Conserved Protein Domain Family
PTKc_Chk

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cd05083: PTKc_Chk (this model, PSSM-Id:133214 is obsolete and has been replaced by 270666)
Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase
Protein Tyrosine Kinase (PTK) family; Csk homologous kinase (Chk); 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. Csk subfamily kinases are cytoplasmic (or nonreceptor) tyr kinases 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. Chk is also referred to as megakaryocyte-associated tyrosine kinase (Matk). To inhibit Src kinases, Chk is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. Chk inhibit 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. 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.
Statistics
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PSSM-Id: 133214
View PSSM: cd05083
Aligned: 3 rows
Threshold Bit Score: 539.93
Threshold Setting Gi: 68398755
Created: 21-Jun-2007
Updated: 17-Jan-2013
Structure
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Aligned Rows:
 
Feature 1:active site [active site]
Evidence:
  • Comment:Based on the structures of other PTK family members bound to substrate peptides and ATP analogs including, the structure of human Csk bound to the inhibitor, staurosporine (1BYG_A).
  • Citation:PMID 9312016
  • Citation:PMID 9878439

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                     #####   #          # #                                         ####
P42679       228 WLLNLQHLTLGAQIGEGEFGAVLQGEYLGQKVAVKNIKCDVtAQAFLDETAVMTKMQHENLVRLLGVILHQGLYIVMEHV 307 human
XP_695792    187 WLLDLSKLTLGEIIGEGEFGAVFAGEYTGQRVAVKIIKCDVtAQAFLEETSVMTNLHHKNLVPLLGVILHNGLHIVTELM 266 zebrafish
XP_001232095 187 WLLNLQQLTLGERIGQGEFGDVLQGEYMGQKVAVKNIKCDVtAQAFLAETAAMTKVRHKNLVRLLGVILHNGLYIVMEFM 266 chicken
Feature 1          ##                                        #   ## #          #            #####
P42679       308 SKGNLVNFLRTRGRALVNTAQLLQFSLHVAEGMEYLESKKLVHRDLAARNILVSEdLVAKVSDFGLAKAERKGLDSSRLP 387 human
XP_695792    267 TKGNLVNFLRSRGRFAVSVIQLLRFALDVCEGMEHLESKKLLHRDLAGRNILVSEdGVAKISDFGLARVGSMAVDNSKLP 346 zebrafish
XP_001232095 267 SKGNLVNFLRTRGRALVPLPQLLQFSLDVAQGMDYLESKKLVHRDLAARNILISEdNVAKVSDFGLASVNPRGADTTLLP 346 chicken
Feature 1                #                                 #                                     
P42679       388 VKWTAPEALKHgKFTSKSDVWSFGVLLWEVFSYGRAPYPKMSLKEVSEAVEKGYRMEPPEGCPGPVHVLMSSCWEAEPAR 467 human
XP_695792    347 VKWTAPEALKNkKFSTQSDVWSYGVLLWEIFSYGRQPYPKMTVNEVKECVEKGYRMDPPDECPADVYSIMTSCWQTEPKK 426 zebrafish
XP_001232095 347 VKWTAPEALKHnKFSSKSDVWSYGILLWEVFSFGRAPYPKLSLKEVTEQLEQGYRMEPPEGCPPTVYVLMRSCWEMEPGK 426 chicken
Feature 1                      
P42679       468 RPPFRKLAEKLARE 481 human
XP_695792    427 RPSFHKLRERLEKE 440 zebrafish
XP_001232095 427 RPSFKKLTEKLQKE 440 chicken

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