ID IGF1R_HUMAN Reviewed; 1367 AA. AC P08069; B1B5Y2; Q14CV2; Q9UCC0; DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1988, sequence version 1. DT 27-MAR-2024, entry version 251. DE RecName: Full=Insulin-like growth factor 1 receptor; DE EC=2.7.10.1; DE AltName: Full=Insulin-like growth factor I receptor; DE Short=IGF-I receptor; DE AltName: CD_antigen=CD221; DE Contains: DE RecName: Full=Insulin-like growth factor 1 receptor alpha chain; DE Contains: DE RecName: Full=Insulin-like growth factor 1 receptor beta chain; DE Flags: Precursor; GN Name=IGF1R; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 31-56; 446-453; RP 503-524; 561-579; 668-672 AND 721-729. RC TISSUE=Placenta; RX PubMed=2877871; DOI=10.1002/j.1460-2075.1986.tb04528.x; RA Ullrich A., Gray A., Tam A.W., Yang-Feng T., Tsubokawa M., Collins C., RA Henzel W., Bon T.L., Kathuria S., Chen E., Jacobs S., Francke U., RA Ramachandran J., Fujita-Yamaguchi Y.; RT "Insulin-like growth factor I receptor primary structure: comparison with RT insulin receptor suggests structural determinants that define functional RT specificity."; RL EMBO J. 5:2503-2512(1986). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=1316909; DOI=10.1016/s0021-9258(19)50083-7; RA Abbot A.M., Bueno R., Pedrini M.T., Murray J.M., Smith R.J.; RT "Insulin-like growth factor I receptor gene structure."; RL J. Biol. Chem. 267:10759-10763(1992). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Fetal brain; RA Nagase T., Kikuno R.F., Yamakawa H., Ohara O.; RL Submitted (FEB-2008) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS MET-388 AND HIS-605. RG NIEHS SNPs program; RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16572171; DOI=10.1038/nature04601; RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S., RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.; RT "Analysis of the DNA sequence and duplication history of human chromosome RT 15."; RL Nature 440:671-675(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-31. RX PubMed=1711844; DOI=10.1016/0006-291x(91)90654-p; RA Cooke D.W., Bankert L.A., Roberts C.T. Jr., Leroith D., Casella S.J.; RT "Analysis of the human type I insulin-like growth factor receptor promoter RT region."; RL Biochem. Biophys. Res. Commun. 177:1113-1120(1991). RN [8] RP PROTEIN SEQUENCE OF 31-45 AND 741-750, FUNCTION, AND FORMATION OF A HYBRID RP RECEPTOR WITH INSR. RC TISSUE=Placenta; RX PubMed=8257688; DOI=10.1021/bi00212a019; RA Kasuya J., Paz I.B., Maddux B.A., Goldfine I.D., Hefta S.A., RA Fujita-Yamaguchi Y.; RT "Characterization of human placental insulin-like growth factor-I/insulin RT hybrid receptors by protein microsequencing and purification."; RL Biochemistry 32:13531-13536(1993). RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1137-1193, AND TISSUE SPECIFICITY. RC TISSUE=Melanocyte; RX PubMed=8247543; RA Lee S.-T., Strunk K.M., Spritz R.A.; RT "A survey of protein tyrosine kinase mRNAs expressed in normal human RT melanocytes."; RL Oncogene 8:3403-3410(1993). RN [10] RP FUNCTION, SUBUNIT, AND AUTOPHOSPHORYLATION. RX PubMed=1846292; DOI=10.1021/bi00215a008; RA Tollefsen S.E., Stoszek R.M., Thompson K.; RT "Interaction of the alpha beta dimers of the insulin-like growth factor I RT receptor is required for receptor autophosphorylation."; RL Biochemistry 30:48-54(1991). RN [11] RP FUNCTION, AND FORMATION OF A HYBRID RECEPTOR WITH INSR. RX PubMed=8452530; DOI=10.1042/bj2900419; RA Soos M.A., Field C.E., Siddle K.; RT "Purified hybrid insulin/insulin-like growth factor-I receptors bind RT insulin-like growth factor-I, but not insulin, with high affinity."; RL Biochem. J. 290:419-426(1993). RN [12] RP FUNCTION, CATALYTIC ACTIVITY, AND AUTOPHOSPHORYLATION. RX PubMed=7679099; DOI=10.1016/s0021-9258(18)53824-2; RA Kato H., Faria T.N., Stannard B., Roberts C.T. Jr., LeRoith D.; RT "Role of tyrosine kinase activity in signal transduction by the insulin- RT like growth factor-I (IGF-I) receptor. Characterization of kinase-deficient RT IGF-I receptors and the action of an IGF-I-mimetic antibody (alpha IR-3)."; RL J. Biol. Chem. 268:2655-2661(1993). RN [13] RP INTERACTION WITH IRS1; SHC1 AND PIK3R1, MUTAGENESIS OF TYR-980 AND RP LYS-1033, AND PHOSPHORYLATION AT TYR-980. RX PubMed=7541045; DOI=10.1074/jbc.270.26.15639; RA Craparo A., O'Neill T.J., Gustafson T.A.; RT "Non-SH2 domains within insulin receptor substrate-1 and SHC mediate their RT phosphotyrosine-dependent interaction with the NPEY motif of the insulin- RT like growth factor I receptor."; RL J. Biol. Chem. 270:15639-15643(1995). RN [14] RP FORMATION OF A HYBRID RECEPTOR WITH INSR, AND TISSUE SPECIFICITY. RX PubMed=9355755; DOI=10.1042/bj3270209; RA Bailyes E.M., Nave B.T., Soos M.A., Orr S.R., Hayward A.C., Siddle K.; RT "Insulin receptor/IGF-I receptor hybrids are widely distributed in RT mammalian tissues: quantification of individual receptor species by RT selective immunoprecipitation and immunoblotting."; RL Biochem. J. 327:209-215(1997). RN [15] RP INTERACTION WITH 14-3-3 PROTEINS. RX PubMed=9581554; DOI=10.1042/bj3270765; RA Furlanetto R.W., Dey B.R., Lopaczynski W., Nissley S.P.; RT "14-3-3 proteins interact with the insulin-like growth factor receptor but RT not the insulin receptor."; RL Biochem. J. 327:765-771(1997). RN [16] RP FORMATION OF A HYBRID RECEPTOR WITH INSR, AND TISSUE SPECIFICITY. RX PubMed=9202395; DOI=10.1016/s0303-7207(97)04050-1; RA Federici M., Porzio O., Zucaro L., Fusco A., Borboni P., Lauro D., RA Sesti G.; RT "Distribution of insulin/insulin-like growth factor-I hybrid receptors in RT human tissues."; RL Mol. Cell. Endocrinol. 129:121-126(1997). RN [17] RP INTERACTION WITH SOCS1 AND SOCS2. RX PubMed=9727029; DOI=10.1074/jbc.273.37.24095; RA Dey B.R., Spence S.L., Nissley P., Furlanetto R.W.; RT "Interaction of human suppressor of cytokine signaling (SOCS)-2 with the RT insulin-like growth factor-I receptor."; RL J. Biol. Chem. 273:24095-24101(1998). RN [18] RP INTERACTION WITH ARRB1 AND ARRB2. RX PubMed=9822622; DOI=10.1074/jbc.273.48.31640; RA Lin F.-T., Daaka Y., Lefkowitz R.J.; RT "beta-arrestins regulate mitogenic signaling and clathrin-mediated RT endocytosis of the insulin-like growth factor I receptor."; RL J. Biol. Chem. 273:31640-31643(1998). RN [19] RP FUNCTION IN CANCER. RX PubMed=10579905; DOI=10.1006/excr.1999.4667; RA Baserga R.; RT "The IGF-I receptor in cancer research."; RL Exp. Cell Res. 253:1-6(1999). RN [20] RP INTERACTION WITH GRB10, AND MUTAGENESIS OF TYR-980; TYR-1280; TYR-1281 AND RP TYR-1346. RX PubMed=10454568; DOI=10.1128/mcb.19.9.6217; RA Wang J., Dai H., Yousaf N., Moussaif M., Deng Y., Boufelliga A., RA Swamy O.R., Leone M.E., Riedel H.; RT "Grb10, a positive, stimulatory signaling adapter in platelet-derived RT growth factor BB-, insulin-like growth factor I-, and insulin-mediated RT mitogenesis."; RL Mol. Cell. Biol. 19:6217-6228(1999). RN [21] RP INTERACTION WITH SOCS3. RX PubMed=11071852; DOI=10.1006/bbrc.2000.3762; RA Dey B.R., Furlanetto R.W., Nissley P.; RT "Suppressor of cytokine signaling (SOCS)-3 protein interacts with the RT insulin-like growth factor-I receptor."; RL Biochem. Biophys. Res. Commun. 278:38-43(2000). RN [22] RP AUTOPHOSPHORYLATION. RX PubMed=11162456; DOI=10.1006/bbrc.2000.4046; RA Lopaczynski W., Terry C., Nissley P.; RT "Autophosphorylation of the insulin-like growth factor I receptor RT cytoplasmic domain."; RL Biochem. Biophys. Res. Commun. 279:955-960(2000). RN [23] RP FUNCTION IN ACTIVATION OF STAT3. RX PubMed=10747872; DOI=10.1074/jbc.m000089200; RA Zong C.S., Chan J., Levy D.E., Horvath C., Sadowski H.B., Wang L.H.; RT "Mechanism of STAT3 activation by insulin-like growth factor I receptor."; RL J. Biol. Chem. 275:15099-15105(2000). RN [24] RP TISSUE SPECIFICITY. RX PubMed=12019176; RA Hellawell G.O., Turner G.D., Davies D.R., Poulsom R., Brewster S.F., RA Macaulay V.M.; RT "Expression of the type 1 insulin-like growth factor receptor is up- RT regulated in primary prostate cancer and commonly persists in metastatic RT disease."; RL Cancer Res. 62:2942-2950(2002). RN [25] RP FUNCTION, AND FORMATION OF A HYBRID RECEPTOR WITH INSR. RX PubMed=12138094; DOI=10.1074/jbc.m202766200; RA Pandini G., Frasca F., Mineo R., Sciacca L., Vigneri R., Belfiore A.; RT "Insulin/insulin-like growth factor I hybrid receptors have different RT biological characteristics depending on the insulin receptor isoform RT involved."; RL J. Biol. Chem. 277:39684-39695(2002). RN [26] RP INTERACTION WITH RACK1. RX PubMed=11884618; DOI=10.1128/mcb.22.7.2345-2365.2002; RA Hermanto U., Zong C.S., Li W., Wang L.H.; RT "RACK1, an insulin-like growth factor I (IGF-I) receptor-interacting RT protein, modulates IGF-I-dependent integrin signaling and promotes cell RT spreading and contact with extracellular matrix."; RL Mol. Cell. Biol. 22:2345-2365(2002). RN [27] RP FUNCTION, AND INTERACTION WITH MAP3K5. RX PubMed=12556535; DOI=10.1074/jbc.m211398200; RA Galvan V., Logvinova A., Sperandio S., Ichijo H., Bredesen D.E.; RT "Type 1 insulin-like growth factor receptor (IGF-IR) signaling inhibits RT apoptosis signal-regulating kinase 1 (ASK1)."; RL J. Biol. Chem. 278:13325-13332(2003). RN [28] RP UBIQUITINATION BY MDM2, AND INTERACTION WITH MDM2. RX PubMed=12821780; DOI=10.1073/pnas.1431613100; RA Girnita L., Girnita A., Larsson O.; RT "Mdm2-dependent ubiquitination and degradation of the insulin-like growth RT factor 1 receptor."; RL Proc. Natl. Acad. Sci. U.S.A. 100:8247-8252(2003). RN [29] RP ACTIVITY REGULATION. RX PubMed=14729630; DOI=10.1158/0008-5472.can-03-2522; RA Girnita A., Girnita L., del Prete F., Bartolazzi A., Larsson O., RA Axelson M.; RT "Cyclolignans as inhibitors of the insulin-like growth factor-1 receptor RT and malignant cell growth."; RL Cancer Res. 64:236-242(2004). RN [30] RP INTERACTION WITH ARRB1 AND ARRB2. RX PubMed=15878855; DOI=10.1074/jbc.m501129200; RA Girnita L., Shenoy S.K., Sehat B., Vasilcanu R., Girnita A., RA Lefkowitz R.J., Larsson O.; RT "{beta}-Arrestin is crucial for ubiquitination and down-regulation of the RT insulin-like growth factor-1 receptor by acting as adaptor for the MDM2 E3 RT ligase."; RL J. Biol. Chem. 280:24412-24419(2005). RN [31] RP INTERACTION WITH STAT3. RX PubMed=15998644; DOI=10.1074/jbc.m501316200; RA Yadav A., Kalita A., Dhillon S., Banerjee K.; RT "JAK/STAT3 pathway is involved in survival of neurons in response to RT insulin-like growth factor and negatively regulated by suppressor of RT cytokine signaling-3."; RL J. Biol. Chem. 280:31830-31840(2005). RN [32] RP FUNCTION, AND FORMATION OF A HYBRID RECEPTOR WITH INSR. RX PubMed=16831875; DOI=10.1074/jbc.m605189200; RA Slaaby R., Schaeffer L., Lautrup-Larsen I., Andersen A.S., Shaw A.C., RA Mathiasen I.S., Brandt J.; RT "Hybrid receptors formed by insulin receptor (IR) and insulin-like growth RT factor I receptor (IGF-IR) have low insulin and high IGF-1 affinity RT irrespective of the IR splice variant."; RL J. Biol. Chem. 281:25869-25874(2006). RN [33] RP SUBCELLULAR LOCATION, AND PROTEOLYTIC PROCESSING. RX PubMed=17524361; DOI=10.1016/j.bbrc.2007.05.062; RA McElroy B., Powell J.C., McCarthy J.V.; RT "The insulin-like growth factor 1 (IGF-1) receptor is a substrate for RT gamma-secretase-mediated intramembrane proteolysis."; RL Biochem. Biophys. Res. Commun. 358:1136-1141(2007). RN [34] RP REVIEW ON IGF1R IN CANCER. RX PubMed=17624760; DOI=10.1016/j.ejca.2007.05.021; RA Hartog H., Wesseling J., Boezen H.M., van der Graaf W.T.; RT "The insulin-like growth factor 1 receptor in cancer: old focus, new RT future."; RL Eur. J. Cancer 43:1895-1904(2007). RN [35] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [36] RP BINDING TO IGF1, AND IDENTIFICATION IN A COMPLEX WITH INTEGRIN AND IGF1. RX PubMed=19578119; DOI=10.1074/jbc.m109.013201; RA Saegusa J., Yamaji S., Ieguchi K., Wu C.Y., Lam K.S., Liu F.T., RA Takada Y.K., Takada Y.; RT "The direct binding of insulin-like growth factor-1 (IGF-1) to integrin RT alphavbeta3 is involved in IGF-1 signaling."; RL J. Biol. Chem. 284:24106-24114(2009). RN [37] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [38] RP SUMOYLATION. RX PubMed=20596523; DOI=10.1371/journal.pone.0011332; RA Del Rincon S.V., Rogers J., Widschwendter M., Sun D., Sieburg H.B., RA Spruck C.; RT "Development and validation of a method for profiling post-translational RT modification activities using protein microarrays."; RL PLoS ONE 5:E11332-E11332(2010). RN [39] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [40] RP UBIQUITINATION AT LYS-1168 AND LYS-1171. RX PubMed=21994939; DOI=10.1074/jbc.m111.288514; RA Mao Y., Shang Y., Pham V.C., Ernst J.A., Lill J.R., Scales S.J., Zha J.; RT "Polyubiquitination of insulin-like growth factor I receptor (IGF-IR) RT activation loop promotes antibody-induced receptor internalization and RT down-regulation."; RL J. Biol. Chem. 286:41852-41861(2011). RN [41] RP BINDING TO IGF1, AND IDENTIFICATION IN A COMPLEX WITH INTEGRIN AND IGF1. RX PubMed=22351760; DOI=10.1074/jbc.m111.304170; RA Fujita M., Ieguchi K., Davari P., Yamaji S., Taniguchi Y., Sekiguchi K., RA Takada Y.K., Takada Y.; RT "Cross-talk between integrin alpha6beta4 and insulin-like growth factor-1 RT receptor (IGF1R) through direct alpha6beta4 binding to IGF1 and subsequent RT alpha6beta4-IGF1-IGF1R ternary complex formation in anchorage-independent RT conditions."; RL J. Biol. Chem. 287:12491-12500(2012). RN [42] RP INTERACTION WITH ZFAND2B. RX PubMed=26692333; DOI=10.1038/nm.4013; RA Osorio F.G., Soria-Valles C., Santiago-Fernandez O., Bernal T., RA Mittelbrunn M., Colado E., Rodriguez F., Bonzon-Kulichenko E., Vazquez J., RA Porta-de-la-Riva M., Ceron J., Fueyo A., Li J., Green A.R., Freije J.M., RA Lopez-Otin C.; RT "Loss of the proteostasis factor AIRAPL causes myeloid transformation by RT deregulating IGF-1 signaling."; RL Nat. Med. 22:91-96(2016). RN [43] RP INTERACTION WITH HRSV FUSION GLYCOPROTEIN F1/F2 HETERODIMER (MICROBIAL RP INFECTION). RX PubMed=32494007; DOI=10.1038/s41586-020-2369-7; RA Griffiths C.D., Bilawchuk L.M., McDonough J.E., Jamieson K.C., Elawar F., RA Cen Y., Duan W., Lin C., Song H., Casanova J.L., Ogg S., Jensen L.D., RA Thienpont B., Kumar A., Hobman T.C., Proud D., Moraes T.J., Marchant D.J.; RT "IGF1R is an entry receptor for respiratory syncytial virus."; RL Nature 583:615-619(2020). RN [44] RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 31-492, DISULFIDE BONDS, AND RP GLYCOSYLATION AT ASN-51; ASN-135; ASN-244 AND ASN-314. RX PubMed=9690478; DOI=10.1038/28668; RA Garrett T.P., McKern N.M., Lou M., Frenkel M.J., Bentley J.D., RA Lovrecz G.O., Elleman T.C., Cosgrove L.J., Ward C.W.; RT "Crystal structure of the first three domains of the type-1 insulin-like RT growth factor receptor."; RL Nature 394:395-399(1998). RN [45] RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 988-1286 IN COMPLEX WITH AMP-PCP RP AND PEPTIDE SUBSTRATE, CATALYTIC ACTIVITY, ACTIVE SITE, ACTIVITY RP REGULATION, IDENTIFICATION BY MASS SPECTROMETRY, AND PHOSPHORYLATION AT RP TYR-1161; TYR-1165 AND TYR-1166. RX PubMed=11694888; DOI=10.1038/nsb721; RA Favelyukis S., Till J.H., Hubbard S.R., Miller W.T.; RT "Structure and autoregulation of the insulin-like growth factor 1 receptor RT kinase."; RL Nat. Struct. Biol. 8:1058-1063(2001). RN [46] RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 981-1286 IN COMPLEX WITH ANP, RP AUTOPHOSPHORYLATION, ACTIVE SITE, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=11591350; DOI=10.1016/s0969-2126(01)00655-4; RA Pautsch A., Zoephel A., Ahorn H., Spevak W., Hauptmann R., Nar H.; RT "Crystal structure of bisphosphorylated IGF-1 receptor kinase: insight into RT domain movements upon kinase activation."; RL Structure 9:955-965(2001). RN [47] RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 974-1294. RX PubMed=12138114; DOI=10.1074/jbc.m205580200; RA Munshi S., Kornienko M., Hall D.L., Reid J.C., Waxman L., Stirdivant S.M., RA Darke P.L., Kuo L.C.; RT "Crystal structure of the Apo, unactivated insulin-like growth factor-1 RT receptor kinase. Implication for inhibitor specificity."; RL J. Biol. Chem. 277:38797-38802(2002). RN [48] RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 974-1294. RX PubMed=14501110; DOI=10.1107/s0907444903015415; RA Munshi S., Hall D.L., Kornienko M., Darke P.L., Kuo L.C.; RT "Structure of apo, unactivated insulin-like growth factor-1 receptor kinase RT at 1.5 A resolution."; RL Acta Crystallogr. D 59:1725-1730(2003). RN [49] RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 982-1286 IN COMPLEX WITH RP BENZIMIDAZOLE PYRIDINONE INHIBITOR, CATALYTIC ACTIVITY, AND ACTIVITY RP REGULATION. RX PubMed=17317169; DOI=10.1016/j.bmcl.2007.01.102; RA Velaparthi U., Wittman M., Liu P., Stoffan K., Zimmermann K., Sang X., RA Carboni J., Li A., Attar R., Gottardis M., Greer A., Chang C.Y., RA Jacobsen B.L., Sack J.S., Sun Y., Langley D.R., Balasubramanian B., RA Vyas D.; RT "Discovery and initial SAR of 3-(1H-benzo[d]imidazol-2-yl)pyridin-2(1H)- RT ones as inhibitors of insulin-like growth factor 1-receptor (IGF-1R)."; RL Bioorg. Med. Chem. Lett. 17:2317-2321(2007). RN [50] RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 981-1286, AND PHOSPHORYLATION AT RP TYR-1161; TYR-1165 AND TYR-1166. RX PubMed=18501599; DOI=10.1016/j.bmcl.2008.04.044; RA Mayer S.C., Banker A.L., Boschelli F., Di L., Johnson M., Kenny C.H., RA Krishnamurthy G., Kutterer K., Moy F., Petusky S., Ravi M., Tkach D., RA Tsou H.R., Xu W.; RT "Lead identification to generate isoquinolinedione inhibitors of insulin- RT like growth factor receptor (IGF-1R) for potential use in cancer RT treatment."; RL Bioorg. Med. Chem. Lett. 18:3641-3645(2008). RN [51] RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 986-1286 IN COMPLEX WITH RP INHIBITOR PQIP, SUBUNIT, AUTOPHOSPHORYLATION, CATALYTIC ACTIVITY, ACTIVE RP SITE, AND ACTIVITY REGULATION. RX PubMed=18566589; DOI=10.1038/emboj.2008.116; RA Wu J., Li W., Craddock B.P., Foreman K.W., Mulvihill M.J., Ji Q.S., RA Miller W.T., Hubbard S.R.; RT "Small-molecule inhibition and activation-loop trans-phosphorylation of the RT IGF1 receptor."; RL EMBO J. 27:1985-1994(2008). RN [52] RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 981-1286 IN COMPLEX WITH RP 3-CYANOQUINOLINE INHIBITOR, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND RP PHOSPHORYLATION AT TYR-1161; TYR-1165 AND TYR-1166. RX PubMed=19041240; DOI=10.1016/j.bmcl.2008.11.037; RA Miller L.M., Mayer S.C., Berger D.M., Boschelli D.H., Boschelli F., Di L., RA Du X., Dutia M., Floyd M.B., Johnson M., Kenny C.H., Krishnamurthy G., RA Moy F., Petusky S., Tkach D., Torres N., Wu B., Xu W.; RT "Lead identification to generate 3-cyanoquinoline inhibitors of insulin- RT like growth factor receptor (IGF-1R) for potential use in cancer RT treatment."; RL Bioorg. Med. Chem. Lett. 19:62-66(2009). RN [53] RP X-RAY CRYSTALLOGRAPHY (2.08 ANGSTROMS) OF 982-1286 IN COMPLEX WITH RP BMS-754807, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION. RX PubMed=19778024; DOI=10.1021/jm900786r; RA Wittman M.D., Carboni J.M., Yang Z., Lee F.Y., Antman M., Attar R., RA Balimane P., Chang C., Chen C., Discenza L., Frennesson D., Gottardis M.M., RA Greer A., Hurlburt W., Johnson W., Langley D.R., Li A., Li J., Liu P., RA Mastalerz H., Mathur A., Menard K., Patel K., Sack J., Sang X., RA Saulnier M., Smith D., Stefanski K., Trainor G., Velaparthi U., Zhang G., RA Zimmermann K., Vyas D.M.; RT "Discovery of a 2,4-disubstituted pyrrolo[1,2-f][1,2,4]triazine inhibitor RT (BMS-754807) of insulin-like growth factor receptor (IGF-1R) kinase in RT clinical development."; RL J. Med. Chem. 52:7360-7363(2009). RN [54] RP X-RAY CRYSTALLOGRAPHY (1.79 ANGSTROMS) OF 983-1286 IN COMPLEX WITH RP MSC1609119A-1, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION. RX DOI=10.1021/ml100044h; RA Heinrich T., Graedler U., Boettcher H., Blaukat A., Shutes A.; RT "Allosteric IGF-1R Inhibitors."; RL ACS Med. Chem. Lett. 1:199-203(2010). RN [55] RP X-RAY CRYSTALLOGRAPHY (2.11 ANGSTROMS) OF 982-1286 IN COMPLEXES WITH RP INHIBITORS, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION. RX PubMed=20675137; DOI=10.1016/j.bmcl.2010.07.045; RA Sampognaro A.J., Wittman M.D., Carboni J.M., Chang C., Greer A.F., RA Hurlburt W.W., Sack J.S., Vyas D.M.; RT "Proline isosteres in a series of 2,4-disubstituted pyrrolo[1,2- RT f][1,2,4]triazine inhibitors of IGF-1R kinase and IR kinase."; RL Bioorg. Med. Chem. Lett. 20:5027-5030(2010). RN [56] RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 951-1286 IN COMPLEX WITH RP BIS-AZAINDOLE INHIBITOR, AUTOPHOSPHORYLATION, AND ACTIVITY REGULATION. RX PubMed=20545947; DOI=10.1111/j.1747-0285.2010.00991.x; RA Nemecek C., Metz W.A., Wentzler S., Ding F.X., Venot C., Souaille C., RA Dagallier A., Maignan S., Guilloteau J.P., Bernard F., Henry A., RA Grapinet S., Lesuisse D.; RT "Design of potent IGF1-R inhibitors related to bis-azaindoles."; RL Chem. Biol. Drug Des. 76:100-106(2010). RN [57] RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 982-1286 IN COMPLEX WITH RP HYDANTOIN DERIVATIVE, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION. RX PubMed=21441024; DOI=10.1016/j.bmcl.2011.03.003; RA Lesuisse D., Mauger J., Nemecek C., Maignan S., Boiziau J., Harlow G., RA Hittinger A., Ruf S., Strobel H., Nair A., Ritter K., Malleron J.L., RA Dagallier A., El-Ahmad Y., Guilloteau J.P., Guizani H., Bouchard H., RA Venot C.; RT "Discovery of the first non-ATP competitive IGF-1R kinase inhibitors: RT advantages in comparison with competitive inhibitors."; RL Bioorg. Med. Chem. Lett. 21:2224-2228(2011). RN [58] RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 988-1286 IN COMPLEX WITH RP 2,4-BIS-ARYLAMINO-1,3-PYRIMIDINE INHIBITOR, CATALYTIC ACTIVITY, AND RP ACTIVITY REGULATION. RX PubMed=21414779; DOI=10.1016/j.bmcl.2011.02.075; RA Buchanan J.L., Newcomb J.R., Carney D.P., Chaffee S.C., Chai L., RA Cupples R., Epstein L.F., Gallant P., Gu Y., Harmange J.C., Hodge K., RA Houk B.E., Huang X., Jona J., Joseph S., Jun H.T., Kumar R., Li C., Lu J., RA Menges T., Morrison M.J., Novak P.M., van der Plas S., Radinsky R., RA Rose P.E., Sawant S., Sun J.R., Surapaneni S., Turci S.M., Xu K., Yanez E., RA Zhao H., Zhu X.; RT "Discovery of 2,4-bis-arylamino-1,3-pyrimidines as insulin-like growth RT factor-1 receptor (IGF-1R) inhibitors."; RL Bioorg. Med. Chem. Lett. 21:2394-2399(2011). RN [59] RP VARIANTS IGF1RES GLN-138 AND ASN-145, AND CHARACTERIZATION OF VARIANTS RP IGF1RES GLN-138 AND ASN-145. RX PubMed=14657428; DOI=10.1056/nejmoa010107; RG The intrauterine growth retardation (IUGR) study group; RA Abuzzahab M.J., Schneider A., Goddard A., Grigorescu F., Lautier C., RA Keller E., Kiess W., Klammt J., Kratzsch J., Osgood D., Pfaeffle R., RA Raile K., Seidel B., Smith R.J., Chernausek S.D.; RT "IGF-I receptor mutations resulting in intrauterine and postnatal growth RT retardation."; RL N. Engl. J. Med. 349:2211-2222(2003). RN [60] RP VARIANT IGF1RES GLN-739, AND CHARACTERIZATION OF VARIANT IGF1RES GLN-739. RX PubMed=15928254; DOI=10.1210/jc.2004-1947; RA Kawashima Y., Kanzaki S., Yang F., Kinoshita T., Hanaki K., Nagaishi J., RA Ohtsuka Y., Hisatome I., Ninomoya H., Nanba E., Fukushima T., Takahashi S.; RT "Mutation at cleavage site of insulin-like growth factor receptor in a RT short-stature child born with intrauterine growth retardation."; RL J. Clin. Endocrinol. Metab. 90:4679-4687(2005). RN [61] RP VARIANTS [LARGE SCALE ANALYSIS] LEU-105; HIS-437; HIS-595; SER-857; RP THR-1338 AND VAL-1347. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., RA Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). RN [62] RP VARIANTS IGF1RES TYR-359; CYS-865; SER-1256 AND CYS-1337, AND RP CHARACTERIZATION OF VARIANTS IGF1RES TYR-359; CYS-865; SER-1256 AND RP CYS-1337. RX PubMed=25040157; DOI=10.1111/cen.12555; RA Juanes M., Guercio G., Marino R., Berensztein E., Warman D.M., Ciaccio M., RA Gil S., Bailez M., Rivarola M.A., Belgorosky A.; RT "Three novel IGF1R mutations in microcephalic patients with prenatal and RT postnatal growth impairment."; RL Clin. Endocrinol. (Oxf.) 82:704-711(2015). CC -!- FUNCTION: Receptor tyrosine kinase which mediates actions of insulin- CC like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and CC insulin (INS) with a lower affinity. The activated IGF1R is involved in CC cell growth and survival control. IGF1R is crucial for tumor CC transformation and survival of malignant cell. Ligand binding activates CC the receptor kinase, leading to receptor autophosphorylation, and CC tyrosines phosphorylation of multiple substrates, that function as CC signaling adapter proteins including, the insulin-receptor substrates CC (IRS1/2), Shc and 14-3-3 proteins. Phosphorylation of IRSs proteins CC lead to the activation of two main signaling pathways: the PI3K-AKT/PKB CC pathway and the Ras-MAPK pathway. The result of activating the MAPK CC pathway is increased cellular proliferation, whereas activating the CC PI3K pathway inhibits apoptosis and stimulates protein synthesis. CC Phosphorylated IRS1 can activate the 85 kDa regulatory subunit of PI3K CC (PIK3R1), leading to activation of several downstream substrates, CC including protein AKT/PKB. AKT phosphorylation, in turn, enhances CC protein synthesis through mTOR activation and triggers the CC antiapoptotic effects of IGFIR through phosphorylation and inactivation CC of BAD. In parallel to PI3K-driven signaling, recruitment of Grb2/SOS CC by phosphorylated IRS1 or Shc leads to recruitment of Ras and CC activation of the ras-MAPK pathway. In addition to these two main CC signaling pathways IGF1R signals also through the Janus kinase/signal CC transducer and activator of transcription pathway (JAK/STAT). CC Phosphorylation of JAK proteins can lead to phosphorylation/activation CC of signal transducers and activators of transcription (STAT) proteins. CC In particular activation of STAT3, may be essential for the CC transforming activity of IGF1R. The JAK/STAT pathway activates gene CC transcription and may be responsible for the transforming activity. JNK CC kinases can also be activated by the IGF1R. IGF1 exerts inhibiting CC activities on JNK activation via phosphorylation and inhibition of CC MAP3K5/ASK1, which is able to directly associate with the IGF1R. CC -!- FUNCTION: When present in a hybrid receptor with INSR, binds IGF1. CC PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR CC isoform Long are activated with a high affinity by IGF1, with low CC affinity by IGF2 and not significantly activated by insulin, and that CC hybrid receptors composed of IGF1R and INSR isoform Short are activated CC by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that CC hybrid receptors composed of IGF1R and INSR isoform Long and hybrid CC receptors composed of IGF1R and INSR isoform Short have similar binding CC characteristics, both bind IGF1 and have a low affinity for insulin. 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 ECO:0000269|PubMed:11694888, ECO:0000269|PubMed:17317169, CC ECO:0000269|PubMed:18566589, ECO:0000269|PubMed:19041240, CC ECO:0000269|PubMed:19778024, ECO:0000269|PubMed:20675137, CC ECO:0000269|PubMed:21414779, ECO:0000269|PubMed:21441024, CC ECO:0000269|PubMed:7679099, ECO:0000269|Ref.54}; CC -!- ACTIVITY REGULATION: Activated by autophosphorylation at Tyr-1165, Tyr- CC 1161 and Tyr-1166 on the kinase activation loop; phosphorylation at all CC three tyrosine residues is required for optimal kinase activity. CC Inhibited by MSC1609119A-1, BMS-754807, PQIP, benzimidazole pyridinone, CC isoquinolinedione, bis-azaindole, 3-cyanoquinoline, 2,4-bis-arylamino- CC 1,3-pyrimidine, pyrrolopyrimidine, pyrrole-5-carboxaldehyde, CC picropodophyllin (PPP), tyrphostin derivatives. While most inhibitors CC bind to the ATP binding pocket, MSC1609119A-1 functions as allosteric CC inhibitor and binds close to the DFG motif and the activation loop. CC {ECO:0000269|PubMed:11694888, ECO:0000269|PubMed:14729630, CC ECO:0000269|PubMed:17317169, ECO:0000269|PubMed:18566589, CC ECO:0000269|PubMed:19041240, ECO:0000269|PubMed:19778024, CC ECO:0000269|PubMed:20545947, ECO:0000269|PubMed:20675137, CC ECO:0000269|PubMed:21414779, ECO:0000269|PubMed:21441024, CC ECO:0000269|Ref.54}. CC -!- SUBUNIT: Tetramer of 2 alpha and 2 beta chains linked by disulfide CC bonds. The alpha chains contribute to the formation of the ligand- CC binding domain, while the beta chain carries the kinase domain. CC Interacts with PIK3R1 and with the PTB/PID domains of IRS1 and SHC1 in CC vitro when autophosphorylated on tyrosine residues. Forms a hybrid CC receptor with INSR, the hybrid is a tetramer consisting of 1 alpha CC chain and 1 beta chain of INSR and 1 alpha chain and 1 beta chain of CC IGF1R. Interacts with ARRB1 and ARRB2. Interacts with GRB10. Interacts CC with RACK1. Interacts with SOCS1, SOCS2 and SOCS3. Interacts with 14-3- CC 3 proteins. Interacts with NMD2. Interacts with MAP3K5. Interacts with CC STAT3. Found in a ternary complex with IGF1 and ITGAV:ITGB3 or CC ITGA6:ITGB4 (PubMed:19578119, PubMed:22351760). Interacts (nascent CC precursor form) with ZFAND2B (PubMed:26692333). CC {ECO:0000269|PubMed:10454568, ECO:0000269|PubMed:11071852, CC ECO:0000269|PubMed:11591350, ECO:0000269|PubMed:11694888, CC ECO:0000269|PubMed:11884618, ECO:0000269|PubMed:12556535, CC ECO:0000269|PubMed:12821780, ECO:0000269|PubMed:15878855, CC ECO:0000269|PubMed:15998644, ECO:0000269|PubMed:17317169, CC ECO:0000269|PubMed:1846292, ECO:0000269|PubMed:18566589, CC ECO:0000269|PubMed:19041240, ECO:0000269|PubMed:19578119, CC ECO:0000269|PubMed:19778024, ECO:0000269|PubMed:20545947, CC ECO:0000269|PubMed:21414779, ECO:0000269|PubMed:21441024, CC ECO:0000269|PubMed:22351760, ECO:0000269|PubMed:26692333, CC ECO:0000269|PubMed:7541045, ECO:0000269|PubMed:9581554, CC ECO:0000269|PubMed:9727029, ECO:0000269|PubMed:9822622, CC ECO:0000269|Ref.54}. CC -!- SUBUNIT: (Microbial infection) Interacts with human respiratory CC syncytial virus (HRSV) fusion glycoprotein F1/F2 heterodimer. CC {ECO:0000269|PubMed:32494007}. CC -!- INTERACTION: CC P08069; Q9NZN5: ARHGEF12; NbExp=7; IntAct=EBI-475981, EBI-821440; CC P08069; PRO_0000004724 [P49913]: CAMP; NbExp=3; IntAct=EBI-475981, EBI-6378485; CC P08069; P41240: CSK; NbExp=5; IntAct=EBI-475981, EBI-1380630; CC P08069; P35222: CTNNB1; NbExp=3; IntAct=EBI-475981, EBI-491549; CC P08069; P05019: IGF1; NbExp=8; IntAct=EBI-475981, EBI-7902275; CC P08069; P08069: IGF1R; NbExp=6; IntAct=EBI-475981, EBI-475981; CC P08069; P06213: INSR; NbExp=5; IntAct=EBI-475981, EBI-475899; CC P08069; P05556: ITGB1; NbExp=2; IntAct=EBI-475981, EBI-703066; CC P08069; Q9Y2W7: KCNIP3; NbExp=6; IntAct=EBI-475981, EBI-751501; CC P08069; Q9UJU2: LEF1; NbExp=5; IntAct=EBI-475981, EBI-926131; CC P08069; P27986: PIK3R1; NbExp=6; IntAct=EBI-475981, EBI-79464; CC P08069; O00459: PIK3R2; NbExp=3; IntAct=EBI-475981, EBI-346930; CC P08069; P35813: PPM1A; NbExp=2; IntAct=EBI-475981, EBI-989143; CC P08069; P18031: PTPN1; NbExp=4; IntAct=EBI-475981, EBI-968788; CC P08069; Q06124: PTPN11; NbExp=5; IntAct=EBI-475981, EBI-297779; CC P08069; P29350: PTPN6; NbExp=3; IntAct=EBI-475981, EBI-78260; CC P08069; P29353-2: SHC1; NbExp=2; IntAct=EBI-475981, EBI-1000553; CC P08069; Q01995: TAGLN; NbExp=2; IntAct=EBI-475981, EBI-1054248; CC P08069; P62258: YWHAE; NbExp=2; IntAct=EBI-475981, EBI-356498; CC P08069; Q64010: Crk; Xeno; NbExp=3; IntAct=EBI-475981, EBI-2906540; CC P08069; P01317: INS; Xeno; NbExp=4; IntAct=EBI-475981, EBI-3989070; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17524361}; CC Single-pass type I membrane protein {ECO:0000269|PubMed:17524361}. CC -!- TISSUE SPECIFICITY: Found as a hybrid receptor with INSR in muscle, CC heart, kidney, adipose tissue, skeletal muscle, hepatoma, fibroblasts, CC spleen and placenta (at protein level). Expressed in a variety of CC tissues. Overexpressed in tumors, including melanomas, cancers of the CC colon, pancreas prostate and kidney. {ECO:0000269|PubMed:12019176, CC ECO:0000269|PubMed:8247543, ECO:0000269|PubMed:9202395, CC ECO:0000269|PubMed:9355755}. CC -!- PTM: Autophosphorylated on tyrosine residues in response to ligand CC binding. Autophosphorylation occurs in trans, i.e. one subunit of the CC dimeric receptor phosphorylates tyrosine residues on the other subunit. CC Autophosphorylation occurs in a sequential manner; Tyr-1165 is CC predominantly phosphorylated first, followed by phosphorylation of Tyr- CC 1161 and Tyr-1166. While every single phosphorylation increases kinase CC activity, all three tyrosine residues in the kinase activation loop CC (Tyr-1165, Tyr-1161 and Tyr-1166) have to be phosphorylated for optimal CC activity. Can be autophosphorylated at additional tyrosine residues (in CC vitro). Autophosphorylated is followed by phosphorylation of CC juxtamembrane tyrosines and C-terminal serines. Phosphorylation of Tyr- CC 980 is required for IRS1- and SHC1-binding. Phosphorylation of Ser-1278 CC by GSK-3beta restrains kinase activity and promotes cell surface CC expression, it requires a priming phosphorylation at Ser-1282. CC Dephosphorylated by PTPN1 (By similarity). {ECO:0000250}. CC -!- PTM: Polyubiquitinated at Lys-1168 and Lys-1171 through both 'Lys-48' CC and 'Lys-29' linkages, promoting receptor endocytosis and subsequent CC degradation by the proteasome. Ubiquitination is facilitated by pre- CC existing phosphorylation. {ECO:0000269|PubMed:11694888, CC ECO:0000269|PubMed:12821780, ECO:0000269|PubMed:18501599, CC ECO:0000269|PubMed:19041240, ECO:0000269|PubMed:21994939, CC ECO:0000269|PubMed:7541045}. CC -!- PTM: Sumoylated with SUMO1. {ECO:0000269|PubMed:20596523}. CC -!- PTM: Controlled by regulated intramembrane proteolysis (RIP). Undergoes CC metalloprotease-dependent constitutive ectodomain shedding to produce a CC membrane-anchored 52 kDa C-Terminal fragment which is further processed CC by presenilin gamma-secretase to yield an intracellular 50 kDa CC fragment. {ECO:0000269|PubMed:17524361}. CC -!- DISEASE: Insulin-like growth factor 1 resistance (IGF1RES) CC [MIM:270450]: A disorder characterized by intrauterine growth CC retardation, poor postnatal growth and increased plasma IGF1 levels. CC {ECO:0000269|PubMed:14657428, ECO:0000269|PubMed:15928254, CC ECO:0000269|PubMed:25040157}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. Insulin receptor subfamily. {ECO:0000255|PROSITE- CC ProRule:PRU00159}. CC -!- SEQUENCE CAUTION: CC Sequence=BAG11657.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/40928/IGF1R"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/igf1r/"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=IGF-1 receptor entry; CC URL="https://en.wikipedia.org/wiki/IGF-1_receptor"; 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; X04434; CAA28030.1; -; mRNA. DR EMBL; AB425196; BAG11657.1; ALT_INIT; mRNA. DR EMBL; AY332722; AAP81165.1; -; Genomic_DNA. DR EMBL; AC055807; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC069029; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC118658; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC118660; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC113610; AAI13611.1; -; mRNA. DR EMBL; BC113612; AAI13613.1; -; mRNA. DR EMBL; M69229; AAB59399.1; -; Genomic_DNA. DR CCDS; CCDS10378.1; -. DR PIR; A25690; IGHUR1. DR RefSeq; NP_000866.1; NM_000875.4. DR RefSeq; NP_001278787.1; NM_001291858.1. DR PDB; 1IGR; X-ray; 2.60 A; A=31-492. DR PDB; 1JQH; X-ray; 2.10 A; A/B/C=979-1286. DR PDB; 1K3A; X-ray; 2.10 A; A=988-1286. DR PDB; 1M7N; X-ray; 2.70 A; A/B=974-1294. DR PDB; 1P4O; X-ray; 1.50 A; A/B=974-1294. DR PDB; 2OJ9; X-ray; 2.00 A; A=982-1286. DR PDB; 2ZM3; X-ray; 2.50 A; A/B/C/D=981-1286. DR PDB; 3D94; X-ray; 2.30 A; A=986-1286. DR PDB; 3F5P; X-ray; 2.90 A; A/B/C/D/E/F/G/H/I/J/K/L/M/R/S/T=981-1286. DR PDB; 3I81; X-ray; 2.08 A; A=982-1286. DR PDB; 3LVP; X-ray; 3.00 A; A/B/C/D=951-1286. DR PDB; 3LW0; X-ray; 1.79 A; A/B/C/D=983-1286. DR PDB; 3NW5; X-ray; 2.14 A; A=982-1286. DR PDB; 3NW6; X-ray; 2.20 A; A=982-1286. DR PDB; 3NW7; X-ray; 2.11 A; A=982-1286. DR PDB; 3O23; X-ray; 2.10 A; A=982-1286. DR PDB; 3QQU; X-ray; 2.90 A; A/B/C/D=988-1286. DR PDB; 4D2R; X-ray; 2.10 A; A=985-1286. DR PDB; 4XSS; X-ray; 3.00 A; F=721-736. DR PDB; 5FXQ; X-ray; 2.30 A; A=980-1286. DR PDB; 5FXR; X-ray; 2.40 A; A=980-1286. DR PDB; 5FXS; X-ray; 1.90 A; A=980-1286. DR PDB; 5HZN; X-ray; 2.20 A; A/B/C/D/E/F/G/H=983-1286. DR PDB; 5U8Q; X-ray; 3.27 A; A=31-935. DR PDB; 5U8R; X-ray; 3.00 A; A=31-935. DR PDB; 6JK8; EM; 4.70 A; A/B=1-1367. DR PDB; 6VWG; EM; 3.21 A; A/B=31-935. DR PDB; 6VWH; EM; 4.26 A; A/B=31-935. DR PDB; 6VWI; EM; 3.70 A; A/B=31-935. DR PDB; 6VWJ; EM; 4.21 A; A/B=31-935. DR PDB; 7PH8; NMR; -; A=932-962. DR PDB; 7S0Q; EM; 3.70 A; A=31-935. DR PDB; 7S8V; EM; 3.73 A; A=31-935. DR PDB; 7U23; EM; 4.60 A; E/F=31-935. DR PDB; 7V3P; EM; 3.60 A; A/B=1-931. DR PDB; 7XGD; EM; 4.00 A; A/B=31-927. DR PDB; 7XLC; EM; 5.00 A; A/B=31-927. DR PDB; 7YRR; EM; 4.30 A; A/B=31-927. DR PDB; 8PYI; X-ray; 3.06 A; AAA/BBB/CCC/DDD/EEE/FFF/GGG/HHH=973-1286. DR PDB; 8PYJ; X-ray; 2.70 A; AAA=973-1286. DR PDB; 8PYK; X-ray; 2.23 A; AAA=973-1286. DR PDB; 8PYL; X-ray; 2.93 A; AAA=973-1286. DR PDB; 8PYM; X-ray; 2.65 A; AAA=973-1286. DR PDB; 8PYN; X-ray; 1.71 A; AAA=973-1286. DR PDBsum; 1IGR; -. DR PDBsum; 1JQH; -. DR PDBsum; 1K3A; -. DR PDBsum; 1M7N; -. DR PDBsum; 1P4O; -. DR PDBsum; 2OJ9; -. DR PDBsum; 2ZM3; -. DR PDBsum; 3D94; -. DR PDBsum; 3F5P; -. DR PDBsum; 3I81; -. DR PDBsum; 3LVP; -. DR PDBsum; 3LW0; -. DR PDBsum; 3NW5; -. DR PDBsum; 3NW6; -. DR PDBsum; 3NW7; -. DR PDBsum; 3O23; -. DR PDBsum; 3QQU; -. DR PDBsum; 4D2R; -. DR PDBsum; 4XSS; -. DR PDBsum; 5FXQ; -. DR PDBsum; 5FXR; -. DR PDBsum; 5FXS; -. DR PDBsum; 5HZN; -. DR PDBsum; 5U8Q; -. DR PDBsum; 5U8R; -. DR PDBsum; 6JK8; -. DR PDBsum; 6VWG; -. DR PDBsum; 6VWH; -. DR PDBsum; 6VWI; -. DR PDBsum; 6VWJ; -. DR PDBsum; 7PH8; -. DR PDBsum; 7S0Q; -. DR PDBsum; 7S8V; -. DR PDBsum; 7U23; -. DR PDBsum; 7V3P; -. DR PDBsum; 7XGD; -. DR PDBsum; 7XLC; -. DR PDBsum; 7YRR; -. DR PDBsum; 8PYI; -. DR PDBsum; 8PYJ; -. DR PDBsum; 8PYK; -. DR PDBsum; 8PYL; -. DR PDBsum; 8PYM; -. DR PDBsum; 8PYN; -. DR AlphaFoldDB; P08069; -. DR EMDB; EMD-0741; -. DR EMDB; EMD-24791; -. DR EMDB; EMD-24927; -. DR EMDB; EMD-26306; -. DR EMDB; EMD-33186; -. DR EMDB; EMD-34065; -. DR EMDB; EMD-9838; -. DR SASBDB; P08069; -. DR SMR; P08069; -. DR BioGRID; 109701; 494. DR CORUM; P08069; -. DR DIP; DIP-476N; -. DR IntAct; P08069; 355. DR MINT; P08069; -. DR STRING; 9606.ENSP00000497069; -. DR BindingDB; P08069; -. DR ChEMBL; CHEMBL1957; -. DR DrugBank; DB07156; (4Z)-6-bromo-4-({[4-(pyrrolidin-1-ylmethyl)phenyl]amino}methylidene)isoquinoline-1,3(2H,4H)-dione. DR DrugBank; DB07474; 3-[5-(1H-IMIDAZOL-1-YL)-7-METHYL-1H-BENZIMIDAZOL-2-YL]-4-[(PYRIDIN-2-YLMETHYL)AMINO]PYRIDIN-2(1H)-ONE. DR DrugBank; DB05023; ATL1101. DR DrugBank; DB15399; BMS-754807. DR DrugBank; DB12267; Brigatinib. DR DrugBank; DB12250; Cixutumumab. DR DrugBank; DB11840; Dalotuzumab. DR DrugBank; DB11564; Insulin argine. DR DrugBank; DB01306; Insulin aspart. DR DrugBank; DB09456; Insulin beef. DR DrugBank; DB09564; Insulin degludec. DR DrugBank; DB01307; Insulin detemir. DR DrugBank; DB00047; Insulin glargine. DR DrugBank; DB01309; Insulin glulisine. DR DrugBank; DB00030; Insulin human. DR DrugBank; DB00046; Insulin lispro. DR DrugBank; DB11567; Insulin peglispro. DR DrugBank; DB00071; Insulin pork. DR DrugBank; DB11568; Insulin tregopil. DR DrugBank; DB16637; KW-2450 free base. DR DrugBank; DB06075; Linsitinib. DR DrugBank; DB01277; Mecasermin. DR DrugBank; DB14751; Mecasermin rinfabate. DR DrugBank; DB08804; Nandrolone decanoate. DR DrugBank; DB04395; Phosphoaminophosphonic Acid-Adenylate Ester. DR DrugBank; DB05897; rhIGFBP-3. DR DrugBank; DB09098; Somatrem. DR DrugBank; DB06343; Teprotumumab. DR DrugBank; DB05184; XL228. DR DrugCentral; P08069; -. DR GuidetoPHARMACOLOGY; 1801; -. DR GlyCosmos; P08069; 17 sites, 1 glycan. DR GlyGen; P08069; 18 sites, 1 O-linked glycan (1 site). DR iPTMnet; P08069; -. DR PhosphoSitePlus; P08069; -. DR SwissPalm; P08069; -. DR BioMuta; IGF1R; -. DR DMDM; 124240; -. DR CPTAC; CPTAC-3060; -. DR CPTAC; CPTAC-3061; -. DR EPD; P08069; -. DR jPOST; P08069; -. DR MassIVE; P08069; -. DR MaxQB; P08069; -. DR PaxDb; 9606-ENSP00000268035; -. DR PeptideAtlas; P08069; -. DR ProteomicsDB; 52065; -. DR Pumba; P08069; -. DR ABCD; P08069; 27 sequenced antibodies. DR Antibodypedia; 4140; 2863 antibodies from 49 providers. DR DNASU; 3480; -. DR Ensembl; ENST00000650285.1; ENSP00000497069.1; ENSG00000140443.15. DR GeneID; 3480; -. DR KEGG; hsa:3480; -. DR MANE-Select; ENST00000650285.1; ENSP00000497069.1; NM_000875.5; NP_000866.1. DR UCSC; uc002bul.4; human. DR AGR; HGNC:5465; -. DR CTD; 3480; -. DR DisGeNET; 3480; -. DR GeneCards; IGF1R; -. DR HGNC; HGNC:5465; IGF1R. DR HPA; ENSG00000140443; Low tissue specificity. DR MalaCards; IGF1R; -. DR MIM; 147370; gene. DR MIM; 270450; phenotype. DR neXtProt; NX_P08069; -. DR OpenTargets; ENSG00000140443; -. DR Orphanet; 73273; Growth delay due to insulin-like growth factor I resistance. DR PharmGKB; PA29698; -. DR VEuPathDB; HostDB:ENSG00000140443; -. DR eggNOG; KOG4258; Eukaryota. DR GeneTree; ENSGT00940000156682; -. DR InParanoid; P08069; -. DR OMA; HRCWHHR; -. DR OrthoDB; 1614410at2759; -. DR PhylomeDB; P08069; -. DR TreeFam; TF351636; -. DR BRENDA; 2.7.10.1; 2681. DR PathwayCommons; P08069; -. DR Reactome; R-HSA-2404192; Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R). DR Reactome; R-HSA-2428928; IRS-related events triggered by IGF1R. DR Reactome; R-HSA-2428933; SHC-related events triggered by IGF1R. DR Reactome; R-HSA-9009391; Extra-nuclear estrogen signaling. DR SignaLink; P08069; -. DR SIGNOR; P08069; -. DR BioGRID-ORCS; 3480; 212 hits in 1220 CRISPR screens. DR ChiTaRS; IGF1R; human. DR EvolutionaryTrace; P08069; -. DR GeneWiki; Insulin-like_growth_factor_1_receptor; -. DR GenomeRNAi; 3480; -. DR Pharos; P08069; Tclin. DR PRO; PR:P08069; -. DR Proteomes; UP000005640; Chromosome 15. DR RNAct; P08069; Protein. DR Bgee; ENSG00000140443; Expressed in caput epididymis and 208 other cell types or tissues. DR ExpressionAtlas; P08069; baseline and differential. DR GO; GO:0035867; C:alphav-beta3 integrin-IGF-1-IGF1R complex; IDA:UniProtKB. DR GO; GO:0030424; C:axon; IBA:GO_Central. DR GO; GO:0005901; C:caveola; IEA:Ensembl. DR GO; GO:0005899; C:insulin receptor complex; IBA:GO_Central. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:BHF-UCL. DR GO; GO:0016020; C:membrane; IDA:BHF-UCL. DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; ISS:AgBase. DR GO; GO:1902911; C:protein kinase complex; IDA:UniProtKB. DR GO; GO:0043235; C:receptor complex; IDA:MGI. DR GO; GO:0030315; C:T-tubule; IEA:Ensembl. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0001965; F:G-protein alpha-subunit binding; IEA:Ensembl. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0043559; F:insulin binding; IPI:BHF-UCL. DR GO; GO:0005009; F:insulin receptor activity; IBA:GO_Central. DR GO; GO:0005158; F:insulin receptor binding; IDA:BHF-UCL. DR GO; GO:0043560; F:insulin receptor substrate binding; IPI:UniProtKB. DR GO; GO:0005520; F:insulin-like growth factor binding; IDA:UniProtKB. DR GO; GO:0031994; F:insulin-like growth factor I binding; IDA:UniProtKB. DR GO; GO:0005010; F:insulin-like growth factor receptor activity; IDA:UniProtKB. DR GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; IPI:UniProtKB. DR GO; GO:0140318; F:protein transporter activity; IMP:ARUK-UCL. DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB. DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl. DR GO; GO:0097242; P:amyloid-beta clearance; IMP:ARUK-UCL. DR GO; GO:0007409; P:axonogenesis; IEA:Ensembl. DR GO; GO:0003230; P:cardiac atrium development; IEA:Ensembl. DR GO; GO:1904045; P:cellular response to aldosterone; IEA:Ensembl. DR GO; GO:1904646; P:cellular response to amyloid-beta; IGI:ARUK-UCL. DR GO; GO:1904385; P:cellular response to angiotensin; IEA:Ensembl. DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEA:Ensembl. DR GO; GO:0071392; P:cellular response to estradiol stimulus; IEA:Ensembl. DR GO; GO:0071333; P:cellular response to glucose stimulus; IBA:GO_Central. DR GO; GO:1990314; P:cellular response to insulin-like growth factor stimulus; IEA:Ensembl. DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl. DR GO; GO:0071393; P:cellular response to progesterone stimulus; IEA:Ensembl. DR GO; GO:0071394; P:cellular response to testosterone stimulus; IEA:Ensembl. DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEA:Ensembl. DR GO; GO:0034224; P:cellular response to zinc ion starvation; IEA:Ensembl. DR GO; GO:0090398; P:cellular senescence; IEA:Ensembl. DR GO; GO:0021549; P:cerebellum development; IEA:Ensembl. DR GO; GO:0097062; P:dendritic spine maintenance; ISS:ARUK-UCL. DR GO; GO:0030010; P:establishment of cell polarity; IEA:Ensembl. DR GO; GO:0044849; P:estrous cycle; IEA:Ensembl. DR GO; GO:0021766; P:hippocampus development; IEA:Ensembl. DR GO; GO:0006955; P:immune response; IMP:BHF-UCL. DR GO; GO:0008286; P:insulin receptor signaling pathway; ISS:ARUK-UCL. DR GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:1904193; P:negative regulation of cholangiocyte apoptotic process; IEA:Ensembl. DR GO; GO:1903944; P:negative regulation of hepatocyte apoptotic process; IEA:Ensembl. DR GO; GO:0043409; P:negative regulation of MAPK cascade; IDA:GO_Central. DR GO; GO:0010656; P:negative regulation of muscle cell apoptotic process; IEA:Ensembl. DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; IMP:MGI. DR GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; IC:BHF-UCL. DR GO; GO:0048680; P:positive regulation of axon regeneration; IEA:Ensembl. DR GO; GO:0030335; P:positive regulation of cell migration; IMP:BHF-UCL. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:BHF-UCL. DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab. DR GO; GO:0032467; P:positive regulation of cytokinesis; IEA:Ensembl. DR GO; GO:0051054; P:positive regulation of DNA metabolic process; IEA:Ensembl. DR GO; GO:0043410; P:positive regulation of MAPK cascade; IBA:GO_Central. DR GO; GO:0033690; P:positive regulation of osteoblast proliferation; IEA:Ensembl. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:BHF-UCL. DR GO; GO:0043243; P:positive regulation of protein-containing complex disassembly; ISS:ARUK-UCL. DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IEA:Ensembl. DR GO; GO:0090031; P:positive regulation of steroid hormone biosynthetic process; IEA:Ensembl. DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB. DR GO; GO:0046328; P:regulation of JNK cascade; IDA:UniProtKB. DR GO; GO:0043279; P:response to alkaloid; IEA:Ensembl. DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl. DR GO; GO:1902065; P:response to L-glutamate; IEA:Ensembl. DR GO; GO:0035094; P:response to nicotine; IEA:Ensembl. DR GO; GO:0033197; P:response to vitamin E; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0045056; P:transcytosis; IMP:ARUK-UCL. DR CDD; cd00063; FN3; 3. DR CDD; cd00064; FU; 1. DR CDD; cd05032; PTKc_InsR_like; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 3. 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; 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:SF106; INSULIN-LIKE GROWTH FACTOR 1 RECEPTOR; 1. DR PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 1. DR Pfam; PF00041; fn3; 1. DR Pfam; PF00757; Furin-like; 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; 4. 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. DR Genevisible; P08069; HS. PE 1: Evidence at protein level; KW 3D-structure; ATP-binding; Cell membrane; KW Cleavage on pair of basic residues; Direct protein sequencing; KW Disease variant; Disulfide bond; Glycoprotein; Host-virus interaction; KW Isopeptide bond; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; KW Receptor; Reference proteome; Repeat; Signal; Transferase; Transmembrane; KW Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation. FT SIGNAL 1..30 FT /evidence="ECO:0000269|PubMed:2877871, FT ECO:0000269|PubMed:8257688" FT CHAIN 31..736 FT /note="Insulin-like growth factor 1 receptor alpha chain" FT /id="PRO_0000016681" FT CHAIN 741..1367 FT /note="Insulin-like growth factor 1 receptor beta chain" FT /id="PRO_0000016682" FT TOPO_DOM 741..935 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 936..959 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 960..1367 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 491..609 FT /note="Fibronectin type-III 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 610..708 FT /note="Fibronectin type-III 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 735..828 FT /note="Fibronectin type-III 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 834..927 FT /note="Fibronectin type-III 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 999..1274 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 1288..1367 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 977..980 FT /note="IRS1- and SHC1-binding" FT ACT_SITE 1135 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10028" FT BINDING 1005..1013 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 1033 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT MOD_RES 980 FT /note="Phosphotyrosine" FT /evidence="ECO:0000305|PubMed:7541045" FT MOD_RES 1161 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:11694888, FT ECO:0000269|PubMed:18501599, ECO:0000269|PubMed:19041240" FT MOD_RES 1165 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:11694888, FT ECO:0000269|PubMed:18501599, ECO:0000269|PubMed:19041240" FT MOD_RES 1166 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:11694888, FT ECO:0000269|PubMed:18501599, ECO:0000269|PubMed:19041240" FT MOD_RES 1278 FT /note="Phosphoserine; by GSK3-beta" FT /evidence="ECO:0000250|UniProtKB:Q60751" FT MOD_RES 1282 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q60751" FT CARBOHYD 51 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:9690478" FT CARBOHYD 102 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 135 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:9690478" FT CARBOHYD 244 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:9690478" FT CARBOHYD 314 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:9690478" FT CARBOHYD 417 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 438 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 534 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 607 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 622 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 640 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 747 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 756 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 764 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 900 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 913 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 33..52 FT /evidence="ECO:0000269|PubMed:9690478" FT DISULFID 150..178 FT /evidence="ECO:0000269|PubMed:9690478" FT DISULFID 182..205 FT /evidence="ECO:0000269|PubMed:9690478" FT DISULFID 192..211 FT /evidence="ECO:0000269|PubMed:9690478" FT DISULFID 215..224 FT /evidence="ECO:0000269|PubMed:9690478" FT DISULFID 219..230 FT /evidence="ECO:0000269|PubMed:9690478" FT DISULFID 231..239 FT /evidence="ECO:0000269|PubMed:9690478" FT DISULFID 235..248 FT /evidence="ECO:0000269|PubMed:9690478" FT DISULFID 251..260 FT /evidence="ECO:0000269|PubMed:9690478" FT DISULFID 264..276 FT /evidence="ECO:0000269|PubMed:9690478" FT DISULFID 282..303 FT /evidence="ECO:0000269|PubMed:9690478" FT DISULFID 307..321 FT /evidence="ECO:0000269|PubMed:9690478" FT DISULFID 324..328 FT /evidence="ECO:0000269|PubMed:9690478" FT DISULFID 332..353 FT /evidence="ECO:0000269|PubMed:9690478" FT DISULFID 455..488 FT /evidence="ECO:0000269|PubMed:9690478" FT CROSSLNK 1168 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:21994939" FT CROSSLNK 1171 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:21994939" FT VARIANT 105 FT /note="V -> L (in a renal chromophobe sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041424" FT VARIANT 138 FT /note="R -> Q (in IGF1RES; has decreased IGF1R function; FT dbSNP:rs121912426)" FT /evidence="ECO:0000269|PubMed:14657428" FT /id="VAR_034891" FT VARIANT 145 FT /note="K -> N (in IGF1RES; has decreased IGF1R function; FT dbSNP:rs121912427)" FT /evidence="ECO:0000269|PubMed:14657428" FT /id="VAR_034892" FT VARIANT 359 FT /note="N -> Y (in IGF1RES; significant decrease in FT IGF1-induced DNA synthesis and AKT1 phosphorylation in FT patient fibroblasts)" FT /evidence="ECO:0000269|PubMed:25040157" FT /id="VAR_076247" FT VARIANT 388 FT /note="V -> M (in dbSNP:rs45445894)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_018855" FT VARIANT 437 FT /note="R -> H (in dbSNP:rs34516635)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_034893" FT VARIANT 511 FT /note="R -> Q (in dbSNP:rs33958176)" FT /id="VAR_034894" FT VARIANT 595 FT /note="R -> H (in dbSNP:rs56248469)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041425" FT VARIANT 605 FT /note="R -> H (in dbSNP:rs45553041)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_018856" FT VARIANT 739 FT /note="R -> Q (in IGF1RES; leads to failure of processing FT of the IGF1R proreceptor to mature IGF1R; FT dbSNP:rs121912429)" FT /evidence="ECO:0000269|PubMed:15928254" FT /id="VAR_034895" FT VARIANT 808 FT /note="H -> R (in dbSNP:rs34061581)" FT /id="VAR_034896" FT VARIANT 828 FT /note="A -> T (in dbSNP:rs35224135)" FT /id="VAR_034897" FT VARIANT 857 FT /note="N -> S (in dbSNP:rs45611935)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041426" FT VARIANT 865 FT /note="Y -> C (in IGF1RES; significant decrease in FT IGF1-induced DNA synthesis and AKT1 phosphorylation in FT patient fibroblasts)" FT /evidence="ECO:0000269|PubMed:25040157" FT /id="VAR_076248" FT VARIANT 1256 FT /note="R -> S (in IGF1RES; significant decrease in FT IGF1-induced DNA synthesis and AKT1 phosphorylation in FT patient fibroblasts)" FT /evidence="ECO:0000269|PubMed:25040157" FT /id="VAR_076249" FT VARIANT 1337 FT /note="R -> C (in IGF1RES; uncertain significance; FT significant decrease in IGF1-induced DNA synthesis; FT significant increase in IGF1-induced AKT1 phosphorylation FT in patient fibroblasts; dbSNP:rs141802822)" FT /evidence="ECO:0000269|PubMed:25040157" FT /id="VAR_076250" FT VARIANT 1338 FT /note="A -> T (in dbSNP:rs34102392)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041427" FT VARIANT 1347 FT /note="A -> V (in a lung squamous cell carcinoma sample; FT somatic mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041428" FT MUTAGEN 980 FT /note="Y->F: Reduces tyrosine phosphorylation. Abolishes FT interaction with IRS1 and SHC1. Does not abolish FT interaction with PIK3R1, nor with GRB10." FT /evidence="ECO:0000269|PubMed:10454568, FT ECO:0000269|PubMed:7541045" FT MUTAGEN 1033 FT /note="K->A: Kinase inactive. Abolishes tyrosine FT phosphorylation and abolishes interaction with IRS1, SHC1 FT and PIK3R1." FT /evidence="ECO:0000269|PubMed:7541045" FT MUTAGEN 1280 FT /note="Y->F: No effect on GRB10-binding." FT /evidence="ECO:0000269|PubMed:10454568" FT MUTAGEN 1281 FT /note="Y->F: No effect on GRB10-binding." FT /evidence="ECO:0000269|PubMed:10454568" FT MUTAGEN 1346 FT /note="Y->F: Loss of GRB10-binding." FT /evidence="ECO:0000269|PubMed:10454568" FT CONFLICT 928..929 FT /note="TG -> R (in Ref. 3; BAG11657)" FT /evidence="ECO:0000305" FT STRAND 37..41 FT /evidence="ECO:0007829|PDB:1IGR" FT HELIX 43..49 FT /evidence="ECO:0007829|PDB:1IGR" FT STRAND 53..57 FT /evidence="ECO:0007829|PDB:1IGR" FT STRAND 59..65 FT /evidence="ECO:0007829|PDB:1IGR" FT STRAND 68..70 FT /evidence="ECO:0007829|PDB:1IGR" FT STRAND 80..83 FT /evidence="ECO:0007829|PDB:1IGR" FT STRAND 85..92 FT /evidence="ECO:0007829|PDB:1IGR" FT HELIX 96..98 FT /evidence="ECO:0007829|PDB:1IGR" FT STRAND 115..121 FT /evidence="ECO:0007829|PDB:1IGR" FT STRAND 138..144 FT /evidence="ECO:0007829|PDB:1IGR" FT STRAND 152..154 FT /evidence="ECO:0007829|PDB:6VWG" FT HELIX 157..160 FT /evidence="ECO:0007829|PDB:1IGR" FT HELIX 164..166 FT /evidence="ECO:0007829|PDB:1IGR" FT STRAND 168..171 FT /evidence="ECO:0007829|PDB:1IGR" FT HELIX 175..178 FT /evidence="ECO:0007829|PDB:1IGR" FT TURN 183..188 FT /evidence="ECO:0007829|PDB:1IGR" FT STRAND 194..199 FT /evidence="ECO:0007829|PDB:1IGR" FT STRAND 201..203 FT /evidence="ECO:0007829|PDB:1IGR" FT STRAND 205..209 FT /evidence="ECO:0007829|PDB:1IGR" FT HELIX 217..219 FT /evidence="ECO:0007829|PDB:1IGR" FT STRAND 222..224 FT /evidence="ECO:0007829|PDB:5U8R" FT HELIX 226..228 FT /evidence="ECO:0007829|PDB:6VWG" FT STRAND 235..241 FT /evidence="ECO:0007829|PDB:1IGR" FT STRAND 247..255 FT /evidence="ECO:0007829|PDB:1IGR" FT STRAND 257..263 FT /evidence="ECO:0007829|PDB:1IGR" FT STRAND 269..271 FT /evidence="ECO:0007829|PDB:1IGR" FT TURN 272..274 FT /evidence="ECO:0007829|PDB:1IGR" FT STRAND 275..277 FT /evidence="ECO:0007829|PDB:1IGR" FT HELIX 279..283 FT /evidence="ECO:0007829|PDB:1IGR" FT STRAND 297..299 FT /evidence="ECO:0007829|PDB:1IGR" FT STRAND 302..306 FT /evidence="ECO:0007829|PDB:1IGR" FT STRAND 311..315 FT /evidence="ECO:0007829|PDB:1IGR" FT STRAND 321..323 FT /evidence="ECO:0007829|PDB:1IGR" FT STRAND 325..327 FT /evidence="ECO:0007829|PDB:1IGR" FT STRAND 331..341 FT /evidence="ECO:0007829|PDB:1IGR" FT HELIX 345..347 FT /evidence="ECO:0007829|PDB:1IGR" FT TURN 349..352 FT /evidence="ECO:0007829|PDB:1IGR" FT STRAND 354..362 FT /evidence="ECO:0007829|PDB:1IGR" FT HELIX 375..378 FT /evidence="ECO:0007829|PDB:1IGR" FT STRAND 383..386 FT /evidence="ECO:0007829|PDB:1IGR" FT STRAND 388..392 FT /evidence="ECO:0007829|PDB:1IGR" FT STRAND 397..399 FT /evidence="ECO:0007829|PDB:6VWG" FT TURN 415..417 FT /evidence="ECO:0007829|PDB:1IGR" FT STRAND 418..423 FT /evidence="ECO:0007829|PDB:1IGR" FT TURN 434..436 FT /evidence="ECO:0007829|PDB:1IGR" FT STRAND 440..443 FT /evidence="ECO:0007829|PDB:1IGR" FT STRAND 445..451 FT /evidence="ECO:0007829|PDB:1IGR" FT STRAND 452..454 FT /evidence="ECO:0007829|PDB:5U8Q" FT HELIX 456..466 FT /evidence="ECO:0007829|PDB:1IGR" FT TURN 469..471 FT /evidence="ECO:0007829|PDB:5U8R" FT STRAND 474..477 FT /evidence="ECO:0007829|PDB:1IGR" FT TURN 479..481 FT /evidence="ECO:0007829|PDB:1IGR" FT STRAND 482..485 FT /evidence="ECO:0007829|PDB:5U8R" FT STRAND 491..493 FT /evidence="ECO:0007829|PDB:5U8R" FT STRAND 495..500 FT /evidence="ECO:0007829|PDB:5U8R" FT STRAND 505..509 FT /evidence="ECO:0007829|PDB:5U8R" FT HELIX 517..519 FT /evidence="ECO:0007829|PDB:6VWG" FT STRAND 520..529 FT /evidence="ECO:0007829|PDB:5U8R" FT STRAND 531..533 FT /evidence="ECO:0007829|PDB:5U8R" FT TURN 542..544 FT /evidence="ECO:0007829|PDB:5U8Q" FT STRAND 550..552 FT /evidence="ECO:0007829|PDB:5U8R" FT STRAND 565..568 FT /evidence="ECO:0007829|PDB:5U8R" FT STRAND 576..586 FT /evidence="ECO:0007829|PDB:5U8R" FT STRAND 591..593 FT /evidence="ECO:0007829|PDB:5U8R" FT STRAND 597..599 FT /evidence="ECO:0007829|PDB:5U8R" FT STRAND 602..605 FT /evidence="ECO:0007829|PDB:5U8R" FT STRAND 615..620 FT /evidence="ECO:0007829|PDB:5U8R" FT STRAND 626..632 FT /evidence="ECO:0007829|PDB:5U8R" FT STRAND 644..650 FT /evidence="ECO:0007829|PDB:5U8R" FT STRAND 655..660 FT /evidence="ECO:0007829|PDB:5U8R" FT TURN 662..664 FT /evidence="ECO:0007829|PDB:5U8R" FT HELIX 724..730 FT /evidence="ECO:0007829|PDB:4XSS" FT STRAND 777..782 FT /evidence="ECO:0007829|PDB:5U8R" FT STRAND 786..792 FT /evidence="ECO:0007829|PDB:5U8R" FT STRAND 798..805 FT /evidence="ECO:0007829|PDB:5U8R" FT HELIX 810..813 FT /evidence="ECO:0007829|PDB:5U8R" FT STRAND 821..824 FT /evidence="ECO:0007829|PDB:5U8R" FT STRAND 839..843 FT /evidence="ECO:0007829|PDB:5U8R" FT TURN 844..846 FT /evidence="ECO:0007829|PDB:5U8R" FT STRAND 847..851 FT /evidence="ECO:0007829|PDB:5U8R" FT STRAND 862..873 FT /evidence="ECO:0007829|PDB:5U8R" FT STRAND 876..881 FT /evidence="ECO:0007829|PDB:5U8R" FT HELIX 882..888 FT /evidence="ECO:0007829|PDB:5U8R" FT STRAND 889..893 FT /evidence="ECO:0007829|PDB:5U8R" FT STRAND 898..911 FT /evidence="ECO:0007829|PDB:5U8R" FT STRAND 920..924 FT /evidence="ECO:0007829|PDB:5U8R" FT HELIX 933..960 FT /evidence="ECO:0007829|PDB:7PH8" FT STRAND 980..982 FT /evidence="ECO:0007829|PDB:1P4O" FT HELIX 983..985 FT /evidence="ECO:0007829|PDB:2ZM3" FT TURN 990..992 FT /evidence="ECO:0007829|PDB:2OJ9" FT HELIX 996..998 FT /evidence="ECO:0007829|PDB:1P4O" FT STRAND 999..1007 FT /evidence="ECO:0007829|PDB:1P4O" FT STRAND 1009..1022 FT /evidence="ECO:0007829|PDB:1P4O" FT STRAND 1025..1034 FT /evidence="ECO:0007829|PDB:1P4O" FT STRAND 1037..1039 FT /evidence="ECO:0007829|PDB:3F5P" FT HELIX 1041..1053 FT /evidence="ECO:0007829|PDB:1P4O" FT HELIX 1054..1056 FT /evidence="ECO:0007829|PDB:1P4O" FT STRAND 1065..1069 FT /evidence="ECO:0007829|PDB:1P4O" FT STRAND 1071..1074 FT /evidence="ECO:0007829|PDB:1P4O" FT STRAND 1076..1080 FT /evidence="ECO:0007829|PDB:1P4O" FT HELIX 1087..1100 FT /evidence="ECO:0007829|PDB:1P4O" FT HELIX 1109..1128 FT /evidence="ECO:0007829|PDB:1P4O" FT HELIX 1138..1140 FT /evidence="ECO:0007829|PDB:1P4O" FT STRAND 1141..1143 FT /evidence="ECO:0007829|PDB:1P4O" FT STRAND 1149..1151 FT /evidence="ECO:0007829|PDB:1P4O" FT HELIX 1155..1157 FT /evidence="ECO:0007829|PDB:3D94" FT HELIX 1159..1164 FT /evidence="ECO:0007829|PDB:1P4O" FT TURN 1165..1167 FT /evidence="ECO:0007829|PDB:3LVP" FT HELIX 1168..1170 FT /evidence="ECO:0007829|PDB:1P4O" FT STRAND 1171..1174 FT /evidence="ECO:0007829|PDB:1P4O" FT HELIX 1176..1178 FT /evidence="ECO:0007829|PDB:1P4O" FT HELIX 1181..1186 FT /evidence="ECO:0007829|PDB:1P4O" FT HELIX 1191..1207 FT /evidence="ECO:0007829|PDB:1P4O" FT TURN 1212..1215 FT /evidence="ECO:0007829|PDB:1P4O" FT HELIX 1218..1226 FT /evidence="ECO:0007829|PDB:1P4O" FT HELIX 1239..1248 FT /evidence="ECO:0007829|PDB:1P4O" FT HELIX 1253..1255 FT /evidence="ECO:0007829|PDB:1P4O" FT HELIX 1259..1266 FT /evidence="ECO:0007829|PDB:1P4O" FT HELIX 1267..1269 FT /evidence="ECO:0007829|PDB:1P4O" FT HELIX 1274..1277 FT /evidence="ECO:0007829|PDB:1P4O" FT TURN 1279..1281 FT /evidence="ECO:0007829|PDB:3O23" FT TURN 1283..1285 FT /evidence="ECO:0007829|PDB:3LVP" FT STRAND 1286..1288 FT /evidence="ECO:0007829|PDB:1P4O" SQ SEQUENCE 1367 AA; 154793 MW; AE8A735F87F745C8 CRC64; MKSGSGGGSP TSLWGLLFLS AALSLWPTSG EICGPGIDIR NDYQQLKRLE NCTVIEGYLH ILLISKAEDY RSYRFPKLTV ITEYLLLFRV AGLESLGDLF PNLTVIRGWK LFYNYALVIF EMTNLKDIGL YNLRNITRGA IRIEKNADLC YLSTVDWSLI LDAVSNNYIV GNKPPKECGD LCPGTMEEKP MCEKTTINNE YNYRCWTTNR CQKMCPSTCG KRACTENNEC CHPECLGSCS APDNDTACVA CRHYYYAGVC VPACPPNTYR FEGWRCVDRD FCANILSAES SDSEGFVIHD GECMQECPSG FIRNGSQSMY CIPCEGPCPK VCEEEKKTKT IDSVTSAQML QGCTIFKGNL LINIRRGNNI ASELENFMGL IEVVTGYVKI RHSHALVSLS FLKNLRLILG EEQLEGNYSF YVLDNQNLQQ LWDWDHRNLT IKAGKMYFAF NPKLCVSEIY RMEEVTGTKG RQSKGDINTR NNGERASCES DVLHFTSTTT SKNRIIITWH RYRPPDYRDL ISFTVYYKEA PFKNVTEYDG QDACGSNSWN MVDVDLPPNK DVEPGILLHG LKPWTQYAVY VKAVTLTMVE NDHIRGAKSE ILYIRTNASV PSIPLDVLSA SNSSSQLIVK WNPPSLPNGN LSYYIVRWQR QPQDGYLYRH NYCSKDKIPI RKYADGTIDI EEVTENPKTE VCGGEKGPCC ACPKTEAEKQ AEKEEAEYRK VFENFLHNSI FVPRPERKRR DVMQVANTTM SSRSRNTTAA DTYNITDPEE LETEYPFFES RVDNKERTVI SNLRPFTLYR IDIHSCNHEA EKLGCSASNF VFARTMPAEG ADDIPGPVTW EPRPENSIFL KWPEPENPNG LILMYEIKYG SQVEDQRECV SRQEYRKYGG AKLNRLNPGN YTARIQATSL SGNGSWTDPV FFYVQAKTGY ENFIHLIIAL PVAVLLIVGG LVIMLYVFHR KRNNSRLGNG VLYASVNPEY FSAADVYVPD EWEVAREKIT MSRELGQGSF GMVYEGVAKG VVKDEPETRV AIKTVNEAAS MRERIEFLNE ASVMKEFNCH HVVRLLGVVS QGQPTLVIME LMTRGDLKSY LRSLRPEMEN NPVLAPPSLS KMIQMAGEIA DGMAYLNANK FVHRDLAARN CMVAEDFTVK IGDFGMTRDI YETDYYRKGG KGLLPVRWMS PESLKDGVFT TYSDVWSFGV VLWEIATLAE QPYQGLSNEQ VLRFVMEGGL LDKPDNCPDM LFELMRMCWQ YNPKMRPSFL EIISSIKEEM EPGFREVSFY YSEENKLPEP EELDLEPENM ESVPLDPSAS SSSLPLPDRH SGHKAENGPG PGVLVLRASF DERQPYAHMN GGRKNERALP LPQSSTC //