IGF1R_HUMAN
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 03-AUG-2022, entry version 242.
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; 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=4; IntAct=EBI-475981, EBI-79464;
CC P08069; P35813: PPM1A; NbExp=2; IntAct=EBI-475981, EBI-989143;
CC P08069; P18031: PTPN1; NbExp=3; IntAct=EBI-475981, EBI-968788;
CC P08069; Q06124: PTPN11; NbExp=4; 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; 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="http://atlasgeneticsoncology.org/Genes/IGF1RID40928ch15q26.html";
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";
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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 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 AlphaFoldDB; P08069; -.
DR SASBDB; P08069; -.
DR SMR; P08069; -.
DR BioGRID; 109701; 270.
DR CORUM; P08069; -.
DR DIP; DIP-476N; -.
DR IntAct; P08069; 135.
DR MINT; P08069; -.
DR STRING; 9606.ENSP00000268035; -.
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; 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 GlyGen; P08069; 18 sites, 1 O-linked glycan (1 site).
DR iPTMnet; P08069; -.
DR PhosphoSitePlus; P08069; -.
DR BioMuta; IGF1R; -.
DR DMDM; 124240; -.
DR EPD; P08069; -.
DR jPOST; P08069; -.
DR MassIVE; P08069; -.
DR MaxQB; P08069; -.
DR PaxDb; P08069; -.
DR PeptideAtlas; P08069; -.
DR PRIDE; P08069; -.
DR ProteomicsDB; 52065; -.
DR ABCD; P08069; 27 sequenced antibodies.
DR Antibodypedia; 4140; 2345 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 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; KFRGYAF; -.
DR OrthoDB; 223327at2759; -.
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; 189 hits in 1122 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 206 other tissues.
DR ExpressionAtlas; P08069; baseline and differential.
DR Genevisible; P08069; HS.
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:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0005899; C:insulin receptor complex; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; 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:0005634; C:nucleus; 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:0005198; F:structural molecule activity; IDA:UniProtKB.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0007568; P:aging; 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: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:0042593; P:glucose homeostasis; IBA:GO_Central.
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:0014065; P:phosphatidylinositol 3-kinase signaling; IC:BHF-UCL.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; IDA: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:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
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:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IBA:GO_Central.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IBA:GO_Central.
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: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 GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd00063; FN3; 3.
DR CDD; cd00064; FU; 1.
DR Gene3D; 2.60.40.10; -; 3.
DR Gene3D; 3.80.20.20; -; 2.
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 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; SSF49265; 3.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57184; SSF57184; 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.
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 IGF1-
FT induced DNA synthesis and AKT1 phosphorylation in patient
FT 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 IGF1-
FT induced DNA synthesis and AKT1 phosphorylation in patient
FT fibroblasts)"
FT /evidence="ECO:0000269|PubMed:25040157"
FT /id="VAR_076248"
FT VARIANT 1256
FT /note="R -> S (in IGF1RES; significant decrease in IGF1-
FT induced DNA synthesis and AKT1 phosphorylation in patient
FT fibroblasts)"
FT /evidence="ECO:0000269|PubMed:25040157"
FT /id="VAR_076249"
FT VARIANT 1337
FT /note="R -> C (in IGF1RES; unknown pathological
FT significance; significant decrease in IGF1-induced DNA
FT synthesis; significant increase in IGF1-induced AKT1
FT phosphorylation 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 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
