1IR3,1RQQ,1I44,2B4S,2AUH,1IRK


Conserved Protein Domain Family
PTKc_InsR

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cd05061: PTKc_InsR 
Click on image for an interactive view with Cn3D
Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor
PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. InsR is a receptor PTK (RTK) that is composed of two alphabeta heterodimers. Binding of the insulin ligand to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, stimulating downstream kinase activities, which initiate signaling cascades and biological function. InsR signaling plays an important role in many cellular processes including glucose homeostasis, glycogen synthesis, lipid and protein metabolism, ion and amino acid transport, cell cycle and proliferation, cell differentiation, gene transcription, and nitric oxide synthesis. Insulin resistance, caused by abnormalities in InsR signaling, has been described in diabetes, hypertension, cardiovascular disease, metabolic syndrome, heart failure, and female infertility. The InsR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.
Statistics
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PSSM-Id: 133192
View PSSM: cd05061
Aligned: 10 rows
Threshold Bit Score: 631.619
Threshold Setting Gi: 3135370
Created: 7-May-2007
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
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Conserved site includes 22 residues -Click on image for an interactive view with Cn3D
Feature 1:active site [active site]
Evidence:
  • Comment:includes ATP binding and substrate binding sites
  • Structure:1RQQ; Human InsR tyr kinase binds thiophosphoric acid diester and 18-amino acid peptide substrate; defined at 3.5A contacts.
    View structure with Cn3D
  • Structure:1IR3; Human InsR tyr kinase binds ATP analog and peptide substrate; defined at 3.5A contacts.
    View structure with Cn3D
  • Citation:PMID 9312016

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                      ##   #                 # #                                      
1IR3_A      12 WEVSREKITLLRELGQGSFGMVYEGNARDiIKGEAETRVAVKTVNESasLRERIEFLNEASVMKGFTCHHVVRLLGVVSk 91   human
1RQQ_A      12 WEVSREKITLLRELGQGSFGMVYEGNARDiIKGEAETRVAVKTVNESasLRERIEFLNEASVMKGFTCHHVVRLLGVVSk 91   human
1I44_A      12 WEVSREKITLLRELGQGSFGMVYEGNARDiIKGEAETRVAVKTVNESasLRERIEFLNEASVMKGFTCHHVVRLLGVVSk 91   human
2B4S_D      12 WEVSREKITLLRELGQGSFGMVYEGNARDiIKGEAETRVAVKTVNESasLRERIEFLNEASVMKGFTCHHVVRLLGVVSk 91   human
2AUH_A      12 WEVSREKITLLRELGQGSFGMVYEGNARDiIKGEAETRVAVKTVNESasLRERIEFLNEASVMKGFTCHHVVRLLGVVSk 91   human
1IRK_A      12 WEVSREKITLLRELGQGSFGMVYEGNARDiIKGEAETRVAVKTVNESasLRERIEFLNEASVMKGFTCHHVVRLLGVVSk 91   human
Q9PVZ4    1005 WEVPRDKINLLRELGQGSFGMVYEGIAKDiIKGEPEVRVAVKTVNESasLRERIEFLNEASVMKAFNCHHVVRLLGVVSk 1084 African clawed frog
AAD26153   623 WEVPREKITLLRELGQGSFGMVYEGIAKDiVKGELETRVAVKTVNESasLRERIEFLNEASVMKGFICHHVVRLLGVVSk 702  chicken
CAA12279   878 WEVPREKITVLRELGQGSFGMVYEGIAKDiIKGDPDTRVAVKTVNESasLRERIEFLNEASVMKAFSCHHVVRLLGVVSk 957  turbot
AAC16490   655 WEVAREKINILKELGQGSFGMVYEGVAKDiVKGEPDTRVAVKTVNESasLRERIEFLNEASVMKGFSCHHVVRLLGVVSk 734  rainbow trout
Feature 1              # #   #                                                 #   ##          
1IR3_A      92 gqPTLVVMELMAHGDLKSYLRSLRPeae-nnpGRPPPTLQEMIQMAAEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVK 170  human
1RQQ_A      92 gqPTLVVMELMAHGDLKSYLRSLRPeae-nnpGRPPPTLQEMIQMAAEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVK 170  human
1I44_A      92 gqPTLVVMELMAHGDLKSYLRSLRPeae-nnpGRPPPTLQEMIQMAAEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVK 170  human
2B4S_D      92 gqPTLVVMELMAHGDLKSYLRSLRPeae-nnpGRPPPTLQEMIQMAAEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVK 170  human
2AUH_A      92 gqPTLVVMELMAHGDLKSYLRSLRPeae-nnpGRPPPTLQEMIQMAAEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVK 170  human
1IRK_A      92 gqPTLVVMELMAHGDLKSYLRSLRPeae-nnpGRPPPTLQEMIQMAAEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVK 170  human
Q9PVZ4    1085 gqPTLVIMELMAHGDLKSYLRSLRPdae-nnpGRLAPTLKEIIQMAAEISDGMAYLNAKKFVHRDLAARNCMVADDYAVK 1163 African clawed frog
AAD26153   703 gqPTLVVMELMAHGDFKSYLRSLRPdae-nnpGRPPPTLREMIQMAAEIADGMAYLNAKKFVHRDLAARNCMVAEDFTVK 781  chicken
CAA12279   958 aqPTLVVMELMTHGDLKSYLRCLRSdsennptGRPPPTLKEMIQMAAEIADGMAYLNAKKFVHRDLAARNCMVAEDFTVK 1037 turbot
AAC16490   735 gqPTLVVMELMTHGDLKSFLRALRPdsesnpqGSPLPHLKEMIQMSGEIADGMAYLNAKKFVHRDLAARNCMVAEDNTVK 814  rainbow trout
Feature 1        #              # ### ##        ## #                              #            
1IR3_A     171 IGDFGMTRDIXETDXXRKGGKGLLPVRWMAPESLKDGVFTTSSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGY 250  human
1RQQ_A     171 IGDFGMTRDIXETDXXRKGGKGLLPVRWMAPESLKDGVFTTSSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGY 250  human
1I44_A     171 IGDFGMTRDIYETAYYRKGGKGLLPVRWMAPESLKDGVFTTSSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGY 250  human
2B4S_D     171 IGDFGMTRDIXETDXXRKGGKGLLPVRWMAPESLKDGVFTTSSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGY 250  human
2AUH_A     171 IGDFGMTRDIXETDXXRKGGKGLLPVRWMAPESLKDGVFTTSSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGY 250  human
1IRK_A     171 IGDFGMTRDIYETDYYRKGGKGLLPVRWMAPESLKDGVFTTSSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGY 250  human
Q9PVZ4    1164 IGDFGMTRDIYETDYYRKGGKGLLPVRWMSPESLKDGVFTAFSDVWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGS 1243 African clawed frog
AAD26153   782 IGDFGMTRDIYETDYYRKGGKGLLPVRWMAPESLKDGVFTTYSDVWSFGVVLWEISSLAEQPYQGLSNEQVLKFVMDGGY 861  chicken
CAA12279  1038 IGDFGMTRDIYETDYYRKGGKGLLPVRWMAPESLKDGVFTPHSDCWSFGVVLWEISTLAEQPYQGLSNEQVLKFVMDGGY 1117 turbot
AAC16490   815 IGYFGMTRDIYETDYYRKGGKGLLPVSGMASRSLKDGSVTAYSDCWSFGVVLWEVSTLAEQPYQGLSNEQVLKFVMDGGY 894  rainbow trout
Feature 1                                                       
1IR3_A     251 LDQPDNcpERVTDLMRMCWQFnPKMRPTFLEIVNLLKDdlHPSFPEVSF 299  human
1RQQ_A     251 LDQPDNcpERVTDLMRMCWQFnPNMRPTFLEIVNLLKDdlHPSFPEVSF 299  human
1I44_A     251 LDQPDNcpERVTDLMRMCWQFnPKMRPTFLEIVNLLKDdlHPSFPEVSF 299  human
2B4S_D     251 LDQPDNcpERVTDLMRMCWQFnPNMRPTFLEIVNLLKDdlHPSFPEVSF 299  human
2AUH_A     251 LDQPDNcpERVTDLMRMCWQFnPNMRPTFLEIVNLLKDdlHPSFPEVSF 299  human
1IRK_A     251 LDQPDNcpERVTDLMRMCWQFnPKMRPTFLEIVNLLKDdlHPSFPEVSF 299  human
Q9PVZ4    1244 LDHPENcpPRLHSLMQMCWQYnPKMRPTFLEIIDMLKDdlRPSFQDVSF 1292 African clawed frog
AAD26153   862 LDQPDNcpERLHNLMQMCWQYnPKMRPTFIEVIEMLKEdlHPSFQEVSF 910  chicken
CAA12279  1118 LDRPENcpERMHSLMQMCWQYnPKMRPMFYEIIEMLREdlHPSFQEVSF 1166 turbot
AAC16490   895 LDRPENceQRIHNLMSMCWQYnPKMRPTFQEIIEMLKEdlHPSFQEVSF 943  rainbow trout

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