DGWSVEDVGEWLESIGLGQYIDSFR-AGYIDGDALLQLTEDDLLKLGVTLLGHRKKILYAIQRLK 64
SAM smart00454
Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related ...
910-977 1.79e-21

Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. In many cases mediates homodimerisation.


Pssm-ID: 197735  Cd Length: 68  Bit Score: 88.89  E-value: 1.79e-21
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 111118978   910 PDYTSFNTVDEWLEAIKMGQYKESFANAGFTSFDVVSQMMMEDILRVGVTLAGHQKKILNSIQVMRAQ 977
Cdd:smart00454   1 VSQWSPESVADWLESIGLEQYADNFRKNGIDGALLLLLTSEEDLKELGITKLGHRKKILKAIQKLKEQ 68
fn3 pfam00041
Fibronectin type III domain;
437-520 4.34e-19

Fibronectin type III domain;


Pssm-ID: 394996 [Multi-domain]  Cd Length: 85  Bit Score: 82.85  E-value: 4.34e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  437 SAVSIMHQVSRTVDSITLSWSQPDQPNGVILDYELQYYEKELSEYNATA-IKSPTNTVTVQGLKAGAIYVFQVRARTVAG 515
Cdd:pfam00041   1 SAPSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEPWNEItVPGTTTSVTLTGLKPGTEYEVRVQAVNGGG 80

                  ....*
gi 111118978  516 YGRYS 520
Cdd:pfam00041  81 EGPPS 85
PLN00034 PLN00034
mitogen-activated protein kinase kinase; Provisional
627-818 8.41e-18

mitogen-activated protein kinase kinase; Provisional


Pssm-ID: 215036 [Multi-domain]  Cd Length: 353  Bit Score: 86.03  E-value: 8.41e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGS 706
Cdd:PLN00034  82 IGSGAGGTVYKVIHRPTGR---LYALKVIYGNHEDTVRRQICREIEILRDVNHPNVVKCHDMFDHNGEIQVLLEFMDGGS 158
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 707 LDSfLRQNDGQFtviqLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLeDDTSDPTyTSALGg 786
Cdd:PLN00034 159 LEG-THIADEQF----LADVARQILSGIAYLHRRHIVHRDIKPSNLLINSAKNVKIADFGVSRIL-AQTMDPC-NSSVG- 230
                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 111118978 787 kiPIRWTAPEAI-------QYRKFtsASDVWSYGIVMWE 818
Cdd:PLN00034 231 --TIAYMSPERIntdlnhgAYDGY--AGDIWSLGVSILE 265
FN3 cd00063
Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein ...
436-527 1.98e-15

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.


Pssm-ID: 238020 [Multi-domain]  Cd Length: 93  Bit Score: 72.53  E-value: 1.98e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 436 PSAVSIMHQVSRTVDSITLSWSQPDQPNGVILDYELQYYEKELSEY-NATAIKSPTNTVTVQGLKAGAIYVFQVRARTVA 514
Cdd:cd00063    1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGDWkEVEVTPGSETSYTLTGLKPGTEYEFRVRAVNGG 80
                         90
                 ....*....|...
gi 111118978 515 GYGRYSGKMYFQT 527
Cdd:cd00063   81 GESPPSESVTVTT 93
PknB_PASTA_kin NF033483
Stk1 family PASTA domain-containing Ser/Thr kinase;
622-872 1.91e-13

Stk1 family PASTA domain-containing Ser/Thr kinase;


Pssm-ID: 468045 [Multi-domain]  Cd Length: 563  Bit Score: 74.06  E-value: 1.91e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGH-LKLpgKREifVAIKTLKSGYTEK---QRRdFLSEASIMGQFDHPNVIhleGV----VTKST 693
Cdd:NF033483  10 EIGERIGRGGMAEVYLAKdTRL--DRD--VAVKVLRPDLARDpefVAR-FRREAQSAASLSHPNIV---SVydvgEDGGI 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 694 P--VMiitEFMENGSLDSFLRQNdGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFL 771
Cdd:NF033483  82 PyiVM---EYVDGRTLKDYIREH-GPLSPEEAVEIMIQILSALEHAHRNGIVHRDIKPQNILITKDGRVKVTDFGIARAL 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 772 edDTSDPTYTSALGGkipirwTA----PEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYwdmT------------NQDV 835
Cdd:NF033483 158 --SSTTMTQTNSVLG------TVhylsPEQARGGTVDARSDIYSLGIVLYE-MLTGRPPF---DgdspvsvaykhvQEDP 225
                        250       260       270
                 ....*....|....*....|....*....|....*..
gi 111118978 836 INAIEQDYRLPPPMDcpsalhQLMLDCWQKDRNHRPK 872
Cdd:NF033483 226 PPPSELNPGIPQSLD------AVVLKATAKDPDDRYQ 256
FN3 smart00060
Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, ...
436-517 6.04e-13

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.


Pssm-ID: 214495 [Multi-domain]  Cd Length: 83  Bit Score: 65.33  E-value: 6.04e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978   436 PSAVSIMHQVSRTVDSITLSWSQPDQPNGV--ILDYELQYYEKELSEYNATAiKSPTNTVTVQGLKAGAIYVFQVRARTV 513
Cdd:smart00060   1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGITgyIVGYRVEYREEGSEWKEVNV-TPSSTSYTLTGLKPGTEYEFRVRAVNG 79

                   ....
gi 111118978   514 AGYG 517
Cdd:smart00060  80 AGEG 83
fn3 pfam00041
Fibronectin type III domain;
326-421 1.95e-12

Fibronectin type III domain;


Pssm-ID: 394996 [Multi-domain]  Cd Length: 85  Bit Score: 63.59  E-value: 1.95e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  326 SAPQAV-ISSVNETSLMLEWTPPRDSGGrEDLVYNIICKSCGSGRGActrcgdnvqyAPRQLGLTEPRIYISDLLAHTQY 404
Cdd:pfam00041   1 SAPSNLtVTDVTSTSLTVSWTPPPDGNG-PITGYEVEYRPKNSGEPW----------NEITVPGTTTSVTLTGLKPGTEY 69
                          90
                  ....*....|....*..
gi 111118978  405 TFEIQAVNGVTdQSPFS 421
Cdd:pfam00041  70 EVRVQAVNGGG-EGPPS 85
FN3 cd00063
Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein ...
325-431 6.11e-11

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.


Pssm-ID: 238020 [Multi-domain]  Cd Length: 93  Bit Score: 59.82  E-value: 6.11e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 325 PSAPQAV-ISSVNETSLMLEWTPPRDSGGREDLvYNIICKSCGSGRGacTRCGDNVqyaprqlgLTEPRIYISDLLAHTQ 403
Cdd:cd00063    1 PSPPTNLrVTDVTSTSVTLSWTPPEDDGGPITG-YVVEYREKGSGDW--KEVEVTP--------GSETSYTLTGLKPGTE 69
                         90       100
                 ....*....|....*....|....*...
gi 111118978 404 YTFEIQAVNGVTDqSPFSPqfaSVNITT 431
Cdd:cd00063   70 YEFRVRAVNGGGE-SPPSE---SVTVTT 93
FN3 smart00060
Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, ...
325-414 2.81e-08

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.


Pssm-ID: 214495 [Multi-domain]  Cd Length: 83  Bit Score: 51.85  E-value: 2.81e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978   325 PSAPQAV-ISSVNETSLMLEWTPPRDSGGREDLVYNIICKScgsgrgactrcGDNVQYAPRQLGLTEPRIYISDLLAHTQ 403
Cdd:smart00060   1 PSPPSNLrVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEYR-----------EEGSEWKEVNVTPSSTSYTLTGLKPGTE 69
                           90
                   ....*....|.
gi 111118978   404 YTFEIQAVNGV 414
Cdd:smart00060  70 YEFRVRAVNGA 80
FN3 COG3401
Fibronectin type 3 domain [General function prediction only];
402-515 1.54e-07

Fibronectin type 3 domain [General function prediction only];


Pssm-ID: 442628 [Multi-domain]  Cd Length: 603  Bit Score: 55.39  E-value: 1.54e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 402 TQYTFEIQAVNGVTDqSPFSPQFASVNITTNQAAPSAVSImhqVSRTVDSITLSWSqpDQPNGVILDYELQYYEKELSEY 481
Cdd:COG3401  203 TTYYYRVAATDTGGE-SAPSNEVSVTTPTTPPSAPTGLTA---TADTPGSVTLSWD--PVTESDATGYRVYRSNSGDGPF 276
                         90       100       110
                 ....*....|....*....|....*....|....*
gi 111118978 482 naTAIKSPTNTV-TVQGLKAGAIYVFQVRARTVAG 515
Cdd:COG3401  277 --TKVATVTTTSyTDTGLTNGTTYYYRVTAVDAAG 309
 
Name Accession Description Interval E-value
PTKc_EphR_B cd05065
Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze ...
616-884 0e+00

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: 614.57  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 616 IDISCVKIEQVIGAGEFGEVCSGHLKLPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPV 695
Cdd:cd05065    1 IDVSCVKIEEVIGAGEFGEVCRGRLKLPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNIIHLEGVVTKSRPV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 696 MIITEFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDT 775
Cdd:cd05065   81 MIITEFMENGALDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLSEMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDT 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 776 SDPTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSAL 855
Cdd:cd05065  161 SDPTYTSSLGGKIPIRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSYGERPYWDMSNQDVINAIEQDYRLPPPMDCPTAL 240
                        250       260
                 ....*....|....*....|....*....
gi 111118978 856 HQLMLDCWQKDRNHRPKFGQIVNTLDKMI 884
Cdd:cd05065  241 HQLMLDCWQKDRNLRPKFGQIVNTLDKMI 269
PTKc_EphR cd05033
Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
616-884 0e+00

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: 581.64  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 616 IDISCVKIEQVIGAGEFGEVCSGHLKLPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPV 695
Cdd:cd05033    1 IDASYVTIEKVIGGGEFGEVCSGSLKLPGKKEIDVAIKTLKSGYSDKQRLDFLTEASIMGQFDHPNVIRLEGVVTKSRPV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 696 MIITEFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDdt 775
Cdd:cd05033   81 MIVTEYMENGSLDKFLRENDGKFTVTQLVGMLRGIASGMKYLSEMNYVHRDLAARNILVNSDLVCKVSDFGLSRRLED-- 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 776 SDPTYTSAlGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSAL 855
Cdd:cd05033  159 SEATYTTK-GGKIPIRWTAPEAIAYRKFTSASDVWSFGIVMWEVMSYGERPYWDMSNQDVIKAVEDGYRLPPPMDCPSAL 237
                        250       260
                 ....*....|....*....|....*....
gi 111118978 856 HQLMLDCWQKDRNHRPKFGQIVNTLDKMI 884
Cdd:cd05033  238 YQLMLDCWQKDRNERPTFSQIVSTLDKMI 266
PTKc_EphR_A cd05066
Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze ...
616-884 0e+00

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: 559.87  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 616 IDISCVKIEQVIGAGEFGEVCSGHLKLPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPV 695
Cdd:cd05066    1 IDASCIKIEKVIGAGEFGEVCSGRLKLPGKREIPVAIKTLKAGYTEKQRRDFLSEASIMGQFDHPNIIHLEGVVTRSKPV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 696 MIITEFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDt 775
Cdd:cd05066   81 MIVTEYMENGSLDAFLRKHDGQFTVIQLVGMLRGIASGMKYLSDMGYVHRDLAARNILVNSNLVCKVSDFGLSRVLEDD- 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 776 SDPTYTSAlGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSAL 855
Cdd:cd05066  160 PEAAYTTR-GGKIPIRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSYGERPYWEMSNQDVIKAIEEGYRLPAPMDCPAAL 238
                        250       260
                 ....*....|....*....|....*....
gi 111118978 856 HQLMLDCWQKDRNHRPKFGQIVNTLDKMI 884
Cdd:cd05066  239 HQLMLDCWQKDRNERPKFEQIVSILDKLI 267
PTKc_EphR_A2 cd05063
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the ...
615-884 5.31e-167

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: 489.10  E-value: 5.31e-167
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 615 EIDISCVKIEQVIGAGEFGEVCSGHLKLPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTP 694
Cdd:cd05063    1 EIHPSHITKQKVIGAGEFGEVFRGILKMPGRKEVAVAIKTLKPGYTEKQRQDFLSEASIMGQFSHHNIIRLEGVVTKFKP 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 695 VMIITEFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDD 774
Cdd:cd05063   81 AMIITEYMENGALDKYLRDHDGEFSSYQLVGMLRGIAAGMKYLSDMNYVHRDLAARNILVNSNLECKVSDFGLSRVLEDD 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 775 tSDPTYTSAlGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSA 854
Cdd:cd05063  161 -PEGTYTTS-GGKIPIRWTAPEAIAYRKFTSASDVWSFGIVMWEVMSFGERPYWDMSNHEVMKAINDGFRLPAPMDCPSA 238
                        250       260       270
                 ....*....|....*....|....*....|
gi 111118978 855 LHQLMLDCWQKDRNHRPKFGQIVNTLDKMI 884
Cdd:cd05063  239 VYQLMLQCWQQDRARRPRFVDIVNLLDKLL 268
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
621-880 4.46e-143

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


Pssm-ID: 462242 [Multi-domain]  Cd Length: 258  Bit Score: 426.91  E-value: 4.46e-143
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  621 VKIEQVIGAGEFGEVCSGHLK-LPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIIT 699
Cdd:pfam07714   1 LTLGEKLGEGAFGEVYKGTLKgEGENTKIKVAVKTLKEGADEEEREDFLEEASIMKKLDHPNIVKLLGVCTQGEPLYIVT 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  700 EFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDdtsDPT 779
Cdd:pfam07714  81 EYMPGGDLLDFLRKHKRKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVVKISDFGLSRDIYD---DDY 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  780 YTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSALHQLM 859
Cdd:pfam07714 158 YRKRGGGKLPIKWMAPESLKDGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEFLEDGYRLPQPENCPDELYDLM 237
                         250       260
                  ....*....|....*....|.
gi 111118978  860 LDCWQKDRNHRPKFGQIVNTL 880
Cdd:pfam07714 238 KQCWAYDPEDRPTFSELVEDL 258
PTKc_EphR_A10 cd05064
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the ...
615-884 2.32e-139

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: 417.79  E-value: 2.32e-139
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 615 EIDISCVKIEQVIGAGEFGEVCSGHLKLPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTP 694
Cdd:cd05064    1 ELDNKSIKIERILGTGRFGELCRGCLKLPSKRELPVAIHTLRAGCSDKQRRGFLAEALTLGQFDHSNIVRLEGVITRGNT 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 695 VMIITEFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFglsRFLEDD 774
Cdd:cd05064   81 MMIVTEYMSNGALDSFLRKHEGQLVAGQLMGMLPGLASGMKYLSEMGYVHKGLAAHKVLVNSDLVCKISGF---RRLQED 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 775 TSDPTYTSaLGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSA 854
Cdd:cd05064  158 KSEAIYTT-MSGKSPVLWAAPEAIQYHHFSSASDVWSFGIVMWEVMSYGERPYWDMSGQDVIKAVEDGFRLPAPRNCPNL 236
                        250       260       270
                 ....*....|....*....|....*....|
gi 111118978 855 LHQLMLDCWQKDRNHRPKFGQIVNTLDKMI 884
Cdd:cd05064  237 LHQLMLDCWQKERGERPRFSQIHSILSKMV 266
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
621-880 2.01e-137

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


Pssm-ID: 197581 [Multi-domain]  Cd Length: 257  Bit Score: 412.31  E-value: 2.01e-137
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978   621 VKIEQVIGAGEFGEVCSGHLK-LPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIIT 699
Cdd:smart00219   1 LTLGKKLGEGAFGEVYKGKLKgKGGKKKVEVAVKTLKEDASEQQIEEFLREARIMRKLDHPNVVKLLGVCTEEEPLYIVM 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978   700 EFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDtsdpT 779
Cdd:smart00219  81 EYMEGGDLLSYLRKNRPKLSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRDLYDD----D 156
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978   780 YTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSALHQLM 859
Cdd:smart00219 157 YYRKRGGKLPIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEYLKNGYRLPQPPNCPPELYDLM 236
                          250       260
                   ....*....|....*....|.
gi 111118978   860 LDCWQKDRNHRPKFGQIVNTL 880
Cdd:smart00219 237 LQCWAEDPEDRPTFSELVEIL 257
STYKc smart00221
Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class ...
621-880 4.28e-135

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: 406.16  E-value: 4.28e-135
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978   621 VKIEQVIGAGEFGEVCSGHLK-LPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIIT 699
Cdd:smart00221   1 LTLGKKLGEGAFGEVYKGTLKgKGDGKEVEVAVKTLKEDASEQQIEEFLREARIMRKLDHPNIVKLLGVCTEEEPLMIVM 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978   700 EFMENGSLDSFLRQNDGQF-TVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTsdp 778
Cdd:smart00221  81 EYMPGGDLLDYLRKNRPKElSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRDLYDDD--- 157
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978   779 tYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSALHQL 858
Cdd:smart00221 158 -YYKVKGGKLPIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEEPYPGMSNAEVLEYLKKGYRLPKPPNCPPELYKL 236
                          250       260
                   ....*....|....*....|..
gi 111118978   859 MLDCWQKDRNHRPKFGQIVNTL 880
Cdd:smart00221 237 MLQCWAEDPEDRPTFSELVEIL 258
EphR_LBD_B2 cd10477
Ligand Binding Domain of Ephrin type-B Receptor 2; Ephrin receptors (EphRs) comprise the ...
19-196 2.55e-134

Ligand Binding Domain of Ephrin type-B Receptor 2; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EhpB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. EphB2 plays a role in cell positioning in the gastrointestinal tract by being expressed in proliferating progenitor cells. It also has been implicated in colorectal cancer. A loss of EphB2, as well as EphA4, also precedes memory decline in a murine model of Alzheimers disease. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine 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).


Pssm-ID: 198445  Cd Length: 178  Bit Score: 400.97  E-value: 2.55e-134
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  19 VEETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCS 98
Cdd:cd10477    1 AEETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIRTYQVCNVFESSQNNWLRTKYIRRRGAHRIHVEMKFSVRDCS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  99 SIPSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGFYLAF 178
Cdd:cd10477   81 SIPSVPGSCKETFNLYYYESDFDSATKTFPNWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRNGFYLAF 160
                        170
                 ....*....|....*...
gi 111118978 179 QDYGGCMSLIAVRVFYRK 196
Cdd:cd10477  161 QDYGGCMSLIAVRVFYRK 178
EphR_LBD_B cd10472
Ligand Binding Domain of Ephrin type-B receptors; Ephrin receptors (EphRs) comprise the ...
21-196 1.52e-130

Ligand Binding Domain of Ephrin type-B receptors; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphB receptors bind to transmembrane ephrin-B ligands. They play important roles in synapse formation and plasticity, spine morphogenesis, axon guidance, and angiogenesis. In the intestinal epithelium, EphB receptors are Wnt signaling target genes that control cell compartmentalization. They function as suppressors of colon cancer progression. There are six vertebrate EhpB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. One exception is EphB2, which also interacts with ephrin A5. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine 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.


Pssm-ID: 198440  Cd Length: 176  Bit Score: 391.16  E-value: 1.52e-130
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  21 ETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSI 100
Cdd:cd10472    1 ETLMDTRTATAELGWTAHPPSGWEEVSGYDENMNTIRTYQVCNVFESNQNNWLRTKFIRRRGAHRVYVEMKFTVRDCSSI 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 101 PSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGFYLAFQD 180
Cdd:cd10472   81 PNVPGSCKETFNLYYYESDSDIATKTSPFWMENPYVKVDTIAADESFSQVDLGGRVMKVNTEVRSFGPLSRNGFYLAFQD 160
                        170
                 ....*....|....*.
gi 111118978 181 YGGCMSLIAVRVFYRK 196
Cdd:cd10472  161 YGACMSLISVRVFYKK 176
PTKc cd00192
Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
626-881 1.80e-124

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: 378.81  E-value: 1.80e-124
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 626 VIGAGEFGEVCSGHLKLPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENG 705
Cdd:cd00192    2 KLGEGAFGEVYKGKLKGGDGKTVDVAVKTLKEDASESERKDFLKEARVMKKLGHPNVVRLLGVCTEEEPLYLVMEYMEGG 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 706 SLDSFLRQN--------DGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSd 777
Cdd:cd00192   82 DLLDFLRKSrpvfpspePSTLSLKDLLSFAIQIAKGMEYLASKKFVHRDLAARNCLVGEDLVVKISDFGLSRDIYDDDY- 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 778 ptYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSALHQ 857
Cdd:cd00192  161 --YRKKTGGKLPIRWMAPESLKDGIFTSKSDVWSFGVLLWEIFTLGATPYPGLSNEEVLEYLRKGYRLPKPENCPDELYE 238
                        250       260
                 ....*....|....*....|....
gi 111118978 858 LMLDCWQKDRNHRPKFGQIVNTLD 881
Cdd:cd00192  239 LMLSCWQLDPEDRPTFSELVERLE 262
EPH_lbd smart00615
Ephrin receptor ligand binding domain;
20-196 3.28e-112

Ephrin receptor ligand binding domain;


Pssm-ID: 128877  Cd Length: 177  Bit Score: 343.11  E-value: 3.28e-112
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978    20 EETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSS 99
Cdd:smart00615   1 EVVLLDTKTETGELGWTTYPPEGWEEVSGMDENGTPIRTYQVCNVQEGNQNNWLRTNFIRRRGAQRIYVELKFTVRDCSS 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978   100 IPSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGFYLAFQ 179
Cdd:smart00615  81 LPGVGGSCKETFNLYYYESDTDTATNTLPNWMENPYTKVDTIAADESFTGGDVGKRNVKLNTEVRSLGPLSKKGFYLAFQ 160
                          170
                   ....*....|....*..
gi 111118978   180 DYGGCMSLIAVRVFYRK 196
Cdd:smart00615 161 DQGACVALVSVRVFYKK 177
EphR_LBD_B1 cd10476
Ligand Binding Domain of Ephrin type-B Receptor 1; Ephrin receptors (EphRs) comprise the ...
21-196 2.34e-107

Ligand Binding Domain of Ephrin type-B Receptor 1; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EhpB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. Using EphB1 knockout-mice, EphB1 has been shown to be essential to the development of long-term potentiation (LTP), a cellular model of synaptic plasticity, learning and memory formation. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine 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).


Pssm-ID: 198444  Cd Length: 176  Bit Score: 330.48  E-value: 2.34e-107
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  21 ETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSI 100
Cdd:cd10476    1 ETLMDTRTATAELGWTANPASGWEEVSGYDENLNTIRTYQVCNVFEPNQNNWLLTTFINRRGAHRIYTEMRFTVRDCSSL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 101 PSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGFYLAFQD 180
Cdd:cd10476   81 PNVPGSCKETFNLYYYETDSVIATKKSAFWTEAPYLKVDTIAADESFSQVDFGGRLMKVNTEVRSFGPLTRNGFYLAFQD 160
                        170
                 ....*....|....*.
gi 111118978 181 YGGCMSLIAVRVFYRK 196
Cdd:cd10476  161 YGACMSLLSVRVFFKK 176
Ephrin_lbd pfam01404
Ephrin receptor ligand binding domain; The Eph receptors, which bind to ephrins pfam00812 are ...
21-197 1.66e-103

Ephrin receptor ligand binding domain; The Eph receptors, which bind to ephrins pfam00812 are a large family of receptor tyrosine kinases. This family represents the amino terminal domain which binds the ephrin ligand.


Pssm-ID: 460198  Cd Length: 177  Bit Score: 320.38  E-value: 1.66e-103
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978   21 ETLMDSTTATAELGWMVHPPS-GWEEVSGYDENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSS 99
Cdd:pfam01404   1 EVLLDTTSATSDLGWTTYPYDgGWEEVSGLDENGRTIRTYQVCNVEEPNQNNWLRTPFIPRGGASRVYVELKFTVRDCSS 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  100 IPSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADESFSQVDlGGRVMKINTEVRSFGPVSRSGFYLAFQ 179
Cdd:pfam01404  81 IPGVSGTCKETFNLYYYESDADAATATPPAWRENPYKKIDTIAADESFTDTG-KGRVMKLNTETRSIGPLSKRGFYLAFQ 159
                         170
                  ....*....|....*...
gi 111118978  180 DYGGCMSLIAVRVFYRKC 197
Cdd:pfam01404 160 DQGACIALLSVRVFYKKC 177
EphR_LBD_B3 cd10478
Ligand Binding Domain of Ephrin type-B Receptor 3; Ephrin receptors (EphRs) comprise the ...
20-196 2.10e-101

Ligand Binding Domain of Ephrin type-B Receptor 3; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EhpB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. EphB3 plays a role in cell positioning in the gastrointestinal tract by being preferentially expressed in Paneth cells. It also has been implicated in early colorectal cancer and early stage squamous cell lung cancer. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine 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).


Pssm-ID: 198446  Cd Length: 173  Bit Score: 314.64  E-value: 2.10e-101
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  20 EETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSS 99
Cdd:cd10478    1 EETLMDTKWVTSELAWTTHPESGWEEVSGYDEAMNPIRTYQVCNVRESNQNNWLRTGFIPRRDVQRVYVELKFTVRDCNS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 100 IPSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADESFSQVDLGgrvmKINTEVRSFGPVSRSGFYLAFQ 179
Cdd:cd10478   81 IPNIPGSCKETFNLFYYESDSDSASASSPFWMENPYVKVDTIAPDESFSRLDSG----RVNTKVRSFGPLSKAGFYLAFQ 156
                        170
                 ....*....|....*..
gi 111118978 180 DYGGCMSLIAVRVFYRK 196
Cdd:cd10478  157 DLGACMSLISVRAFFKK 173
PTKc_Src_like cd05034
Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
627-881 9.04e-100

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: 313.06  E-value: 9.04e-100
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKlpgkREIFVAIKTLKSGYTEKQrrDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGS 706
Cdd:cd05034    3 LGAGQFGEVWMGVWN----GTTKVAVKTLKPGTMSPE--AFLQEAQIMKKLRHDKLVQLYAVCSDEEPIYIVTELMSKGS 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 707 LDSFLRQNDGQFTVI-QLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTsdptYTSALG 785
Cdd:cd05034   77 LLDYLRTGEGRALRLpQLIDMAAQIASGMAYLESRNYIHRDLAARNILVGENNVCKVADFGLARLIEDDE----YTAREG 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 786 GKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSALHQLMLDCWQK 865
Cdd:cd05034  153 AKFPIKWTAPEAALYGRFTIKSDVWSFGILLYEIVTYGRVPYPGMTNREVLEQVERGYRMPKPPGCPDELYDIMLQCWKK 232
                        250
                 ....*....|....*.
gi 111118978 866 DRNHRPKFGQIVNTLD 881
Cdd:cd05034  233 EPEERPTFEYLQSFLE 248
EphR_LBD cd10319
Ligand Binding Domain of Ephrin Receptors; Ephrin receptors (EphRs) comprise the largest ...
21-196 1.49e-98

Ligand Binding Domain of Ephrin Receptors; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). They are subdivided into 2 groups, A and B type receptors, depending on their ligand ephrin-A or ephrin-B, respectively. 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. Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EhpB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. One exception is EphB2, which also interacts with ephrin A5. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine 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.


Pssm-ID: 198439  Cd Length: 177  Bit Score: 307.02  E-value: 1.49e-98
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  21 ETLMDSTTATAELGWMVHPPS--GWEEVSGYDENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCS 98
Cdd:cd10319    1 VVLLDTTLATSDLGWLTYPYGhgGWDEESGLDPDGANIRTYVVCNVAMPNQDNWLRTPFIERRGAQRIYVELKFTVRDCE 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  99 SIPSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADESFSQVDlGGRVMKINTEVRSFGPVSRSGFYLAF 178
Cdd:cd10319   81 SFPGNARSCKETFNLYYYESDHDTATKEFPPWNEDPYTKIDTIAADESFKSSN-EDTTEKLNTETRSIGPLTKRGFYLAF 159
                        170
                 ....*....|....*...
gi 111118978 179 QDYGGCMSLIAVRVFYRK 196
Cdd:cd10319  160 QDQGACMSLLSVKVYYKK 177
PTKc_Frk_like cd05068
Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
615-873 2.26e-95

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: 302.40  E-value: 2.26e-95
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 615 EIDISCVKIEQVIGAGEFGEVCSGHLKlpgkREIFVAIKTLKSGYTEKQrrDFLSEASIMGQFDHPNVIHLEGVVTKSTP 694
Cdd:cd05068    4 EIDRKSLKLLRKLGSGQFGEVWEGLWN----NTTPVAVKTLKPGTMDPE--DFLREAQIMKKLRHPKLIQLYAVCTLEEP 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 695 VMIITEFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDD 774
Cdd:cd05068   78 IYIITELMKHGSLLEYLQGKGRSLQLPQLIDMAAQVASGMAYLESQNYIHRDLAARNVLVGENNICKVADFGLARVIKVE 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 775 TsdpTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSA 854
Cdd:cd05068  158 D---EYEAREGAKFPIKWTAPEAANYNRFSIKSDVWSFGILLTEIVTYGRIPYPGMTNAEVLQQVERGYRMPCPPNCPPQ 234
                        250
                 ....*....|....*....
gi 111118978 855 LHQLMLDCWQKDRNHRPKF 873
Cdd:cd05068  235 LYDIMLECWKADPMERPTF 253
PTKc_Fes_like cd05041
Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; ...
625-881 1.75e-92

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: 293.97  E-value: 1.75e-92
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKlPGKREifVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMEN 704
Cdd:cd05041    1 EKIGRGNFGDVYRGVLK-PDNTE--VAVKTCRETLPPDLKRKFLQEARILKQYDHPNIVKLIGVCVQKQPIMIVMELVPG 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 705 GSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRflEDDtsDPTYTSAL 784
Cdd:cd05041   78 GSLLTFLRKKGARLTVKQLLQMCLDAAAGMEYLESKNCIHRDLAARNCLVGENNVLKISDFGMSR--EEE--DGEYTVSD 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 785 G-GKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSALHQLMLDCW 863
Cdd:cd05041  154 GlKQIPIKWTAPEALNYGRYTSESDVWSFGILLWEIFSLGATPYPGMSNQQTREQIESGYRMPAPELCPEAVYRLMLQCW 233
                        250
                 ....*....|....*...
gi 111118978 864 QKDRNHRPKFGQIVNTLD 881
Cdd:cd05041  234 AYDPENRPSFSEIYNELQ 251
PTKc_Syk_like cd05060
Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
627-880 5.27e-90

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: 287.71  E-value: 5.27e-90
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVvTKSTPVMIITEFMENGS 706
Cdd:cd05060    3 LGHGNFGSVRKGVYLMKSGKEVEVAVKTLKQEHEKAGKKEFLREASVMAQLDHPCIVRLIGV-CKGEPLMLVMELAPLGP 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 707 LDSFLRQNdGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSdpTYTSALGG 786
Cdd:cd05060   82 LLKYLKKR-REIPVSDLKELAHQVAMGMAYLESKHFVHRDLAARNVLLVNRHQAKISDFGMSRALGAGSD--YYRATTAG 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 787 KIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSALHQLMLDCWQKD 866
Cdd:cd05060  159 RWPLKWYAPECINYGKFSSKSDVWSYGVTLWEAFSYGAKPYGEMKGPEVIAMLESGERLPRPEECPQEIYSIMLSCWKYR 238
                        250
                 ....*....|....
gi 111118978 867 RNHRPKFGQIVNTL 880
Cdd:cd05060  239 PEDRPTFSELESTF 252
EphR_LBD_A cd10473
Ligand Binding Domain of Ephrin type-A Receptors; Ephrin receptors (EphRs) comprise the ...
20-196 1.61e-86

Ligand Binding Domain of Ephrin type-A Receptors; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (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 a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine 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.


Pssm-ID: 198441  Cd Length: 173  Bit Score: 275.09  E-value: 1.61e-86
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  20 EETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSS 99
Cdd:cd10473    1 EVVLLDSKTAQGELGWITYPPNGWEEISEMDEDYTPIRTYQVCNVMEPNQNNWLRTNWIYRGEAQRIYIELKFTLRDCNS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 100 IPSVPGSCKETFNLYYYEADFDSATKTfpnwMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGFYLAFQ 179
Cdd:cd10473   81 FPGVLGTCKETFNLYYMESDLDLGRNI----RENQFTKIDTIAADESFTQGDLGDRIMKLNTEVREVGPLTKKGFYLAFQ 156
                        170
                 ....*....|....*..
gi 111118978 180 DYGGCMSLIAVRVFYRK 196
Cdd:cd10473  157 DVGACVALVSVRVYYKK 173
PTKc_Csk_like cd05039
Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
615-880 1.22e-85

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: 275.77  E-value: 1.22e-85
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 615 EIDISCVKIEQVIGAGEFGEVCSGHLKlpGKreiFVAIKTLKSGYTEKQRrdFLSEASIMGQFDHPNVIHLEGVVTKSTP 694
Cdd:cd05039    2 AINKKDLKLGELIGKGEFGDVMLGDYR--GQ---KVAVKCLKDDSTAAQA--FLAEASVMTTLRHPNLVQLLGVVLEGNG 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 695 VMIITEFMENGSLDSFLRQNDGQ-FTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFlED 773
Cdd:cd05039   75 LYIVTEYMAKGSLVDYLRSRGRAvITRKDQLGFALDVCEGMEYLESKKFVHRDLAARNVLVSEDNVAKVSDFGLAKE-AS 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 774 DTSDptytsalGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPS 853
Cdd:cd05039  154 SNQD-------GGKLPIKWTAPEALREKKFSTKSDVWSFGILLWEIYSFGRVPYPRIPLKDVVPHVEKGYRMEAPEGCPP 226
                        250       260
                 ....*....|....*....|....*..
gi 111118978 854 ALHQLMLDCWQKDRNHRPKFGQIVNTL 880
Cdd:cd05039  227 EVYKVMKNCWELDPAKRPTFKQLREKL 253
PTKc_FAK cd05056
Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the ...
615-880 1.63e-83

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: 270.83  E-value: 1.63e-83
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 615 EIDISCVKIEQVIGAGEFGEVCSGHLKLPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKStP 694
Cdd:cd05056    2 EIQREDITLGRCIGEGQFGDVYQGVYMSPENEKIAVAVKTCKNCTSPSVREKFLQEAYIMRQFDHPHIVKLIGVITEN-P 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 695 VMIITEFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDD 774
Cdd:cd05056   81 VWIVMELAPLGELRSYLQVNKYSLDLASLILYAYQLSTALAYLESKRFVHRDIAARNVLVSSPDCVKLGDFGLSRYMEDE 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 775 TsdptYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSA 854
Cdd:cd05056  161 S----YYKASKGKLPIKWMAPESINFRRFTSASDVWMFGVCMWEILMLGVKPFQGVKNNDVIGRIENGERLPMPPNCPPT 236
                        250       260
                 ....*....|....*....|....*.
gi 111118978 855 LHQLMLDCWQKDRNHRPKFGQIVNTL 880
Cdd:cd05056  237 LYSLMTKCWAYDPSKRPRFTELKAQL 262
PTKc_Tec_like cd05059
Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
616-880 2.20e-83

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: 269.70  E-value: 2.20e-83
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 616 IDISCVKIEQVIGAGEFGEVCSGHLKlpGKREifVAIKTLKSGYTEKQrrDFLSEASIMGQFDHPNVIHLEGVVTKSTPV 695
Cdd:cd05059    1 IDPSELTFLKELGSGQFGVVHLGKWR--GKID--VAIKMIKEGSMSED--DFIEEAKVMMKLSHPKLVQLYGVCTKQRPI 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 696 MIITEFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDt 775
Cdd:cd05059   75 FIVTEYMANGCLLNYLRERRGKFQTEQLLEMCKDVCEAMEYLESNGFIHRDLAARNCLVGEQNVVKVSDFGLARYVLDD- 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 776 sdpTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSAL 855
Cdd:cd05059  154 ---EYTSSVGTKFPVKWSPPEVFMYSKFSSKSDVWSFGVLMWEVFSEGKMPYERFSNSEVVEHISQGYRLYRPHLAPTEV 230
                        250       260
                 ....*....|....*....|....*
gi 111118978 856 HQLMLDCWQKDRNHRPKFGQIVNTL 880
Cdd:cd05059  231 YTIMYSCWHEKPEERPTFKILLSQL 255
PTKc_Srm_Brk cd05148
Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal ...
623-881 3.46e-82

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: 266.61  E-value: 3.46e-82
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 623 IEQVIGAGEFGEVCSGHLKlpgkREIFVAIKTLKSGYTEKQRrDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFM 702
Cdd:cd05148   10 LERKLGSGYFGEVWEGLWK----NRVRVAIKILKSDDLLKQQ-DFQKEVQALKRLRHKHLISLFAVCSVGEPVYIITELM 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 703 ENGSLDSFLRQNDGQ-FTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTsdptYT 781
Cdd:cd05148   85 EKGSLLAFLRSPEGQvLPVASLIDMACQVAEGMAYLEEQNSIHRDLAARNILVGEDLVCKVADFGLARLIKEDV----YL 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 782 SAlGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSALHQLMLD 861
Cdd:cd05148  161 SS-DKKIPYKWTAPEAASHGTFSTKSDVWSFGILLYEMFTYGQVPYPGMNNHEVYDQITAGYRMPCPAKCPQEIYKIMLE 239
                        250       260
                 ....*....|....*....|
gi 111118978 862 CWQKDRNHRPKFGQIVNTLD 881
Cdd:cd05148  240 CWAAEPEDRPSFKALREELD 259
PTKc_Lck_Blk cd05067
Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs ...
615-881 1.15e-80

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: 262.90  E-value: 1.15e-80
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 615 EIDISCVKIEQVIGAGEFGEVCSGHLKLPGKreifVAIKTLKSGYTEKQRrdFLSEASIMGQFDHPNVIHLEGVVTKStP 694
Cdd:cd05067    3 EVPRETLKLVERLGAGQFGEVWMGYYNGHTK----VAIKSLKQGSMSPDA--FLAEANLMKQLQHQRLVRLYAVVTQE-P 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 695 VMIITEFMENGSLDSFLRQNDG-QFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLED 773
Cdd:cd05067   76 IYIITEYMENGSLVDFLKTPSGiKLTINKLLDMAAQIAEGMAFIEERNYIHRDLRAANILVSDTLSCKIADFGLARLIED 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 774 DTsdptYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPS 853
Cdd:cd05067  156 NE----YTAREGAKFPIKWTAPEAINYGTFTIKSDVWSFGILLTEIVTHGRIPYPGMTNPEVIQNLERGYRMPRPDNCPE 231
                        250       260
                 ....*....|....*....|....*...
gi 111118978 854 ALHQLMLDCWQKDRNHRPKFGQIVNTLD 881
Cdd:cd05067  232 ELYQLMRLCWKERPEDRPTFEYLRSVLE 259
PTKc_Ror cd05048
Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan ...
615-880 7.09e-80

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: 261.16  E-value: 7.09e-80
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 615 EIDISCVKIEQVIGAGEFGEVCSGHLKLPGKRE--IFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKS 692
Cdd:cd05048    1 EIPLSAVRFLEELGEGAFGKVYKGELLGPSSEEsaISVAIKTLKENASPKTQQDFRREAELMSDLQHPNIVCLLGVCTKE 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 693 TPVMIITEFMENGSLDSFLRQN------------DGQFTVIQLVGMLR---GIAAGMKYLADMNYVHRDLAARNILVNSN 757
Cdd:cd05048   81 QPQCMLFEYMAHGDLHEFLVRHsphsdvgvssddDGTASSLDQSDFLHiaiQIAAGMEYLSSHHYVHRDLAARNCLVGDG 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 758 LVCKVSDFGLSRfleDDTSDPTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVIN 837
Cdd:cd05048  161 LTVKISDFGLSR---DIYSSDYYRVQSKSLLPVRWMPPEAILYGKFTTESDVWSFGVVLWEIFSYGLQPYYGYSNQEVIE 237
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|...
gi 111118978 838 AIEQDYRLPPPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTL 880
Cdd:cd05048  238 MIRSRQLLPCPEDCPARVYSLMVECWHEIPSRRPRFKEIHTRL 280
PTKc_Abl cd05052
Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of ...
615-884 9.97e-80

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: 260.05  E-value: 9.97e-80
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 615 EIDISCVKIEQVIGAGEFGEVCSGHLKlpgKREIFVAIKTLKSGYTEKQrrDFLSEASIMGQFDHPNVIHLEGVVTKSTP 694
Cdd:cd05052    2 EIERTDITMKHKLGGGQYGEVYEGVWK---KYNLTVAVKTLKEDTMEVE--EFLKEAAVMKEIKHPNLVQLLGVCTREPP 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 695 VMIITEFMENGSLDSFLRQNDGQ-FTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLED 773
Cdd:cd05052   77 FYIITEFMPYGNLLDYLRECNREeLNAVVLLYMATQIASAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTG 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 774 DTsdptYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPS 853
Cdd:cd05052  157 DT----YTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKGYRMERPEGCPP 232
                        250       260       270
                 ....*....|....*....|....*....|.
gi 111118978 854 ALHQLMLDCWQKDRNHRPKFGQIVNTLDKMI 884
Cdd:cd05052  233 KVYELMRACWQWNPSDRPSFAEIHQALETMF 263
STKc_MAP3K-like cd13999
Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine ...
627-880 8.16e-79

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: 257.08  E-value: 8.16e-79
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKlpGKReifVAIKTLKSGY-TEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENG 705
Cdd:cd13999    1 IGSGSFGEVYKGKWR--GTD---VAIKKLKVEDdNDELLKEFRREVSILSKLRHPNIVQFIGACLSPPPLCIVTEYMPGG 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 706 SLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTsdPTYTSALG 785
Cdd:cd13999   76 SLYDLLHKKKIPLSWSLRLKIALDIARGMNYLHSPPIIHRDLKSLNILLDENFTVKIADFGLSRIKNSTT--EKMTGVVG 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 786 GkipIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTN-QDVINAIEQDYRLPPPMDCPSALHQLMLDCWQ 864
Cdd:cd13999  154 T---PRWMAPEVLRGEPYTEKADVYSFGIVLWELLT-GEVPFKELSPiQIAAAVVQKGLRPPIPPDCPPELSKLIKRCWN 229
                        250
                 ....*....|....*.
gi 111118978 865 KDRNHRPKFGQIVNTL 880
Cdd:cd13999  230 EDPEKRPSFSEIVKRL 245
PTKc_InsR_like cd05032
Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer ...
615-881 1.78e-78

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: 257.27  E-value: 1.78e-78
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 615 EIDISCVKIEQVIGAGEFGEVCSGHLK--LPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKS 692
Cdd:cd05032    2 ELPREKITLIRELGQGSFGMVYEGLAKgvVKGEPETRVAIKTVNENASMRERIEFLNEASVMKEFNCHHVVRLLGVVSTG 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 693 TPVMIITEFMENGSLDSFLR-------QNDGQ--FTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVS 763
Cdd:cd05032   82 QPTLVVMELMAKGDLKSYLRsrrpeaeNNPGLgpPTLQKFIQMAAEIADGMAYLAAKKFVHRDLAARNCMVAEDLTVKIG 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 764 DFGLSRFL-EDDTsdptYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQD 842
Cdd:cd05032  162 DFGMTRDIyETDY----YRKGGKGLLPVRWMAPESLKDGVFTTKSDVWSFGVVLWEMATLAEQPYQGLSNEEVLKFVIDG 237
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 111118978 843 YRLPPPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLD 881
Cdd:cd05032  238 GHLDLPENCPDKLLELMRMCWQYNPKMRPTFLEIVSSLK 276
PTKc_Ack_like cd05040
Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs ...
627-880 7.56e-78

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: 254.96  E-value: 7.56e-78
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKREIFVAIKTLKSGYTEKQR--RDFLSEASIMGQFDHPNVIHLEGVVTkSTPVMIITEFMEN 704
Cdd:cd05040    3 LGDGSFGVVRRGEWTTPSGKVIQVAVKCLKSDVLSQPNamDDFLKEVNAMHSLDHPNLIRLYGVVL-SSPLMMVTELAPL 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 705 GSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLedDTSDPTYTSAL 784
Cdd:cd05040   82 GSLLDRLRKDQGHFLISTLCDYAVQIANGMAYLESKRFIHRDLAARNILLASKDKVKIGDFGLMRAL--PQNEDHYVMQE 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 785 GGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDY-RLPPPMDCPSALHQLMLDCW 863
Cdd:cd05040  160 HRKVPFAWCAPESLKTRKFSHASDVWMFGVTLWEMFTYGEEPWLGLNGSQILEKIDKEGeRLERPDDCPQDIYNVMLQCW 239
                        250
                 ....*....|....*..
gi 111118978 864 QKDRNHRPKFGQIVNTL 880
Cdd:cd05040  240 AHKPADRPTFVALRDFL 256
PTKc_Src_Fyn_like cd14203
Catalytic domain of a subset of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
627-873 8.62e-78

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: 254.46  E-value: 8.62e-78
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKreifVAIKTLKSGYTEKQRrdFLSEASIMGQFDHPNVIHLEGVVTKStPVMIITEFMENGS 706
Cdd:cd14203    3 LGQGCFGEVWMGTWNGTTK----VAIKTLKPGTMSPEA--FLEEAQIMKKLRHDKLVQLYAVVSEE-PIYIVTEFMSKGS 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 707 LDSFLRQNDGQFTVI-QLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTsdptYTSALG 785
Cdd:cd14203   76 LLDFLKDGEGKYLKLpQLVDMAAQIASGMAYIERMNYIHRDLRAANILVGDNLVCKIADFGLARLIEDNE----YTARQG 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 786 GKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSALHQLMLDCWQK 865
Cdd:cd14203  152 AKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMNNREVLEQVERGYRMPCPPGCPESLHELMCQCWRK 231

                 ....*...
gi 111118978 866 DRNHRPKF 873
Cdd:cd14203  232 DPEERPTF 239
PTKc_EGFR_like cd05057
Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs ...
625-887 8.98e-78

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: 255.42  E-value: 8.98e-78
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKLPGKR-EIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTpVMIITEFME 703
Cdd:cd05057   13 KVLGSGAFGTVYKGVWIPEGEKvKIPVAIKVLREETGPKANEEILDEAYVMASVDHPHLVRLLGICLSSQ-VQLITQLMP 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 704 NGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNS-NLVcKVSDFGLSRFLEDDTSDPTYTs 782
Cdd:cd05057   92 LGCLLDYVRNHRDNIGSQLLLNWCVQIAKGMSYLEEKRLVHRDLAARNVLVKTpNHV-KITDFGLAKLLDVDEKEYHAE- 169
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 783 alGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSALHQLMLDC 862
Cdd:cd05057  170 --GGKVPIKWMALESIQYRIYTHKSDVWSYGVTVWELMTFGAKPYEGIPAVEIPDLLEKGERLPQPPICTIDVYMVLVKC 247
                        250       260
                 ....*....|....*....|....*
gi 111118978 863 WQKDRNHRPKFGQIVNTLDKMIRNP 887
Cdd:cd05057  248 WMIDAESRPTFKELANEFSKMARDP 272
PTKc_Lyn cd05072
Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the ...
613-881 1.08e-77

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: 254.97  E-value: 1.08e-77
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 613 AKEIDISCVKIEQVIGAGEFGEVCSGHLKLPGKreifVAIKTLKSGYTEKQRrdFLSEASIMGQFDHPNVIHLEGVVTKS 692
Cdd:cd05072    1 AWEIPRESIKLVKKLGAGQFGEVWMGYYNNSTK----VAVKTLKPGTMSVQA--FLEEANLMKTLQHDKLVRLYAVVTKE 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 693 TPVMIITEFMENGSLDSFLRQNDG-QFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFL 771
Cdd:cd05072   75 EPIYIITEYMAKGSLLDFLKSDEGgKVLLPKLIDFSAQIAEGMAYIERKNYIHRDLRAANVLVSESLMCKIADFGLARVI 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 772 EDDTsdptYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDC 851
Cdd:cd05072  155 EDNE----YTAREGAKFPIKWTAPEAINFGSFTIKSDVWSFGILLYEIVTYGKIPYPGMSNSDVMSALQRGYRMPRMENC 230
                        250       260       270
                 ....*....|....*....|....*....|
gi 111118978 852 PSALHQLMLDCWQKDRNHRPKFGQIVNTLD 881
Cdd:cd05072  231 PDELYDIMKTCWKEKAEERPTFDYLQSVLD 260
EphR_LBD_A7 cd10485
Ligand Binding Domain of Ephrin type-A Receptor 7; Ephrin receptors (EphRs) comprise the ...
19-197 1.30e-76

Ligand Binding Domain of Ephrin type-A Receptor 7; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (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. EphA7 has been implicated in various cancers, including prostate, gastic and colorectal cancers. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine 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).


Pssm-ID: 198453  Cd Length: 177  Bit Score: 248.41  E-value: 1.30e-76
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  19 VEETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCS 98
Cdd:cd10485    2 KEVILLDSKAQQTELEWISSPPSGWEEISGLDENYTPIRTYQVCQVMEPNQNNWLRTNWISKGNAQRIFVELKFTLRDCN 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  99 SIPSVPGSCKETFNLYYYEADFDSATktfpNWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGFYLAF 178
Cdd:cd10485   82 SLPGVLGTCKETFNLYYYETDYDTGR----NIRENQYVKIDTIAADESFTQGDLGERKMKLNTEVREIGPLSKKGFYLAF 157
                        170
                 ....*....|....*....
gi 111118978 179 QDYGGCMSLIAVRVFYRKC 197
Cdd:cd10485  158 QDVGACIALVSVKVYYKKC 176
PTKc_Trk cd05049
Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze ...
615-882 1.87e-76

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: 252.00  E-value: 1.87e-76
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 615 EIDISCVKIEQVIGAGEFGEVCSGHLK--LPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKS 692
Cdd:cd05049    1 HIKRDTIVLKRELGEGAFGKVFLGECYnlEPEQDKMLVAVKTLKDASSPDARKDFEREAELLTNLQHENIVKFYGVCTEG 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 693 TPVMIITEFMENGSLDSFLRQND-------------GQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLV 759
Cdd:cd05049   81 DPLLMVFEYMEHGDLNKFLRSHGpdaaflasedsapGELTLSQLLHIAVQIASGMVYLASQHFVHRDLATRNCLVGTNLV 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 760 CKVSDFGLSRfleDDTSDPTYTsaLGGK--IPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVIN 837
Cdd:cd05049  161 VKIGDFGMSR---DIYSTDYYR--VGGHtmLPIRWMPPESILYRKFTTESDVWSFGVVLWEIFTYGKQPWFQLSNTEVIE 235
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*
gi 111118978 838 AIEQDYRLPPPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDK 882
Cdd:cd05049  236 CITQGRLLQRPRTCPSEVYAVMLGCWKREPQQRLNIKDIHKRLQE 280
EphR_LBD_A10 cd10487
Ligand Binding Domain of Ephrin type-A Receptor 10; Ephrin receptors (EphRs) comprise the ...
23-196 1.96e-76

Ligand Binding Domain of Ephrin type-A Receptor 10; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (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. 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. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine 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 results in cell-cell repulsion or adhesion.


Pssm-ID: 198455  Cd Length: 173  Bit Score: 247.63  E-value: 1.96e-76
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  23 LMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSIPS 102
Cdd:cd10487    4 LLDSKESQAELGWTSLPSNGWEEISGVDEHYKPIRTYQVCNVMEPNQNNWLQTGWISRGRGQRIFIELQFTLRDCNSIPG 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 103 VPGSCKETFNLYYYEADFDSATKTfpnwMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGFYLAFQDYG 182
Cdd:cd10487   84 VAGTCKETFNLYYAESDADLGRRL----RESRPRKIDTIAADESFTQGDLGERKMKLNTEVREIGHLSRRGFHLAFQDVG 159
                        170
                 ....*....|....
gi 111118978 183 GCMSLIAVRVFYRK 196
Cdd:cd10487  160 ACVALVSVRVYYKQ 173
PTKc_c-ros cd05044
Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the ...
627-880 3.83e-76

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: 250.80  E-value: 3.83e-76
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLK---LPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFME 703
Cdd:cd05044    3 LGSGAFGEVFEGTAKdilGDGSGETKVAVKTLRKGATDQEKAEFLKEAHLMSNFKHPNILKLLGVCLDNDPQYIILELME 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 704 NGSLDSFLRQN------DGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSN----LVCKVSDFGLSRfleD 773
Cdd:cd05044   83 GGDLLSYLRAArptaftPPLLTLKDLLSICVDVAKGCVYLEDMHFVHRDLAARNCLVSSKdyreRVVKIGDFGLAR---D 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 774 DTSDPTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPS 853
Cdd:cd05044  160 IYKNDYYRKEGEGLLPVRWMAPESLVDGVFTTQSDVWAFGVLMWEILTLGQQPYPARNNLEVLHFVRAGGRLDQPDNCPD 239
                        250       260
                 ....*....|....*....|....*..
gi 111118978 854 ALHQLMLDCWQKDRNHRPKFGQIVNTL 880
Cdd:cd05044  240 DLYELMLRCWSTDPEERPSFARILEQL 266
EphR_LBD_B6 cd10475
Ligand Binding Domain of Ephrin type-B Receptor 6; Ephrin receptors (EphRs) comprise the ...
20-196 7.99e-76

Ligand Binding Domain of Ephrin type-B Receptor 6; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EhpB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. EphB6, a kinase-defective member of this family, is downregulated in MDA-MB-231-breast cancer cells and myeloid cancers and upregulated in neuroblasoma and glioblastoma. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine 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).


Pssm-ID: 198443  Cd Length: 180  Bit Score: 246.38  E-value: 7.99e-76
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  20 EETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIRTYQVCNVF--ESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDC 97
Cdd:cd10475    1 EEVLLDTTGETSEIGWLTYPPGGWDEVSVLDDQRRLTRTFEVCNVAaqGPGQDNWLRTHFIERRGAHRVHVRLHFSVRDC 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  98 SSIPSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADESFSQVDL-GGRVMKINTEVRSFGPVSRSGFYL 176
Cdd:cd10475   81 ASLGVPGGTCRETFTLYYRQADEPDEPADKSEWHEGPWTKVDTIAADESFPASLGkGGQGLQMNVKERSFGPLTQRGFYL 160
                        170       180
                 ....*....|....*....|
gi 111118978 177 AFQDYGGCMSLIAVRVFYRK 196
Cdd:cd10475  161 AFQDSGACLSLVAVKVFFYK 180
PTKc_Itk cd05112
Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs ...
616-880 9.41e-76

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: 249.10  E-value: 9.41e-76
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 616 IDISCVKIEQVIGAGEFGEVCSGHLKlpGKREifVAIKTLKSGYTEKQrrDFLSEASIMGQFDHPNVIHLEGVVTKSTPV 695
Cdd:cd05112    1 IDPSELTFVQEIGSGQFGLVHLGYWL--NKDK--VAIKTIREGAMSEE--DFIEEAEVMMKLSHPKLVQLYGVCLEQAPI 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 696 MIITEFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDt 775
Cdd:cd05112   75 CLVFEFMEHGCLSDYLRTQRGLFSAETLLGMCLDVCEGMAYLEEASVIHRDLAARNCLVGENQVVKVSDFGMTRFVLDD- 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 776 sdpTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSAL 855
Cdd:cd05112  154 ---QYTSSTGTKFPVKWSSPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDINAGFRLYKPRLASTHV 230
                        250       260
                 ....*....|....*....|....*
gi 111118978 856 HQLMLDCWQKDRNHRPKFGQIVNTL 880
Cdd:cd05112  231 YEIMNHCWKERPEDRPSFSLLLRQL 255
EphR_LBD_A3 cd10481
Ligand Binding Domain of Ephrin type-A Receptor 3; Ephrin receptors (EphRs) comprise the ...
20-196 1.44e-75

Ligand Binding Domain of Ephrin type-A Receptor 3; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (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. EphA3 has been implicated in leukemia, lung and other cancers. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine 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.


Pssm-ID: 198449  Cd Length: 173  Bit Score: 245.35  E-value: 1.44e-75
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  20 EETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSS 99
Cdd:cd10481    1 EVNLLDSKAIQGELGWISYPSHGWEEISGVDEHYTPIRTYQVCNVMDHSQNNWLRTNWIPRNSAQKIYVELKFTLRDCNS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 100 IPSVPGSCKETFNLYYYEADFDSATKtfpnWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGFYLAFQ 179
Cdd:cd10481   81 IPLVLGTCKETFNLYYMESDEDQGVK----FREHQFTKIDTIAADESFTQMDLGDRILKLNTEVREVGPVSKKGFYLAFQ 156
                        170
                 ....*....|....*..
gi 111118978 180 DYGGCMSLIAVRVFYRK 196
Cdd:cd10481  157 DVGACVALVSVRVYFKK 173
PTKc_Fes cd05084
Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the ...
625-880 9.55e-74

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: 243.68  E-value: 9.55e-74
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKlpgKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMEN 704
Cdd:cd05084    2 ERIGRGNFGEVFSGRLR---ADNTPVAVKSCRETLPPDLKAKFLQEARILKQYSHPNIVRLIGVCTQKQPIYIVMELVQG 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 705 GSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRfledDTSDPTYTSAL 784
Cdd:cd05084   79 GDFLTFLRTEGPRLKVKELIRMVENAAAGMEYLESKHCIHRDLAARNCLVTEKNVLKISDFGMSR----EEEDGVYAATG 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 785 GGK-IPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSALHQLMLDCW 863
Cdd:cd05084  155 GMKqIPVKWTAPEALNYGRYSSESDVWSFGILLWETFSLGAVPYANLSNQQTREAVEQGVRLPCPENCPDEVYRLMEQCW 234
                        250
                 ....*....|....*..
gi 111118978 864 QKDRNHRPKFGQIVNTL 880
Cdd:cd05084  235 EYDPRKRPSFSTVHQDL 251
PTKc_DDR cd05051
Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze ...
622-876 1.51e-73

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: 244.55  E-value: 1.51e-73
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEV--C-----SGHL--KLPGKRE----IFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGV 688
Cdd:cd05051    8 EFVEKLGEGQFGEVhlCeanglSDLTsdDFIGNDNkdepVLVAVKMLRPDASKNAREDFLKEVKIMSQLKDPNIVRLLGV 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 689 VTKSTPVMIITEFMENGSLDSFLRQNDGQFTVIQ-----------LVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSN 757
Cdd:cd05051   88 CTRDEPLCMIVEYMENGDLNQFLQKHEAETQGASatnsktlsygtLLYMATQIASGMKYLESLNFVHRDLATRNCLVGPN 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 758 LVCKVSDFGLSRFLeddtsdptYTS---ALGGK--IPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYG-ERPYWDMT 831
Cdd:cd05051  168 YTIKIADFGMSRNL--------YSGdyyRIEGRavLPIRWMAWESILLGKFTTKSDVWAFGVTLWEILTLCkEQPYEHLT 239
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|..
gi 111118978 832 NQDVI-NAIE--QDYR----LPPPMDCPSALHQLMLDCWQKDRNHRPKFGQI 876
Cdd:cd05051  240 DEQVIeNAGEffRDDGmevyLSRPPNCPKEIYELMLECWRRDEEDRPTFREI 291
EphR_LBD_A8 cd10486
Ligand Binding Domain of Ephrin type-A Receptor 8; Ephrin receptors (EphRs) comprise the ...
20-196 1.33e-72

Ligand Binding Domain of Ephrin type-A Receptor 8; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (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. EphA8 has been implicated in various cancers. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine 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).


Pssm-ID: 198454  Cd Length: 173  Bit Score: 237.24  E-value: 1.33e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  20 EETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSS 99
Cdd:cd10486    1 EVNLLDTSTISGDWGWLTYPSHGWDSINEMDEYFSPIHTYQVCNVMSPNQNNWLRTNWVQRDGARRVYAEIKFTLRDCNS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 100 IPSVPGSCKETFNLYYYEADFDSATKTFpnwmENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGFYLAFQ 179
Cdd:cd10486   81 MPGVLGTCKETFNLYYYESDRDLGTSTW----ESQFLKIDTIAADESFTNVDLGVRRLKLNTEVRGVGPLSKRGFYLAFQ 156
                        170
                 ....*....|....*..
gi 111118978 180 DYGGCMSLIAVRVFYRK 196
Cdd:cd10486  157 DIGACIAIVSVRVYYKK 173
EphR_LBD_A6 cd10484
Ligand Binding Domain of Ephrin type-A Receptor 6; Ephrin receptors (EphRs) comprise the ...
23-196 3.02e-72

Ligand Binding Domain of Ephrin type-A Receptor 6; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (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. EphA6, like other Eph receptors and their ephrin ligands, seems to play a role in neural development, underlying learning and memory. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine 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).


Pssm-ID: 198452  Cd Length: 173  Bit Score: 236.45  E-value: 3.02e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  23 LMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSSIPS 102
Cdd:cd10484    4 LLDTTMVLGELNWKTYPCNGWDAITEMDEYNRPIHTYQVCNVMEPNQNNWLRTNWISRDAAQKIYVEMKFTLRDCNSIPW 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 103 VPGSCKETFNLYYYEADFDSATKTFPnwmeNPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGFYLAFQDYG 182
Cdd:cd10484   84 VVGTCKETFNLHYMESDEAHAVKFKP----NQYSKIDTIAADESFTQMDLGDRILKLNTEVREVGPITRKGFYLAFQDIG 159
                        170
                 ....*....|....
gi 111118978 183 GCMSLIAVRVFYRK 196
Cdd:cd10484  160 ACIALVSVRVYYKK 173
EphR_LBD_A4 cd10482
Ligand Binding Domain of Ephrin type-A Receptor 4; Ephrin receptors (EphRs) comprise the ...
20-196 5.68e-72

Ligand Binding Domain of Ephrin type-A Receptor 4; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (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. A loss of EphA4, as well as EphB2, precedes memory decline in a murine model of Alzheimers disease. EphA4 has been shown to have a negative effect on axon regeneration and functional restoration in corticospinal lesions and is downregulated in some cervical cancers. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine 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).


Pssm-ID: 198450  Cd Length: 174  Bit Score: 235.71  E-value: 5.68e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  20 EETLMDSTTATAELGWMVHP-PSGWEEVSGYDENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCS 98
Cdd:cd10482    1 EVTLLDSRSVQGELGWIASPlEGGWEEVSIMDEKNTPIRTYQVCNVMEPSQNNWLRTDWIPREGAQRVYIEIKFTLRDCN 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  99 SIPSVPGSCKETFNLYYYEADFDSATKTfpnwMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGFYLAF 178
Cdd:cd10482   81 SLPGVMGTCKETFNLYYYESNNDKERFI----RENQFVKIDTIAADESFTQVDIGDRIMKLNTEVRDVGPLSKKGFYLAF 156
                        170
                 ....*....|....*...
gi 111118978 179 QDYGGCMSLIAVRVFYRK 196
Cdd:cd10482  157 QDVGACIALVSVRVFYKK 174
PTKc_Fer cd05085
Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; ...
625-880 6.77e-72

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: 238.37  E-value: 6.77e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKlpgkREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMEN 704
Cdd:cd05085    2 ELLGKGNFGEVYKGTLK----DKTPVAVKTCKEDLPQELKIKFLSEARILKQYDHPNIVKLIGVCTQRQPIYIVMELVPG 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 705 GSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRfLEDDTsdpTYTSAL 784
Cdd:cd05085   78 GDFLSFLRKKKDELKTKQLVKFSLDAAAGMAYLESKNCIHRDLAARNCLVGENNALKISDFGMSR-QEDDG---VYSSSG 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 785 GGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSALHQLMLDCWQ 864
Cdd:cd05085  154 LKQIPIKWTAPEALNYGRYSSESDVWSFGILLWETFSLGVCPYPGMTNQQAREQVEKGYRMSAPQRCPEDIYKIMQRCWD 233
                        250
                 ....*....|....*.
gi 111118978 865 KDRNHRPKFGQIVNTL 880
Cdd:cd05085  234 YNPENRPKFSELQKEL 249
PTKc_Zap-70 cd05115
Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs ...
623-880 9.29e-72

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: 238.69  E-value: 9.29e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 623 IEQV-IGAGEFGEVCSGHLKLPgKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVtKSTPVMIITEF 701
Cdd:cd05115    7 IDEVeLGSGNFGCVKKGVYKMR-KKQIDVAIKVLKQGNEKAVRDEMMREAQIMHQLDNPYIVRMIGVC-EAEALMLVMEM 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 702 MENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDtsDPTYT 781
Cdd:cd05115   85 ASGGPLNKFLSGKKDEITVSNVVELMHQVSMGMKYLEEKNFVHRDLAARNVLLVNQHYAKISDFGLSKALGAD--DSYYK 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 782 SALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSALHQLMLD 861
Cdd:cd05115  163 ARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEAFSYGQKPYKKMKGPEVMSFIEQGKRMDCPAECPPEMYALMSD 242
                        250
                 ....*....|....*....
gi 111118978 862 CWQKDRNHRPKFGQIVNTL 880
Cdd:cd05115  243 CWIYKWEDRPNFLTVEQRM 261
PTKc_Yes cd05069
Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the ...
613-881 3.85e-71

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: 237.28  E-value: 3.85e-71
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 613 AKEIDISCVKIEQVIGAGEFGEVCSGHLKLPGKreifVAIKTLKSGYTEKQRrdFLSEASIMGQFDHPNVIHLEGVVTKS 692
Cdd:cd05069    6 AWEIPRESLRLDVKLGQGCFGEVWMGTWNGTTK----VAIKTLKPGTMMPEA--FLQEAQIMKKLRHDKLVPLYAVVSEE 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 693 tPVMIITEFMENGSLDSFLRQNDGQFTVI-QLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFL 771
Cdd:cd05069   80 -PIYIVTEFMGKGSLLDFLKEGDGKYLKLpQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGDNLVCKIADFGLARLI 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 772 EDDTsdptYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDC 851
Cdd:cd05069  159 EDNE----YTARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMVNREVLEQVERGYRMPCPQGC 234
                        250       260       270
                 ....*....|....*....|....*....|
gi 111118978 852 PSALHQLMLDCWQKDRNHRPKFGQIVNTLD 881
Cdd:cd05069  235 PESLHELMKLCWKKDPDERPTFEYIQSFLE 264
PTKc_Hck cd05073
Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the ...
613-881 8.83e-71

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: 236.08  E-value: 8.83e-71
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 613 AKEIDISCVKIEQVIGAGEFGEVCSGHLKLPGKreifVAIKTLKSGYTEKQRrdFLSEASIMGQFDHPNVIHLEGVVTKS 692
Cdd:cd05073    5 AWEIPRESLKLEKKLGAGQFGEVWMATYNKHTK----VAVKTMKPGSMSVEA--FLAEANVMKTLQHDKLVKLHAVVTKE 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 693 tPVMIITEFMENGSLDSFLRQNDG-QFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFL 771
Cdd:cd05073   79 -PIYIITEFMAKGSLLDFLKSDEGsKQPLPKLIDFSAQIAEGMAFIEQRNYIHRDLRAANILVSASLVCKIADFGLARVI 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 772 EDDTsdptYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDC 851
Cdd:cd05073  158 EDNE----YTAREGAKFPIKWTAPEAINFGSFTIKSDVWSFGILLMEIVTYGRIPYPGMSNPEVIRALERGYRMPRPENC 233
                        250       260       270
                 ....*....|....*....|....*....|
gi 111118978 852 PSALHQLMLDCWQKDRNHRPKFGQIVNTLD 881
Cdd:cd05073  234 PEELYNIMMRCWKNRPEERPTFEYIQSVLD 263
EphR_LBD_A5 cd10483
Ligand Binding Domain of Ephrin type-A Receptor 5; Ephrin receptors (EphRs) comprise the ...
20-196 1.47e-70

Ligand Binding Domain of Ephrin type-A Receptor 5; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (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. EphA5 is almost exclusively expressed in the nervous system. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine 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).


Pssm-ID: 198451  Cd Length: 173  Bit Score: 231.84  E-value: 1.47e-70
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  20 EETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCSS 99
Cdd:cd10483    1 EVNLLDSRSVMGDLGWIAYPKNGWEEIGEVDENYAPIHTYQVCKVMEQNQNNWLLTSWISNEGASRIFIELKFTLRDCNS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 100 IPSVPGSCKETFNLYYYEADFDSATktfpNWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGFYLAFQ 179
Cdd:cd10483   81 LPGGLGTCKETFNVYYFESNDEDGR----NIRENQYIKIDTIAADESFTELDLGDRVMKLNTEVRDVGPLTKKGFYLAFQ 156
                        170
                 ....*....|....*..
gi 111118978 180 DYGGCMSLIAVRVFYRK 196
Cdd:cd10483  157 DLGACIALVSVRVYYKK 173
PTKc_ALK_LTK cd05036
Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte ...
614-882 1.73e-70

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: 235.36  E-value: 1.73e-70
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 614 KEIDISCVKIEQVIGAGEFGEVCSGHLK-LPG-KREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTK 691
Cdd:cd05036    1 KEVPRKNLTLIRALGQGAFGEVYEGTVSgMPGdPSPLQVAVKTLPELCSEQDEMDFLMEALIMSKFNHPNIVRCIGVCFQ 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 692 STPVMIITEFMENGSLDSFLRQN------DGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNL---VCKV 762
Cdd:cd05036   81 RLPRFILLELMAGGDLKSFLRENrprpeqPSSLTMLDLLQLAQDVAKGCRYLEENHFIHRDIAARNCLLTCKGpgrVAKI 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 763 SDFGLSRfledDTSDPTYTSAlGGK--IPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIE 840
Cdd:cd05036  161 GDFGMAR----DIYRADYYRK-GGKamLPVKWMPPEAFLDGIFTSKTDVWSFGVLLWEIFSLGYMPYPGKSNQEVMEFVT 235
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 111118978 841 QDYRLPPPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDK 882
Cdd:cd05036  236 SGGRMDPPKNCPGPVYRIMTQCWQHIPEDRPNFSTILERLNY 277
PTKc_Btk_Bmx cd05113
Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow ...
627-880 2.29e-70

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: 234.39  E-value: 2.29e-70
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGhlKLPGKREifVAIKTLKSGYTEKQrrDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGS 706
Cdd:cd05113   12 LGTGQFGVVKYG--KWRGQYD--VAIKMIKEGSMSED--EFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANGC 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 707 LDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDtsdpTYTSALGG 786
Cdd:cd05113   86 LLNYLREMRKRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVLDD----EYTSSVGS 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 787 KIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSALHQLMLDCWQKD 866
Cdd:cd05113  162 KFPVRWSPPEVLMYSKFSSKSDVWAFGVLMWEVYSLGKMPYERFTNSETVEHVSQGLRLYRPHLASEKVYTIMYSCWHEK 241
                        250
                 ....*....|....
gi 111118978 867 RNHRPKFGQIVNTL 880
Cdd:cd05113  242 ADERPTFKILLSNI 255
PTKc_Fyn cd05070
Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the ...
615-873 2.46e-70

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: 234.96  E-value: 2.46e-70
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 615 EIDISCVKIEQVIGAGEFGEVCSGHLKLPGKreifVAIKTLKSGYTEKQrrDFLSEASIMGQFDHPNVIHLEGVVTKStP 694
Cdd:cd05070    5 EIPRESLQLIKRLGNGQFGEVWMGTWNGNTK----VAIKTLKPGTMSPE--SFLEEAQIMKKLKHDKLVQLYAVVSEE-P 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 695 VMIITEFMENGSLDSFLRQNDGQ-FTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLED 773
Cdd:cd05070   78 IYIVTEYMSKGSLLDFLKDGEGRaLKLPNLVDMAAQVAAGMAYIERMNYIHRDLRSANILVGNGLICKIADFGLARLIED 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 774 DTsdptYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPS 853
Cdd:cd05070  158 NE----YTARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMNNREVLEQVERGYRMPCPQDCPI 233
                        250       260
                 ....*....|....*....|
gi 111118978 854 ALHQLMLDCWQKDRNHRPKF 873
Cdd:cd05070  234 SLHELMIHCWKKDPEERPTF 253
PTKc_Musk cd05050
Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the ...
622-876 1.32e-69

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: 233.57  E-value: 1.32e-69
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQV--IGAGEFGEVCSGHLK--LPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMI 697
Cdd:cd05050    6 NIEYVrdIGQGAFGRVFQARAPglLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDHPNIVKLLGVCAVGKPMCL 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 698 ITEFMENGSLDSFLR---------------------QNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNS 756
Cdd:cd05050   86 LFEYMAYGDLNEFLRhrspraqcslshstssarkcgLNPLPLSCTEQLCIAKQVAAGMAYLSERKFVHRDLATRNCLVGE 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 757 NLVCKVSDFGLSRfleDDTSDPTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVI 836
Cdd:cd05050  166 NMVVKIADFGLSR---NIYSADYYKASENDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGMQPYYGMAHEEVI 242
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 111118978 837 NAIEQDYRLPPPMDCPSALHQLMLDCWQKDRNHRPKFGQI 876
Cdd:cd05050  243 YYVRDGNVLSCPDNCPLELYNLMRLCWSKLPSDRPSFASI 282
PTKc_Src cd05071
Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the ...
613-873 1.98e-69

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: 232.66  E-value: 1.98e-69
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 613 AKEIDISCVKIEQVIGAGEFGEVCSGHLKLPGKreifVAIKTLKSGYTEKQRrdFLSEASIMGQFDHPNVIHLEGVVTKS 692
Cdd:cd05071    3 AWEIPRESLRLEVKLGQGCFGEVWMGTWNGTTR----VAIKTLKPGTMSPEA--FLQEAQVMKKLRHEKLVQLYAVVSEE 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 693 tPVMIITEFMENGSLDSFLRQNDGQFTVI-QLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFL 771
Cdd:cd05071   77 -PIYIVTEYMSKGSLLDFLKGEMGKYLRLpQLVDMAAQIASGMAYVERMNYVHRDLRAANILVGENLVCKVADFGLARLI 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 772 EDDTsdptYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDC 851
Cdd:cd05071  156 EDNE----YTARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELTTKGRVPYPGMVNREVLDQVERGYRMPCPPEC 231
                        250       260
                 ....*....|....*....|..
gi 111118978 852 PSALHQLMLDCWQKDRNHRPKF 873
Cdd:cd05071  232 PESLHDLMCQCWRKEPEERPTF 253
EphR_LBD_B4 cd10474
Ligand Binding Domain of Ephrin type-B Receptor 4; Ephrin receptors (EphRs) comprise the ...
20-196 2.55e-69

Ligand Binding Domain of Ephrin type-B Receptor 4; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EhpB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. EphB4 plays a role in osteoblast differentiation and has been linked to multiple myeloma. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine 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).


Pssm-ID: 198442  Cd Length: 180  Bit Score: 228.69  E-value: 2.55e-69
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  20 EETLMDSTTATAELGWMVHPPSG--WEEVSGYDENMNTIRTYQVCNVFE-SSQNNWLRTKFIRRRGAHRIHVEMKFSVRD 96
Cdd:cd10474    1 EETLLNTKLETADLKWVTYPQVDgqWEELSGLDEEQHSVRTYEVCDAQRaGGQAHWLRTGWVPRRGAVHVYATLRFTMLE 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  97 CSSIPSVPGSCKETFNLYYYEADFDSATKTFPNWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGFYL 176
Cdd:cd10474   81 CLSLPRAGRSCKETFTVFYYESDADTATAHTPAWMENPYIKVDTVAAEHLTRKRPGAEATGKVNVKTLRLGPLSKAGFYL 160
                        170       180
                 ....*....|....*....|
gi 111118978 177 AFQDYGGCMSLIAVRVFYRK 196
Cdd:cd10474  161 AFQDQGACMALLSLHLFYKK 180
PTKc_Tec_Rlk cd05114
Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular ...
627-884 1.37e-68

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: 229.75  E-value: 1.37e-68
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKlpgkREIFVAIKTLKSGYTEKQrrDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGS 706
Cdd:cd05114   12 LGSGLFGVVRLGKWR----AQYKVAIKAIREGAMSEE--DFIEEAKVMMKLTHPKLVQLYGVCTQQKPIYIVTEFMENGC 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 707 LDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDtsdpTYTSALGG 786
Cdd:cd05114   86 LLNYLRQRRGKLSRDMLLSMCQDVCEGMEYLERNNFIHRDLAARNCLVNDTGVVKVSDFGMTRYVLDD----QYTSSSGA 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 787 KIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSALHQLMLDCWQKD 866
Cdd:cd05114  162 KFPVKWSPPEVFNYSKFSSKSDVWSFGVLMWEVFTEGKMPFESKSNYEVVEMVSRGHRLYRPKLASKSVYEVMYSCWHEK 241
                        250
                 ....*....|....*...
gi 111118978 867 RNHRPKFGQIVNTLDKMI 884
Cdd:cd05114  242 PEGRPTFADLLRTITEIA 259
PTKc_Jak_rpt2 cd05038
Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily ...
627-881 3.93e-68

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: 229.19  E-value: 3.93e-68
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPG--KREIfVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTP--VMIITEFM 702
Cdd:cd05038   12 LGEGHFGSVELCRYDPLGdnTGEQ-VAVKSLQPSGEEQHMSDFKREIEILRTLDHEYIVKYKGVCESPGRrsLRLIMEYL 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 703 ENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDtsDPTYTS 782
Cdd:cd05038   91 PSGSLRDYLQRHRDQIDLKRLLLFASQICKGMEYLGSQRYIHRDLAARNILVESEDLVKISDFGLAKVLPED--KEYYYV 168
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 783 ALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPY--------------WDMTNQDVINAIEQDYRLPPP 848
Cdd:cd05038  169 KEPGESPIFWYAPECLRESRFSSASDVWSFGVTLYELFTYGDPSQsppalflrmigiaqGQMIVTRLLELLKSGERLPRP 248
                        250       260       270
                 ....*....|....*....|....*....|...
gi 111118978 849 MDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLD 881
Cdd:cd05038  249 PSCPDEVYDLMKECWEYEPQDRPSFSDLILIID 281
PTKc_Chk cd05083
Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the ...
616-883 1.36e-67

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: 226.68  E-value: 1.36e-67
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 616 IDISCVKIEQVIGAGEFGEVCSGhlKLPGKReifVAIKTLKSGYTEKQrrdFLSEASIMGQFDHPNVIHLEGVVTKSTpV 695
Cdd:cd05083    3 LNLQKLTLGEIIGEGEFGAVLQG--EYMGQK---VAVKNIKCDVTAQA---FLEETAVMTKLQHKNLVRLLGVILHNG-L 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 696 MIITEFMENGSLDSFLRQNdGQFTV--IQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSR--FL 771
Cdd:cd05083   74 YIVMELMSKGNLVNFLRSR-GRALVpvIQLLQFSLDVAEGMEYLESKKLVHRDLAARNILVSEDGVAKISDFGLAKvgSM 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 772 EDDTSdptytsalggKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDC 851
Cdd:cd05083  153 GVDNS----------RLPVKWTAPEALKNKKFSSKSDVWSYGVLLWEVFSYGRAPYPKMSVKEVKEAVEKGYRMEPPEGC 222
                        250       260       270
                 ....*....|....*....|....*....|..
gi 111118978 852 PSALHQLMLDCWQKDRNHRPKFGQIVNTLDKM 883
Cdd:cd05083  223 PPDVYSIMTSCWEAEPGKRPSFKKLREKLEKE 254
PTKc_Ror1 cd05090
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
615-876 1.94e-66

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: 224.51  E-value: 1.94e-66
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 615 EIDISCVKIEQVIGAGEFGEVCSGHLKLPGKREI-FVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKST 693
Cdd:cd05090    1 ELPLSAVRFMEELGECAFGKIYKGHLYLPGMDHAqLVAIKTLKDYNNPQQWNEFQQEASLMTELHHPNIVCLLGVVTQEQ 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 694 PVMIITEFMENGSLDSFL------------RQNDGQFTVI----QLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSN 757
Cdd:cd05090   81 PVCMLFEFMNQGDLHEFLimrsphsdvgcsSDEDGTVKSSldhgDFLHIAIQIAAGMEYLSSHFFVHKDLAARNILVGEQ 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 758 LVCKVSDFGLSRflEDDTSDpTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVIN 837
Cdd:cd05090  161 LHVKISDLGLSR--EIYSSD-YYRVQNKSLLPIRWMPPEAIMYGKFSSDSDIWSFGVVLWEIFSFGLQPYYGFSNQEVIE 237
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 111118978 838 AIEQDYRLPPPMDCPSALHQLMLDCWQKDRNHRPKFGQI 876
Cdd:cd05090  238 MVRKRQLLPCSEDCPPRMYSLMTECWQEIPSRRPRFKDI 276
PTKc_Ror2 cd05091
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
614-880 9.00e-66

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: 222.97  E-value: 9.00e-66
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 614 KEIDISCVKIEQVIGAGEFGEVCSGHL--KLPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTK 691
Cdd:cd05091    1 KEINLSAVRFMEELGEDRFGKVYKGHLfgTAPGEQTQAVAIKTLKDKAEGPLREEFRHEAMLRSRLQHPNIVCLLGVVTK 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 692 STPVMIITEFMENGSLDSFL---------RQNDGQFTV------IQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNS 756
Cdd:cd05091   81 EQPMSMIFSYCSHGDLHEFLvmrsphsdvGSTDDDKTVkstlepADFLHIVTQIAAGMEYLSSHHVVHKDLATRNVLVFD 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 757 NLVCKVSDFGLsrFLEDDTSDptYTSALGGK-IPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDV 835
Cdd:cd05091  161 KLNVKISDLGL--FREVYAAD--YYKLMGNSlLPIRWMSPEAIMYGKFSIDSDIWSYGVVLWEVFSYGLQPYCGYSNQDV 236
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*
gi 111118978 836 INAIEQDYRLPPPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTL 880
Cdd:cd05091  237 IEMIRNRQVLPCPDDCPAWVYTLMLECWNEFPSRRPRFKDIHSRL 281
PTKc_Met_Ron cd05058
Catalytic domain of the Protein Tyrosine Kinases, Met and Ron; PTKs catalyze the transfer of ...
625-877 1.13e-65

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: 221.58  E-value: 1.13e-65
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKLPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVV--TKSTPvMIITEFM 702
Cdd:cd05058    1 EVIGKGHFGCVYHGTLIDSDGQKIHCAVKSLNRITDIEEVEQFLKEGIIMKDFSHPNVLSLLGIClpSEGSP-LVVLPYM 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 703 ENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRfledDTSDPTYTS 782
Cdd:cd05058   80 KHGDLRNFIRSETHNPTVKDLIGFGLQVAKGMEYLASKKFVHRDLAARNCMLDESFTVKVADFGLAR----DIYDKEYYS 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 783 A---LGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSALHQLM 859
Cdd:cd05058  156 VhnhTGAKLPVKWMALESLQTQKFTTKSDVWSFGVLLWELMTRGAPPYPDVDSFDITVYLLQGRRLLQPEYCPDPLYEVM 235
                        250
                 ....*....|....*...
gi 111118978 860 LDCWQKDRNHRPKFGQIV 877
Cdd:cd05058  236 LSCWHPKPEMRPTFSELV 253
PTKc_FGFR cd05053
Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs ...
611-884 2.93e-65

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: 221.91  E-value: 2.93e-65
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 611 EFAKEiDISCVKIeqvIGAGEFGEVCSGHLK-LPGKR--EIFVAIKTLKSGYTEKQRRDFLSEASIM---GQfdHPNVIH 684
Cdd:cd05053    8 ELPRD-RLTLGKP---LGEGAFGQVVKAEAVgLDNKPneVVTVAVKMLKDDATEKDLSDLVSEMEMMkmiGK--HKNIIN 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 685 LEGVVTKSTPVMIITEFMENGSLDSFLRQN---------------DGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAA 749
Cdd:cd05053   82 LLGACTQDGPLYVVVEYASKGNLREFLRARrppgeeaspddprvpEEQLTQKDLVSFAYQVARGMEYLASKKCIHRDLAA 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 750 RNILVNSNLVCKVSDFGLSRfleDDTSDPTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWD 829
Cdd:cd05053  162 RNVLVTEDNVMKIADFGLAR---DIHHIDYYRKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPG 238
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 111118978 830 MTNQDVINAIEQDYRLPPPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKMI 884
Cdd:cd05053  239 IPVEELFKLLKEGHRMEKPQNCTQELYMLMRDCWHEVPSQRPTFKQLVEDLDRIL 293
PTKc_TrkA cd05092
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze ...
627-880 2.02e-64

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: 219.07  E-value: 2.02e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEV----CSgHLkLPGKREIFVAIKTLKSGyTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFM 702
Cdd:cd05092   13 LGEGAFGKVflaeCH-NL-LPEQDKMLVAVKALKEA-TESARQDFQREAELLTVLQHQHIVRFYGVCTEGEPLIMVFEYM 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 703 ENGSLDSFLR--------------QNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLS 768
Cdd:cd05092   90 RHGDLNRFLRshgpdakildggegQAPGQLTLGQMLQIASQIASGMVYLASLHFVHRDLATRNCLVGQGLVVKIGDFGMS 169
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 769 RfleDDTSDPTYTsaLGGK--IPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLP 846
Cdd:cd05092  170 R---DIYSTDYYR--VGGRtmLPIRWMPPESILYRKFTTESDIWSFGVVLWEIFTYGKQPWYQLSNTEAIECITQGRELE 244
                        250       260       270
                 ....*....|....*....|....*....|....
gi 111118978 847 PPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTL 880
Cdd:cd05092  245 RPRTCPPEVYAIMQGCWQREPQQRHSIKDIHSRL 278
PTKc_HER2 cd05109
Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the ...
614-888 1.41e-62

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: 213.73  E-value: 1.41e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 614 KEIDISCVKieqVIGAGEFGEVCSGHLKLPGKR-EIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKS 692
Cdd:cd05109    5 KETELKKVK---VLGSGAFGTVYKGIWIPDGENvKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVCRLLGICLTS 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 693 TpVMIITEFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLE 772
Cdd:cd05109   82 T-VQLVTQLMPYGCLLDYVRENKDRIGSQDLLNWCVQIAKGMSYLEEVRLVHRDLAARNVLVKSPNHVKITDFGLARLLD 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 773 ddtSDPTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCP 852
Cdd:cd05109  161 ---IDETEYHADGGKVPIKWMALESILHRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICT 237
                        250       260       270
                 ....*....|....*....|....*....|....*.
gi 111118978 853 SALHQLMLDCWQKDRNHRPKFGQIVNTLDKMIRNPN 888
Cdd:cd05109  238 IDVYMIMVKCWMIDSECRPRFRELVDEFSRMARDPS 273
PTKc_RET cd05045
Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs ...
623-886 1.88e-62

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: 213.67  E-value: 1.88e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 623 IEQVIGAGEFGEVCSG---HLK-LPGKREifVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMII 698
Cdd:cd05045    4 LGKTLGEGEFGKVVKAtafRLKgRAGYTT--VAVKMLKENASSSELRDLLSEFNLLKQVNHPHVIKLYGACSQDGPLLLI 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 699 TEFMENGSLDSFLRQ---------------------NDGQ--FTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVN 755
Cdd:cd05045   82 VEYAKYGSLRSFLREsrkvgpsylgsdgnrnssyldNPDEraLTMGDLISFAWQISRGMQYLAEMKLVHRDLAARNVLVA 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 756 SNLVCKVSDFGLSRfleDDTSDPTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDV 835
Cdd:cd05045  162 EGRKMKISDFGLSR---DVYEEDSYVKRSKGRIPVKWMAIESLFDHIYTTQSDVWSFGVLLWEIVTLGGNPYPGIAPERL 238
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|.
gi 111118978 836 INAIEQDYRLPPPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKMIRN 886
Cdd:cd05045  239 FNLLKTGYRMERPENCSEEMYNLMLTCWKQEPDKRPTFADISKELEKMMVK 289
PTKc_DDR2 cd05095
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2; PTKs catalyze ...
627-880 9.05e-62

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: 212.16  E-value: 9.05e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEV--CSGH-----------LKLPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKST 693
Cdd:cd05095   13 LGEGQFGEVhlCEAEgmekfmdkdfaLEVSENQPVLVAVKMLRADANKNARNDFLKEIKIMSRLKDPNIIRLLAVCITDD 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 694 PVMIITEFMENGSLDSFL--RQNDGQFTVI---------QLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKV 762
Cdd:cd05095   93 PLCMITEYMENGDLNQFLsrQQPEGQLALPsnaltvsysDLRFMAAQIASGMKYLSSLNFVHRDLATRNCLVGKNYTIKI 172
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 763 SDFGLSRFLeddTSDPTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSY-GERPYWDMTNQDVINAIEQ 841
Cdd:cd05095  173 ADFGMSRNL---YSGDYYRIQGRAVLPIRWMSWESILLGKFTTASDVWAFGVTLWETLTFcREQPYSQLSDEQVIENTGE 249
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*.
gi 111118978 842 DYR-------LPPPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTL 880
Cdd:cd05095  250 FFRdqgrqtyLPQPALCPDSVYKLMLSCWRRDTKDRPSFQEIHTLL 295
PTKc_Syk cd05116
Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the ...
627-873 1.00e-61

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: 210.59  E-value: 1.00e-61
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPgKREIFVAIKTLKSGYTEKQRRD-FLSEASIMGQFDHPNVIHLEGVVtKSTPVMIITEFMENG 705
Cdd:cd05116    3 LGSGNFGTVKKGYYQMK-KVVKTVAVKILKNEANDPALKDeLLREANVMQQLDNPYIVRMIGIC-EAESWMLVMEMAELG 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 706 SLDSFLRQNDgQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLeddTSDPTYTSALG 785
Cdd:cd05116   81 PLNKFLQKNR-HVTEKNITELVHQVSMGMKYLEESNFVHRDLAARNVLLVTQHYAKISDFGLSKAL---RADENYYKAQT 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 786 -GKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSALHQLMLDCWQ 864
Cdd:cd05116  157 hGKWPVKWYAPECMNYYKFSSKSDVWSFGVLMWEAFSYGQKPYKGMKGNEVTQMIEKGERMECPAGCPPEMYDLMKLCWT 236

                 ....*....
gi 111118978 865 KDRNHRPKF 873
Cdd:cd05116  237 YDVDERPGF 245
PTK_CCK4 cd05046
Pseudokinase domain of the Protein Tyrosine Kinase, Colon Carcinoma Kinase 4; CCK4, also ...
626-882 1.06e-61

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: 211.17  E-value: 1.06e-61
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 626 VIGAGEFGEVCSGHLKLP--GKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFME 703
Cdd:cd05046   12 TLGRGEFGEVFLAKAKGIeeEGGETLVLVKALQKTKDENLQSEFRRELDMFRKLSHKNVVRLLGLCREAEPHYMILEYTD 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 704 NGSLDSFLRQNDGQ--------FTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRfledDT 775
Cdd:cd05046   92 LGDLKQFLRATKSKdeklkpppLSTKQKVALCTQIALGMDHLSNARFVHRDLAARNCLVSSQREVKVSLLSLSK----DV 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 776 SDPTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAI-EQDYRLPPPMDCPSA 854
Cdd:cd05046  168 YNSEYYKLRNALIPLRWLAPEAVQEDDFSTKSDVWSFGVLMWEVFTQGELPFYGLSDEEVLNRLqAGKLELPVPEGCPSR 247
                        250       260
                 ....*....|....*....|....*...
gi 111118978 855 LHQLMLDCWQKDRNHRPKFGQIVNTLDK 882
Cdd:cd05046  248 LYKLMTRCWAVNPKDRPSFSELVSALGE 275
PTKc_DDR_like cd05097
Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the ...
621-876 2.28e-61

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: 210.99  E-value: 2.28e-61
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQVIGAGEFGEV----CSGHLKLPGK-------REIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVV 689
Cdd:cd05097    7 LRLKEKLGEGQFGEVhlceAEGLAEFLGEgapefdgQPVLVAVKMLRADVTKTARNDFLKEIKIMSRLKNPNIIRLLGVC 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 690 TKSTPVMIITEFMENGSLDSFLRQND--GQFTVIQ---------LVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNL 758
Cdd:cd05097   87 VSDDPLCMITEYMENGDLNQFLSQREieSTFTHANnipsvsianLLYMAVQIASGMKYLASLNFVHRDLATRNCLVGNHY 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 759 VCKVSDFGLSRFLeddTSDPTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSY-GERPYWDMTNQDVI- 836
Cdd:cd05097  167 TIKIADFGMSRNL---YSGDYYRIQGRAVLPIRWMAWESILLGKFTTASDVWAFGVTLWEMFTLcKEQPYSLLSDEQVIe 243
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*..
gi 111118978 837 -------NAIEQDYRLPPPMdCPSALHQLMLDCWQKDRNHRPKFGQI 876
Cdd:cd05097  244 ntgeffrNQGRQIYLSQTPL-CPSPVFKLMMRCWSRDIKDRPTFNKI 289
PTKc_EGFR cd05108
Catalytic domain of the Protein Tyrosine Kinase, Epidermal Growth Factor Receptor; PTKs ...
622-888 2.43e-61

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: 211.42  E-value: 2.43e-61
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKLPGKR-EIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTpVMIITE 700
Cdd:cd05108   10 KKIKVLGSGAFGTVYKGLWIPEGEKvKIPVAIKELREATSPKANKEILDEAYVMASVDNPHVCRLLGICLTST-VQLITQ 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLeddTSDPTY 780
Cdd:cd05108   89 LMPFGCLLDYVREHKDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAARNVLVKTPQHVKITDFGLAKLL---GAEEKE 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 781 TSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSALHQLML 860
Cdd:cd05108  166 YHAEGGKVPIKWMALESILHRIYTHQSDVWSYGVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDVYMIMV 245
                        250       260
                 ....*....|....*....|....*...
gi 111118978 861 DCWQKDRNHRPKFGQIVNTLDKMIRNPN 888
Cdd:cd05108  246 KCWMIDADSRPKFRELIIEFSKMARDPQ 273
PTKc_Csk cd05082
Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the ...
621-881 1.26e-60

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: 207.53  E-value: 1.26e-60
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQVIGAGEFGEVCSGHLKlpGKReifVAIKTLKSGYTEKQrrdFLSEASIMGQFDHPNVIHLEGV-VTKSTPVMIIT 699
Cdd:cd05082    8 LKLLQTIGKGEFGDVMLGDYR--GNK---VAVKCIKNDATAQA---FLAEASVMTQLRHSNLVQLLGViVEEKGGLYIVT 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENGSLDSFLRQNdGQfTVI---QLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRflEDDTS 776
Cdd:cd05082   80 EYMAKGSLVDYLRSR-GR-SVLggdCLLKFSLDVCEAMEYLEGNNFVHRDLAARNVLVSEDNVAKVSDFGLTK--EASST 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 777 DPTytsalgGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSALH 856
Cdd:cd05082  156 QDT------GKLPVKWTAPEALREKKFSTKSDVWSFGILLWEIYSFGRVPYPRIPLKDVVPRVEKGYKMDAPDGCPPAVY 229
                        250       260
                 ....*....|....*....|....*
gi 111118978 857 QLMLDCWQKDRNHRPKFGQIVNTLD 881
Cdd:cd05082  230 DVMKNCWHLDAAMRPSFLQLREQLE 254
PTKc_TAM cd05035
Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer ...
621-884 2.08e-60

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: 207.39  E-value: 2.08e-60
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQVIGAGEFGEVCSGHLKLPGKREIFVAIKTLK-SGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPV---- 695
Cdd:cd05035    1 LKLGKILGEGEFGSVMEAQLKQDDGSQLKVAVKTMKvDIHTYSEIEEFLSEAACMKDFDHPNVMRLIGVCFTASDLnkpp 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 696 --MIITEFMENGSLDSFL---RQNDG--QFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLS 768
Cdd:cd05035   81 spMVILPFMKHGDLHSYLlysRLGGLpeKLPLQTLLKFMVDIAKGMEYLSNRNFIHRDLAARNCMLDENMTVCVADFGLS 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 769 RFLeddTSDPTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPP 848
Cdd:cd05035  161 RKI---YSGDYYRQGRISKMPVKWIALESLADNVYTSKSDVWSFGVTMWEIATRGQTPYPGVENHEIYDYLRNGNRLKQP 237
                        250       260       270
                 ....*....|....*....|....*....|....*.
gi 111118978 849 MDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKMI 884
Cdd:cd05035  238 EDCLDEVYFLMYFCWTVDPKDRPTFTKLREVLENIL 273
PTKc_DDR1 cd05096
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze ...
619-876 2.17e-59

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: 205.55  E-value: 2.17e-59
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 619 SCVKIEQVIGAGEFGEVcsgHL-------KLPG---------KREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNV 682
Cdd:cd05096    5 GHLLFKEKLGEGQFGEV---HLcevvnpqDLPTlqfpfnvrkGRPLLVAVKILRPDANKNARNDFLKEVKILSRLKDPNI 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 683 IHLEGVVTKSTPVMIITEFMENGSLDSFLRQN---------------DGQFTVIQ---LVGMLRGIAAGMKYLADMNYVH 744
Cdd:cd05096   82 IRLLGVCVDEDPLCMITEYMENGDLNQFLSSHhlddkeengndavppAHCLPAISyssLLHVALQIASGMKYLSSLNFVH 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 745 RDLAARNILVNSNLVCKVSDFGLSRFLeddTSDPTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSY-G 823
Cdd:cd05096  162 RDLATRNCLVGENLTIKIADFGMSRNL---YAGDYYRIQGRAVLPIRWMAWECILMGKFTTASDVWAFGVTLWEILMLcK 238
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 111118978 824 ERPYWDMTNQDVI-NAIE-------QDYRLPPPMdCPSALHQLMLDCWQKDRNHRPKFGQI 876
Cdd:cd05096  239 EQPYGELTDEQVIeNAGEffrdqgrQVYLFRPPP-CPQGLYELMLQCWSRDCRERPSFSDI 298
PTKc_Axl cd05075
Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the ...
621-886 3.41e-59

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: 204.09  E-value: 3.41e-59
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQVIGAGEFGEVCSGHLKLPGKReIFVAIKTLKSGY-TEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKST------ 693
Cdd:cd05075    2 LALGKTLGEGEFGSVMEGQLNQDDSV-LKVAVKTMKIAIcTRSEMEDFLSEAVCMKEFDHPNVMRLIGVCLQNTesegyp 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 694 -PVMIITeFMENGSLDSFL---RQNDGQ-FTVIQ-LVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGL 767
Cdd:cd05075   81 sPVVILP-FMKHGDLHSFLlysRLGDCPvYLPTQmLVKFMTDIASGMEYLSSKNFIHRDLAARNCMLNENMNVCVADFGL 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 768 SRFLEDDTsdpTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPP 847
Cdd:cd05075  160 SKKIYNGD---YYRQGRISKMPVKWIAIESLADRVYTTKSDVWSFGVTMWEIATRGQTPYPGVENSEIYDYLRQGNRLKQ 236
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 111118978 848 PMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKMIRN 886
Cdd:cd05075  237 PPDCLDGLYELMSSCWLLNPKDRPSFETLRCELEKILKD 275
S_TKc smart00220
Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or ...
622-878 5.53e-59

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


Pssm-ID: 214567 [Multi-domain]  Cd Length: 254  Bit Score: 202.76  E-value: 5.53e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978   622 KIEQVIGAGEFGEVCSGHLKLPGKReifVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEF 701
Cdd:smart00220   2 EILEKLGEGSFGKVYLARDKKTGKL---VAIKVIKKKKIKKDRERILREIKILKKLKHPNIVRLYDVFEDEDKLYLVMEY 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978   702 MENGSLDSFLRQNdGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTsdpTYT 781
Cdd:smart00220  79 CEGGDLFDLLKKR-GRLSEDEARFYLRQILSALEYLHSKGIVHRDLKPENILLDEDGHVKLADFGLARQLDPGE---KLT 154
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978   782 SALGgkiPIRWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVI--NAIEQDYRLPPPM-DCPSALHQL 858
Cdd:smart00220 155 TFVG---TPEYMAPEVLLGKGYGKAVDIWSLGVILYE-LLTGKPPFPGDDQLLELfkKIGKPKPPFPPPEwDISPEAKDL 230
                          250       260
                   ....*....|....*....|
gi 111118978   859 MLDCWQKDRNHRPKFGQIVN 878
Cdd:smart00220 231 IRKLLVKDPEKRLTAEEALQ 250
PTKc_TrkB cd05093
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze ...
621-885 1.01e-58

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: 203.35  E-value: 1.01e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQVIGAGEFGEV--CSGHLKLPGKREIFVAIKTLKSGyTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMII 698
Cdd:cd05093    7 IVLKRELGEGAFGKVflAECYNLCPEQDKILVAVKTLKDA-SDNARKDFHREAELLTNLQHEHIVKFYGVCVEGDPLIMV 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 699 TEFMENGSLDSFLRQN--------DGQ----FTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFG 766
Cdd:cd05093   86 FEYMKHGDLNKFLRAHgpdavlmaEGNrpaeLTQSQMLHIAQQIAAGMVYLASQHFVHRDLATRNCLVGENLLVKIGDFG 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 767 LSRfleDDTSDPTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLP 846
Cdd:cd05093  166 MSR---DVYSTDYYRVGGHTMLPIRWMPPESIMYRKFTTESDVWSLGVVLWEIFTYGKQPWYQLSNNEVIECITQGRVLQ 242
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 111118978 847 PPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKMIR 885
Cdd:cd05093  243 RPRTCPKEVYDLMLGCWQREPHMRLNIKEIHSLLQNLAK 281
PTKc_InsR cd05061
Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer ...
627-880 2.45e-58

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: 202.12  E-value: 2.45e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLK--LPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMEN 704
Cdd:cd05061   14 LGQGSFGMVYEGNARdiIKGEAETRVAVKTVNESASLRERIEFLNEASVMKGFTCHHVVRLLGVVSKGQPTLVVMELMAH 93
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 705 GSLDSFLR-------QNDGQF--TVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRfledDT 775
Cdd:cd05061   94 GDLKSYLRslrpeaeNNPGRPppTLQEMIQMAAEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVKIGDFGMTR----DI 169
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 776 SDPTYTSALG-GKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSA 854
Cdd:cd05061  170 YETDYYRKGGkGLLPVRWMAPESLKDGVFTTSSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGYLDQPDNCPER 249
                        250       260
                 ....*....|....*....|....*.
gi 111118978 855 LHQLMLDCWQKDRNHRPKFGQIVNTL 880
Cdd:cd05061  250 VTDLMRMCWQFNPKMRPTFLEIVNLL 275
PTKc_HER4 cd05110
Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the ...
614-887 2.92e-58

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: 202.60  E-value: 2.92e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 614 KEIDISCVKieqVIGAGEFGEVCSGHLKLPGKR-EIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKS 692
Cdd:cd05110    5 KETELKRVK---VLGSGAFGTVYKGIWVPEGETvKIPVAIKILNETTGPKANVEFMDEALIMASMDHPHLVRLLGVCLSP 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 693 TpVMIITEFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLE 772
Cdd:cd05110   82 T-IQLVTQLMPHGCLLDYVHEHKDNIGSQLLLNWCVQIAKGMMYLEERRLVHRDLAARNVLVKSPNHVKITDFGLARLLE 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 773 DDTSDptyTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCP 852
Cdd:cd05110  161 GDEKE---YNADGGKMPIKWMALECIHYRKFTHQSDVWSYGVTIWELMTFGGKPYDGIPTREIPDLLEKGERLPQPPICT 237
                        250       260       270
                 ....*....|....*....|....*....|....*
gi 111118978 853 SALHQLMLDCWQKDRNHRPKFGQIVNTLDKMIRNP 887
Cdd:cd05110  238 IDVYMVMVKCWMIDADSRPKFKELAAEFSRMARDP 272
PTKc_Mer cd14204
Catalytic Domain of the Protein Tyrosine Kinase, Mer; PTKs catalyze the transfer of the ...
616-884 4.18e-58

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: 201.32  E-value: 4.18e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 616 IDISCVKIEQVIGAGEFGEVCSGHLKLPGKREIFVAIKTLK-SGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTP 694
Cdd:cd14204    4 IDRNLLSLGKVLGEGEFGSVMEGELQQPDGTNHKVAVKTMKlDNFSQREIEEFLSEAACMKDFNHPNVIRLLGVCLEVGS 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 695 -----VMIITEFMENGSLDSFLRQN----DGQFTVIQ-LVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSD 764
Cdd:cd14204   84 qripkPMVILPFMKYGDLHSFLLRSrlgsGPQHVPLQtLLKFMIDIALGMEYLSSRNFLHRDLAARNCMLRDDMTVCVAD 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 765 FGLSRFLeddTSDPTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYR 844
Cdd:cd14204  164 FGLSKKI---YSGDYYRQGRIAKMPVKWIAVESLADRVYTVKSDVWAFGVTMWEIATRGMTPYPGVQNHEIYDYLLHGHR 240
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 111118978 845 LPPPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKMI 884
Cdd:cd14204  241 LKQPEDCLDELYDIMYSCWRSDPTDRPTFTQLRENLEKLL 280
EphR_LBD_A2 cd10480
Ligand Binding Domain of Ephrin type-A Receptor 2; EphRs comprise the largest subfamily of ...
20-197 1.66e-57

Ligand Binding Domain of Ephrin type-A Receptor 2; EphRs comprise the largest subfamily of receptor tyr kinases (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. EphA2 negatively regulates cell differentiation and has been shown to be 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 contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine 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.


Pssm-ID: 198448  Cd Length: 174  Bit Score: 195.45  E-value: 1.66e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  20 EETLMDSTTATAELGWMVHP-PSGWEEVSGYdENMNTIRTYQVCNVFESSQNNWLRTKFIRRRGAHRIHVEMKFSVRDCS 98
Cdd:cd10480    1 EVVLLDFAAAGGELGWLTHPyGKGWDLMQNV-MNDSPIYMYSVCNVMSGEQDNWLRTNWIYRSEAERIFIELKFTVRDCN 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  99 SIPSVPGSCKETFNLYYYEADFDSATktfpNWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSGFYLAF 178
Cdd:cd10480   80 SFPGGAGSCKETFNLYYAESDVDYGT----NFQKRQFRKIDTIAPDEITVSSDFETRNVKLNVEERSVGPLTRKGFYLAF 155
                        170
                 ....*....|....*....
gi 111118978 179 QDYGGCMSLIAVRVFYRKC 197
Cdd:cd10480  156 QDIGACVALLSVRVYYKKC 174
PTKc_PDGFR cd05055
Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; ...
595-884 3.04e-57

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: 199.63  E-value: 3.04e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 595 IYIDPFTYedPNEAVREFAKEidisCVKIEQVIGAGEFGEVCSGHLKLPGKRE--IFVAIKTLKSGYTEKQRRDFLSEAS 672
Cdd:cd05055   17 VYIDPTQL--PYDLKWEFPRN----NLSFGKTLGAGAFGKVVEATAYGLSKSDavMKVAVKMLKPTAHSSEREALMSELK 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 673 IMGQF-DHPNVIHLEGVVTKSTPVMIITEFMENGSLDSFLRQNDGQF-TVIQLVGMLRGIAAGMKYLADMNYVHRDLAAR 750
Cdd:cd05055   91 IMSHLgNHENIVNLLGACTIGGPILVITEYCCYGDLLNFLRRKRESFlTLEDLLSFSYQVAKGMAFLASKNCIHRDLAAR 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 751 NILVNSNLVCKVSDFGLSRfleDDTSDPTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDM 830
Cdd:cd05055  171 NVLLTHGKIVKICDFGLAR---DIMNDSNYVVKGNARLPVKWMAPESIFNCVYTFESDVWSYGILLWEIFSLGSNPYPGM 247
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 111118978 831 -TNQDVINAIEQDYRLPPPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKMI 884
Cdd:cd05055  248 pVDSKFYKLIKEGYRMAQPEHAPAEIYDIMKTCWDADPLKRPTFKQIVQLIGKQL 302
PTKc_Tie cd05047
Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
626-883 3.15e-57

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: 198.34  E-value: 3.15e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 626 VIGAGEFGEVCSGHLKLPGKReIFVAIKTLKSGYTEKQRRDFLSEASIMGQF-DHPNVIHLEGVVTKSTPVMIITEFMEN 704
Cdd:cd05047    2 VIGEGNFGQVLKARIKKDGLR-MDAAIKRMKEYASKDDHRDFAGELEVLCKLgHHPNIINLLGACEHRGYLYLAIEYAPH 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 705 GSLDSFLRQN-----DGQF----------TVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSR 769
Cdd:cd05047   81 GNLLDFLRKSrvletDPAFaianstastlSSQQLLHFAADVARGMDYLSQKQFIHRDLAARNILVGENYVAKIADFGLSR 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 770 FLEddtsdpTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPM 849
Cdd:cd05047  161 GQE------VYVKKTMGRLPVRWMAIESLNYSVYTTNSDVWSYGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYRLEKPL 234
                        250       260       270
                 ....*....|....*....|....*....|....
gi 111118978 850 DCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKM 883
Cdd:cd05047  235 NCDDEVYDLMRQCWREKPYERPSFAQILVSLNRM 268
PTKc_Tyro3 cd05074
Catalytic domain of the Protein Tyrosine Kinase, Tyro3; PTKs catalyze the transfer of the ...
625-881 4.76e-57

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: 198.60  E-value: 4.76e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKLPGKREIFVAIKTLKSG-YTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPV------MI 697
Cdd:cd05074   15 RMLGKGEFGSVREAQLKSEDGSFQKVAVKMLKADiFSSSDIEEFLREAACMKEFDHPNVIKLIGVSLRSRAKgrlpipMV 94
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 698 ITEFMENGSLDSFL---RQNDGQFTVIQ--LVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLe 772
Cdd:cd05074   95 ILPFMKHGDLHTFLlmsRIGEEPFTLPLqtLVRFMIDIASGMEYLSSKNFIHRDLAARNCMLNENMTVCVADFGLSKKI- 173
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 773 ddTSDPTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCP 852
Cdd:cd05074  174 --YSGDYYRQGCASKLPVKWLALESLADNVYTTHSDVWAFGVTMWEIMTRGQTPYAGVENSEIYNYLIKGNRLKQPPDCL 251
                        250       260
                 ....*....|....*....|....*....
gi 111118978 853 SALHQLMLDCWQKDRNHRPKFGQIVNTLD 881
Cdd:cd05074  252 EDVYELMCQCWSPEPKCRPSFQHLRDQLE 280
PTKc_FGFR2 cd05101
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2; PTKs ...
602-884 1.00e-56

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: 198.70  E-value: 1.00e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 602 YEDPNEAVREFAKEIdiscVKIEQVIGAGEFGEVCS----GHLKLPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQF 677
Cdd:cd05101   11 YELPEDPKWEFPRDK----LTLGKPLGEGCFGQVVMaeavGIDKDKPKEAVTVAVKMLKDDATEKDLSDLVSEMEMMKMI 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 678 -DHPNVIHLEGVVTKSTPVMIITEFMENGSLDSFLRQN---------------DGQFTVIQLVGMLRGIAAGMKYLADMN 741
Cdd:cd05101   87 gKHKNIINLLGACTQDGPLYVIVEYASKGNLREYLRARrppgmeysydinrvpEEQMTFKDLVSCTYQLARGMEYLASQK 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 742 YVHRDLAARNILVNSNLVCKVSDFGLSRfleDDTSDPTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMS 821
Cdd:cd05101  167 CIHRDLAARNVLVTENNVMKIADFGLAR---DINNIDYYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLMWEIFT 243
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 111118978 822 YGERPYWDMTNQDVINAIEQDYRLPPPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKMI 884
Cdd:cd05101  244 LGGSPYPGIPVEELFKLLKEGHRMDKPANCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRIL 306
PTKc_Tie1 cd05089
Catalytic domain of the Protein Tyrosine Kinase, Tie1; Protein Tyrosine Kinase (PTK) family; ...
621-894 1.64e-55

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: 194.45  E-value: 1.64e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQVIGAGEFGEVCSGHLKLPGKReIFVAIKTLKSGYTEKQRRDFLSEASIMGQF-DHPNVIHLEGVVTKSTPVMIIT 699
Cdd:cd05089    4 IKFEDVIGEGNFGQVIKAMIKKDGLK-MNAAIKMLKEFASENDHRDFAGELEVLCKLgHHPNIINLLGACENRGYLYIAI 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENGSLDSFLRQN-----DGQF----------TVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSD 764
Cdd:cd05089   83 EYAPYGNLLDFLRKSrvletDPAFakehgtastlTSQQLLQFASDVAKGMQYLSEKQFIHRDLAARNVLVGENLVSKIAD 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 765 FGLSRfleddtSDPTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYR 844
Cdd:cd05089  163 FGLSR------GEEVYVKKTMGRLPVRWMAIESLNYSVYTTKSDVWSFGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYR 236
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|
gi 111118978 845 LPPPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKMIRNPNSLKAMA 894
Cdd:cd05089  237 MEKPRNCDDEVYELMRQCWRDRPYERPPFSQISVQLSRMLEARKAYVNMA 286
PTKc_TrkC cd05094
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze ...
623-883 3.58e-55

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: 193.30  E-value: 3.58e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 623 IEQVIGAGEFGEV--CSGHLKLPGKREIFVAIKTLKSGyTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITE 700
Cdd:cd05094    9 LKRELGEGAFGKVflAECYNLSPTKDKMLVAVKTLKDP-TLAARKDFQREAELLTNLQHDHIVKFYGVCGDGDPLIMVFE 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMENGSLDSFLR---------------QNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDF 765
Cdd:cd05094   88 YMKHGDLNKFLRahgpdamilvdgqprQAKGELGLSQMLHIATQIASGMVYLASQHFVHRDLATRNCLVGANLLVKIGDF 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 766 GLSRfleDDTSDPTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRL 845
Cdd:cd05094  168 GMSR---DVYSTDYYRVGGHTMLPIRWMPPESIMYRKFTTESDVWSFGVILWEIFTYGKQPWFQLSNTEVIECITQGRVL 244
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 111118978 846 PPPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKM 883
Cdd:cd05094  245 ERPRVCPKEVYDIMLGCWQREPQQRLNIKEIYKILHAL 282
PTKc_FGFR4 cd05099
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs ...
627-884 4.17e-55

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: 194.03  E-value: 4.17e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCS----GHLKLPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFD-HPNVIHLEGVVTKSTPVMIITEF 701
Cdd:cd05099   20 LGEGCFGQVVRaeayGIDKSRPDQTVTVAVKMLKDNATDKDLADLISEMELMKLIGkHKNIINLLGVCTQEGPLYVIVEY 99
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 702 MENGSLDSFLRQ---------------NDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFG 766
Cdd:cd05099  100 AAKGNLREFLRArrppgpdytfditkvPEEQLSFKDLVSCAYQVARGMEYLESRRCIHRDLAARNVLVTEDNVMKIADFG 179
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 767 LSRFLEDDTsdpTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLP 846
Cdd:cd05099  180 LARGVHDID---YYKKTSNGRLPVKWMAPEALFDRVYTHQSDVWSFGILMWEIFTLGGSPYPGIPVEELFKLLREGHRMD 256
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 111118978 847 PPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKMI 884
Cdd:cd05099  257 KPSNCTHELYMLMRECWHAVPTQRPTFKQLVEALDKVL 294
PTK_HER3 cd05111
Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR ...
625-887 5.27e-54

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


Pssm-ID: 173656 [Multi-domain]  Cd Length: 279  Bit Score: 189.78  E-value: 5.27e-54
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSG-------HLKLPgkreifVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTpVMI 697
Cdd:cd05111   13 KVLGSGVFGTVHKGiwipegdSIKIP------VAIKVIQDRSGRQSFQAVTDHMLAIGSLDHAYIVRLLGICPGAS-LQL 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 698 ITEFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSD 777
Cdd:cd05111   86 VTQLLPLGSLLDHVRQHRGSLGPQLLLNWCVQIAKGMYYLEEHRMVHRNLAARNVLLKSPSQVQVADFGVADLLYPDDKK 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 778 PTYTSAlggKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSALHQ 857
Cdd:cd05111  166 YFYSEA---KTPIKWMALESIHFGKYTHQSDVWSYGVTVWEMMTFGAEPYAGMRLAEVPDLLEKGERLAQPQICTIDVYM 242
                        250       260       270
                 ....*....|....*....|....*....|
gi 111118978 858 LMLDCWQKDRNHRPKFGQIVNTLDKMIRNP 887
Cdd:cd05111  243 VMVKCWMIDENIRPTFKELANEFTRMARDP 272
PTKc_Tie2 cd05088
Catalytic domain of the Protein Tyrosine Kinase, Tie2; PTKs catalyze the transfer of the ...
616-884 3.67e-53

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: 188.28  E-value: 3.67e-53
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 616 IDISCVKIEQVIGAGEFGEVCSGHLKLPGKReIFVAIKTLKSGYTEKQRRDFLSEASIMGQF-DHPNVIHLEGVVTKSTP 694
Cdd:cd05088    4 LEWNDIKFQDVIGEGNFGQVLKARIKKDGLR-MDAAIKRMKEYASKDDHRDFAGELEVLCKLgHHPNIINLLGACEHRGY 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 695 VMIITEFMENGSLDSFLRQN-----DGQFTVI----------QLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLV 759
Cdd:cd05088   83 LYLAIEYAPHGNLLDFLRKSrvletDPAFAIAnstastlssqQLLHFAADVARGMDYLSQKQFIHRDLAARNILVGENYV 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 760 CKVSDFGLSRFLEddtsdpTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAI 839
Cdd:cd05088  163 AKIADFGLSRGQE------VYVKKTMGRLPVRWMAIESLNYSVYTTNSDVWSYGVLLWEIVSLGGTPYCGMTCAELYEKL 236
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*
gi 111118978 840 EQDYRLPPPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKMI 884
Cdd:cd05088  237 PQGYRLEKPLNCDDEVYDLMRQCWREKPYERPSFAQILVSLNRML 281
PKc cd00180
Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group ...
627-880 1.60e-52

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: 182.86  E-value: 1.60e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGS 706
Cdd:cd00180    1 LGKGSFGKVYKARDKETGK---KVAVKVIPKEKLKKLLEELLREIEILKKLNHPNIVKLYDVFETENFLYLVMEYCEGGS 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 707 LDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDPTYTsalGG 786
Cdd:cd00180   78 LKDLLKENKGPLSEEEALSILRQLLSALEYLHSNGIIHRDLKPENILLDSDGTVKLADFGLAKDLDSDDSLLKTT---GG 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 787 KIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEvmsygerpywdmtnqdvinaieqdyrlpppMDCpsaLHQLMLDCWQKD 866
Cdd:cd00180  155 TTPPYYAPPELLGGRYYGPKVDIWSLGVILYE------------------------------LEE---LKDLIRRMLQYD 201
                        250
                 ....*....|....
gi 111118978 867 RNHRPKFGQIVNTL 880
Cdd:cd00180  202 PKKRPSAKELLEHL 215
PTKc_FGFR1 cd05098
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs ...
627-884 5.71e-52

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: 184.83  E-value: 5.71e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEV----CSGHLKLPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQF-DHPNVIHLEGVVTKSTPVMIITEF 701
Cdd:cd05098   21 LGEGCFGQVvlaeAIGLDKDKPNRVTKVAVKMLKSDATEKDLSDLISEMEMMKMIgKHKNIINLLGACTQDGPLYVIVEY 100
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 702 MENGSLDSFLRQN---------------DGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFG 766
Cdd:cd05098  101 ASKGNLREYLQARrppgmeycynpshnpEEQLSSKDLVSCAYQVARGMEYLASKKCIHRDLAARNVLVTEDNVMKIADFG 180
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 767 LSRfleDDTSDPTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLP 846
Cdd:cd05098  181 LAR---DIHHIDYYKKTTNGRLPVKWMAPEALFDRIYTHQSDVWSFGVLLWEIFTLGGSPYPGVPVEELFKLLKEGHRMD 257
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 111118978 847 PPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKMI 884
Cdd:cd05098  258 KPSNCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRIV 295
PTKc_IGF-1R cd05062
Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs ...
627-880 8.53e-52

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: 183.31  E-value: 8.53e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLK--LPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMEN 704
Cdd:cd05062   14 LGQGSFGMVYEGIAKgvVKDEPETRVAIKTVNEAASMRERIEFLNEASVMKEFNCHHVVRLLGVVSQGQPTLVIMELMTR 93
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 705 GSLDSFLRQ-------NDGQF--TVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRfleDDT 775
Cdd:cd05062   94 GDLKSYLRSlrpemenNPVQAppSLKKMIQMAGEIADGMAYLNANKFVHRDLAARNCMVAEDFTVKIGDFGMTR---DIY 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 776 SDPTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPSAL 855
Cdd:cd05062  171 ETDYYRKGGKGLLPVRWMSPESLKDGVFTTYSDVWSFGVVLWEIATLAEQPYQGMSNEQVLRFVMEGGLLDKPDNCPDML 250
                        250       260
                 ....*....|....*....|....*
gi 111118978 856 HQLMLDCWQKDRNHRPKFGQIVNTL 880
Cdd:cd05062  251 FELMRMCWQYNPKMRPSFLEIISSI 275
PTKc_VEGFR cd05054
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
611-880 1.26e-51

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: 183.46  E-value: 1.26e-51
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 611 EFAKEIdiscVKIEQVIGAGEFGEVCS----GHLKLPGKREifVAIKTLKSGYTEKQRRDFLSEASIMGQF-DHPNVIHL 685
Cdd:cd05054    3 EFPRDR----LKLGKPLGRGAFGKVIQasafGIDKSATCRT--VAVKMLKEGATASEHKALMTELKILIHIgHHLNVVNL 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 686 EGVVTKST-PVMIITEFMENGSLDSFLRQN-------------------------DGQFTVIQLVGMLRGIAAGMKYLAD 739
Cdd:cd05054   77 LGACTKPGgPLMVIVEFCKFGNLSNYLRSKreefvpyrdkgardveeeedddelyKEPLTLEDLICYSFQVARGMEFLAS 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 740 MNYVHRDLAARNILVNSNLVCKVSDFGLSRfleDDTSDPTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEV 819
Cdd:cd05054  157 RKCIHRDLAARNILLSENNVVKICDFGLAR---DIYKDPDYVRKGDARLPLKWMAPESIFDKVYTTQSDVWSFGVLLWEI 233
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 111118978 820 MSYGERPYWDMT-NQDVINAIEQDYRLPPPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTL 880
Cdd:cd05054  234 FSLGASPYPGVQmDEEFCRRLKEGTRMRAPEYTTPEIYQIMLDCWHGEPKERPTFSELVEKL 295
PTK_Ryk cd05043
Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase ...
621-880 6.53e-50

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: 178.03  E-value: 6.53e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQVIGAGEFGEVCSGHLKLPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTK-STPVMIIT 699
Cdd:cd05043    8 VTLSDLLQEGTFGRIFHGILRDEKGKEEEVLVKTVKDHASEIQVTMLLQESSLLYGLSHQNLLPILHVCIEdGEKPMVLY 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENGSLDSFLRQ------NDGQ-FTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLE 772
Cdd:cd05043   88 PYMNWGNLKLFLQQcrlseaNNPQaLSTQQLVHMALQIACGMSYLHRRGVIHKDIAARNCVIDDELQVKITDNALSRDLF 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 773 ddtsdPTYTSALGGK--IPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMD 850
Cdd:cd05043  168 -----PMDYHCLGDNenRPIKWMSLESLVNKEYSSASDVWSFGVLLWELMTLGQTPYVEIDPFEMAAYLKDGYRLAQPIN 242
                        250       260       270
                 ....*....|....*....|....*....|
gi 111118978 851 CPSALHQLMLDCWQKDRNHRPKFGQIVNTL 880
Cdd:cd05043  243 CPDELFAVMACCWALDPEERPSFQQLVQCL 272
PTKc_Jak2_rpt2 cd14205
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the ...
621-883 8.27e-50

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: 177.90  E-value: 8.27e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQVIGAGEFG--EVCSGHLKLPGKREIfVAIKTLKSGyTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKS--TPVM 696
Cdd:cd14205    6 LKFLQQLGKGNFGsvEMCRYDPLQDNTGEV-VAVKKLQHS-TEEHLRDFEREIEILKSLQHDNIVKYKGVCYSAgrRNLR 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 697 IITEFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTS 776
Cdd:cd14205   84 LIMEYLPYGSLRDYLQKHKERIDHIKLLQYTSQICKGMEYLGTKRYIHRDLATRNILVENENRVKIGDFGLTKVLPQDKE 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 777 dpTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERP------YWDMTNQD---------VINAIEQ 841
Cdd:cd14205  164 --YYKVKEPGESPIFWYAPESLTESKFSVASDVWSFGVVLYELFTYIEKSksppaeFMRMIGNDkqgqmivfhLIELLKN 241
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 111118978 842 DYRLPPPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKM 883
Cdd:cd14205  242 NGRLPRPDGCPDEIYMIMTECWNNNVNQRPSFRDLALRVDQI 283
PTKc_FGFR3 cd05100
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs ...
627-884 1.06e-49

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: 179.45  E-value: 1.06e-49
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCS----GHLKLPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQF-DHPNVIHLEGVVTKSTPVMIITEF 701
Cdd:cd05100   20 LGEGCFGQVVMaeaiGIDKDKPNKPVTVAVKMLKDDATDKDLSDLVSEMEMMKMIgKHKNIINLLGACTQDGPLYVLVEY 99
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 702 MENGSLDSFLRQN---------------DGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFG 766
Cdd:cd05100  100 ASKGNLREYLRARrppgmdysfdtcklpEEQLTFKDLVSCAYQVARGMEYLASQKCIHRDLAARNVLVTEDNVMKIADFG 179
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 767 LSRfleDDTSDPTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLP 846
Cdd:cd05100  180 LAR---DVHNIDYYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIPVEELFKLLKEGHRMD 256
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 111118978 847 PPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKMI 884
Cdd:cd05100  257 KPANCTHELYMIMRECWHAVPSQRPTFKQLVEDLDRVL 294
EphR_LBD_A1 cd10479
Ligand Binding Domain of Ephrin type-A Receptor 1; Ephrin receptors (EphRs) comprise the ...
20-196 6.27e-48

Ligand Binding Domain of Ephrin type-A Receptor 1; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (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. EphA1 is downregulated in some advanced colorectal and myeloid cancers and upregulated in neuroblasoma and glioblastoma. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine 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.


Pssm-ID: 198447  Cd Length: 177  Bit Score: 168.67  E-value: 6.27e-48
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  20 EETLMDSTTATAELGWMVHPP-SGWEEVSGYdENMNTIRTYQVCNVF-ESSQNNWLRTKFIRR-RGAHRIHVEMKFSVRD 96
Cdd:cd10479    1 EVTLMDTSTAQGELGWLLDPPeVGWSEVQQM-LNGTPLYMYQDCPVQsEGDTDHWLRSNWIYRgEEASRIYVELQFTVRD 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  97 CSSIP--SVPGSCKETFNLYYYEADFDSATKtfpnwMENP-WVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRSG 173
Cdd:cd10479   80 CKSFPggAGPLGCKETFNLYYMESDQDVGIQ-----LRRPlFQKVTTVAADQSFTIRDLASGSVKLNVERCSLGKLTRRG 154
                        170       180
                 ....*....|....*....|...
gi 111118978 174 FYLAFQDYGGCMSLIAVRVFYRK 196
Cdd:cd10479  155 LYLAFHNPGACVALVSVRVFYQR 177
PTKc_VEGFR1 cd14207
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
611-880 9.24e-47

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: 170.95  E-value: 9.24e-47
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 611 EFAKEIdiscVKIEQVIGAGEFGEVCS----GHLKLPGKReiFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHP-NVIHL 685
Cdd:cd14207    3 EFARER----LKLGKSLGRGAFGKVVQasafGIKKSPTCR--VVAVKMLKEGATASEYKALMTELKILIHIGHHlNVVNL 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 686 EGVVTKST-PVMIITEFMENGSLDSFLR-------------------------------------------------QND 715
Cdd:cd14207   77 LGACTKSGgPLMVIVEYCKYGNLSNYLKskrdffvtnkdtslqeelikekkeaeptggkkkrlesvtssesfassgfQED 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 716 -------------GQF-----TVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRfleDDTSD 777
Cdd:cd14207  157 kslsdveeeeedsGDFykrplTMEDLISYSFQVARGMEFLSSRKCIHRDLAARNILLSENNVVKICDFGLAR---DIYKN 233
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 778 PTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMT-NQDVINAIEQDYRLPPPMDCPSALH 856
Cdd:cd14207  234 PDYVRKGDARLPLKWMAPESIFDKIYSTKSDVWSYGVLLWEIFSLGASPYPGVQiDEDFCSKLKEGIRMRAPEFATSEIY 313
                        330       340
                 ....*....|....*....|....
gi 111118978 857 QLMLDCWQKDRNHRPKFGQIVNTL 880
Cdd:cd14207  314 QIMLDCWQGDPNERPRFSELVERL 337
SAM_EPH-B2 cd09552
SAM domain of EPH-B2 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
910-980 1.69e-46

SAM domain of EPH-B2 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B2 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B2 receptors and appears to mediate cell-cell initiated signal transduction. SAM domains of this subfamily form homodimers/oligomers (in head-to-head/tail-to-tail orientation); apparently such clustering is necessary for signaling. EPH-B2 receptor is involved in regulation of synaptic function; it is needed for normal vestibular function, proper formation of anterior commissure, control of cell positioning, and ordered migration in the intestinal epithelium. EPH-B2 plays a tumor suppressor role in colorectal cancer. It was found to be downregulated in gastric cancer and thus may be a negative biomarker for it.


Pssm-ID: 188951  Cd Length: 71  Bit Score: 160.17  E-value: 1.69e-46
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 111118978 910 PDYTSFNTVDEWLEAIKMGQYKESFANAGFTSFDVVSQMMMEDILRVGVTLAGHQKKILNSIQVMRAQMNQ 980
Cdd:cd09552    1 PDYTSFSTVDEWLDAIKMGQYKESFANAGFTSFDVVSQMTMEDILRVGVTLAGHQKKILNSIQVMRAQMNQ 71
PTKc_Jak1_rpt2 cd05079
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the ...
627-884 5.44e-46

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: 167.03  E-value: 5.44e-46
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFG--EVCSGHLKLPGKREIfVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKS--TPVMIITEFM 702
Cdd:cd05079   12 LGEGHFGkvELCRYDPEGDNTGEQ-VAVKSLKPESGGNHIADLKKEIEILRNLYHENIVKYKGICTEDggNGIKLIMEFL 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 703 ENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDPTYTS 782
Cdd:cd05079   91 PSGSLKEYLPRNKNKINLKQQLKYAVQICKGMDYLGSRQYVHRDLAARNVLVESEHQVKIGDFGLTKAIETDKEYYTVKD 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 783 ALGGkiPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPY--------------WDMTNQDVINAIEQDYRLPPP 848
Cdd:cd05079  171 DLDS--PVFWYAPECLIQSKFYIASDVWSFGVTLYELLTYCDSESspmtlflkmigpthGQMTVTRLVRVLEEGKRLPRP 248
                        250       260       270
                 ....*....|....*....|....*....|....*.
gi 111118978 849 MDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKMI 884
Cdd:cd05079  249 PNCPEEVYQLMRKCWEFQPSKRTTFQNLIEGFEAIL 284
PTKc_VEGFR2 cd05103
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; ...
621-885 2.29e-45

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: 167.08  E-value: 2.29e-45
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQVIGAGEFGEVCS----GHLKLPGKREifVAIKTLKSGYTEKQRRDFLSEASIMGQFDHP-NVIHLEGVVTK-STP 694
Cdd:cd05103    9 LKLGKPLGRGAFGQVIEadafGIDKTATCRT--VAVKMLKEGATHSEHRALMSELKILIHIGHHlNVVNLLGACTKpGGP 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 695 VMIITEFMENGSLDSFLRQNDGQF-------------------------------------------------------- 718
Cdd:cd05103   87 LMVIVEFCKFGNLSAYLRSKRSEFvpyktkgarfrqgkdyvgdisvdlkrrldsitssqssassgfveekslsdveeeea 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 719 ----------TVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRfleDDTSDPTYTSALGGKI 788
Cdd:cd05103  167 gqedlykdflTLEDLICYSFQVAKGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLAR---DIYKDPDYVRKGDARL 243
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 789 PIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDM-TNQDVINAIEQDYRLPPPMDCPSALHQLMLDCWQKDR 867
Cdd:cd05103  244 PLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVkIDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHGEP 323
                        330
                 ....*....|....*...
gi 111118978 868 NHRPKFGQIVNTLDKMIR 885
Cdd:cd05103  324 SQRPTFSELVEHLGNLLQ 341
STKc_PknB_like cd14014
Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs ...
622-872 1.91e-44

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: 161.60  E-value: 1.91e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGYT--EKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIIT 699
Cdd:cd14014    3 RLVRLLGRGGMGEVYRARDTLLGR---PVAIKVLRPELAedEEFRERFLREARALARLSHPNIVRVYDVGEDDGRPYIVM 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENGSLDSFLRQNdGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTsdPT 779
Cdd:cd14014   80 EYVEGGSLADLLRER-GPLPPREALRILAQIADALAAAHRAGIVHRDIKPANILLTEDGRVKLTDFGIARALGDSG--LT 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 780 YTSALGGKIPirWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAIEQDYRLPPP---MDCPSALH 856
Cdd:cd14014  157 QTGSVLGTPA--YMAPEQARGGPVDPRSDIYSLGVVLYELLT-GRPPFDGDSPAAVLAKHLQEAPPPPSplnPDVPPALD 233
                        250
                 ....*....|....*.
gi 111118978 857 QLMLDCWQKDRNHRPK 872
Cdd:cd14014  234 AIILRALAKDPEERPQ 249
PTKc_VEGFR3 cd05102
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; ...
621-885 5.00e-44

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: 162.84  E-value: 5.00e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQVIGAGEFGEVCS----GHLKlpGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQF-DHPNVIHLEGVVTKST-P 694
Cdd:cd05102    9 LRLGKVLGHGAFGKVVEasafGIDK--SSSCETVAVKMLKEGATASEHKALMSELKILIHIgNHLNVVNLLGACTKPNgP 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 695 VMIITEFMENGSLDSFLRQNDGQF---------TVIQLVGMLRG------------------------------------ 729
Cdd:cd05102   87 LMVIVEFCKYGNLSNFLRAKREGFspyrersprTRSQVRSMVEAvradrrsrqgsdrvasftestsstnqprqevddlwq 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 730 --------------IAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRfleDDTSDPTYTSALGGKIPIRWTAP 795
Cdd:cd05102  167 spltmedlicysfqVARGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLAR---DIYKDPDYVRKGSARLPLKWMAP 243
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 796 EAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMT-NQDVINAIEQDYRLPPPMDCPSALHQLMLDCWQKDRNHRPKFG 874
Cdd:cd05102  244 ESIFDKVYTTQSDVWSFGVLLWEIFSLGASPYPGVQiNEEFCQRLKDGTRMRAPEYATPEIYRIMLSCWHGDPKERPTFS 323
                        330
                 ....*....|.
gi 111118978 875 QIVNTLDKMIR 885
Cdd:cd05102  324 DLVEILGDLLQ 334
STKc_TAK1 cd14058
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated ...
627-880 9.08e-43

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: 156.44  E-value: 9.08e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLklpgkREIFVAIKTLKSgytEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGS 706
Cdd:cd14058    1 VGRGSFGVVCKARW-----RNQIVAVKIIES---ESEKKAFEVEVRQLSRVDHPNIIKLYGACSNQKPVCLVMEYAEGGS 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 707 LDSFL--RQNDGQFTVIQLVGMLRGIAAGMKYLADMN---YVHRDLAARNIL-VNSNLVCKVSDFGLSrfleddTSDPTY 780
Cdd:cd14058   73 LYNVLhgKEPKPIYTAAHAMSWALQCAKGVAYLHSMKpkaLIHRDLKPPNLLlTNGGTVLKICDFGTA------CDISTH 146
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 781 TSALGGKIPirWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYgERPYWDMTNQD--VINAIEQDYRLPPPMDCPSALHQL 858
Cdd:cd14058  147 MTNNKGSAA--WMAPEVFEGSKYSEKCDVFSWGIILWEVITR-RKPFDHIGGPAfrIMWAVHNGERPPLIKNCPKPIESL 223
                        250       260
                 ....*....|....*....|..
gi 111118978 859 MLDCWQKDRNHRPKFGQIVNTL 880
Cdd:cd14058  224 MTRCWSKDPEKRPSMKEIVKIM 245
PTKc_PDGFR_beta cd05107
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta; ...
600-884 5.92e-42

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: 159.02  E-value: 5.92e-42
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 600 FTYEDPNEAVREFAKEIDISCVKIEQVIGAGEFGEV--CSGHLKLPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQF 677
Cdd:cd05107   18 YIYVDPMQLPYDSAWEMPRDNLVLGRTLGSGAFGRVveATAHGLSHSQSTMKVAVKMLKSTARSSEKQALMSELKIMSHL 97
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 678 D-HPNVIHLEGVVTKSTPVMIITEFMENGSLDSFLRQN---------------------------------------DGQ 717
Cdd:cd05107   98 GpHLNIVNLLGACTKGGPIYIITEYCRYGDLVDYLHRNkhtflqyyldknrddgslisggstplsqrkshvslgsesDGG 177
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 718 F-------------------------------------------------TVIQ---------LVGMLRGIAAGMKYLAD 739
Cdd:cd05107  178 YmdmskdesadyvpmqdmkgtvkyadiessnyespydqylpsapertrrdTLINespalsymdLVGFSYQVANGMEFLAS 257
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 740 MNYVHRDLAARNILVNSNLVCKVSDFGLSRfleDDTSDPTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEV 819
Cdd:cd05107  258 KNCVHRDLAARNVLICEGKLVKICDFGLAR---DIMRDSNYISKGSTFLPLKWMAPESIFNNLYTTLSDVWSFGILLWEI 334
                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 111118978 820 MSYGERPYWDM-TNQDVINAIEQDYRLPPPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKMI 884
Cdd:cd05107  335 FTLGGTPYPELpMNEQFYNAIKRGYRMAKPAHASDEIYEIMQKCWEEKFEIRPDFSQLVHLVGDLL 400
PTKc_CSF-1R cd05106
Catalytic domain of the Protein Tyrosine Kinase, Colony-Stimulating Factor-1 Receptor; PTKs ...
621-885 3.14e-41

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: 155.77  E-value: 3.14e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQVIGAGEFGEVCSGHLKLPGKRE--IFVAIKTLKSGYTEKQRRDFLSEASIMGQF-DHPNVIHLEGVVTKSTPVMI 697
Cdd:cd05106   40 LQFGKTLGAGAFGKVVEATAFGLGKEDnvLRVAVKMLKASAHTDEREALMSELKILSHLgQHKNIVNLLGACTHGGPVLV 119
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 698 ITEFMENGSLDSFLRQ--------------------------------------------------------NDGQFTV- 720
Cdd:cd05106  120 ITEYCCYGDLLNFLRKkaetflnfvmalpeisetssdyknitlekkyirsdsgfssqgsdtyvemrpvssssSQSSDSKd 199
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 721 ---------IQLVGMLR---GIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSdptYTSALGGKI 788
Cdd:cd05106  200 eedtedswpLDLDDLLRfssQVAQGMDFLASKNCIHRDVAARNVLLTDGRVAKICDFGLARDIMNDSN---YVVKGNARL 276
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 789 PIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDM-TNQDVINAIEQDYRLPPPMDCPSALHQLMLDCWQKDR 867
Cdd:cd05106  277 PVKWMAPESIFDCVYTVQSDVWSYGILLWEIFSLGKSPYPGIlVNSKFYKMVKRGYQMSRPDFAPPEIYSIMKMCWNLEP 356
                        330
                 ....*....|....*...
gi 111118978 868 NHRPKFGQIVNTLDKMIR 885
Cdd:cd05106  357 TERPTFSQISQLIQRQLG 374
PTKc_Tyk2_rpt2 cd05080
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze ...
621-883 3.35e-41

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: 153.13  E-value: 3.35e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQVIGAGEFGEVcSGHLKLP---GKREIfVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKS--TPV 695
Cdd:cd05080    6 LKKIRDLGEGHFGKV-SLYCYDPtndGTGEM-VAVKALKADCGPQHRSGWKQEIDILKTLYHENIVKYKGCCSEQggKSL 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 696 MIITEFMENGSLDSFLRQNdgQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEddT 775
Cdd:cd05080   84 QLIMEYVPLGSLRDYLPKH--SIGLAQLLLFAQQICEGMAYLHSQHYIHRDLAARNVLLDNDRLVKIGDFGLAKAVP--E 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 776 SDPTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGErPYWD---------------MTNQDVINAIE 840
Cdd:cd05080  160 GHEYYRVREDGDSPVFWYAPECLKEYKFYYASDVWSFGVTLYELLTHCD-SSQSpptkflemigiaqgqMTVVRLIELLE 238
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|...
gi 111118978 841 QDYRLPPPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKM 883
Cdd:cd05080  239 RGERLPCPDKCPQEVYHLMKNCWETEASFRPTFENLIPILKTV 281
STKc_RIP cd13978
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze ...
627-880 8.67e-41

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: 151.07  E-value: 8.67e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSG-HLKLPGKreifVAIKTLKSGYT-EKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMEN 704
Cdd:cd13978    1 LGSGGFGTVSKArHVSWFGM----VAIKCLHSSPNcIEERKALLKEAEKMERARHSYVLPLLGVCVERRSLGLVMEYMEN 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 705 GSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMN--YVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDPTYTS 782
Cdd:cd13978   77 GSLKSLLEREIQDVPWSLRFRIIHEIALGMNFLHNMDppLLHHDLKPENILLDNHFHVKISDFGLSKLGMKSISANRRRG 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 783 A--LGGKipIRWTAPEAIQ--YRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAIEQ--------DYRLPPPMD 850
Cdd:cd13978  157 TenLGGT--PIYMAPEAFDdfNKKPTSKSDVYSFAIVIWAVLT-RKEPFENAINPLLIMQIVSkgdrpsldDIGRLKQIE 233
                        250       260       270
                 ....*....|....*....|....*....|
gi 111118978 851 CPSALHQLMLDCWQKDRNHRPKFGQIVNTL 880
Cdd:cd13978  234 NVQELISLMIRCWDGNPDARPTFLECLDRL 263
STKc_Raf cd14062
Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) ...
627-881 1.27e-40

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: 150.24  E-value: 1.27e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPgkreifVAIKTLK-SGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTpVMIITEFMENG 705
Cdd:cd14062    1 IGSGSFGTVYKGRWHGD------VAVKKLNvTDPTPSQLQAFKNEVAVLRKTRHVNILLFMGYMTKPQ-LAIVTQWCEGS 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 706 SLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSrfleddTSDPTYTSALG 785
Cdd:cd14062   74 SLYKHLHVLETKFEMLQLIDIARQTAQGMDYLHAKNIIHRDLKSNNIFLHEDLTVKIGDFGLA------TVKTRWSGSQQ 147
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 786 GKIP---IRWTAPEAIQYRK---FTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAIEQDYRLPPPM-----DCPSA 854
Cdd:cd14062  148 FEQPtgsILWMAPEVIRMQDenpYSFQSDVYAFGIVLYELLT-GQLPYSHINNRDQILFMVGRGYLRPDLskvrsDTPKA 226
                        250       260
                 ....*....|....*....|....*..
gi 111118978 855 LHQLMLDCWQKDRNHRPKFGQIVNTLD 881
Cdd:cd14062  227 LRRLMEDCIKFQRDERPLFPQILASLE 253
PTKc_PDGFR_alpha cd05105
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor alpha; ...
595-884 2.53e-40

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: 154.03  E-value: 2.53e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 595 IYIDPFTYedPNEAVREFAKEidisCVKIEQVIGAGEFGEVCSGHLKLPGKRE--IFVAIKTLKSGYTEKQRRDFLSEAS 672
Cdd:cd05105   19 IYVDPMQL--PYDSRWEFPRD----GLVLGRILGSGAFGKVVEGTAYGLSRSQpvMKVAVKMLKPTARSSEKQALMSELK 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 673 IMGQFD-HPNVIHLEGVVTKSTPVMIITEFMENGSLDSFLRQNDGQF--------------------------------- 718
Cdd:cd05105   93 IMTHLGpHLNIVNLLGACTKSGPIYIITEYCFYGDLVNYLHKNRDNFlsrhpekpkkdldifginpadestrsyvilsfe 172
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 719 --------------------------------------------------------------TVIQLVGMLRGIAAGMKY 736
Cdd:cd05105  173 nkgdymdmkqadttqyvpmleikeaskysdiqrsnydrpasykgsndsevknllsddgseglTTLDLLSFTYQVARGMEF 252
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 737 LADMNYVHRDLAARNILVNSNLVCKVSDFGLSRfleDDTSDPTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVM 816
Cdd:cd05105  253 LASKNCVHRDLAARNVLLAQGKIVKICDFGLAR---DIMHDSNYVSKGSTFLPVKWMAPESIFDNLYTTLSDVWSYGILL 329
                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 111118978 817 WEVMSYGERPYWDM-TNQDVINAIEQDYRLPPPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKMI 884
Cdd:cd05105  330 WEIFSLGGTPYPGMiVDSTFYNKIKSGYRMAKPDHATQEVYDIMVKCWNSEPEKRPSFLHLSDIVESLL 398
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
623-871 4.74e-40

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 155.17  E-value: 4.74e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 623 IEQVIGAGEFGEVCSGHLKLPGKReifVAIKTLKSGYT--EKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITE 700
Cdd:COG0515   11 ILRLLGRGGMGVVYLARDLRLGRP---VALKVLRPELAadPEARERFRREARALARLNHPNIVRVYDVGEEDGRPYLVME 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMENGSLDSFLRQNdGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLedDTSDPTY 780
Cdd:COG0515   88 YVEGESLADLLRRR-GPLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDGRVKLIDFGIARAL--GGATLTQ 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 781 TSALGGKIPirWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVINAIEQDYRLPPP---MDCPSALHQ 857
Cdd:COG0515  165 TGTVVGTPG--YMAPEQARGEPVDPRSDVYSLGVTLYE-LLTGRPPFDGDSPAELLRAHLREPPPPPSelrPDLPPALDA 241
                        250
                 ....*....|....
gi 111118978 858 LMLDCWQKDRNHRP 871
Cdd:COG0515  242 IVLRALAKDPEERY 255
STKc_MAP3K12_13 cd14059
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase ...
627-881 4.95e-40

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: 148.03  E-value: 4.95e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLklpgkREIFVAIKTLKSgytekqrrdfLSEASI--MGQFDHPNVIHLEGVVTKSTPVMIITEFMEN 704
Cdd:cd14059    1 LGSGAQGAVFLGKF-----RGEEVAVKKVRD----------EKETDIkhLRKLNHPNIIKFKGVCTQAPCYCILMEYCPY 65
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 705 GSLDSFLRQNDgQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDPTYTSAl 784
Cdd:cd14059   66 GQLYEVLRAGR-EITPSLLVDWSKQIASGMNYLHLHKIIHRDLKSPNVLVTYNDVLKISDFGTSKELSEKSTKMSFAGT- 143
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 785 ggkipIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAI-EQDYRLPPPMDCPSALHQLMLDCW 863
Cdd:cd14059  144 -----VAWMAPEVIRNEPCSEKVDIWSFGVVLWELLT-GEIPYKDVDSSAIIWGVgSNSLQLPVPSTCPDGFKLLMKQCW 217
                        250
                 ....*....|....*....
gi 111118978 864 Q-KDRNhRPKFGQIVNTLD 881
Cdd:cd14059  218 NsKPRN-RPSFRQILMHLD 235
STKc_MLK cd14061
Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the ...
626-883 2.37e-39

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: 146.77  E-value: 2.37e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 626 VIGAGEFGEVCSGHLklpgkREIFVAIKTLKSGYTE---KQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFM 702
Cdd:cd14061    1 VIGVGGFGKVYRGIW-----RGEEVAVKAARQDPDEdisVTLENVRQEARLFWMLRHPNIIALRGVCLQPPNLCLVMEYA 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 703 ENGSLDSFLRQNDGQFTViqLVGMLRGIAAGMKYLAD---MNYVHRDLAARNILVN--------SNLVCKVSDFGLSRfl 771
Cdd:cd14061   76 RGGALNRVLAGRKIPPHV--LVDWAIQIARGMNYLHNeapVPIIHRDLKSSNILILeaienedlENKTLKITDFGLAR-- 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 772 edDTSDPTYTSALGgkiPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDmtnqdvINAIEQDYR------- 844
Cdd:cd14061  152 --EWHKTTRMSAAG---TYAWMAPEVIKSSTFSKASDVWSYGVLLWELLT-GEVPYKG------IDGLAVAYGvavnklt 219
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 111118978 845 LPPPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKM 883
Cdd:cd14061  220 LPIPSTCPEPFAQLMKDCWQPDPHDRPSFADILKQLENI 258
PKc_STE cd05122
Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the ...
620-871 2.97e-39

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: 146.58  E-value: 2.97e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 620 CVKIEQVIGAGEFGEVCSGHLKLPGKReifVAIKTLKsgYTEKQRRDF-LSEASIMGQFDHPNVIHLEGVVTKSTPVMII 698
Cdd:cd05122    1 LFEILEKIGKGGFGVVYKARHKKTGQI---VAIKKIN--LESKEKKESiLNEIAILKKCKHPNIVKYYGSYLKKDELWIV 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 699 TEFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDP 778
Cdd:cd05122   76 MEFCSGGSLKDLLKNTNKTLTEQQIAYVCKEVLKGLEYLHSHGIIHRDIKAANILLTSDGEVKLIDFGLSAQLSDGKTRN 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 779 TYTSALGgkipirWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVI--NAIEQDYRLPPPMDCPSALH 856
Cdd:cd05122  156 TFVGTPY------WMAPEVIQGKPYGFKADIWSLGITAIE-MAEGKPPYSELPPMKALflIATNGPPGLRNPKKWSKEFK 228
                        250
                 ....*....|....*
gi 111118978 857 QLMLDCWQKDRNHRP 871
Cdd:cd05122  229 DFLKKCLQKDPEKRP 243
PTKc_Jak3_rpt2 cd05081
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the ...
621-883 3.02e-39

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: 147.35  E-value: 3.02e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQVIGAGEFG--EVCSgHLKLPGKREIFVAIKTLKSgYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKS--TPVM 696
Cdd:cd05081    6 LKYISQLGKGNFGsvELCR-YDPLGDNTGALVAVKQLQH-SGPDQQRDFQREIQILKALHSDFIVKYRGVSYGPgrRSLR 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 697 IITEFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTS 776
Cdd:cd05081   84 LVMEYLPSGCLRDFLQRHRARLDASRLLLYSSQICKGMEYLGSRRCVHRDLAARNILVESEAHVKIADFGLAKLLPLDKD 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 777 dpTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERP------YWDMTNQD--------VINAIEQD 842
Cdd:cd05081  164 --YYVVREPGQSPIFWYAPESLSDNIFSRQSDVWSFGVVLYELFTYCDKScspsaeFLRMMGCErdvpalcrLLELLEEG 241
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|.
gi 111118978 843 YRLPPPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKM 883
Cdd:cd05081  242 QRLPAPPACPAEVHELMKLCWAPSPQDRPSFSALGPQLDML 282
STKc_MAPKKK cd06606
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase ...
625-871 7.41e-39

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: 145.36  E-value: 7.41e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKLPGKreiFVAIKTLK-SGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFME 703
Cdd:cd06606    6 ELLGKGSFGSVYLALNLDTGE---LMAVKEVElSGDSEEELEALEREIRILSSLKHPNIVRYLGTERTENTLNIFLEYVP 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 704 NGSLDSFLRQNdGQF--TVIQLVgmLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEdDTSDPTYT 781
Cdd:cd06606   83 GGSLASLLKKF-GKLpePVVRKY--TRQILEGLEYLHSNGIVHRDIKGANILVDSDGVVKLADFGCAKRLA-EIATGEGT 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 782 SALGGKipIRWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQ-DVINAIEQDYRLPP-PMDCPSALHQLM 859
Cdd:cd06606  159 KSLRGT--PYWMAPEVIRGEGYGRAADIWSLGCTVIE-MATGKPPWSELGNPvAALFKIGSSGEPPPiPEHLSEEAKDFL 235
                        250
                 ....*....|..
gi 111118978 860 LDCWQKDRNHRP 871
Cdd:cd06606  236 RKCLQRDPKKRP 247
PTKc_Kit cd05104
Catalytic domain of the Protein Tyrosine Kinase, Kit; PTKs catalyze the transfer of the ...
595-884 1.66e-38

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: 148.13  E-value: 1.66e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 595 IYIDPftYEDPNEAVREFAKEIdiscVKIEQVIGAGEFGEV--CSGHLKLPGKREIFVAIKTLKSGYTEKQRRDFLSEAS 672
Cdd:cd05104   17 VYIDP--TQLPYDHKWEFPRDR----LRFGKTLGAGAFGKVveATAYGLAKADSAMTVAVKMLKPSAHSTEREALMSELK 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 673 IMGQF-DHPNVIHLEGVVTKSTPVMIITEFMENGSLDSFLRQNDGQFTVIQ----------------------------- 722
Cdd:cd05104   91 VLSYLgNHINIVNLLGACTVGGPTLVITEYCCYGDLLNFLRRKRDSFICPKfedlaeaalyrnllhqremacdslneymd 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 723 ---------------------------------------------LVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSN 757
Cdd:cd05104  171 mkpsvsyvvptkadkrrgvrsgsyvdqdvtseileedelaldtedLLSFSYQVAKGMEFLASKNCIHRDLAARNILLTHG 250
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 758 LVCKVSDFGLSRfleDDTSDPTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDM-TNQDVI 836
Cdd:cd05104  251 RITKICDFGLAR---DIRNDSNYVVKGNARLPVKWMAPESIFECVYTFESDVWSYGILLWEIFSLGSSPYPGMpVDSKFY 327
                        330       340       350       360
                 ....*....|....*....|....*....|....*....|....*...
gi 111118978 837 NAIEQDYRLPPPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKMI 884
Cdd:cd05104  328 KMIKEGYRMDSPEFAPSEMYDIMRSCWDADPLKRPTFKQIVQLIEQQL 375
STKc_Cdc7_like cd06627
Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs ...
627-871 3.14e-38

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: 143.52  E-value: 3.14e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKreiFVAIKTLK-SGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENG 705
Cdd:cd06627    8 IGRGAFGSVYKGLNLNTGE---FVAIKQISlEKIPKSDLKSVMGEIDLLKKLNHPNIVKYIGSVKTKDSLYIILEYVENG 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 706 SLDSFLRQNdGQF----TVIQLVGMLRGIAagmkYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDPtyT 781
Cdd:cd06627   85 SLASIIKKF-GKFpeslVAVYIYQVLEGLA----YLHEQGVIHRDIKGANILTTKDGLVKLADFGVATKLNEVEKDE--N 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 782 SALGGkiPiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAIEQDYRLPPPMDCPSALHQLMLD 861
Cdd:cd06627  158 SVVGT--P-YWMAPEVIEMSGVTTASDIWSVGCTVIELLT-GNPPYYDLQPMAALFRIVQDDHPPLPENISPELRDFLLQ 233
                        250
                 ....*....|
gi 111118978 862 CWQKDRNHRP 871
Cdd:cd06627  234 CFQKDPTLRP 243
STKc_IRAK cd14066
Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases ...
627-883 1.17e-37

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: 142.41  E-value: 1.17e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKreifVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGS 706
Cdd:cd14066    1 IGSGGFGTVYKGVLENGTV----VAVKRLNEMNCAASKKEFLTELEMLGRLRHPNLVRLLGYCLESDEKLLVYEYMPNGS 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 707 LDSFLRQNDGQ--FTVIQLVGMLRGIAAGMKYL---ADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDtSDPTYT 781
Cdd:cd14066   77 LEDRLHCHKGSppLPWPQRLKIAKGIARGLEYLheeCPPPIIHGDIKSSNILLDEDFEPKLTDFGLARLIPPS-ESVSKT 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 782 SALGGKIPirWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPY--------------WDMTNQDVINAIEQDYRLPP 847
Cdd:cd14066  156 SAVKGTIG--YLAPEYIRTGRVSTKSDVYSFGVVLLELLT-GKPAVdenrenasrkdlveWVESKGKEELEDILDKRLVD 232
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 111118978 848 PM----DCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKM 883
Cdd:cd14066  233 DDgveeEEVEALLRLALLCTRSDPSLRPSMKEVVQMLEKL 272
STKc_MLTK cd14060
Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated ...
628-883 1.85e-37

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: 140.86  E-value: 1.85e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 628 GAGEFGEVCSGHLKLPGKReifVAIKTLKSgyTEKqrrdflsEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGSL 707
Cdd:cd14060    2 GGGSFGSVYRAIWVSQDKE---VAVKKLLK--IEK-------EAEILSVLSHRNIIQFYGAILEAPNYGIVTEYASYGSL 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 708 DSFLRQNDGQ-FTVIQLVGMLRGIAAGMKYL---ADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDdtsdpTYTSA 783
Cdd:cd14060   70 FDYLNSNESEeMDMDQIMTWATDIAKGMHYLhmeAPVKVIHRDLKSRNVVIAADGVLKICDFGASRFHSH-----TTHMS 144
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 784 LGGKIPirWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYgERPYWDMTNQDVI-NAIEQDYRLPPPMDCPSALHQLMLDC 862
Cdd:cd14060  145 LVGTFP--WMAPEVIQSLPVSETCDTYSYGVVLWEMLTR-EVPFKGLEGLQVAwLVVEKNERPTIPSSCPRSFAELMRRC 221
                        250       260
                 ....*....|....*....|.
gi 111118978 863 WQKDRNHRPKFGQIVNTLDKM 883
Cdd:cd14060  222 WEADVKERPSFKQIIGILESM 242
STKc_MLK1 cd14145
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the ...
615-880 2.44e-37

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: 141.33  E-value: 2.44e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 615 EIDISCVKIEQVIGAGEFGEVcsgHLKLPGKREifVAIKTLKSGYTEKQRRDFLS---EASIMGQFDHPNVIHLEGVVTK 691
Cdd:cd14145    2 EIDFSELVLEEIIGIGGFGKV---YRAIWIGDE--VAVKAARHDPDEDISQTIENvrqEAKLFAMLKHPNIIALRGVCLK 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 692 STPVMIITEFMENGSLDSFLrqNDGQFTVIQLVGMLRGIAAGMKYLADMNYV---HRDLAARNILVN--------SNLVC 760
Cdd:cd14145   77 EPNLCLVMEFARGGPLNRVL--SGKRIPPDILVNWAVQIARGMNYLHCEAIVpviHRDLKSSNILILekvengdlSNKIL 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 761 KVSDFGLSRfledDTSDPTYTSALGGkipIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAIE 840
Cdd:cd14145  155 KITDFGLAR----EWHRTTKMSAAGT---YAWMAPEVIRSSMFSKGSDVWSYGVLLWELLT-GEVPFRGIDGLAVAYGVA 226
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|.
gi 111118978 841 QD-YRLPPPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTL 880
Cdd:cd14145  227 MNkLSLPIPSTCPEPFARLMEDCWNPDPHSRPPFTNILDQL 267
STKc_A-Raf cd14150
Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) ...
621-885 6.62e-37

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: 140.15  E-value: 6.62e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQVIGAGEFGEVCSGhlKLPGKreifVAIKTLK-SGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTpVMIIT 699
Cdd:cd14150    2 VSMLKRIGTGSFGTVFRG--KWHGD----VAVKILKvTEPTPEQLQAFKNEMQVLRKTRHVNILLFMGFMTRPN-FAIIT 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSrfleddTSDPT 779
Cdd:cd14150   75 QWCEGSSLYRHLHVTETRFDTMQLIDVARQTAQGMDYLHAKNIIHRDLKSNNIFLHEGLTVKIGDFGLA------TVKTR 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 780 YTSALGGKIP---IRWTAPEAIQYRK---FTSASDVWSYGIVMWEVMSyGERPYWDMTNQD-VINAIEQDYrLPPPM--- 849
Cdd:cd14150  149 WSGSQQVEQPsgsILWMAPEVIRMQDtnpYSFQSDVYAYGVVLYELMS-GTLPYSNINNRDqIIFMVGRGY-LSPDLskl 226
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 111118978 850 --DCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKMIR 885
Cdd:cd14150  227 ssNCPKAMKRLLIDCLKFKREERPLFPQILVSIELLQR 264
STKc_LIMK cd14154
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer ...
627-883 9.31e-37

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: 139.95  E-value: 9.31e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGkrEIFVAIKTLKsgYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGS 706
Cdd:cd14154    1 LGKGFFGQAIKVTHRETG--EVMVMKELIR--FDEEAQRNFLKEVKVMRSLDHPNVLKFIGVLYKDKKLNLITEYIPGGT 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 707 LDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDPTYTSALGG 786
Cdd:cd14154   77 LKDVLKDMARPLPWAQRVRFAKDIASGMAYLHSMNIIHRDLNSHNCLVREDKTVVVADFGLARLIVEERLPSGNMSPSET 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 787 KIPIR---------------WTAPEAIQYRKFTSASDVWSYGIVMWEVMS--YGERPYWDMTNQDVINaiEQDYRLPPPM 849
Cdd:cd14154  157 LRHLKspdrkkrytvvgnpyWMAPEMLNGRSYDEKVDIFSFGIVLCEIIGrvEADPDYLPRTKDFGLN--VDSFREKFCA 234
                        250       260       270
                 ....*....|....*....|....*....|....
gi 111118978 850 DCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKM 883
Cdd:cd14154  235 GCPPPFFKLAFLCCDLDPEKRPPFETLEEWLEAL 268
PTKc_Aatyk cd05042
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs ...
625-863 1.38e-35

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: 136.56  E-value: 1.38e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLkLPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMEN 704
Cdd:cd05042    1 QEIGNGWFGKVLLGEI-YSGTSVAQVVVKELKASANPKEQDTFLKEGQPYRILQHPNILQCLGQCVEAIPYLLVMEFCDL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 705 GSLDSFLRQN------DGQFTVIQLVGMlrGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGL--SRFLED--D 774
Cdd:cd05042   80 GDLKAYLRSErehergDSDTRTLQRMAC--EVAAGLAHLHKLNFVHSDLALRNCLLTSDLTVKIGDYGLahSRYKEDyiE 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 775 TSDPTYtsalggkIPIRWTAPEAIQ--YRKF-----TSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAI--EQDYRL 845
Cdd:cd05042  158 TDDKLW-------FPLRWTAPELVTefHDRLlvvdqTKYSNIWSLGVTLWELFENGAQPYSNLSDLDVLAQVvrEQDTKL 230
                        250       260
                 ....*....|....*....|.
gi 111118978 846 PPP-MDCPSA--LHQLMLDCW 863
Cdd:cd05042  231 PKPqLELPYSdrWYEVLQFCW 251
STKc_C-Raf cd14149
Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) ...
615-881 1.98e-35

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: 136.31  E-value: 1.98e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 615 EIDISCVKIEQVIGAGEFGEVCSGhlKLPGKreifVAIKTLK-SGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKST 693
Cdd:cd14149    8 EIEASEVMLSTRIGSGSFGTVYKG--KWHGD----VAVKILKvVDPTPEQFQAFRNEVAVLRKTRHVNILLFMGYMTKDN 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 694 pVMIITEFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRfLED 773
Cdd:cd14149   82 -LAIVTQWCEGSSLYKHLHVQETKFQMFQLIDIARQTAQGMDYLHAKNIIHRDMKSNNIFLHEGLTVKIGDFGLAT-VKS 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 774 DTSDPTYTSALGGKipIRWTAPEAIQYRK---FTSASDVWSYGIVMWEVMSyGERPYWDMTNQD-VINAIEQDYRLPPP- 848
Cdd:cd14149  160 RWSGSQQVEQPTGS--ILWMAPEVIRMQDnnpFSFQSDVYSYGIVLYELMT-GELPYSHINNRDqIIFMVGRGYASPDLs 236
                        250       260       270
                 ....*....|....*....|....*....|....*.
gi 111118978 849 ---MDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLD 881
Cdd:cd14149  237 klyKNCPKAMKRLVADCIKKVKEERPLFPQILSSIE 272
Pkinase pfam00069
Protein kinase domain;
623-878 1.99e-35

Protein kinase domain;


Pssm-ID: 459660 [Multi-domain]  Cd Length: 217  Bit Score: 134.29  E-value: 1.99e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  623 IEQVIGAGEFGEVCSGHLKLPGKreiFVAIKTL-KSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEF 701
Cdd:pfam00069   3 VLRKLGSGSFGTVYKAKHRDTGK---IVAIKKIkKEKIKKKKDKNILREIKILKKLNHPNIVRLYDAFEDKDNLYLVLEY 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  702 MENGSLDSFLRQNdGQFTVIQLVGMLRGIAAGMKyladmnyvhrdlaarnilvnsnlvckvsdfglsrfleddtSDPTYT 781
Cdd:pfam00069  80 VEGGSLFDLLSEK-GAFSEREAKFIMKQILEGLE----------------------------------------SGSSLT 118
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  782 SALGgkiPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYW-DMTNQDVINAIEQDYRLPP-PMDCPSALHQLM 859
Cdd:pfam00069 119 TFVG---TPWYMAPEVLGGNPYGPKVDVWSLGCILYELLT-GKPPFPgINGNEIYELIIDQPYAFPElPSNLSEEAKDLL 194
                         250
                  ....*....|....*....
gi 111118978  860 LDCWQKDRNHRPKFGQIVN 878
Cdd:pfam00069 195 KKLLKKDPSKRLTATQALQ 213
STKc_MLK4 cd14146
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the ...
626-880 3.95e-35

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: 135.17  E-value: 3.95e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 626 VIGAGEFGEVCSGHLKLpgkREifVAIKTLK-------SGYTEKQRRdflsEASIMGQFDHPNVIHLEGVVTKSTPVMII 698
Cdd:cd14146    1 IIGVGGFGKVYRATWKG---QE--VAVKAARqdpdediKATAESVRQ----EAKLFSMLRHPNIIKLEGVCLEEPNLCLV 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 699 TEFMENGSLDSFLRQNDGQFTVIQ--------LVGMLRGIAAGMKYLADMNYV---HRDLAARNIL----VNSNLVC--- 760
Cdd:cd14146   72 MEFARGGTLNRALAAANAAPGPRRarripphiLVNWAVQIARGMLYLHEEAVVpilHRDLKSSNILllekIEHDDICnkt 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 761 -KVSDFGLSRfledDTSDPTYTSALGgkiPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAI 839
Cdd:cd14146  152 lKITDFGLAR----EWHRTTKMSAAG---TYAWMAPEVIKSSLFSKGSDIWSYGVLLWELLT-GEVPYRGIDGLAVAYGV 223
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 111118978 840 E-QDYRLPPPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTL 880
Cdd:cd14146  224 AvNKLTLPIPSTCPEPFAKLMKECWEQDPHIRPSFALILEQL 265
STKc_B-Raf cd14151
Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) ...
615-886 7.51e-35

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: 134.42  E-value: 7.51e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 615 EIDISCVKIEQVIGAGEFGEVCSGhlKLPGKreifVAIKTLK-SGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKST 693
Cdd:cd14151    4 EIPDGQITVGQRIGSGSFGTVYKG--KWHGD----VAVKMLNvTAPTPQQLQAFKNEVGVLRKTRHVNILLFMGYSTKPQ 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 694 pVMIITEFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLED 773
Cdd:cd14151   78 -LAIVTQWCEGSSLYHHLHIIETKFEMIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGLATVKSR 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 774 DTSDPTYTSALGGkipIRWTAPEAIQYRK---FTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAIEQDYRLPPPM- 849
Cdd:cd14151  157 WSGSHQFEQLSGS---ILWMAPEVIRMQDknpYSFQSDVYAFGIVLYELMT-GQLPYSNINNRDQIIFMVGRGYLSPDLs 232
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|.
gi 111118978 850 ----DCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKMIRN 886
Cdd:cd14151  233 kvrsNCPKAMKRLMAECLKKKRDERPLFPQILASIELLARS 273
STKc_LIMK1 cd14221
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the ...
627-886 1.00e-34

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: 133.93  E-value: 1.00e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGkrEIFVAIKTLKsgYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGS 706
Cdd:cd14221    1 LGKGCFGQAIKVTHRETG--EVMVMKELIR--FDEETQRTFLKEVKVMRCLEHPNVLKFIGVLYKDKRLNFITEYIKGGT 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 707 LDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDPTYTSALgg 786
Cdd:cd14221   77 LRGIIKSMDSHYPWSQRVSFAKDIASGMAYLHSMNIIHRDLNSHNCLVRENKSVVVADFGLARLMVDEKTQPEGLRSL-- 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 787 KIPIR-----------WTAPEAIQYRKFTSASDVWSYGIVMWEVMSY--GERPYWDMTNQDVINAIEQDYRLPPPmDCPS 853
Cdd:cd14221  155 KKPDRkkrytvvgnpyWMAPEMINGRSYDEKVDVFSFGIVLCEIIGRvnADPDYLPRTMDFGLNVRGFLDRYCPP-NCPP 233
                        250       260       270
                 ....*....|....*....|....*....|...
gi 111118978 854 ALHQLMLDCWQKDRNHRPKFGQIVNTLDKMIRN 886
Cdd:cd14221  234 SFFPIAVLCCDLDPEKRPSFSKLEHWLETLRMH 266
PTKc_Aatyk2 cd05086
Catalytic domain of the Protein Tyrosine Kinase, Apoptosis-associated tyrosine kinase 2; PTKs ...
625-863 2.59e-34

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: 132.68  E-value: 2.59e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLkLPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMEN 704
Cdd:cd05086    3 QEIGNGWFGKVLLGEI-YTGTSVARVVVKELKASANPKEQDDFLQQGEPYYILQHPNILQCVGQCVEAIPYLLVFEFCDL 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 705 GSLDSFLRQND----GQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGL--SRFLED--DTS 776
Cdd:cd05086   82 GDLKTYLANQQeklrGDSQIMLLQRMACEIAAGLAHMHKHNFLHSDLALRNCYLTSDLTVKVGDYGIgfSRYKEDyiETD 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 777 DPTYtsalggkIPIRWTAPEAIQYRK-------FTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAI--EQDYRLPP 847
Cdd:cd05086  162 DKKY-------APLRWTAPELVTSFQdgllaaeQTKYSNIWSLGVTLWELFENAAQPYSDLSDREVLNHVikERQVKLFK 234
                        250
                 ....*....|....*....
gi 111118978 848 P-MDCPSA--LHQLMLDCW 863
Cdd:cd05086  235 PhLEQPYSdrWYEVLQFCW 253
STKc_MLK2 cd14148
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the ...
626-881 2.68e-34

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: 132.42  E-value: 2.68e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 626 VIGAGEFGEVCSGHLklpgkREIFVAIKTLKS------GYTEKQRRdflSEASIMGQFDHPNVIHLEGVVTKSTPVMIIT 699
Cdd:cd14148    1 IIGVGGFGKVYKGLW-----RGEEVAVKAARQdpdediAVTAENVR---QEARLFWMLQHPNIIALRGVCLNPPHLCLVM 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENGSLDSFLRQNDGQFTViqLVGMLRGIAAGMKYLADMNYV---HRDLAARNILV-----NSNL---VCKVSDFGLS 768
Cdd:cd14148   73 EYARGGALNRALAGKKVPPHV--LVNWAVQIARGMNYLHNEAIVpiiHRDLKSSNILIlepieNDDLsgkTLKITDFGLA 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 769 RfledDTSDPTYTSALGgkiPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAIEQD-YRLPP 847
Cdd:cd14148  151 R----EWHKTTKMSAAG---TYAWMAPEVIRLSLFSKSSDVWSFGVLLWELLT-GEVPYREIDALAVAYGVAMNkLTLPI 222
                        250       260       270
                 ....*....|....*....|....*....|....
gi 111118978 848 PMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLD 881
Cdd:cd14148  223 PSTCPEPFARLLEECWDPDPHGRPDFGSILKRLE 256
STKc_AMPK-like cd14003
Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze ...
622-878 5.79e-34

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: 131.10  E-value: 5.79e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKLPGKreiFVAIKTL-KSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITE 700
Cdd:cd14003    3 ELGKTLGEGSFGKVKLARHKLTGE---KVAIKIIdKSKLKEEIEEKIKREIEIMKLLNHPNIIKLYEVIETENKIYLVME 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMENGSLDSFLRQNDG------QFTVIQLVgmlrgiaAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDD 774
Cdd:cd14003   80 YASGGELFDYIVNNGRlsedeaRRFFQQLI-------SAVDYCHSNGIVHRDLKLENILLDKNGNLKIIDFGLSNEFRGG 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 775 tsDPTYTSAlgGKIPirWTAPEAIQYRKF-TSASDVWSYGIVMWeVMSYGERPyWDMTNQDVINA--IEQDYRLPP--PM 849
Cdd:cd14003  153 --SLLKTFC--GTPA--YAAPEVLLGRKYdGPKADVWSLGVILY-AMLTGYLP-FDDDNDSKLFRkiLKGKYPIPShlSP 224
                        250       260
                 ....*....|....*....|....*....
gi 111118978 850 DCPSALHQLMldcwQKDRNHRPKFGQIVN 878
Cdd:cd14003  225 DARDLIRRML----VVDPSKRITIEEILN 249
PTKc_Aatyk3 cd14206
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 3; PTKs ...
625-876 6.60e-34

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: 131.61  E-value: 6.60e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGhlklpgkrEIF-------VAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMI 697
Cdd:cd14206    3 QEIGNGWFGKVILG--------EIFsdytpaqVVVKELRVSAGPLEQRKFISEAQPYRSLQHPNILQCLGLCTETIPFLL 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 698 ITEFMENGSLDSFLRQN---DG--------QFTVIQLVGMlrGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFG 766
Cdd:cd14206   75 IMEFCQLGDLKRYLRAQrkaDGmtpdlptrDLRTLQRMAY--EITLGLLHLHKNNYIHSDLALRNCLLTSDLTVRIGDYG 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 767 LSrflEDDTSDPTYTSALGGKIPIRWTAPEAI-QYR------KFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAI 839
Cdd:cd14206  153 LS---HNNYKEDYYLTPDRLWIPLRWVAPELLdELHgnlivvDQSKESNVWSLGVTIWELFEFGAQPYRHLSDEEVLTFV 229
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 111118978 840 --EQDYRLPPP-MDCPSA--LHQLMLDCWQKDrNHRPKFGQI 876
Cdd:cd14206  230 vrEQQMKLAKPrLKLPYAdyWYEIMQSCWLPP-SQRPSVEEL 270
SAM_EPH-B3 cd09553
SAM domain of EPH-B3 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
910-978 1.98e-33

SAM domain of EPH-B3 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B3 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B3 receptors and appears to mediate cell-cell initiated signal transduction. EPH-B3 receptor protein kinase performs kinase-dependent and kinase-independent functions. It is known to be involved in thymus morphogenesis, in regulation of cell adhesion and migration. Also EphB3 controls cell positioning and ordered migration in the intestinal epithelium and plays a role in the regulation of adult retinal ganglion cell axon plasticity after optic nerve injury. In some experimental models overexpression of EphB3 enhances cell/cell contacts and suppresses colon tumor growth.


Pssm-ID: 188952  Cd Length: 69  Bit Score: 122.83  E-value: 1.98e-33
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 111118978 910 PDYTSFNTVDEWLEAIKMGQYKESFANAGFTSFDVVSQMMMEDILRVGVTLAGHQKKILNSIQVMRAQM 978
Cdd:cd09553    1 PDYTTFTTVGDWLDAIKMGRYKENFVSAGFASFDLVAQMTAEDLLRIGVTLAGHQKKILSSIQDMRLQM 69
STKc_MLK3 cd14147
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the ...
621-883 2.24e-33

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: 129.76  E-value: 2.24e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQVIGAGEFGEVCSGHLklpgkREIFVAIKTLKSGYTEK---QRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMI 697
Cdd:cd14147    5 LRLEEVIGIGGFGKVYRGSW-----RGELVAVKAARQDPDEDisvTAESVRQEARLFAMLAHPNIIALKAVCLEEPNLCL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 698 ITEFMENGSLDSFLRQNDGQFTViqLVGMLRGIAAGMKYL---ADMNYVHRDLAARNILVNSNLV--------CKVSDFG 766
Cdd:cd14147   80 VMEYAAGGPLSRALAGRRVPPHV--LVNWAVQIARGMHYLhceALVPVIHRDLKSNNILLLQPIEnddmehktLKITDFG 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 767 LSRfledDTSDPTYTSALGgkiPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAIE-QDYRL 845
Cdd:cd14147  158 LAR----EWHKTTQMSAAG---TYAWMAPEVIKASTFSKGSDVWSFGVLLWELLT-GEVPYRGIDCLAVAYGVAvNKLTL 229
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 111118978 846 PPPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKM 883
Cdd:cd14147  230 PIPSTCPEPFAQLMADCWAQDPHRRPDFASILQQLEAL 267
PK_GC cd13992
Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows ...
641-883 2.63e-33

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: 129.82  E-value: 2.63e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 641 KLPGKReiFVAIKTL-KSGYTEKQRRDFLSEasiMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGSLDSFLRQNDGQFT 719
Cdd:cd13992   21 GVYGGR--TVAIKHItFSRTEKRTILQELNQ---LKELVHDNLNKFIGICINPPNIAVVTEYCTRGSLQDVLLNREIKMD 95
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 720 VIQLVGMLRGIAAGMKYL-ADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDT-----SDPTYTSALggkipirWT 793
Cdd:cd13992   96 WMFKSSFIKDIVKGMNYLhSSSIGYHGRLKSSNCLVDSRWVVKLTDFGLRNLLEEQTnhqldEDAQHKKLL-------WT 168
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 794 APEAIQ----YRKFTSASDVWSYGIVMWEVMSYgERPYWDMTN----QDVINAiEQDYRLPPPMD----CPSALHQLMLD 861
Cdd:cd13992  169 APELLRgsllEVRGTQKGDVYSFAIILYEILFR-SDPFALEREvaivEKVISG-GNKPFRPELAVlldeFPPRLVLLVKQ 246
                        250       260
                 ....*....|....*....|..
gi 111118978 862 CWQKDRNHRPKFGQIVNTLDKM 883
Cdd:cd13992  247 CWAENPEKRPSFKQIKKTLTEN 268
STKc_Nek cd08215
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; ...
622-879 2.88e-33

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: 129.12  E-value: 2.88e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVcsgHL---KLPGKReifVAIKTLK-SGYTEKQRRDFLSEASIMGQFDHPNVI-HLEGVVTKSTpVM 696
Cdd:cd08215    3 EKIRVIGKGSFGSA---YLvrrKSDGKL---YVLKEIDlSNMSEKEREEALNEVKLLSKLKHPNIVkYYESFEENGK-LC 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 697 IITEFMENGSLDSFL---RQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLED 773
Cdd:cd08215   76 IVMEYADGGDLAQKIkkqKKKGQPFPEEQILDWFVQICLALKYLHSRKILHRDLKTQNIFLTKDGVVKLGDFGISKVLES 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 774 DTSD-------PTYTSalggkipirwtaPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYwDMTN-QDVINAIEQDYRL 845
Cdd:cd08215  156 TTDLaktvvgtPYYLS------------PELCENKPYNYKSDIWALGCVLYELCT-LKHPF-EANNlPALVYKIVKGQYP 221
                        250       260       270
                 ....*....|....*....|....*....|....
gi 111118978 846 PPPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNT 879
Cdd:cd08215  222 PIPSQYSSELRDLVNSMLQKDPEKRPSANEILSS 255
SAM_EPH-R cd09488
SAM domain of EPH family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH ...
914-974 5.07e-33

SAM domain of EPH family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH (erythropoietin-producing hepatocyte) family of receptor tyrosine kinases is a C-terminal signal transduction module located in the cytoplasmic region of these receptors. SAM appears to mediate cell-cell initiated signal transduction via binding proteins to a conserved tyrosine that is phosphorylated. In some cases the SAM domain mediates homodimerization/oligomerization and plays a role in the clustering process necessary for signaling. EPH kinases are the largest family of receptor tyrosine kinases. They are classified into two groups based on their abilities to bind ephrin-A and ephrin-B ligands. The EPH receptors are involved in regulation of cell movement, shape, and attachment during embryonic development; they control cell-cell interactions in the vascular, nervous, epithelial, and immune systems, and in many tumors. They are potential molecular markers for cancer diagnostics and potential targets for cancer therapy.


Pssm-ID: 188887  Cd Length: 61  Bit Score: 121.57  E-value: 5.07e-33
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 111118978 914 SFNTVDEWLEAIKMGQYKESFANAGFTSFDVVSQMMMEDILRVGVTLAGHQKKILNSIQVM 974
Cdd:cd09488    1 AFRSVGEWLESIKMGRYKENFTAAGYTSLDAVAQMTAEDLTRLGVTLVGHQKKILNSIQAL 61
STKc_CAMK cd05117
The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of ...
622-848 1.64e-31

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: 124.13  E-value: 1.64e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKLPGKReifVAIKTL-KSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGV-VTKSTpVMIIT 699
Cdd:cd05117    3 ELGKVLGRGSFGVVRLAVHKKTGEE---YAVKIIdKKKLKSEDEEMLRREIEILKRLDHPNIVKLYEVfEDDKN-LYLVM 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENGSLDSFLRQNdGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNS---NLVCKVSDFGLSRFLEDdts 776
Cdd:cd05117   79 ELCTGGELFDRIVKK-GSFSEREAAKIMKQILSAVAYLHSQGIVHRDLKPENILLASkdpDSPIKIIDFGLAKIFEE--- 154
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 111118978 777 DPTYTSALGgkipirwT----APEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAIEQ-DYRLPPP 848
Cdd:cd05117  155 GEKLKTVCG-------TpyyvAPEVLKGKGYGKKCDIWSLGVILYILLC-GYPPFYGETEQELFEKILKgKYSFDSP 223
STKc_LIMK2 cd14222
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the ...
627-883 3.81e-31

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: 123.52  E-value: 3.81e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKreIFVAIKTLKsgYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGS 706
Cdd:cd14222    1 LGKGFFGQAIKVTHKATGK--VMVMKELIR--CDEETQKTFLTEVKVMRSLDHPNVLKFIGVLYKDKRLNLLTEFIEGGT 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 707 LDSFLRQNDgQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDPTYTSALGG 786
Cdd:cd14222   77 LKDFLRADD-PFPWQQKVSFAKGIASGMAYLHSMSIIHRDLNSHNCLIKLDKTVVVADFGLSRLIVEEKKKPPPDKPTTK 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 787 KIPIR---------------WTAPEAIQYRKFTSASDVWSYGIVMWEVMS--YGERPYWDMTNQDVINaIEQDYRLPPPM 849
Cdd:cd14222  156 KRTLRkndrkkrytvvgnpyWMAPEMLNGKSYDEKVDIFSFGIVLCEIIGqvYADPDCLPRTLDFGLN-VRLFWEKFVPK 234
                        250       260       270
                 ....*....|....*....|....*....|....
gi 111118978 850 DCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKM 883
Cdd:cd14222  235 DCPPAFFPLAAICCRLEPDSRPAFSKLEDSFEAL 268
SAM_EPH-B1 cd09551
SAM domain of EPH-B1 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
910-977 7.64e-31

SAM domain of EPH-B1 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B1 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH- B1 receptors. In human vascular endothelial cells it appears to mediate cell-cell initiated signal transduction via the binding of the adaptor protein GRB10 (growth factor) through its SH2 domain to a conserved tyrosine that is phosphorylated. EPH-B1 receptors play a role in neurogenesis, in particular in regulation of proliferation and migration of neural progenitors in the hippocampus and in corneal neovascularization; they are involved in converting the crossed retinal projection to ipsilateral retinal projection. They may be potential targets in angiogenesis-related disorders.


Pssm-ID: 188950  Cd Length: 68  Bit Score: 115.52  E-value: 7.64e-31
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 111118978 910 PDYTSFNTVDEWLEAIKMGQYKESFANAGFTSFDVVSQMMMEDILRVGVTLAGHQKKILNSIQVMRAQ 977
Cdd:cd09551    1 PDFTAFTSVEDWLSAIKMSQYRDNFLSSGFTSLQLVAQMTSEDLLRIGVTLAGHQKKILNSIQSMRVQ 68
PTKc_Aatyk1 cd05087
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 1; PTKs ...
627-871 2.03e-30

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: 121.63  E-value: 2.03e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKlPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGS 706
Cdd:cd05087    5 IGHGWFGKVFLGEVN-SGLSSTQVVVKELKASASVQDQMQFLEEAQPYRALQHTNLLQCLAQCAEVTPYLLVMEFCPLGD 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 707 LDSFLRQNDGQFTV----IQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLS--RFLEDD--TSDP 778
Cdd:cd05087   84 LKGYLRSCRAAESMapdpLTLQRMACEVACGLLHLHRNNFVHSDLALRNCLLTADLTVKIGDYGLShcKYKEDYfvTADQ 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 779 TYtsalggkIPIRWTAPEAIQ-------YRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAI--EQDYRLPPP- 848
Cdd:cd05087  164 LW-------VPLRWIAPELVDevhgnllVVDQTKQSNVWSLGVTIWELFELGNQPYRHYSDRQVLTYTvrEQQLKLPKPq 236
                        250       260
                 ....*....|....*....|....*.
gi 111118978 849 --MDCPSALHQLMLDCW-QKDRnhRP 871
Cdd:cd05087  237 lkLSLAERWYEVMQFCWlQPEQ--RP 260
PKc_TNNI3K cd14064
Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting kinase; ...
627-881 2.60e-30

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: 120.71  E-value: 2.60e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLklpgkREIFVAIKTLKS-GYTEKQRRD-FLSEASIMGQFDHPNVIHLEGV-VTKSTPVMIITEFME 703
Cdd:cd14064    1 IGSGSFGKVYKGRC-----RNKIVAIKRYRAnTYCSKSDVDmFCREVSILCRLNHPCVIQFVGAcLDDPSQFAIVTQYVS 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 704 NGSLDSFLrqnDGQFTVIQLVGMLR---GIAAGMKYLADMNY--VHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDp 778
Cdd:cd14064   76 GGSLFSLL---HEQKRVIDLQSKLIiavDVAKGMEYLHNLTQpiIHRDLNSHNILLYEDGHAVVADFGESRFLQSLDED- 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 779 TYTSALGGkipIRWTAPEAI-QYRKFTSASDVWSYGIVMWEVMSyGERPYWDMtnQDVINAIEQDY---RLPPPMDCPSA 854
Cdd:cd14064  152 NMTKQPGN---LRWMAPEVFtQCTRYSIKADVFSYALCLWELLT-GEIPFAHL--KPAAAAADMAYhhiRPPIGYSIPKP 225
                        250       260
                 ....*....|....*....|....*..
gi 111118978 855 LHQLMLDCWQKDRNHRPKFGQIVNTLD 881
Cdd:cd14064  226 ISSLLMRGWNAEPESRPSFVEIVALLE 252
PTK_Jak_rpt1 cd05037
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak ...
623-880 4.54e-30

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: 119.89  E-value: 4.54e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 623 IEQVIGAGEFGEVCSGHLKLPGK---REIFVAIKTLKSGYtekqrRD----FLSEASIMGQFDHPNVIHLEGVvTKSTPV 695
Cdd:cd05037    3 FHEHLGQGTFTNIYDGILREVGDgrvQEVEVLLKVLDSDH-----RDisesFFETASLMSQISHKHLVKLYGV-CVADEN 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 696 MIITEFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNIlvnsnLVCKVSDFGLSRFLEddT 775
Cdd:cd05037   77 IMVQEYVRYGPLDKYLRRMGNNVPLSWKLQVAKQLASALHYLEDKKLIHGNVRGRNI-----LLAREGLDGYPPFIK--L 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 776 SDPTYTSALGGK----IPIRWTAPEAIQ--YRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPm 849
Cdd:cd05037  150 SDPGVPITVLSReervDRIPWIAPECLRnlQANLTIAADKWSFGTTLWEICSGGEEPLSALSSQEKLQFYEDQHQLPAP- 228
                        250       260       270
                 ....*....|....*....|....*....|.
gi 111118978 850 DCPSaLHQLMLDCWQKDRNHRPKFGQIVNTL 880
Cdd:cd05037  229 DCAE-LAELIMQCWTYEPTKRPSFRAILRDL 258
PKc_MAPKK_plant_like cd06623
Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and ...
617-886 2.73e-29

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: 118.08  E-value: 2.73e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 617 DISCVKieqVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVM 696
Cdd:cd06623    2 DLERVK---VLGQGSSGVVYKVRHKPTGK---IYALKKIHVDGDEEFRKQLLRELKTLRSCESPYVVKCYGAFYKEGEIS 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 697 IITEFMENGSLDSFLRQNdGQFTVIQLVGMLRGIAAGMKYL-ADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEdDT 775
Cdd:cd06623   76 IVLEYMDGGSLADLLKKV-GKIPEPVLAYIARQILKGLDYLhTKRHIIHRDIKPSNLLINSKGEVKIADFGISKVLE-NT 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 776 SDPTYTsALGgkipirwTA----PEAIQYRKFTSASDVWSYGIVMWEvMSYGERPY--------WDMtnqdvINAIEQDY 843
Cdd:cd06623  154 LDQCNT-FVG-------TVtymsPERIQGESYSYAADIWSLGLTLLE-CALGKFPFlppgqpsfFEL-----MQAICDGP 219
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....
gi 111118978 844 RLPPPMDCPSA-LHQLMLDCWQKDRNHRPKFGQIVNTldKMIRN 886
Cdd:cd06623  220 PPSLPAEEFSPeFRDFISACLQKDPKKRPSAAELLQH--PFIKK 261
PKc_LIMK_like cd14065
Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of ...
627-880 4.80e-29

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: 116.82  E-value: 4.80e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKreifvaIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGS 706
Cdd:cd14065    1 LGKGFFGEVYKVTHRETGK------VMVMKELKRFDEQRSFLKEVKLMRRLSHPNILRFIGVCVKDNKLNFITEYVNGGT 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 707 LDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILV---NSNLVCKVSDFGLSRFLEDD-TSDPTYTS 782
Cdd:cd14065   75 LEELLKSMDEQLPWSQRVSLAKDIASGMAYLHSKNIIHRDLNSKNCLVreaNRGRNAVVADFGLAREMPDEkTKKPDRKK 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 783 ALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSY--GERPYWDMTNQDVINAieQDYRLPPPMDCPSALHQLML 860
Cdd:cd14065  155 RLTVVGSPYWMAPEMLRGESYDEKVDVFSFGIVLCEIIGRvpADPDYLPRTMDFGLDV--RAFRTLYVPDCPPSFLPLAI 232
                        250       260
                 ....*....|....*....|
gi 111118978 861 DCWQKDRNHRPKFGQIVNTL 880
Cdd:cd14065  233 RCCQLDPEKRPSFVELEHHL 252
STKc_ATG1_ULK_like cd14009
Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like ...
627-859 1.20e-28

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: 115.78  E-value: 1.20e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKreiFVAIKTL-KSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENG 705
Cdd:cd14009    1 IGRGSFATVWKGRHKQTGE---VVAIKEIsRKKLNKKLQENLESEIAILKSIKHPNIVRLYDVQKTEDFIYLVLEYCAGG 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 706 SLDSFLRQNDGQFTVIQLVgMLRGIAAGMKYLADMNYVHRDLAARNILVNS---NLVCKVSDFGLSRFLEDDtsdpTYTS 782
Cdd:cd14009   78 DLSQYIRKRGRLPEAVARH-FMQQLASGLKFLRSKNIIHRDLKPQNLLLSTsgdDPVLKIADFGFARSLQPA----SMAE 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 783 ALGGKiPIrWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVINAIE-QDYRLPPPM------DCPSAL 855
Cdd:cd14009  153 TLCGS-PL-YMAPEILQFQKYDAKADLWSVGAILFE-MLVGKPPFRGSNHVQLLRNIErSDAVIPFPIaaqlspDCKDLL 229

                 ....
gi 111118978 856 HQLM 859
Cdd:cd14009  230 RRLL 233
STKc_PAK cd06614
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the ...
625-871 8.52e-28

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: 113.46  E-value: 8.52e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKLPGKReifVAIKTLKsgyTEKQRRDFL-SEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFME 703
Cdd:cd06614    6 EKIGEGASGEVYKATDRATGKE---VAIKKMR---LRKQNKELIiNEILIMKECKHPNIVDYYDSYLVGDELWVVMEYMD 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 704 NGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLedDTSDPTYTSA 783
Cdd:cd06614   80 GGSLTDIITQNPVRMNESQIAYVCREVLQGLEYLHSQNVIHRDIKSDNILLSKDGSVKLADFGFAAQL--TKEKSKRNSV 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 784 LGgkIPIrWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVINAIEQdyRLPPPMDCPSALHQLMLD-- 861
Cdd:cd06614  158 VG--TPY-WMAPEVIKRKDYGPKVDIWSLGIMCIE-MAEGEPPYLEEPPLRALFLITT--KGIPPLKNPEKWSPEFKDfl 231
                        250
                 ....*....|..
gi 111118978 862 --CWQKDRNHRP 871
Cdd:cd06614  232 nkCLVKDPEKRP 243
STKc_LKB1_CaMKK cd14008
Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent ...
627-876 8.65e-28

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: 113.80  E-value: 8.65e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGYTEKQRR-------------DFLSEASIMGQFDHPNVIHLEGVVT--K 691
Cdd:cd14008    1 LGRGSFGKVKLALDTETGQ---LYAIKIFNKSRLRKRREgkndrgkiknaldDVRREIAIMKKLDHPNIVRLYEVIDdpE 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 692 STPVMIITEFMENGSLDSFLR-QNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRF 770
Cdd:cd14008   78 SDKLYLVLEYCEGGPVMELDSgDRVPPLPEETARKYFRDLVLGLEYLHENGIVHRDIKPENLLLTADGTVKISDFGVSEM 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 771 LEDDtsDPTYTSALGgkipirwT----APEAIQ-----YRKFtsASDVWSYGIVMWeVMSYGERPYWDMTNQDVINAI-E 840
Cdd:cd14008  158 FEDG--NDTLQKTAG-------TpaflAPELCDgdsktYSGK--AADIWALGVTLY-CLVFGRLPFNGDNILELYEAIqN 225
                        250       260       270
                 ....*....|....*....|....*....|....*.
gi 111118978 841 QDYRLPPPMDCPSALHQLMLDCWQKDRNHRPKFGQI 876
Cdd:cd14008  226 QNDEFPIPPELSPELKDLLRRMLEKDPEKRITLKEI 261
SAM_EPH-B4 cd09554
SAM domain of EPH-B4 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
913-977 1.28e-27

SAM domain of EPH-B4 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B4 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B4 receptors and appears to mediate cell-cell initiated signal transduction. EPH-B4 protein kinase performs kinase-dependent and kinase-independent functions. These receptors play a role in the regular vascular system development during embryogenesis. They were found overexpressed in a variety of cancers, including carcinoma of the head and neck, ovarian cancer, bladder cancer, and downregulated in bone myeloma. Thus, EphB4 is a potential biomarker and a target for drug design.


Pssm-ID: 188953  Cd Length: 67  Bit Score: 106.49  E-value: 1.28e-27
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 111118978 913 TSFNTVDEWLEAIKMGQYKESFANAGFTSFDVVSQMMMEDILRVGVTLAGHQKKILNSIQVMRAQ 977
Cdd:cd09554    1 SSCGSVGEWLRAIKMERYEDSFLQAGFTTFQLVSQISTEDLLRMGVTLAGHQKKILSSIQAMGIQ 65
STKc_TSSK-like cd14080
Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs ...
623-878 1.44e-27

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: 113.05  E-value: 1.44e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 623 IEQVIGAGEFGEVCSGHLKLPGKREiFVAIKTLKsgyTEKQRRDFLS-----EASIMGQFDHPNVIHLEGVVTKSTPVMI 697
Cdd:cd14080    4 LGKTIGEGSYSKVKLAEYTKSGLKE-KVACKIID---KKKAPKDFLEkflprELEILRKLRHPNIIQVYSIFERGSKVFI 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 698 ITEFMENGSLDSFLRQNdGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSD 777
Cdd:cd14080   80 FMEYAEHGDLLEYIQKR-GALSESQARIWFRQLALAVQYLHSLDIAHRDLKCENILLDSNNNVKLSDFGFARLCPDDDGD 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 778 P---TYTSALGgkipirWTAPEAIQYRKFTS-ASDVWSYGIVMWeVMSYGERPYwDMTN--QDVINAIEQDYRLPPPMDC 851
Cdd:cd14080  159 VlskTFCGSAA------YAAPEILQGIPYDPkKYDIWSLGVILY-IMLCGSMPF-DDSNikKMLKDQQNRKVRFPSSVKK 230
                        250       260       270
                 ....*....|....*....|....*....|..
gi 111118978 852 PSA-----LHQLMldcwQKDRNHRPKFGQIVN 878
Cdd:cd14080  231 LSPeckdlIDQLL----EPDPTKRATIEEILN 258
STKc_MST1_2 cd06612
Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; ...
623-871 2.62e-27

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: 111.97  E-value: 2.62e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 623 IEQVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKsgyTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFM 702
Cdd:cd06612    7 ILEKLGEGSYGSVYKAIHKETGQ---VVAIKVVP---VEEDLQEIIKEISILKQCDSPYIVKYYGSYFKNTDLWIVMEYC 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 703 ENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDptyTS 782
Cdd:cd06612   81 GAGSVSDIMKITNKTLTEEEIAAILYQTLKGLEYLHSNKKIHRDIKAGNILLNEEGQAKLADFGVSGQLTDTMAK---RN 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 783 ALGGKiPIrWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVINAIEQdyRLPPPMDCPSALHQLMLD- 861
Cdd:cd06612  158 TVIGT-PF-WMAPEVIQEIGYNNKADIWSLGITAIE-MAEGKPPYSDIHPMRAIFMIPN--KPPPTLSDPEKWSPEFNDf 232
                        250
                 ....*....|...
gi 111118978 862 ---CWQKDRNHRP 871
Cdd:cd06612  233 vkkCLVKDPEERP 245
STKc_Byr2_like cd06628
Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein ...
626-871 9.77e-27

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: 110.70  E-value: 9.77e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 626 VIGAGEFGEVCSGHLKLPGKreiFVAIKTLK----SGYTEKQRRDFLS----EASIMGQFDHPNVIHLEGVVTKSTPVMI 697
Cdd:cd06628    7 LIGSGSFGSVYLGMNASSGE---LMAVKQVElpsvSAENKDRKKSMLDalqrEIALLRELQHENIVQYLGSSSDANHLNI 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 698 ITEFMENGSLDSFLrQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDD--- 774
Cdd:cd06628   84 FLEYVPGGSVATLL-NNYGAFEESLVRNFVRQILKGLNYLHNRGIIHRDIKGANILVDNKGGIKISDFGISKKLEANsls 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 775 TSDPTYTSALGGKipIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAIEQDYRLPPPMDCPSA 854
Cdd:cd06628  163 TKNNGARPSLQGS--VFWMAPEVVKQTSYTRKADIWSLGCLVVEMLT-GTHPFPDCTQMQAIFKIGENASPTIPSNISSE 239
                        250
                 ....*....|....*..
gi 111118978 855 LHQLMLDCWQKDRNHRP 871
Cdd:cd06628  240 ARDFLEKTFEIDHNKRP 256
STKc_MEKK1_plant cd06632
Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP) ...
625-878 1.37e-26

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: 109.80  E-value: 1.37e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGYTEKQRRDFLS----EASIMGQFDHPNVIHLEGVVTKSTPVMIITE 700
Cdd:cd06632    6 QLLGSGSFGSVYEGFNGDTGD---FFAVKEVSLVDDDKKSRESVKqleqEIALLSKLRHPNIVQYYGTEREEDNLYIFLE 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMENGSLDSFLrQNDGQFT--VIQLvgMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEddtsdp 778
Cdd:cd06632   83 YVPGGSIHKLL-QRYGAFEepVIRL--YTRQILSGLAYLHSRNTVHRDIKGANILVDTNGVVKLADFGMAKHVE------ 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 779 TYTSALGGKIPIRWTAPEAI--QYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVINAIEQDYRLPP-PMDCPSAL 855
Cdd:cd06632  154 AFSFAKSFKGSPYWMAPEVImqKNSGYGLAVDIWSLGCTVLE-MATGKPPWSQYEGVAAIFKIGNSGELPPiPDHLSPDA 232
                        250       260
                 ....*....|....*....|...
gi 111118978 856 HQLMLDCWQKDRNHRPKFGQIVN 878
Cdd:cd06632  233 KDFIRLCLQRDPEDRPTASQLLE 255
STKc_MST4 cd06640
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs ...
627-871 1.81e-26

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: 110.14  E-value: 1.81e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGhlkLPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGS 706
Cdd:cd06640   12 IGKGSFGEVFKG---IDNRTQQVVAIKIIDLEEAEDEIEDIQQEITVLSQCDSPYVTKYYGSYLKGTKLWIIMEYLGGGS 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 707 LDSFLRQndGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDdtSDPTYTSALGG 786
Cdd:cd06640   89 ALDLLRA--GPFDEFQIATMLKEILKGLDYLHSEKKIHRDIKAANVLLSEQGDVKLADFGVAGQLTD--TQIKRNTFVGT 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 787 KIpirWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVINAIEqdyRLPPPM---DCPSALHQLMLDCW 863
Cdd:cd06640  165 PF---WMAPEVIQQSAYDSKADIWSLGITAIE-LAKGEPPNSDMHPMRVLFLIP---KNNPPTlvgDFSKPFKEFIDACL 237

                 ....*...
gi 111118978 864 QKDRNHRP 871
Cdd:cd06640  238 NKDPSFRP 245
STKc_RIP2 cd14026
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2; STKs catalyze ...
650-885 2.62e-26

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: 110.01  E-value: 2.62e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 650 VAIKTLK--SGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGSLDSFLRQNDGQFTVIQLV--G 725
Cdd:cd14026   25 VAIKCLKldSPVGDSERNCLLKEAEILHKARFSYILPILGICNEPEFLGIVTEYMTNGSLNELLHEKDIYPDVAWPLrlR 104
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 726 MLRGIAAGMKYLADMN--YVHRDLAARNILVNSNLVCKVSDFGLS--RFLEDDTSDPTYTSALGGKIPirWTAPEAIQYR 801
Cdd:cd14026  105 ILYEIALGVNYLHNMSppLLHHDLKTQNILLDGEFHVKIADFGLSkwRQLSISQSRSSKSAPEGGTII--YMPPEEYEPS 182
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 802 KFTSAS---DVWSYGIVMWEVMSYgERPYWDMTNQ-DVINAIEQDYRL-----PPPMDCPS--ALHQLMLDCWQKDRNHR 870
Cdd:cd14026  183 QKRRASvkhDIYSYAIIMWEVLSR-KIPFEEVTNPlQIMYSVSQGHRPdtgedSLPVDIPHraTLINLIESGWAQNPDER 261
                        250
                 ....*....|....*
gi 111118978 871 PKFGQIVNTLDKMIR 885
Cdd:cd14026  262 PSFLKCLIELEPVLR 276
STKc_CDK9_like cd07840
Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs ...
622-818 3.36e-26

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: 109.58  E-value: 3.36e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQvIGAGEFGEVCSGHLKLPGKReifVAIKTLKsgyTEKQRRDF----LSEASIMGQFDHPNVIHLEGVVTKSTP--- 694
Cdd:cd07840    3 KIAQ-IGEGTYGQVYKARNKKTGEL---VALKKIR---MENEKEGFpitaIREIKLLQKLDHPNVVRLKEIVTSKGSaky 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 695 ---VMIITEFMENgSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFL 771
Cdd:cd07840   76 kgsIYMVFEYMDH-DLTGLLDNPEVKFTESQIKCYMKQLLEGLQYLHSNGILHRDIKGSNILINNDGVLKLADFGLARPY 154
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 111118978 772 EDDtSDPTYTSalggKIPIRW-TAPE----AIQYrkfTSASDVWSYGIVMWE 818
Cdd:cd07840  155 TKE-NNADYTN----RVITLWyRPPElllgATRY---GPEVDMWSVGCILAE 198
STKc_RIP4_like cd14025
Catalytic domain of the Serine/Threonine kinases, Receptor Interacting Protein 4 and similar ...
627-876 4.27e-26

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: 108.74  E-value: 4.27e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKlpgKREIFVAIKTLKSGYT-EKQRRDFLSEASIMGQFDHPNVIHLEGVVtkSTPVMIITEFMENG 705
Cdd:cd14025    4 VGSGGFGQVYKVRHK---HWKTWLAIKCPPSLHVdDSERMELLEEAKKMEMAKFRHILPVYGIC--SEPVGLVMEYMETG 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 706 SLDSFLRQN----DGQFTVIQlvgmlrGIAAGMKYLADMN--YVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDPT 779
Cdd:cd14025   79 SLEKLLASEplpwELRFRIIH------ETAVGMNFLHCMKppLLHLDLKPANILLDAHYHVKISDFGLAKWNGLSHSHDL 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 780 YTSALGGKIPirWTAPEAI--QYRKFTSASDVWSYGIVMWEVMSYgERPYWDMTN-QDVINAIEQDYR--LPP-----PM 849
Cdd:cd14025  153 SRDGLRGTIA--YLPPERFkeKNRCPDTKHDVYSFAIVIWGILTQ-KKPFAGENNiLHIMVKVVKGHRpsLSPiprqrPS 229
                        250       260
                 ....*....|....*....|....*..
gi 111118978 850 DCpSALHQLMLDCWQKDRNHRPKFGQI 876
Cdd:cd14025  230 EC-QQMICLMKRCWDQDPRKRPTFQDI 255
STKc_MST3_like cd06609
Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs ...
622-871 5.60e-26

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: 108.49  E-value: 5.60e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEF 701
Cdd:cd06609    4 TLLERIGKGSFGEVYKGIDKRTNQ---VVAIKVIDLEEAEDEIEDIQQEIQFLSQCDSPYITKYYGSFLKGSKLWIIMEY 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 702 MENGSLDSFLRQndGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSD-PTY 780
Cdd:cd06609   81 CGGGSVLDLLKP--GPLDETYIAFILREVLLGLEYLHSEGKIHRDIKAANILLSEEGDVKLADFGVSGQLTSTMSKrNTF 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 781 TSAlggkiPIrWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVINAIEQDyrlPPPMDCPSALHQLML 860
Cdd:cd06609  159 VGT-----PF-WMAPEVIKQSGYDEKADIWSLGITAIE-LAKGEPPLSDLHPMRVLFLIPKN---NPPSLEGNKFSKPFK 228
                        250
                 ....*....|....*
gi 111118978 861 D----CWQKDRNHRP 871
Cdd:cd06609  229 DfvelCLNKDPKERP 243
STKc_Bck1_like cd06629
Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein ...
625-871 7.94e-26

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: 108.24  E-value: 7.94e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVcsgHLKLPGKREIFVAIKTLKSGYTEKQRRDFL---------SEASIMGQFDHPNVIHLEGVVTKSTPV 695
Cdd:cd06629    7 ELIGKGTYGRV---YLAMNATTGEMLAVKQVELPKTSSDRADSRqktvvdalkSEIDTLKDLDHPNIVQYLGFEETEDYF 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 696 MIITEFMENGSLDSFLRqNDGQFTViQLV-GMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRfLEDD 774
Cdd:cd06629   84 SIFLEYVPGGSIGSCLR-KYGKFEE-DLVrFFTRQILDGLAYLHSKGILHRDLKADNILVDLEGICKISDFGISK-KSDD 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 775 TSDPTYTSALGGKIPirWTAPEAIQ-YRKFTSAS-DVWSYGIVMWEvMSYGERPYWDMTNQDVINAIEQDYRLPP-PMD- 850
Cdd:cd06629  161 IYGNNGATSMQGSVF--WMAPEVIHsQGQGYSAKvDIWSLGCVVLE-MLAGRRPWSDDEAIAAMFKLGNKRSAPPvPEDv 237
                        250       260
                 ....*....|....*....|...
gi 111118978 851 --CPSAlHQLMLDCWQKDRNHRP 871
Cdd:cd06629  238 nlSPEA-LDFLNACFAIDPRDRP 259
EphA2_TM pfam14575
Ephrin type-A receptor 2 transmembrane domain; Epha2_TM represents the left-handed dimer ...
544-617 1.62e-25

Ephrin type-A receptor 2 transmembrane domain; Epha2_TM represents the left-handed dimer transmembrane domain of of EphA2 receptor. This domain oligomerises and is important for the active signalling process.


Pssm-ID: 464211  Cd Length: 72  Bit Score: 100.37  E-value: 1.62e-25
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 111118978  544 IIGSSAAGLVFLIAVVVIAIVCNRR-GFERADSEYTDKLQHYtsghMTPGMKIYIDPFTYEDPNEAVREFAKEID 617
Cdd:pfam14575   1 VVASVAGGLVLLLVVGVVLIRRRRCcGRKKSQDDDEEEFHQY----KPPGRKTYIDPHTYEDPNQAVLEFAKEID 71
PK_KSR cd14063
Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to ...
621-885 1.73e-25

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: 107.05  E-value: 1.73e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQVIGAGEFGEVCSGHLKlpGKreifVAIKTLKSGY-TEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIIT 699
Cdd:cd14063    2 LEIKEVIGKGRFGRVHRGRWH--GD----VAIKLLNIDYlNEEQLEAFKEEVAAYKNTRHDNLVLFMGACMDPPHLAIVT 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCkVSDFGL---SRFLEDDTS 776
Cdd:cd14063   76 SLCKGRTLYSLIHERKEKFDFNKTVQIAQQICQGMGYLHAKGIIHKDLKSKNIFLENGRVV-ITDFGLfslSGLLQPGRR 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 777 DPTYtsalggKIPIRWT---APEAIQ----------YRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAIEQDY 843
Cdd:cd14063  155 EDTL------VIPNGWLcylAPEIIRalspdldfeeSLPFTKASDVYAFGTVWYELLA-GRWPFKEQPAESIIWQVGCGK 227
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|...
gi 111118978 844 RLPPP-MDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKMIR 885
Cdd:cd14063  228 KQSLSqLDIGREVKDILMQCWAYDPEKRPTFSDLLRMLERLPK 270
STKc_STK36 cd14002
Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the ...
625-870 1.88e-25

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: 106.57  E-value: 1.88e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKLPGKreiFVAIK-TLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFME 703
Cdd:cd14002    7 ELIGEGSFGKVYKGRRKYTGQ---VVALKfIPKRGKSEKELRNLRQEIEILRKLNHPNIIEMLDSFETKKEFVVVTEYAQ 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 704 nGSLDSFLrQNDGQFTVIQLvgmlRGIAA----GMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSdpT 779
Cdd:cd14002   84 -GELFQIL-EDDGTLPEEEV----RSIAKqlvsALHYLHSNRIIHRDMKPQNILIGKGGVVKLCDFGFARAMSCNTL--V 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 780 YTSALGgkIPIrWTAPEAIQYRKFTSASDVWSYGIVMWEVMsYGERPYWdmTNQ--DVINAI-EQDYRLPPPM--DCPSA 854
Cdd:cd14002  156 LTSIKG--TPL-YMAPELVQEQPYDHTADLWSLGCILYELF-VGQPPFY--TNSiyQLVQMIvKDPVKWPSNMspEFKSF 229
                        250
                 ....*....|....*.
gi 111118978 855 LHQLMldcwQKDRNHR 870
Cdd:cd14002  230 LQGLL----NKDPSKR 241
STKc_RIP1 cd14027
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze ...
629-878 1.88e-25

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: 106.82  E-value: 1.88e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 629 AGEFGEVCSGHLKLPGkreiFVAIKTLKSGYTEKQRRD-FLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGSL 707
Cdd:cd14027    3 SGGFGKVSLCFHRTQG----LVVLKTVYTGPNCIEHNEaLLEEGKMMNRLRHSRVVKLLGVILEEGKYSLVMEYMEKGNL 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 708 DSFLRQNDGQFTVIQLVgmLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRF-----LEDDTS------ 776
Cdd:cd14027   79 MHVLKKVSVPLSVKGRI--ILEIIEGMAYLHGKGVIHKDLKPENILVDNDFHIKIADLGLASFkmwskLTKEEHneqrev 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 777 DPTYTSALGGKIpirWTAPEAIQ--YRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQD-VINAIEQDYR-----LPPp 848
Cdd:cd14027  157 DGTAKKNAGTLY---YMAPEHLNdvNAKPTEKSDVYSFAIVLWAIFA-NKEPYENAINEDqIIMCIKSGNRpdvddITE- 231
                        250       260       270
                 ....*....|....*....|....*....|
gi 111118978 849 mDCPSALHQLMLDCWQKDRNHRPKFGQIVN 878
Cdd:cd14027  232 -YCPREIIDLMKLCWEANPEARPTFPGIEE 260
SAM_EPH-A5 cd09546
SAM domain of EPH-A5 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
914-978 3.13e-25

SAM domain of EPH-A5 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A5 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A5 receptors and appears to mediate cell-cell initiated signal transduction. Eph-A5 gene is almost exclusively expressed in the nervous system. Murine EPH-A5 receptors participate in axon guidance during embryogenesis and play a role in the adult synaptic plasticity, particularly in neuron-target interactions in multiple neural circuits. Additionally EPH-A5 receptors and its ligand ephrin A5 regulate dopaminergic axon outgrowth and influence the formation of the midbrain dopaminergic pathways. EphA5 gene expression was found decreased in a few different breast cancer cell lines, thus it might be a potential molecular marker for breast cancer carcinogenesis and progression.


Pssm-ID: 188945  Cd Length: 66  Bit Score: 99.62  E-value: 3.13e-25
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 111118978 914 SFNTVDEWLEAIKMGQYKESFANAGFTSFDVVSQMMMEDILRVGVTLAGHQKKILNSIQVMRAQM 978
Cdd:cd09546    2 AYRSVGEWLEAIKMGRYTEIFMENGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSIQEMRVQL 66
SAM_EPH-A7 cd09548
SAM domain of EPH-A7 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
910-978 4.29e-25

SAM domain of EPH-A7 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A7 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A7 receptors and appears to mediate cell-cell initiated signal transduction. EphA7 was found expressed in human embryonic stem (ES) cells, neural tissues, kidney vasculature. EphA7 knockout mice show decrease in cortical progenitor cell death at mid-neurogenesis and significant increase in cortical size. EphA7 may be involved in the pathogenesis and development of different cancers; in particular, EphA7 was found upregulated in glioblastoma and downregulated in colorectal cancer and gastric cancer. Thus, it is a potential molecular marker and/or therapy target for these types of cancers.


Pssm-ID: 188947  Cd Length: 70  Bit Score: 99.33  E-value: 4.29e-25
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 111118978 910 PDYTSFNTVDEWLEAIKMGQYKESFANAGFTSFDVVSQMMMEDILRVGVTLAGHQKKILNSIQVMRAQM 978
Cdd:cd09548    2 PDFTSFCSVGEWLEAIKMERYKDNFTAAGYNSLESVARMTIEDVMSLGITLVGHQKKIMSSIQTMRAQM 70
STKc_MAPK cd07834
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs ...
622-820 5.53e-25

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: 107.23  E-value: 5.53e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKLPGKReifVAIKtlksgyteKQRRDF---------LSEASIMGQFDHPNVIHLEGVVTKS 692
Cdd:cd07834    3 ELLKPIGSGAYGVVCSAYDKRTGRK---VAIK--------KISNVFddlidakriLREIKILRHLKHENIIGLLDILRPP 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 693 TP-----VMIITEFMENgSLDSFLRQND------GQFTVIQlvgMLRGIaagmKYLADMNYVHRDLAARNILVNSNLVCK 761
Cdd:cd07834   72 SPeefndVYIVTELMET-DLHKVIKSPQpltddhIQYFLYQ---ILRGL----KYLHSAGVIHRDLKPSNILVNSNCDLK 143
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 111118978 762 VSDFGLSRFLEDDTSDPTYTsalgGKIPIRW-TAPEAI-QYRKFTSASDVWSYGIVMWEVM 820
Cdd:cd07834  144 ICDFGLARGVDPDEDKGFLT----EYVVTRWyRAPELLlSSKKYTKAIDIWSVGCIFAELL 200
STKc_OSR1_SPAK cd06610
Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and ...
622-887 6.07e-25

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: 105.52  E-value: 6.07e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLkLPGKREifVAIKTLKsgyTEKQRRDF---LSEASIMGQFDHPNVIHLEGVVTKSTPVMII 698
Cdd:cd06610    4 ELIEVIGSGATAVVYAAYC-LPKKEK--VAIKRID---LEKCQTSMdelRKEIQAMSQCNHPNVVSYYTSFVVGDELWLV 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 699 TEFMENGSLDSFLRQ---NDGQFTVIqLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLED-- 773
Cdd:cd06610   78 MPLLSGGSLLDIMKSsypRGGLDEAI-IATVLKEVLKGLEYLHSNGQIHRDVKAGNILLGEDGSVKIADFGVSASLATgg 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 774 DTSDPTYTSALGgkIPIrWTAPEAI-QYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVINAIEQDYrlPPPMD-- 850
Cdd:cd06610  157 DRTRKVRKTFVG--TPC-WMAPEVMeQVRGYDFKADIWSFGITAIE-LATGAAPYSKYPPMKVLMLTLQND--PPSLEtg 230
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 111118978 851 -----CPSALHQLMLDCWQKDRNHRPkfgqivnTLDKMIRNP 887
Cdd:cd06610  231 adykkYSKSFRKMISLCLQKDPSKRP-------TAEELLKHK 265
STKc_BMPR2_AMHR2 cd14054
Catalytic domain of the Serine/Threonine Kinases, Bone Morphogenetic Protein and ...
625-870 9.23e-25

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: 105.91  E-value: 9.23e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKlpgkrEIFVAIKTlksgYTEKQRRDFLSEASIMGQF--DHPNVIHLEGVVTKSTPV-----MI 697
Cdd:cd14054    1 QLIGQGRYGTVWKGSLD-----ERPVAVKV----FPARHRQNFQNEKDIYELPlmEHSNILRFIGADERPTADgrmeyLL 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 698 ITEFMENGSLDSFLRQNDGQFTviQLVGMLRGIAAGMKYL------ADMN---YVHRDLAARNILVNSNLVCKVSDFGLS 768
Cdd:cd14054   72 VLEYAPKGSLCSYLRENTLDWM--SSCRMALSLTRGLAYLhtdlrrGDQYkpaIAHRDLNSRNVLVKADGSCVICDFGLA 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 769 RFLEDDTSDPTYTSALGGKIP-----IRWTAPE----AIQYRKFTSA---SDVWSYGIVMWEV------MSYGER-PYWD 829
Cdd:cd14054  150 MVLRGSSLVRGRPGAAENASIsevgtLRYMAPEvlegAVNLRDCESAlkqVDVYALGLVLWEIamrcsdLYPGESvPPYQ 229
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 111118978 830 M----------TNQDVINAI-EQDYR--LPPPMDC----PSALHQLMLDCWQKDRNHR 870
Cdd:cd14054  230 MpyeaelgnhpTFEDMQLLVsREKARpkFPDAWKEnslaVRSLKETIEDCWDQDAEAR 287
PKc_TESK cd14155
Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; ...
627-885 1.71e-24

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: 103.71  E-value: 1.71e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKreifvaIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGS 706
Cdd:cd14155    1 IGSGFFSEVYKVRHRTSGQ------VMALKMNTLSSNRANMLREVQLMNRLSHPNILRFMGVCVHQGQLHALTEYINGGN 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 707 LDSFLrQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILV---NSNLVCKVSDFGLSRFLEDDTSDPTYTSA 783
Cdd:cd14155   75 LEQLL-DSNEPLSWTVRVKLALDIARGLSYLHSKGIFHRDLTSKNCLIkrdENGYTAVVGDFGLAEKIPDYSDGKEKLAV 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 784 LGGKIpirWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGErpywdmTNQDVINAIEQ---DYRLPPPM--DCPSALHQL 858
Cdd:cd14155  154 VGSPY---WMAPEVLRGEPYNEKADVFSYGIILCEIIARIQ------ADPDYLPRTEDfglDYDAFQHMvgDCPPDFLQL 224
                        250       260
                 ....*....|....*....|....*..
gi 111118978 859 MLDCWQKDRNHRPKFGQIVNTLDKMIR 885
Cdd:cd14155  225 AFNCCNMDPKSRPSFHDIVKTLEEILE 251
STK_BAK1_like cd14664
Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; ...
627-826 2.14e-24

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: 103.73  E-value: 2.14e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKlpgkREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGS 706
Cdd:cd14664    1 IGRGGAGTVYKGVMP----NGTLVAVKRLKGEGTQGGDHGFQAEIQTLGMIRHRNIVRLRGYCSNPTTNLLVYEYMPNGS 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 707 LDSFLRQNDGQFTVIQLVGMLR---GIAAGMKYL---ADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDptY 780
Cdd:cd14664   77 LGELLHSRPESQPPLDWETRQRialGSARGLAYLhhdCSPLIIHRDVKSNNILLDEEFEAHVADFGLAKLMDDKDSH--V 154
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 111118978 781 TSALGGKIPirWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERP 826
Cdd:cd14664  155 MSSVAGSYG--YIAPEYAYTGKVSEKSDVYSYGVVLLELIT-GKRP 197
STKc_Mos cd13979
Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze ...
621-871 2.69e-24

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: 103.62  E-value: 2.69e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQVIGAGEFGEVCSGHLKlpGKReifVAIKTLK-SGYTEKQRRDFLSEASIMgQFDHPNVIHL---EGVVTKSTPVM 696
Cdd:cd13979    5 LRLQEPLGSGGFGSVYKATYK--GET---VAVKIVRrRRKNRASRQSFWAELNAA-RLRHENIVRVlaaETGTDFASLGL 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 697 IITEFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTS 776
Cdd:cd13979   79 IIMEYCGNGTLQQLIYEGSEPLPLAHRILISLDIARALRFCHSHGIVHLDVKPANILISEQGVCKLCDFGCSVKLGEGNE 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 777 DPTYTSALGGKipIRWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWDMtNQDVINAIEQdYRLPPPMDCPS--- 853
Cdd:cd13979  159 VGTPRSHIGGT--YTYRAPELLKGERVTPKADIYSFGITLWQ-MLTRELPYAGL-RQHVLYAVVA-KDLRPDLSGLEdse 233
                        250       260
                 ....*....|....*....|.
gi 111118978 854 ---ALHQLMLDCWQKDRNHRP 871
Cdd:cd13979  234 fgqRLRSLISRCWSAQPAERP 254
SAM_EPH-B6 cd09555
SAM domain of EPH-B6 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
910-978 3.62e-24

SAM domain of EPH-B6 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B6 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B6 receptors and appears to mediate cell-cell initiated signal transduction. Receptors of this type are highly expressed in embryo and adult nervous system, in thymus and also in T-cells. They are involved in regulation of cell adhesion and migration. (EPH-B6 receptor is unusual; it fails to show catalytic activity due to alteration in kinase domain). EPH-B6 may be considered as a biomarker in some types of tumors; EPH-B6 activates MAP kinase signaling in lung adenocarcinoma, suppresses metastasis formation in non-small cell lung cancer, and slows invasiveness in some breast cancer cell lines.


Pssm-ID: 188954  Cd Length: 69  Bit Score: 96.54  E-value: 3.62e-24
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 111118978 910 PDYTSFNTVDEWLEAIKMGQYKESFANAGFTSFDVVSQMMMEDILRVGVTLAGHQKKILNSIQVMRAQM 978
Cdd:cd09555    1 LDFPCLDSPQAWLSAIGLECYQDNFSKFGLCTFSDVAQLSLEDLPALGITLAGHQKKLLHHIQLLQQHL 69
STKc_Aurora cd14007
Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of ...
622-878 4.23e-24

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: 102.55  E-value: 4.23e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEV------CSGHLklpgkreifVAIK-----TLKSGYTEKQ-RRdflsEASIMGQFDHPNVIHLEGVV 689
Cdd:cd14007    3 EIGKPLGKGKFGNVylarekKSGFI---------VALKvisksQLQKSGLEHQlRR----EIEIQSHLRHPNILRLYGYF 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 690 TKSTPVMIITEFMENGSLDSFLRQNdGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSR 769
Cdd:cd14007   70 EDKKRIYLILEYAPNGELYKELKKQ-KRFDEKEAAKYIYQLALALDYLHSKNIIHRDIKPENILLGSNGELKLADFGWSV 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 770 FLEDDTsdptytsalggkipiRWT--------APEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVINAI-E 840
Cdd:cd14007  149 HAPSNR---------------RKTfcgtldylPPEMVEGKEYDYKVDIWSLGVLCYE-LLVGKPPFESKSHQETYKRIqN 212
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 111118978 841 QDYRLPPPMdcPSALHQLMLDCWQKDRNHRPKFGQIVN 878
Cdd:cd14007  213 VDIKFPSSV--SPEAKDLISKLLQKDPSKRLSLEQVLN 248
STKc_MST3 cd06641
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs ...
604-877 9.50e-24

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


Pssm-ID: 270809 [Multi-domain]  Cd Length: 277  Bit Score: 102.07  E-value: 9.50e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 604 DPNEAVREFAKeidiscvkieqvIGAGEFGEVCSGhlkLPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVI 683
Cdd:cd06641    1 DPEELFTKLEK------------IGKGSFGEVFKG---IDNRTQKVVAIKIIDLEEAEDEIEDIQQEITVLSQCDSPYVT 65
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 684 HLEGVVTKSTPVMIITEFMENGSLDSFLRQndGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVS 763
Cdd:cd06641   66 KYYGSYLKDTKLWIIMEYLGGGSALDLLEP--GPLDETQIATILREILKGLDYLHSEKKIHRDIKAANVLLSEHGEVKLA 143
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 764 DFGLSRFLEDdtSDPTYTSALGGKIpirWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVINAIEQDy 843
Cdd:cd06641  144 DFGVAGQLTD--TQIKRN*FVGTPF---WMAPEVIKQSAYDSKADIWSLGITAIE-LARGEPPHSELHPMKVLFLIPKN- 216
                        250       260       270
                 ....*....|....*....|....*....|....*..
gi 111118978 844 rlPPPM---DCPSALHQLMLDCWQKDRNHRPKFGQIV 877
Cdd:cd06641  217 --NPPTlegNYSKPLKEFVEACLNKEPSFRPTAKELL 251
PKc_Byr1_like cd06620
Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; ...
627-871 9.60e-24

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: 102.52  E-value: 9.60e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVcSGHLKLPgkREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGV-VTKSTPVMIITEFMENG 705
Cdd:cd06620   13 LGAGNGGSV-SKVLHIP--TGTIMAKKVIHIDAKSSVRKQILRELQILHECHSPYIVSFYGAfLNENNNIIICMEYMDCG 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 706 SLDSFLRQNdGQFTViQLVGMLR-GIAAGMKYLADMNY-VHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDpTY--T 781
Cdd:cd06620   90 SLDKILKKK-GPFPE-EVLGKIAvAVLEGLTYLYNVHRiIHRDIKPSNILVNSKGQIKLCDFGVSGELINSIAD-TFvgT 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 782 SAlggkipirWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWD-----------MTNQDVINAI--EQDYRLPPP 848
Cdd:cd06620  167 ST--------YMSPERIQGGKYSVKSDVWSLGLSIIELAL-GEFPFAGsnddddgyngpMGILDLLQRIvnEPPPRLPKD 237
                        250       260
                 ....*....|....*....|...
gi 111118978 849 MDCPSALHQLMLDCWQKDRNHRP 871
Cdd:cd06620  238 RIFPKDLRDFVDRCLLKDPRERP 260
PKc_MAPKK cd06605
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase ...
626-878 1.70e-23

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: 101.27  E-value: 1.70e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 626 VIGAGEFGEVCSGHLKLPGkreIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENG 705
Cdd:cd06605    8 ELGEGNGGVVSKVRHRPSG---QIMAVKVIRLEIDEALQKQILRELDVLHKCNSPYIVGFYGAFYSEGDISICMEYMDGG 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 706 SLDSFLRQNDGqftvI---QLVGMLRGIAAGMKYL-ADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDD---TSDP 778
Cdd:cd06605   85 SLDKILKEVGR----IperILGKIAVAVVKGLIYLhEKHKIIHRDVKPSNILVNSRGQVKLCDFGVSGQLVDSlakTFVG 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 779 TYTsalggkipirWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVINAIEQ-DY-------RLPPPMD 850
Cdd:cd06605  161 TRS----------YMAPERISGGKYTVKSDIWSLGLSLVE-LATGRFPYPPPNAKPSMMIFELlSYivdepppLLPSGKF 229
                        250       260
                 ....*....|....*....|....*...
gi 111118978 851 CPSALHqLMLDCWQKDRNHRPKFGQIVN 878
Cdd:cd06605  230 SPDFQD-FVSQCLQKDPTERPSYKELME 256
STKc_SLK_like cd06611
Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the ...
627-885 1.79e-23

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: 101.36  E-value: 1.79e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGkreIFVAIKTLKSGyTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGS 706
Cdd:cd06611   13 LGDGAFGKVYKAQHKETG---LFAAAKIIQIE-SEEELEDFMVEIDILSECKHPNIVGLYEAYFYENKLWILIEFCDGGA 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 707 LDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDdtSDPTYTSALGG 786
Cdd:cd06611   89 LDSIMLELERGLTEPQIRYVCRQMLEALNFLHSHKVIHRDLKAGNILLTLDGDVKLADFGVSAKNKS--TLQKRDTFIGT 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 787 KipiRWTAPEAIQYRKFTSA-----SDVWSYGIVMWEvMSYGERPYWDMTNQDVINAIEQDYrlPPPMDCPS----ALHQ 857
Cdd:cd06611  167 P---YWMAPEVVACETFKDNpydykADIWSLGITLIE-LAQMEPPHHELNPMRVLLKILKSE--PPTLDQPSkwssSFND 240
                        250       260       270
                 ....*....|....*....|....*....|....*
gi 111118978 858 LMLDCWQKDRNHRPKFGQI-------VNTLDKMIR 885
Cdd:cd06611  241 FLKSCLVKDPDDRPTAAELlkhpfvsDQSDNKAIK 275
STKc_IRAK4 cd14158
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; ...
627-821 2.61e-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: 101.04  E-value: 2.61e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKlpgkrEIFVAIKTLKS---GYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFME 703
Cdd:cd14158   23 LGEGGFGVVFKGYIN-----DKNVAVKKLAAmvdISTEDLTKQFEQEIQVMAKCQHENLVELLGYSCDGPQLCLVYTYMP 97
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 704 NGSLDSFLRQNDGQ--FTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDpTYT 781
Cdd:cd14158   98 NGSLLDRLACLNDTppLSWHMRCKIAQGTANGINYLHENNHIHRDIKSANILLDETFVPKISDFGLARASEKFSQT-IMT 176
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 111118978 782 SALGGKIPirWTAPEAIQYrKFTSASDVWSYGIVMWEVMS 821
Cdd:cd14158  177 ERIVGTTA--YMAPEALRG-EITPKSDIFSFGVVLLEIIT 213
STKc_Nek11 cd08222
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
623-879 3.60e-23

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: 100.19  E-value: 3.60e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 623 IEQVIGAGEFGEV---------CSGHLKLpgKREIFVAikTLKSGYTEkqrrDFLSEASIMGQFDHPNVIHLEGVVTKST 693
Cdd:cd08222    4 VVRKLGSGNFGTVylvsdlkatADEELKV--LKEISVG--ELQPDETV----DANREAKLLSKLDHPAIVKFHDSFVEKE 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 694 PVMIITEFMENGSLD---SFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVcKVSDFGLSRF 770
Cdd:cd08222   76 SFCIVTEYCEGGDLDdkiSEYKKSGTTIDENQILDWFIQLLLAVQYMHERRILHRDLKAKNIFLKNNVI-KVGDFGISRI 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 771 LEdDTSD--------PTYTSalggkipirwtaPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVINAI-EQ 841
Cdd:cd08222  155 LM-GTSDlattftgtPYYMS------------PEVLKHEGYNSKSDIWSLGCILYE-MCCLKHAFDGQNLLSVMYKIvEG 220
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 111118978 842 DyrLPPPMDC-PSALHQLMLDCWQKDRNHRPKFGQIVNT 879
Cdd:cd08222  221 E--TPSLPDKySKELNAIYSRMLNKDPALRPSAAEILKI 257
PTK_Jak2_rpt1 cd05078
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 2; Jak2 is widely ...
624-881 4.29e-23

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


Pssm-ID: 270663 [Multi-domain]  Cd Length: 262  Bit Score: 100.02  E-value: 4.29e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 624 EQVIGAGEFGEVCSGHLKLPGK----REIFVAIKTLKS---GYTEKqrrdFLSEASIMGQFDHPNVIHLEGVVTKSTPVM 696
Cdd:cd05078    4 NESLGQGTFTKIFKGIRREVGDygqlHETEVLLKVLDKahrNYSES----FFEAASMMSQLSHKHLVLNYGVCVCGDENI 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 697 IITEFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILV-------NSNL-VCKVSDFGLS 768
Cdd:cd05078   80 LVQEYVKFGSLDTYLKKNKNCINILWKLEVAKQLAWAMHFLEEKTLVHGNVCAKNILLireedrkTGNPpFIKLSDPGIS 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 769 RfleddTSDPtyTSALGGKIPirWTAPEAIQY-RKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPP 847
Cdd:cd05078  160 I-----TVLP--KDILLERIP--WVPPECIENpKNLSLATDKWSFGTTLWEICSGGDKPLSALDSQRKLQFYEDRHQLPA 230
                        250       260       270
                 ....*....|....*....|....*....|....
gi 111118978 848 PMdcPSALHQLMLDCWQKDRNHRPKFGQIVNTLD 881
Cdd:cd05078  231 PK--WTELANLINNCMDYEPDHRPSFRAIIRDLN 262
STKc_ACVR2 cd14053
Catalytic domain of the Serine/Threonine Kinase, Activin Type II Receptor; STKs catalyze the ...
625-821 5.29e-23

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: 100.48  E-value: 5.29e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKlpgkrEIFVAIKTLKsgytEKQRRDFLSEASIMG--QFDHPNVIHLEGV----VTKSTPVMII 698
Cdd:cd14053    1 EIKARGRFGAVWKAQYL-----NRLVAVKIFP----LQEKQSWLTEREIYSlpGMKHENILQFIGAekhgESLEAEYWLI 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 699 TEFMENGSLDSFLRQNdgqftVIQLVGMLR---GIAAGMKYL-ADMNY---------VHRDLAARNILVNSNLVCKVSDF 765
Cdd:cd14053   72 TEFHERGSLCDYLKGN-----VISWNELCKiaeSMARGLAYLhEDIPAtngghkpsiAHRDFKSKNVLLKSDLTACIADF 146
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 111118978 766 GLSRFLEDDTSDPTYTSALGGKipiRWTAPE----AIQYRK--FTsASDVWSYGIVMWEVMS 821
Cdd:cd14053  147 GLALKFEPGKSCGDTHGQVGTR---RYMAPEvlegAINFTRdaFL-RIDMYAMGLVLWELLS 204
STKc_CMGC cd05118
Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
626-859 9.73e-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: 98.46  E-value: 9.73e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 626 VIGAGEFGEVCSGHLKLPGKReifVAIKTLKSgYTEKQRRDfLSEASIMGQF----DHPNVIHLEGVVT--KSTPVMIIT 699
Cdd:cd05118    6 KIGEGAFGTVWLARDKVTGEK---VAIKKIKN-DFRHPKAA-LREIKLLKHLndveGHPNIVKLLDVFEhrGGNHLCLVF 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENgSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNL-VCKVSDFGLSRFLEDDTSDP 778
Cdd:cd05118   81 ELMGM-NLYELIKDYPRGLPLDLIKSYLYQLLQALDFLHSNGIIHRDLKPENILINLELgQLKLADFGLARSFTSPPYTP 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 779 TYTSalggkipiRW-TAPEAI-QYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAIEqdyRLPPPMDCPSALH 856
Cdd:cd05118  160 YVAT--------RWyRAPEVLlGAKPYGSSIDIWSLGCILAELLT-GRPLFPGDSEVDQLAKIV---RLLGTPEALDLLS 227

                 ...
gi 111118978 857 QLM 859
Cdd:cd05118  228 KML 230
STKc_PAK_II cd06648
Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze ...
627-848 1.32e-22

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: 98.28  E-value: 1.32e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKReifVAIKtlKSGYTEKQRRDFL-SEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENG 705
Cdd:cd06648   15 IGEGSTGIVCIATDKSTGRQ---VAVK--KMDLRKQQRRELLfNEVVIMRDYQHPNIVEMYSSYLVGDELWVVMEFLEGG 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 706 SLDSFLRQndGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTsdPTYTSALG 785
Cdd:cd06648   90 ALTDIVTH--TRMNEEQIATVCRAVLKALSFLHSQGVIHRDIKSDSILLTSDGRVKLSDFGFCAQVSKEV--PRRKSLVG 165
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 111118978 786 gkIPIrWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWdmtNQDVINAIEQDYRLPPP 848
Cdd:cd06648  166 --TPY-WMAPEVISRLPYGTEVDIWSLGIMVIE-MVDGEPPYF---NEPPLQAMKRIRDNEPP 221
STKc_ULK1 cd14202
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the ...
624-873 1.66e-22

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: 98.16  E-value: 1.66e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 624 EQVIGAGEFGEVCSGHLKlpGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFME 703
Cdd:cd14202    7 KDLIGHGAFAVVFKGRHK--EKHDLEVAVKCINKKNLAKSQTLLGKEIKILKELKHENIVALYDFQEIANSVYLVMEYCN 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 704 NGSLDSFLrQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILV--------NSNLVC-KVSDFGLSRFLEDD 774
Cdd:cd14202   85 GGDLADYL-HTMRTLSEDTIRLFLQQIAGAMKMLHSKGIIHRDLKPQNILLsysggrksNPNNIRiKIADFGFARYLQNN 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 775 TSDPTYTSAlggkiPIrWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAIEQDYRLPP--PMDCP 852
Cdd:cd14202  164 MMAATLCGS-----PM-YMAPEVIMSQHYDAKADLWSIGTIIYQCLT-GKAPFQASSPQDLRLFYEKNKSLSPniPRETS 236
                        250       260
                 ....*....|....*....|.
gi 111118978 853 SALHQLMLDCWQKDRNHRPKF 873
Cdd:cd14202  237 SHLRQLLLGLLQRNQKDRMDF 257
STKc_FA2-like cd08529
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar ...
627-887 1.74e-22

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: 97.87  E-value: 1.74e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKreiFVAIKTLK-SGYTEKQRRDFLSEASIMGQFDHPNVI-HLEGVVTKSTpVMIITEFMEN 704
Cdd:cd08529    8 LGKGSFGVVYKVVRKVDGR---VYALKQIDiSRMSRKMREEAIDEARVLSKLNSPYVIkYYDSFVDKGK-LNIVMEYAEN 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 705 GSLDSFL-RQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTS------- 776
Cdd:cd08529   84 GDLHSLIkSQRGRPLPEDQIWKFFIQTLLGLSHLHSKKILHRDIKSMNIFLDKGDNVKIGDLGVAKILSDTTNfaqtivg 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 777 DPTYTSalggkipirwtaPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYwDMTNQD-VINAIEQDYRLPPPMDCPSAL 855
Cdd:cd08529  164 TPYYLS------------PELCEDKPYNEKSDVWALGCVLYE-LCTGKHPF-EAQNQGaLILKIVRGKYPPISASYSQDL 229
                        250       260       270
                 ....*....|....*....|....*....|..
gi 111118978 856 HQLMLDCWQKDRNHRPkfgqivnTLDKMIRNP 887
Cdd:cd08529  230 SQLIDSCLTKDYRQRP-------DTTELLRNP 254
STKc_MAK_like cd07830
Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs ...
622-871 1.98e-22

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: 98.37  E-value: 1.98e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGYTEKQRRDFLSEA-SIMGQFDHPNVIHLEGVVTKSTPVMIITE 700
Cdd:cd07830    2 KVIKQLGDGTFGSVYLARNKETGE---LVAIKKMKKKFYSWEECMNLREVkSLRKLNEHPNIVKLKEVFRENDELYFVFE 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEddtSDPTY 780
Cdd:cd07830   79 YMEGNLYQLMKDRKGKPFSESVIRSIIYQILQGLAHIHKHGFFHRDLKPENLLVSGPEVVKIADFGLAREIR---SRPPY 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 781 TSAlggkIPIRW-TAPEAI-QYRKFTSASDVWSYGIVMWEVmsYGERPYWDMTNQ-DVINAI--------EQD----YRL 845
Cdd:cd07830  156 TDY----VSTRWyRAPEILlRSTSYSSPVDIWALGCIMAEL--YTLRPLFPGSSEiDQLYKIcsvlgtptKQDwpegYKL 229
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|...
gi 111118978 846 ------------PPPMD-----CPSALHQLMLDCWQKDRNHRP 871
Cdd:cd07830  230 asklgfrfpqfaPTSLHqlipnASPEAIDLIKDMLRWDPKKRP 272
STKc_TGFbR_I cd14056
Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta family Type ...
626-863 2.66e-22

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: 98.11  E-value: 2.66e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 626 VIGAGEFGEVCSGHLklpgkREIFVAIKTLKSgyteKQRRDFLSEASI----MGQfdHPNVIHLEGVVTKS----TPVMI 697
Cdd:cd14056    2 TIGKGRYGEVWLGKY-----RGEKVAVKIFSS----RDEDSWFRETEIyqtvMLR--HENILGFIAADIKStgswTQLWL 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 698 ITEFMENGSLDSFLRQNdgQFTVIQLVGMLRGIAAGMKYL--ADMNY------VHRDLAARNILVNSNLVCKVSDFGLS- 768
Cdd:cd14056   71 ITEYHEHGSLYDYLQRN--TLDTEEALRLAYSAASGLAHLhtEIVGTqgkpaiAHRDLKSKNILVKRDGTCCIADLGLAv 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 769 RFLED-DTSDPTYTSALGGKipiRWTAPE----AIQYRKFTS--ASDVWSYGIVMWEVMSYGER---------PYWDMTN 832
Cdd:cd14056  149 RYDSDtNTIDIPPNPRVGTK---RYMAPEvlddSINPKSFESfkMADIYSFGLVLWEIARRCEIggiaeeyqlPYFGMVP 225
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....
gi 111118978 833 QD--------VInaIEQDYRLPPP---MDCP--SALHQLMLDCW 863
Cdd:cd14056  226 SDpsfeemrkVV--CVEKLRPPIPnrwKSDPvlRSMVKLMQECW 267
PKc_Wee1_like cd13997
Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the ...
624-877 3.39e-22

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: 97.07  E-value: 3.39e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 624 EQVIGAGEFGEVCSGHLKLPGKreIFVAIKTLKSGYTEKQRRDFLSEASI---MGQfdHPNVIHLEGVVTKSTPVMIITE 700
Cdd:cd13997    5 LEQIGSGSFSEVFKVRSKVDGC--LYAVKKSKKPFRGPKERARALREVEAhaaLGQ--HPNIVRYYSSWEEGGHLYIQME 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMENGSLDSFLRQN--DGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFG----LSRFLEDD 774
Cdd:cd13997   81 LCENGSLQDALEELspISKLSEAEVWDLLLQVALGLAFIHSKGIVHLDIKPDNIFISNKGTCKIGDFGlatrLETSGDVE 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 775 TSDPtytsalggkipiRWTAPEAIQ-YRKFTSASDVWSYGIVMWEVMSYGERPywdmTNQDVINAIEQDYRLPPPMDCPS 853
Cdd:cd13997  161 EGDS------------RYLAPELLNeNYTHLPKADIFSLGVTVYEAATGEPLP----RNGQQWQQLRQGKLPLPPGLVLS 224
                        250       260
                 ....*....|....*....|....*
gi 111118978 854 A-LHQLMLDCWQKDRNHRPKFGQIV 877
Cdd:cd13997  225 QeLTRLLKVMLDPDPTRRPTADQLL 249
STKc_CDK_like cd07829
Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs ...
622-888 3.51e-22

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: 97.55  E-value: 3.51e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQvIGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGYTEkqrrD-----FLSEASIMGQFDHPNVIHLEGVVTKSTPVM 696
Cdd:cd07829    3 KLEK-LGEGTYGVVYKAKDKKTGE---IVALKKIRLDNEE----EgipstALREISLLKELKHPNIVKLLDVIHTENKLY 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 697 IITEFMENgSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRfleddts 776
Cdd:cd07829   75 LVFEYCDQ-DLKKYLDKRPGPLPPNLIKSIMYQLLRGLAYCHSHRILHRDLKPQNLLINRDGVLKLADFGLAR------- 146
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 777 dpTYTsalggkIPIR---------W-TAPEAI-QYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVINAIEQDYRL 845
Cdd:cd07829  147 --AFG------IPLRtythevvtlWyRAPEILlGSKHYSTAVDIWSVGCIFAE-LITGKPLFPGDSEIDQLFKIFQILGT 217
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 111118978 846 PPPMDCPSAlhqLMLDCWQKDRNHRPK--FGQIVNTLD--------KMIR-NPN 888
Cdd:cd07829  218 PTEESWPGV---TKLPDYKPTFPKWPKndLEKVLPRLDpegidllsKMLQyNPA 268
STKc_PLK cd14099
Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the ...
627-878 4.38e-22

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: 96.85  E-value: 4.38e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKReifVAIKTL-KSGYT-EKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMEN 704
Cdd:cd14099    9 LGKGGFAKCYEVTDMSTGKV---YAGKVVpKSSLTkPKQREKLKSEIKIHRSLKHPNIVKFHDCFEDEENVYILLELCSN 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 705 GSLDSFLRQNdGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDD---------T 775
Cdd:cd14099   86 GSLMELLKRR-KALTEPEVRYFMRQILSGVKYLHSNRIIHRDLKLGNLFLDENMNVKIGDFGLAARLEYDgerkktlcgT 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 776 sdPTYtsalggkipirwTAPEAIQYRKFTS-ASDVWSYGIVMWeVMSYGERPYWDMTNQDVINAIEQ-DYRLPPPMDCPS 853
Cdd:cd14099  165 --PNY------------IAPEVLEKKKGHSfEVDIWSLGVILY-TLLVGKPPFETSDVKETYKRIKKnEYSFPSHLSISD 229
                        250       260
                 ....*....|....*....|....*
gi 111118978 854 ALHQLMLDCWQKDRNHRPKFGQIVN 878
Cdd:cd14099  230 EAKDLIRSMLQPDPTKRPSLDEILS 254
PK_GC-2D cd14043
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain ...
650-876 5.16e-22

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: 96.71  E-value: 5.16e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 650 VAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGSLDSFLRQNDgqftvIQLVGMLRG 729
Cdd:cd14043   26 VWLKKFPGGSHTELRPSTKNVFSKLRELRHENVNLFLGLFVDCGILAIVSEHCSRGSLEDLLRNDD-----MKLDWMFKS 100
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 730 -----IAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSdPTYTSALGGKIpirWTAPEAIQ----Y 800
Cdd:cd14043  101 sllldLIKGMRYLHHRGIVHGRLKSRNCVVDGRFVLKITDYGYNEILEAQNL-PLPEPAPEELL---WTAPELLRdprlE 176
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 801 RKFTSASDVWSYGIVMWEVMSYGErPY--WDMTNQDVINAIeqdyRLPPP-------MD-CPSALHQLMLDCWQKDRNHR 870
Cdd:cd14043  177 RRGTFPGDVFSFAIIMQEVIVRGA-PYcmLGLSPEEIIEKV----RSPPPlcrpsvsMDqAPLECIQLMKQCWSEAPERR 251

                 ....*.
gi 111118978 871 PKFGQI 876
Cdd:cd14043  252 PTFDQI 257
SAM_EPH-A6 cd09547
SAM domain of EPH-A6 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
915-975 6.93e-22

SAM domain of EPH-A6 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A6 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A6 receptors and appears to mediate cell-cell initiated signal transduction. Eph-A6 gene is preferentially expressed in the nervous system. EPH-A6 receptors are involved in primate retina vascular and axon guidance, and in neural circuits responsible for learning and memory. EphA6 gene was significantly down regulated in colorectal cancer and in malignant melanomas. It is a potential molecular marker for these cancers.


Pssm-ID: 188946  Cd Length: 64  Bit Score: 89.95  E-value: 6.93e-22
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 111118978 915 FNTVDEWLEAIKMGQYKESFANAGFTSFDVVSQMMMEDILRVGVTLAGHQKKILNSIQVMR 975
Cdd:cd09547    3 FVTVSDWLDSIKMGQYKNNFMAAGFTTLDMVSRMTIDDIRRIGVTLIGHQRRIVSSIQTLR 63
SAM_EPH-A8 cd09550
SAM domain of EPH-A8 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
917-978 7.30e-22

SAM domain of EPH-A8 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A8 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A8 receptors and appears to mediate cell-cell initiated signal transduction. EPH-A8 receptors are involved in ligand dependent (ephirin A2, A3, A5) regulation of cell adhesion and migration, and in ligand independent regulation of neurite outgrowth in neuronal cells. They perform signaling in kinase dependent and kinase independent manner. EPH-A8 receptors are known to interact with a number of different proteins including PI 3-kinase and AIDA1-like subfamily SAM repeat domain containing proteins. However other domains (not SAM) of EPH-A8 receptors are involved in these interactions.


Pssm-ID: 188949  Cd Length: 65  Bit Score: 89.93  E-value: 7.30e-22
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 111118978 917 TVDEWLEAIKMGQYKESFANAGFTSFDVVSQMMMEDILRVGVTLAGHQKKILNSIQVMRAQM 978
Cdd:cd09550    4 SVDDWLDSIKMGRYKDHFAAGGYSSLGMVMRMNIEDIRRLGITLMGHQKKILTSIQVMRAQL 65
STKc_LRRK cd14000
Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the ...
626-880 8.43e-22

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: 96.53  E-value: 8.43e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 626 VIGAGEFGEV----CSG--------HLKLPGKR---EIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVT 690
Cdd:cd14000    1 LLGDGGFGSVyrasYKGepvavkifNKHTSSNFanvPADTMLRHLRATDAMKNFRLLRQELTVLSHLHHPSIVYLLGIGI 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 691 KstPVMIITEFMENGSLDSFLRQNDGQFtvIQLVGMLRG-----IAAGMKYLADMNYVHRDLAARNILV-----NSNLVC 760
Cdd:cd14000   81 H--PLMLVLELAPLGSLDHLLQQDSRSF--ASLGRTLQQrialqVADGLRYLHSAMIIYRDLKSHNVLVwtlypNSAIII 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 761 KVSDFGLSRFleddtSDPTYTSALGGKIPIRwtAPEAIQYR-KFTSASDVWSYGIVMWEVMSyGERPYwdMTNQDVINAI 839
Cdd:cd14000  157 KIADYGISRQ-----CCRMGAKGSEGTPGFR--APEIARGNvIYNEKVDVFSFGMLLYEILS-GGAPM--VGHLKFPNEF 226
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*.
gi 111118978 840 EQDYRLPPPM---DC--PSALHQLMLDCWQKDRNHRPKFGQIVNTL 880
Cdd:cd14000  227 DIHGGLRPPLkqyECapWPEVEVLMKKCWKENPQQRPTAVTVVSIL 272
STKc_STK25 cd06642
Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); ...
627-871 1.04e-21

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: 96.28  E-value: 1.04e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGhlkLPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGS 706
Cdd:cd06642   12 IGKGSFGEVYKG---IDNRTKEVVAIKIIDLEEAEDEIEDIQQEITVLSQCDSPYITRYYGSYLKGTKLWIIMEYLGGGS 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 707 LDSFLRQndGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDdtSDPTYTSALGG 786
Cdd:cd06642   89 ALDLLKP--GPLEETYIATILREILKGLDYLHSERKIHRDIKAANVLLSEQGDVKLADFGVAGQLTD--TQIKRNTFVGT 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 787 KIpirWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVINAIEQDYrlPPPMDCPSA--LHQLMLDCWQ 864
Cdd:cd06642  165 PF---WMAPEVIKQSAYDFKADIWSLGITAIE-LAKGEPPNSDLHPMRVLFLIPKNS--PPTLEGQHSkpFKEFVEACLN 238

                 ....*..
gi 111118978 865 KDRNHRP 871
Cdd:cd06642  239 KDPRFRP 245
SAM_1 pfam00536
SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily ...
911-975 1.10e-21

SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily conserved protein binding domain that is involved in the regulation of numerous developmental processes in diverse eukaryotes. The SAM domain can potentially function as a protein interaction module through its ability to homo- and heterooligomerise with other SAM domains.


Pssm-ID: 425739  Cd Length: 64  Bit Score: 89.25  E-value: 1.10e-21
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 111118978  911 DYTSFNTVDEWLEAIKMGQYKESFAnAGFTSFDVVSQMMMEDILRVGVTLAGHQKKILNSIQVMR 975
Cdd:pfam00536   1 DGWSVEDVGEWLESIGLGQYIDSFR-AGYIDGDALLQLTEDDLLKLGVTLLGHRKKILYAIQRLK 64
STKc_TGFbR-like cd13998
Catalytic domain of Transforming Growth Factor beta Receptor-like Serine/Threonine Kinases; ...
625-866 1.28e-21

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: 96.35  E-value: 1.28e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKlpgkrEIFVAIKTLKSGytekQRRDFLSEASIMG--QFDHPNVIHL----EGVVTKSTPVMII 698
Cdd:cd13998    1 EVIGKGRFGEVWKASLK-----NEPVAVKIFSSR----DKQSWFREKEIYRtpMLKHENILQFiaadERDTALRTELWLV 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 699 TEFMENGSLDSFLRQNdgqftVIQLVGMLR---GIAAGMKYL---------ADMNYVHRDLAARNILVNSNLVCKVSDFG 766
Cdd:cd13998   72 TAFHPNGSL*DYLSLH-----TIDWVSLCRlalSVARGLAHLhseipgctqGKPAIAHRDLKSKNILVKNDGTCCIADFG 146
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 767 LS-RFLEDDTSDPTYTSALGGKipIRWTAPE----AIQYRKFTS--ASDVWSYGIVMWEVMS-----YGERPYWDMTNQD 834
Cdd:cd13998  147 LAvRLSPSTGEEDNANNGQVGT--KRYMAPEvlegAINLRDFESfkRVDIYAMGLVLWEMASrctdlFGIVEEYKPPFYS 224
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*...
gi 111118978 835 VI-----------NAIEQDYR--LPPPMDCPSALHQL---MLDCWQKD 866
Cdd:cd13998  225 EVpnhpsfedmqeVVVRDKQRpnIPNRWLSHPGLQSLaetIEECWDHD 272
STKc_EIF2AK cd13996
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
622-880 1.41e-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: 95.82  E-value: 1.41e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEV-CSGHlKLPGKReifVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITE 700
Cdd:cd13996    9 EEIELLGSGGFGSVyKVRN-KVDGVT---YAIKKIRLTEKSSASEKVLREVKALAKLNHPNIVRYYTAWVEEPPLYIQME 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMENGSLDSFL----RQNDGQFTVIqlVGMLRGIAAGMKYLADMNYVHRDLAARNILV-NSNLVCKVSDFGLSRFLEDDT 775
Cdd:cd13996   85 LCEGGTLRDWIdrrnSSSKNDRKLA--LELFKQILKGVSYIHSKGIVHRDLKPSNIFLdNDDLQVKIGDFGLATSIGNQK 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 776 ------------SDPTYTSALGgkiPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGErpywdmTNQDVINAIEQ-- 841
Cdd:cd13996  163 relnnlnnnnngNTSNNSVGIG---TPLYASPEQLDGENYNEKADIYSLGIILFEMLHPFK------TAMERSTILTDlr 233
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|...
gi 111118978 842 DYRLPP----PMDCPSALHQLMLDcwqKDRNHRPKFGQIVNTL 880
Cdd:cd13996  234 NGILPEsfkaKHPKEADLIQSLLS---KNPEERPSAEQLLRSL 273
STKc_TGFbR2_like cd14055
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Type II ...
625-870 1.63e-21

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: 95.91  E-value: 1.63e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLK--LPGKREIfVAIKTLKsgYTE----KQRRDFLSEASImgqfDHPNVIHL----EGVVTKSTP 694
Cdd:cd14055    1 KLVGKGRFAEVWKAKLKqnASGQYET-VAVKIFP--YEEyaswKNEKDIFTDASL----KHENILQFltaeERGVGLDRQ 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 695 VMIITEFMENGSLDSFLRQNdgQFTVIQLVGMLRGIAAGMKYL---------ADMNYVHRDLAARNILVNSNLVCKVSDF 765
Cdd:cd14055   74 YWLITAYHENGSLQDYLTRH--ILSWEDLCKMAGSLARGLAHLhsdrtpcgrPKIPIAHRDLKSSNILVKNDGTCVLADF 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 766 GLSRFLeddtsDPTYTS---ALGGKI-PIRWTAPEAIQYR-------KFTSAsDVWSYGIVMWEVMS----------Y-- 822
Cdd:cd14055  152 GLALRL-----DPSLSVdelANSGQVgTARYMAPEALESRvnledleSFKQI-DVYSMALVLWEMASrceasgevkpYel 225
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 111118978 823 ------GERPYWDMTNQDVInaieQDYRLPP-PmdcPSAL-HQLM-------LDCWQKDRNHR 870
Cdd:cd14055  226 pfgskvRERPCVESMKDLVL----RDRGRPEiP---DSWLtHQGMcvlcdtiTECWDHDPEAR 281
PK_GC-A_B cd14042
Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The ...
649-883 1.66e-21

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: 95.74  E-value: 1.66e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 649 FVAIKtlksgYTEKQR----RDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGSLDSFLRqNDGqftvIQLV 724
Cdd:cd14042   32 LVAIK-----KVNKKRidltREVLKELKHMRDLQHDNLTRFIGACVDPPNICILTEYCPKGSLQDILE-NED----IKLD 101
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 725 GMLRG-----IAAGMKYLADMNYV-HRDLAARNILVNSNLVCKVSDFGLSRF----LEDDTSDPTYTSALggkipirWTA 794
Cdd:cd14042  102 WMFRYslihdIVKGMHYLHDSEIKsHGNLKSSNCVVDSRFVLKITDFGLHSFrsgqEPPDDSHAYYAKLL-------WTA 174
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 795 PEAIQYRKF----TSASDVWSYGIVMWEVMSYgERPYW----DMTNQDVINAIEQDYRLPP------PMDCPSALHQLML 860
Cdd:cd14042  175 PELLRDPNPpppgTQKGDVYSFGIILQEIATR-QGPFYeegpDLSPKEIIKKKVRNGEKPPfrpsldELECPDEVLSLMQ 253
                        250       260
                 ....*....|....*....|...
gi 111118978 861 DCWQKDRNHRPKFGQIVNTLDKM 883
Cdd:cd14042  254 RCWAEDPEERPDFSTLRNKLKKL 276
SAM smart00454
Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related ...
910-977 1.79e-21

Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. In many cases mediates homodimerisation.


Pssm-ID: 197735  Cd Length: 68  Bit Score: 88.89  E-value: 1.79e-21
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 111118978   910 PDYTSFNTVDEWLEAIKMGQYKESFANAGFTSFDVVSQMMMEDILRVGVTLAGHQKKILNSIQVMRAQ 977
Cdd:smart00454   1 VSQWSPESVADWLESIGLEQYADNFRKNGIDGALLLLLTSEEDLKELGITKLGHRKKILKAIQKLKEQ 68
STKc_Chk1 cd14069
Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the ...
621-829 1.85e-21

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: 95.09  E-value: 1.85e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQVIGAGEFGEVCSGHLKLPgkrEIFVAIKTL-KSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIIT 699
Cdd:cd14069    3 WDLVQTLGEGAFGEVFLAVNRNT---EEAVAVKFVdMKRAPGDCPENIKKEVCIQKMLSHKNVVRFYGHRREGEFQYLFL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENGSL------DSFLRQNDGQFTVIQLVgmlrgiaAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGL-SRFLE 772
Cdd:cd14069   80 EYASGGELfdkiepDVGMPEDVAQFYFQQLM-------AGLKYLHSCGITHRDIKPENLLLDENDNLKISDFGLaTVFRY 152
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 111118978 773 DDTSdpTYTSALGGKIPirWTAPEAIQYRKF-TSASDVWSYGIVMWeVMSYGERPyWD 829
Cdd:cd14069  153 KGKE--RLLNKMCGTLP--YVAPELLAKKKYrAEPVDVWSCGIVLF-AMLAGELP-WD 204
STKc_SIK cd14071
Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the ...
623-861 2.41e-21

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


Pssm-ID: 270973 [Multi-domain]  Cd Length: 253  Bit Score: 94.38  E-value: 2.41e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 623 IEQVIGAGEFGEVcsghlKLPGKR--EIFVAIKTL-KSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIIT 699
Cdd:cd14071    4 IERTIGKGNFAVV-----KLARHRitKTEVAIKIIdKSQLDEENLKKIYREVQIMKMLNHPHIIKLYQVMETKDMLYLVT 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENGSLDSFLRQNdGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDPT 779
Cdd:cd14071   79 EYASNGEIFDYLAQH-GRMSEKEARKKFWQILSAVEYCHKRHIVHRDLKAENLLLDANMNIKIADFGFSNFFKPGELLKT 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 780 YTsalgGKIPirWTAPEAIQYRKFTSAS-DVWSYGIVMWeVMSYGERPYwDMTNQDVINA--IEQDYRLPPPM--DCPSA 854
Cdd:cd14071  158 WC----GSPP--YAAPEVFEGKEYEGPQlDIWSLGVVLY-VLVCGALPF-DGSTLQTLRDrvLSGRFRIPFFMstDCEHL 229

                 ....*...
gi 111118978 855 L-HQLMLD 861
Cdd:cd14071  230 IrRMLVLD 237
STKc_ULK1_2-like cd14120
Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar ...
627-874 2.76e-21

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


Pssm-ID: 271022 [Multi-domain]  Cd Length: 256  Bit Score: 94.36  E-value: 2.76e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKlpGKREIFVAIKTL-KSGYTEKQrrDFLS-EASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMEN 704
Cdd:cd14120    1 IGHGAFAVVFKGRHR--KKPDLPVAIKCItKKNLSKSQ--NLLGkEIKILKELSHENVVALLDCQETSSSVYLVMEYCNG 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 705 GSLDSFLrQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVN---------SNLVCKVSDFGLSRFLEDDT 775
Cdd:cd14120   77 GDLADYL-QAKGTLSEDTIRVFLQQIAAAMKALHSKGIVHRDLKPQNILLShnsgrkpspNDIRLKIADFGFARFLQDGM 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 776 SDPTytsaLGGKiPIrWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAIEQDYRLPP--PMDCPS 853
Cdd:cd14120  156 MAAT----LCGS-PM-YMAPEVIMSLQYDAKADLWSIGTIVYQCLT-GKAPFQAQTPQELKAFYEKNANLRPniPSGTSP 228
                        250       260
                 ....*....|....*....|....
gi 111118978 854 ALHQL---MLDCWQKDRNHRPKFG 874
Cdd:cd14120  229 ALKDLllgLLKRNPKDRIDFEDFF 252
STKc_ULK3 cd14121
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the ...
627-873 3.31e-21

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: 94.28  E-value: 3.31e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKlPGKREIfVAIK-TLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENG 705
Cdd:cd14121    3 LGSGTYATVYKAYRK-SGAREV-VAVKcVSKSSLNKASTENLLTEIELLKKLKHPHIVELKDFQWDEEHIYLIMEYCSGG 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 706 SLDSFLRQNdGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNS--NLVCKVSDFGLSRFLEDDTSDptytSA 783
Cdd:cd14121   81 DLSRFIRSR-RTLPESTVRRFLQQLASALQFLREHNISHMDLKPQNLLLSSryNPVLKLADFGFAQHLKPNDEA----HS 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 784 LGGKiPIrWTAPEAIQYRKFTSASDVWSYGIVMWEVMsYGERPYWDMTNQDVINAIEQD--YRLPPPMDCPSALHQLMLD 861
Cdd:cd14121  156 LRGS-PL-YMAPEMILKKKYDARVDLWSVGVILYECL-FGRAPFASRSFEELEEKIRSSkpIEIPTRPELSADCRDLLLR 232
                        250
                 ....*....|..
gi 111118978 862 CWQKDRNHRPKF 873
Cdd:cd14121  233 LLQRDPDRRISF 244
PTK_Jak1_rpt1 cd05077
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 1; Jak1 is widely ...
645-877 3.36e-21

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


Pssm-ID: 270662 [Multi-domain]  Cd Length: 266  Bit Score: 94.62  E-value: 3.36e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 645 KREIFVAIKTLKSGYtekqrRD----FLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGSLDSFLRQNDGQFTV 720
Cdd:cd05077   34 EKEIKVILKVLDPSH-----RDislaFFETASMMRQVSHKHIVLLYGVCVRDVENIMVEEFVEFGPLDLFMHRKSDVLTT 108
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 721 IQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLV-------CKVSDFG-----LSRfleDDTSDptytsalggKI 788
Cdd:cd05077  109 PWKFKVAKQLASALSYLEDKDLVHGNVCTKNILLAREGIdgecgpfIKLSDPGipitvLSR---QECVE---------RI 176
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 789 PirWTAPEAIQ-YRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPmDCpSALHQLMLDCWQKDR 867
Cdd:cd05077  177 P--WIAPECVEdSKNLSIAADKWSFGTTLWEICYNGEIPLKDKTLAEKERFYEGQCMLVTP-SC-KELADLMTHCMNYDP 252
                        250
                 ....*....|
gi 111118978 868 NHRPKFGQIV 877
Cdd:cd05077  253 NQRPFFRAIM 262
STKc_Chk2 cd14084
Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze ...
610-816 5.33e-21

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: 94.00  E-value: 5.33e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 610 REFAKEIDIScvkieQVIGAGEFGEVcsghlKLPGKREIF--VAIKTL-KSGYTEKQRRDF------LSEASIMGQFDHP 680
Cdd:cd14084    2 KELRKKYIMS-----RTLGSGACGEV-----KLAYDKSTCkkVAIKIInKRKFTIGSRREInkprniETEIEILKKLSHP 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 681 NVIHLEGVVTKSTPVMIITEFMENGSL------DSFLRQNDGQFTVIQlvgMLRGIaagmKYLADMNYVHRDLAARNILV 754
Cdd:cd14084   72 CIIKIEDFFDAEDDYYIVLELMEGGELfdrvvsNKRLKEAICKLYFYQ---MLLAV----KYLHSNGIIHRDLKPENVLL 144
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 111118978 755 NSN---LVCKVSDFGLSRFLEDDT------SDPTYtsalggkipirwTAPEAIQY---RKFTSASDVWSYGIVM 816
Cdd:cd14084  145 SSQeeeCLIKITDFGLSKILGETSlmktlcGTPTY------------LAPEVLRSfgtEGYTRAVDCWSLGVIL 206
PTK_Tyk2_rpt1 cd05076
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; Tyk2 is ...
667-880 7.32e-21

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


Pssm-ID: 270661 [Multi-domain]  Cd Length: 273  Bit Score: 93.82  E-value: 7.32e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 667 FLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRD 746
Cdd:cd05076   62 FFETASLMSQVSHTHLVFVHGVCVRGSENIMVEEFVEHGPLDVWLRKEKGHVPMAWKFVVARQLASALSYLENKNLVHGN 141
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 747 LAARNILV-------NSNLVCKVSDFG-----LSRflEDDTSdptytsalggKIPirWTAPEAIQY-RKFTSASDVWSYG 813
Cdd:cd05076  142 VCAKNILLarlgleeGTSPFIKLSDPGvglgvLSR--EERVE----------RIP--WIAPECVPGgNSLSTAADKWGFG 207
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 111118978 814 IVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPmDCPSaLHQLMLDCWQKDRNHRPKFGQIVNTL 880
Cdd:cd05076  208 ATLLEICFNGEAPLQSRTPSEKERFYQRQHRLPEP-SCPE-LATLISQCLTYEPTQRPSFRTILRDL 272
STKc_AGC cd05123
Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
627-874 9.33e-21

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: 92.58  E-value: 9.33e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKreIFvAIKTLKSG--YTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMEN 704
Cdd:cd05123    1 LGKGSFGKVLLVRKKDTGK--LY-AMKVLRKKeiIKRKEVEHTLNERNILERVNHPFIVKLHYAFQTEEKLYLVLDYVPG 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 705 GSLDSFLRQNdGQFTViqlvGMLRGIAA----GMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDtSDPTY 780
Cdd:cd05123   78 GELFSHLSKE-GRFPE----ERARFYAAeivlALEYLHSLGIIYRDLKPENILLDSDGHIKLTDFGLAKELSSD-GDRTY 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 781 TSAlggkIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVINAI-EQDYRLPPpmDCPSALHQLM 859
Cdd:cd05123  152 TFC----GTPEYLAPEVLLGKGYGKAVDWWSLGVLLYE-MLTGKPPFYAENRKEIYEKIlKSPLKFPE--YVSPEAKSLI 224
                        250
                 ....*....|....*
gi 111118978 860 LDCWQKDRNHRPKFG 874
Cdd:cd05123  225 SGLLQKDPTKRLGSG 239
SAM_EPH-A4 cd09545
SAM domain of EPH-A4 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
913-982 9.62e-21

SAM domain of EPH-A4 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A4 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A4 receptors and appears to mediate cell-cell initiated signal transduction. SAM domains of EPH-A4 receptors can form homodimers. EPH-A4 receptors bind ligands such as erphirin A1, A4, A5. They are known to interact with a number of different proteins, including meltrin beta metalloprotease, Cdk5, and EFS2alpha, however SAM domain doesn't participate in these interactions. EPH-A4 receptors are involved in regulation of corticospinal tract formation, in pathway controlling voluntary movements, in formation of motor neurons, and in axon guidance (SAM domain is not required for axon guidance or for EPH-A4 kinase signaling). In Xenopus embryos EPH-A4 induces loss of cell adhesion, ventro-lateral protrusions, and severely expanded posterior structures. Mutations in SAM domain conserved tyrosine (Y928F) enhance the ability of EPH-A4 to induce these phenotypes, thus supporting the idea that the SAM domain may negatively regulate some aspects of EPH-A4 activity. EphA4 gene was found overexpressed in a number of different cancers including human gastric cancer, colorectal cancer, and pancreatic ductal adenocarcinoma. It is likely to be a promising molecular target for the cancer therapy.


Pssm-ID: 188944  Cd Length: 71  Bit Score: 86.93  E-value: 9.62e-21
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 913 TSFNTVDEWLEAIKMGQYKESFANAGFTSFDVVSQMMMEDILRVGVTLAGHQKKILNSIQVMRAQMNQIQ 982
Cdd:cd09545    1 SAVASVDDWLQAIKMERYKDNFTAAGYTTLEAVVHMNQDDLARIGISAIAHQNKILSSVQGMRSQMQQMQ 70
STKc_ULK2 cd14201
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the ...
626-873 1.15e-20

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: 93.15  E-value: 1.15e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 626 VIGAGEFGEVCSG-HLKlpgKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMEN 704
Cdd:cd14201   13 LVGHGAFAVVFKGrHRK---KTDWEVAIKSINKKNLSKSQILLGKEIKILKELQHENIVALYDVQEMPNSVFLVMEYCNG 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 705 GSLDSFLrQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVN---------SNLVCKVSDFGLSRFLEDDT 775
Cdd:cd14201   90 GDLADYL-QAKGTLSEDTIRVFLQQIAAAMRILHSKGIIHRDLKPQNILLSyasrkkssvSGIRIKIADFGFARYLQSNM 168
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 776 SDPTYTSAlggkiPIrWTAPEAIQYRKFTSASDVWSYGIVMWEVMsYGERPYWDMTNQDVINAIEQDYRLPP--PMDCPS 853
Cdd:cd14201  169 MAATLCGS-----PM-YMAPEVIMSQHYDAKADLWSIGTVIYQCL-VGKPPFQANSPQDLRMFYEKNKNLQPsiPRETSP 241
                        250       260
                 ....*....|....*....|
gi 111118978 854 ALHQLMLDCWQKDRNHRPKF 873
Cdd:cd14201  242 YLADLLLGLLQRNQKDRMDF 261
PK_GC_unk cd14045
Pseudokinase domain of the unknown subfamily of membrane Guanylate Cyclase receptors; The ...
650-883 1.19e-20

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: 93.00  E-value: 1.19e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 650 VAIKTL-KSGYTEKQRrdFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGSLDSFLRQNDgqftvIQLVGMLR 728
Cdd:cd14045   33 VAIKKIaKKSFTLSKR--IRKEVKQVRELDHPNLCKFIGGCIEVPNVAIITEYCPKGSLNDVLLNED-----IPLNWGFR 105
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 729 -----GIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDP--TYTSALggkIPIrWTAPEA--IQ 799
Cdd:cd14045  106 fsfatDIARGMAYLHQHKIYHGRLKSSNCVIDDRWVCKIADYGLTTYRKEDGSENasGYQQRL---MQV-YLPPENhsNT 181
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 800 YRKFTSASDVWSYGIVMWEVMSYGErpywdmTNQDVINAIEQDYRLPPP----------MDCPSALHQLMLDCWQKDRNH 869
Cdd:cd14045  182 DTEPTQATDVYSYAIILLEIATRND------PVPEDDYSLDEAWCPPLPelisgktensCPCPADYVELIRRCRKNNPAQ 255
                        250
                 ....*....|....
gi 111118978 870 RPKFGQIVNTLDKM 883
Cdd:cd14045  256 RPTFEQIKKTLHKI 269
STKc_NUAK cd14073
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze ...
623-878 1.22e-20

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: 92.45  E-value: 1.22e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 623 IEQVIGAGEFGEVCSGHLKLPGKReifVAIKTLKSGY--TEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITE 700
Cdd:cd14073    5 LLETLGKGTYGKVKLAIERATGRE---VAIKSIKKDKieDEQDMVRIRREIEIMSSLNHPHIIRIYEVFENKDKIVIVME 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMENGSLDSFLrQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDPTY 780
Cdd:cd14073   82 YASGGELYDYI-SERRRLPEREARRIFRQIVSAVHYCHKNGVVHRDLKLENILLDQNGNAKIADFGLSNLYSKDKLLQTF 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 781 TSAlggkiPIrWTAPEAIQYRKFTSAS-DVWSYGIVMWeVMSYGERPYWDMTNQDVINAIEQ-DYRLPPPmdcPSALHQL 858
Cdd:cd14073  161 CGS-----PL-YASPEIVNGTPYQGPEvDCWSLGVLLY-TLVYGTMPFDGSDFKRLVKQISSgDYREPTQ---PSDASGL 230
                        250       260
                 ....*....|....*....|
gi 111118978 859 MLDCWQKDRNHRPKFGQIVN 878
Cdd:cd14073  231 IRWMLTVNPKRRATIEDIAN 250
STKc_p38 cd07851
Catalytic domain of the Serine/Threonine Kinase, p38 Mitogen-Activated Protein Kinase; STKs ...
623-818 1.37e-20

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: 94.28  E-value: 1.37e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 623 IEQVIGAGEFGEVCSGHLKLPGKReifVAIKtlksgyteKQRRDFLS---------EASIMGQFDHPNVIHLEGVVTKST 693
Cdd:cd07851   19 NLSPVGSGAYGQVCSAFDTKTGRK---VAIK--------KLSRPFQSaihakrtyrELRLLKHMKHENVIGLLDVFTPAS 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 694 PVM------IITEFMeNGSLDSFLRQ---NDG--QFTVIQlvgMLRGiaagMKYLADMNYVHRDLAARNILVNSNLVCKV 762
Cdd:cd07851   88 SLEdfqdvyLVTHLM-GADLNNIVKCqklSDDhiQFLVYQ---ILRG----LKYIHSAGIIHRDLKPSNLAVNEDCELKI 159
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 111118978 763 SDFGLSRFLEDDtsdptytsaLGGKIPIRW-TAPEAI-QYRKFTSASDVWSYGIVMWE 818
Cdd:cd07851  160 LDFGLARHTDDE---------MTGYVATRWyRAPEIMlNWMHYNQTVDIWSVGCIMAE 208
STKc_Nek6_7 cd08224
Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related ...
622-876 2.08e-20

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: 91.95  E-value: 2.08e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKLPGKreiFVAIKTLK--SGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIIT 699
Cdd:cd08224    3 EIEKKIGKGQFSVVYRARCLLDGR---LVALKKVQifEMMDAKARQDCLKEIDLLQQLNHPNIIKYLASFIENNELNIVL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENGSLDSFLRQNDGQFTVIQLVGMLR---GIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTS 776
Cdd:cd08224   80 ELADAGDLSRLIKHFKKQKRLIPERTIWKyfvQLCSALEHMHSKRIMHRDIKPANVFITANGVVKLGDLGLGRFFSSKTT 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 777 D-------PTYTSalggkipirwtaPEAIQYRKFTSASDVWSYGIVMWEVMS-----YGERpywdMTNQDVINAIEQ-DY 843
Cdd:cd08224  160 AahslvgtPYYMS------------PERIREQGYDFKSDIWSLGCLLYEMAAlqspfYGEK----MNLYSLCKKIEKcEY 223
                        250       260       270
                 ....*....|....*....|....*....|....*
gi 111118978 844 rlPP-PMDCPSA-LHQLMLDCWQKDRNHRPKFGQI 876
Cdd:cd08224  224 --PPlPADLYSQeLRDLVAACIQPDPEKRPDISYV 256
STKc_ERK1_2_like cd07849
Catalytic domain of Extracellular signal-Regulated Kinase 1 and 2-like Serine/Threonine ...
622-821 2.45e-20

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: 93.52  E-value: 2.45e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKLPGKReifVAIKTL----KSGYTekQRRdfLSEASIMGQFDHPNVIHLEGVVTKST---- 693
Cdd:cd07849    8 QNLSYIGEGAYGMVCSAVHKPTGQK---VAIKKIspfeHQTYC--LRT--LREIKILLRFKHENIIGILDIQRPPTfesf 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 694 -PVMIITEFMENgSLDSFLR----QNDG-QFTVIQlvgMLRGiaagMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGL 767
Cdd:cd07849   81 kDVYIVQELMET-DLYKLIKtqhlSNDHiQYFLYQ---ILRG----LKYIHSANVLHRDLKPSNLLLNTNCDLKICDFGL 152
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 111118978 768 SRfLEDDTSDPtyTSALGGKIPIRW-TAPE-AIQYRKFTSASDVWSYGIVMWEVMS 821
Cdd:cd07849  153 AR-IADPEHDH--TGFLTEYVATRWyRAPEiMLNSKGYTKAIDIWSVGCILAEMLS 205
STKc_TSSK4-like cd14162
Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs ...
626-846 2.46e-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: 91.59  E-value: 2.46e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 626 VIGAGEFGEVCSGHLKlpgKREIFVAIKTL-KSGYTEKQRRDFL-SEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFME 703
Cdd:cd14162    7 TLGHGSYAVVKKAYST---KHKCKVAIKIVsKKKAPEDYLQKFLpREIEVIKGLKHPNLICFYEAIETTSRVYIIMELAE 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 704 NGSLDSFLRQNdGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRfleddtsdpTYTSA 783
Cdd:cd14162   84 NGDLLDYIRKN-GALPEPQARRWFRQLVAGVEYCHSKGVVHRDLKCENLLLDKNNNLKITDFGFAR---------GVMKT 153
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 111118978 784 LGGKIPIRWT--------APE---AIQYRKFtsASDVWSYGIVMWeVMSYGERPYwDMTNQDVI-NAIEQDYRLP 846
Cdd:cd14162  154 KDGKPKLSETycgsyayaSPEilrGIPYDPF--LSDIWSMGVVLY-TMVYGRLPF-DDSNLKVLlKQVQRRVVFP 224
STKc_MLCK cd14103
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the ...
627-827 2.65e-20

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: 91.52  E-value: 2.65e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKReifVAIKTLKSgYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGS 706
Cdd:cd14103    1 LGRGKFGTVYRCVEKATGKE---LAAKFIKC-RKAKDREDVRNEIEIMNQLRHPRLLQLYDAFETPREMVLVMEYVAGGE 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 707 LdsFLRQNDGQFTVIQLVGML--RGIAAGMKYLADMNYVHRDLAARNILV---NSNLVcKVSDFGLSRFLEDDTSdptyT 781
Cdd:cd14103   77 L--FERVVDDDFELTERDCILfmRQICEGVQYMHKQGILHLDLKPENILCvsrTGNQI-KIIDFGLARKYDPDKK----L 149
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 111118978 782 SALGGKiPiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPY 827
Cdd:cd14103  150 KVLFGT-P-EFVAPEVVNYEPISYATDMWSVGVICYVLLS-GLSPF 192
STKc_Nek5 cd08225
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
625-877 3.49e-20

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


Pssm-ID: 173765 [Multi-domain]  Cd Length: 257  Bit Score: 91.17  E-value: 3.49e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKLPGKREIFVAIKTLKSGYTEKQRRDflSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMEN 704
Cdd:cd08225    6 KKIGEGSFGKIYLAKAKSDSEHCVIKEIDLTKMPVKEKEASK--KEVILLAKMKHPNIVTFFASFQENGRLFIVMEYCDG 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 705 GSL-DSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSN-LVCKVSDFGLSRFLeDDTSDPTYTS 782
Cdd:cd08225   84 GDLmKRINRQRGVLFSEDQILSWFVQISLGLKHIHDRKILHRDIKSQNIFLSKNgMVAKLGDFGIARQL-NDSMELAYTC 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 783 AlggKIPIrWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYgERPYWDMTNQDVINAIEQDYRLPPPMDCPSALHQLMLDC 862
Cdd:cd08225  163 V---GTPY-YLSPEICQNRPYNNKTDIWSLGCVLYELCTL-KHPFEGNNLHQLVLKICQGYFAPISPNFSRDLRSLISQL 237
                        250
                 ....*....|....*
gi 111118978 863 WQKDRNHRPKFGQIV 877
Cdd:cd08225  238 FKVSPRDRPSITSIL 252
PTKc_Wee1_fungi cd14052
Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the ...
627-879 4.33e-20

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: 91.33  E-value: 4.33e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCS-GHLKLPGKREIFVAIKTLKSGYTEKQRRdfLSEASIMGQFD---HPNVIHLEGVVTKSTPVMIITEFM 702
Cdd:cd14052    8 IGSGEFSQVYKvSERVPTGKVYAVKKLKPNYAGAKDRLRR--LEEVSILRELTldgHDNIVQLIDSWEYHGHLYIQTELC 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 703 ENGSLDSFLRQNdGQFTVI---QLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTS--- 776
Cdd:cd14052   86 ENGSLDVFLSEL-GLLGRLdefRVWKILVELSLGLRFIHDHHFVHLDLKPANVLITFEGTLKIGDFGMATVWPLIRGier 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 777 --DPTYtsalggkipirwTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERP----YW------DMTNQD-----VINAI 839
Cdd:cd14052  165 egDREY------------IAPEILSEHMYDKPADIFSLGLILLEAAANVVLPdngdAWqklrsgDLSDAPrlsstDLHSA 232
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*
gi 111118978 840 EQDYRLPPPMDCPSALHQLMLDC---W--QKDRNHRPKFGQIVNT 879
Cdd:cd14052  233 SSPSSNPPPDPPNMPILSGSLDRvvrWmlSPEPDRRPTADDVLAT 277
STKc_CaMKI_alpha cd14167
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
625-887 4.66e-20

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


Pssm-ID: 271069 [Multi-domain]  Cd Length: 263  Bit Score: 91.24  E-value: 4.66e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKlpgKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMEN 704
Cdd:cd14167    9 EVLGTGAFSEVVLAEEK---RTQKLVAIKCIAKKALEGKETSIENEIAVLHKIKHPNIVALDDIYESGGHLYLIMQLVSG 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 705 GSL-DSFLRQndGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNIL---VNSNLVCKVSDFGLSRfLEDDTSdpTY 780
Cdd:cd14167   86 GELfDRIVEK--GFYTERDASKLIFQILDAVKYLHDMGIVHRDLKPENLLyysLDEDSKIMISDFGLSK-IEGSGS--VM 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 781 TSALGGKipiRWTAPEAIQYRKFTSASDVWSYGIVMWeVMSYGERPYWDMTNQDVINAI-EQDYRLPPPM--DCPSALHQ 857
Cdd:cd14167  161 STACGTP---GYVAPEVLAQKPYSKAVDCWSIGVIAY-ILLCGYPPFYDENDAKLFEQIlKAEYEFDSPYwdDISDSAKD 236
                        250       260       270
                 ....*....|....*....|....*....|
gi 111118978 858 LMLDCWQKDRNHRpkfgqivNTLDKMIRNP 887
Cdd:cd14167  237 FIQHLMEKDPEKR-------FTCEQALQHP 259
SAM_2 pfam07647
SAM domain (Sterile alpha motif);
910-975 5.69e-20

SAM domain (Sterile alpha motif);


Pssm-ID: 429573  Cd Length: 66  Bit Score: 84.63  E-value: 5.69e-20
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 111118978  910 PDYTSFNTVDEWLEAIKMGQYKESFANAGFTSFDVVSQMMMEDILRVGVTLAGHQKKILNSIQVMR 975
Cdd:pfam07647   1 VESWSLESVADWLRSIGLEQYTDNFRDQGITGAELLLRLTLEDLKRLGITSVGHRRKILKKIQELK 66
STKc_BUR1 cd07866
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), ...
622-826 7.26e-20

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: 91.61  E-value: 7.26e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKLPGKReifVAIKTLksgyTEKQRRD-F----LSEASIMGQFDHPNVIHLEGVVTKSTP-- 694
Cdd:cd07866   11 EILGKLGEGTFGEVYKARQIKTGRV---VALKKI----LMHNEKDgFpitaLREIKILKKLKHPNVVPLIDMAVERPDks 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 695 ------VMIITEFMENgSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLS 768
Cdd:cd07866   84 krkrgsVYMVTPYMDH-DLSGLLENPSVKLTESQIKCYMLQLLEGINYLHENHILHRDIKAANILIDNQGILKIADFGLA 162
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 111118978 769 RFLEDDTSDPTYTSALGGK-----IPIRW-TAPEAI-QYRKFTSASDVWSYGIVMWEVmsYGERP 826
Cdd:cd07866  163 RPYDGPPPNPKGGGGGGTRkytnlVVTRWyRPPELLlGERRYTTAVDIWGIGCVFAEM--FTRRP 225
STKc_GSK3 cd14137
The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze ...
622-820 7.84e-20

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: 91.02  E-value: 7.84e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKLPGKReifVAIK-TLKSG-YteKQRrdflsEASIMGQFDHPNVIHLEG---VVTKSTPVM 696
Cdd:cd14137    7 TIEKVIGSGSFGVVYQAKLLETGEV---VAIKkVLQDKrY--KNR-----ELQIMRRLKHPNIVKLKYffySSGEKKDEV 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 697 ---IITEFMENgSLDSFLRQNDGQFTVIQLV-------GMLRGIAagmkYLADMNYVHRDLAARNILVN-SNLVCKVSDF 765
Cdd:cd14137   77 ylnLVMEYMPE-TLYRVIRHYSKNKQTIPIIyvklysyQLFRGLA----YLHSLGICHRDIKPQNLLVDpETGVLKLCDF 151
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 111118978 766 GLSRFLEDDTSDPTYtsalggkIPIR-WTAPEAIQ-YRKFTSASDVWSYGIVMWEVM 820
Cdd:cd14137  152 GSAKRLVPGEPNVSY-------ICSRyYRAPELIFgATDYTTAIDIWSAGCVLAELL 201
STKc_MLCK2 cd14190
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze ...
624-839 8.85e-20

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


Pssm-ID: 271092 [Multi-domain]  Cd Length: 261  Bit Score: 90.36  E-value: 8.85e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 624 EQVIGAGEFGEVCSGHLKLPGKReifVAIKTLKSgYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFME 703
Cdd:cd14190    9 KEVLGGGKFGKVHTCTEKRTGLK---LAAKVINK-QNSKDKEMVLLEIQVMNQLNHRNLIQLYEAIETPNEIVLFMEYVE 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 704 NGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNIL-VN-SNLVCKVSDFGLSRfleddTSDPTYT 781
Cdd:cd14190   85 GGELFERIVDEDYHLTEVDAMVFVRQICEGIQFMHQMRVLHLDLKPENILcVNrTGHQVKIIDFGLAR-----RYNPREK 159
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 111118978 782 SALGGKIPiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAI 839
Cdd:cd14190  160 LKVNFGTP-EFLSPEVVNYDQVSFPTDMWSMGVITYMLLS-GLSPFLGDDDTETLNNV 215
STKc_TDY_MAPK cd07859
Catalytic domain of the Serine/Threonine Kinases, Plant TDY Mitogen-Activated Protein Kinases; ...
622-821 1.04e-19

Catalytic domain of the Serine/Threonine Kinases, Plant TDY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TDY subtype and is composed of Group D plant MAPKs including Arabidopsis thaliana MPK18 (AtMPK18), Oryza sativa Blast- and Wound-induced MAPK1 (OsBWMK1), OsWJUMK1 (Wound- and JA-Uninducible MAPK1), Zea mays MPK6, and the Medicago sativa TDY1 gene product. OsBWMK1 enhances resistance to pathogenic infections. It mediates stress-activated defense responses by activating a transcription factor that affects the expression of stress-related genes. AtMPK18 is involved in microtubule-related functions. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20 while Oryza sativa contains at least 17 MAPKs. Arabidopsis thaliana contains more TEY-type MAPKs than TDY-type, whereas the reverse is true for Oryza sativa. The TDY MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143364 [Multi-domain]  Cd Length: 338  Bit Score: 91.77  E-value: 1.04e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKLPGKReifVAIKTLKSGY---TEKQRrdFLSEASIMGQFDHPNVIHLEGVVTKSTP---- 694
Cdd:cd07859    3 KIQEVIGKGSYGVVCSAIDTHTGEK---VAIKKINDVFehvSDATR--ILREIKLLRLLRHPDIVEIKHIMLPPSRrefk 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 695 -VMIITEFMENgSLDSFLRQNDG------QFTVIQLvgmLRGiaagMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGL 767
Cdd:cd07859   78 dIYVVFELMES-DLHQVIKANDDltpehhQFFLYQL---LRA----LKYIHTANVFHRDLKPKNILANADCKLKICDFGL 149
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 111118978 768 SRFLEDDTSDPTYTSALggkIPIRW-TAPEAIQ--YRKFTSASDVWSYGIVMWEVMS 821
Cdd:cd07859  150 ARVAFNDTPTAIFWTDY---VATRWyRAPELCGsfFSKYTPAIDIWSIGCIFAEVLT 203
SAM_EPH-A2 cd09543
SAM domain of EPH-A2 family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of ...
915-979 1.19e-19

SAM domain of EPH-A2 family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A2 subfamily of receptor tyrosine kinases is a C-terminal protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A2 receptors and appears to mediate cell-cell initiated signal transduction. For example, SAM domain of EPH-A2 receptors interacts with SAM domain of Ship2 proteins (SH2 containing phosphoinositide 5-phosphotase-2) forming heterodimers; such recruitment of Ship2 by EPH-A2 attenuates the positive signal for receptor endocytosis. Eph-A2 is found overexpressed in many types of human cancer, including breast, prostate, lung and colon cancer. High level of expression could induce cancer progression by a variety of mechanisms and could be used as a novel tag for cancer immunotherapy. EPH-A2 receptors are attractive targets for drag design.


Pssm-ID: 188942  Cd Length: 70  Bit Score: 83.73  E-value: 1.19e-19
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 111118978 915 FNTVDEWLEAIKMGQYKESFANAGFTSFDVVSQMMMEDILRVGVTLAGHQKKILNSIQVMRAQMN 979
Cdd:cd09543    5 FRTVAEWLESIKMQQYTEHFMAAGYNSIDKVLQMTQEDIKHIGVRLPGHQKRIAYSILGLKEQVS 69
PK_ILK cd14057
Pseudokinase domain of Integrin Linked Kinase; The pseudokinase domain shows similarity to ...
650-883 1.52e-19

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: 89.08  E-value: 1.52e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 650 VAIKTLKSG-YTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGSLDSFLRQNDGqFTV--IQLVGM 726
Cdd:cd14057   21 IVAKILKVRdVTTRISRDFNEEYPRLRIFSHPNVLPVLGACNSPPNLVVISQYMPYGSLYNVLHEGTG-VVVdqSQAVKF 99
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 727 LRGIAAGMKYLADMNYV--HRDLAARNILVNSNLVCKVSdfglsrfleddTSDPTYTSALGGKI--PIrWTAPEAIQYRK 802
Cdd:cd14057  100 ALDIARGMAFLHTLEPLipRHHLNSKHVMIDEDMTARIN-----------MADVKFSFQEPGKMynPA-WMAPEALQKKP 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 803 FT---SASDVWSYGIVMWEVMSYgERPYWDMTNQDVINAIEQDYRLP--PPMDCPSaLHQLMLDCWQKDRNHRPKFGQIV 877
Cdd:cd14057  168 EDinrRSADMWSFAILLWELVTR-EVPFADLSNMEIGMKIALEGLRVtiPPGISPH-MCKLMKICMNEDPGKRPKFDMIV 245

                 ....*.
gi 111118978 878 NTLDKM 883
Cdd:cd14057  246 PILEKM 251
STKc_SnRK3 cd14663
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
622-847 1.87e-19

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: 89.00  E-value: 1.87e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKLPGKReifVAIKTL------KSGYTEKQRRdflsEASIMGQFDHPNVIHLEGVVTKSTPV 695
Cdd:cd14663    3 ELGRTLGEGTFAKVKFARNTKTGES---VAIKIIdkeqvaREGMVEQIKR----EIAIMKLLRHPNIVELHEVMATKTKI 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 696 MIITEFMENGSLDSF------LRQNDGQFTVIQLVgmlrgiaAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSR 769
Cdd:cd14663   76 FFVMELVTGGELFSKiakngrLKEDKARKYFQQLI-------DAVDYCHSRGVFHRDLKPENLLLDEDGNLKISDFGLSA 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 770 FLEDDTSDPTYTSALGgkIPiRWTAPEAIQYRKFTSA-SDVWSYGIVMWeVMSYGERPYWDMTNQDVINAIEQ-DYRLPP 847
Cdd:cd14663  149 LSEQFRQDGLLHTTCG--TP-NYVAPEVLARRGYDGAkADIWSCGVILF-VLLAGYLPFDDENLMALYRKIMKgEFEYPR 224
PK_GC-C cd14044
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-C; The pseudokinase domain ...
645-883 1.95e-19

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: 89.56  E-value: 1.95e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 645 KREIFVAIKTLKSGYTEKQRrdflSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGSLDSFLRQN----DGQFTV 720
Cdd:cd14044   32 KVVILKDLKNNEGNFTEKQK----IELNKLLQIDYYNLTKFYGTVKLDTMIFGVIEYCERGSLRDVLNDKisypDGTFMD 107
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 721 IQL-VGMLRGIAAGMKYLADMNY-VHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSdptytsalggkipiRWTAPEAI 798
Cdd:cd14044  108 WEFkISVMYDIAKGMSYLHSSKTeVHGRLKSTNCVVDSRMVVKITDFGCNSILPPSKD--------------LWTAPEHL 173
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 799 QYRKFTSASDVWSYGIVMWEVMSYGERPY-----------WDMTNQDVINAIEQDYRLPPPMDCPSALHQLMLDCWQKDR 867
Cdd:cd14044  174 RQAGTSQKGDVYSYGIIAQEIILRKETFYtaacsdrkekiYRVQNPKGMKPFRPDLNLESAGEREREVYGLVKNCWEEDP 253
                        250
                 ....*....|....*.
gi 111118978 868 NHRPKFGQIVNTLDKM 883
Cdd:cd14044  254 EKRPDFKKIENTLAKI 269
STKc_YSK4 cd06631
Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs ...
625-878 2.28e-19

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


Pssm-ID: 270801 [Multi-domain]  Cd Length: 266  Bit Score: 89.03  E-value: 2.28e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGhlkLPGKREIF----VAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITE 700
Cdd:cd06631    7 NVLGKGAYGTVYCG---LTSTGQLIavkqVELDTSDKEKAEKEYEKLQEEVDLLKTLKHVNIVGYLGTCLEDNVVSIFME 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMENGSLDSFLRQNdGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDPTY 780
Cdd:cd06631   84 FVPGGSIASILARF-GALEEPVFCRYTKQILEGVAYLHNNNVIHRDIKGNNIMLMPNGVIKLIDFGCAKRLCINLSSGSQ 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 781 TSALGGkipIR----WTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVINAIEQDYRLPPPMD---CPS 853
Cdd:cd06631  163 SQLLKS---MRgtpyWMAPEVINETGHGRKSDIWSIGCTVFE-MATGKPPWADMNPMAAIFAIGSGRKPVPRLPdkfSPE 238
                        250       260
                 ....*....|....*....|....*
gi 111118978 854 AlHQLMLDCWQKDRNHRPKFGQIVN 878
Cdd:cd06631  239 A-RDFVHACLTRDQDERPSAEQLLK 262
STKc_HAL4_like cd13994
Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs ...
627-816 2.69e-19

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: 88.90  E-value: 2.69e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKrEIFVAIKTLKSGYTEKQRRDF----LSEASIMGQFDHPNVIH-LEGVVTKSTPVMIITEF 701
Cdd:cd13994    1 IGKGATSVVRIVTKKNPRS-GVLYAVKEYRRRDDESKRKDYvkrlTSEYIISSKLHHPNIVKvLDLCQDLHGKWCLVMEY 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 702 MENGSLDSFLRQnDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEdDTSDPT-- 779
Cdd:cd13994   80 CPGGDLFTLIEK-ADSLSLEEKDCFFKQILRGVAYLHSHGIAHRDLKPENILLDEDGVLKLTDFGTAEVFG-MPAEKEsp 157
                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 111118978 780 YTSALGGKIPirWTAPEAIQYRKFT-SASDVWSYGIVM 816
Cdd:cd13994  158 MSAGLCGSEP--YMAPEVFTSGSYDgRAVDVWSCGIVL 193
STKc_PKA_like cd05580
Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs ...
621-850 2.75e-19

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: 89.56  E-value: 2.75e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKSG--YTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMII 698
Cdd:cd05580    3 FEFLKTLGTGSFGRVRLVKHKDSGK---YYALKILKKAkiIKLKQVEHVLNEKRILSEVRHPFIVNLLGSFQDDRNLYMV 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 699 TEFMENGSLDSFLRQND------GQFTVIQLVGMLrgiaagmKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLE 772
Cdd:cd05580   80 MEYVPGGELFSLLRRSGrfpndvAKFYAAEVVLAL-------EYLHSLDIVYRDLKPENLLLDSDGHIKITDFGFAKRVK 152
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 111118978 773 DDtsdpTYTsaLGGKiPiRWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVI-NAIEQDYRLPPPMD 850
Cdd:cd05580  153 DR----TYT--LCGT-P-EYLAPEIILSKGHGKAVDWWALGILIYE-MLAGYPPFFDENPMKIYeKILEGKIRFPSFFD 222
STKc_TSSK1_2-like cd14165
Catalytic domain of testis-specific serine/threonine kinase 1, TSSK2, and similar proteins; ...
627-870 3.49e-19

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: 88.30  E-value: 3.49e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHL-KLpgKREifVAIKTLKsgyTEKQRRDFLS-----EASIMGQFDHPNVIHL-EGVVTKSTPVMIIT 699
Cdd:cd14165    9 LGEGSYAKVKSAYSeRL--KCN--VAIKIID---KKKAPDDFVEkflprELEILARLNHKSIIKTyEIFETSDGKVYIVM 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENGSLDSFLrQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLE-DDTSDP 778
Cdd:cd14165   82 ELGVQGDLLEFI-KLRGALPEDVARKMFHQLSSAIKYCHELDIVHRDLKCENLLLDKDFNIKLTDFGFSKRCLrDENGRI 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 779 TYTSALGGKIPirWTAPEAIQYRKFT-SASDVWSYGIVMWeVMSYGERPYWDMTNQDVIN-AIEQDYRLPPPMDCPSALH 856
Cdd:cd14165  161 VLSKTFCGSAA--YAAPEVLQGIPYDpRIYDIWSLGVILY-IMVCGSMPYDDSNVKKMLKiQKEHRVRFPRSKNLTSECK 237
                        250
                 ....*....|....
gi 111118978 857 QLMLDCWQKDRNHR 870
Cdd:cd14165  238 DLIYRLLQPDVSQR 251
fn3 pfam00041
Fibronectin type III domain;
437-520 4.34e-19

Fibronectin type III domain;


Pssm-ID: 394996 [Multi-domain]  Cd Length: 85  Bit Score: 82.85  E-value: 4.34e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  437 SAVSIMHQVSRTVDSITLSWSQPDQPNGVILDYELQYYEKELSEYNATA-IKSPTNTVTVQGLKAGAIYVFQVRARTVAG 515
Cdd:pfam00041   1 SAPSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEPWNEItVPGTTTSVTLTGLKPGTEYEVRVQAVNGGG 80

                  ....*
gi 111118978  516 YGRYS 520
Cdd:pfam00041  81 EGPPS 85
STKc_STK10 cd06644
Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase ...
604-896 4.46e-19

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: 88.94  E-value: 4.46e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 604 DPNEaVREFAKEIdiscvkieqviGAGEFGEVCSGHLKLPGkreIFVAIKTLKSGyTEKQRRDFLSEASIMGQFDHPNVI 683
Cdd:cd06644    9 DPNE-VWEIIGEL-----------GDGAFGKVYKAKNKETG---ALAAAKVIETK-SEEELEDYMVEIEILATCNHPYIV 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 684 HLEGVVTKSTPVMIITEFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVS 763
Cdd:cd06644   73 KLLGAFYWDGKLWIMIEFCPGGAVDAIMLELDRGLTEPQIQVICRQMLEALQYLHSMKIIHRDLKAGNVLLTLDGDIKLA 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 764 DFGLSRflEDDTSDPTYTSALGGKIpirWTAPEAIQYRKFTSA-----SDVWSYGIVMWEvMSYGERPYWDMTNQDVINA 838
Cdd:cd06644  153 DFGVSA--KNVKTLQRRDSFIGTPY---WMAPEVVMCETMKDTpydykADIWSLGITLIE-MAQIEPPHHELNPMRVLLK 226
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 111118978 839 IEQDYrlPPPMDCPSA----LHQLMLDCWQKDRNHRPKFGQIVNtlDKMIRNPNSLKAMAPL 896
Cdd:cd06644  227 IAKSE--PPTLSQPSKwsmeFRDFLKTALDKHPETRPSAAQLLE--HPFVSSVTSNRPLREL 284
STKc_BRSK1_2 cd14081
Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the ...
622-861 4.81e-19

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: 87.69  E-value: 4.81e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKLPGKReifVAIKTL--KSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIIT 699
Cdd:cd14081    4 RLGKTLGKGQTGLVKLAKHCVTGQK---VAIKIVnkEKLSKESVLMKVEREIAIMKLIEHPNVLKLYDVYENKKYLYLVL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENGSLDSFLRQNdGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGL------SRFLED 773
Cdd:cd14081   81 EYVSGGELFDYLVKK-GRLTEKEARKFFRQIISALDYCHSHSICHRDLKPENLLLDEKNNIKIADFGMaslqpeGSLLET 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 774 DTSDPTYTSalggkipirwtaPEAIQYRKFT-SASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAIEQD-YRLPP--PM 849
Cdd:cd14081  160 SCGSPHYAC------------PEVIKGEKYDgRKADIWSCGVILYALLV-GALPFDDDNLRQLLEKVKRGvFHIPHfiSP 226
                        250
                 ....*....|..
gi 111118978 850 DCPSALHQlMLD 861
Cdd:cd14081  227 DAQDLLRR-MLE 237
PKc_LIMK_like_unk cd14156
Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs ...
664-883 5.07e-19

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: 87.96  E-value: 5.07e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 664 RRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYV 743
Cdd:cd14156   32 QHKIVREISLLQKLSHPNIVRYLGICVKDEKLHPILEYVSGGCLEELLAREELPLSWREKVELACDISRGMVYLHSKNIY 111
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 744 HRDLAARNILVNSN---LVCKVSDFGLSRFLED-DTSDPTYTSALGGKipIRWTAPEAIQYRKFTSASDVWSYGIVMWEV 819
Cdd:cd14156  112 HRDLNSKNCLIRVTprgREAVVTDFGLAREVGEmPANDPERKLSLVGS--AFWMAPEMLRGEPYDRKVDVFSFGIVLCEI 189
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 820 MsyGERPywdmTNQDVINAIeQDYRLPPPM------DCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKM 883
Cdd:cd14156  190 L--ARIP----ADPEVLPRT-GDFGLDVQAfkemvpGCPEPFLDLAASCCRMDAFKRPSFAELLDELEDI 252
STKc_IRAK1 cd14159
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 1; ...
627-826 5.11e-19

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: 88.73  E-value: 5.11e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLklpgkREIFVAIKTLKSGYT---EKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFME 703
Cdd:cd14159    1 IGEGGFGCVYQAVM-----RNTEYAVKRLKEDSEldwSVVKNSFLTEVEKLSRFRHPNIVDLAGYSAQQGNYCLIYVYLP 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 704 NGSLDSFLR-QNDG-QFTVIQLVGMLRGIAAGMKYLADMN--YVHRDLAARNILVNSNLVCKVSDFGLSRFLEdDTSDPT 779
Cdd:cd14159   76 NGSLEDRLHcQVSCpCLSWSQRLHVLLGTARAIQYLHSDSpsLIHGDVKSSNILLDAALNPKLGDFGLARFSR-RPKQPG 154
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 111118978 780 YTSALGGKIPIRWT----APEAIQYRKFTSASDVWSYGIVMWEVMSyGERP 826
Cdd:cd14159  155 MSSTLARTQTVRGTlaylPEEYVKTGTLSVEIDVYSFGVVLLELLT-GRRA 204
STKc_Yank1 cd05578
Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the ...
622-859 5.64e-19

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: 87.70  E-value: 5.64e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKLPGKReifVAIKTL-KSGYTEKQR-RDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIIT 699
Cdd:cd05578    3 QILRVIGKGSFGKVCIVQKKDTKKM---FAMKYMnKQKCIEKDSvRNVLNELEILQELEHPFLVNLWYSFQDEEDMYMVV 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENGSLDSFLRQNdGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDtsdpT 779
Cdd:cd05578   80 DLLLGGDLRYHLQQK-VKFSEETVKFYICEIVLALDYLHSKNIIHRDIKPDNILLDEQGHVHITDFNIATKLTDG----T 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 780 YTSALGGKIPirWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTN---QDVINAIEQDYRLPP---PMDCPS 853
Cdd:cd05578  155 LATSTSGTKP--YMAPEVFMRAGYSFAVDWWSLGVTAYE-MLRGKRPYEIHSRtsiEEIRAKFETASVLYPagwSEEAID 231

                 ....*.
gi 111118978 854 ALHQLM 859
Cdd:cd05578  232 LINKLL 237
STKc_Nek8 cd08220
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
624-876 6.42e-19

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: 87.48  E-value: 6.42e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 624 EQVIGAGEFGEVcsgHLKLPGKREIFVAIKTLK-SGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFM 702
Cdd:cd08220    5 IRVVGRGAYGTV---YLCRRKDDNKLVIIKQIPvEQMTKEERQAALNEVKVLSMLHHPNIIEYYESFLEDKALMIVMEYA 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 703 ENGSLDSFLRQNDGQF----TVIQL-VGMLrgiaAGMKYLADMNYVHRDLAARNILVNSN-LVCKVSDFGLSRFLEDDT- 775
Cdd:cd08220   82 PGGTLFEYIQQRKGSLlseeEILHFfVQIL----LALHHVHSKQILHRDLKTQNILLNKKrTVVKIGDFGISKILSSKSk 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 776 -----SDPTYTSalggkipirwtaPEAIQYRKFTSASDVWSYGIVMWEVMSYgERPYWDMTNQDVINAIEQDYRLPPPMD 850
Cdd:cd08220  158 aytvvGTPCYIS------------PELCEGKPYNQKSDIWALGCVLYELASL-KRAFEAANLPALVLKIMRGTFAPISDR 224
                        250       260
                 ....*....|....*....|....*.
gi 111118978 851 CPSALHQLMLDCWQKDRNHRPKFGQI 876
Cdd:cd08220  225 YSEELRHLILSMLHLDPNKRPTLSEI 250
STKc_PAK6 cd06659
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the ...
627-848 7.01e-19

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: 88.50  E-value: 7.01e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKReifVAIKTLKsgYTEKQRRDFL-SEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENG 705
Cdd:cd06659   29 IGEGSTGVVCIAREKHSGRQ---VAVKMMD--LRKQQRRELLfNEVVIMRDYQHPNVVEMYKSYLVGEELWVLMEYLQGG 103
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 706 SLDSFLRQNdgQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTsdPTYTSALG 785
Cdd:cd06659  104 ALTDIVSQT--RLNEEQIATVCEAVLQALAYLHSQGVIHRDIKSDSILLTLDGRVKLSDFGFCAQISKDV--PKRKSLVG 179
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 111118978 786 GKIpirWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWdmtNQDVINAIEQDYRLPPP 848
Cdd:cd06659  180 TPY---WMAPEVISRCPYGTEVDIWSLGIMVIE-MVDGEPPYF---SDSPVQAMKRLRDSPPP 235
STKc_CDC2L1 cd07843
Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze ...
627-821 8.19e-19

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: 88.05  E-value: 8.19e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGkrEIfVAIKTLKsgyTEKQRRDF----LSEASIMGQFDHPNVIHLEGVVTKST--PVMIITE 700
Cdd:cd07843   13 IEEGTYGVVYRARDKKTG--EI-VALKKLK---MEKEKEGFpitsLREINILLKLQHPNIVTVKEVVVGSNldKIYMVME 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMENgSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTsdPTY 780
Cdd:cd07843   87 YVEH-DLKSLMETMKQPFLQSEVKCLMLQLLSGVAHLHDNWILHRDLKTSNLLLNNRGILKICDFGLAREYGSPL--KPY 163
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 111118978 781 TSalggKIPIRW-TAPEAI-QYRKFTSASDVWSYGIVMWEVMS 821
Cdd:cd07843  164 TQ----LVVTLWyRAPELLlGAKEYSTAIDMWSVGCIFAELLT 202
STKc_Nek2 cd08217
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
625-871 1.01e-18

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: 87.21  E-value: 1.01e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKLPGKreIFVaIKTLKSG-YTEKQRRDFLSEASIMGQFDHPNVI--HLEGVVTKSTPVMIITEF 701
Cdd:cd08217    6 ETIGKGSFGTVRKVRRKSDGK--ILV-WKEIDYGkMSEKEKQQLVSEVNILRELKHPNIVryYDRIVDRANTTLYIVMEY 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 702 MENGSLDSFLRQNDGQFTVI----------QLVGML----RGIAAGMKYLadmnyvHRDLAARNILVNSNLVCKVSDFGL 767
Cdd:cd08217   83 CEGGDLAQLIKKCKKENQYIpeefiwkiftQLLLALyechNRSVGGGKIL------HRDLKPANIFLDSDNNVKLGDFGL 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 768 SRFLEDDTSD-------PTYTSalggkipirwtaPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYwDMTNQDVINAIE 840
Cdd:cd08217  157 ARVLSHDSSFaktyvgtPYYMS------------PELLNEQSYDEKSDIWSLGCLIYE-LCALHPPF-QAANQLELAKKI 222
                        250       260       270
                 ....*....|....*....|....*....|..
gi 111118978 841 QDYRLPP-PMDCPSALHQLMLDCWQKDRNHRP 871
Cdd:cd08217  223 KEGKFPRiPSRYSSELNEVIKSMLNVDPDKRP 254
STKc_CNK2-like cd08530
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar ...
622-879 1.26e-18

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: 86.68  E-value: 1.26e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKSG-YTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITE 700
Cdd:cd08530    3 KVLKKLGKGSYGSVYKVKRLSDNQ---VYALKEVNLGsLSQKEREDSVNEIRLLASVNHPNIIRYKEAFLDGNRLCIVME 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMENGSLDSFLRQNDGQFTVIQ-------LVGMLRGIAAgmkyLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLed 773
Cdd:cd08530   80 YAPFGDLSKLISKRKKKRRLFPeddiwriFIQMLRGLKA----LHDQKILHRDLKSANILLSAGDLVKIGDLGISKVL-- 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 774 dTSDPTYTSaLGgkIPIrWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAIEQDYRLPPPMDCPS 853
Cdd:cd08530  154 -KKNLAKTQ-IG--TPL-YAAPEVWKGRPYDYKSDIWSLGCLLYEMAT-FRPPFEARTMQELRYKVCRGKFPPIPPVYSQ 227
                        250       260
                 ....*....|....*....|....*.
gi 111118978 854 ALHQLMLDCWQKDRNHRPKFGQIVNT 879
Cdd:cd08530  228 DLQQIIRSLLQVNPKKRPSCDKLLQS 253
STKc_SLK cd06643
Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer ...
627-853 1.39e-18

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


Pssm-ID: 270811 [Multi-domain]  Cd Length: 283  Bit Score: 87.39  E-value: 1.39e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGkreIFVAIKTLKSGyTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGS 706
Cdd:cd06643   13 LGDGAFGKVYKAQNKETG---ILAAAKVIDTK-SEEELEDYMVEIDILASCDHPNIVKLLDAFYYENNLWILIEFCAGGA 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 707 LDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRflEDDTSDPTYTSALGG 786
Cdd:cd06643   89 VDAVMLELERPLTEPQIRVVCKQTLEALVYLHENKIIHRDLKAGNILFTLDGDIKLADFGVSA--KNTRTLQRRDSFIGT 166
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 111118978 787 KIpirWTAPEAI-----QYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVINAIEQDYrlPPPMDCPS 853
Cdd:cd06643  167 PY---WMAPEVVmcetsKDRPYDYKADVWSLGVTLIE-MAQIEPPHHELNPMRVLLKIAKSE--PPTLAQPS 232
STKc_IKK_beta cd14038
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
627-874 1.57e-18

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


Pssm-ID: 270940 [Multi-domain]  Cd Length: 290  Bit Score: 87.33  E-value: 1.57e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKReifVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVI-------HLEGVVTKSTPVMIIt 699
Cdd:cd14038    2 LGTGGFGNVLRWINQETGEQ---VAIKQCRQELSPKNRERWCLEIQIMKRLNHPNVVaardvpeGLQKLAPNDLPLLAM- 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENGSLDSFLRQ--NDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVN---SNLVCKVSDFGLSRFLEDD 774
Cdd:cd14038   78 EYCQGGDLRKYLNQfeNCCGLREGAILTLLSDISSALRYLHENRIIHRDLKPENIVLQqgeQRLIHKIIDLGYAKELDQG 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 775 TSDPTYTSALggkipiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPY---WD----------------MTNQDV 835
Cdd:cd14038  158 SLCTSFVGTL------QYLAPELLEQQKYTVTVDYWSFGTLAFECIT-GFRPFlpnWQpvqwhgkvrqksnediVVYEDL 230
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*.
gi 111118978 836 INAIEQDYRLPPPMDCPSALH-------QLMLDCWQKDRNHRPKFG 874
Cdd:cd14038  231 TGAVKFSSVLPTPNNLNGILAgklerwlQCMLMWHPRQRGTDPPQN 276
STKc_MEKK1 cd06630
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
670-872 1.58e-18

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: 86.71  E-value: 1.58e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 670 EASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGSLDSFLrQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAA 749
Cdd:cd06630   53 EIRMMARLNHPNIVRMLGATQHKSHFNIFVEWMAGGSVASLL-SKYGAFSENVIINYTLQILRGLAYLHDNQIIHRDLKG 131
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 750 RNILVNSN-LVCKVSDFGLSRFLeddTSDPTYTSALGGKI--PIRWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERP 826
Cdd:cd06630  132 ANLLVDSTgQRLRIADFGAAARL---ASKGTGAGEFQGQLlgTIAFMAPEVLRGEQYGRSCDVWSVGCVIIE-MATAKPP 207
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 111118978 827 yWDmtNQDVINAIEQDYRL-----PPPMdcPSALHQ----LMLDCWQKDRNHRPK 872
Cdd:cd06630  208 -WN--AEKISNHLALIFKIasattPPPI--PEHLSPglrdVTLRCLELQPEDRPP 257
STKc_MARK cd14072
Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; ...
622-860 1.76e-18

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: 86.03  E-value: 1.76e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKLPGKReifVAIKTL-KSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITE 700
Cdd:cd14072    3 RLLKTIGKGNFAKVKLARHVLTGRE---VAIKIIdKTQLNPSSLQKLFREVRIMKILNHPNIVKLFEVIETEKTLYLVME 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMENGSLDSFLrQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDPTY 780
Cdd:cd14072   80 YASGGEVFDYL-VAHGRMKEKEARAKFRQIVSAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFGFSNEFTPGNKLDTF 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 781 TsalgGKIPirWTAPEAIQYRKFTSAS-DVWSYGIVMWEVMSyGERPYwDMTNQDVINA--IEQDYRLPPPM--DCPSAL 855
Cdd:cd14072  159 C----GSPP--YAAPELFQGKKYDGPEvDVWSLGVILYTLVS-GSLPF-DGQNLKELRErvLRGKYRIPFYMstDCENLL 230

                 ....*
gi 111118978 856 HQLML 860
Cdd:cd14072  231 KKFLV 235
STKc_NIM1 cd14075
Catalytic domain of the Serine/Threonine Kinase, NIM1; STKs catalyze the transfer of the ...
618-847 1.84e-18

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: 86.24  E-value: 1.84e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 618 ISCVKIEQVIGAGEFGEVCSGHLKLPGKReifVAIKTL-KSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVM 696
Cdd:cd14075    1 IGFYRIRGELGSGNFSQVKLGIHQLTKEK---VAIKILdKTKLDQKTQRLLSREISSMEKLHHPNIIRLYEVVETLSKLH 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 697 IITEFMENGSLDSFLrQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTS 776
Cdd:cd14075   78 LVMEYASGGELYTKI-STEGKLSESEAKPLFAQIVSAVKHMHENNIIHRDLKAENVFYASNNCVKVGDFGFSTHAKRGET 156
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 111118978 777 DPTYTsalgGKIPirWTAPEAIQYRKFTSAS-DVWSYGIVMWeVMSYGERPYWDMTNQDVINAI-EQDYRLPP 847
Cdd:cd14075  157 LNTFC----GSPP--YAAPELFKDEHYIGIYvDIWALGVLLY-FMVTGVMPFRAETVAKLKKCIlEGTYTIPS 222
STKc_STK33 cd14097
Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the ...
627-827 2.03e-18

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: 86.45  E-value: 2.03e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKREIFVAIKTLKSGYTEKQRRDflSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGS 706
Cdd:cd14097    9 LGQGSFGVVIEATHKETQTKWAIKKINREKAGSSAVKLLE--REVDILKHVNHAHIIHLEEVFETPKRMYLVMELCEDGE 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 707 LDSFLRQnDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLV-------CKVSDFGLSrFLEDDTSDPT 779
Cdd:cd14097   87 LKELLLR-KGFFSENETRHIIQSLASAVAYLHKNDIVHRDLKLENILVKSSIIdnndklnIKVTDFGLS-VQKYGLGEDM 164
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 111118978 780 YTSALGGKIpirWTAPEAIQYRKFTSASDVWSYGIVMWeVMSYGERPY 827
Cdd:cd14097  165 LQETCGTPI---YMAPEVISAHGYSQQCDIWSIGVIMY-MLLCGEPPF 208
STKc_ULK4 cd14010
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the ...
649-878 2.49e-18

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: 86.19  E-value: 2.49e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 649 FVAIKTlksgyTEKQRRD-FLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGSLDSFLRQNDG-QFTVIQLVGm 726
Cdd:cd14010   27 FVAIKC-----VDKSKRPeVLNEVRLTHELKHPNVLKFYEWYETSNHLWLVVEYCTGGDLETLLRQDGNlPESSVRKFG- 100
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 727 lRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDPTYTSALGGKIPIR-----------WTAP 795
Cdd:cd14010  101 -RDLVRGLHYIHSKGIIYCDLKPSNILLDGNGTLKLSDFGLARREGEILKELFGQFSDEGNVNKVskkqakrgtpyYMAP 179
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 796 EAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVINAIEQDyrlPPPMDCPSALHQLMLDCW-------QKDRN 868
Cdd:cd14010  180 ELFQGGVHSFASDLWALGCVLYE-MFTGKPPFVAESFTELVEKILNE---DPPPPPPKVSSKPSPDFKsllkgllEKDPA 255
                        250
                 ....*....|
gi 111118978 869 HRPKFGQIVN 878
Cdd:cd14010  256 KRLSWDELVK 265
STKc_PAK5 cd06658
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the ...
604-847 2.66e-18

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: 86.63  E-value: 2.66e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 604 DPNEAVREFAKeidiscvkieqvIGAGEFGEVCSGHLKLPGKReifVAIKtlKSGYTEKQRRDFL-SEASIMGQFDHPNV 682
Cdd:cd06658   19 DPREYLDSFIK------------IGEGSTGIVCIATEKHTGKQ---VAVK--KMDLRKQQRRELLfNEVVIMRDYHHENV 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 683 IHLEGVVTKSTPVMIITEFMENGSLDSFL---RQNDGQFTVIQLvgmlrGIAAGMKYLADMNYVHRDLAARNILVNSNLV 759
Cdd:cd06658   82 VDMYNSYLVGDELWVVMEFLEGGALTDIVthtRMNEEQIATVCL-----SVLRALSYLHNQGVIHRDIKSDSILLTSDGR 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 760 CKVSDFGLSRFLEDDTsdPTYTSALGGKIpirWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAI 839
Cdd:cd06658  157 IKLSDFGFCAQVSKEV--PKRKSLVGTPY---WMAPEVISRLPYGTEVDIWSLGIMVIEMID-GEPPYFNEPPLQAMRRI 230

                 ....*...
gi 111118978 840 EQDyrLPP 847
Cdd:cd06658  231 RDN--LPP 236
STKc_AMPK_alpha cd14079
Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein ...
622-829 2.66e-18

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: 85.78  E-value: 2.66e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKLPGKReifVAIKTL------KSGYTEKQRRdflsEASIMGQFDHPNVIHLEGVVTKSTPV 695
Cdd:cd14079    5 ILGKTLGVGSFGKVKLAEHELTGHK---VAVKILnrqkikSLDMEEKIRR----EIQILKLFRHPHIIRLYEVIETPTDI 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 696 MIITEFMENGSLDSFLRQNdGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLED-- 773
Cdd:cd14079   78 FMVMEYVSGGELFDYIVQK-GRLSEDEARRFFQQIISGVEYCHRHMVVHRDLKPENLLLDSNMNVKIADFGLSNIMRDge 156
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 111118978 774 --DTS--DPTYtsalggkipirwTAPEAIQYRKFT-SASDVWSYGIVMWeVMSYGERPYWD 829
Cdd:cd14079  157 flKTScgSPNY------------AAPEVISGKLYAgPEVDVWSCGVILY-ALLCGSLPFDD 204
STKc_Nek6 cd08228
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
622-883 4.28e-18

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: 85.46  E-value: 4.28e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKLPGKReifVAIKTLK--SGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIIT 699
Cdd:cd08228    5 QIEKKIGRGQFSEVYRATCLLDRKP---VALKKVQifEMMDAKARQDCVKEIDLLKQLNHPNVIKYLDSFIEDNELNIVL 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENGSLDSFLRQNDGQFTVIQLVGMLR---GIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLeddTS 776
Cdd:cd08228   82 ELADAGDLSQMIKYFKKQKRLIPERTVWKyfvQLCSAVEHMHSRRVMHRDIKPANVFITATGVVKLGDLGLGRFF---SS 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 777 DPTYTSALGGKiPIrWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQ-DVINAIEQ-DYRLPPPMDCPSA 854
Cdd:cd08228  159 KTTAAHSLVGT-PY-YMSPERIHENGYNFKSDIWSLGCLLYEMAALQSPFYGDKMNLfSLCQKIEQcDYPPLPTEHYSEK 236
                        250       260
                 ....*....|....*....|....*....
gi 111118978 855 LHQLMLDCWQKDRNHRPKFGQIVNTLDKM 883
Cdd:cd08228  237 LRELVSMCIYPDPDQRPDIGYVHQIAKQM 265
SAM_EPH-A10 cd09549
SAM domain of EPH-A10 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
910-978 5.07e-18

SAM domain of EPH-A10 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A10 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A10 receptors and appears to mediate cell-cell initiated signal transduction. It was found preferentially expressed in the testis. EphA10 may be involved in the pathogenesis and development of prostate carcinoma and lymphocytic leukemia. It is a potential molecular marker and/or therapy target for these types of cancers.


Pssm-ID: 188948  Cd Length: 70  Bit Score: 79.14  E-value: 5.07e-18
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 111118978 910 PDYTSFNTVDEWLEAIKMGQYKESFANAGFTSFDVVSQMMMEDILRVGVTLAGHQKKILNSIQVMRAQM 978
Cdd:cd09549    2 STFPSFGSVGEWLEALDLCRYKDNFAAAGYGSLEAVARMTAQDVLSLGITSLEHQELLLAGIQALRAQV 70
STKc_ERK5 cd07855
Catalytic domain of the Serine/Threonine Kinase, Extracellular signal-Regulated Kinase 5; ...
622-826 6.74e-18

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: 86.27  E-value: 6.74e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKLPGKReifVAIKTLKSGYTEKQ--RRDfLSEASIMGQFDHPNVIHLEGVVTKSTP----- 694
Cdd:cd07855    8 EPIETIGSGAYGVVCSAIDTKSGQK---VAIKKIPNAFDVVTtaKRT-LRELKILRHFKHDNIIAIRDILRPKVPyadfk 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 695 -VMIITEFMENgSLDSFLRqNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLed 773
Cdd:cd07855   84 dVYVVLDLMES-DLHHIIH-SDQPLTLEHIRYFLYQLLRGLKYIHSANVIHRDLKPSNLLVNENCELKIGDFGMARGL-- 159
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 111118978 774 DTSDPTYTSALGGKIPIRW-TAPEAI-QYRKFTSASDVWSYGIVMWEVMsyGERP 826
Cdd:cd07855  160 CTSPEEHKYFMTEYVATRWyRAPELMlSLPEYTQAIDMWSVGCIFAEML--GRRQ 212
STKc_CDK7 cd07841
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs ...
627-820 7.47e-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: 85.32  E-value: 7.47e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKReifVAIKTLKSGYTEKQR----RDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFM 702
Cdd:cd07841    8 LGEGTYAVVYKARDKETGRI---VAIKKIKLGERKEAKdginFTALREIKLLQELKHPNIIGLLDVFGHKSNINLVFEFM 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 703 EnGSLDSFLRQNDGQFTVIQ----LVGMLRGIAagmkYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFleddTSDP 778
Cdd:cd07841   85 E-TDLEKVIKDKSIVLTPADiksyMLMTLRGLE----YLHSNWILHRDLKPNNLLIASDGVLKLADFGLARS----FGSP 155
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 111118978 779 T--YTSalggKIPIRW-TAPE----AiqyRKFTSASDVWSYGIVMWEVM 820
Cdd:cd07841  156 NrkMTH----QVVTRWyRAPEllfgA---RHYGVGVDMWSVGCIFAELL 197
STKc_NAK1_like cd06917
Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of ...
625-829 7.96e-18

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: 84.83  E-value: 7.96e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGYTEKQRRDFLSEASIMGQFDH---PNVIHLEGVVTKSTPVMIITEF 701
Cdd:cd06917    7 ELVGRGSYGAVYRGYHVKTGR---VVALKVLNLDTDDDDVSDIQKEVALLSQLKLgqpKNIIKYYGSYLKGPSLWIIMDY 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 702 MENGSLDSFLRQNDGQFTVIQLVgmLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDptyT 781
Cdd:cd06917   84 CEGGSIRTLMRAGPIAERYIAVI--MREVLVALKFIHKDGIIHRDIKAANILVTNTGNVKLCDFGVAASLNQNSSK---R 158
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 111118978 782 SALGGKiPIrWTAPEAI-QYRKFTSASDVWSYGIVMWEvMSYGERPYWD 829
Cdd:cd06917  159 STFVGT-PY-WMAPEVItEGKYYDTKADIWSLGITTYE-MATGNPPYSD 204
PLN00034 PLN00034
mitogen-activated protein kinase kinase; Provisional
627-818 8.41e-18

mitogen-activated protein kinase kinase; Provisional


Pssm-ID: 215036 [Multi-domain]  Cd Length: 353  Bit Score: 86.03  E-value: 8.41e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGS 706
Cdd:PLN00034  82 IGSGAGGTVYKVIHRPTGR---LYALKVIYGNHEDTVRRQICREIEILRDVNHPNVVKCHDMFDHNGEIQVLLEFMDGGS 158
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 707 LDSfLRQNDGQFtviqLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLeDDTSDPTyTSALGg 786
Cdd:PLN00034 159 LEG-THIADEQF----LADVARQILSGIAYLHRRHIVHRDIKPSNLLINSAKNVKIADFGVSRIL-AQTMDPC-NSSVG- 230
                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 111118978 787 kiPIRWTAPEAI-------QYRKFtsASDVWSYGIVMWE 818
Cdd:PLN00034 231 --TIAYMSPERIntdlnhgAYDGY--AGDIWSLGVSILE 265
STKc_IKK cd13989
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
627-827 9.36e-18

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: 84.81  E-value: 9.36e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCsghLKLPGKREIFVAIKT--LKSGYTEKQRRDFLSEASIMGQFDHPNVI-------HLEGVVTKSTPVMI 697
Cdd:cd13989    1 LGSGGFGYVT---LWKHQDTGEYVAIKKcrQELSPSDKNRERWCLEVQIMKKLNHPNVVsardvppELEKLSPNDLPLLA 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 698 ItEFMENGSLDSFLRQ--NDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNIL---VNSNLVCKVSDFGLSRFLE 772
Cdd:cd13989   78 M-EYCSGGDLRKVLNQpeNCCGLKESEVRTLLSDISSAISYLHENRIIHRDLKPENIVlqqGGGRVIYKLIDLGYAKELD 156
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 111118978 773 DDTSDPTYTSALggkipiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPY 827
Cdd:cd13989  157 QGSLCTSFVGTL------QYLAPELFESKKYTCTVDYWSFGTLAFECIT-GYRPF 204
STKc_DAPK1 cd14194
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 1; STKs ...
627-843 1.43e-17

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: 83.92  E-value: 1.43e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKReifVAIKTLKSGYTEKQRR-----DFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEF 701
Cdd:cd14194   13 LGSGQFAVVKKCREKSTGLQ---YAAKFIKKRRTKSSRRgvsreDIEREVSILKEIQHPNVITLHEVYENKTDVILILEL 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 702 MENGSLDSFLRQNDgQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNI-LVNSNLV---CKVSDFGLSRFLEddtSD 777
Cdd:cd14194   90 VAGGELFDFLAEKE-SLTEEEATEFLKQILNGVYYLHSLQIAHFDLKPENImLLDRNVPkprIKIIDFGLAHKID---FG 165
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 111118978 778 PTYTSALGGKipiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDV---INAIEQDY 843
Cdd:cd14194  166 NEFKNIFGTP---EFVAPEIVNYEPLGLEADMWSIGVITYILLS-GASPFLGDTKQETlanVSAVNYEF 230
PKc_Pek1_like cd06621
Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ...
630-872 1.51e-17

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: 84.01  E-value: 1.51e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 630 GEFGEVCSGHL---KLPGKREIFvAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVT--KSTPVMIITEFMEN 704
Cdd:cd06621    7 SSLGEGAGGSVtkcRLRNTKTIF-ALKTITTDPNPDVQKQILRELEINKSCASPYIVKYYGAFLdeQDSSIGIAMEYCEG 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 705 GSLDSF---LRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLS-RFLEDDTSDPTY 780
Cdd:cd06621   86 GSLDSIykkVKKKGGRIGEKVLGKIAESVLKGLSYLHSRKIIHRDIKPSNILLTRKGQVKLCDFGVSgELVNSLAGTFTG 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 781 TSAlggkipirWTAPEAIQYRKFTSASDVWSYGIVMWEVmSYGERPYWDMTNQDV--INAIEQDYRLPPPM--DCPS--- 853
Cdd:cd06621  166 TSY--------YMAPERIQGGPYSITSDVWSLGLTLLEV-AQNRFPFPPEGEPPLgpIELLSYIVNMPNPElkDEPEngi 236
                        250       260
                 ....*....|....*....|...
gi 111118978 854 ----ALHQLMLDCWQKDRNHRPK 872
Cdd:cd06621  237 kwseSFKDFIEKCLEKDGTRRPG 259
STKc_KSR1 cd14152
Catalytic domain of the Serine/Threonine Kinase, Kinase Suppressor of Ras 1; STKs catalyze the ...
621-883 1.52e-17

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: 83.86  E-value: 1.52e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQVIGAGEFGEVCSGhlKLPGKreifVAIKTLK-SGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIIT 699
Cdd:cd14152    2 IELGELIGQGRWGKVHRG--RWHGE----VAIRLLEiDGNNQDHLKLFKKEVMNYRQTRHENVVLFMGACMHPPHLAIIT 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCkVSDFGL---SRFLEDDTS 776
Cdd:cd14152   76 SFCKGRTLYSFVRDPKTSLDINKTRQIAQEIIKGMGYLHAKGIVHKDLKSKNVFYDNGKVV-ITDFGLfgiSGVVQEGRR 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 777 DPTYtsalggKIPIRWT---APEAIQYRK---------FTSASDVWSYGIVMWEVMSYGerpyWDMTNQDV------INA 838
Cdd:cd14152  155 ENEL------KLPHDWLcylAPEIVREMTpgkdedclpFSKAADVYAFGTIWYELQARD----WPLKNQPAealiwqIGS 224
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*
gi 111118978 839 IEQDYRLPPPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKM 883
Cdd:cd14152  225 GEGMKQVLTTISLGKEVTEILSACWAFDLEERPSFTLLMDMLEKL 269
STKc_MEKK3_like cd06625
Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) ...
626-871 1.53e-17

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: 83.56  E-value: 1.53e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 626 VIGAGEFGEVCSGHLKLPGKReifVAIKTLKSGY----TEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEF 701
Cdd:cd06625    7 LLGQGAFGQVYLCYDADTGRE---LAVKQVEIDPinteASKEVKALECEIQLLKNLQHERIVQYYGCLQDEKSLSIFMEY 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 702 MENGSLDSFLRQNdGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEddtsdpTYT 781
Cdd:cd06625   84 MPGGSVKDEIKAY-GALTENVTRKYTRQILEGLAYLHSNMIVHRDIKGANILRDSNGNVKLGDFGASKRLQ------TIC 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 782 SALGGKIPI---RWTAPEAIQYRKFTSASDVWSYGIVMWEVMSygERPYWdmTNQDVINAI------EQDYRLPPpmDCP 852
Cdd:cd06625  157 SSTGMKSVTgtpYWMSPEVINGEGYGRKADIWSVGCTVVEMLT--TKPPW--AEFEPMAAIfkiatqPTNPQLPP--HVS 230
                        250
                 ....*....|....*....
gi 111118978 853 SALHQLMLDCWQKDRNHRP 871
Cdd:cd06625  231 EDARDFLSLIFVRNKKQRP 249
STKc_TGFbR1_ACVR1b_ACVR1c cd14143
Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta Type I ...
625-885 1.97e-17

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: 84.03  E-value: 1.97e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLklpgkREIFVAIKTLKSgyteKQRRDFLSEASIMG--QFDHPNVIHLEGVVTK----STPVMII 698
Cdd:cd14143    1 ESIGKGRFGEVWRGRW-----RGEDVAVKIFSS----REERSWFREAEIYQtvMLRHENILGFIAADNKdngtWTQLWLV 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 699 TEFMENGSLDSFLRQNdgQFTVIQLVGMLRGIAAGMKYLaDMNYV---------HRDLAARNILVNSNLVCKVSDFGLSR 769
Cdd:cd14143   72 SDYHEHGSLFDYLNRY--TVTVEGMIKLALSIASGLAHL-HMEIVgtqgkpaiaHRDLKSKNILVKKNGTCCIADLGLAV 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 770 FLED--DTSDPTYTSALGGKipiRWTAPE----AIQYRKFTS--ASDVWSYGIVMWEVmsygerpywdmTNQDVINAIEQ 841
Cdd:cd14143  149 RHDSatDTIDIAPNHRVGTK---RYMAPEvlddTINMKHFESfkRADIYALGLVFWEI-----------ARRCSIGGIHE 214
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*...
gi 111118978 842 DYRLP----PPMDcPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKMIR 885
Cdd:cd14143  215 DYQLPyydlVPSD-PSIEEMRKVVCEQKLRPNIPNRWQSCEALRVMAK 261
STKc_Nek7 cd08229
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
599-883 2.15e-17

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: 83.93  E-value: 2.15e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 599 PFTYEDPNEAVREFAKEIDISCVKIEQVIGAGEFGEVCSGHLKLPGkreIFVAIKTLK--SGYTEKQRRDFLSEASIMGQ 676
Cdd:cd08229    4 PVPQFQPQKALRPDMGYNTLANFRIEKKIGRGQFSEVYRATCLLDG---VPVALKKVQifDLMDAKARADCIKEIDLLKQ 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 677 FDHPNVIHLEGVVTKSTPVMIITEFMENGSLDSFLRQNDGQFTVIQLVGMLR---GIAAGMKYLADMNYVHRDLAARNIL 753
Cdd:cd08229   81 LNHPNVIKYYASFIEDNELNIVLELADAGDLSRMIKHFKKQKRLIPEKTVWKyfvQLCSALEHMHSRRVMHRDIKPANVF 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 754 VNSNLVCKVSDFGLSRFLeddTSDPTYTSALGGKiPIrWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTN- 832
Cdd:cd08229  161 ITATGVVKLGDLGLGRFF---SSKTTAAHSLVGT-PY-YMSPERIHENGYNFKSDIWSLGCLLYEMAALQSPFYGDKMNl 235
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|..
gi 111118978 833 QDVINAIEQ-DYRLPPPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKM 883
Cdd:cd08229  236 YSLCKKIEQcDYPPLPSDHYSEELRQLVNMCINPDPEKRPDITYVYDVAKRM 287
STKc_DAPK2 cd14196
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 2; STKs ...
623-839 3.98e-17

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK2, also called DAPK-related protein 1 (DRP-1), is a Ca2+/calmodulin (CaM)-regulated protein containing an N-terminal kinase domain, a CaM autoinhibitory site and a dimerization module. It lacks the cytoskeletal binding regions of DAPK1 and the exogenous protein has been shown to be soluble and cytoplasmic. FLAG-tagged DAPK2, however, accumulated within membrane-enclosed autophagic vesicles. It is unclear where endogenous DAPK2 is localized. DAPK2 participates in TNF-alpha and FAS-receptor induced cell death and enhances neutrophilic maturation in myeloid leukemic cells. It contributes to the induction of anoikis and its down-regulation is implicated in the beta-catenin induced resistance of malignant epithelial cells to anoikis. The DAPK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271098 [Multi-domain]  Cd Length: 269  Bit Score: 82.70  E-value: 3.98e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 623 IEQVIGAGEFGEVCSGHLKLPGKReifVAIKTLKSGYTEKQRRDFLS-----EASIMGQFDHPNVIHLEGVVTKSTPVMI 697
Cdd:cd14196    9 IGEELGSGQFAIVKKCREKSTGLE---YAAKFIKKRQSRASRRGVSReeierEVSILRQVLHPNIITLHDVYENRTDVVL 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 698 ITEFMENGSLDSFLRQNDgQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNI-LVNSNLV---CKVSDFGLSRFLED 773
Cdd:cd14196   86 ILELVSGGELFDFLAQKE-SLSEEEATSFIKQILDGVNYLHTKKIAHFDLKPENImLLDKNIPiphIKLIDFGLAHEIED 164
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 111118978 774 DTSdptYTSALGGKipiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAI 839
Cdd:cd14196  165 GVE---FKNIFGTP---EFVAPEIVNYEPLGLEADMWSIGVITYILLS-GASPFLGDTKQETLANI 223
STKc_MEKK4 cd06626
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
627-833 4.10e-17

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: 82.35  E-value: 4.10e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVcsghlklpgkreiFVAIkTLKSGY------------TEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTP 694
Cdd:cd06626    8 IGEGTFGKV-------------YTAV-NLDTGElmamkeirfqdnDPKTIKEIADEMKVLEGLDHPNLVRYYGVEVHREE 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 695 VMIITEFMENGSLDSFLRQNDGQ-FTVIQL--VGMLRGIAagmkYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFL 771
Cdd:cd06626   74 VYIFMEYCQEGTLEELLRHGRILdEAVIRVytLQLLEGLA----YLHENGIVHRDIKPANIFLDSNGLIKLGDFGSAVKL 149
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 111118978 772 EDDTSDPTYTSALGGKIPIRWTAPEAIQYRKFTS---ASDVWSYGIVMWEvMSYGERPYWDMTNQ 833
Cdd:cd06626  150 KNNTTTMAPGEVNSLVGTPAYMAPEVITGNKGEGhgrAADIWSLGCVVLE-MATGKRPWSELDNE 213
STKc_PKD cd14082
Catalytic domain of the Serine/Threonine kinase, Protein Kinase D; STKs catalyze the transfer ...
624-821 4.28e-17

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


Pssm-ID: 270984 [Multi-domain]  Cd Length: 260  Bit Score: 82.08  E-value: 4.28e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 624 EQVIGAGEFGEVCSGHLKLPGKReifVAIKTL-KSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFM 702
Cdd:cd14082    8 DEVLGSGQFGIVYGGKHRKTGRD---VAIKVIdKLRFPTKQESQLRNEVAILQQLSHPGVVNLECMFETPERVFVVMEKL 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 703 ENGSLDSFLRQNDG-------QFTVIQlvgmlrgIAAGMKYLADMNYVHRDLAARNILVNSNL---VCKVSDFGLSRFLE 772
Cdd:cd14082   85 HGDMLEMILSSEKGrlperitKFLVTQ-------ILVALRYLHSKNIVHCDLKPENVLLASAEpfpQVKLCDFGFARIIG 157
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 111118978 773 DDT------SDPTYtsalggkipirwTAPEAIQYRKFTSASDVWSYGIVMWEVMS 821
Cdd:cd14082  158 EKSfrrsvvGTPAY------------LAPEVLRNKGYNRSLDMWSVGVIIYVSLS 200
STKc_DAPK cd14105
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase; STKs ...
627-839 4.99e-17

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


Pssm-ID: 271007 [Multi-domain]  Cd Length: 269  Bit Score: 82.15  E-value: 4.99e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKR--EIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMEN 704
Cdd:cd14105   13 LGSGQFAVVKKCREKSTGLEyaAKFIKKRRSKASRRGVSREDIEREVSILRQVLHPNIITLHDVFENKTDVVLILELVAG 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 705 GSLDSFLRQNDGqFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLV----CKVSDFGLSRFLEDDTSdptY 780
Cdd:cd14105   93 GELFDFLAEKES-LSEEEATEFLKQILDGVNYLHTKNIAHFDLKPENIMLLDKNVpiprIKLIDFGLAHKIEDGNE---F 168
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 111118978 781 TSALGGKipiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAI 839
Cdd:cd14105  169 KNIFGTP---EFVAPEIVNYEPLGLEADMWSIGVITYILLS-GASPFLGDTKQETLANI 223
STKc_CDKL cd07833
Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs ...
626-824 5.09e-17

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: 82.75  E-value: 5.09e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 626 VIGAGEFGEVCSGHLKLPGkrEIfVAIKTLKSGY-TEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMEN 704
Cdd:cd07833    8 VVGEGAYGVVLKCRNKATG--EI-VAIKKFKESEdDEDVKKTALREVKVLRQLRHENIVNLKEAFRRKGRLYLVFEYVER 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 705 GSLDSFLRQNDG------QFTVIQLvgmLRGIAagmkYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDP 778
Cdd:cd07833   85 TLLELLEASPGGlppdavRSYIWQL---LQAIA----YCHSHNIIHRDIKPENILVSESGVLKLCDFGFARALTARPASP 157
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 111118978 779 tYTSalggKIPIRW-TAPE----AIQYRKftsASDVWSYGIVMWEvMSYGE 824
Cdd:cd07833  158 -LTD----YVATRWyRAPEllvgDTNYGK---PVDVWAIGCIMAE-LLDGE 199
PTK_Jak3_rpt1 cd14208
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 3; Jak3 is ...
627-881 5.65e-17

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


Pssm-ID: 271110 [Multi-domain]  Cd Length: 260  Bit Score: 81.87  E-value: 5.65e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEV---CSGHLKLPGKREIFVAIKTLKSGYTEKQRrDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMiITEFME 703
Cdd:cd14208    7 LGKGSFTKIyrgLRTDEEDDERCETEVLLKVMDPTHGNCQE-SFLEAASIMSQISHKHLVLLHGVCVGKDSIM-VQEFVC 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 704 NGSLDSFLRQN--DGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILV------NSNLVCKVSDFGLSRFLEDDt 775
Cdd:cd14208   85 HGALDLYLKKQqqKGPVAISWKLQVVKQLAYALNYLEDKQLVHGNVSAKKVLLsregdkGSPPFIKLSDPGVSIKVLDE- 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 776 sdptytSALGGKIPirWTAPEAI-QYRKFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPMdcPSA 854
Cdd:cd14208  164 ------ELLAERIP--WVAPECLsDPQNLALEADKWGFGATLWEIFSGGHMPLSALDPSKKLQFYNDRKQLPAPH--WIE 233
                        250       260
                 ....*....|....*....|....*..
gi 111118978 855 LHQLMLDCWQKDRNHRPKFGQIVNTLD 881
Cdd:cd14208  234 LASLIQQCMSYNPLLRPSFRAIIRDLN 260
STKc_PDK1 cd05581
Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs ...
622-850 5.92e-17

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: 82.26  E-value: 5.92e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKLPGKReifVAIKTLKSGYTEKQRR-DFLS-EASIMGQFDHPNVIHLEGVVTKSTPVMIIT 699
Cdd:cd05581    4 KFGKPLGEGSYSTVVLAKEKETGKE---YAIKVLDKRHIIKEKKvKYVTiEKEVLSRLAHPGIVKLYYTFQDESKLYFVL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENGSLDSFLRQNdGQFTVIqlvgMLRGIAA----GMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFL-EDD 774
Cdd:cd05581   81 EYAPNGDLLEYIRKY-GSLDEK----CTRFYTAeivlALEYLHSKGIIHRDLKPENILLDEDMHIKITDFGTAKVLgPDS 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 775 TSDPTYTSALGGKIPIR-----------WTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVINAIEQ-D 842
Cdd:cd05581  156 SPESTKGDADSQIAYNQaraasfvgtaeYVSPELLNEKPAGKSSDLWALGCIIYQ-MLTGKPPFRGSNEYLTFQKIVKlE 234

                 ....*...
gi 111118978 843 YRLPPPMD 850
Cdd:cd05581  235 YEFPENFP 242
STKc_MLCK-like cd14006
Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs ...
627-850 7.14e-17

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: 81.16  E-value: 7.14e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKReifVAIKTLKsgYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGS 706
Cdd:cd14006    1 LGRGRFGVVKRCIEKATGRE---FAAKFIP--KRDKKKEAVLREISILNQLQHPRIIQLHEAYESPTELVLILELCSGGE 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 707 LDSFLRqNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILV---NSNLVcKVSDFGLSRFLE-DDTSDPTYTS 782
Cdd:cd14006   76 LLDRLA-ERGSLSEEEVRTYMRQLLEGLQYLHNHHILHLDLKPENILLadrPSPQI-KIIDFGLARKLNpGEELKEIFGT 153
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 111118978 783 AlggkipiRWTAPEAIQYRKFTSASDVWSYGIVMWeVMSYGERPYWDMTNQDVINAIEQ-DYRLPPPMD 850
Cdd:cd14006  154 P-------EFVAPEIVNGEPVSLATDMWSIGVLTY-VLLSGLSPFLGEDDQETLANISAcRVDFSEEYF 214
STKc_MLCK1 cd14191
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze ...
623-837 7.47e-17

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: 81.59  E-value: 7.47e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 623 IEQVIGAGEFGEVcsghLKLPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFM 702
Cdd:cd14191    6 IEERLGSGKFGQV----FRLVEKKTKKVWAGKFFKAYSAKEKENIRQEISIMNCLHHPKLVQCVDAFEEKANIVMVLEMV 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 703 ENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNIL-VN-SNLVCKVSDFGLSRFLEDDTSdpty 780
Cdd:cd14191   82 SGGELFERIIDEDFELTERECIKYMRQISEGVEYIHKQGIVHLDLKPENIMcVNkTGTKIKLIDFGLARRLENAGS---- 157
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 111118978 781 TSALGGKiPiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYW-DMTNQDVIN 837
Cdd:cd14191  158 LKVLFGT-P-EFVAPEVINYEPIGYATDMWSIGVICYILVS-GLSPFMgDNDNETLAN 212
STKc_NUAK2 cd14161
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs ...
625-850 9.37e-17

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: 81.15  E-value: 9.37e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVcsghLKLPGKREIFVAIKTLKSGYTeKQRRDFL---SEASIMGQFDHPNVIHLEGVVTKSTPVMIITEF 701
Cdd:cd14161    9 ETLGKGTYGRV----KKARDSSGRLVAIKSIRKDRI-KDEQDLLhirREIEIMSSLNHPHIISVYEVFENSSKIVIVMEY 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 702 MENGSLDSFLRQNDgQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDPTYT 781
Cdd:cd14161   84 ASRGDLYDYISERQ-RLSELEARHFFRQIVSAVHYCHANGIVHRDLKLENILLDANGNIKIADFGLSNLYNQDKFLQTYC 162
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 111118978 782 SAlggkiPIrWTAPEAIQYRKFTSAS-DVWSYGIVMWeVMSYGERPYWDMTNQDVINAIEQ-DYRLPP-PMD 850
Cdd:cd14161  163 GS-----PL-YASPEIVNGRPYIGPEvDSWSLGVLLY-ILVHGTMPFDGHDYKILVKQISSgAYREPTkPSD 227
STKc_Nek3 cd08219
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
623-871 9.78e-17

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: 81.17  E-value: 9.78e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 623 IEQVIGAGEFGEVCSGHLKLPGKREIFVAIKTLKSGY-TEKQRRdflsEASIMGQFDHPNVIHLEGVVTKSTPVMIITEF 701
Cdd:cd08219    4 VLRVVGEGSFGRALLVQHVNSDQKYAMKEIRLPKSSSaVEDSRK----EAVLLAKMKHPNIVAFKESFEADGHLYIVMEY 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 702 MENGSLDSFLRQNDGQ-FTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLeddTSDPTY 780
Cdd:cd08219   80 CDGGDLMQKIKLQRGKlFPEDTILQWFVQMCLGVQHIHEKRVLHRDIKSKNIFLTQNGKVKLGDFGSARLL---TSPGAY 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 781 TSALGGKiPIrWTAPEAIQYRKFTSASDVWSYGIVMWEVMSYgERPYWDMTNQDVINAIEQDYRLPPPMDCPSALHQLML 860
Cdd:cd08219  157 ACTYVGT-PY-YVPPEIWENMPYNNKSDIWSLGCILYELCTL-KHPFQANSWKNLILKVCQGSYKPLPSHYSYELRSLIK 233
                        250
                 ....*....|.
gi 111118978 861 DCWQKDRNHRP 871
Cdd:cd08219  234 QMFKRNPRSRP 244
STKc_myosinIII_N_like cd06608
N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze ...
625-877 1.03e-16

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: 81.58  E-value: 1.03e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKsgYTEKQRRDFLSEASIMGQF-DHPNVIHLEGVVTKSTP--------- 694
Cdd:cd06608   12 EVIGEGTYGKVYKARHKKTGQ---LAAIKIMD--IIEDEEEEIKLEINILRKFsNHPNIATFYGAFIKKDPpggddqlwl 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 695 VMiitEFMENGS---LDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFL 771
Cdd:cd06608   87 VM---EYCGGGSvtdLVKGLRKKGKRLKEEWIAYILRETLRGLAYLHENKVIHRDIKGQNILLTEEAEVKLVDFGVSAQL 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 772 eddtsdptyTSALGGK-----IPIrWTAPEAI---QYRK--FTSASDVWSYGIVMWEvMSYGERPYWDMtnqDVINAIEQ 841
Cdd:cd06608  164 ---------DSTLGRRntfigTPY-WMAPEVIacdQQPDasYDARCDVWSLGITAIE-LADGKPPLCDM---HPMRALFK 229
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|.
gi 111118978 842 DYRLPPP-MDCPS----ALHQLMLDCWQKDRNHRPKFGQIV 877
Cdd:cd06608  230 IPRNPPPtLKSPEkwskEFNDFISECLIKNYEQRPFTEELL 270
STKc_CCRK cd07832
Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the ...
678-820 1.09e-16

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: 81.61  E-value: 1.09e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 678 DHPNVIHLEGVVTKSTPVMIITEFMEnGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSN 757
Cdd:cd07832   58 GHPYVVKLRDVFPHGTGFVLVFEYML-SSLSEVLRDEERPLTEAQVKRYMRMLLKGVAYMHANRIMHRDLKPANLLISST 136
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 111118978 758 LVCKVSDFGLSRFLEDDTSDPtYTSALGgkipIRW-TAPEAIqY--RKFTSASDVWSYGIVMWEVM 820
Cdd:cd07832  137 GVLKIADFGLARLFSEEDPRL-YSHQVA----TRWyRAPELL-YgsRKYDEGVDLWAVGCIFAELL 196
STKc_Sty1_Hog1 cd07856
Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases ...
625-850 1.26e-16

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: 82.23  E-value: 1.26e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKLPGKReifVAIKTL-KSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGV-VTKSTPVMIITEFM 702
Cdd:cd07856   16 QPVGMGAFGLVCSARDQLTGQN---VAVKKImKPFSTPVLAKRTYRELKLLKHLRHENIISLSDIfISPLEDIYFVTELL 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 703 ENgSLDSFL--RQNDGQFTVIQLVGMLRGiaagMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFleddtSDPTY 780
Cdd:cd07856   93 GT-DLHRLLtsRPLEKQFIQYFLYQILRG----LKYVHSAGVIHRDLKPSNILVNENCDLKICDFGLARI-----QDPQM 162
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 111118978 781 TsalgGKIPIR-WTAPE-AIQYRKFTSASDVWSYGIVMWEvMSYGER--PYWDMTNQdviNAIEQDYRLPPPMD 850
Cdd:cd07856  163 T----GYVSTRyYRAPEiMLTWQKYDVEVDIWSAGCIFAE-MLEGKPlfPGKDHVNQ---FSIITELLGTPPDD 228
PKc_TOPK cd14001
Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer ...
651-882 1.74e-16

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


Pssm-ID: 270903 [Multi-domain]  Cd Length: 292  Bit Score: 81.29  E-value: 1.74e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 651 AIKTLKSGYTEKQRRDFLS----EASIMGQFDHPNVIHLEGVVTKSTPVMIITefMENG--SLDSFLRQ----NDGQFTV 720
Cdd:cd14001   32 AVKKINSKCDKGQRSLYQErlkeEAKILKSLNHPNIVGFRAFTKSEDGSLCLA--MEYGgkSLNDLIEEryeaGLGPFPA 109
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 721 IQLVGMLRGIAAGMKYL-ADMNYVHRDLAARNILVNSNL-VCKVSDFGLSRFLEDD---TSDPT--YTsalgGKIPirWT 793
Cdd:cd14001  110 ATILKVALSIARALEYLhNEKKILHGDIKSGNVLIKGDFeSVKLCDFGVSLPLTENlevDSDPKaqYV----GTEP--WK 183
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 794 APEAIQYRK-FTSASDVWSYGIVMWEVMS---------YGERPYWDMTNQDVINAIEQDY-RLPP----PMDCPSALHQL 858
Cdd:cd14001  184 AKEALEEGGvITDKADIFAYGLVLWEMMTlsvphlnllDIEDDDEDESFDEDEEDEEAYYgTLGTrpalNLGELDDSYQK 263
                        250       260
                 ....*....|....*....|....*...
gi 111118978 859 MLD----CWQKDRNHRPKFGQIVNTLDK 882
Cdd:cd14001  264 VIElfyaCTQEDPKDRPSAAHIVEALEA 291
PKc_MKK5 cd06619
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
621-827 1.78e-16

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


Pssm-ID: 132950 [Multi-domain]  Cd Length: 279  Bit Score: 80.69  E-value: 1.78e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQVIGAGEFGEVCSGhLKLPGKReiFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITE 700
Cdd:cd06619    3 IQYQEILGHGNGGTVYKA-YHLLTRR--ILAVKVIPLDITVELQKQIMSELEILYKCDSPYIIGFYGAFFVENRISICTE 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMENGSLDSFLRQNDGQFTVIQLvgmlrGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDpTY 780
Cdd:cd06619   80 FMDGGSLDVYRKIPEHVLGRIAV-----AVVKGLTYLWSLKILHRDVKPSNMLVNTRGQVKLCDFGVSTQLVNSIAK-TY 153
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 111118978 781 --TSAlggkipirWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPY 827
Cdd:cd06619  154 vgTNA--------YMAPERISGEQYGIHSDVWSLGISFME-LALGRFPY 193
STKc_Nek9 cd08221
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
660-887 1.83e-16

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


Pssm-ID: 270860 [Multi-domain]  Cd Length: 256  Bit Score: 80.17  E-value: 1.83e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 660 TEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGSL-DSFLRQNDGQFTVIQLVGMLRGIAAGMKYLA 738
Cdd:cd08221   39 SEKERRDALNEIDILSLLNHDNIITYYNHFLDGESLFIEMEYCNGGNLhDKIAQQKNQLFPEEVVLWYLYQIVSAVSHIH 118
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 739 DMNYVHRDLAARNI-LVNSNLVcKVSDFGLSRFLedDTSDPTYTSALGGKIpirWTAPEAIQYRKFTSASDVWSYGIVMW 817
Cdd:cd08221  119 KAGILHRDIKTLNIfLTKADLV-KLGDFGISKVL--DSESSMAESIVGTPY---YMSPELVQGVKYNFKSDIWAVGCVLY 192
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 111118978 818 EVMSYgeRPYWDMTNQ-DVINAIEQDYRLPPPMDCPSALHQLMLDCWQKDRNHRPkfgqivnTLDKMIRNP 887
Cdd:cd08221  193 ELLTL--KRTFDATNPlRLAVKIVQGEYEDIDEQYSEEIIQLVHDCLHQDPEDRP-------TAEELLERP 254
STKc_MAP4K3_like cd06613
Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like ...
622-871 1.88e-16

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: 80.43  E-value: 1.88e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKsgYTEKQRRDFL-SEASIMGQFDHPNVIHLEGVVTKSTPVMIITE 700
Cdd:cd06613    3 ELIQRIGSGTYGDVYKARNIATGE---LAAVKVIK--LEPGDDFEIIqQEISMLKECRHPNIVAYFGSYLRRDKLWIVME 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMENGSLDSFLRQNdGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLedDTSDPTY 780
Cdd:cd06613   78 YCGGGSLQDIYQVT-GPLSELQIAYVCRETLKGLAYLHSTGKIHRDIKGANILLTEDGDVKLADFGVSAQL--TATIAKR 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 781 TSALGgkIPIrWTAPEAIQYRK---FTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVINAIEQDYRLPPPMDCPS---- 853
Cdd:cd06613  155 KSFIG--TPY-WMAPEVAAVERkggYDGKCDIWALGITAIE-LAELQPPMFDLHPMRALFLIPKSNFDPPKLKDKEkwsp 230
                        250
                 ....*....|....*...
gi 111118978 854 ALHQLMLDCWQKDRNHRP 871
Cdd:cd06613  231 DFHDFIKKCLTKNPKKRP 248
STKc_MLCK3 cd14192
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze ...
625-839 2.04e-16

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: 80.39  E-value: 2.04e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEV--C---SGHLKLPGKreiFVAIKTLKsgytekQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIIT 699
Cdd:cd14192   10 EVLGGGRFGQVhkCtelSTGLTLAAK---IIKVKGAK------EREEVKNEINIMNQLNHVNLIQLYDAFESKTNLTLIM 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENGSLdsFLRQNDGQFTVIQLVGML--RGIAAGMKYLADMNYVHRDLAARNIL-VNS--NLVcKVSDFGLSRFLEdd 774
Cdd:cd14192   81 EYVDGGEL--FDRITDESYQLTELDAILftRQICEGVHYLHQHYILHLDLKPENILcVNStgNQI-KIIDFGLARRYK-- 155
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 111118978 775 tsdPTYTSALGGKIPiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAI 839
Cdd:cd14192  156 ---PREKLKVNFGTP-EFLAPEVVNYDFVSFPTDMWSVGVITYMLLS-GLSPFLGETDAETMNNI 215
STKc_MAPKAPK3 cd14172
Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated ...
624-878 2.18e-16

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 3 (MAPKAP3 or MK3) contains an N-terminal proline-rich region that can bind to SH3 domains, a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK3 is a bonafide substrate for the MAPK p38. It is closely related to MK2 and thus far, MK2/3 show indistinguishable substrate specificity. They are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. MK3 activity is only significant when MK2 is absent. The MK3 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: 271074 [Multi-domain]  Cd Length: 267  Bit Score: 80.42  E-value: 2.18e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 624 EQVIGAGEFGEVCSGHLKLPGKReifVAIKTLKSGYTEKQRRDFLSEASimgqfDHPNVIHL----EGVVTKSTPVMIIT 699
Cdd:cd14172    9 KQVLGLGVNGKVLECFHRRTGQK---CALKLLYDSPKARREVEHHWRAS-----GGPHIVHIldvyENMHHGKRCLLIIM 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENGSLDSFLRQ-NDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILV---NSNLVCKVSDFGLSR--FLED 773
Cdd:cd14172   81 ECMEGGELFSRIQErGDQAFTEREASEIMRDIGTAIQYLHSMNIAHRDVKPENLLYtskEKDAVLKLTDFGFAKetTVQN 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 774 DTSDPTYTSalggkipiRWTAPEAIQYRKFTSASDVWSYGIVMWeVMSYGERPYWDMTNQDVINAIEQ-----DYRLPPP 848
Cdd:cd14172  161 ALQTPCYTP--------YYVAPEVLGPEKYDKSCDMWSLGVIMY-ILLCGFPPFYSNTGQAISPGMKRrirmgQYGFPNP 231
                        250       260       270
                 ....*....|....*....|....*....|..
gi 111118978 849 --MDCPSALHQLMLDCWQKDRNHRPKFGQIVN 878
Cdd:cd14172  232 ewAEVSEEAKQLIRHLLKTDPTERMTITQFMN 263
STKc_BMPR1 cd14144
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type I Receptor; ...
625-883 2.30e-16

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


Pssm-ID: 271046 [Multi-domain]  Cd Length: 287  Bit Score: 80.60  E-value: 2.30e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGhlKLPGKReifVAIKTLKSgyTEKQ---RRDFLSEASIMgqfDHPNVIHLEGVVTKS----TPVMI 697
Cdd:cd14144    1 RSVGKGRYGEVWKG--KWRGEK---VAVKIFFT--TEEAswfRETEIYQTVLM---RHENILGFIAADIKGtgswTQLYL 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 698 ITEFMENGSLDSFLRQNdgqftVIQLVGMLR---GIAAGMKYLADMNY--------VHRDLAARNILVNSNLVCKVSDFG 766
Cdd:cd14144   71 ITDYHENGSLYDFLRGN-----TLDTQSMLKlaySAACGLAHLHTEIFgtqgkpaiAHRDIKSKNILVKKNGTCCIADLG 145
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 767 LS-RFL-EDDTSDPTYTSALGGKipiRWTAPEAI-------QYRKFTSAsDVWSYGIVMWEV----MSYG-----ERPYW 828
Cdd:cd14144  146 LAvKFIsETNEVDLPPNTRVGTK---RYMAPEVLdeslnrnHFDAYKMA-DMYSFGLVLWEIarrcISGGiveeyQLPYY 221
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 111118978 829 DMTNQD----VINAIEQDYRLPPPM-------DCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKM 883
Cdd:cd14144  222 DAVPSDpsyeDMRRVVCVERRRPSIpnrwssdEVLRTMSKLMSECWAHNPAARLTALRVKKTLGKL 287
PTZ00263 PTZ00263
protein kinase A catalytic subunit; Provisional
622-831 2.31e-16

protein kinase A catalytic subunit; Provisional


Pssm-ID: 140289 [Multi-domain]  Cd Length: 329  Bit Score: 81.40  E-value: 2.31e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKSG--YTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIIT 699
Cdd:PTZ00263  21 EMGETLGTGSFGRVRIAKHKGTGE---YYAIKCLKKReiLKMKQVQHVAQEKSILMELSHPFIVNMMCSFQDENRVYFLL 97
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENGSLDSFLRQ-----ND-GQFTVIQLVgmlrgiaAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRfled 773
Cdd:PTZ00263  98 EFVVGGELFTHLRKagrfpNDvAKFYHAELV-------LAFEYLHSKDIIYRDLKPENLLLDNKGHVKVTDFGFAK---- 166
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 111118978 774 DTSDPTYTsaLGGKiPiRWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWDMT 831
Cdd:PTZ00263 167 KVPDRTFT--LCGT-P-EYLAPEVIQSKGHGKAVDWWTMGVLLYE-FIAGYPPFFDDT 219
PTZ00024 PTZ00024
cyclin-dependent protein kinase; Provisional
627-821 2.40e-16

cyclin-dependent protein kinase; Provisional


Pssm-ID: 240233 [Multi-domain]  Cd Length: 335  Bit Score: 81.35  E-value: 2.40e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKReifVAIKTLK----SGYTEKQRRDF---------LSEASIMGQFDHPNVIHLEGVVTKST 693
Cdd:PTZ00024  17 LGEGTYGKVEKAYDTLTGKI---VAIKKVKiieiSNDVTKDRQLVgmcgihfttLRELKIMNEIKHENIMGLVDVYVEGD 93
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 694 PVMIITEFMENG---SLDSFLRQNDGQFTVIqLVGMLRGIAAGMKYladmNYVHRDLAARNILVNSNLVCKVSDFGLSR- 769
Cdd:PTZ00024  94 FINLVMDIMASDlkkVVDRKIRLTESQVKCI-LLQILNGLNVLHKW----YFMHRDLSPANIFINSKGICKIADFGLARr 168
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 111118978 770 ----FLEDDTSDPTYTSA---LGGKIPIRW-TAPEAIQ-YRKFTSASDVWSYGIVMWEVMS 821
Cdd:PTZ00024 169 ygypPYSDTLSKDETMQRreeMTSKVVTLWyRAPELLMgAEKYHFAVDMWSVGCIFAELLT 229
PKc_PBS2_like cd06622
Catalytic domain of fungal PBS2-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ...
627-878 2.86e-16

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


Pssm-ID: 132953 [Multi-domain]  Cd Length: 286  Bit Score: 80.28  E-value: 2.86e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVcsgHLKLPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGS 706
Cdd:cd06622    9 LGKGNYGSV---YKVLHRPTGVTMAMKEIRLELDESKFNQIIMELDILHKAVSPYIVDFYGAFFIEGAVYMCMEYMDAGS 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 707 LDSFLrqNDGQFTVIQLVGMLRGIAA----GMKYLAD-MNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSdptyT 781
Cdd:cd06622   86 LDKLY--AGGVATEGIPEDVLRRITYavvkGLKFLKEeHNIIHRDVKPTNVLVNGNGQVKLCDFGVSGNLVASLA----K 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 782 SALGGKipiRWTAPEAI------QYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVINAIEQDYRLPPPmDCPSAL 855
Cdd:cd06622  160 TNIGCQ---SYMAPERIksggpnQNPTYTVQSDVWSLGLSILE-MALGRYPYPPETYANIFAQLSAIVDGDPP-TLPSGY 234
                        250       260
                 ....*....|....*....|....*..
gi 111118978 856 HQLMLD----CWQKDRNHRPKFGQIVN 878
Cdd:cd06622  235 SDDAQDfvakCLNKIPNRRPTYAQLLE 261
STKc_Kin1_2 cd14077
Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the ...
627-829 2.87e-16

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: 79.80  E-value: 2.87e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKReifVAIK----TLKSGYTEKQRRDFLS----------EASIMGQFDHPNVIHLEGVVTKS 692
Cdd:cd14077    9 IGAGSMGKVKLAKHIRTGEK---CAIKiiprASNAGLKKEREKRLEKeisrdirtirEAALSSLLNHPHICRLRDFLRTP 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 693 TPVMIITEFMENGSLDSFLRQNdGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLE 772
Cdd:cd14077   86 NHYYMLFEYVDGGQLLDYIISH-GKLKEKQARKFARQIASALDYLHRNSIVHRDLKIENILISKSGNIKIIDFGLSNLYD 164
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 111118978 773 DDTSDPTYTSALggkipiRWTAPEAIQYRKFTSAS-DVWSYGIVMWeVMSYGERPYWD 829
Cdd:cd14077  165 PRRLLRTFCGSL------YFAAPELLQAQPYTGPEvDVWSFGVVLY-VLVCGKVPFDD 215
STKc_ACVR1_ALK1 cd14142
Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin ...
610-883 3.57e-16

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


Pssm-ID: 271044 [Multi-domain]  Cd Length: 298  Bit Score: 80.18  E-value: 3.57e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 610 REFAKEIDIscvkIEQvIGAGEFGEVCSGHLKlpGKReifVAIKTLKSGYTEKQRRDFLSEASIMgqFDHPNVIHLEG-- 687
Cdd:cd14142    1 RTVARQITL----VEC-IGKGRYGEVWRGQWQ--GES---VAVKIFSSRDEKSWFRETEIYNTVL--LRHENILGFIAsd 68
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 688 --VVTKSTPVMIITEFMENGSLDSFLrqndgQFTVIQLVGMLR---GIAAGMKYLADMNY--------VHRDLAARNILV 754
Cdd:cd14142   69 mtSRNSCTQLWLITHYHENGSLYDYL-----QRTTLDHQEMLRlalSAASGLVHLHTEIFgtqgkpaiAHRDLKSKNILV 143
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 755 NSNLVCKVSDFGLS--RFLEDDTSDPTYTSALGGKipiRWTAP----EAIQYRKFTS--ASDVWSYGIVMWEV----MSY 822
Cdd:cd14142  144 KSNGQCCIADLGLAvtHSQETNQLDVGNNPRVGTK---RYMAPevldETINTDCFESykRVDIYAFGLVLWEVarrcVSG 220
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 111118978 823 G-----ERPYWDMTNQD-------VINAIEQdYRLPPPM-----DCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKM 883
Cdd:cd14142  221 GiveeyKPPFYDVVPSDpsfedmrKVVCVDQ-QRPNIPNrwssdPTLTAMAKLMKECWYQNPSARLTALRIKKTLLKI 297
STKc_PAK4 cd06657
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the ...
627-849 3.78e-16

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK4 regulates cell morphology and cytoskeletal organization. It is essential for embryonic viability and proper neural development. Mice lacking PAK4 die due to defects in the fetal heart. In addition, their spinal cord motor neurons showed failure to differentiate and migrate. PAK4 also plays a role in cell survival and tumorigenesis. It is overexpressed in many primary tumors including colon, esophageal, and mammary tumors. PAK4 has also been implicated in viral and bacterial infection pathways. PAK4 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132988 [Multi-domain]  Cd Length: 292  Bit Score: 80.07  E-value: 3.78e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKreiFVAIKtlKSGYTEKQRRDFL-SEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENG 705
Cdd:cd06657   28 IGEGSTGIVCIATVKSSGK---LVAVK--KMDLRKQQRRELLfNEVVIMRDYQHENVVEMYNSYLVGDELWVVMEFLEGG 102
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 706 SLDSFL---RQNDGQFTVIQLvgmlrGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTsdPTYTS 782
Cdd:cd06657  103 ALTDIVthtRMNEEQIAAVCL-----AVLKALSVLHAQGVIHRDIKSDSILLTHDGRVKLSDFGFCAQVSKEV--PRRKS 175
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 111118978 783 ALGGKIpirWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVINAIEQDyrLPPPM 849
Cdd:cd06657  176 LVGTPY---WMAPELISRLPYGPEVDIWSLGIMVIE-MVDGEPPYFNEPPLKAMKMIRDN--LPPKL 236
PHA03209 PHA03209
serine/threonine kinase US3; Provisional
648-822 3.82e-16

serine/threonine kinase US3; Provisional


Pssm-ID: 177557 [Multi-domain]  Cd Length: 357  Bit Score: 81.08  E-value: 3.82e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 648 IFVAIK-------TLKSGytekQRRDFLSEASIMGQFDHPNVIHL-EGVVTKSTPVMIITEFmeNGSLDSFLRQNDGQFT 719
Cdd:PHA03209  82 VFVATKpgqpdpvVLKIG----QKGTTLIEAMLLQNVNHPSVIRMkDTLVSGAITCMVLPHY--SSDLYTYLTKRSRPLP 155
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 720 VIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNS-NLVCkVSDFGLSRFledDTSDPTYtsaLGGKIPIRWTAPEAI 798
Cdd:PHA03209 156 IDQALIIEKQILEGLRYLHAQRIIHRDVKTENIFINDvDQVC-IGDLGAAQF---PVVAPAF---LGLAGTVETNAPEVL 228
                        170       180
                 ....*....|....*....|....
gi 111118978 799 QYRKFTSASDVWSYGIVMWEVMSY 822
Cdd:PHA03209 229 ARDKYNSKADIWSAGIVLFEMLAY 252
STKc_WNK cd13983
Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze ...
657-832 3.91e-16

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: 79.19  E-value: 3.91e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 657 SGYTEKQRRDFLSEASIMGQFDHPNVI----HLEGVVTKStpVMIITEFMENGSLDSFLRqndgQFTVIQ---LVGMLRG 729
Cdd:cd13983   37 RKLPKAERQRFKQEIEILKSLKHPNIIkfydSWESKSKKE--VIFITELMTSGTLKQYLK----RFKRLKlkvIKSWCRQ 110
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 730 IAAGMKYLADMNY--VHRDLAARNILVNSNL-VCKVSDFGLSRFLEDDTSdptyTSALGgkIPiRWTAPEAIQyRKFTSA 806
Cdd:cd13983  111 ILEGLNYLHTRDPpiIHRDLKCDNIFINGNTgEVKIGDLGLATLLRQSFA----KSVIG--TP-EFMAPEMYE-EHYDEK 182
                        170       180
                 ....*....|....*....|....*.
gi 111118978 807 SDVWSYGIVMWEvMSYGERPYWDMTN 832
Cdd:cd13983  183 VDIYAFGMCLLE-MATGEYPYSECTN 207
STKc_PRKX_like cd05612
Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of ...
627-839 4.46e-16

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


Pssm-ID: 270763 [Multi-domain]  Cd Length: 292  Bit Score: 79.79  E-value: 4.46e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKreiFVAIKTLKsgYTE----KQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFM 702
Cdd:cd05612    9 IGTGTFGRVHLVRDRISEH---YYALKVMA--IPEvirlKQEQHVHNEKRVLKEVSHPFIIRLFWTEHDQRFLYMLMEYV 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 703 ENGSLDSFLRqNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLeddtSDPTYTs 782
Cdd:cd05612   84 PGGELFSYLR-NSGRFSNSTGLFYASEIVCALEYLHSKEIVYRDLKPENILLDKEGHIKLTDFGFAKKL----RDRTWT- 157
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 111118978 783 aLGGKiPiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAI 839
Cdd:cd05612  158 -LCGT-P-EYLAPEVIQSKGHNKAVDWWALGILIYEMLV-GYPPFFDDNPFGIYEKI 210
STKc_ASK cd06624
Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase; STKs ...
611-832 4.83e-16

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: 79.37  E-value: 4.83e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 611 EFAKEIDISCVKIeqVIGAGEFGEVCSGHLKLPGKReifVAIKTLKsgytEKQRRDFLS---EASIMGQFDHPNVIHLEG 687
Cdd:cd06624    2 EYEYEYDESGERV--VLGKGTFGVVYAARDLSTQVR---IAIKEIP----ERDSREVQPlheEIALHSRLSHKNIVQYLG 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 688 VVTKSTPVMIITEFMENGSLDSFLRQNDGQF----TVIQLVGmlRGIAAGMKYLADMNYVHRDLAARNILVNS-NLVCKV 762
Cdd:cd06624   73 SVSEDGFFKIFMEQVPGGSLSALLRSKWGPLkdneNTIGYYT--KQILEGLKYLHDNKIVHRDIKGDNVLVNTySGVVKI 150
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 111118978 763 SDFGLSRFLEDdtSDPtYTSALGGKipIRWTAPEAIQY--RKFTSASDVWSYGIVMWEvMSYGERPYWDMTN 832
Cdd:cd06624  151 SDFGTSKRLAG--INP-CTETFTGT--LQYMAPEVIDKgqRGYGPPADIWSLGCTIIE-MATGKPPFIELGE 216
PK_IRAK3 cd14160
Pseudokinase domain of Interleukin-1 Receptor Associated Kinase 3; The pseudokinase domain ...
627-881 4.94e-16

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: 79.54  E-value: 4.94e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLklpGKREIFVAI-KTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENG 705
Cdd:cd14160    1 IGEGEIFEVYRVRI---GNRSYAVKLfKQEKKMQWKKHWKRFLSELEVLLLFQHPNILELAAYFTETEKFCLVYPYMQNG 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 706 SLDSFLRQNDGQ--FTVIQLVGMLRGIAAGMKYLADMN---YVHRDLAARNILVNSNLVCKVSDFGLSRF---LEDDTSD 777
Cdd:cd14160   78 TLFDRLQCHGVTkpLSWHERINILIGIAKAIHYLHNSQpctVICGNISSANILLDDQMQPKLTDFALAHFrphLEDQSCT 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 778 PTYTSALGGKIpirWTAPEA-IQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTN----QDVINAIEQ----------- 841
Cdd:cd14160  158 INMTTALHKHL---WYMPEEyIRQGKLSVKTDVYSFGIVIMEVLT-GCKVVLDDPKhlqlRDLLHELMEkrgldsclsfl 233
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|.
gi 111118978 842 DYRLPP-PMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLD 881
Cdd:cd14160  234 DLKFPPcPRNFSAKLFRLAGRCTATKAKLRPDMDEVLQRLE 274
STKc_TEY_MAPK cd07858
Catalytic domain of the Serine/Threonine Kinases, Plant TEY Mitogen-Activated Protein Kinases; ...
627-820 5.24e-16

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: 80.49  E-value: 5.24e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKReifVAIKTLKSGYTEK--QRRDfLSEASIMGQFDHPNVIHLEGVVTKS-----TPVMIIT 699
Cdd:cd07858   13 IGRGAYGIVCSAKNSETNEK---VAIKKIANAFDNRidAKRT-LREIKLLRHLDHENVIAIKDIMPPPhreafNDVYIVY 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENgSLDSFLRQNDG------QFTVIQLvgmLRGiaagMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRfLED 773
Cdd:cd07858   89 ELMDT-DLHQIIRSSQTlsddhcQYFLYQL---LRG----LKYIHSANVLHRDLKPSNLLLNANCDLKICDFGLAR-TTS 159
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 111118978 774 DTSD--PTYtsalggkIPIRW-TAPEAI-QYRKFTSASDVWSYGIVMWEVM 820
Cdd:cd07858  160 EKGDfmTEY-------VVTRWyRAPELLlNCSEYTTAIDVWSVGCIFAELL 203
STKc_BMPR1a cd14220
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IA Receptor; ...
627-883 5.62e-16

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: 79.70  E-value: 5.62e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGhlKLPGKReifVAIKTlksgYTEKQRRDFLSEASIMGQ--FDHPNVIHLEGVVTK----STPVMIITE 700
Cdd:cd14220    3 IGKGRYGEVWMG--KWRGEK---VAVKV----FFTTEEASWFRETEIYQTvlMRHENILGFIAADIKgtgsWTQLYLITD 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMENGSLDSFLRqndgqFTVIQLVGMLR---GIAAGMKYLADMNY--------VHRDLAARNILVNSNLVCKVSDFGLSR 769
Cdd:cd14220   74 YHENGSLYDFLK-----CTTLDTRALLKlaySAACGLCHLHTEIYgtqgkpaiAHRDLKSKNILIKKNGTCCIADLGLAV 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 770 FLEDDTS--DPTYTSALGGKipiRWTAPEAI-------QYRKFTSAsDVWSYGIVMWE---------VMSYGERPYWDMT 831
Cdd:cd14220  149 KFNSDTNevDVPLNTRVGTK---RYMAPEVLdeslnknHFQAYIMA-DIYSFGLIIWEmarrcvtggIVEEYQLPYYDMV 224
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 111118978 832 NQDV----INAIEQDYRLPPPM-------DCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKM 883
Cdd:cd14220  225 PSDPsyedMREVVCVKRLRPTVsnrwnsdECLRAVLKLMSECWAHNPASRLTALRIKKTLAKM 287
STKc_DRAK cd14106
Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
627-841 5.84e-16

Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs, also called STK17, were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. They may play a role in apoptotic signaling. The DRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271008 [Multi-domain]  Cd Length: 268  Bit Score: 78.93  E-value: 5.84e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKReifVAIKTLKsgyteKQRR--DFLSE-----ASIMGQFDHPNVIHLEGVVTKSTPVMIIT 699
Cdd:cd14106   16 LGRGKFAVVRKCIHKETGKE---YAAKFLR-----KRRRgqDCRNEilheiAVLELCKDCPRVVNLHEVYETRSELILIL 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENGSLDSFLrQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVC---KVSDFGLSRFLEDdts 776
Cdd:cd14106   88 ELAAGGELQTLL-DEEECLTEADVRRLMRQILEGVQYLHERNIVHLDLKPQNILLTSEFPLgdiKLCDFGISRVIGE--- 163
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 111118978 777 dptytsalggKIPIR-------WTAPEAIQYRKFTSASDVWSYGIVMWeVMSYGERPYWDMTNQDVINAIEQ 841
Cdd:cd14106  164 ----------GEEIReilgtpdYVAPEILSYEPISLATDMWSIGVLTY-VLLTGHSPFGGDDKQETFLNISQ 224
STKc_IRE1 cd13982
Catalytic domain of the Serine/Threonine kinase, Inositol-requiring protein 1; STKs catalyze ...
678-871 7.02e-16

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: 78.85  E-value: 7.02e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 678 DHPNVIHLEGVVTKSTPVMIITEFMeNGSLDSFLRQ----NDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNIL 753
Cdd:cd13982   53 EHPNVIRYFCTEKDRQFLYIALELC-AASLQDLVESpresKLFLRPGLEPVRLLRQIASGLAHLHSLNIVHRDLKPQNIL 131
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 754 V-----NSNLVCKVSDFGLSRFLEDDTSDPTYTSALGGKIPirWTAPEAI---QYRKFTSASDVWSYGIVMWEVMSYGER 825
Cdd:cd13982  132 IstpnaHGNVRAMISDFGLCKKLDVGRSSFSRRSGVAGTSG--WIAPEMLsgsTKRRQTRAVDIFSLGCVFYYVLSGGSH 209
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 111118978 826 PYWDMTNQDViNAIEQDYRLPPPMD---CPSALHQLMLDCWQKDRNHRP 871
Cdd:cd13982  210 PFGDKLEREA-NILKGKYSLDKLLSlgeHGPEAQDLIERMIDFDPEKRP 257
STKc_CaMKI_gamma cd14166
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
625-843 7.59e-16

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: 79.27  E-value: 7.59e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGYTEKQRrDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMEN 704
Cdd:cd14166    9 EVLGSGAFSEVYLVKQRSTGK---LYALKCIKKSPLSRDS-SLENEIAVLKRIKHENIVTLEDIYESTTHYYLVMQLVSG 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 705 GSL-DSFLRQndGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILV---NSNLVCKVSDFGLSRfLEDDTSDPTY 780
Cdd:cd14166   85 GELfDRILER--GVYTEKDASRVINQVLSAVKYLHENGIVHRDLKPENLLYltpDENSKIMITDFGLSK-MEQNGIMSTA 161
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 111118978 781 TSALGgkipirWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAIEQDY 843
Cdd:cd14166  162 CGTPG------YVAPEVLAQKPYSKAVDCWSIGVITYILLC-GYPPFYEETESRLFEKIKEGY 217
PKc_MKK3_6 cd06617
Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase ...
647-876 7.82e-16

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


Pssm-ID: 173729 [Multi-domain]  Cd Length: 283  Bit Score: 79.01  E-value: 7.82e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 647 EIFVAIKTLKSGYTEKQRRDFLSEASI-MGQFDHPNVIHLEGVVTKSTPVMIITEFMENgSLDSFLRQ--NDGQFTVIQL 723
Cdd:cd06617   26 GTIMAVKRIRATVNSQEQKRLLMDLDIsMRSVDCPYTVTFYGALFREGDVWICMEVMDT-SLDKFYKKvyDKGLTIPEDI 104
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 724 VG-MLRGIAAGMKYL-ADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDptyTSALGGKipiRWTAPEAI--- 798
Cdd:cd06617  105 LGkIAVSIVKALEYLhSKLSVIHRDVKPSNVLINRNGQVKLCDFGISGYLVDSVAK---TIDAGCK---PYMAPERInpe 178
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 799 -QYRKFTSASDVWSYGIVMWEvMSYGERPY--WDMTNQDVINAIEQDyrlPP--PMDCPSALHQLMLDCW-QKDRNHRPK 872
Cdd:cd06617  179 lNQKGYDVKSDVWSLGITMIE-LATGRFPYdsWKTPFQQLKQVVEEP---SPqlPAEKFSPEFQDFVNKClKKNYKERPN 254

                 ....
gi 111118978 873 FGQI 876
Cdd:cd06617  255 YPEL 258
STKc_MLCK4 cd14193
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze ...
621-839 8.16e-16

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: 78.42  E-value: 8.16e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQVIGAGEFGEVCSGHLKLPGkreIFVAIKTLKSgYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITE 700
Cdd:cd14193    6 VNKEEILGGGRFGQVHKCEEKSSG---LKLAAKIIKA-RSQKEKEEVKNEIEVMNQLNHANLIQLYDAFESRNDIVLVME 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMENGSLdsFLRQNDGQFTVIQL--VGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLV--CKVSDFGLSRFLEddts 776
Cdd:cd14193   82 YVDGGEL--FDRIIDENYNLTELdtILFIKQICEGIQYMHQMYILHLDLKPENILCVSREAnqVKIIDFGLARRYK---- 155
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 111118978 777 dPTYTSALGGKIPiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAI 839
Cdd:cd14193  156 -PREKLRVNFGTP-EFLAPEVVNYEFVSFPTDMWSLGVIAYMLLS-GLSPFLGEDDNETLNNI 215
STKc_p38beta cd07878
Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase ...
627-820 8.62e-16

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: 80.09  E-value: 8.62e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGH-LKLPGKreifVAIKTLKSGYTE--KQRRDFlSEASIMGQFDHPNVIHLEGVVTKSTP------VMI 697
Cdd:cd07878   23 VGSGAYGSVCSAYdTRLRQK----VAVKKLSRPFQSliHARRTY-RELRLLKHMKHENVIGLLDVFTPATSienfneVYL 97
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 698 ITEFM--ENGSLDSFLRQNDG--QFTVIQLvgmLRGiaagMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLED 773
Cdd:cd07878   98 VTNLMgaDLNNIVKCQKLSDEhvQFLIYQL---LRG----LKYIHSAGIIHRDLKPSNVAVNEDCELRILDFGLARQADD 170
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 111118978 774 DTSdptytsalgGKIPIRW-TAPE-AIQYRKFTSASDVWSYGIVMWEVM 820
Cdd:cd07878  171 EMT---------GYVATRWyRAPEiMLNWMHYNQTVDIWSVGCIMAELL 210
STKc_p38alpha cd07877
Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase ...
627-848 9.63e-16

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: 79.70  E-value: 9.63e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKReifVAIKTLKSGYTE--KQRRDFlSEASIMGQFDHPNVIHLEGVVTKSTP------VMII 698
Cdd:cd07877   25 VGSGAYGSVCAAFDTKTGLR---VAVKKLSRPFQSiiHAKRTY-RELRLLKHMKHENVIGLLDVFTPARSleefndVYLV 100
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 699 TEFMeNGSLDSF-----LRQNDGQFTVIQLvgmLRGiaagMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLED 773
Cdd:cd07877  101 THLM-GADLNNIvkcqkLTDDHVQFLIYQI---LRG----LKYIHSADIIHRDLKPSNLAVNEDCELKILDFGLARHTDD 172
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 774 DTSdptytsalgGKIPIRW-TAPE-AIQYRKFTSASDVWSYGIVMWEVMSygERPYWDMTnqDVINAIEQDYRL---PPP 848
Cdd:cd07877  173 EMT---------GYVATRWyRAPEiMLNWMHYNQTVDIWSVGCIMAELLT--GRTLFPGT--DHIDQLKLILRLvgtPGA 239
STKc_CDK9 cd07865
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs ...
611-818 1.05e-15

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: 78.95  E-value: 1.05e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 611 EFAKEIDISCVKIEQVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKsgyTEKQRRDF----LSEASIMGQFDHPNVIHL- 685
Cdd:cd07865    4 EFPFCDEVSKYEKLAKIGQGTFGEVFKARHRKTGQ---IVALKKVL---MENEKEGFpitaLREIKILQLLKHENVVNLi 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 686 EGVVTKSTP-------VMIITEFMENgSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNL 758
Cdd:cd07865   78 EICRTKATPynrykgsIYLVFEFCEH-DLAGLLSNKNVKFTLSEIKKVMKMLLNGLYYIHRNKILHRDMKAANILITKDG 156
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 111118978 759 VCKVSDFGLSR-FLEDDTSDPT-YTsalgGKIPIRW-TAPE-AIQYRKFTSASDVWSYGIVMWE 818
Cdd:cd07865  157 VLKLADFGLARaFSLAKNSQPNrYT----NRVVTLWyRPPElLLGERDYGPPIDMWGAGCIMAE 216
STKc_TLK cd13990
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase; STKs catalyze the ...
627-836 1.28e-15

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: 78.13  E-value: 1.28e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGhLKLPGKREIFVAIKTLKSGYTEKQRRDF----LSEASIMGQFDHPNVIHLEGVVTKSTPVMI-ITEF 701
Cdd:cd13990    8 LGKGGFSEVYKA-FDLVEQRYVACKIHQLNKDWSEEKKQNYikhaLREYEIHKSLDHPRIVKLYDVFEIDTDSFCtVLEY 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 702 MENGSLDSFLRQNdGQFTVIQLVGMLRGIAAGMKYLADMN--YVHRDLAARNILVNSNLVC---KVSDFGLSRFLEDDTS 776
Cdd:cd13990   87 CDGNDLDFYLKQH-KSIPEREARSIIMQVVSALKYLNEIKppIIHYDLKPGNILLHSGNVSgeiKITDFGLSKIMDDESY 165
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 111118978 777 DPT---YTSALGGKIpirWTAPEAI-----QYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVI 836
Cdd:cd13990  166 NSDgmeLTSQGAGTY---WYLPPECfvvgkTPPKISSKVDVWSVGVIFYQ-MLYGRKPFGHNQSQEAI 229
STKc_TAO cd06607
Catalytic domain of the Serine/Threonine Kinases, Thousand-and-One Amino acids proteins; STKs ...
627-871 1.37e-15

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: 77.88  E-value: 1.37e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLpgKREIfVAIKtlKSGYTEKQR----RDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFM 702
Cdd:cd06607    9 IGHGSFGAVYYARNKR--TSEV-VAIK--KMSYSGKQStekwQDIIKEVKFLRQLRHPNTIEYKGCYLREHTAWLVMEYC 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 703 EnGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLeddtsDPTyTS 782
Cdd:cd06607   84 L-GSASDIVEVHKKPLQEVEIAAICHGALQGLAYLHSHNRIHRDVKAGNILLTEPGTVKLADFGSASLV-----CPA-NS 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 783 ALGgkIPIrWTAPEAI------QYrkfTSASDVWSYGIVMWEVmsyGER--PYWDMTNQDVINAIEQDYrlPP---PMDC 851
Cdd:cd06607  157 FVG--TPY-WMAPEVIlamdegQY---DGKVDVWSLGITCIEL---AERkpPLFNMNAMSALYHIAQND--SPtlsSGEW 225
                        250       260
                 ....*....|....*....|
gi 111118978 852 PSALHQLMLDCWQKDRNHRP 871
Cdd:cd06607  226 SDDFRNFVDSCLQKIPQDRP 245
PKc_MKK7 cd06618
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
615-876 1.43e-15

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


Pssm-ID: 270791 [Multi-domain]  Cd Length: 295  Bit Score: 78.57  E-value: 1.43e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 615 EIDISCVKIEQVIGAGEFGEVCSGHLKLPGKreiFVAIKTL-KSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKST 693
Cdd:cd06618   11 KADLNDLENLGEIGSGTCGQVYKMRHKKTGH---VMAVKQMrRSGNKEENKRILMDLDVVLKSHDCPYIVKCYGYFITDS 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 694 PVMIITEFMENgSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADM-NYVHRDLAARNILVNSNLVCKVSDFGLSRFLE 772
Cdd:cd06618   88 DVFICMELMST-CLDKLLKRIQGPIPEDILGKMTVSIVKALHYLKEKhGVIHRDVKPSNILLDESGNVKLCDFGISGRLV 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 773 DDTSdptYTSALGGKIpirWTAPEAIQYRKFTS---ASDVWSYGIVMWEVMSyGERPYWDM-TNQDVINAIEQDY--RLP 846
Cdd:cd06618  167 DSKA---KTRSAGCAA---YMAPERIDPPDNPKydiRADVWSLGISLVELAT-GQFPYRNCkTEFEVLTKILNEEppSLP 239
                        250       260       270
                 ....*....|....*....|....*....|
gi 111118978 847 PPMDCPSALHQLMLDCWQKDRNHRPKFGQI 876
Cdd:cd06618  240 PNEGFSPDFCSFVDLCLTKDHRYRPKYREL 269
STKc_LRRK2 cd14068
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze ...
626-881 1.85e-15

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: 77.30  E-value: 1.85e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 626 VIGAGEFGEVCSGHLKlpgKREifVAIKTLKSGYTEKQRRdflSEASIMGQFDHPNVIHLegVVTKSTPVMIITEFMENG 705
Cdd:cd14068    1 LLGDGGFGSVYRAVYR---GED--VAVKIFNKHTSFRLLR---QELVVLSHLHHPSLVAL--LAAGTAPRMLVMELAPKG 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 706 SLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILV-----NSNLVCKVSDFGLSRfleddtsdptY 780
Cdd:cd14068   71 SLDALLQQDNASLTRTLQHRIALHVADGLRYLHSAMIIYRDLKPHNVLLftlypNCAIIAKIADYGIAQ----------Y 140
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 781 TSALGGKI---PIRWTAPEAIQYR-KFTSASDVWSYGIVMWEVMSYGERPYWDMTNQDVINAIEQDYRLPPPM---DCP- 852
Cdd:cd14068  141 CCRMGIKTsegTPGFRAPEVARGNvIYNQQADVYSFGLLLYDILTCGERIVEGLKFPNEFDELAIQGKLPDPVkeyGCAp 220
                        250       260       270
                 ....*....|....*....|....*....|
gi 111118978 853 -SALHQLMLDCWQKDRNHRPKFGQIVNTLD 881
Cdd:cd14068  221 wPGVEALIKDCLKENPQCRPTSAQVFDILN 250
FN3 cd00063
Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein ...
436-527 1.98e-15

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.


Pssm-ID: 238020 [Multi-domain]  Cd Length: 93  Bit Score: 72.53  E-value: 1.98e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 436 PSAVSIMHQVSRTVDSITLSWSQPDQPNGVILDYELQYYEKELSEY-NATAIKSPTNTVTVQGLKAGAIYVFQVRARTVA 514
Cdd:cd00063    1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGDWkEVEVTPGSETSYTLTGLKPGTEYEFRVRAVNGG 80
                         90
                 ....*....|...
gi 111118978 515 GYGRYSGKMYFQT 527
Cdd:cd00063   81 GESPPSESVTVTT 93
STKc_Nek4 cd08223
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
625-819 2.07e-15

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: 77.09  E-value: 2.07e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKLPGKREIFVAIKTLKSgyTEKQRRDFLSEASIMGQFDHPNVI-HLEGVVTKSTPVMIITEFME 703
Cdd:cd08223    6 RVIGKGSYGEVWLVRHKRDRKQYVIKKLNLKNA--SKRERKAAEQEAKLLSKLKHPNIVsYKESFEGEDGFLYIVMGFCE 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 704 NGSLDSFLRQNDGQ-FTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEddTSDPTYTS 782
Cdd:cd08223   84 GGDLYTRLKEQKGVlLEERQVVEWFVQIAMALQYMHERNILHRDLKTQNIFLTKSNIIKVGDLGIARVLE--SSSDMATT 161
                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 111118978 783 ALGgkIPIrWTAPEAIQYRKFTSASDVWSYGIVMWEV 819
Cdd:cd08223  162 LIG--TPY-YMSPELFSNKPYNHKSDVWALGCCVYEM 195
STKc_Rad53_Cds1 cd14098
Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the ...
623-878 2.10e-15

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: 77.52  E-value: 2.10e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 623 IEQVIGAGEFGEVCSGHLKLPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFM 702
Cdd:cd14098    4 IIDRLGSGTFAEVKKAVEVETGKMRAIKQIVKRKVAGNDKNLQLFQREINILKSLEHPGIVRLIDWYEDDQHIYLVMEYV 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 703 ENGSLDSFLRQNDGqftVIQLVG--MLRGIAAGMKYLADMNYVHRDLAARNILVNSN--LVCKVSDFGLSRFLEDDTSDP 778
Cdd:cd14098   84 EGGDLMDFIMAWGA---IPEQHAreLTKQILEAMAYTHSMGITHRDLKPENILITQDdpVIVKISDFGLAKVIHTGTFLV 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 779 TYTSALGgkipirWTAPEAIQYRK------FTSASDVWSYGIVMWeVMSYGERPYWDMTNQDVINAIEQ-DYRLPPPMD- 850
Cdd:cd14098  161 TFCGTMA------YLAPEILMSKEqnlqggYSNLVDMWSVGCLVY-VMLTGALPFDGSSQLPVEKRIRKgRYTQPPLVDf 233
                        250       260       270
                 ....*....|....*....|....*....|
gi 111118978 851 --CPSALhQLMLDCWQKDRNHRPKFGQIVN 878
Cdd:cd14098  234 niSEEAI-DFILRLLDVDPEKRMTAAQALD 262
STKc_PLK4 cd14186
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the ...
622-846 2.47e-15

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: 76.82  E-value: 2.47e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKLPGkreIFVAIKTL------KSGYTEKQRrdflSEASIMGQFDHPNVIHLEGVVTKSTPV 695
Cdd:cd14186    4 KVLNLLGKGSFACVYRARSLHTG---LEVAIKMIdkkamqKAGMVQRVR----NEVEIHCQLKHPSILELYNYFEDSNYV 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 696 MIITEFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEddT 775
Cdd:cd14186   77 YLVLEMCHNGEMSRYLKNRKKPFTEDEARHFMHQIVTGMLYLHSHGILHRDLTLSNLLLTRNMNIKIADFGLATQLK--M 154
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 111118978 776 SDPTYTSALGGKipiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAIE-QDYRLP 846
Cdd:cd14186  155 PHEKHFTMCGTP---NYISPEIATRSAHGLESDVWSLGCMFYTLLV-GRPPFDTDTVKNTLNKVVlADYEMP 222
STKc_CDK12 cd07864
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs ...
626-833 3.30e-15

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: 77.54  E-value: 3.30e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 626 VIGAGEFGEVCSGHLKLPGKreiFVAIKTLKsgyTEKQRRDF----LSEASIMGQFDHPNVIHLEGVVTKSTPVM----- 696
Cdd:cd07864   14 IIGEGTYGQVYKAKDKDTGE---LVALKKVR---LDNEKEGFpitaIREIKILRQLNHRSVVNLKEIVTDKQDALdfkkd 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 697 -----IITEFMEN---GSLDSFLRQndgqFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLS 768
Cdd:cd07864   88 kgafyLVFEYMDHdlmGLLESGLVH----FSEDHIKSFMKQLLEGLNYCHKKNFLHRDIKCSNILLNNKGQIKLADFGLA 163
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 111118978 769 RFLEDDTSDPtYTSALggkIPIRWTAPE-AIQYRKFTSASDVWSYGIVMWEVmsYGERPYWDMTNQ 833
Cdd:cd07864  164 RLYNSEESRP-YTNKV---ITLWYRPPElLLGEERYGPAIDVWSCGCILGEL--FTKKPIFQANQE 223
STKc_LRRK1 cd14067
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 1; STKs catalyze ...
652-877 3.33e-15

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


Pssm-ID: 270969 [Multi-domain]  Cd Length: 276  Bit Score: 76.93  E-value: 3.33e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 652 IKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKstPVMIITEFMENGSLDSFLRQNDGQFTVIQLVGMLR--- 728
Cdd:cd14067   42 LKHLRAADAMKNFSEFRQEASMLHSLQHPCIVYLIGISIH--PLCFALELAPLGSLNTVLEENHKGSSFMPLGHMLTfki 119
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 729 --GIAAGMKYLADMNYVHRDLAARNILVNS-----NLVCKVSDFGLSRfleddtsDPTYTSALGGKIPIRWTAPEAIQYR 801
Cdd:cd14067  120 ayQIAAGLAYLHKKNIIFCDLKSDNILVWSldvqeHINIKLSDYGISR-------QSFHEGALGVEGTPGYQAPEIRPRI 192
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 802 KFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAIEQDYRlpPPMDCPSA-----LHQLMLDCWQKDRNHRPKFGQI 876
Cdd:cd14067  193 VYDEKVDMFSYGMVLYELLS-GQRPSLGHHQLQIAKKLSKGIR--PVLGQPEEvqffrLQALMMECWDTKPEKRPLACSV 269

                 .
gi 111118978 877 V 877
Cdd:cd14067  270 V 270
STKc_RSK1_C cd14175
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 1 (also called ...
623-827 3.39e-15

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


Pssm-ID: 271077 [Multi-domain]  Cd Length: 291  Bit Score: 77.37  E-value: 3.39e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 623 IEQVIGAGEFgEVCSGHLKLPGKREifVAIKTLksgytEKQRRDFLSEASIMGQF-DHPNVIHLEGVVTKSTPVMIITEF 701
Cdd:cd14175    5 VKETIGVGSY-SVCKRCVHKATNME--YAVKVI-----DKSKRDPSEEIEILLRYgQHPNIITLKDVYDDGKHVYLVTEL 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 702 MENGS-LDSFLRQNdgQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILV---NSNLVC-KVSDFGLSRFLEDDTS 776
Cdd:cd14175   77 MRGGElLDKILRQK--FFSEREASSVLHTICKTVEYLHSQGVVHRDLKPSNILYvdeSGNPESlRICDFGFAKQLRAENG 154
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 111118978 777 ---DPTYTSalggkipiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPY 827
Cdd:cd14175  155 llmTPCYTA--------NFVAPEVLKRQGYDEGCDIWSLGILLYTMLA-GYTPF 199
STKc_Nek1 cd08218
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
621-877 3.55e-15

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: 76.39  E-value: 3.55e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQvIGAGEFGEVCSGHLKLPGKREIFVAIKTLKsgYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITE 700
Cdd:cd08218    3 VRIKK-IGEGSFGKALLVKSKEDGKQYVIKEINISK--MSPKEREESRKEVAVLSKMKHPNIVQYQESFEENGNLYIVMD 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMENGSLDSFLRQNDG-QFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTS--- 776
Cdd:cd08218   80 YCDGGDLYKRINAQRGvLFPEDQILDWFVQLCLALKHVHDRKILHRDIKSQNIFLTKDGIIKLGDFGIARVLNSTVElar 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 777 ----DPTYTSalggkipirwtaPEAIQYRKFTSASDVWSYGIVMWEVMSYgERPY--WDMTNQdVINAIEQDYrlPP-PM 849
Cdd:cd08218  160 tcigTPYYLS------------PEICENKPYNNKSDIWALGCVLYEMCTL-KHAFeaGNMKNL-VLKIIRGSY--PPvPS 223
                        250       260
                 ....*....|....*....|....*...
gi 111118978 850 DCPSALHQLMLDCWQKDRNHRPKFGQIV 877
Cdd:cd08218  224 RYSYDLRSLVSQLFKRNPRDRPSINSIL 251
PKc_Myt1 cd14050
Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze ...
620-826 3.61e-15

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: 76.19  E-value: 3.61e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 620 CVKIEQVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGY-TEKQRRDFLSEASIMGQF-DHPNVIHLEGVVTKSTPVMI 697
Cdd:cd14050    2 CFTILSKLGEGSFGEVFKVRSREDGK---LYAVKRSRSRFrGEKDRKRKLEEVERHEKLgEHPNCVRFIKAWEEKGILYI 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 698 ITEfMENGSLDSFLRQNDgQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLsrFLEDDTSD 777
Cdd:cd14050   79 QTE-LCDTSLQQYCEETH-SLPESEVWNILLDLLKGLKHLHDHGLIHLDIKPANIFLSKDGVCKLGDFGL--VVELDKED 154
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 111118978 778 PTYTSALGGkipiRWTAPEAIQyRKFTSASDVWSYGIVMWEVMSYGERP 826
Cdd:cd14050  155 IHDAQEGDP----RYMAPELLQ-GSFTKAADIFSLGITILELACNLELP 198
STKc_Aurora-A cd14116
Catalytic domain of the Serine/Threonine kinase, Aurora-A kinase; STKs catalyze the transfer ...
622-847 4.61e-15

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: 76.15  E-value: 4.61e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVcsgHLKLPGKREIFVAIKTL------KSGYTEKQRRdflsEASIMGQFDHPNVIHLEGVVTKSTPV 695
Cdd:cd14116    8 EIGRPLGKGKFGNV---YLAREKQSKFILALKVLfkaqleKAGVEHQLRR----EVEIQSHLRHPNILRLYGYFHDATRV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 696 MIITEFMENGSLDSFLrQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFleddt 775
Cdd:cd14116   81 YLILEYAPLGTVYREL-QKLSKFDEQRTATYITELANALSYCHSKRVIHRDIKPENLLLGSAGELKIADFGWSVH----- 154
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 111118978 776 SDPTYTSALGGKIPirWTAPEAIQYRKFTSASDVWSYGIVMWEVMsYGERPYWDMTNQDVINAIEQ-DYRLPP 847
Cdd:cd14116  155 APSSRRTTLCGTLD--YLPPEMIEGRMHDEKVDLWSLGVLCYEFL-VGKPPFEANTYQETYKRISRvEFTFPD 224
STKc_SGK1 cd05602
Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced ...
625-870 5.50e-15

Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK1 is ubiquitously expressed and is under transcriptional control of numerous stimuli including cell stress (cell shrinkage), serum, hormones (gluco- and mineralocorticoids), gonadotropins, growth factors, interleukin-6, and other cytokines. It plays roles in sodium retention and potassium elimination in the kidney, nutrient transport, salt sensitivity, memory consolidation, and cardiac repolarization. A common SGK1 variant is associated with increased blood pressure and body weight. SGK1 may also contribute to tumor growth, neurodegeneration, fibrosing disease, and ischemia. The SGK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270753 [Multi-domain]  Cd Length: 339  Bit Score: 77.36  E-value: 5.50e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKlpgKREIFVAIKTL--KSGYTEKQRRDFLSEASIM-GQFDHPNVIHLEGVVTKSTPVMIITEF 701
Cdd:cd05602   13 KVIGKGSFGKVLLARHK---SDEKFYAVKVLqkKAILKKKEEKHIMSERNVLlKNVKHPFLVGLHFSFQTTDKLYFVLDY 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 702 MENGSLDSFLrQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRfledDTSDPTYT 781
Cdd:cd05602   90 INGGELFYHL-QRERCFLEPRARFYAAEIASALGYLHSLNIVYRDLKPENILLDSQGHIVLTDFGLCK----ENIEPNGT 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 782 SALGGKIPiRWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVI-NAIEQDYRLPPpmDCPSALHQLML 860
Cdd:cd05602  165 TSTFCGTP-EYLAPEVLHKQPYDRTVDWWCLGAVLYE-MLYGLPPFYSRNTAEMYdNILNKPLQLKP--NITNSARHLLE 240
                        250
                 ....*....|
gi 111118978 861 DCWQKDRNHR 870
Cdd:cd05602  241 GLLQKDRTKR 250
STKc_Nek10 cd08528
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
627-822 5.80e-15

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


Pssm-ID: 270867 [Multi-domain]  Cd Length: 270  Bit Score: 76.00  E-value: 5.80e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVC-----SGHLKLPGKREIFVaiKTLKSGYTEKQR----RDFLSEASIMG-QFDHPNVIHLEGVVTKSTPVM 696
Cdd:cd08528    8 LGSGAFGCVYkvrkkSNGQTLLALKEINM--TNPAFGRTEQERdksvGDIISEVNIIKeQLRHPNIVRYYKTFLENDRLY 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 697 IITEFMENGSLD---SFLRQNDGQFTVIQLVGMLRGIAAGMKYL-ADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLE 772
Cdd:cd08528   86 IVMELIEGAPLGehfSSLKEKNEHFTEDRIWNIFVQMVLALRYLhKEKQIVHRDLKPNNIMLGEDDKVTITDFGLAKQKG 165
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 111118978 773 DDTSdpTYTSALGgkiPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSY 822
Cdd:cd08528  166 PESS--KMTSVVG---TILYSCPEIVQNEPYGEKADIWALGCILYQMCTL 210
STKc_DAPK3 cd14195
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 3; STKs ...
627-843 6.04e-15

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


Pssm-ID: 271097 [Multi-domain]  Cd Length: 271  Bit Score: 76.20  E-value: 6.04e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKREI--FVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMEN 704
Cdd:cd14195   13 LGSGQFAIVRKCREKGTGKEYAakFIKKRRLSSSRRGVSREEIEREVNILREIQHPNIITLHDIFENKTDVVLILELVSG 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 705 GSLDSFLRQNDgQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILV----NSNLVCKVSDFGLSRFLEddtSDPTY 780
Cdd:cd14195   93 GELFDFLAEKE-SLTEEEATQFLKQILDGVHYLHSKRIAHFDLKPENIMLldknVPNPRIKLIDFGIAHKIE---AGNEF 168
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 111118978 781 TSALGGKipiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDV---INAIEQDY 843
Cdd:cd14195  169 KNIFGTP---EFVAPEIVNYEPLGLEADMWSIGVITYILLS-GASPFLGETKQETltnISAVNYDF 230
STKc_CaMKI cd14083
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
622-829 6.30e-15

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: 75.87  E-value: 6.30e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEF 701
Cdd:cd14083    6 EFKEVLGTGAFSEVVLAEDKATGK---LVAIKCIDKKALKGKEDSLENEIAVLRKIKHPNIVQLLDIYESKSHLYLVMEL 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 702 MENGSL-DSFLRQndGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNIL-----VNSNLVckVSDFGLSRfLEDDT 775
Cdd:cd14083   83 VTGGELfDRIVEK--GSYTEKDASHLIRQVLEAVDYLHSLGIVHRDLKPENLLyyspdEDSKIM--ISDFGLSK-MEDSG 157
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 111118978 776 SDPTYTSALGgkipirWTAPEAIQYRKFTSASDVWSYGivmweVMSY----GERPYWD 829
Cdd:cd14083  158 VMSTACGTPG------YVAPEVLAQKPYGKAVDCWSIG-----VISYillcGYPPFYD 204
STKc_RSK2_C cd14176
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called ...
622-906 7.55e-15

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


Pssm-ID: 271078 [Multi-domain]  Cd Length: 339  Bit Score: 76.98  E-value: 7.55e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFgEVCSGHLKLPGKREIFVAIktlksgyTEKQRRDFLSEASIMGQF-DHPNVIHLEGVVTKSTPVMIITE 700
Cdd:cd14176   22 EVKEDIGVGSY-SVCKRCIHKATNMEFAVKI-------IDKSKRDPTEEIEILLRYgQHPNIITLKDVYDDGKYVYVVTE 93
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMENGSL-DSFLRQNdgQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILV-----NSNLVcKVSDFGLSRFLEDD 774
Cdd:cd14176   94 LMKGGELlDKILRQK--FFSEREASAVLFTITKTVEYLHAQGVVHRDLKPSNILYvdesgNPESI-RICDFGFAKQLRAE 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 775 TS---DPTYTSalggkipiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERP------------------------- 826
Cdd:cd14176  171 NGllmTPCYTA--------NFVAPEVLERQGYDAACDIWSLGVLLYTMLT-GYTPfangpddtpeeilarigsgkfslsg 241
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 827 -YWDMTNQDVINAIEQDYRLPPPMDCPSAlhQLMLDCWQKDRNHRPKFGqiVNTLDKmirnPNSLK-AMAPLSSGINL-- 902
Cdd:cd14176  242 gYWNSVSDTAKDLVSKMLHVDPHQRLTAA--LVLRHPWIVHWDQLPQYQ--LNRQDA----PHLVKgAMAATYSALNRnq 313

                 ....*
gi 111118978 903 -PLLD 906
Cdd:cd14176  314 sPVLE 318
STKc_MAPKAPK cd14089
Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase-activated ...
625-817 7.61e-15

Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase-activated 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 MAPK-activated protein kinases MK2, MK3, MK5 (also called PRAK for p38-regulated/activated protein kinase), and related proteins. These proteins contain a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. In addition, MK2 and MK3 contain an N-terminal proline-rich region that can bind to SH3 domains. MK2 and MK3 are bonafide substrates for the MAPK p38, while MK5 plays a functional role in the p38 MAPK pathway although their direct interaction has been difficult to detect. MK2 and MK3 are closely related and show, thus far, indistinguishable substrate specificity, while MK5 shows a distinct spectrum of substrates. MK2 and MK3 are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. MK5 is a ubiquitous protein that is implicated in neuronal morphogenesis, cell migration, and tumor angiogenesis. It interacts with PKA, which induces cytoplasmic translocation of MK5. Its substrates includes p53, ERK3/4, Hsp27, and cytosolic phospholipase A2 (cPLA2). The MAPKAPK 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: 270991 [Multi-domain]  Cd Length: 263  Bit Score: 75.79  E-value: 7.61e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKLPGKReifVAIKTLKSgyTEKQRR--DFLSEASimgqfDHPNVIHL----EGVVTKSTPVMII 698
Cdd:cd14089    7 QVLGLGINGKVLECFHKKTGEK---FALKVLRD--NPKARRevELHWRAS-----GCPHIVRIidvyENTYQGRKCLLVV 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 699 TEFMENGSL-DSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNS---NLVCKVSDFGLSRflEDD 774
Cdd:cd14089   77 MECMEGGELfSRIQERADSAFTEREAAEIMRQIGSAVAHLHSMNIAHRDLKPENLLYSSkgpNAILKLTDFGFAK--ETT 154
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 111118978 775 TSD----PTYTsalggkiPIrWTAPEAIQYRKFTSASDVWSYGIVMW 817
Cdd:cd14089  155 TKKslqtPCYT-------PY-YVAPEVLGPEKYDKSCDMWSLGVIMY 193
PKc_MKK4 cd06616
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
627-879 8.15e-15

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


Pssm-ID: 270790 [Multi-domain]  Cd Length: 291  Bit Score: 76.25  E-value: 8.15e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVcSGHLKLPGKREIfvAIKTLKSGYTEKQRRDFLSEA-SIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENg 705
Cdd:cd06616   14 IGRGAFGTV-NKMLHKPSGTIM--AVKRIRSTVDEKEQKRLLMDLdVVMRSSDCPYIVKFYGALFREGDCWICMELMDI- 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 706 SLDSFLRQ-NDGQFTVI--QLVGMLR-GIAAGMKYLA-DMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDD---TSD 777
Cdd:cd06616   90 SLDKFYKYvYEVLDSVIpeEILGKIAvATVKALNYLKeELKIIHRDVKPSNILLDRNGNIKLCDFGISGQLVDSiakTRD 169
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 778 ptytsalGGKIPirWTAPEAIQ----YRKFTSASDVWSYGIVMWEVmSYGERPY--WDMTNQDVINAIEQDyrlPPPMDC 851
Cdd:cd06616  170 -------AGCRP--YMAPERIDpsasRDGYDVRSDVWSLGITLYEV-ATGKFPYpkWNSVFDQLTQVVKGD---PPILSN 236
                        250       260       270
                 ....*....|....*....|....*....|....
gi 111118978 852 PSALH------QLMLDCWQKDRNHRPKFGQIVNT 879
Cdd:cd06616  237 SEEREfspsfvNFVNLCLIKDESKRPKYKELLKH 270
STKc_TAO3 cd06633
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze ...
627-891 8.22e-15

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: 76.61  E-value: 8.22e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVcsgHLKLPGKREIFVAIKtlKSGYTEKQR----RDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFM 702
Cdd:cd06633   29 IGHGSFGAV---YFATNSHTNEVVAIK--KMSYSGKQTnekwQDIIKEVKFLQQLKHPNTIEYKGCYLKDHTAWLVMEYC 103
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 703 EnGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSrfledDTSDPTyTS 782
Cdd:cd06633  104 L-GSASDLLEVHKKPLQEVEIAAITHGALQGLAYLHSHNMIHRDIKAGNILLTEPGQVKLADFGSA-----SIASPA-NS 176
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 783 ALGGKIpirWTAPE---AIQYRKFTSASDVWSYGIVMWEVmsyGER--PYWDMTNQDVINAIEQ---------------- 841
Cdd:cd06633  177 FVGTPY---WMAPEvilAMDEGQYDGKVDIWSLGITCIEL---AERkpPLFNMNAMSALYHIAQndsptlqsnewtdsfr 250
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 111118978 842 ---DYRLPP-PMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKmIRNPNSLK 891
Cdd:cd06633  251 gfvDYCLQKiPQERPSSAELLRHDFVRRERPPRVLIDLIQRTKDA-VRELDNLQ 303
STKc_Kin4 cd14076
Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the ...
623-829 9.29e-15

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: 75.60  E-value: 9.29e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 623 IEQVIGAGEFGEVCSGHLKLPGKRE--IFVAIKTLKSG--YTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMII 698
Cdd:cd14076    5 LGRTLGEGEFGKVKLGWPLPKANHRsgVQVAIKLIRRDtqQENCQTSKIMREINILKGLTHPNIVRLLDVLKTKKYIGIV 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 699 TEFMENGSL------DSFLRQNDGQFTVIQLVgmlrgiaAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLE 772
Cdd:cd14076   85 LEFVSGGELfdyilaRRRLKDSVACRLFAQLI-------SGVAYLHKKGVVHRDLKLENLLLDKNRNLVITDFGFANTFD 157
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 111118978 773 DDTSDPTYTSAlGGKIpirWTAPEAIQYRKFTSAS--DVWSYGIVMWeVMSYGERPYWD 829
Cdd:cd14076  158 HFNGDLMSTSC-GSPC---YAAPELVVSDSMYAGRkaDIWSCGVILY-AMLAGYLPFDD 211
STKc_nPKC_delta cd05620
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze ...
625-842 9.52e-15

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


Pssm-ID: 173710 [Multi-domain]  Cd Length: 316  Bit Score: 76.52  E-value: 9.52e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKlpGKREIFvAIKTLKSGYT--EKQRRDFLSEASIMG-QFDHPNVIHLEGVVTKSTPVMIITEF 701
Cdd:cd05620    1 KVLGKGSFGKVLLAELK--GKGEYF-AVKALKKDVVliDDDVECTMVEKRVLAlAWENPFLTHLYCTFQTKEHLFFVMEF 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 702 MENGSLdSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRflEDDTSDPTYT 781
Cdd:cd05620   78 LNGGDL-MFHIQDKGRFDLYRATFYAAEIVCGLQFLHSKGIIYRDLKLDNVMLDRDGHIKIADFGMCK--ENVFGDNRAS 154
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 111118978 782 SALGGKipiRWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVINAIEQD 842
Cdd:cd05620  155 TFCGTP---DYIAPEILQGLKYTFSVDWWSFGVLLYE-MLIGQSPFHGDDEDELFESIRVD 211
STKc_EIF2AK2_PKR cd14047
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
606-880 9.78e-15

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: 75.61  E-value: 9.78e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 606 NEAVREFAKEIdiscvkieQVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGYTEKQRrdflsEASIMGQFDHPNVIHL 685
Cdd:cd14047    1 DERFRQDFKEI--------ELIGSGGFGQVFKAKHRIDGK---TYAIKRVKLNNEKAER-----EVKALAKLDHPNIVRY 64
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 686 EGV----------------VTKSTPVMIITEFMENGSLDSFL-RQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLA 748
Cdd:cd14047   65 NGCwdgfdydpetsssnssRSKTKCLFIQMEFCEKGTLESWIeKRNGEKLDKVLALEIFEQITKGVEYIHSKKLIHRDLK 144
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 749 ARNILVNSNLVCKVSDFGLSrfleddTSDPTYTSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMS-----YG 823
Cdd:cd14047  145 PSNIFLVDTGKVKIGDFGLV------TSLKNDGKRTKSKGTLSYMSPEQISSQDYGKEVDIYALGLILFELLHvcdsaFE 218
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 111118978 824 ERPYW-DMTNQDVINAIEQDYRLPPPmdcpsaLHQLMLdcwQKDRNHRPKFGQIVNTL 880
Cdd:cd14047  219 KSKFWtDLRNGILPDIFDKRYKIEKT------IIKKML---SKKPEDRPNASEILRTL 267
STKc_IKK_alpha cd14039
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
627-827 1.06e-14

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: 75.72  E-value: 1.06e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKReifVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGV------VTKSTPVMIItE 700
Cdd:cd14039    1 LGTGGFGNVCLYQNQETGEK---IAIKSCRLELSVKNKDRWCHEIQIMKKLNHPNVVKACDVpeemnfLVNDVPLLAM-E 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMENGSLDSFLR--QNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNIL---VNSNLVCKVSDFGLSRFLEDDT 775
Cdd:cd14039   77 YCSGGDLRKLLNkpENCCGLKESQVLSLLSDIGSGIQYLHENKIIHRDLKPENIVlqeINGKIVHKIIDLGYAKDLDQGS 156
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 111118978 776 sdpTYTSALGgkiPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPY 827
Cdd:cd14039  157 ---LCTSFVG---TLQYLAPELFENKSYTVTVDYWSFGTMVFECIA-GFRPF 201
STKc_CaMKI_beta cd14169
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
619-848 1.54e-14

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: 74.93  E-value: 1.54e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 619 SCVKIEQVIGAGEFGEV------CSGHLklpgkreifVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKS 692
Cdd:cd14169    3 SVYELKEKLGEGAFSEVvlaqerGSQRL---------VALKCIPKKALRGKEAMVENEIAVLRRINHENIVSLEDIYESP 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 693 TPVMIITEFMENGSL-DSFLRQndGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILV-----NSNLVckVSDFG 766
Cdd:cd14169   74 THLYLAMELVTGGELfDRIIER--GSYTEKDASQLIGQVLQAVKYLHQLGIVHRDLKPENLLYatpfeDSKIM--ISDFG 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 767 LSRFlEDDTSDPTYTSALGgkipirWTAPEAIQYRKFTSASDVWSYGIVMWeVMSYGERPYWDMTNQDVINAI-EQDYRL 845
Cdd:cd14169  150 LSKI-EAQGMLSTACGTPG------YVAPELLEQKPYGKAVDVWAIGVISY-ILLCGYPPFYDENDSELFNQIlKAEYEF 221

                 ...
gi 111118978 846 PPP 848
Cdd:cd14169  222 DSP 224
STKc_RSK4_C cd14177
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 4 (also called ...
622-832 1.56e-14

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


Pssm-ID: 271079 [Multi-domain]  Cd Length: 295  Bit Score: 75.44  E-value: 1.56e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFgEVCSGHLKLPGKREIFVAIktlksgyTEKQRRDFLSEASIMGQF-DHPNVIHLEGVVTKSTPVMIITE 700
Cdd:cd14177    7 ELKEDIGVGSY-SVCKRCIHRATNMEFAVKI-------IDKSKRDPSEEIEILMRYgQHPNIITLKDVYDDGRYVYLVTE 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMENGS-LDSFLRQNdgQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILV-----NSNLVcKVSDFGLSRFLEDD 774
Cdd:cd14177   79 LMKGGElLDRILRQK--FFSEREASAVLYTITKTVDYLHCQGVVHRDLKPSNILYmddsaNADSI-RICDFGFAKQLRGE 155
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 111118978 775 TS---DPTYTSalggkipiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTN 832
Cdd:cd14177  156 NGlllTPCYTA--------NFVAPEVLMRQGYDAACDIWSLGVLLYTMLA-GYTPFANGPN 207
STKc_CaMKI_delta cd14168
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
622-887 1.67e-14

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


Pssm-ID: 271070 [Multi-domain]  Cd Length: 301  Bit Score: 75.47  E-value: 1.67e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEF 701
Cdd:cd14168   13 EFKEVLGTGAFSEVVLAEERATGK---LFAVKCIPKKALKGKESSIENEIAVLRKIKHENIVALEDIYESPNHLYLVMQL 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 702 MENGSL-DSFLRQndGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILV---NSNLVCKVSDFGLSRFleDDTSD 777
Cdd:cd14168   90 VSGGELfDRIVEK--GFYTEKDASTLIRQVLDAVYYLHRMGIVHRDLKPENLLYfsqDEESKIMISDFGLSKM--EGKGD 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 778 pTYTSALGGKipiRWTAPEAIQYRKFTSASDVWSYGIVMWeVMSYGERPYWDMTNQDVINAI-EQDYRLPPPM--DCPSA 854
Cdd:cd14168  166 -VMSTACGTP---GYVAPEVLAQKPYSKAVDCWSIGVIAY-ILLCGYPPFYDENDSKLFEQIlKADYEFDSPYwdDISDS 240
                        250       260       270
                 ....*....|....*....|....*....|...
gi 111118978 855 LHQLMLDCWQKDRNHRpkfgqivNTLDKMIRNP 887
Cdd:cd14168  241 AKDFIRNLMEKDPNKR-------YTCEQALRHP 266
STKc_SGK3 cd05604
Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced ...
625-870 2.52e-14

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: 75.38  E-value: 2.52e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKSG--YTEKQRRDFLSEASIM-GQFDHPNVIHLEGVVTKSTPVMIITEF 701
Cdd:cd05604    2 KVIGKGSFGKVLLAKRKRDGK---YYAVKVLQKKviLNRKEQKHIMAERNVLlKNVKHPFLVGLHYSFQTTDKLYFVLDF 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 702 MENGSLdSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRflEDDTSDPTYT 781
Cdd:cd05604   79 VNGGEL-FFHLQRERSFPEPRARFYAAEIASALGYLHSINIVYRDLKPENILLDSQGHIVLTDFGLCK--EGISNSDTTT 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 782 SALGGKipiRWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWdmtNQDVI----NAIEQDYRLPPPMDCP--SAL 855
Cdd:cd05604  156 TFCGTP---EYLAPEVIRKQPYDNTVDWWCLGSVLYE-MLYGLPPFY---CRDTAemyeNILHKPLVLRPGISLTawSIL 228
                        250
                 ....*....|....*
gi 111118978 856 HQLMldcwQKDRNHR 870
Cdd:cd05604  229 EELL----EKDRQLR 239
STKc_p38gamma cd07880
Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase ...
625-932 2.75e-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: 75.37  E-value: 2.75e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGhlkLPGKREIFVAIKTLKSGYTEK--QRRDFlSEASIMGQFDHPNVIHLEGVVT------KSTPVM 696
Cdd:cd07880   21 KQVGSGAYGTVCSA---LDRRTGAKVAIKKLYRPFQSElfAKRAY-RELRLLKHMKHENVIGLLDVFTpdlsldRFHDFY 96
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 697 IITEFM--ENGSLDSF--LRQNDGQFTVIQlvgMLRGiaagMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLE 772
Cdd:cd07880   97 LVMPFMgtDLGKLMKHekLSEDRIQFLVYQ---MLKG----LKYIHAAGIIHRDLKPGNLAVNEDCELKILDFGLARQTD 169
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 773 ddtsdptytSALGGKIPIRW-TAPEAI-QYRKFTSASDVWSYGIVMWEVmsYGERPYWdmTNQDVINAIEQDYRL--PPP 848
Cdd:cd07880  170 ---------SEMTGYVVTRWyRAPEVIlNWMHYTQTVDIWSVGCIMAEM--LTGKPLF--KGHDHLDQLMEIMKVtgTPS 236
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 849 MDCPSALH--------QLMLDCWQKD-----RNHRPkfgQIVNTLDKMI-----RNPNSLKAMA-PLSSGINLPLLDRTI 909
Cdd:cd07880  237 KEFVQKLQsedaknyvKKLPRFRKKDfrsllPNANP---LAVNVLEKMLvldaeSRITAAEALAhPYFEEFHDPEDETEA 313
                        330       340
                 ....*....|....*....|....
gi 111118978 910 PDYT-SFNTVDEWLEAIKMGQYKE 932
Cdd:cd07880  314 PPYDdSFDEVDQSLEEWKRLTFTE 337
STKc_DCKL2 cd14184
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 2 (also called ...
622-839 3.53e-14

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: 73.53  E-value: 3.53e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKLPGKReifVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEF 701
Cdd:cd14184    4 KIGKVIGDGNFAVVKECVERSTGKE---FALKIIDKAKCCGKEHLIENEVSILRRVKHPNIIMLIEEMDTPAELYLVMEL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 702 MENGSLDSFLRQNDgQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILV----NSNLVCKVSDFGLSRFLEddtsD 777
Cdd:cd14184   81 VKGGDLFDAITSST-KYTERDASAMVYNLASALKYLHGLCIVHRDIKPENLLVceypDGTKSLKLGDFGLATVVE----G 155
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 111118978 778 PTYTSAlggKIPIrWTAPEAIQYRKFTSASDVWSYGIVMWeVMSYGERPYWDMTN--QDVINAI 839
Cdd:cd14184  156 PLYTVC---GTPT-YVAPEIIAETGYGLKVDIWAAGVITY-ILLCGFPPFRSENNlqEDLFDQI 214
STKc_MPK1 cd07857
Catalytic domain of the Serine/Threonine Kinase, Fungal Mitogen-Activated Protein Kinase MPK1; ...
622-847 3.88e-14

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: 74.75  E-value: 3.88e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKlPGKREIFVAIKTLKSGYTEK--QRRDfLSEASIMGQF-DHPNVIHL--EGVVTKS--TP 694
Cdd:cd07857    3 ELIKELGQGAYGIVCSARNA-ETSEEETVAIKKITNVFSKKilAKRA-LRELKLLRHFrGHKNITCLydMDIVFPGnfNE 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 695 VMIITEFMEnGSLDSFLRqNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSR-FLED 773
Cdd:cd07857   81 LYLYEELME-ADLHQIIR-SGQPLTDAHFQSFIYQILCGLKYIHSANVLHRDLKPGNLLVNADCELKICDFGLARgFSEN 158
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 111118978 774 DTSDPTYtsaLGGKIPIRW-TAPE-AIQYRKFTSASDVWSYGIVMWEVmsYGERPYW---DMTNQdvINAIEQDYRLPP 847
Cdd:cd07857  159 PGENAGF---MTEYVATRWyRAPEiMLSFQSYTKAIDVWSVGCILAEL--LGRKPVFkgkDYVDQ--LNQILQVLGTPD 230
STKc_MAST_like cd05579
Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs ...
627-851 3.99e-14

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: 73.79  E-value: 3.99e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKreiFVAIKTLKSgyTEKQRRD----FLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFM 702
Cdd:cd05579    1 ISRGAYGRVYLAKKKSTGD---LYAIKVIKK--RDMIRKNqvdsVLAERNILSQAQNPFVVKLYYSFQGKKNLYLVMEYL 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 703 ENGSLDSFLRqNDGQFTViqlvGMLRGIAA----GMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRF-LEDDTSD 777
Cdd:cd05579   76 PGGDLYSLLE-NVGALDE----DVARIYIAeivlALEYLHSHGIIHRDLKPDNILIDANGHLKLTDFGLSKVgLVRRQIK 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 778 PTYTSALGGKIPIR---------WTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAIeQDYRLPPP 848
Cdd:cd05579  151 LSIQKKSNGAPEKEdrrivgtpdYLAPEILLGQGHGKTVDWWSLGVILYEFLV-GIPPFHAETPEEIFQNI-LNGKIEWP 228

                 ...
gi 111118978 849 MDC 851
Cdd:cd05579  229 EDP 231
STKc_TSSK6-like cd14164
Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs ...
627-876 4.05e-14

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: 73.36  E-value: 4.05e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVcsgHLKLPGKREIFVAIKTL--KSGYTEKQRRDFLSEASIMGQFDHPNVIHL-EGVVTKSTPVMIITEFME 703
Cdd:cd14164    8 IGEGSFSKV---KLATSQKYCCKVAIKIVdrRRASPDFVQKFLPRELSILRRVNHPNIVQMfECIEVANGRLYIVMEAAA 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 704 NGSLDSFlrQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSN-LVCKVSDFGLSRFLEDdtsDPTYTS 782
Cdd:cd14164   85 TDLLQKI--QEVHHIPKDLARDMFAQMVGAVNYLHDMNIVHRDLKCENILLSADdRKIKIADFGFARFVED---YPELST 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 783 ALGGKIPirWTAPEAIQYRKFTSAS-DVWSYGIVMWeVMSYGERPYwDMTNQDVINAIEQDYRLPPPMDCPSALHQLMLD 861
Cdd:cd14164  160 TFCGSRA--YTPPEVILGTPYDPKKyDVWSLGVVLY-VMVTGTMPF-DETNVRRLRLQQRGVLYPSGVALEEPCRALIRT 235
                        250
                 ....*....|....*
gi 111118978 862 CWQKDRNHRPKFGQI 876
Cdd:cd14164  236 LLQFNPSTRPSIQQV 250
STKc_PKA cd14209
Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze ...
626-846 4.43e-14

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: 73.98  E-value: 4.43e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 626 VIGAGEFGEVCSGHLKLPGKreiFVAIKTL-KSGYTE-KQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFME 703
Cdd:cd14209    8 TLGTGSFGRVMLVRHKETGN---YYAMKILdKQKVVKlKQVEHTLNEKRILQAINFPFLVKLEYSFKDNSNLYMVMEYVP 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 704 NGSLDSFLRQNdGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTS----DPT 779
Cdd:cd14209   85 GGEMFSHLRRI-GRFSEPHARFYAAQIVLAFEYLHSLDLIYRDLKPENLLIDQQGYIKVTDFGFAKRVKGRTWtlcgTPE 163
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 111118978 780 YtsalggkipirwTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVINAI-EQDYRLP 846
Cdd:cd14209  164 Y------------LAPEIILSKGYNKAVDWWALGVLIYE-MAAGYPPFFADQPIQIYEKIvSGKVRFP 218
STKc_RSK3_C cd14178
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called ...
622-827 4.54e-14

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called Ribosomal protein S6 kinase alpha-2 or 90kDa ribosomal protein S6 kinase 2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK3 is also called S6K-alpha-2, RPS6KA2, p90RSK2 or MAPK-activated protein kinase 1c (MAPKAPK-1c). RSK3 binds muscle A-kinase anchoring protein (mAKAP)-b directly and regulates concentric cardiac myocyte growth. The RSK3 gene, RPS6KA2, is a putative tumor suppressor gene in sporadic epithelial ovarian cancer and variations to the gene may be associated with rectal cancer risk. RSK3 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271080 [Multi-domain]  Cd Length: 293  Bit Score: 73.90  E-value: 4.54e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGeVCSGHLKLPGKREIFVAIktlksgyTEKQRRDFLSEASIMGQF-DHPNVIHLEGVVTKSTPVMIITE 700
Cdd:cd14178    6 EIKEDIGIGSYS-VCKRCVHKATSTEYAVKI-------IDKSKRDPSEEIEILLRYgQHPNIITLKDVYDDGKFVYLVME 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMENGSL-DSFLRQNdgQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNIL----VNSNLVCKVSDFGLSRFLEDDT 775
Cdd:cd14178   78 LMRGGELlDRILRQK--CFSEREASAVLCTITKTVEYLHSQGVVHRDLKPSNILymdeSGNPESIRICDFGFAKQLRAEN 155
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 111118978 776 S---DPTYTSalggkipiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPY 827
Cdd:cd14178  156 GllmTPCYTA--------NFVAPEVLKRQGYDAACDIWSLGILLYTMLA-GFTPF 201
STKc_RSK_N cd05582
N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase; ...
625-839 4.85e-14

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: 74.36  E-value: 4.85e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVC---------SGHLklpgkreifVAIKTLKSGyTEKQRRDFLS--EASIMGQFDHPNVIHLEGVVTKST 693
Cdd:cd05582    1 KVLGQGSFGKVFlvrkitgpdAGTL---------YAMKVLKKA-TLKVRDRVRTkmERDILADVNHPFIVKLHYAFQTEG 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 694 PVMIITEFMENGSLdsFLR-QNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLE 772
Cdd:cd05582   71 KLYLILDFLRGGDL--FTRlSKEVMFTEEDVKFYLAELALALDHLHSLGIIYRDLKPENILLDEDGHIKLTDFGLSKESI 148
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 111118978 773 DDtSDPTYtSALGgkiPIRWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVINAI 839
Cdd:cd05582  149 DH-EKKAY-SFCG---TVEYMAPEVVNRRGHTQSADWWSFGVLMFE-MLTGSLPFQGKDRKETMTMI 209
STKc_16 cd13986
Catalytic domain of Serine/Threonine Kinase 16; STKs catalyze the transfer of the ...
622-884 4.96e-14

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: 73.48  E-value: 4.96e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGYTEkQRRDFLSEASIMGQFDHPNVIHLE--GVVTK---STPVM 696
Cdd:cd13986    3 RIQRLLGEGGFSFVYLVEDLSTGR---LYALKKILCHSKE-DVKEAMREIENYRLFNHPNILRLLdsQIVKEaggKKEVY 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 697 IITEFMENGSLDSFLRQND--GQF-TVIQLVGMLRGIAAGMKYLADMN---YVHRDLAARNILVNSNLVCKVSDFG---L 767
Cdd:cd13986   79 LLLPYYKRGSLQDEIERRLvkGTFfPEDRILHIFLGICRGLKAMHEPElvpYAHRDIKPGNVLLSEDDEPILMDLGsmnP 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 768 SRFLEDDTSDPTYTSALGGK---IPirWTAPE---AIQYRKFTSASDVWSYGIVMWEVMsYGERPYwDMTNQD------- 834
Cdd:cd13986  159 ARIEIEGRREALALQDWAAEhctMP--YRAPElfdVKSHCTIDEKTDIWSLGCTLYALM-YGESPF-ERIFQKgdslala 234
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|
gi 111118978 835 VINAIeqdYRLPPPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKMI 884
Cdd:cd13986  235 VLSGN---YSFPDNSRYSEELHQLVKSMLVVNPAERPSIDDLLSRVHDLI 281
STKc_phototropin_like cd05574
Catalytic domain of Phototropin-like Serine/Threonine Kinases; STKs catalyze the transfer of ...
622-870 5.17e-14

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: 74.20  E-value: 5.17e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQvIGAGEFGEVcsgHL-KLPGKREIFvAIKTL-KSGYTE--KQRRdFLSEASIMGQFDHPNVIHLEGVVTKSTPVMI 697
Cdd:cd05574    5 KIKL-LGKGDVGRV---YLvRLKGTGKLF-AMKVLdKEEMIKrnKVKR-VLTEREILATLDHPFLPTLYASFQTSTHLCF 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 698 ITEFMENGSLDSFL-RQNDGQFTvIQLVgmlRGIAA----GMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSrFLE 772
Cdd:cd05574   79 VMDYCPGGELFRLLqKQPGKRLP-EEVA---RFYAAevllALEYLHLLGFVYRDLKPENILLHESGHIMLTDFDLS-KQS 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 773 DDTSDPTYTSALGG-------KIPIR------------------WTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPY 827
Cdd:cd05574  154 SVTPPPVRKSLRKGsrrssvkSIEKEtfvaepsarsnsfvgteeYIAPEVIKGDGHGSAVDWWTLGILLYE-MLYGTTPF 232
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....
gi 111118978 828 WDMTNQDVINAI-EQDYRLPPPMDCPSALHQLMLDCWQKDRNHR 870
Cdd:cd05574  233 KGSNRDETFSNIlKKELTFPESPPVSSEAKDLIRKLLVKDPSKR 276
STKc_PLK3 cd14189
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the ...
651-877 1.11e-13

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: 72.27  E-value: 1.11e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 651 AIKTLKSGYTEK--QRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIiteFMENGSLDSFLRQNDGQFTVI--QLVGM 726
Cdd:cd14189   30 AVKVIPHSRVAKphQREKIVNEIELHRDLHHKHVVKFSHHFEDAENIYI---FLELCSRKSLAHIWKARHTLLepEVRYY 106
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 727 LRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEddTSDPTYTSALGGKipiRWTAPEAIQYRKFTSA 806
Cdd:cd14189  107 LKQIISGLKYLHLKGILHRDLKLGNFFINENMELKVGDFGLAARLE--PPEQRKKTICGTP---NYLAPEVLLRQGHGPE 181
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 111118978 807 SDVWSYGIVMWEVMSyGERPYWDMTNQDVINAIEQ-DYRLPPPMDCPSalHQLMLDCWQKDRNHRPKFGQIV 877
Cdd:cd14189  182 SDVWSLGCVMYTLLC-GNPPFETLDLKETYRCIKQvKYTLPASLSLPA--RHLLAGILKRNPGDRLTLDQIL 250
STKc_LKB1 cd14119
Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer ...
650-876 1.25e-13

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: 71.90  E-value: 1.25e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 650 VAIKTLKSgytEKQRR------DFLSEASIMGQFDHPNVIHLEGVVT--KSTPVMIITEFMENGSLDSFLRQNDGQFTVI 721
Cdd:cd14119   21 RAVKILKK---RKLRRipngeaNVKREIQILRRLNHRNVIKLVDVLYneEKQKLYMVMEYCVGGLQEMLDSAPDKRLPIW 97
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 722 QLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFG----LSRFLEDDTSDPTYTSalggkiPiRWTAPE- 796
Cdd:cd14119   98 QAHGYFVQLIDGLEYLHSQGIIHKDIKPGNLLLTTDGTLKISDFGvaeaLDLFAEDDTCTTSQGS------P-AFQPPEi 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 797 AIQYRKFTS-ASDVWSYGIVMWEvMSYGERPYWDMTNQDVINAI-EQDYRLPPpmDCPSALHQLMLDCWQKDRNHRPKFG 874
Cdd:cd14119  171 ANGQDSFSGfKVDIWSAGVTLYN-MTTGKYPFEGDNIYKLFENIgKGEYTIPD--DVDPDLQDLLRGMLEKDPEKRFTIE 247

                 ..
gi 111118978 875 QI 876
Cdd:cd14119  248 QI 249
STKc_EIF2AK4_GCN2_rpt2 cd14046
Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation ...
625-878 1.41e-13

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: 72.02  E-value: 1.41e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMEN 704
Cdd:cd14046   12 QVLGKGAFGQVVKVRNKLDGR---YYAIKKIKLRSESKNNSRILREVMLLSRLNHQHVVRYYQAWIERANLYIQMEYCEK 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 705 GSLDSFLRQNDGQfTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLE------------ 772
Cdd:cd14046   89 STLRDLIDSGLFQ-DTDRLWRLFRQILEGLAYIHSQGIIHRDLKPVNIFLDSNGNVKIGDFGLATSNKlnvelatqdink 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 773 ----DDTSDPTYTSALGGKIpirWTAPEAIQYRK--FTSASDVWSYGIVMWEvMSYgeRPYWDMTNQDVINAI-EQDYRL 845
Cdd:cd14046  168 stsaALGSSGDLTGNVGTAL---YVAPEVQSGTKstYNEKVDMYSLGIIFFE-MCY--PFSTGMERVQILTALrSVSIEF 241
                        250       260       270
                 ....*....|....*....|....*....|....*
gi 111118978 846 PPPMDCPSALHQLMLDCW--QKDRNHRPKFGQIVN 878
Cdd:cd14046  242 PPDFDDNKHSKQAKLIRWllNHDPAKRPSAQELLK 276
STKc_TLK2 cd14041
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 2; STKs catalyze the ...
625-854 1.52e-13

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 2; 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 TLK2 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: 270943 [Multi-domain]  Cd Length: 309  Bit Score: 72.79  E-value: 1.52e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGhLKLPGKREIFVAIKTLKSGYTEKQRRDF----LSEASIMGQFDHPNVIHLEGVVTKST-PVMIIT 699
Cdd:cd14041   12 HLLGRGGFSEVYKA-FDLTEQRYVAVKIHQLNKNWRDEKKENYhkhaCREYRIHKELDHPRIVKLYDYFSLDTdSFCTVL 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENGSLDSFLRQN------DGQFTVIQLVGMLrgiaagmKYLADMN--YVHRDLAARNILVNSNLVC---KVSDFGLS 768
Cdd:cd14041   91 EYCEGNDLDFYLKQHklmsekEARSIIMQIVNAL-------KYLNEIKppIIHYDLKPGNILLVNGTACgeiKITDFGLS 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 769 RFLEDDtsdpTYTSALGGKIPIR------WTAPEAI----QYRKFTSASDVWSYGIVMWEVMsYGERPY-WDMTNQDVI- 836
Cdd:cd14041  164 KIMDDD----SYNSVDGMELTSQgagtywYLPPECFvvgkEPPKISNKVDVWSVGVIFYQCL-YGRKPFgHNQSQQDILq 238
                        250       260
                 ....*....|....*....|..
gi 111118978 837 -NAI--EQDYRLPP-PMDCPSA 854
Cdd:cd14041  239 eNTIlkATEVQFPPkPVVTPEA 260
PknB_PASTA_kin NF033483
Stk1 family PASTA domain-containing Ser/Thr kinase;
622-872 1.91e-13

Stk1 family PASTA domain-containing Ser/Thr kinase;


Pssm-ID: 468045 [Multi-domain]  Cd Length: 563  Bit Score: 74.06  E-value: 1.91e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGH-LKLpgKREifVAIKTLKSGYTEK---QRRdFLSEASIMGQFDHPNVIhleGV----VTKST 693
Cdd:NF033483  10 EIGERIGRGGMAEVYLAKdTRL--DRD--VAVKVLRPDLARDpefVAR-FRREAQSAASLSHPNIV---SVydvgEDGGI 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 694 P--VMiitEFMENGSLDSFLRQNdGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFL 771
Cdd:NF033483  82 PyiVM---EYVDGRTLKDYIREH-GPLSPEEAVEIMIQILSALEHAHRNGIVHRDIKPQNILITKDGRVKVTDFGIARAL 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 772 edDTSDPTYTSALGGkipirwTA----PEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYwdmT------------NQDV 835
Cdd:NF033483 158 --SSTTMTQTNSVLG------TVhylsPEQARGGTVDARSDIYSLGIVLYE-MLTGRPPF---DgdspvsvaykhvQEDP 225
                        250       260       270
                 ....*....|....*....|....*....|....*..
gi 111118978 836 INAIEQDYRLPPPMDcpsalhQLMLDCWQKDRNHRPK 872
Cdd:NF033483 226 PPPSELNPGIPQSLD------AVVLKATAKDPDDRYQ 256
STKc_MAP4K4_6_N cd06636
N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase ...
615-877 1.94e-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: 71.96  E-value: 1.94e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 615 EIDISCVK-------IEQVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKsgYTEKQRRDFLSEASIMGQFDH-PNVIHLE 686
Cdd:cd06636    5 DIDLSALRdpagifeLVEVVGNGTYGQVYKGRHVKTGQ---LAAIKVMD--VTEDEEEEIKLEINMLKKYSHhRNIATYY 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 687 GVVTKSTP------VMIITEFMENGSLDSFLRQNDGQ-FTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLV 759
Cdd:cd06636   80 GAFIKKSPpghddqLWLVMEFCGAGSVTDLVKNTKGNaLKEDWIAYICREILRGLAHLHAHKVIHRDIKGQNVLLTENAE 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 760 CKVSDFGLSRFLedDTSDPTYTSALGGKIpirWTAPEAIQYRKFTSA-----SDVWSYGIVMWEvMSYGERPYWDMTNQD 834
Cdd:cd06636  160 VKLVDFGVSAQL--DRTVGRRNTFIGTPY---WMAPEVIACDENPDAtydyrSDIWSLGITAIE-MAEGAPPLCDMHPMR 233
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*..
gi 111118978 835 VINAIEqdyRLPPPMDCPSALHQLMLD----CWQKDRNHRPKFGQIV 877
Cdd:cd06636  234 ALFLIP---RNPPPKLKSKKWSKKFIDfiegCLVKNYLSRPSTEQLL 277
STKc_CDK10 cd07845
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs ...
627-820 2.00e-13

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: 72.40  E-value: 2.00e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGkrEIfVAIKTLKsgyTEKQRRDF----LSEASIMGQFDHPNVIHLEGVVTKS--TPVMIITE 700
Cdd:cd07845   15 IGEGTYGIVYRARDTTSG--EI-VALKKVR---MDNERDGIpissLREITLLLNLRHPNIVELKEVVVGKhlDSIFLVME 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMENgSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDPTy 780
Cdd:cd07845   89 YCEQ-DLASLLDNMPTPFSESQVKCLMLQLLRGLQYLHENFIIHRDLKVSNLLLTDKGCLKIADFGLARTYGLPAKPMT- 166
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 111118978 781 tsalgGKIPIRW-TAPEAI-QYRKFTSASDVWSYGIVMWEVM 820
Cdd:cd07845  167 -----PKVVTLWyRAPELLlGCTTYTTAIDMWAVGCILAELL 203
STKc_SGK2 cd05603
Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 2; ...
625-870 2.86e-13

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: 71.92  E-value: 2.86e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKLPGKreiFVAIKTL--KSGYTEKQRRDFLSEASIM-GQFDHPNVIHLEGVVTKSTPVMIITEF 701
Cdd:cd05603    1 KVIGKGSFGKVLLAKRKCDGK---FYAVKVLqkKTILKKKEQNHIMAERNVLlKNLKHPFLVGLHYSFQTSEKLYFVLDY 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 702 MENGSLdSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRfledDTSDPTYT 781
Cdd:cd05603   78 VNGGEL-FFHLQRERCFLEPRARFYAAEVASAIGYLHSLNIIYRDLKPENILLDCQGHVVLTDFGLCK----EGMEPEET 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 782 SALGGKIPiRWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWdmtNQDVI----NAIEQDYRLPPPMDCPSALhq 857
Cdd:cd05603  153 TSTFCGTP-EYLAPEVLRKEPYDRTVDWWCLGAVLYE-MLYGLPPFY---SRDVSqmydNILHKPLHLPGGKTVAACD-- 225
                        250
                 ....*....|...
gi 111118978 858 LMLDCWQKDRNHR 870
Cdd:cd05603  226 LLQGLLHKDQRRR 238
STKc_DCKL cd14095
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called ...
669-817 3.65e-13

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: 70.43  E-value: 3.65e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 669 SEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGSLDSFLRQNdGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLA 748
Cdd:cd14095   47 NEVAILRRVKHPNIVQLIEEYDTDTELYLVMELVKGGDLFDAITSS-TKFTERDASRMVTDLAQALKYLHSLSIVHRDIK 125
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 111118978 749 ARNILVNSN----LVCKVSDFGLSRFLEDDTS----DPTYtsalggkipirwTAPEAIQYRKFTSASDVWSYGIVMW 817
Cdd:cd14095  126 PENLLVVEHedgsKSLKLADFGLATEVKEPLFtvcgTPTY------------VAPEILAETGYGLKVDIWAAGVITY 190
STKc_GAK_like cd13985
Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of ...
621-882 3.66e-13

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: 70.83  E-value: 3.66e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQVIGAGEFGEVCSGHLKLPGKReifVAIKTLKSGYTEKQRRdFLSEASIMGQF-DHPNVI-HLEGVVTKSTP---V 695
Cdd:cd13985    2 YQVTKQLGEGGFSYVYLAHDVNTGRR---YALKRMYFNDEEQLRV-AIKEIEIMKRLcGHPNIVqYYDSAILSSEGrkeV 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 696 MIITEFMEnGSLDSFLRQN-DGQFTVIQLVGMLRGIAAGMKYLADMN--YVHRDLAARNILVNSNLVCKVSDFG----LS 768
Cdd:cd13985   78 LLLMEYCP-GSLVDILEKSpPSPLSEEEVLRIFYQICQAVGHLHSQSppIIHRDIKIENILFSNTGRFKLCDFGsattEH 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 769 RFLEDDTSDPTYTSALGGKIPIRWTAPEAIQ-YRKF--TSASDVWSYGIVMWeVMSYGERPYWDMTnqdVINAIEQDYRL 845
Cdd:cd13985  157 YPLERAEEVNIIEEEIQKNTTPMYRAPEMIDlYSKKpiGEKADIWALGCLLY-KLCFFKLPFDESS---KLAIVAGKYSI 232
                        250       260       270
                 ....*....|....*....|....*....|....*..
gi 111118978 846 PPPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDK 882
Cdd:cd13985  233 PEQPRYSPELHDLIRHMLTPDPAERPDIFQVINIITK 269
STKc_p38delta cd07879
Catalytic domain of the Serine/Threonine Kinase, p38delta Mitogen-Activated Protein Kinase ...
600-821 4.41e-13

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: 71.86  E-value: 4.41e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 600 FTYEDPNEAVREFAKEIDISCVkieqvIGAGEFGEVCSGHLKLPGKReifVAIKTLKSGYTEK--QRRDFlSEASIMGQF 677
Cdd:cd07879    1 FYREEVNKTVWELPERYTSLKQ-----VGSGAYGSVCSAIDKRTGEK---VAIKKLSRPFQSEifAKRAY-RELTLLKHM 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 678 DHPNVIHLEGVVTKSTPV------MIITEFME---NGSLDSFLRQNDGQFTVIQLVgmlrgiaAGMKYLADMNYVHRDLA 748
Cdd:cd07879   72 QHENVIGLLDVFTSAVSGdefqdfYLVMPYMQtdlQKIMGHPLSEDKVQYLVYQML-------CGLKYIHSAGIIHRDLK 144
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 111118978 749 ARNILVNSNLVCKVSDFGLSRfleddTSDPTYTsalgGKIPIRW-TAPEAI-QYRKFTSASDVWSYGIVMWEVMS 821
Cdd:cd07879  145 PGNLAVNEDCELKILDFGLAR-----HADAEMT----GYVVTRWyRAPEVIlNWMHYNQTVDIWSVGCIMAEMLT 210
STKc_NLK cd07853
Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer ...
627-821 4.51e-13

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: 72.08  E-value: 4.51e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKReifVAIKTLKS---GYTEKQRrdFLSEASIMGQFDHPNVIHLEGVVTKSTP-----VMII 698
Cdd:cd07853    8 IGYGAFGVVWSVTDPRDGKR---VALKKMPNvfqNLVSCKR--VFRELKMLCFFKHDNVLSALDILQPPHIdpfeeIYVV 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 699 TEFMENGSLDSFLRQNDGQFTVIQLvgMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDp 778
Cdd:cd07853   83 TELMQSDLHKIIVSPQPLSSDHVKV--FLYQILRGLKYLHSAGILHRDIKPGNLLVNSNCVLKICDFGLARVEEPDESK- 159
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 111118978 779 TYTSALggkIPIRWTAPEAIQ-YRKFTSASDVWSYGIVMWEVMS 821
Cdd:cd07853  160 HMTQEV---VTQYYRAPEILMgSRHYTSAVDIWSVGCIFAELLG 200
STKc_DCKL1 cd14183
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called ...
622-817 4.51e-13

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


Pssm-ID: 271085 [Multi-domain]  Cd Length: 268  Bit Score: 70.41  E-value: 4.51e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEV--CSGHlklPGKREifVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIIT 699
Cdd:cd14183    9 KVGRTIGDGNFAVVkeCVER---STGRE--YALKIINKSKCRGKEHMIQNEVSILRRVKHPNIVLLIEEMDMPTELYLVM 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENGSL-DSFLRQNdgQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILV----NSNLVCKVSDFGLSRFLEdd 774
Cdd:cd14183   84 ELVKGGDLfDAITSTN--KYTERDASGMLYNLASAIKYLHSLNIVHRDIKPENLLVyehqDGSKSLKLGDFGLATVVD-- 159
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 111118978 775 tsDPTYTSAlggKIPIrWTAPEAIQYRKFTSASDVWSYGIVMW 817
Cdd:cd14183  160 --GPLYTVC---GTPT-YVAPEIIAETGYGLKVDIWAAGVITY 196
STKc_SNRK cd14074
Catalytic domain of the Serine/Threonine Kinase, SNF1-related kinase; STKs catalyze the ...
623-879 4.59e-13

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: 70.13  E-value: 4.59e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 623 IEQVIGAGEFGEVCSGHLKLPGKReifVAIKTL-KSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEF 701
Cdd:cd14074    7 LEETLGRGHFAVVKLARHVFTGEK---VAVKVIdKTKLDDVSKAHLFQEVRCMKLVQHPNVVRLYEVIDTQTKLYLILEL 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 702 MENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVC-KVSDFGLSRFLEDDTSDPTY 780
Cdd:cd14074   84 GDGGDMYDYIMKHENGLNEDLARKYFRQIVSAISYCHKLHVVHRDLKPENVVFFEKQGLvKLTDFGFSNKFQPGEKLETS 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 781 TSALGgkipirWTAPEAIQYRKFTS-ASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAI-EQDYRLPPPM--DCPSALH 856
Cdd:cd14074  164 CGSLA------YSAPEILLGDEYDApAVDIWSLGVILYMLVC-GQPPFQEANDSETLTMImDCKYTVPAHVspECKDLIR 236
                        250       260
                 ....*....|....*....|...
gi 111118978 857 QlMLdcwQKDRNHRPKFGQIVNT 879
Cdd:cd14074  237 R-ML---IRDPKKRASLEEIENH 255
STKc_TAO2 cd06634
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze ...
627-842 4.94e-13

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: 71.21  E-value: 4.94e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVcsgHLKLPGKREIFVAIKtlKSGYTEKQR----RDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFM 702
Cdd:cd06634   23 IGHGSFGAV---YFARDVRNNEVVAIK--KMSYSGKQSnekwQDIIKEVKFLQKLRHPNTIEYRGCYLREHTAWLVMEYC 97
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 703 EnGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEddtsdPTyTS 782
Cdd:cd06634   98 L-GSASDLLEVHKKPLQEVEIAAITHGALQGLAYLHSHNMIHRDVKAGNILLTEPGLVKLGDFGSASIMA-----PA-NS 170
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 111118978 783 ALGGKIpirWTAPE---AIQYRKFTSASDVWSYGIVMWEVmsyGER--PYWDMTNQDVINAIEQD 842
Cdd:cd06634  171 FVGTPY---WMAPEvilAMDEGQYDGKVDVWSLGITCIEL---AERkpPLFNMNAMSALYHIAQN 229
STKc_PKC cd05570
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer ...
626-870 5.55e-13

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: 71.09  E-value: 5.55e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 626 VIGAGEFGEVCSGHLKlpGKREIFvAIKTLK-----------SGYTEKQrrdFLSEASimgqfDHPNVIHLEGVVTKSTP 694
Cdd:cd05570    2 VLGKGSFGKVMLAERK--KTDELY-AIKVLKkeviiedddveCTMTEKR---VLALAN-----RHPFLTGLHACFQTEDR 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 695 VMIITEFMENGSLdSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRflEDD 774
Cdd:cd05570   71 LYFVMEYVNGGDL-MFHIQRARRFTEERARFYAAEICLALQFLHERGIIYRDLKLDNVLLDAEGHIKIADFGMCK--EGI 147
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 775 TSDPTyTSALGGKiPiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAI-EQDYRLPPPM--DC 851
Cdd:cd05570  148 WGGNT-TSTFCGT-P-DYIAPEILREQDYGFSVDWWALGVLLYEMLA-GQSPFEGDDEDELFEAIlNDEVLYPRWLsrEA 223
                        250
                 ....*....|....*....
gi 111118978 852 PSALHQLMLdcwqKDRNHR 870
Cdd:cd05570  224 VSILKGLLT----KDPARR 238
FN3 smart00060
Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, ...
436-517 6.04e-13

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.


Pssm-ID: 214495 [Multi-domain]  Cd Length: 83  Bit Score: 65.33  E-value: 6.04e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978   436 PSAVSIMHQVSRTVDSITLSWSQPDQPNGV--ILDYELQYYEKELSEYNATAiKSPTNTVTVQGLKAGAIYVFQVRARTV 513
Cdd:smart00060   1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGITgyIVGYRVEYREEGSEWKEVNV-TPSSTSYTLTGLKPGTEYEFRVRAVNG 79

                   ....
gi 111118978   514 AGYG 517
Cdd:smart00060  80 AGEG 83
STKc_DRAK2 cd14198
The catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
627-841 6.89e-13

The catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2 (also called STK17B). Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. DRAK2 has been implicated in inducing or enhancing apoptosis in beta cells, fibroblasts, and lymphoid cells, where it is highly expressed. It is involved in regulating many immune processes including the germinal center (GC) reaction, responses to thymus-dependent antigens, activated T cell survival, memory T cell responses. It may be involved in the development of autoimmunity. The DRAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271100 [Multi-domain]  Cd Length: 270  Bit Score: 69.95  E-value: 6.89e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKReifVAIKTLKsgyteKQRRDFLSEASIMGQF-------DHPNVIHLEGVVTKSTPVMIIT 699
Cdd:cd14198   16 LGRGKFAVVRQCISKSTGQE---YAAKFLK-----KRRRGQDCRAEILHEIavlelakSNPRVVNLHEVYETTSEIILIL 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENGSLDSF-LRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLV---CKVSDFGLSRFLEDDT 775
Cdd:cd14198   88 EYAAGGEIFNLcVPDLAEMVSENDIIRLIRQILEGVYYLHQNNIVHLDLKPQNILLSSIYPlgdIKIVDFGMSRKIGHAC 167
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 111118978 776 SdptYTSALGGKipiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAIEQ 841
Cdd:cd14198  168 E---LREIMGTP---EYLAPEILNYDPITTATDMWNIGVIAYMLLT-HESPFVGEDNQETFLNISQ 226
PKc_DYRK_like cd14133
Catalytic domain of Dual-specificity tYrosine-phosphorylated and -Regulated Kinase-like ...
622-848 6.92e-13

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: 69.99  E-value: 6.92e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKLPGKReifVAIKTLKSgytekqRRDF----LSEASIM------GQFDHPNVIHLEGVVTK 691
Cdd:cd14133    2 EVLEVLGKGTFGQVVKCYDLLTGEE---VALKIIKN------NKDYldqsLDEIRLLellnkkDKADKYHIVRLKDVFYF 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 692 STPVMIITEFMENgSLDSFLRQNDGQ-FTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVC--KVSDFGLS 768
Cdd:cd14133   73 KNHLCIVFELLSQ-NLYEFLKQNKFQyLSLPRIRKIAQQILEALVFLHSLGLIHCDLKPENILLASYSRCqiKIIDFGSS 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 769 RFLEDDTSdpTYtsalggkIPIR-WTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVINAIEQDYRLPP 847
Cdd:cd14133  152 CFLTQRLY--SY-------IQSRyYRAPEVILGLPYDEKIDMWSLGCILAE-LYTGEPLFPGASEVDQLARIIGTIGIPP 221

                 .
gi 111118978 848 P 848
Cdd:cd14133  222 A 222
PTZ00426 PTZ00426
cAMP-dependent protein kinase catalytic subunit; Provisional
625-820 8.10e-13

cAMP-dependent protein kinase catalytic subunit; Provisional


Pssm-ID: 173616 [Multi-domain]  Cd Length: 340  Bit Score: 70.78  E-value: 8.10e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKlpgkREIF--VAIKTLKSGYTEKQRR--DFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITE 700
Cdd:PTZ00426  36 RTLGTGSFGRVILATYK----NEDFppVAIKRFEKSKIIKQKQvdHVFSERKILNYINHPFCVNLYGSFKDESYLYLVLE 111
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMENGSLDSFLRQND------GQFTVIQLVGMLrgiaagmKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEdd 774
Cdd:PTZ00426 112 FVIGGEFFTFLRRNKrfpndvGCFYAAQIVLIF-------EYLQSLNIVYRDLKPENLLLDKDGFIKMTDFGFAKVVD-- 182
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 111118978 775 tsdpTYTSALGGKipIRWTAPEAIQYRKFTSASDVWSYGIVMWEVM 820
Cdd:PTZ00426 183 ----TRTYTLCGT--PEYIAPEILLNVGHGKAADWWTLGIFIYEIL 222
STKc_TLK1 cd14040
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 1; STKs catalyze the ...
625-836 8.12e-13

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. A splice variant of TLK1, called TLK1B, is expressed in the presence of double strand breaks (DSBs). It lacks the N-terminal part of TLK1, but is expected to phosphorylate the same substrates. TLK1/1B interacts with Rad9, which is critical in DNA damage-activated checkpoint response, and plays a role in the repair of linearized DNA with incompatible ends. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. The TLK1 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: 270942 [Multi-domain]  Cd Length: 299  Bit Score: 70.47  E-value: 8.12e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGhLKLPGKREIFVAIKTLKSGYTEKQRRDF----LSEASIMGQFDHPNVIHLEGVVTKSTPVM-IIT 699
Cdd:cd14040   12 HLLGRGGFSEVYKA-FDLYEQRYAAVKIHQLNKSWRDEKKENYhkhaCREYRIHKELDHPRIVKLYDYFSLDTDTFcTVL 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENGSLDSFLRQN------DGQFTVIQLVGMLRgiaagmkYLADMN--YVHRDLAARNILVNSNLVC---KVSDFGLS 768
Cdd:cd14040   91 EYCEGNDLDFYLKQHklmsekEARSIVMQIVNALR-------YLNEIKppIIHYDLKPGNILLVDGTACgeiKITDFGLS 163
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 111118978 769 RFLEDDTSDPTYTSALGGKIPIRWTAPEAI-----QYRKFTSASDVWSYGIVMWEVMsYGERPY-WDMTNQDVI 836
Cdd:cd14040  164 KIMDDDSYGVDGMDLTSQGAGTYWYLPPECfvvgkEPPKISNKVDVWSVGVIFFQCL-YGRKPFgHNQSQQDIL 236
STKc_PhKG cd14093
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs ...
664-828 8.64e-13

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: 69.69  E-value: 8.64e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 664 RRDFLSEASIMGQFD-HPNVIHLEGVVTKSTPVMIITEFMENGSLDSFLRQndgqftVIQLV-----GMLRGIAAGMKYL 737
Cdd:cd14093   52 REATRREIEILRQVSgHPNIIELHDVFESPTFIFLVFELCRKGELFDYLTE------VVTLSekktrRIMRQLFEAVEFL 125
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 738 ADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDtsdpTYTSALGGKiPiRWTAPEAIQYRKFTSAS------DVWS 811
Cdd:cd14093  126 HSLNIVHRDLKPENILLDDNLNVKISDFGFATRLDEG----EKLRELCGT-P-GYLAPEVLKCSMYDNAPgygkevDMWA 199
                        170
                 ....*....|....*..
gi 111118978 812 YGIVMWEVMSyGERPYW 828
Cdd:cd14093  200 CGVIMYTLLA-GCPPFW 215
SAM_EPH-A1 cd09542
SAM domain of EPH-A1 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
915-972 9.02e-13

SAM domain of EPH-A1 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A1 subfamily of the receptor tyrosine kinases is a C-terminal protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A1 receptors and appears to mediate cell-cell initiated signal transduction. Activation of these receptors leads to inhibition of cell spreading and migration in a RhoA-ROCK-dependent manner. EPH-A1 receptors are known to bind ILK (integrin-linked kinase) which is the mediator of interactions between integrin and the actin cytoskeleton. However SAM is not sufficient for this interaction; it rather plays an ancillary role. SAM domains of Eph-A1 receptors do not form homo/hetero dimers/oligomers. EphA1 gene was found expressed widely in differentiated epithelial cells. In a number of different malignant tumors EphA1 genes are downregulated. In breast carcinoma the downregulation is associated with invasive behavior of the cell.


Pssm-ID: 188941  Cd Length: 63  Bit Score: 63.87  E-value: 9.02e-13
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 111118978 915 FNTVDEWLEAIKMGQYKESFANAGFTSFDVVSQMMMEDILRVGVTLAGHQKKILNSIQ 972
Cdd:cd09542    4 YRSVSEWLESIRMKRYILHFRSAGLDTMECVLELTAEDLTQMGITLPGHQKRILCSIQ 61
STKc_CDK6 cd07862
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 6; STKs ...
627-853 9.51e-13

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: 70.06  E-value: 9.51e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGH-LKLPGKreiFVAIKTLKSGYTEK-QRRDFLSEASIMGQ---FDHPNVIHLEGVVTKS-----TPVM 696
Cdd:cd07862    9 IGEGAYGKVFKARdLKNGGR---FVALKRVRVQTGEEgMPLSTIREVAVLRHletFEHPNVVRLFDVCTVSrtdreTKLT 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 697 IITEFMENgSLDSFL-RQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLeddt 775
Cdd:cd07862   86 LVFEHVDQ-DLTTYLdKVPEPGVPTETIKDMMFQLLRGLDFLHSHRVVHRDLKPQNILVTSSGQIKLADFGLARIY---- 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 776 sdpTYTSALGGKIPIRW-TAPEAIQYRKFTSASDVWSYGIVMWEVmsYGERPYWdMTNQDV--INAIEQDYRLPPPMDCP 852
Cdd:cd07862  161 ---SFQMALTSVVVTLWyRAPEVLLQSSYATPVDLWSVGCIFAEM--FRRKPLF-RGSSDVdqLGKILDVIGLPGEEDWP 234

                 .
gi 111118978 853 S 853
Cdd:cd07862  235 R 235
STKc_Pho85 cd07836
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; ...
621-839 1.05e-12

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: 69.82  E-value: 1.05e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQvIGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITE 700
Cdd:cd07836    3 KQLEK-LGEGTYATVYKGRNRTTGE---IVALKEIHLDAEEGTPSTAIREISLMKELKHENIVRLHDVIHTENKLMLVFE 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMEN------------GSLD-----SFLRQndgqftviqlvgMLRGIAagmkYLADMNYVHRDLAARNILVNSNLVCKVS 763
Cdd:cd07836   79 YMDKdlkkymdthgvrGALDpntvkSFTYQ------------LLKGIA----FCHENRVLHRDLKPQNLLINKRGELKLA 142
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 764 DFGLSRfleddtsdptytsALGgkIPIR----------WTAPEAIQ-YRKFTSASDVWSYGIVMWEvMSYGERPYWDMTN 832
Cdd:cd07836  143 DFGLAR-------------AFG--IPVNtfsnevvtlwYRAPDVLLgSRTYSTSIDIWSVGCIMAE-MITGRPLFPGTNN 206

                 ....*..
gi 111118978 833 QDVINAI 839
Cdd:cd07836  207 EDQLLKI 213
STKc_TBK1 cd13988
Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1; STKs catalyze the ...
627-827 1.08e-12

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: 70.21  E-value: 1.08e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKreiFVAIKTLKS-GY---TEKQRRDFlseaSIMGQFDHPNVIHLEGVVTKSTPV--MIITE 700
Cdd:cd13988    1 LGQGATANVFRGRHKKTGD---LYAVKVFNNlSFmrpLDVQMREF----EVLKKLNHKNIVKLFAIEEELTTRhkVLVME 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMENGSLDSFLRQNDGQFTVIQ--LVGMLRGIAAGMKYLADMNYVHRDLAARNILV----NSNLVCKVSDFGLSRFLEDD 774
Cdd:cd13988   74 LCPCGSLYTVLEEPSNAYGLPEseFLIVLRDVVAGMNHLRENGIVHRDIKPGNIMRvigeDGQSVYKLTDFGAARELEDD 153
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 111118978 775 TSdptYTSALGGK------IPIRWTAPEAIQyRKFTSASDVWSYGIVMWEVMSyGERPY 827
Cdd:cd13988  154 EQ---FVSLYGTEeylhpdMYERAVLRKDHQ-KKYGATVDLWSIGVTFYHAAT-GSLPF 207
STKc_Twitchin_like cd14114
The catalytic domain of the Giant Serine/Threonine Kinases, Twitchin and Projectin; STKs ...
623-827 1.08e-12

The catalytic domain of the Giant Serine/Threonine Kinases, Twitchin and Projectin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. Twitchin and Projectin are both associated with thick filaments. Twitchin is localized in the outer parts of A-bands and is involved in regulating muscle contraction. It interacts with the myofibrillar proteins myosin and actin in a phosphorylation-dependent manner, and may be involved in regulating the myosin cross-bridge cycle. The kinase activity of Twitchen is activated by Ca2+ and the Ca2+ binding protein S100A1. Projectin is associated with the end of thick filaments and is a component of flight muscle connecting filaments. The kinase domain of Projectin may play roles in autophosphorylation and transphosphorylation, which impact the formation of myosin filaments. The Twitchin-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271016 [Multi-domain]  Cd Length: 259  Bit Score: 69.15  E-value: 1.08e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 623 IEQVIGAGEFGEVCSGHLKLPGKreIFVA--IKTLKSGYTEKQRRdflsEASIMGQFDHPNVIHLEGVVTKSTPVMIITE 700
Cdd:cd14114    6 ILEELGTGAFGVVHRCTERATGN--NFAAkfIMTPHESDKETVRK----EIQIMNQLHHPKLINLHDAFEDDNEMVLILE 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILV---NSNLVcKVSDFGLSRFLEDDTSD 777
Cdd:cd14114   80 FLSGGELFERIAAEHYKMSEAEVINYMRQVCEGLCHMHENNIVHLDIKPENIMCttkRSNEV-KLIDFGLATHLDPKESV 158
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 111118978 778 PTYTSAlggkipIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPY 827
Cdd:cd14114  159 KVTTGT------AEFAAPEIVEREPVGFYTDMWAVGVLSYVLLS-GLSPF 201
STKc_nPKC_theta_like cd05592
Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and ...
625-827 1.08e-12

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


Pssm-ID: 270744 [Multi-domain]  Cd Length: 320  Bit Score: 70.11  E-value: 1.08e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKlpgKREIFVAIKTLK-----------SGYTEKQrrdFLSEASImgqfdHPNVIHLEGVVTKST 693
Cdd:cd05592    1 KVLGKGSFGKVMLAELK---GTNQYFAIKALKkdvvledddveCTMIERR---VLALASQ-----HPFLTHLFCTFQTES 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 694 PVMIITEFMENGSLdSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRflED 773
Cdd:cd05592   70 HLFFVMEYLNGGDL-MFHIQQSGRFDEDRARFYGAEIICGLQFLHSRGIIYRDLKLDNVLLDREGHIKIADFGMCK--EN 146
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 111118978 774 DTSDPTYTSALGgkIPiRWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPY 827
Cdd:cd05592  147 IYGENKASTFCG--TP-DYIAPEILKGQKYNQSVDWWSFGVLLYE-MLIGQSPF 196
STKc_MSK1_C cd14179
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
679-827 1.33e-12

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


Pssm-ID: 271081 [Multi-domain]  Cd Length: 310  Bit Score: 69.68  E-value: 1.33e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 679 HPNVIHLEGVVTKSTPVMIITEFMENGSLDSFLRQNDgQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILV---N 755
Cdd:cd14179   61 HPNIVKLHEVYHDQLHTFLVMELLKGGELLERIKKKQ-HFSETEASHIMRKLVSAVSHMHDVGVVHRDLKPENLLFtdeS 139
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 111118978 756 SNLVCKVSDFGLSRFLEDDTS---DPTYTsalggkipIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPY 827
Cdd:cd14179  140 DNSEIKIIDFGFARLKPPDNQplkTPCFT--------LHYAAPELLNYNGYDESCDLWSLGVILYTMLS-GQVPF 205
STKc_TAO1 cd06635
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 1; STKs catalyze ...
627-842 1.43e-12

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


Pssm-ID: 270805 [Multi-domain]  Cd Length: 317  Bit Score: 69.69  E-value: 1.43e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHlklPGKREIFVAIKtlKSGYTEKQR----RDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFM 702
Cdd:cd06635   33 IGHGSFGAVYFAR---DVRTSEVVAIK--KMSYSGKQSnekwQDIIKEVKFLQRIKHPNSIEYKGCYLREHTAWLVMEYC 107
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 703 EnGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFleddtSDPTyTS 782
Cdd:cd06635  108 L-GSASDLLEVHKKPLQEIEIAAITHGALQGLAYLHSHNMIHRDIKAGNILLTEPGQVKLADFGSASI-----ASPA-NS 180
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 111118978 783 ALGGKIpirWTAPE---AIQYRKFTSASDVWSYGIVMWEVmsyGER--PYWDMTNQDVINAIEQD 842
Cdd:cd06635  181 FVGTPY---WMAPEvilAMDEGQYDGKVDVWSLGITCIEL---AERkpPLFNMNAMSALYHIAQN 239
STKc_PLK2 cd14188
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the ...
663-877 1.70e-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: 68.50  E-value: 1.70e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 663 QRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGSLDSFLRQNDgQFTVIQLVGMLRGIAAGMKYLADMNY 742
Cdd:cd14188   44 QREKIDKEIELHRILHHKHVVQFYHYFEDKENIYILLEYCSRRSMAHILKARK-VLTEPEVRYYLRQIVSGLKYLHEQEI 122
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 743 VHRDLAARNILVNSNLVCKVSDFGLSRFLE-------DDTSDPTYTSalggkipirwtaPEAIQYRKFTSASDVWSYGIV 815
Cdd:cd14188  123 LHRDLKLGNFFINENMELKVGDFGLAARLEplehrrrTICGTPNYLS------------PEVLNKQGHGCESDIWALGCV 190
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 111118978 816 MWeVMSYGeRPYWDMTN-QDVINAI-EQDYRLPPPMDCPSalHQLMLDCWQKDRNHRPKFGQIV 877
Cdd:cd14188  191 MY-TMLLG-RPPFETTNlKETYRCIrEARYSLPSSLLAPA--KHLIASMLSKNPEDRPSLDEII 250
fn3 pfam00041
Fibronectin type III domain;
326-421 1.95e-12

Fibronectin type III domain;


Pssm-ID: 394996 [Multi-domain]  Cd Length: 85  Bit Score: 63.59  E-value: 1.95e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  326 SAPQAV-ISSVNETSLMLEWTPPRDSGGrEDLVYNIICKSCGSGRGActrcgdnvqyAPRQLGLTEPRIYISDLLAHTQY 404
Cdd:pfam00041   1 SAPSNLtVTDVTSTSLTVSWTPPPDGNG-PITGYEVEYRPKNSGEPW----------NEITVPGTTTSVTLTGLKPGTEY 69
                          90
                  ....*....|....*..
gi 111118978  405 TFEIQAVNGVTdQSPFS 421
Cdd:pfam00041  70 EVRVQAVNGGG-EGPPS 85
STKc_Rim15_like cd05611
Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the ...
627-840 2.03e-12

Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include Saccharomyces cerevisiae Rim15, Schizosaccharomyces pombe cek1, and similar fungal proteins. They contain a central catalytic domain, which contains an insert relative to MAST kinases. In addition, Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. Rim15 (or Rim15p) functions as a regulator of meiosis. It acts as a downstream effector of PKA and regulates entry into stationary phase (G0). Thus, it plays a crucial role in regulating yeast proliferation, differentiation, and aging. Cek1 may facilitate progression of mitotic anaphase. The Rim15-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: 270762 [Multi-domain]  Cd Length: 263  Bit Score: 68.66  E-value: 2.03e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKreiFVAIKTLK--SGYTEKQRRDFLSEASI-MGQFDHPNVIHLEGVVTKSTPVMIITEFME 703
Cdd:cd05611    4 ISKGAFGSVYLAKKRSTGD---YFAIKVLKksDMIAKNQVTNVKAERAImMIQGESPYVAKLYYSFQSKDYLYLVMEYLN 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 704 NGSLDsflrqndgqfTVIQLVGML-----RGIAA----GMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDD 774
Cdd:cd05611   81 GGDCA----------SLIKTLGGLpedwaKQYIAevvlGVEDLHQRGIIHRDIKPENLLIDQTGHLKLTDFGLSRNGLEK 150
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 111118978 775 TSDPTYTSAlggkiPiRWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVINAIE 840
Cdd:cd05611  151 RHNKKFVGT-----P-DYLAPETILGVGDDKMSDWWSLGCVIFE-FLFGYPPFHAETPDAVFDNIL 209
STKc_PSKH1 cd14087
Catalytic domain of the Protein Serine/Threonine kinase H1; STKs catalyze the transfer of the ...
623-829 2.38e-12

Catalytic domain of the Protein Serine/Threonine kinase H1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PSKH1 is an autophosphorylating STK that is expressed ubiquitously and exhibits multiple intracellular localizations including the centrosome, Golgi apparatus, and splice factor compartments. It contains a catalytic kinase domain and an N-terminal SH4-like motif that is acylated to facilitate membrane attachment. PSKH1 plays a rile in the maintenance of the Golgi apparatus, an important organelle within the secretory pathway. It may also function as a novel splice factor and a regulator of prostate cancer cell growth. The PSKH1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270989 [Multi-domain]  Cd Length: 259  Bit Score: 68.33  E-value: 2.38e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 623 IEQVIGAGEFGEVCSGHLKLpgKREIFvAIKTLKSGYTEKQRrdFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFM 702
Cdd:cd14087    5 IKALIGRGSFSRVVRVEHRV--TRQPY-AIKMIETKCRGREV--CESELNVLRRVRHTNIIQLIEVFETKERVYMVMELA 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 703 ENGSL-DSFLRQndGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNIL-----VNSNLVckVSDFGLSRFlEDDTS 776
Cdd:cd14087   80 TGGELfDRIIAK--GSFTERDATRVLQMVLDGVKYLHGLGITHRDLKPENLLyyhpgPDSKIM--ITDFGLAST-RKKGP 154
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 111118978 777 DPTYTSALGGKipiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWD 829
Cdd:cd14087  155 NCLMKTTCGTP---EYIAPEILLRKPYTQSVDMWAVGVIAYILLS-GTMPFDD 203
STKc_PLK1 cd14187
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; STKs catalyze the ...
646-878 2.85e-12

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: 68.04  E-value: 2.85e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 646 REIFVAIKTLKSGYTEKQRRDFLS-EASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGSLDSfLRQNDGQFTVIQLV 724
Cdd:cd14187   32 KEVFAGKIVPKSLLLKPHQKEKMSmEIAIHRSLAHQHVVGFHGFFEDNDFVYVVLELCRRRSLLE-LHKRRKALTEPEAR 110
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 725 GMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDtSDPTYTsaLGGKiPiRWTAPEAIQYRKFT 804
Cdd:cd14187  111 YYLRQIILGCQYLHRNRVIHRDLKLGNLFLNDDMEVKIGDFGLATKVEYD-GERKKT--LCGT-P-NYIAPEVLSKKGHS 185
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 111118978 805 SASDVWSYGIVMWEVMsYGERPYWDMTNQDVINAIEQ-DYRLPPPMD-CPSALHQLMLdcwQKDRNHRPKFGQIVN 878
Cdd:cd14187  186 FEVDIWSIGCIMYTLL-VGKPPFETSCLKETYLRIKKnEYSIPKHINpVAASLIQKML---QTDPTARPTINELLN 257
STKc_MAPK15-like cd07852
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15 and ...
660-818 2.91e-12

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15 and similar MAPKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human MAPK15 is also called Extracellular signal Regulated Kinase 8 (ERK8) while the rat protein is called ERK7. ERK7 and ERK8 display both similar and different biochemical properties. They autophosphorylate and activate themselves and do not require upstream activating kinases. ERK7 is constitutively active and is not affected by extracellular stimuli whereas ERK8 shows low basal activity and is activated by DNA-damaging agents. ERK7 and ERK8 also have different substrate profiles. Genome analysis shows that they are orthologs with similar gene structures. ERK7 and ERK 8 may be involved in the signaling of some nuclear receptor transcription factors. ERK7 regulates hormone-dependent degradation of estrogen receptor alpha while ERK8 down-regulates the transcriptional co-activation androgen and glucocorticoid receptors. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK15 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270841 [Multi-domain]  Cd Length: 337  Bit Score: 69.12  E-value: 2.91e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 660 TEKQR--RD--FLSEASimgqfDHPNVIHLEGVV--TKSTPVMIITEFMENgSLDSFLRQN-----DGQFTVIQLvgmLR 728
Cdd:cd07852   48 TDAQRtfREimFLQELN-----DHPNIIKLLNVIraENDKDIYLVFEYMET-DLHAVIRANilediHKQYIMYQL---LK 118
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 729 GIaagmKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFL---EDDTSDPTYTSAlggkIPIRW-TAPEA-IQYRKF 803
Cdd:cd07852  119 AL----KYLHSGGVIHRDLKPSNILLNSDCRVKLADFGLARSLsqlEEDDENPVLTDY----VATRWyRAPEIlLGSTRY 190
                        170
                 ....*....|....*
gi 111118978 804 TSASDVWSYGIVMWE 818
Cdd:cd07852  191 TKGVDMWSVGCILGE 205
PK_KSR2 cd14153
Pseudokinase domain of Kinase Suppressor of Ras 2; The pseudokinase domain shows similarity to ...
621-883 3.11e-12

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: 68.11  E-value: 3.11e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQVIGAGEFGEVCSGhlKLPGKreifVAIKTLK-SGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIIT 699
Cdd:cd14153    2 LEIGELIGKGRFGQVYHG--RWHGE----VAIRLIDiERDNEEQLKAFKREVMAYRQTRHENVVLFMGACMSPPHLAIIT 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCkVSDFGL---SRFL----- 771
Cdd:cd14153   76 SLCKGRTLYSVVRDAKVVLDVNKTRQIAQEIVKGMGYLHAKGILHKDLKSKNVFYDNGKVV-ITDFGLftiSGVLqagrr 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 772 EDDTSDPT-YTSALGGKIpIRWTAPEAIQYR-KFTSASDVWSYGIVMWEVMSYgerpYWDMTNQDVINAIEQDYRLPPP- 848
Cdd:cd14153  155 EDKLRIQSgWLCHLAPEI-IRQLSPETEEDKlPFSKHSDVFAFGTIWYELHAR----EWPFKTQPAEAIIWQVGSGMKPn 229
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 111118978 849 ---MDCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKM 883
Cdd:cd14153  230 lsqIGMGKEISDILLFCWAYEQEERPTFSKLMEMLEKL 267
STKc_GRK6 cd05630
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6; STKs ...
625-827 3.16e-12

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: 68.13  E-value: 3.16e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGYTEKQRRD--FLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFM 702
Cdd:cd05630    6 RVLGKGGFGEVCACQVRATGK---MYACKKLEKKRIKKRKGEamALNEKQILEKVNSRFVVSLAYAYETKDALCLVLTLM 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 703 ENGSLDSFL-RQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDPTYT 781
Cdd:cd05630   83 NGGDLKFHIyHMGQAGFPEARAVFYAAEICCGLEDLHRERIVYRDLKPENILLDDHGHIRISDLGLAVHVPEGQTIKGRV 162
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 111118978 782 SALGgkipirWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPY 827
Cdd:cd05630  163 GTVG------YMAPEVVKNERYTFSPDWWALGCLLYEMIA-GQSPF 201
PK_eIF2AK_GCN2_rpt1 cd14012
Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or ...
676-871 3.46e-12

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: 67.77  E-value: 3.46e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 676 QFDHPNVIHLEGVVTKSTP------VMIITEFMENGSLDSFLrQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAA 749
Cdd:cd14012   54 KLRHPNLVSYLAFSIERRGrsdgwkVYLLTEYAPGGSLSELL-DSVGSVPLDTARRWTLQLLEALEYLHRNGVVHKSLHA 132
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 750 RNILVNSNL---VCKVSDFGLSRFLEDDTSDPTYTSAlggkIPIRWTAPEAIQ-YRKFTSASDVWSYGIVMWEVMSYGER 825
Cdd:cd14012  133 GNVLLDRDAgtgIVKLTDYSLGKTLLDMCSRGSLDEF----KQTYWLPPELAQgSKSPTRKTDVWDLGLLFLQMLFGLDV 208
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 111118978 826 PYWDMTNQDVINaieqdyrlppPMDCPSALHQLMLDCWQKDRNHRP 871
Cdd:cd14012  209 LEKYTSPNPVLV----------SLDLSASLQDFLSKCLSLDPKKRP 244
STKc_RSK_C cd14091
C-terminal catalytic domain of the Serine/Threonine Kinases, Ribosomal S6 kinases; STKs ...
623-827 3.86e-12

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: 68.04  E-value: 3.86e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 623 IEQVIGAGEFGEVCSGHLKLPGKReifVAIKTLKsgyteKQRRDFLSEASIM---GQfdHPNVIHLEGVVTKSTPVMIIT 699
Cdd:cd14091    4 IKEEIGKGSYSVCKRCIHKATGKE---YAVKIID-----KSKRDPSEEIEILlryGQ--HPNIITLRDVYDDGNSVYLVT 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENGSL-DSFLRQndGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNL----VCKVSDFGLSRFLEDD 774
Cdd:cd14091   74 ELLRGGELlDRILRQ--KFFSEREASAVMKTLTKTVEYLHSQGVVHRDLKPSNILYADESgdpeSLRICDFGFAKQLRAE 151
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 111118978 775 TS---DPTYTSalggkipiRWTAPEAIQYRKFTSASDVWSYGIVMWeVMSYGERPY 827
Cdd:cd14091  152 NGllmTPCYTA--------NFVAPEVLKKQGYDAACDIWSLGVLLY-TMLAGYTPF 198
STKc_CDK2_3 cd07860
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase 2 and 3; ...
622-821 4.11e-12

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: 67.91  E-value: 4.11e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQvIGAGEFGEVCSGHLKLPGKreiFVAIKTLK-SGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITE 700
Cdd:cd07860    4 KVEK-IGEGTYGVVYKARNKLTGE---VVALKKIRlDTETEGVPSTAIREISLLKELNHPNIVKLLDVIHTENKLYLVFE 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMeNGSLDSFLRQNDGQFTVIQLV-GMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRfleddtsdpt 779
Cdd:cd07860   80 FL-HQDLKKFMDASALTGIPLPLIkSYLFQLLQGLAFCHSHRVLHRDLKPQNLLINTEGAIKLADFGLAR---------- 148
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 111118978 780 ytsALGgkIPIR----------WTAPEAIQYRKF-TSASDVWSYGIVMWEVMS 821
Cdd:cd07860  149 ---AFG--VPVRtythevvtlwYRAPEILLGCKYySTAVDIWSLGCIFAEMVT 196
STKc_Pat1_like cd13993
Catalytic domain of Fungal Pat1-like Serine/Threonine kinases; STKs catalyze the transfer of ...
622-816 4.30e-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: 67.76  E-value: 4.30e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGH-LKLPGKreifVAIKTL-KSGYTEK-----QRRDFLSEASIMGQF-DHPNVIHLEGVVTKST 693
Cdd:cd13993    3 QLISPIGEGAYGVVYLAVdLRTGRK----YAIKCLyKSGPNSKdgndfQKLPQLREIDLHRRVsRHPNIITLHDVFETEV 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 694 PVMIITEFMENGSLDSFLRQND---GQFTVIQLVgMLRgIAAGMKYLADMNYVHRDLAARNILVNSN-LVCKVSDFGLSr 769
Cdd:cd13993   79 AIYIVLEYCPNGDLFEAITENRiyvGKTELIKNV-FLQ-LIDAVKHCHSLGIYHRDIKPENILLSQDeGTVKLCDFGLA- 155
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 111118978 770 fleddTSDPT-YTSALGGKipiRWTAPEAI----QYRKF--TSASDVWSYGIVM 816
Cdd:cd13993  156 -----TTEKIsMDFGVGSE---FYMAPECFdevgRSLKGypCAAGDIWSLGIIL 201
PKc_Mps1 cd14131
Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle ...
621-871 4.50e-12

Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle 1 (also called TTK); Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TTK/Mps1 is a spindle checkpoint kinase that was first discovered due to its necessity in centrosome duplication in budding yeast. It was later found to function in the spindle assembly checkpoint, which monitors the proper attachment of chromosomes to the mitotic spindle. In yeast, substrates of Mps1 include the spindle pole body components Spc98p, Spc110p, and Spc42p. The TTK/Mps1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271033 [Multi-domain]  Cd Length: 271  Bit Score: 67.62  E-value: 4.50e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQvIGAGEFGEVcsgHLKLPGKREIFvAIKTLK-SGYTEKQRRDFLSEASIMGQF-DHPNVIHL---EGVVTKSTPV 695
Cdd:cd14131    4 EILKQ-LGKGGSSKV---YKVLNPKKKIY-ALKRVDlEGADEQTLQSYKNEIELLKKLkGSDRIIQLydyEVTDEDDYLY 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 696 MIitefMENGSLD--SFLRQNDGQ-----FTVIQLVGMLRGIaagmKYLADMNYVHRDLAARN-ILVNSNLvcKVSDFGL 767
Cdd:cd14131   79 MV----MECGEIDlaTILKKKRPKpidpnFIRYYWKQMLEAV----HTIHEEGIVHSDLKPANfLLVKGRL--KLIDFGI 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 768 SRFLEDDTSDPTYTSALGgkiPIRWTAPEAIQYRKFTS----------ASDVWSYGIVMWEvMSYGERPYWDMTNQ-DVI 836
Cdd:cd14131  149 AKAIQNDTTSIVRDSQVG---TLNYMSPEAIKDTSASGegkpkskigrPSDVWSLGCILYQ-MVYGKTPFQHITNPiAKL 224
                        250       260       270
                 ....*....|....*....|....*....|....*..
gi 111118978 837 NAI-EQDYRLP-PPMDCPSALHqLMLDCWQKDRNHRP 871
Cdd:cd14131  225 QAIiDPNHEIEfPDIPNPDLID-VMKRCLQRDPKKRP 260
STKc_CDK4_6_like cd07838
Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; ...
627-818 4.51e-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: 67.69  E-value: 4.51e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKreiFVAIKTLK-SGYTEKQRRDFLSEASIMGQ---FDHPNVIHLEGV-----VTKSTPVMI 697
Cdd:cd07838    7 IGEGAYGTVYKARDLQDGR---FVALKKVRvPLSEEGIPLSTIREIALLKQlesFEHPNVVRLLDVchgprTDRELKLTL 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 698 ITEFMENgSLDSFLRQ-NDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLeddts 776
Cdd:cd07838   84 VFEHVDQ-DLATYLDKcPKPGLPPETIKDLMRQLLRGLDFLHSHRIVHRDLKPQNILVTSDGQVKLADFGLARIY----- 157
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 111118978 777 dpTYTSALGGKIPIRW-TAPEAIQYRKFTSASDVWSYGIVMWE 818
Cdd:cd07838  158 --SFEMALTSVVVTLWyRAPEVLLQSSYATPVDMWSVGCIFAE 198
STKc_HUNK cd14070
Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase ...
623-827 4.93e-12

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: 67.15  E-value: 4.93e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 623 IEQVIGAGEFGEVCSGHLKLPGKReifVAIKTL------KSGYTEKQRRdflSEASIMGQFDHPNVIHLEGVVTKSTPVM 696
Cdd:cd14070    6 IGRKLGEGSFAKVREGLHAVTGEK---VAIKVIdkkkakKDSYVTKNLR---REGRIQQMIRHPNITQLLDILETENSYY 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 697 IITEFMENGSL------DSFLRQNDGQFTVIQLVgmlrgiaAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSR- 769
Cdd:cd14070   80 LVMELCPGGNLmhriydKKRLEEREARRYIRQLV-------SAVEHLHRAGVVHRDLKIENLLLDENDNIKLIDFGLSNc 152
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 111118978 770 FLEDDTSDPTYTSAlGGKIpirWTAPEAIQYRKFTSASDVWSYGIVMWeVMSYGERPY 827
Cdd:cd14070  153 AGILGYSDPFSTQC-GSPA---YAAPELLARKKYGPKVDVWSIGVNMY-AMLTGTLPF 205
STKc_MOK cd07831
Catalytic domain of the Serine/Threonine Kinase, MAPK/MAK/MRK Overlapping Kinase; STKs ...
627-848 5.07e-12

Catalytic domain of the Serine/Threonine Kinase, MAPK/MAK/MRK Overlapping Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MOK, also called Renal tumor antigen 1 (RAGE-1), is widely expressed and is enriched in testis, kidney, lung, and brain. It is expressed in approximately 50% of renal cell carcinomas (RCC) and is a potential target for immunotherapy. MOK is stabilized by its association with the HSP90 molecular chaperone. It is induced by the transcription factor Cdx2 and may be involved in regulating intestinal epithelial development and differentiation. The MOK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270825 [Multi-domain]  Cd Length: 282  Bit Score: 67.68  E-value: 5.07e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGYTEKQRRDFLSEASIMGQF-DHPNVIHLEGVVTKSTP--VMIITEFME 703
Cdd:cd07831    7 IGEGTFSEVLKAQSRKTGK---YYAIKCMKKHFKSLEQVNNLREIQALRRLsPHPNILRLIEVLFDRKTgrLALVFELMD 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 704 nGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVcKVSDFGLSRFLeddTSDPTYTSA 783
Cdd:cd07831   84 -MNLYELIKGRKRPLPEKRVKNYMYQLLKSLDHMHRNGIFHRDIKPENILIKDDIL-KLADFGSCRGI---YSKPPYTEY 158
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 784 lggkIPIRW-TAPEAI---QYrkFTSASDVWSYGIVMWEVMSYgeRPYWDMTNQ-DVINAIEQDYRLPPP 848
Cdd:cd07831  159 ----ISTRWyRAPECLltdGY--YGPKMDIWAVGCVFFEILSL--FPLFPGTNElDQIAKIHDVLGTPDA 220
STKc_nPKC_theta cd05619
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze ...
615-842 6.25e-12

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: 68.03  E-value: 6.25e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 615 EIDISCVKIEQVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGY---------TEKQRRdFLSEAsimgqFDHPNVIHL 685
Cdd:cd05619    1 KLTIEDFVLHKMLGKGSFGKVFLAELKGTNQ---FFAIKALKKDVvlmdddvecTMVEKR-VLSLA-----WEHPFLTHL 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 686 EGVVTKSTPVMIITEFMENGSLdSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDF 765
Cdd:cd05619   72 FCTFQTKENLFFVMEYLNGGDL-MFHIQSCHKFDLPRATFYAAEIICGLQFLHSKGIVYRDLKLDNILLDKDGHIKIADF 150
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 111118978 766 GLSRflEDDTSDPTYTSALGGKipiRWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVINAIEQD 842
Cdd:cd05619  151 GMCK--ENMLGDAKTSTFCGTP---DYIAPEILLGQKYNTSVDWWSFGVLLYE-MLIGQSPFHGQDEEELFQSIRMD 221
PKc_MEK cd06615
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
664-826 6.29e-12

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 and MEK2 are MAPK kinases (MAPKKs or MKKs), and are dual-specificity PKs that phosphorylate and activate the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1/2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. This cascade has also been implicated in synaptic plasticity, migration, morphological determination, and stress response immunological reactions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1/2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132946 [Multi-domain]  Cd Length: 308  Bit Score: 67.85  E-value: 6.29e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 664 RRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGSLDSFLRQNdGQFTVIQLVGMLRGIAAGMKYLAD-MNY 742
Cdd:cd06615   43 RNQIIRELKVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVLKKA-GRIPENILGKISIAVLRGLTYLREkHKI 121
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 743 VHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDptytSALGGKipiRWTAPEAIQYRKFTSASDVWSYGIVMWEvMSY 822
Cdd:cd06615  122 MHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMAN----SFVGTR---SYMSPERLQGTHYTVQSDIWSLGLSLVE-MAI 193

                 ....
gi 111118978 823 GERP 826
Cdd:cd06615  194 GRYP 197
STKc_CRIK cd05601
Catalytic domain of the Serine/Threonine Kinase, Citron Rho-interacting kinase; STKs catalyze ...
623-827 6.39e-12

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: 68.11  E-value: 6.39e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 623 IEQVIGAGEFGEVcsgHL-KLPGKREIFvAIKTLKSGYTEKQRRD--FLSEASIMGQFDHPNVIHLEGVVTKSTPVMIIT 699
Cdd:cd05601    5 VKNVIGRGHFGEV---QVvKEKATGDIY-AMKVLKKSETLAQEEVsfFEEERDIMAKANSPWITKLQYAFQDSENLYLVM 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLeddTSDPT 779
Cdd:cd05601   81 EYHPGGDLLSLLSRYDDIFEESMARFYLAELVLAIHSLHSMGYVHRDIKPENILIDRTGHIKLADFGSAAKL---SSDKT 157
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 111118978 780 YTSalggKIPI---RWTAPEAIQYRKFTSAS------DVWSYGIVMWEvMSYGERPY 827
Cdd:cd05601  158 VTS----KMPVgtpDYIAPEVLTSMNGGSKGtygvecDWWSLGIVAYE-MLYGKTPF 209
STKc_JNK cd07850
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase; STKs catalyze the ...
625-818 6.61e-12

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. They are also essential regulators of physiological and pathological processes and are involved in the pathogenesis of several diseases such as diabetes, atherosclerosis, stroke, Parkinson's and Alzheimer's. Vetebrates harbor three different JNK genes (Jnk1, Jnk2, and Jnk3) that are alternatively spliced to produce at least 10 isoforms. JNKs are specifically activated by the MAPK kinases MKK4 and MKK7, which are in turn activated by upstream MAPK kinase kinases as a result of different stimuli including stresses such as ultraviolet (UV) irradiation, hyperosmolarity, heat shock, or cytokines. JNKs activate a large number of different substrates based on specific stimulus, cell type, and cellular condition, and may be implicated in seemingly contradictory functions. The JNK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270840 [Multi-domain]  Cd Length: 337  Bit Score: 67.82  E-value: 6.61e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKLPGKReifVAIKTLKSGY---TEKQR--RDFLseasIMGQFDHPNVIHLEGVVTKSTP----- 694
Cdd:cd07850    6 KPIGSGAQGIVCAAYDTVTGQN---VAIKKLSRPFqnvTHAKRayRELV----LMKLVNHKNIIGLLNVFTPQKSleefq 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 695 -VMIITEFMengslDSFLRQndgqftVIQ-----------LVGMLRGIaagmKYLADMNYVHRDLAARNILVNSNLVCKV 762
Cdd:cd07850   79 dVYLVMELM-----DANLCQ------VIQmdldhermsylLYQMLCGI----KHLHSAGIIHRDLKPSNIVVKSDCTLKI 143
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 111118978 763 SDFGLSRFLEDDTSDPTYTsalggkIPIRWTAPEAIQYRKFTSASDVWSYGIVMWE 818
Cdd:cd07850  144 LDFGLARTAGTSFMMTPYV------VTRYYRAPEVILGMGYKENVDIWSVGCIMGE 193
PKc_MEK1 cd06650
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
664-826 6.71e-12

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 1; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 is a dual-specificity PK and a MAPK kinase (MAPKK or MKK) that phosphorylates and activates the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. MEK1 also plays a role in cell cycle control. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270816 [Multi-domain]  Cd Length: 319  Bit Score: 67.77  E-value: 6.71e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 664 RRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGSLDSFLRQNdGQFTViQLVGMLR-GIAAGMKYLADMNY 742
Cdd:cd06650   47 RNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVLKKA-GRIPE-QILGKVSiAVIKGLTYLREKHK 124
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 743 V-HRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDptytSALGGKipiRWTAPEAIQYRKFTSASDVWSYGIVMWEvMS 821
Cdd:cd06650  125 ImHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMAN----SFVGTR---SYMSPERLQGTHYSVQSDIWSMGLSLVE-MA 196

                 ....*
gi 111118978 822 YGERP 826
Cdd:cd06650  197 VGRYP 201
STKc_DRAK1 cd14197
Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
678-841 7.15e-12

Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 (also called STK17A) and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. Rabbit DRAK1 has been shown to induce apoptosis in osteoclasts and overexpressio of human DRAK1 induces apoptosis in cultured fibroblast cells. DRAK1 may be involved in apoptotic signaling. The DRAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271099 [Multi-domain]  Cd Length: 271  Bit Score: 66.88  E-value: 7.15e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 678 DHPNVIHLEGVVTKSTPVMIITEFMENGSL-DSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNS 756
Cdd:cd14197   67 ANPWVINLHEVYETASEMILVLEYAAGGEIfNQCVADREEAFKEKDVKRLMKQILEGVSFLHNNNVVHLDLKPQNILLTS 146
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 757 NLV---CKVSDFGLSRFLEDD------TSDPTYTsalggkipirwtAPEAIQYRKFTSASDVWSYGIVMWeVMSYGERPY 827
Cdd:cd14197  147 ESPlgdIKIVDFGLSRILKNSeelreiMGTPEYV------------APEILSYEPISTATDMWSIGVLAY-VMLTGISPF 213
                        170
                 ....*....|....
gi 111118978 828 WDMTNQDVINAIEQ 841
Cdd:cd14197  214 LGDDKQETFLNISQ 227
STKc_CaMKIV cd14085
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
651-829 8.16e-12

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: 67.16  E-value: 8.16e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 651 AIKTLKSGYTEKQRRdflSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGSLdsFLR-QNDGQFTVIQLVGMLRG 729
Cdd:cd14085   32 AVKKLKKTVDKKIVR---TEIGVLLRLSHPNIIKLKEIFETPTEISLVLELVTGGEL--FDRiVEKGYYSERDAADAVKQ 106
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 730 IAAGMKYLADMNYVHRDLAARNILVNS---NLVCKVSDFGLSRFLEDDTSDPTYTSALGgkipirWTAPEAIQYRKFTSA 806
Cdd:cd14085  107 ILEAVAYLHENGIVHRDLKPENLLYATpapDAPLKIADFGLSKIVDQQVTMKTVCGTPG------YCAPEILRGCAYGPE 180
                        170       180
                 ....*....|....*....|...
gi 111118978 807 SDVWSYGIVMWeVMSYGERPYWD 829
Cdd:cd14085  181 VDMWSVGVITY-ILLCGFEPFYD 202
STKc_cGK cd05572
Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); ...
627-827 1.07e-11

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: 66.48  E-value: 1.07e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKReifVAIKTLKSGY--TEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMEN 704
Cdd:cd05572    1 LGVGGFGRVELVQLKSKGRT---FALKCVKKRHivQTRQQEHIFSEKEILEECNSPFIVKLYRTFKDKKYLYMLMEYCLG 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 705 GSLDSFLRQN------DGQFTVIQLVgmlrgiaAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSdp 778
Cdd:cd05572   78 GELWTILRDRglfdeyTARFYTACVV-------LAFEYLHSRGIIYRDLKPENLLLDSNGYVKLVDFGFAKKLGSGRK-- 148
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 111118978 779 TYTsaLGGKiPiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPY 827
Cdd:cd05572  149 TWT--FCGT-P-EYVAPEIILNKGYDFSVDYWSLGILLYELLT-GRPPF 192
STKc_PKB_gamma cd05593
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); ...
625-870 1.31e-11

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-gamma is predominantly expressed in neuronal tissues. Mice deficient in PKB-gamma show a reduction in brain weight due to the decreases in cell size and cell number. PKB-gamma has also been shown to be upregulated in estrogen-deficient breast cancer cells, androgen-independent prostate cancer cells, and primary ovarian tumors. It acts as a key mediator in the genesis of ovarian cancer. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270745 [Multi-domain]  Cd Length: 348  Bit Score: 67.41  E-value: 1.31e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGY--TEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFM 702
Cdd:cd05593   21 KLLGKGTFGKVILVREKASGK---YYAMKILKKEViiAKDEVAHTLTESRVLKNTRHPFLTSLKYSFQTKDRLCFVMEYV 97
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 703 ENGSLdSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRflEDDTSDPTYTS 782
Cdd:cd05593   98 NGGEL-FFHLSRERVFSEDRTRFYGAEIVSALDYLHSGKIVYRDLKLENLMLDKDGHIKITDFGLCK--EGITDAATMKT 174
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 783 ALGGKipiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAI-EQDYRLPPPM--DCPSALHQLM 859
Cdd:cd05593  175 FCGTP---EYLAPEVLEDNDYGRAVDWWGLGVVMYEMMC-GRLPFYNQDHEKLFELIlMEDIKFPRTLsaDAKSLLSGLL 250
                        250
                 ....*....|.
gi 111118978 860 LdcwqKDRNHR 870
Cdd:cd05593  251 I----KDPNKR 257
STKc_MSK2_C cd14180
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
679-827 1.35e-11

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271082 [Multi-domain]  Cd Length: 309  Bit Score: 66.82  E-value: 1.35e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 679 HPNVIHLEGVVTKSTPVMIITEFMENGSLDSFLRQNDgQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNS-- 756
Cdd:cd14180   60 HPNIVALHEVLHDQYHTYLVMELLRGGELLDRIKKKA-RFSESEASQLMRSLVSAVSFMHEAGVVHRDLKPENILYADes 138
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 111118978 757 -NLVCKVSDFGLSRfLEDDTSDPTYTSALggkiPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPY 827
Cdd:cd14180  139 dGAVLKVIDFGFAR-LRPQGSRPLQTPCF----TLQYAAPELFSNQGYDESCDLWSLGVILYTMLS-GQVPF 204
STKc_TNIK cd06637
Catalytic domain of the Serine/Threonine Kinase, Traf2- and Nck-Interacting Kinase; STKs ...
625-901 1.37e-11

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: 66.67  E-value: 1.37e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKsgYTEKQRRDFLSEASIMGQFDH-PNVIHLEGVVTKSTP------VMI 697
Cdd:cd06637   12 ELVGNGTYGQVYKGRHVKTGQ---LAAIKVMD--VTGDEEEEIKQEINMLKKYSHhRNIATYYGAFIKKNPpgmddqLWL 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 698 ITEFMENGSLDSFLRQNDGQFTVIQLVGML-RGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLedDTS 776
Cdd:cd06637   87 VMEFCGAGSVTDLIKNTKGNTLKEEWIAYIcREILRGLSHLHQHKVIHRDIKGQNVLLTENAEVKLVDFGVSAQL--DRT 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 777 DPTYTSALGGKIpirWTAPEAIQYRKFTSA-----SDVWSYGIVMWEvMSYGERPYWDMTNQDVINAIEQDyrlPPP--- 848
Cdd:cd06637  165 VGRRNTFIGTPY---WMAPEVIACDENPDAtydfkSDLWSLGITAIE-MAEGAPPLCDMHPMRALFLIPRN---PAPrlk 237
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 111118978 849 -MDCPSALHQLMLDCWQKDRNHRPKFGQIVNtlDKMIRN-PNSLKAMAPLSSGIN 901
Cdd:cd06637  238 sKKWSKKFQSFIESCLVKNHSQRPSTEQLMK--HPFIRDqPNERQVRIQLKDHID 290
FN3 COG3401
Fibronectin type 3 domain [General function prediction only];
319-515 1.40e-11

Fibronectin type 3 domain [General function prediction only];


Pssm-ID: 442628 [Multi-domain]  Cd Length: 603  Bit Score: 68.49  E-value: 1.40e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 319 MPCTTIPSAPQAV-ISSVNETSLMLEWTPPRDSGGREdlvYNIICKSCGSGRgactrcgdnvqyaPRQLGLTEPRIYI-S 396
Cdd:COG3401  227 TTPTTPPSAPTGLtATADTPGSVTLSWDPVTESDATG---YRVYRSNSGDGP-------------FTKVATVTTTSYTdT 290
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 397 DLLAHTQYTFEIQAVNGVTDQSPFSpqfASVNITTNQAAPSAVSIMHQVSRTVDSITLSWSQPDQPNgvILDYELQYYEK 476
Cdd:COG3401  291 GLTNGTTYYYRVTAVDAAGNESAPS---NVVSVTTDLTPPAAPSGLTATAVGSSSITLSWTASSDAD--VTGYNVYRSTS 365
                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 111118978 477 ELSEYNATAIKSPTNTVTVQGLKAGAIYVFQVRARTVAG 515
Cdd:COG3401  366 GGGTYTKIAETVTTTSYTDTGLTPGTTYYYKVTAVDAAG 404
PK_Unc-89_rpt1 cd14109
Pseudokinase domain, first repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein ...
665-827 1.51e-11

Pseudokinase domain, first repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein 89; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. The nematode Unc-89 gene, through alternative promoter use and splicing, encodes at least six major isoforms (Unc-89A to Unc-89F) of giant muscle proteins that are homologs for the vetebrate obscurin. In flies, five isoforms of Unc-89 have been detected: four in the muscles of adult flies (two in the indirect flight muscle and two in other muscles) and another isoform in the larva. Unc-89 in nematodes is required for normal muscle cell architecture. In flies, it is necessary for the development of a symmetrical sarcomere in the flight muscles. Unc-89 proteins contain several adhesion and signaling domains including multiple copies of the immunoglobulin (Ig) domain, as well as fibronectin type III (FN3), SH3, RhoGEF, and PH domains. The nematode Unc-89 isoforms D, C, D, and F contain two kinase domain with B and F having two complete kinase domains while the first repeat of C and D are partial domains. Homology modeling suggests that the first kinase repeat of Unc-89 may be catalytically inactive, a pseudokinase, while the second kinase repeat may be active. The pseudokinase domain may function as a regulatory domain or a protein interaction domain. The Unc-89 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: 271011 [Multi-domain]  Cd Length: 255  Bit Score: 65.61  E-value: 1.51e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 665 RDFL-SEASIMGQFDHPNVIHL-EGVVTKSTPVMIITEFMENG--SLDSFLRQNDgQFTVIQLVGMLRGIAAGMKYLADM 740
Cdd:cd14109   40 DPFLmREVDIHNSLDHPNIVQMhDAYDDEKLAVTVIDNLASTIelVRDNLLPGKD-YYTERQVAVFVRQLLLALKHMHDL 118
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 741 NYVHRDLAARNILVNSNLVCkVSDFGLSRFLEDDTsdpTYTSALGgkIPiRWTAPEAIQYRKFTSASDVWSYGIVMWEVM 820
Cdd:cd14109  119 GIAHLDLRPEDILLQDDKLK-LADFGQSRRLLRGK---LTTLIYG--SP-EFVSPEIVNSYPVTLATDMWSVGVLTYVLL 191

                 ....*..
gi 111118978 821 SyGERPY 827
Cdd:cd14109  192 G-GISPF 197
STKc_CDK4 cd07863
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4; STKs ...
627-819 1.64e-11

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 partners with all three D-type cyclins (D1, D2, and D3) and is also regulated by INK4 inhibitors. It is active towards the retinoblastoma (pRb) protein and plays a role in regulating the early G1 phase of the cell cycle. It is expressed ubiquitously and is localized in the nucleus. CDK4 also shows kinase activity towards Smad3, a signal transducer of TGF-beta signaling which modulates transcription and plays a role in cell proliferation and apoptosis. CDK4 is inhibited by the p21 inhibitor and is specifically mutated in human melanoma. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143368 [Multi-domain]  Cd Length: 288  Bit Score: 66.14  E-value: 1.64e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGYTEkqrrDFLSEASI--------MGQFDHPNVIHLEGVVTKS-----T 693
Cdd:cd07863    8 IGVGAYGTVYKARDPHSGH---FVALKSVRVQTNE----DGLPLSTVrevallkrLEAFDHPNIVRLMDVCATSrtdreT 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 694 PVMIITEFMENgSLDSFLRQNDGQ-FTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLe 772
Cdd:cd07863   81 KVTLVFEHVDQ-DLRTYLDKVPPPgLPAETIKDLMRQFLRGLDFLHANCIVHRDLKPENILVTSGGQVKLADFGLARIY- 158
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 111118978 773 ddtsdpTYTSALGGKIPIRW-TAPEAIQYRKFTSASDVWSYGIVMWEV 819
Cdd:cd07863  159 ------SCQMALTPVVVTLWyRAPEVLLQSTYATPVDMWSVGCIFAEM 200
STKc_PAK2 cd06655
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the ...
627-898 1.74e-11

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


Pssm-ID: 132986 [Multi-domain]  Cd Length: 296  Bit Score: 66.29  E-value: 1.74e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKReifVAIKTLKsgyTEKQRRD--FLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMEN 704
Cdd:cd06655   27 IGQGASGTVFTAIDVATGQE---VAIKQIN---LQKQPKKelIINEILVMKELKNPNIVNFLDSFLVGDELFVVMEYLAG 100
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 705 GSLDSFLRQNdgQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGlsrFLEDDTSDPTYTSAL 784
Cdd:cd06655  101 GSLTDVVTET--CMDEAQIAAVCRECLQALEFLHANQVIHRDIKSDNVLLGMDGSVKLTDFG---FCAQITPEQSKRSTM 175
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 785 GGKiPIrWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYwdmTNQDVINAIeqdYRLP----PPMDCPSALHQLML 860
Cdd:cd06655  176 VGT-PY-WMAPEVVTRKAYGPKVDIWSLGIMAIE-MVEGEPPY---LNENPLRAL---YLIAtngtPELQNPEKLSPIFR 246
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 111118978 861 D----CWQKDRNHRpkfgqivNTLDKMIRNPnSLKAMAPLSS 898
Cdd:cd06655  247 DflnrCLEMDVEKR-------GSAKELLQHP-FLKLAKPLSS 280
STKc_PhKG2 cd14181
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 2 subunit; STKs ...
661-828 1.82e-11

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: 65.76  E-value: 1.82e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 661 EKQRRDFLSEASIMGQF-DHPNVIHLEGVVTKSTPVMIITEFMENGSLDSFLRQNDgQFTVIQLVGMLRGIAAGMKYLAD 739
Cdd:cd14181   56 EEVRSSTLKEIHILRQVsGHPSIITLIDSYESSTFIFLVFDLMRRGELFDYLTEKV-TLSEKETRSIMRSLLEAVSYLHA 134
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 740 MNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDPTYTSALGgkipirWTAPEAIQ------YRKFTSASDVWSYG 813
Cdd:cd14181  135 NNIVHRDLKPENILLDDQLHIKLSDFGFSCHLEPGEKLRELCGTPG------YLAPEILKcsmdetHPGYGKEVDLWACG 208
                        170
                 ....*....|....*
gi 111118978 814 IVMWEVMSyGERPYW 828
Cdd:cd14181  209 VILFTLLA-GSPPFW 222
STKc_SnRK2-3 cd14665
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
627-829 1.86e-11

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2, group 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. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. 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: 271135 [Multi-domain]  Cd Length: 257  Bit Score: 65.39  E-value: 1.86e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGevcSGHLKLPGKREIFVAIKTLKSG--YTEKQRRDFLSEASIMgqfdHPNVIHLEGVVTKSTPVMIITEFMEN 704
Cdd:cd14665    8 IGSGNFG---VARLMRDKQTKELVAVKYIERGekIDENVQREIINHRSLR----HPNIVRFKEVILTPTHLAIVMEYAAG 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 705 GSLdsFLRQ-NDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLV--CKVSDFGLSR--FLEDDTSDPT 779
Cdd:cd14665   81 GEL--FERIcNAGRFSEDEARFFFQQLISGVSYCHSMQICHRDLKLENTLLDGSPAprLKICDFGYSKssVLHSQPKSTV 158
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 111118978 780 YTSAlggkipirWTAPEAIQYRKFTSA-SDVWSYGIVMWeVMSYGERPYWD 829
Cdd:cd14665  159 GTPA--------YIAPEVLLKKEYDGKiADVWSCGVTLY-VMLVGAYPFED 200
STKc_PAK3 cd06656
Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine ...
627-898 1.88e-11

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


Pssm-ID: 132987 [Multi-domain]  Cd Length: 297  Bit Score: 66.28  E-value: 1.88e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGhLKLPGKREIFVAIKTLKSgytEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGS 706
Cdd:cd06656   27 IGQGASGTVYTA-IDIATGQEVAIKQMNLQQ---QPKKELIINEILVMRENKNPNIVNYLDSYLVGDELWVVMEYLAGGS 102
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 707 LDSFLRQ---NDGQftviqLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGlsrFLEDDTSDPTYTSA 783
Cdd:cd06656  103 LTDVVTEtcmDEGQ-----IAAVCRECLQALDFLHSNQVIHRDIKSDNILLGMDGSVKLTDFG---FCAQITPEQSKRST 174
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 784 LGGKiPIrWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYwdmTNQDVINAIeqdYRLP----PPMDCPSALHQLM 859
Cdd:cd06656  175 MVGT-PY-WMAPEVVTRKAYGPKVDIWSLGIMAIE-MVEGEPPY---LNENPLRAL---YLIAtngtPELQNPERLSAVF 245
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|...
gi 111118978 860 LD----CWQKDRNHRpkfgqivNTLDKMIRNPnSLKAMAPLSS 898
Cdd:cd06656  246 RDflnrCLEMDVDRR-------GSAKELLQHP-FLKLAKPLSS 280
STKc_PAK_I cd06647
Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze ...
604-827 1.95e-11

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: 65.72  E-value: 1.95e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 604 DPNEAVREFAKeidiscvkieqvIGAGEFGEVCSGHLKLPGKReifVAIKTLKSGYTEKQRRdFLSEASIMGQFDHPNVI 683
Cdd:cd06647    4 DPKKKYTRFEK------------IGQGASGTVYTAIDVATGQE---VAIKQMNLQQQPKKEL-IINEILVMRENKNPNIV 67
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 684 HLEGVVTKSTPVMIITEFMENGSLDSFLRQ---NDGQftviqLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVC 760
Cdd:cd06647   68 NYLDSYLVGDELWVVMEYLAGGSLTDVVTEtcmDEGQ-----IAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSV 142
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 111118978 761 KVSDFGlsrFLEDDTSDPTYTSALGGKiPIrWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPY 827
Cdd:cd06647  143 KLTDFG---FCAQITPEQSKRSTMVGT-PY-WMAPEVVTRKAYGPKVDIWSLGIMAIE-MVEGEPPY 203
STKc_ROCK_NDR_like cd05573
Catalytic domain of Rho-associated coiled-coil containing protein kinase (ROCK)- and Nuclear ...
625-867 2.58e-11

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: 66.15  E-value: 2.58e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKSgyTE----KQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITE 700
Cdd:cd05573    7 KVIGRGAFGEVWLVRDKDTGQ---VYAMKILRK--SDmlkrEQIAHVRAERDILADADSPWIVRLHYAFQDEDHLYLVME 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMENGSLDSFLrQNDGQFTViqlvGMLRGIAAGM----KYLADMNYVHRDLAARNILVNSNLVCKVSDFGLS-RFLEDDT 775
Cdd:cd05573   82 YMPGGDLMNLL-IKYDVFPE----ETARFYIAELvlalDSLHKLGFIHRDIKPDNILLDADGHIKLADFGLCtKMNKSGD 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 776 S-----DPTYTSALGGKIPIRW------------------TAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTN 832
Cdd:cd05573  157 ResylnDSVNTLFQDNVLARRRphkqrrvraysavgtpdyIAPEVLRGTGYGPECDWWSLGVILYE-MLYGFPPFYSDSL 235
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 111118978 833 QDVINAI---EQDYRLPPPMDCPSALHQLM--LDCWQKDR 867
Cdd:cd05573  236 VETYSKImnwKESLVFPDDPDVSPEAIDLIrrLLCDPEDR 275
STKc_Aurora-B_like cd14117
Catalytic domain of the Serine/Threonine kinase, Aurora-B kinase and similar proteins; STKs ...
614-849 2.71e-11

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


Pssm-ID: 271019 [Multi-domain]  Cd Length: 270  Bit Score: 65.27  E-value: 2.71e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 614 KEIDISCVKIEQVIGAGEFGEVCSGHLKlpgKREIFVAIKTL------KSGYTEKQRRdflsEASIMGQFDHPNVIHLEG 687
Cdd:cd14117    1 RKFTIDDFDIGRPLGKGKFGNVYLAREK---QSKFIVALKVLfksqieKEGVEHQLRR----EIEIQSHLRHPNILRLYN 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 688 VVTKSTPVMIITEFMENGSLDSFLrQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGL 767
Cdd:cd14117   74 YFHDRKRIYLILEYAPRGELYKEL-QKHGRFDEQRTATFMEELADALHYCHEKKVIHRDIKPENLLMGYKGELKIADFGW 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 768 SrfleddtsdpTYTSALGGKI---PIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMsYGERPYWDMTNQDVINAIEQ-DY 843
Cdd:cd14117  153 S----------VHAPSLRRRTmcgTLDYLPPEMIEGRTHDEKVDLWCIGVLCYELL-VGMPPFESASHTETYRRIVKvDL 221

                 ....*.
gi 111118978 844 RLPPPM 849
Cdd:cd14117  222 KFPPFL 227
STKc_MEKK2 cd06652
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular ...
622-828 2.87e-11

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: 65.07  E-value: 2.87e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKLPGKReifVAIKTLK----SGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVV--TKSTPV 695
Cdd:cd06652    5 RLGKLLGQGAFGRVYLCYDADTGRE---LAVKQVQfdpeSPETSKEVNALECEIQLLKNLLHERIVQYYGCLrdPQERTL 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 696 MIITEFMENGSLDSFLRQNdGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDT 775
Cdd:cd06652   82 SIFMEYMPGGSIKDQLKSY-GALTENVTRKYTRQILEGVHYLHSNMIVHRDIKGANILRDSVGNVKLGDFGASKRLQTIC 160
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 111118978 776 SDPTYTSALGGKiPIrWTAPEAIQYRKFTSASDVWSYGIVMWEVMSygERPYW 828
Cdd:cd06652  161 LSGTGMKSVTGT-PY-WMSPEVISGEGYGRKADIWSVGCTVVEMLT--EKPPW 209
STKc_cPKC_alpha cd05615
Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha; STKs ...
626-834 3.02e-11

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: 66.17  E-value: 3.02e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 626 VIGAGEFGEVCSGHLKlpGKREIFvAIKTLKSGYTeKQRRDF---LSEASIMGQFDHPNVI-HLEGVVTKSTPVMIITEF 701
Cdd:cd05615   17 VLGKGSFGKVMLAERK--GSDELY-AIKILKKDVV-IQDDDVectMVEKRVLALQDKPPFLtQLHSCFQTVDRLYFVMEY 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 702 MENGSLDSFLRQNdGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRfleDDTSDPTYT 781
Cdd:cd05615   93 VNGGDLMYHIQQV-GKFKEPQAVFYAAEISVGLFFLHKKGIIYRDLKLDNVMLDSEGHIKIADFGMCK---EHMVEGVTT 168
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 111118978 782 SALGGKiPiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYwDMTNQD 834
Cdd:cd05615  169 RTFCGT-P-DYIAPEIIAYQPYGRSVDWWAYGVLLYEMLA-GQPPF-DGEDED 217
STKc_PCTAIRE3 cd07871
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-3 kinase; STKs catalyze the transfer ...
621-826 3.02e-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: 65.42  E-value: 3.02e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQvIGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITE 700
Cdd:cd07871    8 VKLDK-LGEGTYATVFKGRSKLTEN---LVALKEIRLEHEEGAPCTAIREVSLLKNLKHANIVTLHDIIHTERCLTLVFE 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMENgSLDSFLrQNDGQFTVIQLVG-----MLRGIAagmkYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRfledDT 775
Cdd:cd07871   84 YLDS-DLKQYL-DNCGNLMSMHNVKifmfqLLRGLS----YCHKRKILHRDLKPQNLLINEKGELKLADFGLAR----AK 153
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 111118978 776 SDPTYTSAlgGKIPIRWTAPEAIQY--RKFTSASDVWSYGIVMWEvMSYGeRP 826
Cdd:cd07871  154 SVPTKTYS--NEVVTLWYRPPDVLLgsTEYSTPIDMWGVGCILYE-MATG-RP 202
STKc_Titin cd14104
Catalytic domain of the Giant Serine/Threonine Kinase Titin; STKs catalyze the transfer of the ...
623-839 3.12e-11

Catalytic domain of the Giant Serine/Threonine Kinase Titin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Titin, also called connectin, is a muscle-specific elastic protein and is the largest known protein to date. It contains multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains, and a single kinase domain near the C-terminus. It spans half of the sarcomere, the repeating contractile unit of striated muscle, and performs mechanical and catalytic functions. Titin contributes to the passive force generated when muscle is stretched during relaxation. Its kinase domain phosphorylates and regulates the muscle protein telethonin, which is required for sarcomere formation in differentiating myocytes. In addition, titin binds many sarcomere proteins and acts as a molecular scaffold for filament formation during myofibrillogenesis. The Titin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271006 [Multi-domain]  Cd Length: 277  Bit Score: 65.27  E-value: 3.12e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 623 IEQVIGAGEFGEV--CSGHLKLPGKREIFVAIKTLKSGYTEKqrrdflsEASIMGQFDHPNVIHLEGVVTKSTPVMIITE 700
Cdd:cd14104    4 IAEELGRGQFGIVhrCVETSSKKTYMAKFVKVKGADQVLVKK-------EISILNIARHRNILRLHESFESHEELVMIFE 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMEngSLDSFLRQNDGQF--TVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNL--VCKVSDFGLSRFLE-DDT 775
Cdd:cd14104   77 FIS--GVDIFERITTARFelNEREIVSYVRQVCEALEFLHSKNIGHFDIRPENIIYCTRRgsYIKIIEFGQSRQLKpGDK 154
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 111118978 776 SDPTYTSAlggkipiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAI 839
Cdd:cd14104  155 FRLQYTSA-------EFYAPEVHQHESVSTATDMWSLGCLVYVLLS-GINPFEAETNQQTIENI 210
STKc_CDK1_euk cd07861
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher ...
621-826 3.66e-11

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: 65.13  E-value: 3.66e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQvIGAGEFGEVCSGHLKLPGKreiFVAIKTLKsgyTEKQRRDFLS----EASIMGQFDHPNVIHLEGVVTKSTPVM 696
Cdd:cd07861    3 TKIEK-IGEGTYGVVYKGRNKKTGQ---IVAMKKIR---LESEEEGVPStairEISLLKELQHPNIVCLEDVLMQENRLY 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 697 IITEFME---NGSLDSFlrqNDGQFTVIQLV-GMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRfle 772
Cdd:cd07861   76 LVFEFLSmdlKKYLDSL---PKGKYMDAELVkSYLYQILQGILFCHSRRVLHRDLKPQNLLIDNKGVIKLADFGLAR--- 149
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 111118978 773 ddtsdptytsALGgkIPIR----------WTAPEAI-QYRKFTSASDVWSYGIVMWEVMSygERP 826
Cdd:cd07861  150 ----------AFG--IPVRvythevvtlwYRAPEVLlGSPRYSTPVDIWSIGTIFAEMAT--KKP 200
STKc_CaMK_like cd14088
Catalytic domain of an Uncharacterized group of Serine/Threonine kinases with similarity to ...
625-834 4.11e-11

Catalytic domain of an Uncharacterized group of Serine/Threonine kinases with similarity to Calcium/calmodulin-dependent protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of uncharacterized STKs with similarity to CaMKs, which are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). CaMKs contain an N-terminal catalytic domain followed by a regulatory domain that harbors a CaM binding site. This uncharacterized subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270990 [Multi-domain]  Cd Length: 265  Bit Score: 64.66  E-value: 4.11e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKLPGKreIFVAIKTLKSGyTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIiteFMEN 704
Cdd:cd14088    7 QVIKTEEFCEIFRAKDKTTGK--LYTCKKFLKRD-GRKVRKAAKNEINILKMVKHPNILQLVDVFETRKEYFI---FLEL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 705 GS----LDSFLRQndGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNI-----LVNSNLVckVSDFGLSRFLEDDT 775
Cdd:cd14088   81 ATgrevFDWILDQ--GYYSERDTSNVIRQVLEAVAYLHSLKIVHRNLKLENLvyynrLKNSKIV--ISDFHLAKLENGLI 156
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 111118978 776 SDPTYTSalggkipiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQD 834
Cdd:cd14088  157 KEPCGTP--------EYLAPEVVGRQRYGRPVDCWAIGVIMYILLS-GNPPFYDEAEED 206
STKc_MAPK4_6 cd07854
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also ...
650-821 4.93e-11

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also called ERK4) and 6 (also called ERK3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK4 (also called ERK4 or p63MAPK) and MAPK6 (also called ERK3 or p97MAPK) are atypical MAPKs that are not regulated by MAPK kinases. MAPK6 is expressed ubiquitously with highest amounts in brain and skeletal muscle. It may be involved in the control of cell differentiation by negatively regulating cell cycle progression in certain conditions. It may also play a role in glucose-induced insulin secretion. MAPK6 and MAPK4 cooperate to regulate the activity of MAPK-activated protein kinase 5 (MK5), leading to its relocation to the cytoplasm and exclusion from the nucleus. The MAPK6/MK5 and MAPK4/MK5 pathways may play critical roles in embryonic and post-natal development. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK4/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143359 [Multi-domain]  Cd Length: 342  Bit Score: 65.57  E-value: 4.93e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 650 VAIKtlKSGYTEKQR-RDFLSEASIMGQFDHPNVIHL--------------EGVVTKSTPVMIITEFMENgSLDSFLRQN 714
Cdd:cd07854   33 VAVK--KIVLTDPQSvKHALREIKIIRRLDHDNIVKVyevlgpsgsdltedVGSLTELNSVYIVQEYMET-DLANVLEQG 109
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 715 DGQFTVIQLVG--MLRGiaagMKYLADMNYVHRDLAARNILVNS-NLVCKVSDFGLSRFLEDDTSDPTYTSAlgGKIPIR 791
Cdd:cd07854  110 PLSEEHARLFMyqLLRG----LKYIHSANVLHRDLKPANVFINTeDLVLKIGDFGLARIVDPHYSHKGYLSE--GLVTKW 183
                        170       180       190
                 ....*....|....*....|....*....|.
gi 111118978 792 WTAPE-AIQYRKFTSASDVWSYGIVMWEVMS 821
Cdd:cd07854  184 YRSPRlLLSPNNYTKAIDMWAAGCIFAEMLT 214
STKc_CDKL2_3 cd07846
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; ...
626-824 5.47e-11

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: 64.75  E-value: 5.47e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 626 VIGAGEFGEVCSGHLKLPGKreiFVAIKT-LKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMEN 704
Cdd:cd07846    8 LVGEGSYGMVMKCRHKETGQ---IVAIKKfLESEDDKMVKKIAMREIKMLKQLRHENLVNLIEVFRRKKRWYLVFEFVDH 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 705 GSLDSFLRQNDG-QFTVIQ--LVGMLRGIAagmkYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEddTSDPTYT 781
Cdd:cd07846   85 TVLDDLEKYPNGlDESRVRkyLFQILRGID----FCHSHNIIHRDIKPENILVSQSGVVKLCDFGFARTLA--APGEVYT 158
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 111118978 782 SalggKIPIRW-TAPE-AIQYRKFTSASDVWSYGIVMWEvMSYGE 824
Cdd:cd07846  159 D----YVATRWyRAPElLVGDTKYGKAVDVWAVGCLVTE-MLTGE 198
STKc_MAPKAPK2 cd14170
Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated ...
695-828 5.53e-11

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 2 (MAPKAP2 or MK2) contains an N-terminal proline-rich region that can bind to SH3 domains, a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK2 is a bonafide substrate for the MAPK p38. It is closely related to MK3 and thus far, MK2/3 show indistinguishable substrate specificity. They are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. The MK2 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: 271072 [Multi-domain]  Cd Length: 303  Bit Score: 64.67  E-value: 5.53e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 695 VMIITEFMENGSLDSFLR-QNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNS---NLVCKVSDFGLSR- 769
Cdd:cd14170   74 LLIVMECLDGGELFSRIQdRGDQAFTEREASEIMKSIGEAIQYLHSINIAHRDVKPENLLYTSkrpNAILKLTDFGFAKe 153
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 770 -FLEDDTSDPTYTSalggkipiRWTAPEAIQYRKFTSASDVWSYGIVMWeVMSYGERPYW 828
Cdd:cd14170  154 tTSHNSLTTPCYTP--------YYVAPEVLGPEKYDKSCDMWSLGVIMY-ILLCGYPPFY 204
STKc_cPKC_beta cd05616
Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C beta; STKs ...
626-849 5.66e-11

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: 65.02  E-value: 5.66e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 626 VIGAGEFGEVCSGHLKlpGKREIFvAIKTLKSGYTeKQRRDF---LSEASIMGQFDHPNVI-HLEGVVTKSTPVMIITEF 701
Cdd:cd05616    7 VLGKGSFGKVMLAERK--GTDELY-AVKILKKDVV-IQDDDVectMVEKRVLALSGKPPFLtQLHSCFQTMDRLYFVMEY 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 702 MENGSLdSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRfleDDTSDPTYT 781
Cdd:cd05616   83 VNGGDL-MYHIQQVGRFKEPHAVFYAAEIAIGLFFLQSKGIIYRDLKLDNVMLDSEGHIKIADFGMCK---ENIWDGVTT 158
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 111118978 782 SALGGKiPiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAI-EQDYRLPPPM 849
Cdd:cd05616  159 KTFCGT-P-DYIAPEIIAYQPYGKSVDWWAFGVLLYEMLA-GQAPFEGEDEDELFQSImEHNVAYPKSM 224
FN3 cd00063
Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein ...
325-431 6.11e-11

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.


Pssm-ID: 238020 [Multi-domain]  Cd Length: 93  Bit Score: 59.82  E-value: 6.11e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 325 PSAPQAV-ISSVNETSLMLEWTPPRDSGGREDLvYNIICKSCGSGRGacTRCGDNVqyaprqlgLTEPRIYISDLLAHTQ 403
Cdd:cd00063    1 PSPPTNLrVTDVTSTSVTLSWTPPEDDGGPITG-YVVEYREKGSGDW--KEVEVTP--------GSETSYTLTGLKPGTE 69
                         90       100
                 ....*....|....*....|....*...
gi 111118978 404 YTFEIQAVNGVTDqSPFSPqfaSVNITT 431
Cdd:cd00063   70 YEFRVRAVNGGGE-SPPSE---SVTVTT 93
SAM_EPH-A3 cd09544
SAM domain of EPH-A3 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
914-974 6.50e-11

SAM domain of EPH-A3 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A3 subfamily of receptor tyrosine kinases is a C-terminal putative protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A3 receptors and appears to mediate cell-cell initiated signal transduction. EPH-A3 receptors bind SH2/SH3 containing adaptor protein Nck1 and this adaptor is a key factor in EPH-A3 mediated signaling. However SAM domain is not implemented in this interaction. Activation of EPH-A3 receptors inhibits outgrowth and cell migration. Mutations in SAM domain may play a role in development of hepatocellular carcinoma. Expression of EPH-A3 is associated with lymphocytic leukemia and defines the subset of rhabdomyosarcoma tumors. EPH-A3 receptors are attractive targets for drug design.


Pssm-ID: 188943  Cd Length: 63  Bit Score: 58.91  E-value: 6.50e-11
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 111118978 914 SFNTVDEWLEAIKMGQYKESFANAGFTSFDVVSQMMMEDILRVGVTLAGHQKKILNSIQVM 974
Cdd:cd09544    1 TFHTTGDWLNGARTAHCKEIFTGVEYSSCDTIAKISTDDMKKVGVTVVGPQKKIVSSIKTL 61
STKc_EIF2AK3_PERK cd14048
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
625-854 6.64e-11

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


Pssm-ID: 270950 [Multi-domain]  Cd Length: 281  Bit Score: 64.12  E-value: 6.64e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKLPgkrEIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTP---------- 694
Cdd:cd14048   12 QCLGRGGFGVVFEAKNKVD---DCNYAVKRIRLPNNELAREKVLREVRALAKLDHPGIVRYFNAWLERPPegwqekmdev 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 695 -VMIITEFMENGSLDSFLRQN----DGQFTViqLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLS- 768
Cdd:cd14048   89 yLYIQMQLCRKENLKDWMNRRctmeSRELFV--CLNIFKQIASAVEYLHSKGLIHRDLKPSNVFFSLDDVVKVGDFGLVt 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 769 ---------RFLEDDTSDPTYTSALGGKIpirWTAPEAIQYRKFTSASDVWSYGIVMWEVM-SYGE-----RPYWDMTNQ 833
Cdd:cd14048  167 amdqgepeqTVLTPMPAYAKHTGQVGTRL---YMSPEQIHGNQYSEKVDIFALGLILFELIySFSTqmeriRTLTDVRKL 243
                        250       260       270
                 ....*....|....*....|....*....|.
gi 111118978 834 DV----INAIEQDYRL------PPPMDCPSA 854
Cdd:cd14048  244 KFpalfTNKYPEERDMvqqmlsPSPSERPEA 274
STKc_GRK4 cd05631
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4; STKs ...
625-841 7.41e-11

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK4 has a limited tissue distribution. It is mainly found in the testis, but is also present in the cerebellum and kidney. It is expressed as multiple splice variants with different domain architectures and is post-translationally palmitoylated and localized in the membrane. GRK4 polymorphisms are associated with hypertension and salt sensitivity, as they cause hyperphosphorylation, desensitization, and internalization of the dopamine 1 (D1) receptor while increasing the expression of the angiotensin II type 1 receptor. GRK4 plays a crucial role in the D1 receptor regulation of sodium excretion and blood pressure. 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 GRK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173720 [Multi-domain]  Cd Length: 285  Bit Score: 64.24  E-value: 7.41e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGYTEKQRRD--FLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFM 702
Cdd:cd05631    6 RVLGKGGFGEVCACQVRATGK---MYACKKLEKKRIKKRKGEamALNEKRILEKVNSRFVVSLAYAYETKDALCLVLTIM 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 703 ENGSLdSFLRQNDGQ--FTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSrfleddTSDPTY 780
Cdd:cd05631   83 NGGDL-KFHIYNMGNpgFDEQRAIFYAAELCCGLEDLQRERIVYRDLKPENILLDDRGHIRISDLGLA------VQIPEG 155
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 111118978 781 TSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMS-------YGERPYWDMTNQDVINAIEQ 841
Cdd:cd05631  156 ETVRGRVGTVGYMAPEVINNEKYTFSPDWWGLGCLIYEMIQgqspfrkRKERVKREEVDRRVKEDQEE 223
STKc_myosinIIIA_N cd06638
N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIA myosin; STKs catalyze ...
622-871 7.46e-11

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: 64.26  E-value: 7.46e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKLPGKReifVAIKTLKSGYTEKQrrDFLSEASIMGQF-DHPNVIHLEGV-----VTKSTPV 695
Cdd:cd06638   21 EIIETIGKGTYGKVFKVLNKKNGSK---AAVKILDPIHDIDE--EIEAEYNILKALsDHPNVVKFYGMyykkdVKNGDQL 95
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 696 MIITEFMENGSL----DSFLRQNDGQFTVIqLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFL 771
Cdd:cd06638   96 WLVLELCNGGSVtdlvKGFLKRGERMEEPI-IAYILHEALMGLQHLHVNKTIHRDVKGNNILLTTEGGVKLVDFGVSAQL 174
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 772 EddTSDPTYTSALGGKIpirWTAPEAIQYRK-----FTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVINAIEqdyRLP 846
Cdd:cd06638  175 T--STRLRRNTSVGTPF---WMAPEVIACEQqldstYDARCDVWSLGITAIE-LGDGDPPLADLHPMRALFKIP---RNP 245
                        250       260       270
                 ....*....|....*....|....*....|
gi 111118978 847 PP-MDCP----SALHQLMLDCWQKDRNHRP 871
Cdd:cd06638  246 PPtLHQPelwsNEFNDFIRKCLTKDYEKRP 275
STKc_GRK5 cd05632
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 5; STKs ...
625-827 7.67e-11

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK5 is widely expressed in many tissues. It associates with the membrane though an N-terminal PIP2 binding domain and also binds phospholipids via its C-terminus. GRK5 deficiency is associated with early Alzheimer's disease in humans and mouse models. GRK5 also plays a crucial role in the pathogenesis of sporadic Parkinson's disease. It participates in the regulation and desensitization of PDGFRbeta, a receptor tyrosine kinase involved in a variety of downstream cellular effects including cell growth, chemotaxis, apoptosis, and angiogenesis. GRK5 also regulates Toll-like receptor 4, which is involved in innate and adaptive immunity. 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 GRK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270780 [Multi-domain]  Cd Length: 313  Bit Score: 64.61  E-value: 7.67e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGYTEKQRRD--FLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFM 702
Cdd:cd05632    8 RVLGKGGFGEVCACQVRATGK---MYACKRLEKKRIKKRKGEsmALNEKQILEKVNSQFVVNLAYAYETKDALCLVLTIM 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 703 ENGSLdSFLRQNDGQ--FTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSrfleddTSDPTY 780
Cdd:cd05632   85 NGGDL-KFHIYNMGNpgFEEERALFYAAEILCGLEDLHRENTVYRDLKPENILLDDYGHIRISDLGLA------VKIPEG 157
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 111118978 781 TSALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPY 827
Cdd:cd05632  158 ESIRGRVGTVGYMAPEVLNNQRYTLSPDYWGLGCLIYEMIE-GQSPF 203
STKc_PKB_beta cd05595
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); ...
625-870 7.73e-11

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


Pssm-ID: 173686 [Multi-domain]  Cd Length: 323  Bit Score: 64.64  E-value: 7.73e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGY--TEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFM 702
Cdd:cd05595    1 KLLGKGTFGKVILVREKATGR---YYAMKILRKEViiAKDEVAHTVTESRVLQNTRHPFLTALKYAFQTHDRLCFVMEYA 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 703 ENGSLdSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRflEDDTSDPTYTS 782
Cdd:cd05595   78 NGGEL-FFHLSRERVFTEDRARFYGAEIVSALEYLHSRDVVYRDIKLENLMLDKDGHIKITDFGLCK--EGITDGATMKT 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 783 ALGGKipiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAI-EQDYRLPPPMDcPSAlHQLMLD 861
Cdd:cd05595  155 FCGTP---EYLAPEVLEDNDYGRAVDWWGLGVVMYEMMC-GRLPFYNQDHERLFELIlMEEIRFPRTLS-PEA-KSLLAG 228

                 ....*....
gi 111118978 862 CWQKDRNHR 870
Cdd:cd05595  229 LLKKDPKQR 237
STKc_YPK1_like cd05585
Catalytic domain of Yeast Protein Kinase 1-like Serine/Threonine Kinases; STKs catalyze the ...
626-850 7.89e-11

Catalytic domain of Yeast Protein Kinase 1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of fungal proteins with similarity to the AGC STKs, Saccharomyces cerevisiae YPK1 and Schizosaccharomyces pombe Gad8p. YPK1 is required for cell growth and acts as a downstream kinase in the sphingolipid-mediated signaling pathway of yeast. It also plays a role in efficient endocytosis and in the maintenance of cell wall integrity. Gad8p is a downstream target of Tor1p, the fission yeast homolog of mTOR. It plays a role in cell growth and sexual development. The YPK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270737 [Multi-domain]  Cd Length: 313  Bit Score: 64.51  E-value: 7.89e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 626 VIGAGEFGEVCsgHLKLPGKREIFvAIKTLKSGY--TEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFME 703
Cdd:cd05585    1 VIGKGSFGKVM--QVRKKDTSRIY-ALKTIRKAHivSRSEVTHTLAERTVLAQVDCPFIVPLKFSFQSPEKLYLVLAFIN 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 704 NGSLDSFLrQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRF--LEDDTSDpTYT 781
Cdd:cd05585   78 GGELFHHL-QREGRFDLSRARFYTAELLCALECLHKFNVIYRDLKPENILLDYTGHIALCDFGLCKLnmKDDDKTN-TFC 155
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 782 SAlggkiPiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAIEQD-YRLPPPMD 850
Cdd:cd05585  156 GT-----P-EYLAPELLLGHGYTKAVDWWTLGVLLYEMLT-GLPPFYDENTNEMYRKILQEpLRFPDGFD 218
PHA03212 PHA03212
serine/threonine kinase US3; Provisional
663-819 7.95e-11

serine/threonine kinase US3; Provisional


Pssm-ID: 165478 [Multi-domain]  Cd Length: 391  Bit Score: 65.02  E-value: 7.95e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 663 QRRDFLSEASIMGQFDHPNVIHLEGVVT-KSTPVMIITEFMENgsLDSFL--RQNdgqFTVIQLVGMLRGIAAGMKYLAD 739
Cdd:PHA03212 126 QRGGTATEAHILRAINHPSIIQLKGTFTyNKFTCLILPRYKTD--LYCYLaaKRN---IAICDILAIERSVLRAIQYLHE 200
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 740 MNYVHRDLAARNILVN-SNLVCkVSDFGLSRFLEDDTSDPTYTSAlgGKIPIrwTAPEAIQYRKFTSASDVWSYGIVMWE 818
Cdd:PHA03212 201 NRIIHRDIKAENIFINhPGDVC-LGDFGAACFPVDINANKYYGWA--GTIAT--NAPELLARDPYGPAVDIWSAGIVLFE 275

                 .
gi 111118978 819 V 819
Cdd:PHA03212 276 M 276
STKc_JNK3 cd07874
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 3; STKs catalyze the ...
627-890 8.00e-11

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK3 is expressed primarily in the brain, and to a lesser extent in the heart and testis. Mice deficient in JNK3 are protected against kainic acid-induced seizures, stroke, sciatic axotomy neural death, and neuronal death due to NGF deprivation, oxidative stress, or exposure to beta-amyloid peptide. This suggests that JNK3 may play roles in the pathogenesis of these diseases. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143379 [Multi-domain]  Cd Length: 355  Bit Score: 64.72  E-value: 8.00e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKReifVAIKTLKSGY-TEKQRRDFLSEASIMGQFDHPNVIHLEGVVTkstPVMIITEFMENG 705
Cdd:cd07874   25 IGSGAQGIVCAAYDAVLDRN---VAIKKLSRPFqNQTHAKRAYRELVLMKCVNHKNIISLLNVFT---PQKSLEEFQDVY 98
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 706 SLDSFLRQNDGQFTVIQL-----VGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDPTY 780
Cdd:cd07874   99 LVMELMDANLCQVIQMELdhermSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTAGTSFMMTPY 178
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 781 TsalggkIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMS----YGERPYWDMTNQdvinAIEQdyrLPPPmdCPSALH 856
Cdd:cd07874  179 V------VTRYYRAPEVILGMGYKENVDIWSVGCIMGEMVRhkilFPGRDYIDQWNK----VIEQ---LGTP--CPEFMK 243
                        250       260       270
                 ....*....|....*....|....*....|....
gi 111118978 857 QLMLDCWQKDRNhRPKFGQIvnTLDKMIrnPNSL 890
Cdd:cd07874  244 KLQPTVRNYVEN-RPKYAGL--TFPKLF--PDSL 272
STKc_PhKG1 cd14182
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 1 subunit; STKs ...
679-828 8.57e-11

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 1 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 1 subunit (PhKG1) is also referred to as the muscle gamma isoform. 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 PhKG1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271084 [Multi-domain]  Cd Length: 276  Bit Score: 63.78  E-value: 8.57e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 679 HPNVIHLEGVVTKSTPVMIITEFMENGSLDSFLRQndgQFTVIQ--LVGMLRGIAAGMKYLADMNYVHRDLAARNILVNS 756
Cdd:cd14182   69 HPNIIQLKDTYETNTFFFLVFDLMKKGELFDYLTE---KVTLSEkeTRKIMRALLEVICALHKLNIVHRDLKPENILLDD 145
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 757 NLVCKVSDFGLS------RFLEDDTSDPTYtsalggkipirwTAPEAIQ------YRKFTSASDVWSYGIVMWEVMSyGE 824
Cdd:cd14182  146 DMNIKLTDFGFScqldpgEKLREVCGTPGY------------LAPEIIEcsmddnHPGYGKEVDMWSTGVIMYTLLA-GS 212

                 ....
gi 111118978 825 RPYW 828
Cdd:cd14182  213 PPFW 216
STKc_MSK1_N cd05613
N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
625-827 8.75e-11

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


Pssm-ID: 270764 [Multi-domain]  Cd Length: 290  Bit Score: 63.87  E-value: 8.75e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEV-----CSGH-------LKLPGKREIFVAIKTLKSGYTEKQRRDFLSEAsimgqfdhPNVIHLEGVVTKS 692
Cdd:cd05613    6 KVLGTGAYGKVflvrkVSGHdagklyaMKVLKKATIVQKAKTAEHTRTERQVLEHIRQS--------PFLVTLHYAFQTD 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 693 TPVMIITEFMENGSLDSFLRQNDgQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLE 772
Cdd:cd05613   78 TKLHLILDYINGGELFTHLSQRE-RFTENEVQIYIGEIVLALEHLHKLGIIYRDIKLENILLDSSGHVVLTDFGLSKEFL 156
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 111118978 773 DDTSDPTYtSALGgkiPIRWTAPEAIQ--YRKFTSASDVWSYGIVMWEVMSyGERPY 827
Cdd:cd05613  157 LDENERAY-SFCG---TIEYMAPEIVRggDSGHDKAVDWWSLGVLMYELLT-GASPF 208
STKc_IRAK2 cd14157
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 2; ...
627-821 1.01e-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: 63.70  E-value: 1.01e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHlklpgKREIFVAIKTLKSGYTEKQR---RDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFME 703
Cdd:cd14157    1 ISEGTFADIYKGY-----RHGKQYVIKRLKETECESPKsteRFFQTEVQICFRCCHPNILPLLGFCVESDCHCLIYPYMP 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 704 NGSLDSFLRQNDGQ--FTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDPTYT 781
Cdd:cd14157   76 NGSLQDRLQQQGGShpLPWEQRLSISLGLLKAVQHLHNFGILHGNIKSSNVLLDGNLLPKLGHSGLRLCPVDKKSVYTMM 155
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 111118978 782 SALGGKIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMS 821
Cdd:cd14157  156 KTKVLQISLAYLPEDFVRHGQLTEKVDIFSCGVVLAEILT 195
PKc_MEK2 cd06649
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
664-826 1.05e-10

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 2; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK2 is a dual-specificity PK and a MAPK kinase (MAPKK or MKK) that phosphorylates and activates the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132980 [Multi-domain]  Cd Length: 331  Bit Score: 64.30  E-value: 1.05e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 664 RRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGSLDSFLRQND-------GQFTViqlvGMLRGIAagmkY 736
Cdd:cd06649   47 RNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVLKEAKripeeilGKVSI----AVLRGLA----Y 118
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 737 LADMNYV-HRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDptytSALGGKipiRWTAPEAIQYRKFTSASDVWSYGIV 815
Cdd:cd06649  119 LREKHQImHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMAN----SFVGTR---SYMSPERLQGTHYSVQSDIWSMGLS 191
                        170
                 ....*....|.
gi 111118978 816 MWEvMSYGERP 826
Cdd:cd06649  192 LVE-LAIGRYP 201
STKc_RCK1-like cd14096
Catalytic domain of RCK1-like Serine/Threonine Kinases; STKs catalyze the transfer of the ...
622-829 1.28e-10

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: 63.61  E-value: 1.28e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSG-HLKLPGKreiFVAIKTLK------SGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTP 694
Cdd:cd14096    4 RLINKIGEGAFSNVYKAvPLRNTGK---PVAIKVVRkadlssDNLKGSSRANILKEVQIMKRLSHPNIVKLLDFQESDEY 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 695 VMIITEFMENGSL------DSFLRQNDGQFTVIQLvgmlrgiAAGMKYLADMNYVHRDLAARNILVNS------------ 756
Cdd:cd14096   81 YYIVLELADGGEIfhqivrLTYFSEDLSRHVITQV-------ASAVKYLHEIGVVHRDIKPENLLFEPipfipsivklrk 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 757 ----------------------NLVcKVSDFGLSRFLED-DTSDPTYTsalggkipIRWTAPEAIQYRKFTSASDVWSYG 813
Cdd:cd14096  154 adddetkvdegefipgvggggiGIV-KLADFGLSKQVWDsNTKTPCGT--------VGYTAPEVVKDERYSKKVDMWALG 224
                        250
                 ....*....|....*.
gi 111118978 814 IVMWEVMSyGERPYWD 829
Cdd:cd14096  225 CVLYTLLC-GFPPFYD 239
STKc_MEKK3_like_u1 cd06653
Catalytic domain of an Uncharacterized subfamily of Mitogen-Activated Protein (MAP) ...
622-828 1.36e-10

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: 63.12  E-value: 1.36e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKLPGkREIfvAIKTL----KSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKST--PV 695
Cdd:cd06653    5 RLGKLLGRGAFGEVYLCYDADTG-REL--AVKQVpfdpDSQETSKEVNALECEIQLLKNLRHDRIVQYYGCLRDPEekKL 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 696 MIITEFMENGSLDSFLRQNdGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDT 775
Cdd:cd06653   82 SIFVEYMPGGSVKDQLKAY-GALTENVTRRYTRQILQGVSYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASKRIQTIC 160
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 111118978 776 SDPTYTSALGGKiPIrWTAPEAIQYRKFTSASDVWSYGIVMWEVMSygERPYW 828
Cdd:cd06653  161 MSGTGIKSVTGT-PY-WMSPEVISGEGYGRKADVWSVACTVVEMLT--EKPPW 209
STKc_PAK1 cd06654
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the ...
627-827 1.50e-10

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


Pssm-ID: 270820 [Multi-domain]  Cd Length: 296  Bit Score: 63.59  E-value: 1.50e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKReifVAIKTLKSGYTEKQRRdFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGS 706
Cdd:cd06654   28 IGQGASGTVYTAMDVATGQE---VAIRQMNLQQQPKKEL-IINEILVMRENKNPNIVNYLDSYLVGDELWVVMEYLAGGS 103
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 707 LDSFLRQ---NDGQftviqLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGlsrFLEDDTSDPTYTSA 783
Cdd:cd06654  104 LTDVVTEtcmDEGQ-----IAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFG---FCAQITPEQSKRST 175
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 111118978 784 LGGKiPIrWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPY 827
Cdd:cd06654  176 MVGT-PY-WMAPEVVTRKAYGPKVDIWSLGIMAIEMIE-GEPPY 216
STKc_BMPR1b cd14219
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IB; STKs ...
610-883 1.55e-10

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: 63.53  E-value: 1.55e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 610 REFAKEIDIscvkIEQvIGAGEFGEVCSGHLKlpGKReifVAIKTlksgYTEKQRRDFLSEASIMGQ--FDHPNVIHLEG 687
Cdd:cd14219    1 RTIAKQIQM----VKQ-IGKGRYGEVWMGKWR--GEK---VAVKV----FFTTEEASWFRETEIYQTvlMRHENILGFIA 66
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 688 VVTKST----PVMIITEFMENGSLDSFLRQndgqfTVIQLVGMLRGIAAGMKYLADMN-----------YVHRDLAARNI 752
Cdd:cd14219   67 ADIKGTgswtQLYLITDYHENGSLYDYLKS-----TTLDTKAMLKLAYSSVSGLCHLHteifstqgkpaIAHRDLKSKNI 141
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 753 LVNSNLVCKVSDFGLS-RFLED-DTSDPTYTSALGGKipiRWTAP----EAIQYRKFTS--ASDVWSYGIVMWEV----M 820
Cdd:cd14219  142 LVKKNGTCCIADLGLAvKFISDtNEVDIPPNTRVGTK---RYMPPevldESLNRNHFQSyiMADMYSFGLILWEVarrcV 218
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 111118978 821 SYG-----ERPYWDMTNQDV----INAIEQDYRLPPPM-------DCPSALHQLMLDCWQKDRNHRPKFGQIVNTLDKM 883
Cdd:cd14219  219 SGGiveeyQLPYHDLVPSDPsyedMREIVCIKRLRPSFpnrwssdECLRQMGKLMTECWAHNPASRLTALRVKKTLAKM 297
STKc_GRK7 cd05607
Catalytic domain of the Protein Serine/Threonine Kinase, G protein-coupled Receptor Kinase 7; ...
625-829 1.60e-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: 63.00  E-value: 1.60e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGYTEKQ--RRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFM 702
Cdd:cd05607    8 RVLGKGGFGEVCAVQVKNTGQ---MYACKKLDKKRLKKKsgEKMALLEKEILEKVNSPFIVSLAYAFETKTHLCLVMSLM 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 703 ENGSLdSFLRQNDGQ--FTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTsdpTY 780
Cdd:cd05607   85 NGGDL-KYHIYNVGErgIEMERVIFYSAQITCGILHLHSLKIVYRDMKPENVLLDDNGNCRLSDLGLAVEVKEGK---PI 160
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 111118978 781 TSALGGKipiRWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWD 829
Cdd:cd05607  161 TQRAGTN---GYMAPEILKEESYSYPVDWFAMGCSIYE-MVAGRTPFRD 205
STKc_Trio_C cd14113
C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide ...
631-846 1.62e-10

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


Pssm-ID: 271015 [Multi-domain]  Cd Length: 263  Bit Score: 62.68  E-value: 1.62e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 631 EFGEVCSGHLKLPGKREIFVAIKTLKSGYTEKQ--RRDFLS-EASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGSL 707
Cdd:cd14113   11 EVAELGRGRFSVVKKCDQRGTKRAVATKFVNKKlmKRDQVThELGVLQSLQHPQLVGLLDTFETPTSYILVLEMADQGRL 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 708 DSFLRQNdGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNL---VCKVSDFGLSRFLeddTSDPTYTSAL 784
Cdd:cd14113   91 LDYVVRW-GNLTEEKIRFYLREILEALQYLHNCRIAHLDLKPENILVDQSLskpTIKLADFGDAVQL---NTTYYIHQLL 166
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 111118978 785 GGKipiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDV-INAIEQDYRLP 846
Cdd:cd14113  167 GSP---EFAAPEIILGNPVSLTSDLWSIGVLTYVLLS-GVSPFLDESVEETcLNICRLDFSFP 225
STKc_EIF2AK1_HRI cd14049
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
610-839 2.05e-10

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Heme-Regulated Inhibitor kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HRI (or EIF2AK1) contains an N-terminal regulatory heme-binding domain and a C-terminal catalytic kinase domain. It is suppressed under normal conditions by binding of the heme iron, and is activated during heme deficiency. It functions as a critical regulator that ensures balanced synthesis of globins and heme, in order to form stable hemoglobin during erythroid differentiation and maturation. HRI also protects cells and enhances survival under iron-deficient conditions. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The HRI 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: 270951 [Multi-domain]  Cd Length: 284  Bit Score: 62.91  E-value: 2.05e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 610 REFaKEIDIscvkieqvIGAGEFGEVCSGHLKLPGkreIFVAIKT-LKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGV 688
Cdd:cd14049    6 NEF-EEIAR--------LGKGGYGKVYKVRNKLDG---QYYAIKKiLIKKVTKRDCMKVLREVKVLAGLQHPNIVGYHTA 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 689 VTKSTPVMI--------------ITEFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILV 754
Cdd:cd14049   74 WMEHVQLMLyiqmqlcelslwdwIVERNKRPCEEEFKSAPYTPVDVDVTTKILQQLLEGVTYIHSMGIVHRDLKPRNIFL 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 755 N-SNLVCKVSDFGLS--RFLEDDT--------SDPTYTSALGGKIpirWTAPEAIQYRKFTSASDVWSYGIVMWEVMsyg 823
Cdd:cd14049  154 HgSDIHVRIGDFGLAcpDILQDGNdsttmsrlNGLTHTSGVGTCL---YAAPEQLEGSHYDFKSDMYSIGVILLELF--- 227
                        250
                 ....*....|....*..
gi 111118978 824 eRPY-WDMTNQDVINAI 839
Cdd:cd14049  228 -QPFgTEMERAEVLTQL 243
STKc_DCKL3 cd14185
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called ...
662-848 2.16e-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: 62.27  E-value: 2.16e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 662 KQRRDFL-SEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGSLDSFLRQNDgQFTVIQLVGMLRGIAAGMKYLADM 740
Cdd:cd14185   39 KGKEDMIeSEILIIKSLSHPNIVKLFEVYETEKEIYLILEYVRGGDLFDAIIESV-KFTEHDAALMIIDLCEALVYIHSK 117
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 741 NYVHRDLAARNILVNSN----LVCKVSDFGLSRFLeddtSDPTYTSAlggKIPIrWTAPEAIQYRKFTSASDVWSYGIVM 816
Cdd:cd14185  118 HIVHRDLKPENLLVQHNpdksTTLKLADFGLAKYV----TGPIFTVC---GTPT-YVAPEILSEKGYGLEVDMWAAGVIL 189
                        170       180       190
                 ....*....|....*....|....*....|....*
gi 111118978 817 WeVMSYGERPYWDMT-NQDVINAIEQ--DYRLPPP 848
Cdd:cd14185  190 Y-ILLCGFPPFRSPErDQEELFQIIQlgHYEFLPP 223
PTZ00267 PTZ00267
NIMA-related protein kinase; Provisional
661-879 2.33e-10

NIMA-related protein kinase; Provisional


Pssm-ID: 140293 [Multi-domain]  Cd Length: 478  Bit Score: 64.27  E-value: 2.33e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 661 EKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGSLDSFLRQNDGQFTVIQL--VGML-RGIAAGMKYL 737
Cdd:PTZ00267 106 ERQAAYARSELHCLAACDHFGIVKHFDDFKSDDKLLLIMEYGSGGDLNKQIKQRLKEHLPFQEyeVGLLfYQIVLALDEV 185
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 738 ADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDPTYTSALGGKIpirWTAPEAIQYRKFTSASDVWSYGIVMW 817
Cdd:PTZ00267 186 HSRKMMHRDLKSANIFLMPTGIIKLGDFGFSKQYSDSVSLDVASSFCGTPY---YLAPELWERKRYSKKADMWSLGVILY 262
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 111118978 818 EVMSYgERPYWDMTNQDVINAIEQDYRLPPPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNT 879
Cdd:PTZ00267 263 ELLTL-HRPFKGPSQREIMQQVLYGKYDPFPCPVSSGMKALLDPLLSKNPALRPTTQQLLHT 323
STKc_PCTAIRE2 cd07872
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-2 kinase; STKs catalyze the transfer ...
621-821 2.33e-10

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: 63.09  E-value: 2.33e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQvIGAGEFGEVCSGHLKLPgkrEIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITE 700
Cdd:cd07872    9 IKLEK-LGEGTYATVFKGRSKLT---ENLVALKEIRLEHEEGAPCTAIREVSLLKDLKHANIVTLHDIVHTDKSLTLVFE 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMENgSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRfledDTSDPTY 780
Cdd:cd07872   85 YLDK-DLKQYMDDCGNIMSMHNVKIFLYQILRGLAYCHRRKVLHRDLKPQNLLINERGELKLADFGLAR----AKSVPTK 159
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 111118978 781 TSAlgGKIPIRWTAPEAIQY--RKFTSASDVWSYGIVMWEVMS 821
Cdd:cd07872  160 TYS--NEVVTLWYRPPDVLLgsSEYSTQIDMWGVGCIFFEMAS 200
STKc_MELK cd14078
Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; ...
623-820 2.69e-10

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: 62.01  E-value: 2.69e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 623 IEQVIGAGEFGEVCSGHLKLPGKReifVAIKTLKsgytEKQRRDFL----SEASIMGQFDHPNVIHLEGVVTKSTPVMII 698
Cdd:cd14078    7 LHETIGSGGFAKVKLATHILTGEK---VAIKIMD----KKALGDDLprvkTEIEALKNLSHQHICRLYHVIETDNKIFMV 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 699 TEFMENGSLDSFLRQNDgQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGL--------SRF 770
Cdd:cd14078   80 LEYCPGGELFDYIVAKD-RLSEDEARVFFRQIVSAVAYVHSQGYAHRDLKPENLLLDEDQNLKLIDFGLcakpkggmDHH 158
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 111118978 771 LEDDTSDPTYtsalggkipirwTAPEAIQYRKFT-SASDVWSYGIVMWEVM 820
Cdd:cd14078  159 LETCCGSPAY------------AAPELIQGKPYIgSEADVWSMGVLLYALL 197
STKc_SnRK2 cd14662
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
627-829 3.21e-10

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2; 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. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. 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: 271132 [Multi-domain]  Cd Length: 257  Bit Score: 61.71  E-value: 3.21e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVcsghlKLPGKREI--FVAIKTLKSGYT--EKQRRDFLSEASImgqfDHPNVIHLEGVVTKSTPVMIITEFM 702
Cdd:cd14662    8 IGSGNFGVA-----RLMRNKETkeLVAVKYIERGLKidENVQREIINHRSL----RHPNIIRFKEVVLTPTHLAIVMEYA 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 703 ENGSLdsFLR-QNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLV--CKVSDFGLSR--FLEddtSD 777
Cdd:cd14662   79 AGGEL--FERiCNAGRFSEDEARYFFQQLISGVSYCHSMQICHRDLKLENTLLDGSPAprLKICDFGYSKssVLH---SQ 153
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 111118978 778 PTYTSALGGKIpirwtAPEAIQYRKFT-SASDVWSYGIVMWeVMSYGERPYWD 829
Cdd:cd14662  154 PKSTVGTPAYI-----APEVLSRKEYDgKVADVWSCGVTLY-VMLVGAYPFED 200
STKc_MAP4K3 cd06645
Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase ...
625-887 3.29e-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: 61.98  E-value: 3.29e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGYTEkqrrDF---LSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEF 701
Cdd:cd06645   17 QRIGSGTYGDVYKARNVNTGE---LAAIKVIKLEPGE----DFavvQQEIIMMKDCKHSNIVAYFGSYLRRDKLWICMEF 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 702 MENGSLDSfLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRflEDDTSDPTYT 781
Cdd:cd06645   90 CGGGSLQD-IYHVTGPLSESQIAYVSRETLQGLYYLHSKGKMHRDIKGANILLTDNGHVKLADFGVSA--QITATIAKRK 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 782 SALGGKIpirWTAPE-AIQYRK--FTSASDVWSYGIVMWEVMSYgERPYWDMTNQDVINAIEQDYRLPP----PMDCPSA 854
Cdd:cd06645  167 SFIGTPY---WMAPEvAAVERKggYNQLCDIWAVGITAIELAEL-QPPMFDLHPMRALFLMTKSNFQPPklkdKMKWSNS 242
                        250       260       270
                 ....*....|....*....|....*....|...
gi 111118978 855 LHQLMLDCWQKDRNHRPkfgqivnTLDKMIRNP 887
Cdd:cd06645  243 FHHFVKMALTKNPKKRP-------TAEKLLQHP 268
STKc_Kalirin_C cd14115
C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide ...
627-871 3.57e-10

C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide Exchange Factor, Kalirin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Kalirin, also called Duo or Duet, is a large multidomain protein containing a series of spectrin-like repeats, two each of RhoGEF and SH3 domains, an immunoglobulin-like (Ig) domain and a C-terminal kinase. As a GEF, it activates Rac1, RhoA, and RhoG. It is highly expressed in neurons and is required for spine formation. The kalirin gene produces at least 10 isoforms from alternative promoter use and splicing. Of the major isoforms (Kalirin-7, -9, and -12), only kalirin-12 contains the C-terminal kinase domain. Kalirin-12 is highly expressed during embryonic development and it plays an important role in axon outgrowth. The Kalirin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271017 [Multi-domain]  Cd Length: 248  Bit Score: 61.51  E-value: 3.57e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFgEVCSGHLKLPGKREIFVAIKTLKSgyteKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGS 706
Cdd:cd14115    1 IGRGRF-SIVKKCLHKATRKDVAVKFVSKKM----KKKEQAAHEAALLQHLQHPQYITLHDTYESPTSYILVLELMDDGR 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 707 LDSFLRQNDgQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNL---VCKVSDfglsrfLED--DTSDPTYT 781
Cdd:cd14115   76 LLDYLMNHD-ELMEEKVAFYIRDIMEALQYLHNCRVAHLDIKPENLLIDLRIpvpRVKLID------LEDavQISGHRHV 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 782 SALGGKiPiRWTAPEAIQYRKFTSASDVWSYGIVMWeVMSYGERPYWDMTNQDV-INAIEQDYRLPPPM--DCPSALHQL 858
Cdd:cd14115  149 HHLLGN-P-EFAAPEVIQGTPVSLATDIWSIGVLTY-VMLSGVSPFLDESKEETcINVCRVDFSFPDEYfgDVSQAARDF 225
                        250
                 ....*....|...
gi 111118978 859 MLDCWQKDRNHRP 871
Cdd:cd14115  226 INVILQEDPRRRP 238
STKc_CaMKII cd14086
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
622-848 3.70e-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: 62.05  E-value: 3.70e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGhLKLPGKREIFVAI---KTLKSGYTEKQRRdflsEASIMGQFDHPNVIHLEGVVTKSTPVMII 698
Cdd:cd14086    4 DLKEELGKGAFSVVRRC-VQKSTGQEFAAKIintKKLSARDHQKLER----EARICRLLKHPNIVRLHDSISEEGFHYLV 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 699 TEFMENGSL------DSFLRQNDGQFTVIQlvgmlrgIAAGMKYLADMNYVHRDLAARNILVNS---NLVCKVSDFGLSR 769
Cdd:cd14086   79 FDLVTGGELfedivaREFYSEADASHCIQQ-------ILESVNHCHQNGIVHRDLKPENLLLASkskGAAVKLADFGLAI 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 770 FLEDDTsdPTYTSALGGKIpirWTAPEAIQYRKFTSASDVWSYGIVMWeVMSYGERPYWDMTNQDVINAIEQ-DYRLPPP 848
Cdd:cd14086  152 EVQGDQ--QAWFGFAGTPG---YLSPEVLRKDPYGKPVDIWACGVILY-ILLVGYPPFWDEDQHRLYAQIKAgAYDYPSP 225
STKc_PCTAIRE1 cd07873
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer ...
621-826 3.96e-10

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: 61.94  E-value: 3.96e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQvIGAGEFGEVCSGHLKLPgkrEIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITE 700
Cdd:cd07873    5 IKLDK-LGEGTYATVYKGRSKLT---DNLVALKEIRLEHEEGAPCTAIREVSLLKDLKHANIVTLHDIIHTEKSLTLVFE 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FmengsLDSFLRQN-DGQFTVIQ-------LVGMLRGIAagmkYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRfle 772
Cdd:cd07873   81 Y-----LDKDLKQYlDDCGNSINmhnvklfLFQLLRGLA----YCHRRKVLHRDLKPQNLLINERGELKLADFGLAR--- 148
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 111118978 773 dDTSDPTYTSAlgGKIPIRWTAPEAIQY--RKFTSASDVWSYGIVMWEvMSYGeRP 826
Cdd:cd07873  149 -AKSIPTKTYS--NEVVTLWYRPPDILLgsTDYSTQIDMWGVGCIFYE-MSTG-RP 199
STKc_MAP3K8 cd13995
Catalytic domain of the Serine/Threonine kinase, Mitogen-Activated Protein Kinase (MAPK) ...
669-878 4.19e-10

Catalytic domain of the Serine/Threonine kinase, Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K8 is also called Tumor progression locus 2 (Tpl2) or Cancer Osaka thyroid (Cot), and was first identified as a proto-oncogene in T-cell lymphoma induced by MoMuL virus and in breast carcinoma induced by MMTV. Activated MAP3K8 induces various MAPK pathways including Extracellular Regulated Kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), and p38. It plays a pivotal role in innate immunity, linking Toll-like receptors to the production of TNF and the activation of ERK in macrophages. It is also required in interleukin-1beta production and is critical in host defense against Gram-positive bacteria. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The MAP3K8 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270897 [Multi-domain]  Cd Length: 256  Bit Score: 61.56  E-value: 4.19e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 669 SEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGSLDSFLrQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLA 748
Cdd:cd13995   45 SDVEIQACFRHENIAELYGALLWEETVHLFMEAGEGGSVLEKL-ESCGPMREFEIIWVTKHVLKGLDFLHSKNIIHHDIK 123
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 749 ARNILVNSNLVCKVsDFGLSRFLEDDTSDPTytSALGGKIpirWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERP-- 826
Cdd:cd13995  124 PSNIVFMSTKAVLV-DFGLSVQMTEDVYVPK--DLRGTEI---YMSPEVILCRGHNTKADIYSLGATIIHMQT-GSPPwv 196
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 111118978 827 --YWDMTNQDVINAIEQdyRLPP----PMDCPSALHQLMLDCWQKDRNHRPKFGQIVN 878
Cdd:cd13995  197 rrYPRSAYPSYLYIIHK--QAPPlediAQDCSPAMRELLEAALERNPNHRSSAAELLK 252
PK_STRAD_beta cd08226
Pseudokinase domain of STE20-related kinase adapter protein beta; The pseudokinase domain ...
677-830 4.81e-10

Pseudokinase domain of STE20-related kinase adapter protein beta; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity.STRAD-beta is also referred to as ALS2CR2 (Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 2 protein), since the human gene encoding it is located within the juvenile ALS2 critical region on chromosome 2q33-q34. It is not linked to the development of ALS2. 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. The STRAD-beta 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: 270864 [Multi-domain]  Cd Length: 328  Bit Score: 62.19  E-value: 4.81e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 677 FDHPNVIHLEGVVTKSTPVMIITEFMENGSLDSFLRQNDGQFTVIQLVG-MLRGIAAGMKYLADMNYVHRDLAARNILVN 755
Cdd:cd08226   56 FRHPNIMTHWTVFTEGSWLWVISPFMAYGSARGLLKTYFPEGMNEALIGnILYGAIKALNYLHQNGCIHRSVKASHILIS 135
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 756 ----------SNLVCKVSDFGLSRFLEDdtsDPTYTSALggkipIRWTAPEAIQ--YRKFTSASDVWSYGIVMWEVMSyG 823
Cdd:cd08226  136 gdglvslsglSHLYSMVTNGQRSKVVYD---FPQFSTSV-----LPWLSPELLRqdLHGYNVKSDIYSVGITACELAR-G 206

                 ....*..
gi 111118978 824 ERPYWDM 830
Cdd:cd08226  207 QVPFQDM 213
STKc_PKN cd05589
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N; STKs catalyze the transfer ...
626-846 4.88e-10

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: 62.32  E-value: 4.88e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 626 VIGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGytEKQRRD----FLSEASIM---GQFDHPNVIHLEGVVTKSTPVMII 698
Cdd:cd05589    6 VLGRGHFGKVLLAEYKPTGE---LFAIKALKKG--DIIARDevesLMCEKRIFetvNSARHPFLVNLFACFQTPEHVCFV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 699 TEFMENGslDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSR---FLEDDT 775
Cdd:cd05589   81 MEYAAGG--DLMMHIHEDVFSEPRAVFYAACVVLGLQFLHEHKIVYRDLKLDNLLLDTEGYVKIADFGLCKegmGFGDRT 158
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 111118978 776 SdpTYTSAlggkiPiRWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWDMTNQDVINAI-EQDYRLP 846
Cdd:cd05589  159 S--TFCGT-----P-EFLAPEVLTDTSYTRAVDWWGLGVLIYE-MLVGESPFPGDDEEEVFDSIvNDEVRYP 221
STKc_nPKC_eta cd05590
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta; STKs catalyze the ...
625-842 5.08e-10

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


Pssm-ID: 270742 [Multi-domain]  Cd Length: 323  Bit Score: 62.23  E-value: 5.08e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKSG-----------YTEKQrrdFLSEASimgqfDHPNVIHLEGVVTKST 693
Cdd:cd05590    1 RVLGKGSFGKVMLARLKESGR---LYAVKVLKKDvilqdddvectMTEKR---ILSLAR-----NHPFLTQLYCCFQTPD 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 694 PVMIITEFMENGSLdSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRfleD 773
Cdd:cd05590   70 RLFFVMEFVNGGDL-MFHIQKSRRFDEARARFYAAEITSALMFLHDKGIIYRDLKLDNVLLDHEGHCKLADFGMCK---E 145
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 111118978 774 DTSDPTYTSALGGKiPiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAIEQD 842
Cdd:cd05590  146 GIFNGKTTSTFCGT-P-DYIAPEILQEMLYGPSVDWWAMGVLLYEMLC-GHAPFEAENEDDLFEAILND 211
STKc_MEKK3 cd06651
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular ...
625-828 5.21e-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: 5.21e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVcsgHL--KLPGKREIfvAIKTLK----SGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTK--STPVM 696
Cdd:cd06651   13 KLLGQGAFGRV---YLcyDVDTGREL--AAKQVQfdpeSPETSKEVSALECEIQLLKNLQHERIVQYYGCLRDraEKTLT 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 697 IITEFMENGSLDSFLRQNdGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTS 776
Cdd:cd06651   88 IFMEYMPGGSVKDQLKAY-GALTESVTRKYTRQILEGMSYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASKRLQTICM 166
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 111118978 777 DPTYTSALGGKiPIrWTAPEAIQYRKFTSASDVWSYGIVMWEVMSygERPYW 828
Cdd:cd06651  167 SGTGIRSVTGT-PY-WMSPEVISGEGYGRKADVWSLGCTVVEMLT--EKPPW 214
STKc_SGK cd05575
Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase; ...
626-870 6.23e-10

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGKs are activated by insulin and growth factors via phosphoinositide 3-kinase and PDK1. They activate ion channels, ion carriers, and the Na-K-ATPase, as well as regulate the activity of enzymes and transcription factors. SGKs play important roles in transport, hormone release, neuroexcitability, cell proliferation, and apoptosis. There are three isoforms of SGK, named SGK1, SGK2, and SGK3 (also called cytokine-independent survival kinase CISK). The SGK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270727 [Multi-domain]  Cd Length: 323  Bit Score: 61.95  E-value: 6.23e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 626 VIGAGEFGEVCSGHLKLPGKreiFVAIKTL--KSGYTEKQRRDFLSEASI-MGQFDHPNVIHLEGVVTKSTPVMIITEFM 702
Cdd:cd05575    2 VIGKGSFGKVLLARHKAEGK---LYAVKVLqkKAILKRNEVKHIMAERNVlLKNVKHPFLVGLHYSFQTKDKLYFVLDYV 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 703 ENGSLDSFLrQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRfleDDTSDPTYTS 782
Cdd:cd05575   79 NGGELFFHL-QRERHFPEPRARFYAAEIASALGYLHSLNIIYRDLKPENILLDSQGHVVLTDFGLCK---EGIEPSDTTS 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 783 ALGGKiPiRWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPYWdmtNQDVI----NAIEQDYRLPP--PMDCPSALH 856
Cdd:cd05575  155 TFCGT-P-EYLAPEVLRKQPYDRTVDWWCLGAVLYE-MLYGLPPFY---SRDTAemydNILHKPLRLRTnvSPSARDLLE 228
                        250
                 ....*....|....
gi 111118978 857 QLMldcwQKDRNHR 870
Cdd:cd05575  229 GLL----QKDRTKR 238
STKc_CDK5 cd07839
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 5; STKs ...
622-826 6.48e-10

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: 61.29  E-value: 6.48e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQvIGAGEFGEVCSGHLKLPGkrEIfVAIKTLK-SGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITE 700
Cdd:cd07839    4 KLEK-IGEGTYGTVFKAKNRETH--EI-VALKRVRlDDDDEGVPSSALREICLLKELKHKNIVRLYDVLHSDKKLTLVFE 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FME----------NGSLD-----SFLRQndgqftviqlvgMLRGIAagmkYLADMNYVHRDLAARNILVNSNLVCKVSDF 765
Cdd:cd07839   80 YCDqdlkkyfdscNGDIDpeivkSFMFQ------------LLKGLA----FCHSHNVLHRDLKPQNLLINKNGELKLADF 143
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 111118978 766 GLSRfleddtsdptytsALGgkIPIRWTAPEAIQ--YRK---------FTSASDVWSYGIVMWEvMSYGERP 826
Cdd:cd07839  144 GLAR-------------AFG--IPVRCYSAEVVTlwYRPpdvlfgaklYSTSIDMWSAGCIFAE-LANAGRP 199
STKc_CaMKK2 cd14199
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2; ...
670-876 6.67e-10

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: 61.13  E-value: 6.67e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 670 EASIMGQFDHPNVIHLEGVVTKSTP--VMIITEFMENGSL-----DSFLRQNDGQFTVIQLVgmlrgiaAGMKYLADMNY 742
Cdd:cd14199   75 EIAILKKLDHPNVVKLVEVLDDPSEdhLYMVFELVKQGPVmevptLKPLSEDQARFYFQDLI-------KGIEYLHYQKI 147
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 743 VHRDLAARNILVNSNLVCKVSDFGLSRFLEDdtSDPTYTSALGGKIpirWTAPEAI-QYRKFTS--ASDVWSYGIVMWeV 819
Cdd:cd14199  148 IHRDVKPSNLLVGEDGHIKIADFGVSNEFEG--SDALLTNTVGTPA---FMAPETLsETRKIFSgkALDVWAMGVTLY-C 221
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 111118978 820 MSYGERPYWDMTNQDVINAIE-QDYRLPPPMDCPSALHQLMLDCWQKDRNHRPKFGQI 876
Cdd:cd14199  222 FVFGQCPFMDERILSLHSKIKtQPLEFPDQPDISDDLKDLLFRMLDKNPESRISVPEI 279
STKc_PASK cd14004
Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs ...
623-878 7.34e-10

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: 60.86  E-value: 7.34e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 623 IEQVIGAGEFGEVCSGHLKlpGKREIFVaiktLKSGYTEKQRRDFL----------SEASIMGQ---FDHPNVIHLEGVV 689
Cdd:cd14004    4 ILKEMGEGAYGQVNLAIYK--SKGKEVV----IKFIFKERILVDTWvrdrklgtvpLEIHILDTlnkRSHPNIVKLLDFF 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 690 TKSTPVMIITEFMENGsLDSF----LRQNDGQFTVIQLvgmLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDF 765
Cdd:cd14004   78 EDDEFYYLVMEKHGSG-MDLFdfieRKPNMDEKEAKYI---FRQVADAVKHLHDQGIVHRDIKDENVILDGNGTIKLIDF 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 766 GLSRFLEDDTSDPTYTSalggkipIRWTAPEAIQYRKFTSAS-DVWSYGIVMWEVMsYGERPYWDMtnqdvinaieqDYR 844
Cdd:cd14004  154 GSAAYIKSGPFDTFVGT-------IDYAAPEVLRGNPYGGKEqDIWALGVLLYTLV-FKENPFYNI-----------EEI 214
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 111118978 845 LPPPMDCPSALHQ----LMLDCWQKDRNHRPKFGQIVN 878
Cdd:cd14004  215 LEADLRIPYAVSEdlidLISRMLNRDVGDRPTIEELLT 252
STKc_ACVR2a cd14141
Catalytic domain of the Serine/Threonine Kinase, Activin Type IIA Receptor; STKs catalyze the ...
679-821 7.41e-10

Catalytic domain of the Serine/Threonine Kinase, Activin Type IIA Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR2a (or ActRIIA) 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 ACVR2a subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271043 [Multi-domain]  Cd Length: 290  Bit Score: 61.21  E-value: 7.41e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 679 HPNVIHLEGVVTKSTPV----MIITEFMENGSLDSFLRQNDGQFTVIQLVG--MLRGIA------AGMKYLADMNYVHRD 746
Cdd:cd14141   48 HENILQFIGAEKRGTNLdvdlWLITAFHEKGSLTDYLKANVVSWNELCHIAqtMARGLAylhediPGLKDGHKPAIAHRD 127
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 747 LAARNILVNSNLVCKVSDFGLSRFLEDDTSDPTYTSALGGKipiRWTAPE----AIQYRKFTSAS-DVWSYGIVMWEVMS 821
Cdd:cd14141  128 IKSKNVLLKNNLTACIADFGLALKFEAGKSAGDTHGQVGTR---RYMAPEvlegAINFQRDAFLRiDMYAMGLVLWELAS 204
STKc_WNK3 cd14031
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3; STKs catalyze ...
660-832 7.44e-10

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: 60.89  E-value: 7.44e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 660 TEKQRRDFLSEASIMGQFDHPNVIHL----EGVVTKSTPVMIITEFMENGSLDSFLRqndgQFTVIQ---LVGMLRGIAA 732
Cdd:cd14031   49 TKAEQQRFKEEAEMLKGLQHPNIVRFydswESVLKGKKCIVLVTELMTSGTLKTYLK----RFKVMKpkvLRSWCRQILK 124
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 733 GMKYLADMN--YVHRDLAARNILVNSNL-VCKVSDFGLSRFLEDDTSdptyTSALGGKipiRWTAPEAIQyRKFTSASDV 809
Cdd:cd14031  125 GLQFLHTRTppIIHRDLKCDNIFITGPTgSVKIGDLGLATLMRTSFA----KSVIGTP---EFMAPEMYE-EHYDESVDV 196
                        170       180
                 ....*....|....*....|...
gi 111118978 810 WSYGIVMWEvMSYGERPYWDMTN 832
Cdd:cd14031  197 YAFGMCMLE-MATSEYPYSECQN 218
STKc_NIK cd13991
Catalytic domain of the Serine/Threonine kinase, NF-kappaB Inducing Kinase (NIK); STKs ...
621-870 7.54e-10

Catalytic domain of the Serine/Threonine kinase, NF-kappaB Inducing Kinase (NIK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NIK, also called mitogen activated protein kinase kinase kinase 14 (MAP3K14), phosphorylates and activates Inhibitor of NF-KappaB Kinase (IKK) alpha, which is a regulator of 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. NIK is essential in the IKKalpha-mediated non-canonical NF-kB signaling pathway, in which IKKalpha processes the IkB-like C-terminus of NF-kB2/p100 to produce p52, allowing the p52/RelB dimer to migrate to the nucleus where it regulates gene transcription. NIK also plays an important role in Toll-like receptor 7/9 signaling cascades. The NIK 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: 270893 [Multi-domain]  Cd Length: 268  Bit Score: 60.99  E-value: 7.54e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQVIGAGEFGEVCSGHLKLPGKReifVAIKTLKsgytekQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITE 700
Cdd:cd13991    8 ATHQLRIGRGSFGEVHRMEDKQTGFQ---CAVKKVR------LEVFRAEELMACAGLTSPRVVPLYGAVREGPWVNIFMD 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMENGSLDSFLRQNdGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSN----LVCkvsDFGLSRFLEDD-T 775
Cdd:cd13991   79 LKEGGSLGQLIKEQ-GCLPEDRALHYLGQALEGLEYLHSRKILHGDVKADNVLLSSDgsdaFLC---DFGHAECLDPDgL 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 776 SDPTYTsalGGKIPIRWT--APEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAIEQDyrlPPPM---- 849
Cdd:cd13991  155 GKSLFT---GDYIPGTEThmAPEVVLGKPCDAKVDVWSSCCMMLHMLN-GCHPWTQYYSGPLCLKIANE---PPPLreip 227
                        250       260
                 ....*....|....*....|..
gi 111118978 850 -DCPSALHQLMLDCWQKDRNHR 870
Cdd:cd13991  228 pSCAPLTAQAIQAGLRKEPVHR 249
STKc_NDR_like cd05599
Catalytic domain of Nuclear Dbf2-Related kinase-like Protein Serine/Threonine Kinases; STKs ...
626-827 8.51e-10

Catalytic domain of Nuclear Dbf2-Related kinase-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR kinases regulate mitosis, cell growth, embryonic development, and neurological processes. They are also required for proper centrosome duplication. Higher eukaryotes contain two NDR isoforms, NDR1 and NDR2. This subfamily also contains fungal NDR-like kinases. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR 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: 270750 [Multi-domain]  Cd Length: 324  Bit Score: 61.48  E-value: 8.51e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 626 VIGAGEFGEVcsghlKLPGKREI--FVAIKTL-KSGYTEKQR-------RDFLSEAsimgqfDHPNVIHLEGVVTKSTPV 695
Cdd:cd05599    8 VIGRGAFGEV-----RLVRKKDTghVYAMKKLrKSEMLEKEQvahvraeRDILAEA------DNPWVVKLYYSFQDEENL 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 696 MIITEFMENGSLDSFLRQND------GQFTVIQLVgmlrgiaAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSR 769
Cdd:cd05599   77 YLIMEFLPGGDMMTLLMKKDtlteeeTRFYIAETV-------LAIESIHKLGYIHRDIKPDNLLLDARGHIKLSDFGLCT 149
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 111118978 770 FLedDTSDPTYtSALGgkIPiRWTAPEAIQYRKFTSASDVWSYGIVMWEvMSYGERPY 827
Cdd:cd05599  150 GL--KKSHLAY-STVG--TP-DYIAPEVFLQKGYGKECDWWSLGVIMYE-MLIGYPPF 200
STKc_myosinIIIB_N cd06639
N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIB myosin; STKs catalyze ...
623-871 9.71e-10

N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIB myosin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class IIIB myosin is expressed highly in retina. It is also present in the brain and testis. The human class IIIB myosin gene maps to a region that overlaps the locus for Bardet-Biedl syndrome, which is characterized by dysmorphic extremities, retinal dystrophy, obesity, male hypogenitalism, and renal abnormalities. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain. They may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. They may also function as cargo carriers during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The class III myosin subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270808 [Multi-domain]  Cd Length: 291  Bit Score: 60.78  E-value: 9.71e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 623 IEQVIGAGEFGEVcsghLKLPGKRE-IFVAIKTLKSgyTEKQRRDFLSEASIMGQF-DHPNVIHLEGVVTKSTPVM---- 696
Cdd:cd06639   26 IIETIGKGTYGKV----YKVTNKKDgSLAAVKILDP--ISDVDEEIEAEYNILRSLpNHPNVVKFYGMFYKADQYVggql 99
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 697 -IITEFMENGSLDSFLRQ--NDGQFTVIQLVG-MLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLE 772
Cdd:cd06639  100 wLVLELCNGGSVTELVKGllKCGQRLDEAMISyILYGALLGLQHLHNNRIIHRDVKGNNILLTTEGGVKLVDFGVSAQLT 179
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 773 ddTSDPTYTSALGGKIpirWTAPEAI----QY-RKFTSASDVWSYGIVMWEvMSYGERPYWDMtnqDVINAIEQDYRLPP 847
Cdd:cd06639  180 --SARLRRNTSVGTPF---WMAPEVIaceqQYdYSYDARCDVWSLGITAIE-LADGDPPLFDM---HPVKALFKIPRNPP 250
                        250       260       270
                 ....*....|....*....|....*....|
gi 111118978 848 PMD------CPSALHqLMLDCWQKDRNHRP 871
Cdd:cd06639  251 PTLlnpekwCRGFSH-FISQCLIKDFEKRP 279
STKc_JNK2 cd07876
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 2; STKs catalyze the ...
627-820 1.05e-09

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK2 is expressed in every cell and tissue type. It is specifically translocated to the mitochondria during dopaminergic cell death. Specific substrates include the microtubule-associated proteins DCX and Tau, as well as TIF-IA which is involved in ribosomal RNA synthesis regulation. Mice deficient in Jnk2 show protection against arthritis, type 1 diabetes, atherosclerosis, abdominal aortic aneurysm, cardiac cell death, TNF-induced liver damage, and tumor growth, indicating that JNK2 may play roles in the pathogenesis of these diseases. Initially it was thought that JNK1 and JNK2 were functionally redundant as mice deficient in either genes could survive but disruption of both genes resulted in lethality. However, recent studies have shown that JNK1 and JNK2 perform distinct functions through specific binding partners and substrates. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143381 [Multi-domain]  Cd Length: 359  Bit Score: 61.58  E-value: 1.05e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGkreIFVAIKTLKSGY-TEKQRRDFLSEASIMGQFDHPNVIHLEGVVTkstPVMIITEFMENG 705
Cdd:cd07876   29 IGSGAQGIVCAAFDTVLG---INVAVKKLSRPFqNQTHAKRAYRELVLLKCVNHKNIISLLNVFT---PQKSLEEFQDVY 102
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 706 SLDSFLRQNDGQFTVIQL-----VGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDPTY 780
Cdd:cd07876  103 LVMELMDANLCQVIHMELdhermSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTACTNFMMTPY 182
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 111118978 781 TsalggkIPIRWTAPEAIQYRKFTSASDVWSYGIVMWEVM 820
Cdd:cd07876  183 V------VTRYYRAPEVILGMGYKENVDIWSVGCIMGELV 216
STKc_GRK cd05577
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase; STKs ...
627-827 1.09e-09

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: 60.62  E-value: 1.09e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGYTEKQRRD--FLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMEN 704
Cdd:cd05577    1 LGRGGFGEVCACQVKATGK---MYACKKLDKKRIKKKKGEtmALNEKIILEKVSSPFIVSLAYAFETKDKLCLVLTLMNG 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 705 GSLDSFLRQNDGQ-FTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDPTYTSA 783
Cdd:cd05577   78 GDLKYHIYNVGTRgFSEARAIFYAAEIICGLEHLHNRFIVYRDLKPENILLDDHGHVRISDLGLAVEFKGGKKIKGRVGT 157
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 111118978 784 LGgkipirWTAPEAIQY-RKFTSASDVWSYGIVMWEvMSYGERPY 827
Cdd:cd05577  158 HG------YMAPEVLQKeVAYDFSVDWFALGCMLYE-MIAGRSPF 195
STKc_PFTAIRE1 cd07869
Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-1 kinase; STKs catalyze the transfer ...
622-820 1.10e-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: 60.86  E-value: 1.10e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQvIGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEF 701
Cdd:cd07869    9 KLEK-LGEGSYATVYKGKSKVNGK---LVALKVIRLQEEEGTPFTAIREASLLKGLKHANIVLLHDIIHTKETLTLVFEY 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 702 MENgSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRfledDTSDPTYT 781
Cdd:cd07869   85 VHT-DLCQYMDKHPGGLHPENVKLFLFQLLRGLSYIHQRYILHRDLKPQNLLISDTGELKLADFGLAR----AKSVPSHT 159
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 111118978 782 SAlgGKIPIRWTAPEAIQY--RKFTSASDVWSYGIVMWEVM 820
Cdd:cd07869  160 YS--NEVVTLWYRPPDVLLgsTEYSTCLDMWGVGCIFVEMI 198
STKc_WNK4 cd14033
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze ...
621-870 1.30e-09

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: 60.02  E-value: 1.30e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQVIGAGEFGEVCSGhlkLPGKREIFVA---IKTLKSGYTEKQRrdFLSEASIMGQFDHPNVIHL----EGVVTKST 693
Cdd:cd14033    3 LKFNIEIGRGSFKTVYRG---LDTETTVEVAwceLQTRKLSKGERQR--FSEEVEMLKGLQHPNIVRFydswKSTVRGHK 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 694 PVMIITEFMENGSLDSFLRQ-NDGQFTVIQLVGmlRGIAAGMKYLADMN--YVHRDLAARNILVNS-NLVCKVSDFGLSr 769
Cdd:cd14033   78 CIILVTELMTSGTLKTYLKRfREMKLKLLQRWS--RQILKGLHFLHSRCppILHRDLKCDNIFITGpTGSVKIGDLGLA- 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 770 fleddtsdpTYTSALGGKIPI---RWTAPEAIQyRKFTSASDVWSYGIVMWEvMSYGERPYWDMTN-----QDVINAIEQ 841
Cdd:cd14033  155 ---------TLKRASFAKSVIgtpEFMAPEMYE-EKYDEAVDVYAFGMCILE-MATSEYPYSECQNaaqiyRKVTSGIKP 223
                        250       260       270
                 ....*....|....*....|....*....|.
gi 111118978 842 D--YRLPPPmdcpsALHQLMLDCWQKDRNHR 870
Cdd:cd14033  224 DsfYKVKVP-----ELKEIIEGCIRTDKDER 249
STKc_CASK cd14094
Catalytic domain of the Serine/Threonine Kinase, Calcium/calmodulin-dependent serine protein ...
620-849 1.37e-09

Catalytic domain of the Serine/Threonine Kinase, Calcium/calmodulin-dependent serine protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CASK belongs to the MAGUK (membrane-associated guanylate kinase) protein family, which functions as multiple domain adaptor proteins and is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). The enzymatically inactive GuK domain in MAGUK proteins mediates protein-protein interactions and associates intramolecularly with the SH3 domain. In addition, CASK contains a catalytic kinase and two L27 domains. It is highly expressed in the nervous system and plays roles in synaptic protein targeting, neural development, and regulation of gene expression. Binding partners include parkin (a Parkinson's disease molecule), neurexin (adhesion molecule), syndecans, calcium channel proteins, CINAP (nucleosome assembly protein), transcription factor Tbr-1, and the cytoplasmic adaptor proteins Mint1, Veli/mLIN-7/MALS, SAP97, caskin, and CIP98. Deletion or mutations in the CASK gene have been implicated in X-linked mental retardation. The CASK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270996 [Multi-domain]  Cd Length: 300  Bit Score: 60.63  E-value: 1.37e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 620 CVKIEQVIGAGEFGEV--CsghLKLPGKREIFVAIKTLK--SGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPV 695
Cdd:cd14094    4 VYELCEVIGKGPFSVVrrC---IHRETGQQFAVKIVDVAkfTSSPGLSTEDLKREASICHMLKHPHIVELLETYSSDGML 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 696 MIITEFMENGSLD-SFLRQNDGQFTVIQLVG--MLRGIAAGMKYLADMNYVHRDLAARNILV----NSNLVcKVSDFGLS 768
Cdd:cd14094   81 YMVFEFMDGADLCfEIVKRADAGFVYSEAVAshYMRQILEALRYCHDNNIIHRDVKPHCVLLaskeNSAPV-KLGGFGVA 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 769 RFLeddtsdPTYTSALGGKIPI-RWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAIEQDYRLPP 847
Cdd:cd14094  160 IQL------GESGLVAGGRVGTpHFMAPEVVKREPYGKPVDVWGCGVILFILLS-GCLPFYGTKERLFEGIIKGKYKMNP 232

                 ..
gi 111118978 848 PM 849
Cdd:cd14094  233 RQ 234
STKc_CDKL1_4 cd07847
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; ...
627-828 1.93e-09

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


Pssm-ID: 270837 [Multi-domain]  Cd Length: 286  Bit Score: 59.69  E-value: 1.93e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKreiFVAIKTlksgYTEKQ-----RRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEF 701
Cdd:cd07847    9 IGEGSYGVVFKCRNRETGQ---IVAIKK----FVESEddpviKKIALREIRMLKQLKHPNLVNLIEVFRRKRKLHLVFEY 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 702 MENGSLDSfLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFL---EDDTSDP 778
Cdd:cd07847   82 CDHTVLNE-LEKNPRGVPEHLIKKIIWQTLQAVNFCHKHNCIHRDVKPENILITKQGQIKLCDFGFARILtgpGDDYTDY 160
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 111118978 779 TYTsalggkipiRW-TAPEAI----QYrkfTSASDVWSYGIVMWEVMSyGErPYW 828
Cdd:cd07847  161 VAT---------RWyRAPELLvgdtQY---GPPVDVWAIGCVFAELLT-GQ-PLW 201
PTZ00266 PTZ00266
NIMA-related protein kinase; Provisional
599-846 2.30e-09

NIMA-related protein kinase; Provisional


Pssm-ID: 173502 [Multi-domain]  Cd Length: 1021  Bit Score: 61.68  E-value: 2.30e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  599 PFTYEDPNEAVREFakeidiscvKIEQVIGAGEFGEVCSghLKLPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFD 678
Cdd:PTZ00266    2 PGKYDDGESRLNEY---------EVIKKIGNGRFGEVFL--VKHKRTQEFFCWKAISYRGLKEREKSQLVIEVNVMRELK 70
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  679 HPNVI-HLEGVVTKST-PVMIITEFMENGSLDSFLRQNDGQFTVIQ---LVGMLRGIAAGMKYLADMN-------YVHRD 746
Cdd:PTZ00266   71 HKNIVrYIDRFLNKANqKLYILMEFCDAGDLSRNIQKCYKMFGKIEehaIVDITRQLLHALAYCHNLKdgpngerVLHRD 150
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978  747 LAARNILVNSNL-----------------VCKVSDFGLSRFLEDDTsdpTYTSALGgkIPIRWTaPEAI--QYRKFTSAS 807
Cdd:PTZ00266  151 LKPQNIFLSTGIrhigkitaqannlngrpIAKIGDFGLSKNIGIES---MAHSCVG--TPYYWS-PELLlhETKSYDDKS 224
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 111118978  808 DVWSYGIVMWEVMSyGERPYWDMTN-QDVINAIEQDYRLP 846
Cdd:PTZ00266  225 DMWALGCIIYELCS-GKTPFHKANNfSQLISELKRGPDLP 263
STKc_GAK cd14036
Catalytic domain of the Serine/Threonine protein kinase, cyclin G-Associated Kinase; STKs ...
621-880 2.31e-09

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: 59.45  E-value: 2.31e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQVIGAGEFGEVCSGHLKLPGKReifVAIKTLKSGYTEKQRrDFLSEASIMGQFD-HPNVIHLEGVVTKS------- 692
Cdd:cd14036    2 LRIKRVIAEGGFAFVYEAQDVGTGKE---YALKRLLSNEEEKNK-AIIQEINFMKKLSgHPNIVQFCSAASIGkeesdqg 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 693 -TPVMIITEFMEnGSLDSFLRQND--GQFTVIQLVGMLRGIAAGMKYLADMN--YVHRDLAARNILVNSNLVCKVSDFGl 767
Cdd:cd14036   78 qAEYLLLTELCK-GQLVDFVKKVEapGPFSPDTVLKIFYQTCRAVQHMHKQSppIIHRDLKIENLLIGNQGQIKLCDFG- 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 768 SRFLEDDTSDPTYTSALGGKI---------PIrWTAPEAIQ-YRKF--TSASDVWSYGIVMWeVMSYGERPYWDMTNQDV 835
Cdd:cd14036  156 SATTEAHYPDYSWSAQKRSLVedeitrnttPM-YRTPEMIDlYSNYpiGEKQDIWALGCILY-LLCFRKHPFEDGAKLRI 233
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*
gi 111118978 836 INAieqDYRLPPPMDCPSALHQLMLDCWQKDRNHRPKFGQIVNTL 880
Cdd:cd14036  234 INA---KYTIPPNDTQYTVFHDLIRSTLKVNPEERLSITEIVEQL 275
STKc_JNK1 cd07875
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 1; STKs catalyze the ...
627-874 3.05e-09

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK1 is expressed in every cell and tissue type. It specifically binds with JAMP (JNK1-associated membrane protein), which regulates the duration of JNK1 activity in response to stimuli. Specific JNK1 substrates include Itch and SG10, which are implicated in Th2 responses and airway inflammation, and microtubule dynamics and axodendritic length, respectively. Mice deficient in JNK1 are protected against arthritis, obesity, type 2 diabetes, cardiac cell death, and non-alcoholic liver disease, suggesting that JNK1 may play roles in the pathogenesis of these diseases. Initially, it was thought that JNK1 and JNK2 were functionally redundant as mice deficient in either genes could survive but disruption of both genes resulted in lethality. However, recent studies have shown that JNK1 and JNK2 perform distinct functions through specific binding partners and substrates. JNKs are mitogen-activated protein kinases that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143380 [Multi-domain]  Cd Length: 364  Bit Score: 60.06  E-value: 3.05e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLpgkREIFVAIKTLKSGY-TEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTP------VMIIT 699
Cdd:cd07875   32 IGSGAQGIVCAAYDAI---LERNVAIKKLSRPFqNQTHAKRAYRELVLMKCVNHKNIIGLLNVFTPQKSleefqdVYIVM 108
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENGSLDSFLRQNDGQFTVIQLVGMLRGIaagmKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRfleddTSDPT 779
Cdd:cd07875  109 ELMDANLCQVIQMELDHERMSYLLYQMLCGI----KHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLAR-----TAGTS 179
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 780 YTsaLGGKIPIR-WTAPEAIQYRKFTSASDVWSYGIVMWEVMSYG----ERPYWDMTNQdvinAIEQdyrLPPPmdCPSA 854
Cdd:cd07875  180 FM--MTPYVVTRyYRAPEVILGMGYKENVDIWSVGCIMGEMIKGGvlfpGTDHIDQWNK----VIEQ---LGTP--CPEF 248
                        250       260
                 ....*....|....*....|
gi 111118978 855 LHQLMLDCWQKDRNhRPKFG 874
Cdd:cd07875  249 MKKLQPTVRTYVEN-RPKYA 267
PK_STRAD cd08216
Pseudokinase domain of STE20-related kinase adapter protein; The pseudokinase domain shows ...
631-830 3.07e-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: 59.62  E-value: 3.07e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 631 EFGEVCSG----HLKLPGKREIFVAIK--TLKSGYTEKQRRdFLSEASIMGQFDHPNVI-HLEGVVTKSTpVMIITEFME 703
Cdd:cd08216    5 EIGKCFKGggvvHLAKHKPTNTLVAVKkiNLESDSKEDLKF-LQQEILTSRQLQHPNILpYVTSFVVDND-LYVVTPLMA 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 704 NGSLDSFLRQN--DGqF--TVIQLVgmLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDF--GLSRFLEDDTSD 777
Cdd:cd08216   83 YGSCRDLLKTHfpEG-LpeLAIAFI--LRDVLNALEYIHSKGYIHRSVKASHILISGDGKVVLSGLryAYSMVKHGKRQR 159
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 111118978 778 PTYTSALGGKIPIRWTAPEAIQ--YRKFTSASDVWSYGIVMWEvMSYGERPYWDM 830
Cdd:cd08216  160 VVHDFPKSSEKNLPWLSPEVLQqnLLGYNEKSDIYSVGITACE-LANGVVPFSDM 213
STKc_CDKL5 cd07848
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs ...
626-819 3.07e-09

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


Pssm-ID: 270838 [Multi-domain]  Cd Length: 287  Bit Score: 59.24  E-value: 3.07e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 626 VIGAGEFGEVCSGHLKlpgKREIFVAIKTLK-SGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMEN 704
Cdd:cd07848    8 VVGEGAYGVVLKCRHK---ETKEIVAIKKFKdSEENEEVKETTLRELKMLRTLKQENIVELKEAFRRRGKLYLVFEYVEK 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 705 GSLDSFLRQNDG------QFTVIQLVgmlrgiaAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTsDP 778
Cdd:cd07848   85 NMLELLEEMPNGvppekvRSYIYQLI-------KAIHWCHKNDIVHRDIKPENLLISHNDVLKLCDFGFARNLSEGS-NA 156
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 111118978 779 TYTSAlggkIPIRW-TAPEAIQYRKFTSASDVWSYGIVMWEV 819
Cdd:cd07848  157 NYTEY----VATRWyRSPELLLGAPYGKAVDMWSVGCILGEL 194
STKc_MSK2_N cd05614
N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
625-827 3.32e-09

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270765 [Multi-domain]  Cd Length: 332  Bit Score: 59.55  E-value: 3.32e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEV-----CSGH-------LKLPGKREIFVAIKTLKSGYTEKQRRDFLSEAsimgqfdhPNVIHLEGVVTKS 692
Cdd:cd05614    6 KVLGTGAYGKVflvrkVSGHdanklyaMKVLRKAALVQKAKTVEHTRTERNVLEHVRQS--------PFLVTLHYAFQTD 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 693 TPVMIITEFMENGSLDSFLRQNDgQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSR-FL 771
Cdd:cd05614   78 AKLHLILDYVSGGELFTHLYQRD-HFSEDEVRFYSGEIILALEHLHKLGIVYRDIKLENILLDSEGHVVLTDFGLSKeFL 156
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 111118978 772 EDDtSDPTYtSALGgkiPIRWTAPEAIQYRK-FTSASDVWSYGIVMWEVMSyGERPY 827
Cdd:cd05614  157 TEE-KERTY-SFCG---TIEYMAPEIIRGKSgHGKAVDWWSLGILMFELLT-GASPF 207
STKc_PKB cd05571
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B; STKs catalyze the transfer ...
625-834 3.64e-09

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. There are three PKB isoforms from different genes, PKB-alpha (or Akt1), PKB-beta (or Akt2), and PKB-gamma (or Akt3). PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. It is activated downstream of phosphoinositide 3-kinase (PI3K) and plays important roles in diverse cellular functions including cell survival, growth, proliferation, angiogenesis, motility, and migration. PKB also has a central role in a variety of human cancers, having been implicated in tumor initiation, progression, and metastasis. The PKB subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and PI3K.


Pssm-ID: 270723 [Multi-domain]  Cd Length: 322  Bit Score: 59.29  E-value: 3.64e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKS---------GYTekqrrdfLSEASIMGQFDHPNVIHLEGVVTKSTPV 695
Cdd:cd05571    1 KVLGKGTFGKVILCREKATGE---LYAIKILKKeviiakdevAHT-------LTENRVLQNTRHPFLTSLKYSFQTNDRL 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 696 MIITEFMENGSLDSFLRQnDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRfleDDT 775
Cdd:cd05571   71 CFVMEYVNGGELFFHLSR-ERVFSEDRTRFYGAEIVLALGYLHSQGIVYRDLKLENLLLDKDGHIKITDFGLCK---EEI 146
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 111118978 776 SDPTYTSALGGKiPiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWdmtNQD 834
Cdd:cd05571  147 SYGATTKTFCGT-P-EYLAPEVLEDNDYGRAVDWWGLGVVMYEMMC-GRLPFY---NRD 199
STKc_obscurin_rpt1 cd14107
Catalytic kinase domain, first repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs ...
619-858 3.64e-09

Catalytic kinase domain, first repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Obscurin, approximately 800 kDa in size, is one of three giant proteins expressed in vetebrate striated muscle, together with titin and nebulin. It is a multidomain protein composed of tandem adhesion and signaling domains, including 49 immunoglobulin (Ig) and 2 fibronectin type III (FN3) domains at the N-terminus followed by a more complex region containing more Ig domains, a conserved SH3 domain near a RhoGEF and PH domains, non-modular regions, as well as IQ and phosphorylation motifs. The obscurin gene also encode two kinase domains, which are not expressed as part of the 800 kDa protein, but as a smaller, alternatively spliced product present mainly in the heart muscle, also called obscurin-MLCK. Obscurin is localized at the peripheries of Z-disks and M-lines, where it is able to communicate with the surrounding myoplasm. It interacts with diverse proteins including sAnk1, myosin, titin, and MyBP-C. It may act as a scaffold for the assembly of elements of the contractile apparatus. The obscurin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271009 [Multi-domain]  Cd Length: 257  Bit Score: 58.75  E-value: 3.64e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 619 SCVKIEQVIGAGEFGEVCSGHLKlpGKREIFVA-IKTLKSGYTEK--QRRDFLSEASimgqfdHPNVIHL-EGVVTKSTP 694
Cdd:cd14107    2 SVYEVKEEIGRGTFGFVKRVTHK--GNGECCAAkFIPLRSSTRARafQERDILARLS------HRRLTCLlDQFETRKTL 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 695 VMIITEFMENGSLDSFLRQndGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLV--CKVSDFGLSRflE 772
Cdd:cd14107   74 ILILELCSSEELLDRLFLK--GVVTEAEVKLYIQQVLEGIGYLHGMNILHLDIKPDNILMVSPTRedIKICDFGFAQ--E 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 773 DDTSDPTYtSALGGKipiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMS-----YGE------------RPYWDMTN--- 832
Cdd:cd14107  150 ITPSEHQF-SKYGSP---EFVAPEIVHQEPVSAATDIWALGVIAYLSLTchspfAGEndratllnvaegVVSWDTPEith 225
                        250       260       270
                 ....*....|....*....|....*....|.
gi 111118978 833 -----QDVINAIEQdyrlPPPMDCPSALHQL 858
Cdd:cd14107  226 lsedaKDFIKRVLQ----PDPEKRPSASECL 252
STKc_PKB_alpha cd05594
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B alpha (also called Akt1); ...
604-846 3.76e-09

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B alpha (also called Akt1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-alpha is predominantly expressed in endothelial cells. It is critical for the regulation of angiogenesis and the maintenance of vascular integrity. It also plays a role in adipocyte differentiation. Mice deficient in PKB-alpha exhibit perinatal morbidity, growth retardation, reduction in body weight accompanied by reduced sizes of multiple organs, and enhanced apoptosis in some cell types. PKB-alpha activity has been reported to be frequently elevated in breast and prostate cancers. In some cancer cells, PKB-alpha may act as a suppressor of metastasis. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270746 [Multi-domain]  Cd Length: 356  Bit Score: 59.66  E-value: 3.76e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 604 DPNEAvrefAKEIDISCVKIE-----------QVIGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGY--TEKQRRDFLSE 670
Cdd:cd05594    3 SDNSG----AEEMEVSLTKPKhkvtmndfeylKLLGKGTFGKVILVKEKATGR---YYAMKILKKEVivAKDEVAHTLTE 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 671 ASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENGSL------DSFLRQNDGQFTVIQLVgmlrgiaAGMKYL-ADMNYV 743
Cdd:cd05594   76 NRVLQNSRHPFLTALKYSFQTHDRLCFVMEYANGGELffhlsrERVFSEDRARFYGAEIV-------SALDYLhSEKNVV 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 744 HRDLAARNILVNSNLVCKVSDFGLSR-FLEDDTSDPTYTSAlggkiPiRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSy 822
Cdd:cd05594  149 YRDLKLENLMLDKDGHIKITDFGLCKeGIKDGATMKTFCGT-----P-EYLAPEVLEDNDYGRAVDWWGLGVVMYEMMC- 221
                        250       260
                 ....*....|....*....|....*
gi 111118978 823 GERPYWDMTNQDVINAI-EQDYRLP 846
Cdd:cd05594  222 GRLPFYNQDHEKLFELIlMEEIRFP 246
STKc_CaMKK1 cd14200
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 1; ...
670-829 5.00e-09

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: 58.42  E-value: 5.00e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 670 EASIMGQFDHPNVIHLEGVVTKSTP--VMIITEFMENGSLDSFlrQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDL 747
Cdd:cd14200   73 EIAILKKLDHVNIVKLIEVLDDPAEdnLYMVFDLLRKGPVMEV--PSDKPFSEDQARLYFRDIVLGIEYLHYQKIVHRDI 150
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 748 AARNILVNSNLVCKVSDFGLSRFLEDDtsDPTYTSALGGKIpirWTAPEAI--QYRKFT-SASDVWSYGIVMWeVMSYGE 824
Cdd:cd14200  151 KPSNLLLGDDGHVKIADFGVSNQFEGN--DALLSSTAGTPA---FMAPETLsdSGQSFSgKALDVWAMGVTLY-CFVYGK 224

                 ....*
gi 111118978 825 RPYWD 829
Cdd:cd14200  225 CPFID 229
STKc_nPKC_epsilon cd05591
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C epsilon; STKs catalyze ...
625-847 5.94e-09

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C epsilon; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-epsilon has been shown to behave as an oncoprotein. Its overexpression contributes to neoplastic transformation depending on the cell type. It contributes to oncogenesis by inducing disordered cell growth and inhibiting cell death. It also plays a role in tumor invasion and metastasis. PKC-epsilon has also been found to confer cardioprotection against ischemia and reperfusion-mediated damage. Other cellular functions include the regulation of gene expression, cell adhesion, and cell motility. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-epsilon subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270743 [Multi-domain]  Cd Length: 321  Bit Score: 58.66  E-value: 5.94e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHLKlpGKREIFvAIKTLKSGYTeKQRRDF---LSEASIMG-QFDHPNVIHLEGVVTKSTPVMIITE 700
Cdd:cd05591    1 KVLGKGSFGKVMLAERK--GTDEVY-AIKVLKKDVI-LQDDDVdctMTEKRILAlAAKHPFLTALHSCFQTKDRLFFVME 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMENGSLdSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRflEDDTSDPTY 780
Cdd:cd05591   77 YVNGGDL-MFQIQRARKFDEPRARFYAAEVTLALMFLHRHGVIYRDLKLDNILLDAEGHCKLADFGMCK--EGILNGKTT 153
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 111118978 781 TSALGGKIPIrwtAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINAIEQDYRLPP 847
Cdd:cd05591  154 TTFCGTPDYI---APEILQELEYGPSVDWWALGVLMYEMMA-GQPPFEADNEDDLFESILHDDVLYP 216
STKc_TSSK3-like cd14163
Catalytic domain of testis-specific serine/threonine kinase 3 and similar proteins; STKs ...
622-829 5.95e-09

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: 58.08  E-value: 5.95e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKlpgKREIFVAIKTL-KSGYTEKQRRDFL-SEASIMGQFDHPNVIHL-EGVVTKSTPVMII 698
Cdd:cd14163    3 QLGKTIGEGTYSKVKEAFSK---KHQRKVAIKIIdKSGGPEEFIQRFLpRELQIVERLDHKNIIHVyEMLESADGKIYLV 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 699 TEFMENGSL-DSFLRQndGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVcKVSDFGLSRFLEDDTSD 777
Cdd:cd14163   80 MELAEDGDVfDCVLHG--GPLPEHRAKALFRQLVEAIRYCHGCGVAHRDLKCENALLQGFTL-KLTDFGFAKQLPKGGRE 156
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 111118978 778 PTYTsaLGGKIPirWTAPEAIQYRKFTS-ASDVWSYGIVMWeVMSYGERPYWD 829
Cdd:cd14163  157 LSQT--FCGSTA--YAAPEVLQGVPHDSrKGDIWSMGVVLY-VMLCAQLPFDD 204
STKc_SBK1 cd13987
Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the ...
627-828 6.03e-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: 58.10  E-value: 6.03e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEV------CSGHLklpgkreifVAIKTLKSGYTeKQRrDFLSEASIMGQF-DHPNVIHLEGVVTKSTPVMIIT 699
Cdd:cd13987    1 LGEGTYGKVllavhkGSGTK---------MALKFVPKPST-KLK-DFLREYNISLELsVHPHIIKTYDVAFETEDYYVFA 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 -EFMENGSLdsflrqndgqFTVIQ-LVGM--------LRGIAAGMKYLADMNYVHRDLAARNILV--NSNLVCKVSDFGL 767
Cdd:cd13987   70 qEYAPYGDL----------FSIIPpQVGLpeervkrcAAQLASALDFMHSKNLVHRDIKPENVLLfdKDCRRVKLCDFGL 139
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 111118978 768 SRfleddtSDPTYTSALGGKIPirWTAPE---AIQYRKFT--SASDVWSYGIVM---------WEVMSYGERPYW 828
Cdd:cd13987  140 TR------RVGSTVKRVSGTIP--YTAPEvceAKKNEGFVvdPSIDVWAFGVLLfccltgnfpWEKADSDDQFYE 206
PHA02988 PHA02988
hypothetical protein; Provisional
650-880 7.65e-09

hypothetical protein; Provisional


Pssm-ID: 165291 [Multi-domain]  Cd Length: 283  Bit Score: 57.83  E-value: 7.65e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 650 VAIKTLKSGYT--EKQRRDFLSEASIMGQFDHPNVIHLEGV---VTKSTP-VMIITEFMENGSLDSFLRQN-DGQFTViQ 722
Cdd:PHA02988  46 VIIRTFKKFHKghKVLIDITENEIKNLRRIDSNNILKIYGFiidIVDDLPrLSLILEYCTRGYLREVLDKEkDLSFKT-K 124
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 723 LVGML---RGIAAGMKYladMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTSDPTYTSAlggkipirWTAPEAIQ 799
Cdd:PHA02988 125 LDMAIdccKGLYNLYKY---TNKPYKNLTSVSFLVTENYKLKIICHGLEKILSSPPFKNVNFMV--------YFSYKMLN 193
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 800 --YRKFTSASDVWSYGIVMWEVMSyGERPYWDMTNQDVINA-IEQDYRLPPPMDCPSALHQLMLDCWQKDRNHRPKFGQI 876
Cdd:PHA02988 194 diFSEYTIKDDIYSLGVVLWEIFT-GKIPFENLTTKEIYDLiINKNNSLKLPLDCPLEIKCIVEACTSHDSIKRPNIKEI 272

                 ....
gi 111118978 877 VNTL 880
Cdd:PHA02988 273 LYNL 276
STKc_PFTAIRE2 cd07870
Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-2 kinase; STKs catalyze the transfer ...
627-820 7.67e-09

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: 58.05  E-value: 7.67e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 627 IGAGEFGEVCSGHLKLPGKreiFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITEFMENgS 706
Cdd:cd07870    8 LGEGSYATVYKGISRINGQ---LVALKVISMKTEEGVPFTAIREASLLKGLKHANIVLLHDIIHTKETLTFVFEYMHT-D 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 707 LDSFLRQNDGQF----TVIQLVGMLRGIAagmkYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRfledDTSDP--TY 780
Cdd:cd07870   84 LAQYMIQHPGGLhpynVRLFMFQLLRGLA----YIHGQHILHRDLKPQNLLISYLGELKLADFGLAR----AKSIPsqTY 155
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 111118978 781 TSALggkIPIRWTAPEAIQ-YRKFTSASDVWSYGIVMWEVM 820
Cdd:cd07870  156 SSEV---VTLWYRPPDVLLgATDYSSALDIWGAGCIFIEML 193
STKc_MRCK_alpha cd05623
Catalytic domain of the Serine/Threonine Kinase, DMPK-related cell division control protein 42 ...
622-828 8.04e-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: 8.04e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSghLKLPGKREIFvAIKTLKSGYTEKQRRD--FLSEASIMGQFDHPNVIHLEGVVTKSTPVMIIT 699
Cdd:cd05623   75 EILKVIGRGAFGEVAV--VKLKNADKVF-AMKILNKWEMLKRAETacFREERDVLVNGDSQWITTLHYAFQDDNNLYLVM 151
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENGSLDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEDDTsdpT 779
Cdd:cd05623  152 DYYVGGDLLTLLSKFEDRLPEDMARFYLAEMVLAIDSVHQLHYVHRDIKPDNILMDMNGHIRLADFGSCLKLMEDG---T 228
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 111118978 780 YTSALGGKIPiRWTAPEAIQYR-----KFTSASDVWSYGIVMWEvMSYGERPYW 828
Cdd:cd05623  229 VQSSVAVGTP-DYISPEILQAMedgkgKYGPECDWWSLGVCMYE-MLYGETPFY 280
COG4733 COG4733
Phage-related protein, tail protein J [Mobilome: prophages, transposons];
139-521 8.64e-09

Phage-related protein, tail protein J [Mobilome: prophages, transposons];


Pssm-ID: 443767 [Multi-domain]  Cd Length: 978  Bit Score: 59.57  E-value: 8.64e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 139 DTIA-ADESFSQVDLGGRVMKINTEV---RSFGPVSRSGFYLAFQDYGGCMSLiavrvfyrkcpRIIQNGAIFQETLSGA 214
Cdd:COG4733  400 DVIAvADDVLAGRRIGGRVSSVDGRVvtlDRPVTMEAGDRYLRVRLPDGTSVA-----------RTVQSVAGRTLTVSTA 468
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 215 ESTslvAARGSCIANAEEVDVPIKLYcngdgewlvpigRCMckaGFEAVENGTVcrgcpsgTFKANQgdeactHCPINSR 294
Cdd:COG4733  469 YSE---TPEAGAVWAFGPDELETQLF------------RVV---SIEENEDGTY-------TITAVQ------HAPEKYA 517
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 295 TTSEGATncvcrngYYRADLDPLdmpcTTIPSAPQAVISSVN--ETSLMLEWTPPRDSggredLVYNIickscgsgrgAC 372
Cdd:COG4733  518 AIDAGAF-------DDVPPQWPP----VNVTTSESLSVVAQGtaVTTLTVSWDAPAGA-----VAYEV----------EW 571
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 373 TRCGDNVQYAPRQlglTEPRIYISDLLAHtQYTFEIQAVNGVTDQSPFSpqfASVNITTNQ--AAPSAV-SImhQVSRTV 449
Cdd:COG4733  572 RRDDGNWVSVPRT---SGTSFEVPGIYAG-DYEVRVRAINALGVSSAWA---ASSETTVTGktAPPPAPtGL--TATGGL 642
                        330       340       350       360       370       380       390
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 111118978 450 DSITLSWSQPDQPNgvILDYELQYYEkELSEYNATAIKS--PTNTVTVQGLKAGAIYVFqvRARTVAGYGRYSG 521
Cdd:COG4733  643 GGITLSWSFPVDAD--TLRTEIRYST-TGDWASATVAQAlyPGNTYTLAGLKAGQTYYY--RARAVDRSGNVSA 711
pknD PRK13184
serine/threonine-protein kinase PknD;
623-860 9.43e-09

serine/threonine-protein kinase PknD;


Pssm-ID: 183880 [Multi-domain]  Cd Length: 932  Bit Score: 59.40  E-value: 9.43e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 623 IEQVIGAGEFGEVCSGHLKLPGKReifVAIKTLKSGYTEKQ--RRDFLSEASIMGQFDHPNVIHLEGVVTKSTPVMIITE 700
Cdd:PRK13184   6 IIRLIGKGGMGEVYLAYDPVCSRR---VALKKIREDLSENPllKKRFLREAKIAADLIHPGIVPVYSICSDGDPVYYTMP 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 701 FMENGSLDSFLR---QNDG-------QFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVN--SNLVckVSDFGLS 768
Cdd:PRK13184  83 YIEGYTLKSLLKsvwQKESlskelaeKTSVGAFLSIFHKICATIEYVHSKGVLHRDLKPDNILLGlfGEVV--ILDWGAA 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 769 RFL---EDDTSDPTYTS--------ALGGKI--PIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMS----YGERPYWDMT 831
Cdd:PRK13184 161 IFKkleEEDLLDIDVDErnicyssmTIPGKIvgTPDYMAPERLLGVPASESTDIYALGVILYQMLTlsfpYRRKKGRKIS 240
                        250       260
                 ....*....|....*....|....*....
gi 111118978 832 NQDVINAIEQdyrLPPPMDCPSALHQLML 860
Cdd:PRK13184 241 YRDVILSPIE---VAPYREIPPFLSQIAM 266
STKc_MRCK_beta cd05624
Catalytic domain of the Protein Serine/Threonine Kinase, DMPK-related cell division control ...
622-828 9.96e-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: 58.48  E-value: 9.96e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 622 KIEQVIGAGEFGEVCSGHLKlpgKREIFVAIKTLKSGYTEKQRRD--FLSEASIMGQFDHPNVIHLEGVVTKSTPVMIIT 699
Cdd:cd05624   75 EIIKVIGRGAFGEVAVVKMK---NTERIYAMKILNKWEMLKRAETacFREERNVLVNGDCQWITTLHYAFQDENYLYLVM 151
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENGSLDSFLR-------QNDGQFTVIQLVGMLRGIAagmkylaDMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLE 772
Cdd:cd05624  152 DYYVGGDLLTLLSkfedklpEDMARFYIGEMVLAIHSIH-------QLHYVHRDIKPDNVLLDMNGHIRLADFGSCLKMN 224
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 111118978 773 DDTsdpTYTSALGGKIPiRWTAPEAIQYR-----KFTSASDVWSYGIVMWEvMSYGERPYW 828
Cdd:cd05624  225 DDG---TVQSSVAVGTP-DYISPEILQAMedgmgKYGPECDWWSLGVCMYE-MLYGETPFY 280
STKc_MSK_C cd14092
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
624-827 1.20e-08

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: 57.70  E-value: 1.20e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 624 EQVIGAGEFgEVCSGHLKLPGKREIFVAIKTlksgytekQRRDFLSEASI--MGQfDHPNVIHLEGVVTKSTPVMIITEF 701
Cdd:cd14092   11 EEALGDGSF-SVCRKCVHKKTGQEFAVKIVS--------RRLDTSREVQLlrLCQ-GHPNIVKLHEVFQDELHTYLVMEL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 702 MENGSLDSFLRQNDgQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILV---NSNLVCKVSDFGLSRFLEDDT--S 776
Cdd:cd14092   81 LRGGELLERIRKKK-RFTESEASRIMRQLVSAVSFMHSKGVVHRDLKPENLLFtdeDDDAEIKIVDFGFARLKPENQplK 159
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 111118978 777 DPTYTsalggkipIRWTAPE----AIQYRKFTSASDVWSYGIVMWEVMSyGERPY 827
Cdd:cd14092  160 TPCFT--------LPYAAPEvlkqALSTQGYDESCDLWSLGVILYTMLS-GQVPF 205
STKc_p70S6K cd05584
Catalytic domain of the Serine/Threonine Kinase, 70 kDa ribosomal protein S6 kinase; STKs ...
625-827 1.33e-08

Catalytic domain of the Serine/Threonine Kinase, 70 kDa ribosomal protein S6 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p70S6K (or S6K) contains only one catalytic kinase domain, unlike p90 ribosomal S6 kinases (RSKs). It acts as a downstream effector of the STK mTOR (mammalian Target of Rapamycin) and plays a role in the regulation of the translation machinery during protein synthesis. p70S6K also plays a pivotal role in regulating cell size and glucose homeostasis. Its targets include S6, the translation initiation factor eIF3, and the insulin receptor substrate IRS-1, among others. Mammals contain two isoforms of p70S6K, named S6K1 and S6K2 (or S6K-beta). The p70S6K subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270736 [Multi-domain]  Cd Length: 323  Bit Score: 57.80  E-value: 1.33e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 625 QVIGAGEFGEVCSGHlKLPGKRE--IFvAIKTLKSGYTEKQRRDFL---SEASIMGQFDHPNVIHLEGVVTKSTPVMIIT 699
Cdd:cd05584    2 KVLGKGGYGKVFQVR-KTTGSDKgkIF-AMKVLKKASIVRNQKDTAhtkAERNILEAVKHPFIVDLHYAFQTGGKLYLIL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 700 EFMENGSLDSFLrQNDGQFTVIQLVGMLRGIAAGMKYLADMNYVHRDLAARNILVNSNLVCKVSDFGLSR-FLEDDTSDP 778
Cdd:cd05584   80 EYLSGGELFMHL-EREGIFMEDTACFYLAEITLALGHLHSLGIIYRDLKPENILLDAQGHVKLTDFGLCKeSIHDGTVTH 158
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 111118978 779 TYTSAlggkipIRWTAPEAIQYRKFTSASDVWSYGIVMWEVMSyGERPY 827
Cdd:cd05584  159 TFCGT------IEYMAPEILTRSGHGKAVDWWSLGALMYDMLT-GAPPF 200
STKc_CAMKK cd14118
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; ...
670-870 1.79e-08

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: 56.60  E-value: 1.79e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 670 EASIMGQFDHPNVIHLEGVV--TKSTPVMIITEFMENGSL-----DSFLRQNDGQFtviqlvgMLRGIAAGMKYLADMNY 742
Cdd:cd14118   64 EIAILKKLDHPNVVKLVEVLddPNEDNLYMVFELVDKGAVmevptDNPLSEETARS-------YFRDIVLGIEYLHYQKI 136
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 743 VHRDLAARNILVNSNLVCKVSDFGLSRFLEDDtsDPTYTSALGgkIPIrWTAPEAIQ-YRKFTS--ASDVWSYGIVMWEV 819
Cdd:cd14118  137 IHRDIKPSNLLLGDDGHVKIADFGVSNEFEGD--DALLSSTAG--TPA-FMAPEALSeSRKKFSgkALDIWAMGVTLYCF 211
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 111118978 820 MsYGERPYWDMTNQDVINAIEQD-YRLPPPMDCPSALHQLMLDCWQKDRNHR 870
Cdd:cd14118  212 V-FGRCPFEDDHILGLHEKIKTDpVVFPDDPVVSEQLKDLILRMLDKNPSER 262
STKc_WNK1 cd14030
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 1; STKs catalyze ...
621-832 1.90e-08

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: 1.90e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 621 VKIEQVIGAGEFGEVCSGhlkLPGKREIFVAIKTLKS-GYTEKQRRDFLSEASIMGQFDHPNVIHL----EGVVTKSTPV 695
Cdd:cd14030   27 LKFDIEIGRGSFKTVYKG---LDTETTVEVAWCELQDrKLSKSERQRFKEEAGMLKGLQHPNIVRFydswESTVKGKKCI 103
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 696 MIITEFMENGSLDSFLRqndgQFTVIQ---LVGMLRGIAAGMKYLADMN--YVHRDLAARNILVNSNL-VCKVSDFGLSR 769
Cdd:cd14030  104 VLVTELMTSGTLKTYLK----RFKVMKikvLRSWCRQILKGLQFLHTRTppIIHRDLKCDNIFITGPTgSVKIGDLGLAT 179
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 111118978 770 FleddtSDPTYTSALGGKipIRWTAPEAIQyRKFTSASDVWSYGIVMWEvMSYGERPYWDMTN 832
Cdd:cd14030  180 L-----KRASFAKSVIGT--PEFMAPEMYE-EKYDESVDVYAFGMCMLE-MATSEYPYSECQN 233
FN3 smart00060
Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, ...
325-414 2.81e-08

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.


Pssm-ID: 214495 [Multi-domain]  Cd Length: 83  Bit Score: 51.85  E-value: 2.81e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978   325 PSAPQAV-ISSVNETSLMLEWTPPRDSGGREDLVYNIICKScgsgrgactrcGDNVQYAPRQLGLTEPRIYISDLLAHTQ 403
Cdd:smart00060   1 PSPPSNLrVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEYR-----------EEGSEWKEVNVTPSSTSYTLTGLKPGTE 69
                           90
                   ....*....|.
gi 111118978   404 YTFEIQAVNGV 414
Cdd:smart00060  70 YEFRVRAVNGA 80
FN3 COG3401
Fibronectin type 3 domain [General function prediction only];
402-515 1.54e-07

Fibronectin type 3 domain [General function prediction only];


Pssm-ID: 442628 [Multi-domain]  Cd Length: 603  Bit Score: 55.39  E-value: 1.54e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 402 TQYTFEIQAVNGVTDqSPFSPQFASVNITTNQAAPSAVSImhqVSRTVDSITLSWSqpDQPNGVILDYELQYYEKELSEY 481
Cdd:COG3401  203 TTYYYRVAATDTGGE-SAPSNEVSVTTPTTPPSAPTGLTA---TADTPGSVTLSWD--PVTESDATGYRVYRSNSGDGPF 276
                         90       100       110
                 ....*....|....*....|....*....|....*
gi 111118978 482 naTAIKSPTNTV-TVQGLKAGAIYVFQVRARTVAG 515
Cdd:COG3401  277 --TKVATVTTTSyTDTGLTNGTTYYYRVTAVDAAG 309
FN3 COG3401
Fibronectin type 3 domain [General function prediction only];
320-522 1.71e-03

Fibronectin type 3 domain [General function prediction only];


Pssm-ID: 442628 [Multi-domain]  Cd Length: 603  Bit Score: 42.30  E-value: 1.71e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 320 PCTTIPSAPQAV-ISSVNETSLMLEWTPPRDsggrEDLVYNIICKSCGSGrgactrcgdnVQYAPRQLGLTEPRIYISDL 398
Cdd:COG3401  322 TDLTPPAAPSGLtATAVGSSSITLSWTASSD----ADVTGYNVYRSTSGG----------GTYTKIAETVTTTSYTDTGL 387
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111118978 399 LAHTQYTFEIQAVNGVTDQSPFSPQFASVNITTNQAAPSAVSI---MHQVSRTVDSITLSWSQPDQPNGVILDYELQYYE 475
Cdd:COG3401  388 TPGTTYYYKVTAVDAAGNESAPSEEVSATTASAASGESLTASVdavPLTDVAGATAAASAASNPGVSAAVLADGGDTGNA 467
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 111118978 476 KELSEYNATAIKSPTNTVTVQGLKAGAIYVFQVRARTVAGYGRYSGK 522
Cdd:COG3401  468 VPFTTTSSTVTATTTDTTTANLSVTTGSLVGGSGASSVTNSVSVIGA 514
 
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.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH