1K3A,1IR3,1RQQ,1M7N,1JQH


Conserved Protein Domain Family
PTKc_InsR_like

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cd05032: PTKc_InsR_like 
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Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases
PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The InsR subfamily is composed of InsR, Insulin-like Growth Factor-1 Receptor (IGF-1R), and similar proteins. InsR and IGF-1R are receptor PTKs (RTKs) composed of two alphabeta heterodimers. Binding of the ligand (insulin, IGF-1, or IGF-2) 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 and IGF-1R, which share 84% sequence identity in their kinase domains, display physiologically distinct yet overlapping functions in cell growth, differentiation, and metabolism. InsR activation leads primarily to metabolic effects while IGF-1R activation stimulates mitogenic pathways. In cells expressing both receptors, InsR/IGF-1R hybrids are found together with classical receptors. Both receptors can interact with common adaptor molecules such as IRS-1 and IRS-2. The InsR-like subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.
Statistics
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PSSM-Id: 173625
View PSSM: cd05032
Aligned: 14 rows
Threshold Bit Score: 467.205
Threshold Setting Gi: 23663956
Created: 17-Jul-2006
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 23 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:1K3A; Human IGF-1R tyr kinase binds AMP-PCP and substrate IRS-1 peptide; defined at 3.5A contacts.
    View structure with Cn3D
  • 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                   # ###   #                   # #                                    
1K3A_A       5 WEVAREKITMSRELGQGSFGMVYEGVAKGvvk--dePETRVAIKTVNEAasmreRIEFLNEASVMKEFNCHHVVRLLGVV 82   human
1IR3_A      12 WEVSREKITLLRELGQGSFGMVYEGNARDiik--geAETRVAVKTVNESaslreRIEFLNEASVMKGFTCHHVVRLLGVV 89   human
1RQQ_A      12 WEVSREKITLLRELGQGSFGMVYEGNARDiik--geAETRVAVKTVNESaslreRIEFLNEASVMKGFTCHHVVRLLGVV 89   human
Q25197    1037 WELNREKIELIRELGQGSFGMVFEGIAHGig---dhAELRVAVKTTNENasihdRIQILQEASIMKAFNCNHVVKLIGVV 1113 Hydra vulgaris
P09208    1364 WEVLRENIIQLAPLGQGSFGMVYEGILKSfpp--ngVDRECAIKTVNENatdreRTNFLSEASVMKEFDTYHVVRLLGVC 1441 fruit fly
BAE06509    92 YEIPEENVELMDEIGHGHFGKVYEGLAKQvvk--gqPKTKVAVKTLHGNesiskRMEFLKEASVMKAFNSHHVVRLLGVV 169  Ciona intestinalis
ABC61312   692 WEFPRDKLEIIRELGKGSFGMVYEGLAKGilp-eeeEISRVAIKSVQANasmrdRIEFLNEASVMKLIDAHNVVRLLGVV 770  purple urchin
AAW50597  1037 WELKRSAIHLEDEIGRGTFGKVYRGYGDNcksylgvTFGECAIKTVSETansaeRLHFLIEASVMKQFNTPFIVKLYGVV 1116 agent of lymphat...
CAC14729   210 WELVPDSLTMIREVGEGAFGKVYEGLLATve----dGDMTVAIKTLSVCdtmgqRNAFLAEASIMKKFDSPYVMRLMGLV 285  Sycon raphanus
AAK29947  1236 WELRQDDVVLGQQCGEGSFGKVYLGTGNNvvslmgdRFGPCAIKINVDDpasteNLNYLMEANIMKNFKTNFIVKLYGVI 1315 nematode
Feature 1                # #   #                                                            #  
1K3A_A      83 SqgqPTLVIMELMTRGDLKSYLRSLRPemen------------npvlAPPSLSKMIQMAGEIADGMAYLNANKFVHRDLA 150  human
1IR3_A      90 SkgqPTLVVMELMAHGDLKSYLRSLRPeaen------------npgrPPPTLQEMIQMAAEIADGMAYLNAKKFVHRDLA 157  human
1RQQ_A      90 SkgqPTLVVMELMAHGDLKSYLRSLRPeaen------------npgrPPPTLQEMIQMAAEIADGMAYLNAKKFVHRDLA 157  human
Q25197    1114 SqgqPTFVVMELMGRGDLKSYLKERRPdd----------------ggIPLMRQEIYQMVAEIADGMAYLAARKFVHCDLA 1177 Hydra vulgaris
P09208    1442 SrgqPALVVMELMKKGDLKSYLRAHRPeerdeammtylnrigvtgnvQPPTYGRIYQMAIEIADGMAYLAAKKFVHRDLA 1521 fruit fly
BAE06509   170 SmskRPMVIMEFMAKGDLKTYLRSTRPdaei-------------rkgDPPSLQQKLQMCGEIADGMSYLSETKYVHRDLA 236  Ciona intestinalis
ABC61312   771 SkgqPTYVIMEFMAQGDLKNWLRARRPenqq-------------dlpSVPTLEQLLNMAAEIADGMSFLAARKYVHRDLS 837  purple urchin
AAW50597  1117 SdgqPVLVVMEMMKKGNLRDYLRSRRPnaeen-----------vnglPVPGAIDFFRWASQVADGMAYLESLKFCHRDLA 1185 agent of lymphat...
CAC14729   286 StenKPLVVMEFMAEGDLRGYVRKCRPqnrqfsinsietngsaasvyGIPTAERFMLWALQLSKGMAYVHEKHFVHRDLA 365  Sycon raphanus
AAK29947  1316 StvqPAMVVMEMMDLGNLRDYLRSKREdevfne--------tdcnffDIIPRDKFHEWAAQICDGMAYLESLKFCHRDLA 1387 nematode
Feature 1       ## #          #                ### ##        # #                               
1K3A_A     151 ARNCMVAEdFTVKIGDFGMTRDIXETDXXRKGGKGLLPVRWMSPESLKDgVFTTYSDVWSFGVVLWEIATLAEQPYQGLS 230  human
1IR3_A     158 ARNCMVAHdFTVKIGDFGMTRDIXETDXXRKGGKGLLPVRWMAPESLKDgVFTTSSDMWSFGVVLWEITSLAEQPYQGLS 237  human
1RQQ_A     158 ARNCMVAHdFTVKIGDFGMTRDIXETDXXRKGGKGLLPVRWMAPESLKDgVFTTSSDMWSFGVVLWEITSLAEQPYQGLS 237  human
Q25197    1178 ARNCMVASdFTVKIGDFGMARDIYERNYYRKDGKSLLPIRWMAPESLKDgIFSTASDVWSFGVVLWEICTLASQPYQGKT 1257 Hydra vulgaris
P09208    1522 ARNCMVADdLTVKIGDFGMTRDIYETDYYRKGTKGLLPVRWMPPESLRDgVYSSASDVFSFGVVLWEMATLAAQPYQGLS 1601 fruit fly
BAE06509   237 ARNCLVHEdLTVKIGDFGLTRDVYETDYYRIDSRGILPVRWMAPESLKDgVFDSRSDVWSFGIVLWEIATLAEQPYQGQQ 316  Ciona intestinalis
ABC61312   838 ARNCLVSGeGTCKVADFGLARDIYQSDYYRKERGGMLPIRWMAPESVKDgVFQASSDVWSFGILLWEMATLGELPYQGLS 917  purple urchin
AAW50597  1186 ARNCMVNEfDTVKIGDFGMARDIYYHEYYKPAGKRLMPVRWMAPESLMDgKFTMKSDVWSYGITLYEMLTLAQQPYLGLA 1265 agent of lymphat...
CAC14729   366 ARNCMLSSnLTLKIGDFGFTRDIYESDYYRKTGKGALPVRWMGPEALRDgMYIPESDVWSYGVVLWEMATLGDQPYKGKS 445  Sycon raphanus
AAK29947  1388 ARNCMINRdETVKIGDFGMARDLFYHDYYKPSGKRMMPVRWMSPESLKDgKFDSKSDVWSFGVVLYEMVTLGAQPYIGLS 1467 nematode
Feature 1      #                                                      
1K3A_A     231 NEQVLRFVM-EGGLLDKPDNc---pDMLLELMRMCWQYnPKMRPSFLEIISSIKE 281  human
1IR3_A     238 NEQVLKFVM-DGGYLDQPDNc---pERVTDLMRMCWQFnPKMRPTFLEIVNLLKD 288  human
1RQQ_A     238 NEQVLKFVM-DGGYLDQPDNc---pERVTDLMRMCWQFnPNMRPTFLEIVNLLKD 288  human
Q25197    1258 NEQVLNFVL-SNGHLDYPEGc---dYQLREFMSLCWHRdPKMRPSFLEIVHVLEN 1308 Hydra vulgaris
P09208    1602 NEQVLRYVI-DGGVMERPENc---pDFLHKLMQRCWHHrSSARPSFLDIIAYLEP 1652 fruit fly
BAE06509   317 HDQVTRFVI-DGGYMEQPKEc---pSKLYDMMLMCWHYsPSMRPTFLEIVASLSP 367  Ciona intestinalis
ABC61312   918 NEEAGEYIK-GGNVLRPPENc---pEKMQEIMMACWQYqEKLRPLFGEIILNLQD 968  purple urchin
AAW50597  1266 NESVFDYIGvKKKILTRPTGc---pDFWYELMKRCWKYdPRERPTFAQIVGILLR 1317 agent of lymphatic filariasis
CAC14729   446 NEEVISLVI-AGDHMPLPITlhdfpQPCLDLMETCWQFqPAERPTFEKIVSMLDD 499  Sycon raphanus
AAK29947  1468 NDEVLNYIGmARKVIKKPECc---eNYWYKVMKMCWRYsPRDRPTFLQLVHLLAA 1519 nematode

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