1U59


Conserved Protein Domain Family
PTKc_Zap-70

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cd05115: PTKc_Zap-70 (this model, PSSM-Id:133246 is obsolete and has been replaced by 270686)
Click on image for an interactive view with Cn3D
Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa
Protein Tyrosine Kinase (PTK) family; Zeta-chain-associated protein of 70kDa (Zap-70); 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. Zap-70 is a member of the Syk subfamily of kinases, which are cytoplasmic (or nonreceptor) tyr kinases 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.
Statistics
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PSSM-Id: 133246
View PSSM: cd05115
Aligned: 4 rows
Threshold Bit Score: 553.019
Threshold Setting Gi: 52696010
Created: 15-Jun-2007
Updated: 17-Jan-2013
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 27 residues -Click on image for an interactive view with Cn3D
Feature 1:active site [active site]
Evidence:
  • Comment:Based on the structures of other PTK family members bound to substrate peptides and ATP analogs as well as, the structure of human Zap-70 tyr kinase bound with the inhibitor, staurosporine (1U59_A).
  • Citation:PMID 9312016

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1          #####   #              #                               #              ####  ##
1U59_A        16 IELGCGNFGSVRQGVYRMRkkQIDVAIKVLKQGTekadTEEMMREAQIMHQLDNPYIVRLIGVCQaeALMLVMEMAGGGP 95
gi 50416266  330 VELGSGNFGCVKKGVYKLKkrQIDVAIKVLKVQEeknvRDEMMKEAEFMHQLDNPYIVRMIGVCEaeNLMLVMEMASGGP 409
gi 63101276  329 VELGSGNFGCVKKGVFKMEskQIDVAIKVLKNENeksvRDEMMREAEIMHQLSDPFIVRMIGLCEaeALMLVMEMAPAGP 408
gi 118103133 346 VELGAGNFGCVKKGVYKMRkkQIDVAIKVLKSNNektvRDEMMTEAQIMHQLDNPYIVRMIGVCEaeSLMLVMEMASGGP 425
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                               #   ## #         ##                  ####
1U59_A        96 LHKFLVGKreeIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNrHYAKISDFGLSKALGADDSYYTARSAGKW 175
gi 50416266  410 LNKFLGAKkdtITVSNVVELMHQVSMGMKYLEGKNFVHRDLAARNVLMVNqHYAKISDFGLSKALAADDSYYKAKSFGKW 489
gi 63101276  409 LNKFLSGKkdqITTENIVMLMHQVSMGMKYLEGRNFVHRDLAARNVLLVNqQYAKISDFGLSKALGADDNYYKARTGGKW 488
gi 118103133 426 LNKFLSSKkdeITVSNIVELMHQVSMGMKYLEEKNFVHRDLAARNVLLVNqHYAKISDFGLSKALGADDSYYKARTAGKW 505
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1        #        #                                 #                                    
1U59_A       176 PLKWYAPECINFrKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKWE 255
gi 50416266  490 PLKWYAPECINYrKFSSRSDVWSYGITMWEAFSYGQKPYKKLKGTEVMSFIERNERLACPASCPPEMYQLMLDCWIFKME 569
gi 63101276  489 PLKWYAPECIHFhKFSSKSDVWSFGITMWEAFSFGGKPYKKMKGPEVITYIEGGSRLDCPAACPEAMYELMKECWTYKHE 568
gi 118103133 506 PLKWYAPECILYhKFSSKSDVWSYGVTMWEAFSYGQKPYKKMKGPEVISFIEQGKRMDCPTECPAEIYALMMQCWTYSWE 585
                        250
                 ....*....|....*..
Feature 1                         
1U59_A       256 DRPDFLTVEQRMRACYY 272
gi 50416266  570 DRPNFENVEYRMRMYYY 586
gi 63101276  569 ERLNFAKVEEKMRTFYY 585
gi 118103133 586 ERPGFFSVENTIRTYYY 602

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