GenomeNet

Database: UniProt
Entry: INSR_RAT
LinkDB: INSR_RAT
Original site: INSR_RAT 
ID   INSR_RAT                Reviewed;        1383 AA.
AC   P15127; P97681;
DT   01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-APR-1990, sequence version 1.
DT   24-JAN-2024, entry version 214.
DE   RecName: Full=Insulin receptor;
DE            Short=IR;
DE            EC=2.7.10.1;
DE   AltName: CD_antigen=CD220;
DE   Contains:
DE     RecName: Full=Insulin receptor subunit alpha;
DE   Contains:
DE     RecName: Full=Insulin receptor subunit beta;
DE   Flags: Precursor;
GN   Name=Insr;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), AND ALTERNATIVE SPLICING
RP   (ISOFORM SHORT).
RX   PubMed=2330003; DOI=10.1210/mend-4-2-235;
RA   Goldstein B.J., Dudley A.L.;
RT   "The rat insulin receptor: primary structure and conservation of tissue-
RT   specific alternative messenger RNA splicing.";
RL   Mol. Endocrinol. 4:235-244(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 731-756; 758-819; 969-994 AND
RP   1119-1177.
RC   STRAIN=Sprague-Dawley;
RA   Liu Y., Tam J.W.O.;
RL   Submitted (MAY-1997) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   INTERACTION WITH GRB7.
RX   PubMed=10803466; DOI=10.1038/sj.onc.1203469;
RA   Kasus-Jacobi A., Bereziat V., Perdereau D., Girard J., Burnol A.F.;
RT   "Evidence for an interaction between the insulin receptor and Grb7. A role
RT   for two of its binding domains, PIR and SH2.";
RL   Oncogene 19:2052-2059(2000).
RN   [4]
RP   FUNCTION, AND FORMATION OF A HYBRID RECEPTOR WITH IGF1R.
RX   PubMed=16803852; DOI=10.1152/ajpendo.00565.2005;
RA   Johansson G.S., Arnqvist H.J.;
RT   "Insulin and IGF-I action on insulin receptors, IGF-I receptors, and hybrid
RT   insulin/IGF-I receptors in vascular smooth muscle cells.";
RL   Am. J. Physiol. 291:E1124-E1130(2006).
RN   [5]
RP   INTERACTION WITH CAV2.
RX   PubMed=19778377; DOI=10.1111/j.1582-4934.2009.00391.x;
RA   Kwon H., Jeong K., Pak Y.;
RT   "Identification of pY19-caveolin-2 as a positive regulator of insulin-
RT   stimulated actin cytoskeleton-dependent mitogenesis.";
RL   J. Cell. Mol. Med. 13:1549-1564(2009).
RN   [6]
RP   INTERACTION WITH CCDC88A AND GNAI3.
RX   PubMed=25187647; DOI=10.1091/mbc.e14-05-0978;
RA   Lin C., Ear J., Midde K., Lopez-Sanchez I., Aznar N., Garcia-Marcos M.,
RA   Kufareva I., Abagyan R., Ghosh P.;
RT   "Structural basis for activation of trimeric Gi proteins by multiple growth
RT   factor receptors via GIV/Girdin.";
RL   Mol. Biol. Cell 25:3654-3671(2014).
RN   [7]
RP   INTERACTION WITH ATIC.
RX   PubMed=25687571; DOI=10.1074/mcp.m114.047159;
RA   Boutchueng-Djidjou M., Collard-Simard G., Fortier S., Hebert S.S.,
RA   Kelly I., Landry C.R., Faure R.L.;
RT   "The last enzyme of the de novo purine synthesis pathway 5-aminoimidazole-
RT   4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC)
RT   plays a central role in insulin signaling and the Golgi/endosomes protein
RT   network.";
RL   Mol. Cell. Proteomics 14:1079-1092(2015).
CC   -!- FUNCTION: Receptor tyrosine kinase which mediates the pleiotropic
CC       actions of insulin. Binding of insulin leads to phosphorylation of
CC       several intracellular substrates, including, insulin receptor
CC       substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling
CC       intermediates. Each of these phosphorylated proteins serve as docking
CC       proteins for other signaling proteins that contain Src-homology-2
CC       domains (SH2 domain) that specifically recognize different
CC       phosphotyrosine residues, including the p85 regulatory subunit of PI3K
CC       and SHP2. Phosphorylation of IRSs proteins lead to the activation of
CC       two main signaling pathways: the PI3K-AKT/PKB pathway, which is
CC       responsible for most of the metabolic actions of insulin, and the Ras-
CC       MAPK pathway, which regulates expression of some genes and cooperates
CC       with the PI3K pathway to control cell growth and differentiation.
CC       Binding of the SH2 domains of PI3K to phosphotyrosines on IRS1 leads to
CC       the activation of PI3K and the generation of phosphatidylinositol-(3,
CC       4, 5)-triphosphate (PIP3), a lipid second messenger, which activates
CC       several PIP3-dependent serine/threonine kinases, such as PDPK1 and
CC       subsequently AKT/PKB. The net effect of this pathway is to produce a
CC       translocation of the glucose transporter SLC2A4/GLUT4 from cytoplasmic
CC       vesicles to the cell membrane to facilitate glucose transport.
CC       Moreover, upon insulin stimulation, activated AKT/PKB is responsible
CC       for: anti-apoptotic effect of insulin by inducing phosphorylation of
CC       BAD; regulates the expression of gluconeogenic and lipogenic enzymes by
CC       controlling the activity of the winged helix or forkhead (FOX) class of
CC       transcription factors. Another pathway regulated by PI3K-AKT/PKB
CC       activation is mTORC1 signaling pathway which regulates cell growth and
CC       metabolism and integrates signals from insulin. AKT mediates insulin-
CC       stimulated protein synthesis by phosphorylating TSC2 thereby activating
CC       mTORC1 pathway. The Ras/RAF/MAP2K/MAPK pathway is mainly involved in
CC       mediating cell growth, survival and cellular differentiation of
CC       insulin. Phosphorylated IRS1 recruits GRB2/SOS complex, which triggers
CC       the activation of the Ras/RAF/MAP2K/MAPK pathway. In addition to
CC       binding insulin, the insulin receptor can bind insulin-like growth
CC       factors (IGFI and IGFII). When present in a hybrid receptor with IGF1R,
CC       binds IGF1 (By similarity). In adipocytes, inhibits lipolysis (By
CC       similarity). {ECO:0000250, ECO:0000250|UniProtKB:P15208,
CC       ECO:0000269|PubMed:16803852}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC         [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC         COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC         ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC         Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC   -!- ACTIVITY REGULATION: Activated in response to insulin.
CC       Autophosphorylation activates the kinase activity. PTPN1, PTPRE and
CC       PTPRF dephosphorylate important tyrosine residues, thereby reducing
CC       INSR activity. Inhibited by ENPP1. GRB10 and GRB14 inhibit the
CC       catalytic activity of the INSR, they block access of substrates to the
CC       activated receptor. SOCS1 and SOCS3 act as negative regulators of INSR
CC       activity, they bind to the activated INRS and interfere with the
CC       phosphorylation of INSR substrates (By similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Tetramer of 2 alpha and 2 beta chains linked by disulfide
CC       bonds. The alpha chains carry the insulin-binding regions, while the
CC       beta chains carry the kinase domain. Forms a hybrid receptor with
CC       IGF1R, the hybrid is a tetramer consisting of 1 alpha chain and 1 beta
CC       chain of INSR and 1 alpha chain and 1 beta chain of IGF1R. Interacts
CC       with SORBS1 but dissociates from it following insulin stimulation.
CC       Binds SH2B2. Activated form of INSR interacts (via Tyr-1000) with the
CC       PTB/PID domains of IRS1 and SHC1. The sequences surrounding the
CC       phosphorylated NPXY motif contribute differentially to either IRS1 or
CC       SHC1 recognition. Interacts (via tyrosines in the C-terminus) with IRS2
CC       (via PTB domain and 591-786 AA); the 591-786 would be the primary
CC       anchor of IRS2 to INSR while the PTB domain would have a stabilizing
CC       action on the interaction with INSR. Interacts with the SH2 domains of
CC       the 85 kDa regulatory subunit of PI3K (PIK3R1) in vitro, when
CC       autophosphorylated on tyrosine residues. Interacts with SOCS7.
CC       Interacts (via the phosphorylated Tyr-1000), with SOCS3. Interacts (via
CC       the phosphorylated Tyr-1186, Tyr-1190, Tyr-1191) with SOCS1. Interacts
CC       with ARRB2 (By similarity). Interacts with GRB10; this interaction
CC       blocks the association between IRS1/IRS2 and INSR, significantly
CC       reduces insulin-stimulated tyrosine phosphorylation of IRS1 and IRS2
CC       and thus decreases insulin signaling. Interacts with PDPK1. Interacts
CC       (via Tyr-1191) with GRB14 (via BPS domain); this interaction protects
CC       the tyrosines in the activation loop from dephosphorylation, but
CC       promotes dephosphorylation of Tyr-1000, this results in decreased
CC       interaction with, and phosphorylation of, IRS1. Interacts (via subunit
CC       alpha) with ENPP1 (via 485-599 AA); this interaction blocks
CC       autophosphorylation. Interacts with PTPRE; this interaction is
CC       dependent of Tyr-1186, Tyr-1190 and Tyr-1191 of the INSR. Interacts
CC       with STAT5B (via SH2 domain). Interacts with PTPRF (By similarity).
CC       Interacts with GRB7. Interacts with CAV2 (tyrosine-phosphorylated
CC       form); the interaction is increased with 'Tyr-27'phosphorylation of
CC       CAV2. Interacts with ATIC; ATIC together with PRKAA2/AMPK2 and
CC       HACD3/PTPLAD1 is proposed to be part of a signaling netwok regulating
CC       INSR autophosphorylation and endocytosis (PubMed:25687571). Interacts
CC       with the insulin receptor SORL1; this interaction strongly increases
CC       its surface exposure, hence strengthens insulin signal reception (By
CC       similarity). Interacts (tyrosine phosphorylated) with CCDC88A/GIV (via
CC       SH2-like region); binding requires autophosphorylation of the Insr C-
CC       terminal region (PubMed:25187647). Interacts with GNAI3; the
CC       interaction is probably mediated by CCDC88A/GIV (PubMed:25187647).
CC       Interacts with LMBRD1 (By similarity). Interacts (in response to
CC       insulin stimulation) with NCK1; this interaction may recruit PTPN1 to
CC       mediate INSR dephosphorylation (By similarity). {ECO:0000250,
CC       ECO:0000250|UniProtKB:P06213, ECO:0000250|UniProtKB:P15208,
CC       ECO:0000269|PubMed:10803466, ECO:0000269|PubMed:19778377,
CC       ECO:0000269|PubMed:25187647, ECO:0000269|PubMed:25687571}.
CC   -!- INTERACTION:
CC       P15127; Q62689: Jak2; NbExp=2; IntAct=EBI-7472166, EBI-8656708;
CC       PRO_0000016698; O35567: Atic; NbExp=3; IntAct=EBI-10768746, EBI-10768817;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P15208};
CC       Single-pass type I membrane protein {ECO:0000305}. Late endosome
CC       {ECO:0000250|UniProtKB:P15208}. Lysosome
CC       {ECO:0000250|UniProtKB:P15208}. Note=Binding of insulin to INSR induces
CC       internalization and lysosomal degradation of the receptor, a means for
CC       down-regulating this signaling pathway after stimulation. In the
CC       presence of SORL1, internalized INSR molecules are redirected back to
CC       the cell surface, thereby preventing their lysosomal catabolism and
CC       strengthening insulin signal reception. {ECO:0000250|UniProtKB:P15208}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=Long; Synonyms=RIR-B;
CC         IsoId=P15127-1; Sequence=Displayed;
CC       Name=Short; Synonyms=RIR-A;
CC         IsoId=P15127-2; Sequence=VSP_036680;
CC   -!- DOMAIN: The tetrameric insulin receptor binds insulin via non-identical
CC       regions from two alpha chains, primarily via the C-terminal region of
CC       the first INSR alpha chain. Residues from the leucine-rich N-terminus
CC       of the other INSR alpha chain also contribute to this insulin binding
CC       site. A secondary insulin-binding site is formed by residues at the
CC       junction of fibronectin type-III domain 1 and 2 (By similarity).
CC       {ECO:0000250}.
CC   -!- PTM: Autophosphorylated on tyrosine residues in response to insulin.
CC       Phosphorylation of Tyr-1000 is required for binding to IRS1, SHC1, and
CC       STAT5B. Dephosphorylated by PTPRE on Tyr-1000, Tyr-1186, Tyr-1190 and
CC       Tyr-1191 residues. Dephosphorylated by PTPRF and PTPN1.
CC       Dephosphorylated by PTPN2; down-regulates insulin-induced signaling.
CC       {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC       kinase family. Insulin receptor subfamily. {ECO:0000255|PROSITE-
CC       ProRule:PRU00159}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; M29014; AAA41441.1; -; mRNA.
DR   EMBL; AF005776; AAB61414.1; -; Genomic_DNA.
DR   EMBL; AF005777; AAB61415.1; -; Genomic_DNA.
DR   EMBL; AH004882; AAB38967.1; -; Genomic_DNA.
DR   EMBL; AH004883; AAB38968.1; -; Genomic_DNA.
DR   EMBL; U80633; AAB38746.1; -; Genomic_DNA.
DR   PIR; A36080; A36080.
DR   PDB; 4XST; X-ray; 3.00 A; F=726-748.
DR   PDB; 5TQ1; X-ray; 1.49 A; B=1008-1018.
DR   PDBsum; 4XST; -.
DR   PDBsum; 5TQ1; -.
DR   AlphaFoldDB; P15127; -.
DR   BMRB; P15127; -.
DR   SMR; P15127; -.
DR   DIP; DIP-42209N; -.
DR   IntAct; P15127; 454.
DR   MINT; P15127; -.
DR   STRING; 10116.ENSRNOP00000049655; -.
DR   BindingDB; P15127; -.
DR   ChEMBL; CHEMBL5486; -.
DR   DrugCentral; P15127; -.
DR   GlyCosmos; P15127; 18 sites, 5 glycans.
DR   GlyGen; P15127; 18 sites, 5 N-linked glycans (1 site).
DR   iPTMnet; P15127; -.
DR   PhosphoSitePlus; P15127; -.
DR   PaxDb; 10116-ENSRNOP00000060141; -.
DR   PeptideAtlas; P15127; -.
DR   UCSC; RGD:2917; rat. [P15127-1]
DR   AGR; RGD:2917; -.
DR   RGD; 2917; Insr.
DR   eggNOG; KOG4258; Eukaryota.
DR   InParanoid; P15127; -.
DR   PhylomeDB; P15127; -.
DR   BRENDA; 2.7.10.1; 5301.
DR   Reactome; R-RNO-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR   Reactome; R-RNO-74713; IRS activation.
DR   Reactome; R-RNO-74749; Signal attenuation.
DR   Reactome; R-RNO-74751; Insulin receptor signalling cascade.
DR   Reactome; R-RNO-74752; Signaling by Insulin receptor.
DR   Reactome; R-RNO-77387; Insulin receptor recycling.
DR   PRO; PR:P15127; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0030424; C:axon; IBA:GO_Central.
DR   GO; GO:0005901; C:caveola; ISO:RGD.
DR   GO; GO:0032590; C:dendrite membrane; IDA:ARUK-UCL.
DR   GO; GO:0005768; C:endosome; IDA:RGD.
DR   GO; GO:0009897; C:external side of plasma membrane; IDA:ARUK-UCL.
DR   GO; GO:0005899; C:insulin receptor complex; ISO:RGD.
DR   GO; GO:0005770; C:late endosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; ISO:RGD.
DR   GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR   GO; GO:0032809; C:neuronal cell body membrane; IDA:ARUK-UCL.
DR   GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR   GO; GO:0043235; C:receptor complex; ISO:RGD.
DR   GO; GO:0060417; C:yolk; IDA:RGD.
DR   GO; GO:0043423; F:3-phosphoinositide-dependent protein kinase binding; IDA:RGD.
DR   GO; GO:0001540; F:amyloid-beta binding; ISO:RGD.
DR   GO; GO:0005524; F:ATP binding; ISO:RGD.
DR   GO; GO:0038024; F:cargo receptor activity; IMP:ARUK-UCL.
DR   GO; GO:0005525; F:GTP binding; ISO:RGD.
DR   GO; GO:0043559; F:insulin binding; IDA:RGD.
DR   GO; GO:0005009; F:insulin receptor activity; IDA:RGD.
DR   GO; GO:0043560; F:insulin receptor substrate binding; IMP:RGD.
DR   GO; GO:0031994; F:insulin-like growth factor I binding; ISO:RGD.
DR   GO; GO:0031995; F:insulin-like growth factor II binding; ISO:RGD.
DR   GO; GO:0005159; F:insulin-like growth factor receptor binding; ISO:RGD.
DR   GO; GO:0031405; F:lipoic acid binding; IPI:RGD.
DR   GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; ISO:RGD.
DR   GO; GO:0019904; F:protein domain specific binding; IPI:RGD.
DR   GO; GO:0004672; F:protein kinase activity; IDA:RGD.
DR   GO; GO:0019901; F:protein kinase binding; IPI:RGD.
DR   GO; GO:0019903; F:protein phosphatase binding; IMP:RGD.
DR   GO; GO:0004713; F:protein tyrosine kinase activity; IDA:RGD.
DR   GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR   GO; GO:0051425; F:PTB domain binding; ISO:RGD.
DR   GO; GO:0005198; F:structural molecule activity; ISO:RGD.
DR   GO; GO:0030325; P:adrenal gland development; ISO:RGD.
DR   GO; GO:0000380; P:alternative mRNA splicing, via spliceosome; IEP:RGD.
DR   GO; GO:0097242; P:amyloid-beta clearance; IMP:ARUK-UCL.
DR   GO; GO:0009887; P:animal organ morphogenesis; ISO:RGD.
DR   GO; GO:0071363; P:cellular response to growth factor stimulus; ISO:RGD.
DR   GO; GO:0032869; P:cellular response to insulin stimulus; ISO:RGD.
DR   GO; GO:0034224; P:cellular response to zinc ion starvation; IEP:RGD.
DR   GO; GO:0021549; P:cerebellum development; IEP:RGD.
DR   GO; GO:0097062; P:dendritic spine maintenance; IGI:ARUK-UCL.
DR   GO; GO:1990402; P:embryonic liver development; IEP:RGD.
DR   GO; GO:0008544; P:epidermis development; ISO:RGD.
DR   GO; GO:0031017; P:exocrine pancreas development; ISO:RGD.
DR   GO; GO:0045444; P:fat cell differentiation; IEP:RGD.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:RGD.
DR   GO; GO:0042593; P:glucose homeostasis; ISO:RGD.
DR   GO; GO:0003007; P:heart morphogenesis; ISO:RGD.
DR   GO; GO:0021766; P:hippocampus development; IEP:RGD.
DR   GO; GO:0008286; P:insulin receptor signaling pathway; IDA:RGD.
DR   GO; GO:0001889; P:liver development; IEP:RGD.
DR   GO; GO:0097421; P:liver regeneration; IEP:RGD.
DR   GO; GO:0008584; P:male gonad development; ISO:RGD.
DR   GO; GO:0030238; P:male sex determination; ISO:RGD.
DR   GO; GO:2000252; P:negative regulation of feeding behavior; IMP:RGD.
DR   GO; GO:0010629; P:negative regulation of gene expression; IMP:RGD.
DR   GO; GO:0045719; P:negative regulation of glycogen biosynthetic process; IEP:RGD.
DR   GO; GO:0001933; P:negative regulation of protein phosphorylation; IMP:RGD.
DR   GO; GO:1990535; P:neuron projection maintenance; IGI:ARUK-UCL.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:0030335; P:positive regulation of cell migration; ISO:RGD.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR   GO; GO:0048639; P:positive regulation of developmental growth; ISO:RGD.
DR   GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISO:RGD.
DR   GO; GO:0046326; P:positive regulation of glucose import; ISO:RGD.
DR   GO; GO:0045725; P:positive regulation of glycogen biosynthetic process; ISO:RGD.
DR   GO; GO:0045821; P:positive regulation of glycolytic process; ISO:RGD.
DR   GO; GO:0010560; P:positive regulation of glycoprotein biosynthetic process; IMP:RGD.
DR   GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:RGD.
DR   GO; GO:0051446; P:positive regulation of meiotic cell cycle; ISO:RGD.
DR   GO; GO:0045840; P:positive regulation of mitotic nuclear division; ISO:RGD.
DR   GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISO:RGD.
DR   GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISO:RGD.
DR   GO; GO:0042327; P:positive regulation of phosphorylation; IDA:BHF-UCL.
DR   GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:RGD.
DR   GO; GO:0043243; P:positive regulation of protein-containing complex disassembly; IGI:ARUK-UCL.
DR   GO; GO:0002092; P:positive regulation of receptor internalization; ISO:RGD.
DR   GO; GO:0060267; P:positive regulation of respiratory burst; ISO:RGD.
DR   GO; GO:0031623; P:receptor internalization; ISO:RGD.
DR   GO; GO:0006898; P:receptor-mediated endocytosis; IMP:ARUK-UCL.
DR   GO; GO:0006355; P:regulation of DNA-templated transcription; ISO:RGD.
DR   GO; GO:0045995; P:regulation of embryonic development; ISO:RGD.
DR   GO; GO:2000194; P:regulation of female gonad development; ISO:RGD.
DR   GO; GO:0006111; P:regulation of gluconeogenesis; IEP:RGD.
DR   GO; GO:0010310; P:regulation of hydrogen peroxide metabolic process; IDA:RGD.
DR   GO; GO:0014823; P:response to activity; IEP:RGD.
DR   GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR   GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR   GO; GO:0032094; P:response to food; IEP:RGD.
DR   GO; GO:0051384; P:response to glucocorticoid; IEP:RGD.
DR   GO; GO:0009749; P:response to glucose; IEP:BHF-UCL.
DR   GO; GO:0009725; P:response to hormone; IEP:RGD.
DR   GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR   GO; GO:0032868; P:response to insulin; IEP:BHF-UCL.
DR   GO; GO:0010042; P:response to manganese ion; IEP:RGD.
DR   GO; GO:0031667; P:response to nutrient levels; IDA:RGD.
DR   GO; GO:0010033; P:response to organic substance; IEP:RGD.
DR   GO; GO:1904638; P:response to resveratrol; IEP:RGD.
DR   GO; GO:0042594; P:response to starvation; IEP:RGD.
DR   GO; GO:0033574; P:response to testosterone; IEP:RGD.
DR   GO; GO:0034612; P:response to tumor necrosis factor; IMP:RGD.
DR   GO; GO:1902438; P:response to vanadate(3-); IEP:RGD.
DR   GO; GO:0033280; P:response to vitamin D; IEP:RGD.
DR   GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR   GO; GO:0046718; P:viral entry into host cell; ISO:RGD.
DR   CDD; cd00063; FN3; 2.
DR   CDD; cd00064; FU; 1.
DR   CDD; cd05061; PTKc_InsR; 1.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 4.
DR   Gene3D; 3.80.20.20; Receptor L-domain; 2.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR   InterPro; IPR003961; FN3_dom.
DR   InterPro; IPR036116; FN3_sf.
DR   InterPro; IPR006211; Furin-like_Cys-rich_dom.
DR   InterPro; IPR006212; Furin_repeat.
DR   InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR040969; Insulin_TMD.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR000494; Rcpt_L-dom.
DR   InterPro; IPR036941; Rcpt_L-dom_sf.
DR   InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR   InterPro; IPR008266; Tyr_kinase_AS.
DR   InterPro; IPR020635; Tyr_kinase_cat_dom.
DR   InterPro; IPR016246; Tyr_kinase_insulin-like_rcpt.
DR   InterPro; IPR002011; Tyr_kinase_rcpt_2_CS.
DR   PANTHER; PTHR24416:SF535; INSULIN RECEPTOR; 1.
DR   PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 1.
DR   Pfam; PF00041; fn3; 1.
DR   Pfam; PF00757; Furin-like; 1.
DR   Pfam; PF17870; Insulin_TMD; 1.
DR   Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR   Pfam; PF01030; Recep_L_domain; 2.
DR   PIRSF; PIRSF000620; Insulin_receptor; 1.
DR   PRINTS; PR00109; TYRKINASE.
DR   SMART; SM00060; FN3; 3.
DR   SMART; SM00261; FU; 1.
DR   SMART; SM00219; TyrKc; 1.
DR   SUPFAM; SSF49265; Fibronectin type III; 3.
DR   SUPFAM; SSF57184; Growth factor receptor domain; 1.
DR   SUPFAM; SSF52058; L domain-like; 2.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   PROSITE; PS50853; FN3; 3.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR   PROSITE; PS00239; RECEPTOR_TYR_KIN_II; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; ATP-binding; Cell membrane;
KW   Cleavage on pair of basic residues; Disulfide bond; Endosome; Glycoprotein;
KW   Kinase; Lysosome; Membrane; Nucleotide-binding; Phosphoprotein; Receptor;
KW   Reference proteome; Repeat; Signal; Transferase; Transmembrane;
KW   Transmembrane helix; Tyrosine-protein kinase.
FT   SIGNAL          1..26
FT   CHAIN           27..759
FT                   /note="Insulin receptor subunit alpha"
FT                   /id="PRO_0000016696"
FT   CHAIN           764..1383
FT                   /note="Insulin receptor subunit beta"
FT                   /id="PRO_0000016698"
FT   TOPO_DOM        27..759
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TOPO_DOM        764..957
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        958..978
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        979..1383
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   DOMAIN          625..727
FT                   /note="Fibronectin type-III 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT   DOMAIN          754..848
FT                   /note="Fibronectin type-III 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT   DOMAIN          854..948
FT                   /note="Fibronectin type-III 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT   DOMAIN          1024..1299
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REGION          687..709
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          734..742
FT                   /note="Insulin-binding"
FT                   /evidence="ECO:0000250"
FT   REGION          747..783
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          997..1000
FT                   /note="Important for interaction with IRS1, SHC1 and
FT                   STAT5B"
FT   REGION          1361..1383
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1362..1365
FT                   /note="PIK3R1 binding"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        768..783
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        1160
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000250"
FT   BINDING         1034
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         1058
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         1105..1111
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         1164..1165
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         1178
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   SITE            65
FT                   /note="Insulin-binding"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         399
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P06213"
FT   MOD_RES         400
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:P06213"
FT   MOD_RES         406
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P06213"
FT   MOD_RES         1000
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000250|UniProtKB:P06213"
FT   MOD_RES         1186
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000250|UniProtKB:P06213"
FT   MOD_RES         1190
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000250|UniProtKB:P06213"
FT   MOD_RES         1191
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000250|UniProtKB:P06213"
FT   MOD_RES         1356
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000250|UniProtKB:P06213"
FT   MOD_RES         1362
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000250|UniProtKB:P06213"
FT   CARBOHYD        42
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        51
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        104
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        137
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        241
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        281
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        321
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        363
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        423
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        444
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        540
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        634
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        652
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        699
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        770
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        783
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        921
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        934
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        34..52
FT                   /evidence="ECO:0000250"
FT   DISULFID        152..181
FT                   /evidence="ECO:0000250"
FT   DISULFID        185..208
FT                   /evidence="ECO:0000250"
FT   DISULFID        195..214
FT                   /evidence="ECO:0000250"
FT   DISULFID        218..227
FT                   /evidence="ECO:0000250"
FT   DISULFID        222..233
FT                   /evidence="ECO:0000250"
FT   DISULFID        234..242
FT                   /evidence="ECO:0000250"
FT   DISULFID        238..251
FT                   /evidence="ECO:0000250"
FT   DISULFID        254..263
FT                   /evidence="ECO:0000250"
FT   DISULFID        267..279
FT                   /evidence="ECO:0000250"
FT   DISULFID        285..310
FT                   /evidence="ECO:0000250"
FT   DISULFID        292..300
FT                   /evidence="ECO:0000250"
FT   DISULFID        314..327
FT                   /evidence="ECO:0000250"
FT   DISULFID        330..334
FT                   /evidence="ECO:0000250"
FT   DISULFID        338..359
FT                   /evidence="ECO:0000250"
FT   DISULFID        461..494
FT                   /evidence="ECO:0000250"
FT   DISULFID        550
FT                   /note="Interchain"
FT                   /evidence="ECO:0000250"
FT   DISULFID        675..900
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         746..757
FT                   /note="Missing (in isoform Short)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_036680"
FT   HELIX           727..736
FT                   /evidence="ECO:0007829|PDB:4XST"
SQ   SEQUENCE   1383 AA;  156757 MW;  4B919566902A944A CRC64;
     MGSGRGCETT AVPLLMAVAV AGGTAGHLYP GEVCPGMDIR NNLTRLHELE NCSVIEGHLQ
     ILLMFKTRPE DFRDLSFPKL IMITDYLLLF RVYGLESLKD LFPNLTVIRG SRLFFNYALV
     IFEMVHLKEL GLYNLMNITR GSVRIEKNNE LCYLATIDWS RILDYVEDNY IVLNKDDNEE
     CGDVCPGTAK GKTNCPATVI NGQFVERCWT HSHCQKVCPT ICKSHGCTAE GLCCHKECLG
     NCSEPDDPTK CVACRNFYLD GQCVETCPPP YYHFQDWRCV NFSFCQDLHY KCRNSRKPGC
     HQYVIHNNKC IPECPSGYTM NSSNLMCTPC LGPCPKVCQI LEGEKTIDSV TSAQELRGCT
     VINGSLIINI RGGNNLAAEL EANLGLIEEI SGFLKIRRSY ALVSLSFFRK LHLIRGETLE
     IGNYSFYALD NQNLRQLWDW NKHNLTITQG KLFFHYNPKL CLSEIHKMEE VSGTKGRQER
     NDIALKTNGD QASCENELLK FSFIRTSFDK ILLRWEPYWP PDFRDLLGFM LFYKEAPYQN
     VTEFDGQDAC GSNSWTVVDI DPPQRSNDPK SQTPSHPGWL MRGLKPWTQY AIFVKTLVTF
     SDERRTYGAK SDIIYVQTDA TNPSVPLDPI SVSNSSSQII LKWKPPSDPN GNITHYLVYW
     ERQAEDSELF ELDYCLKGLK LPSRTWSPPF ESDDSQKHNQ SEYDDSASEC CSCPKTDSQI
     LKELEESSFR KTFEDYLHNV VFVPRKTSSG NGAEDTRPSR KRRSLEEVGN VTATTPTLPD
     FPNISSTIAP TSHEEHRPFE KVVNKESLVI SGLRHFTGYR IELQACNQDS PEERSGVAAY
     VSARTMPEAK ADDIVGPVTH EIFENNVVHL MWQEPKEPNG LIVLYEVSYR RYGDEELHLC
     VSRKHFALER GCRLRGLSPG NYSVRVRATS LAGNGSWTEP TYFYVTDYLD VPSNIAKIII
     GPLIFVFLFS VVIGSIYLFL RKRQPDGPMG PLYASSNPEY LSASDVFPSS VYVPDEWEVP
     REKITLLREL GQGSFGMVYE GNAKDIIKGE VETRVAVKTV NESASLRERI EFLNEASVMK
     GFTCHHVVRL LGVVSKGQPT LVVMELMAHG DLKSHLRSLR PDAENNPGRP PPTLQEMIQM
     TAEIADGMAY LNAKKFVHRD LAARNCMVAH DFTVKIGDFG MTRDIYETDY YRKGGKGLLP
     VRWMSPESLK DGVFTASSDM WSFGVVLWEI TSLAEQPYQG LSNEQVLKFV MDGGYLDPPD
     NCPERLTDLM RMCWQFNPKM RPTFLEIVNL LKDDLHPSFP EVSFFYSEEN KAPESEELEM
     EFEDMENVPL DRSSHCQREE AGCREGGSSL SIKRTYDEHI PYTHMNGGKK NGRVLTLPRS
     NPS
//
DBGET integrated database retrieval system