Conserved Protein Domain Family
PTKc_Jak2_rpt2

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cd14205: PTKc_Jak2_rpt2 
Click on image for an interactive view with Cn3D
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.
Statistics
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PSSM-Id: 271107
View PSSM: cd14205
Aligned: 6 rows
Threshold Bit Score: 622.806
Threshold Setting Gi: 88192292
Created: 27-Jul-2011
Updated: 2-Mar-2014
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 17 residues -Click on image for an interactive view with Cn3D
Feature 1:ATP binding site [chemical binding site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                    ###     #                #                              #            
2B7A_B          5 FEERHLKFLQQLGKGNFGSVEMCRYDPlqdNTGEVVAVKKLQHSTeehLRDFEREIEILKSLQHDNIVKYKGVCYsagrr 84
gi 18858917   807 FQARHLIFLQLLGKGNFGSVEKCRYDPlqdNTGEVVAVKKLQHSTaehLRDFEREIEILRSLQHENIVRYKGVCYsagrn 886
gi 117558461  841 FEERHLKFLQQLGKGNFGSVELCRYDPlqdNTGEVVAVKKLQHTTeeyLRDFEREIEILKSLQHDNIVRYKGVCYsagrr 920
gi 71896485   841 FEERHLKFLQQLGKGNFGSVEMCRYDPlqdNTGEVVAVKKLQHSTeehLRDFEREIEILKSLQHDNIVKYKGVCYsagrr 920
3LPB_A          7 FEERHLKFLQQLGKGNFGSVEMCRYDPlqdNTGEVVAVKKLQHSTeehLRDFEREIEILKSLQHDNIVKYKGVCYsagrr 86
3Q32_A          7 FEERHLKFLQQLGKGNFGSVEMCRYDPlqdNTGEVVAVKKLQHSTeehLRDFEREIEILKSLQHDNIVKYKGVCYsagrr 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1              ##### #                                            ## #         ##         
2B7A_B         85 NLKLIMEYLPYGSLRDYLQKHkerIDHIKLLQYTSQICKGMEYLGTKRYIHRDLATRNILVENeNRVKIGDFGLTKVLPQ 164
gi 18858917   887 NLRLVMEFLPFGSLRDYLSKNrerFDHSKLLLYASQICKGMDYLAEKRYVHRDLATRNILVESeFRVKIGDFGLTKVLPQ 966
gi 117558461  921 NLRLIMEYLPYGSLRDYLQKHkdrLDFKKLLQYSSQICKGMEYLTIKRYIHRDLATRNILVENeNRVKIGDFGLTKVLPQ 1000
gi 71896485   921 NLRLIMEYLPYGSLRDYLQKHkerLDHKKLLLYASQICKGMEYLGTKRYVHRDLATRNILVENeNRVKIGDFGLTKVLPQ 1000
3LPB_A         87 NLKLIMEYLPYGSLRDYLQKHkerIDHIKLLQYTSQICKGMEYLGTKRYIHRDLATRNILVENeNRVKIGDFGLTKVLPQ 166
3Q32_A         87 NLKLIMEYLPYGSLRDYLQKHkerIDHIKLLQYTSQICKGMEYLGTKRYIHRDLATRNILVENeNRVKIGDFGLTKVLPQ 166
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                         
2B7A_B        165 DKEXXKVKEPGESPIFWYAPESLTEsKFSVASDVWSFGVVLYELFTYIEKSKSPPAEFMRMIGNDKqgQMIVFHLIELLK 244
gi 18858917   967 DKEYYTVREPGESPIFWYAPESLTEsKFSVASDVWSFGVVLYELFTYSEKSCSPPAVFMEQMGEDKqgQMIVYHLIDLLK 1046
gi 117558461 1001 DKEYYKVKEPGESPIFWYAPESLTEsKFSVASDVWSFGVVLYELFTYSEKSKSPPSEFMRMIGNDKqgQMIVFHLIELLK 1080
gi 71896485  1001 DKEYYKVKEPGESPIFWYAPESLTEsKFSVASDVWSFGVVLYELFTYIEKSKSPPAEFMRMIGNDKqgQMIVFHLIELLK 1080
3LPB_A        167 DKEXXKVKEPGESPIFWYAPESLTEsKFSVASDVWSFGVVLYELFTYIEKSKSPPAEFMRMIGNDKqgQMIVFHLIELLK 246
3Q32_A        167 DKEXXKVKEPGESPIFWYAPESLTEsKFSVASDVWSFGVVLYELFTYIEKSKSPPAEFMRMIGNDKqgQMIVFHLIELLK 246
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
Feature 1                                                     
2B7A_B        245 NNGRLPRPDGCPDEIYMIMTECWNNnVNQRPSFRDLALRVDQIR 288
gi 18858917  1047 RNYRLPAPDGCPAEIHALMKQCWAPePADRPLFRDLARTVEDIQ 1090
gi 117558461 1081 NKGRLPQPEGCPDEIYRIMNECWNNsISQRPSFKELTIQVEKAK 1124
gi 71896485  1081 NNGRLPRPDGCPDEIYAIMKECWNNnVAQRPTFRDLAQRVDQIR 1124
3LPB_A        247 NNGRLPRPDGCPDEIYMIMTECWNNnVNQRPSFRDLALRVDQIR 290
3Q32_A        247 NNGRLPRPDGCPDEIYMIMTECWNNnVNQRPSFRDLALRVDQIR 290

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