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cd05083: PTKc_Chk (this model, PSSM-Id:133214 is obsolete and has been replaced by 270666)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:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                     #####   #          # #                                         ####
gi 1169123   228 WLLNLQHLTLGAQIGEGEFGAVLQGEYLGQKVAVKNIKCDVtAQAFLDETAVMTKMQHENLVRLLGVILHQGLYIVMEHV 307
gi 68398755  187 WLLDLSKLTLGEIIGEGEFGAVFAGEYTGQRVAVKIIKCDVtAQAFLEETSVMTNLHHKNLVPLLGVILHNGLHIVTELM 266
gi 118103089 187 WLLNLQQLTLGERIGQGEFGDVLQGEYMGQKVAVKNIKCDVtAQAFLAETAAMTKVRHKNLVRLLGVILHNGLYIVMEFM 266
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1          ##                                        #   ## #          #            #####
gi 1169123   308 SKGNLVNFLRTRGRALVNTAQLLQFSLHVAEGMEYLESKKLVHRDLAARNILVSEdLVAKVSDFGLAKAERKGLDSSRLP 387
gi 68398755  267 TKGNLVNFLRSRGRFAVSVIQLLRFALDVCEGMEHLESKKLLHRDLAGRNILVSEdGVAKISDFGLARVGSMAVDNSKLP 346
gi 118103089 267 SKGNLVNFLRTRGRALVPLPQLLQFSLDVAQGMDYLESKKLVHRDLAARNILISEdNVAKVSDFGLASVNPRGADTTLLP 346
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                #                                 #                                     
gi 1169123   388 VKWTAPEALKHgKFTSKSDVWSFGVLLWEVFSYGRAPYPKMSLKEVSEAVEKGYRMEPPEGCPGPVHVLMSSCWEAEPAR 467
gi 68398755  347 VKWTAPEALKNkKFSTQSDVWSYGVLLWEIFSYGRQPYPKMTVNEVKECVEKGYRMDPPDECPADVYSIMTSCWQTEPKK 426
gi 118103089 347 VKWTAPEALKHnKFSSKSDVWSYGILLWEVFSFGRAPYPKLSLKEVTEQLEQGYRMEPPEGCPPTVYVLMRSCWEMEPGK 426
                        250
                 ....*....|....
Feature 1                      
gi 1169123   468 RPPFRKLAEKLARE 481
gi 68398755  427 RPSFHKLRERLEKE 440
gi 118103089 427 RPSFKKLTEKLQKE 440

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