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cd05038: PTKc_Jak_rpt2 (this model, PSSM-Id:173628 is obsolete and has been replaced by 270634)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
View PSSM: cd05038
Aligned: 7 rows
Threshold Bit Score: 404.479
Threshold Setting Gi: 18150836
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:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                    #####   #                 # #                                       
1YVJ_A         4 FEERHLKYI-SQLGKGNFGSVELCRYDPlg-dNTGALVAVKQLQHSGpd---qQRDFQREIQILKALHSDFIVKYRGVSY 78
2B7A_B         5 FEERHLKFL-QQLGKGNFGSVEMCRYDPlq-dNTGEVVAVKKLQHSTee---hLRDFEREIEILKSLQHDNIVKYKGVCY 79
gi 18150836  541 VPFEQLKLS-KKLGSGHFSNVYAATWTNp--gKQTLEVAVKVPNVDGeeldavMNDLEREITTMHSLDHQYIVKLIGISD 617
gi 56405328  892 FHKRYLKKI-RDLGEGHFGKVSLYCYDPtn-dGTGEMVAVKALKADCgp--qhRSGWKQEIDILRTLYHEHIIKYKGCCE 967
gi 60416388  886 SECRVIYNMeNMIGRGHYGTVYKGHLEFndkdQPREQVAIKMLNTMQv-----STDFHREIGIMRTLSHPNIVKFKYWAE 960
gi 70570038  852 YRDDNLTFV-KQLGEGHFGHVDLYHHDIqr-nGQFERVAIKSLRRSMnnp-qsRSDFRNEIETMRRIDHKYIVKLNGVAE 928
3EYG_A         6 FEKRFLKRI-RDLGEGHFGKVELCRYDPeg-dNTGEQVAVKSLKPESgg--nhIADLKKEIEILRNLYHENIVKYKGICT 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                        ####  #                                                 #   ## #
1YVJ_A        79 gpg------rpELRLVMEYLpSGCLRDFLQRHra---------rLDASRLLLYSSQICKGMEYLGSRRCVHRDLAARNIL 143
2B7A_B        80 sag------rrNLKLIMEYLpYGSLRDYLQKHke---------rIDHIKLLQYTSQICKGMEYLGTKRYIHRDLATRNIL 144
gi 18150836  618 aphfltslggrIPLVIMEYVsRGSLRSYLQELqdrshteprtaqNSRKTLLLFSEQIANGMDYLENQKLVHRDLAARNVL 697
gi 56405328  968 dqg------ekSLQLVMEYVpLGSLRDYLPRHs-----------IGLAQLLLFAQQICEGMAYLHAQHYIHRDLAARNVL 1030
gi 60416388  961 k----------SHCIIMEYLqSGSFDIYLRFTap---------nLNNPRLVSFALDIANGMKYLSDMGLIHRDLAARNIL 1021
gi 70570038  929 p----------SLRIVMEYLpYGSLSHFLRGQrdsg----ialqQLSGLLLRFSFQIAQGMLYLQEKRVIHRDLALRNIL 994
3EYG_A        82 edg------gnGIKLIMEFLpSGSLKEYLPKNkn---------kINLKQQLKYAVQICKGMDYLGSRQYVHRDLAARNVL 146
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                      #                  #####        #                                 
1YVJ_A       144 VESe----AHVKIADFGLAKLLPlDKDXXVVRePGQSPIFWYAPESLSDn---IFSRQSDVWSFGVVLYELFTYC----- 211
2B7A_B       145 VENe----NRVKIGDFGLTKVLPqDKEXXKVKePGESPIFWYAPESLTEs---KFSVASDVWSFGVVLYELFTYI----- 212
gi 18150836  698 IESd----KLIKISDFGLSRVPT-KSDYYYSNnLKELPIFWYAPECLRTr---RFTSKGDVWSYGVTLWEMFTLGrlpth 769
gi 56405328 1031 LDNd----RLVKIGDFGLAKAVPeGHEYYRVReDGDSPVFWYAPECLKEy---KFYYASDVWSFGVTLYELLTHC----- 1098
gi 60416388 1022 VDHng-dgDCVKISDFGLAQFAN-SDGYYYAKsKRDIPIRWYSPEAISTc---RFSSYSDVWSYGVTLFEMFSRGe---- 1092
gi 70570038  995 LDKegsncWNIKISDFGLSRILSeDRDYYTGN-PDEFPAQWYAPECLRLdgrrTFHFESDVWSYGVTLWEMFSYGa---- 1069
3EYG_A       147 VESe----HQVKIGDFGLTKAIEtDKEXXTVKdDRDSPVFWYAPECLMQs---KFYIASDVWSFGVTLHELLTYC----- 214
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                     #                                                  
1YVJ_A       212 ------DKSCSPSAEflrmmgc-erdvpaLCRLLELLE--EGQRLPAPPACP------AEVHELMKLCWAPsPQDRPSFS 276
2B7A_B       213 ------EKSKSPPAEfmrmigndkqgqmiVFHLIELLK--NNGRLPRPDGCP------DEIYMIMTECWNNnVNQRPSFR 278
gi 18150836  770 vfqaqlRHFQHPPGQpav---------niHTQMVRLLTegPSPSLPPPPPLPkmspcsSDVYDIMVECWQVrPEDRPSFH 840
gi 56405328 1099 ------DSSQSPPTKfleligi-aqgqmtVLRLTELLE--RGERLPRPDKCP------CEVYHLMKNCWETeASFRPTFE 1163
gi 60416388 1093 ------EPNLVPIQTs-------------QEDFLNRLQ--SGERLNRPASCP------DFIYDLMQLCWHAtPRSRPSFA 1145
gi 70570038 1070 ------RPTYEPLPNitl---------rqLTQLQELLK--DNVRLSQPEHCP------NEVFHLISRCWEYePQQRVKFD 1126
3EYG_A       215 ------DSDSSPMALflkmigp-thgqmtVTRLVNTLK--EGKRLPCPPNCP------DEVYQLMRKCWEFqPSNRTSFQ 279
                        330
                 ....*....|
Feature 1                  
1YVJ_A       277 ALGPQLDMLW 286
2B7A_B       279 DLALRVDQIR 288
gi 18150836  841 DLQLKVALVA 850
gi 56405328 1164 NLIPILKTVH 1173
gi 60416388 1146 TIVDIITREV 1155
gi 70570038 1127 ELCREFDRLR 1136
3EYG_A       280 NLIEGFEALL 289

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