1YVJ,2B7A,3EYG


Conserved Protein Domain Family
PTKc_Jak_rpt2

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cd05038: PTKc_Jak_rpt2 (this model, PSSM-Id:173628 is obsolete and has been replaced by 270634)
Click on image for an interactive view with Cn3D
Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases
Protein Tyrosine Kinase (PTK) family; Janus kinase (Jak) subfamily; catalytic (c) domain (repeat 2). The Jak subfamily is composed of Jak1, Jak2, Jak3, TYK2, and similar proteins. 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. Jak subfamily proteins 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 tyr kinase catalytic domain. Most Jaks are expressed in a wide variety of tissues, except for Jak3, which is expressed only in hematopoietic cells. 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). Jaks are also involved in regulating the surface expression of some cytokine receptors. The Jak-STAT pathway is involved in many biological processes including hematopoiesis, immunoregulation, host defense, fertility, lactation, growth, and embryogenesis.
Statistics
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PSSM-Id: 173628
Aligned: 7 rows
Threshold Bit Score: 404.479
Created: 17-Jul-2006
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 FEERHLKYI-SQLGKGNFGSVELCRYDPlg-dNTGALVAVKQLQHSGpd---qQRDFQREIQILKALHSDFIVKYRGVSY 78   human
2B7A_B       5 FEERHLKFL-QQLGKGNFGSVEMCRYDPlq-dNTGEVVAVKKLQHSTee---hLRDFEREIEILKSLQHDNIVKYKGVCY 79   human
BAA81718   541 VPFEQLKLS-KKLGSGHFSNVYAATWTNp--gKQTLEVAVKVPNVDGeeldavMNDLEREITTMHSLDHQYIVKLIGISD 617  Ephydatia fluvia...
P29597     892 FHKRYLKKI-RDLGEGHFGKVSLYCYDPtn-dGTGEMVAVKALKADCgp--qhRSGWKQEIDILRTLYHEHIIKYKGCCE 967  human
Q24592     886 SECRVIYNMeNMIGRGHYGTVYKGHLEFndkdQPREQVAIKMLNTMQv-----STDFHREIGIMRTLSHPNIVKFKYWAE 960  fruit fly
BAE06524   852 YRDDNLTFV-KQLGEGHFGHVDLYHHDIqr-nGQFERVAIKSLRRSMnnp-qsRSDFRNEIETMRRIDHKYIVKLNGVAE 928  Ciona intestinalis
3EYG_A       6 FEKRFLKRI-RDLGEGHFGKVELCRYDPeg-dNTGEQVAVKSLKPESgg--nhIADLKKEIEILRNLYHENIVKYKGICT 81   human
Feature 1                      ####  #                                                 #   ## #
1YVJ_A      79 gpg------rpELRLVMEYLpSGCLRDFLQRHra---------rLDASRLLLYSSQICKGMEYLGSRRCVHRDLAARNIL 143  human
2B7A_B      80 sag------rrNLKLIMEYLpYGSLRDYLQKHke---------rIDHIKLLQYTSQICKGMEYLGTKRYIHRDLATRNIL 144  human
BAA81718   618 aphfltslggrIPLVIMEYVsRGSLRSYLQELqdrshteprtaqNSRKTLLLFSEQIANGMDYLENQKLVHRDLAARNVL 697  Ephydatia fluvia...
P29597     968 dqg------ekSLQLVMEYVpLGSLRDYLPRHs-----------IGLAQLLLFAQQICEGMAYLHAQHYIHRDLAARNVL 1030 human
Q24592     961 k----------SHCIIMEYLqSGSFDIYLRFTap---------nLNNPRLVSFALDIANGMKYLSDMGLIHRDLAARNIL 1021 fruit fly
BAE06524   929 p----------SLRIVMEYLpYGSLSHFLRGQrdsg----ialqQLSGLLLRFSFQIAQGMLYLQEKRVIHRDLALRNIL 994  Ciona intestinalis
3EYG_A      82 edg------gnGIKLIMEFLpSGSLKEYLPKNkn---------kINLKQQLKYAVQICKGMDYLGSRQYVHRDLAARNVL 146  human
Feature 1                    #                  #####        #                                 
1YVJ_A     144 VESe----AHVKIADFGLAKLLPlDKDXXVVRePGQSPIFWYAPESLSDn---IFSRQSDVWSFGVVLYELFTYC----- 211  human
2B7A_B     145 VENe----NRVKIGDFGLTKVLPqDKEXXKVKePGESPIFWYAPESLTEs---KFSVASDVWSFGVVLYELFTYI----- 212  human
BAA81718   698 IESd----KLIKISDFGLSRVPT-KSDYYYSNnLKELPIFWYAPECLRTr---RFTSKGDVWSYGVTLWEMFTLGrlpth 769  Ephydatia fluvia...
P29597    1031 LDNd----RLVKIGDFGLAKAVPeGHEYYRVReDGDSPVFWYAPECLKEy---KFYYASDVWSFGVTLYELLTHC----- 1098 human
Q24592    1022 VDHng-dgDCVKISDFGLAQFAN-SDGYYYAKsKRDIPIRWYSPEAISTc---RFSSYSDVWSYGVTLFEMFSRGe---- 1092 fruit fly
BAE06524   995 LDKegsncWNIKISDFGLSRILSeDRDYYTGN-PDEFPAQWYAPECLRLdgrrTFHFESDVWSYGVTLWEMFSYGa---- 1069 Ciona intestinalis
3EYG_A     147 VESe----HQVKIGDFGLTKAIEtDKEXXTVKdDRDSPVFWYAPECLMQs---KFYIASDVWSFGVTLHELLTYC----- 214  human
Feature 1                                   #                                                  
1YVJ_A     212 ------DKSCSPSAEflrmmgc-erdvpaLCRLLELLE--EGQRLPAPPACP------AEVHELMKLCWAPsPQDRPSFS 276  human
2B7A_B     213 ------EKSKSPPAEfmrmigndkqgqmiVFHLIELLK--NNGRLPRPDGCP------DEIYMIMTECWNNnVNQRPSFR 278  human
BAA81718   770 vfqaqlRHFQHPPGQpav---------niHTQMVRLLTegPSPSLPPPPPLPkmspcsSDVYDIMVECWQVrPEDRPSFH 840  Ephydatia fluvia...
P29597    1099 ------DSSQSPPTKfleligi-aqgqmtVLRLTELLE--RGERLPRPDKCP------CEVYHLMKNCWETeASFRPTFE 1163 human
Q24592    1093 ------EPNLVPIQTs-------------QEDFLNRLQ--SGERLNRPASCP------DFIYDLMQLCWHAtPRSRPSFA 1145 fruit fly
BAE06524  1070 ------RPTYEPLPNitl---------rqLTQLQELLK--DNVRLSQPEHCP------NEVFHLISRCWEYePQQRVKFD 1126 Ciona intestinalis
3EYG_A     215 ------DSDSSPMALflkmigp-thgqmtVTRLVNTLK--EGKRLPCPPNCP------DEVYQLMRKCWEFqPSNRTSFQ 279  human
Feature 1                
1YVJ_A     277 ALGPQLDMLW 286  human
2B7A_B     279 DLALRVDQIR 288  human
BAA81718   841 DLQLKVALVA 850  Ephydatia fluviatilis
P29597    1164 NLIPILKTVH 1173 human
Q24592    1146 TIVDIITREV 1155 fruit fly
BAE06524  1127 ELCREFDRLR 1136 Ciona intestinalis
3EYG_A     280 NLIEGFEALL 289  human

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