1YVJ,2B7A


Conserved Protein Domain Family
PTKc_Jak2_Jak3_rpt2

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cd05081: PTKc_Jak2_Jak3_rpt2 (this model, PSSM-Id:133212 is obsolete and has been replaced by 270665)
Click on image for an interactive view with Cn3D
Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases 2 and 3
Protein Tyrosine Kinase (PTK) family; Janus kinase 2 (Jak2) and Jak3; catalytic (c) domain (repeat 2). 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. Jak2 and Jak3 are members of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) tyr kinases 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). Jak2 is widely expressed in many tissues while Jak3 is expressed only in hematopoietic cells. Jak2 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. Jak3 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. 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. Jak3 is important in lymphoid development and myeloid cell differentiation. Inactivating mutations in Jak3 have been reported in humans with severe combined immunodeficiency (SCID).
Statistics
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PSSM-Id: 133212
Aligned: 9 rows
Threshold Bit Score: 540.121
Threshold Setting Gi: 67463918
Created: 19-Jun-2007
Updated: 17-Jan-2013
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 25 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 structures of human Jak2 bound with a pan-Jak inhibitor , and human Jak3 tyr kinase bound with an analog of the inhibitor, staurosporine (1YVJ_A and 2B7A_B respectively).
  • Citation:PMID 9312016

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                    #####   #                # #                                         
1YVJ_A          4 FEERHLKYISQLGKGNFGSVELCRYDPlgdNTGALVAVKQLQHSGpdqQRDFQREIQILKALHSDFIVKYRGVSYgpgrp 83   human
2B7A_B          5 FEERHLKFLQQLGKGNFGSVEMCRYDPlqdNTGEVVAVKKLQHSTeehLRDFEREIEILKSLQHDNIVKYKGVCYsagrr 84   human
AAD50352      816 FEERHLRYISLLGKGNFGSVELCCYDPlgdNTGELVAVKKLQPSKkssMEDFKKEVKTLSVLHCEYIVKYKGVCYsmgrl 895  Tetraodon flu...
NP_571168     807 FQARHLIFLQLLGKGNFGSVEKCRYDPlqdNTGEVVAVKKLQHSTaehLRDFEREIEILRSLQHENIVRYKGVCYsagrn 886  zebrafish
NP_990327     816 FEERHLKYISLLGKGNFGSVELCRYDPlgdSTGELVAVKKLQQDSakeLQDFEREIQILHSLQHDFIVKYRGVCYsrgrr 895  chicken
AAI25683      841 FEERHLKFLQQLGKGNFGSVELCRYDPlqdNTGEVVAVKKLQHTTeeyLRDFEREIEILKSLQHDNIVRYKGVCYsagrr 920  western clawe...
NP_001025709  841 FEERHLKFLQQLGKGNFGSVEMCRYDPlqdNTGEVVAVKKLQHSTeehLRDFEREIEILKSLQHDNIVKYKGVCYsagrr 920  chicken
AAD56051      832 FEERHLIFLQQLGKGNFGSVEMCRYDPlqdNTGEVVAVKKLQHGTaehIRDFEREIEILKSLQHENIVKYKGVCYsagrr 911  Tetraodon flu...
AAO47335      845 FEERHLIFIKQLGKGNFGSVEMCRYDPlqdSTGEVVAVKKLQHSStehLRDFEREIEILKSLHHENIVKYKGVGYsagrr 924  Tetraodon flu...
Feature 1              ####  #                                        #   ## #          #         
1YVJ_A         84 ELRLVMEYLpSGCLRDFLQRHrarLDASRLLLYSSQICKGMEYLGSRRCVHRDLAARNILVESeAHVKIADFGLAKLLPL 163  human
2B7A_B         85 NLKLIMEYLpYGSLRDYLQKHkerIDHIKLLQYTSQICKGMEYLGTKRYIHRDLATRNILVENeNRVKIGDFGLTKVLPQ 164  human
AAD50352      896 SMGLVTEYLpYGSLIGYLENNrhkVDTRRMLLFASQICKGMEYLQSLRFVHRDLAARNILVASeSLVKIADFGLTKIIPC 975  Tetraodon flu...
NP_571168     887 NLRLVMEFLpFGSLRDYLSKNrerFDHSKLLLYASQICKGMDYLAEKRYVHRDLATRNILVESeFRVKIGDFGLTKVLPQ 966  zebrafish
NP_990327     896 GLRLVMEYLpDGCLRDYLQKNqhrLEHRTLLLYAWQICKGMEYLGAQRCVHRDLASRNILVESeTHVKIGDFGLAKLLPQ 975  chicken
AAI25683      921 NLRLIMEYLpYGSLRDYLQKHkdrLDFKKLLQYSSQICKGMEYLTIKRYIHRDLATRNILVENeNRVKIGDFGLTKVLPQ 1000 western clawe...
NP_001025709  921 NLRLIMEYLpYGSLRDYLQKHkerLDHKKLLLYASQICKGMEYLGTKRYVHRDLATRNILVENeNRVKIGDFGLTKVLPQ 1000 chicken
AAD56051      912 NLRLVMEYLpFGSLRDYLIKNkerIDHKKLVHYSSQICKGMEYLSGKRYIHRDLATRNILVESeSRVKIGDFGLTKILPQ 991  Tetraodon flu...
AAO47335      925 NLRLIMEYLpYGSLRDYLIKHrerCFGPSTLLYASQICKGMDYLAAKRYIHRDLATRNILVESeMRVKIGDFGLTKVLPQ 1004 Tetraodon flu...
Feature 1                  #####        #                                                #        
1YVJ_A        164 DKDXXVVREPGQSPIFWYAPESLSDnIFSRQSDVWSFGVVLYELFTYCDKSCSPSAEFLRMMGcerd-vpaLCRLLELLE 242  human
2B7A_B        165 DKEXXKVKEPGESPIFWYAPESLTEsKFSVASDVWSFGVVLYELFTYIEKSKSPPAEFMRMIGndkqgqmiVFHLIELLK 244  human
AAD50352      976 NKEYYRVTQPGESPIFWYAPESINEsRFSHESDVWSFGVVLYELFSYCDINSNPKRLYMQQIGhnvqtpsiSLHLANILK 1055 Tetraodon flu...
NP_571168     967 DKEYYTVREPGESPIFWYAPESLTEsKFSVASDVWSFGVVLYELFTYSEKSCSPPAVFMEQMGedkqgqmiVYHLIDLLK 1046 zebrafish
NP_990327     976 DKDYYVVQEPGQSPVFWYAPESLADnVFSRASDVWSFGVLLYELFTYSNKSRSPSEEFLHMMGpekp-aqiICHLLELLK 1054 chicken
AAI25683     1001 DKEYYKVKEPGESPIFWYAPESLTEsKFSVASDVWSFGVVLYELFTYSEKSKSPPSEFMRMIGndkqgqmiVFHLIELLK 1080 western clawe...
NP_001025709 1001 DKEYYKVKEPGESPIFWYAPESLTEsKFSVASDVWSFGVVLYELFTYIEKSKSPPAEFMRMIGndkqgqmiVFHLIELLK 1080 chicken
AAD56051      992 DKEYYMVREPGESPIFWYAPESLTEsKFSVASDVWSFGVVLYELFTHSSRNSSPPTVFMSMMGndkqgqliVYHLIELLK 1071 Tetraodon flu...
AAO47335     1005 DKEYYTVREPGESPIFWYAPESLTEsKFSVASDVWSFGVVLYELFTYSDKNCSPPMVFMERMGkekqgqmiVYHLIDLLK 1084 Tetraodon flu...
Feature 1                                                     
1YVJ_A        243 EGQRLPAPPACPAEVHELMKLCWAPsPQDRPSFSALGPQLDMLW 286  human
2B7A_B        245 NNGRLPRPDGCPDEIYMIMTECWNNnVNQRPSFRDLALRVDQIR 288  human
AAD50352     1056 SNWRLPAPPDCPAKVYSLMKECWLYdFMERPCFSFLGNQIEVIM 1099 Tetraodon fluviatilis
NP_571168    1047 RNYRLPAPDGCPAEIHALMKQCWAPePADRPLFRDLARTVEDIQ 1090 zebrafish
NP_990327    1055 DSRRLPVPPGCPMEVYAMMLSCWAFaPSARPTFTELAARVEALR 1098 chicken
AAI25683     1081 NKGRLPQPEGCPDEIYRIMNECWNNsISQRPSFKELTIQVEKAK 1124 western clawed frog
NP_001025709 1081 NNGRLPRPDGCPDEIYAIMKECWNNnVAQRPTFRDLAQRVDQIR 1124 chicken
AAD56051     1072 SGSRLPQPLDCPTEIHEIMEQCWDNdPYLRPSFKELALSIDLFR 1115 Tetraodon fluviatilis
AAO47335     1085 QGYRLPTPESCPAEIHAIMLECWNSdPELRPSFKALIHSVEAAR 1128 Tetraodon fluviatilis

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