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Insulin receptor (IR) (EC 2 7 10 1) (CD antigen CD220) [Cleaved into: Insulin receptor subunit alpha; Insulin receptor subunit beta]

 INSR_HUMAN              Reviewed;        1382 AA.
P06213; Q17RW0; Q59H98; Q9UCB7; Q9UCB8; Q9UCB9;
01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
05-OCT-2010, sequence version 4.
10-FEB-2021, entry version 271.
RecName: Full=Insulin receptor;
Short=IR;
EC=2.7.10.1;
AltName: CD_antigen=CD220;
Contains:
RecName: Full=Insulin receptor subunit alpha;
Contains:
RecName: Full=Insulin receptor subunit beta;
Flags: Precursor;
Name=INSR;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), AND VARIANTS GLY-2; HIS-171;
THR-448 AND LYS-492.
PubMed=2859121; DOI=10.1016/0092-8674(85)90334-4;
Ebina Y., Ellis L., Jarnagin K., Edery M., Graf L., Clauser E., Ou J.-H.,
Masiarz F., Kan Y.W., Goldfine I.D., Roth R.A., Rutter W.J.;
"The human insulin receptor cDNA: the structural basis for hormone-
activated transmembrane signalling.";
Cell 40:747-758(1985).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT), PROTEIN SEQUENCE OF 28-49 AND
763-782, GLYCOSYLATION AT ASN-43 AND ASN-769, AND VARIANT GLY-2.
PubMed=2983222; DOI=10.1038/313756a0;
Ullrich A., Bell J.R., Chen E.Y., Herrera R., Petruzzelli L.M., Dull T.J.,
Gray A., Coussens L., Liao Y.-C., Tsubokawa M., Mason A., Seeburg P.H.,
Grunfeld C., Rosen O.M., Ramachandran J.;
"Human insulin receptor and its relationship to the tyrosine kinase family
of oncogenes.";
Nature 313:756-761(1985).
[3]
SEQUENCE REVISION TO 899-900.
Chen E.Y.;
Submitted (JUL-1985) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLY-2.
TISSUE=Fetal liver;
PubMed=2210055; DOI=10.2337/diacare.39.1.123;
Seino S., Seino M., Bell G.I.;
"Human insulin-receptor gene. Partial sequence and amplification of exons
by polymerase chain reaction.";
Diabetes 39:123-128(1990).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=15057824; DOI=10.1038/nature02399;
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
Rubin E.M., Lucas S.M.;
"The DNA sequence and biology of human chromosome 19.";
Nature 428:529-535(2004).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT), AND VARIANT GLY-2.
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project:
the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[7]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-33, AND VARIANT GLY-2.
PubMed=3680248;
Araki E., Shimada F., Uzawa H., Mori M., Ebina Y.;
"Characterization of the promoter region of the human insulin receptor
gene. Evidence for promoter activity.";
J. Biol. Chem. 262:16186-16191(1987).
[8]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-33, AND VARIANT GLY-2.
PubMed=2806055; DOI=10.1016/0168-8227(89)90085-5;
Araki E., Shimada F., Fukushima H., Mori M., Shichiri M., Ebina Y.;
"Characterization of the promoter region of the human insulin receptor
gene.";
Diabetes Res. Clin. Pract. 7:S31-S33(1989).
[9]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-33, AND VARIANT GLY-2.
PubMed=2777789;
Tewari D.S., Cook D.M., Taub R.;
"Characterization of the promoter region and 3' end of the human insulin
receptor gene.";
J. Biol. Chem. 264:16238-16245(1989).
[10]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-33, AND VARIANT GLY-2.
TISSUE=Skin fibroblast;
PubMed=2280779; DOI=10.1210/mend-4-4-647;
McKeon C., Moncada V., Pham T., Salvatore P., Kadowaki T., Accili D.,
Taylor S.I.;
"Structural and functional analysis of the insulin receptor promoter.";
Mol. Endocrinol. 4:647-656(1990).
[11]
PROTEIN SEQUENCE OF 28-44; 192-205; 299-314; 610-627 AND 763-780, ACTIVITY
REGULATION, AND SUBUNIT.
TISSUE=Placenta;
PubMed=2211730;
Xu Q.-Y., Paxton R.J., Fujita-Yamaguchi Y.;
"Substructural analysis of the insulin receptor by microsequence analyses
of limited tryptic fragments isolated by sodium dodecyl sulfate-
polyacrylamide gel electrophoresis in the absence or presence of
dithiothreitol.";
J. Biol. Chem. 265:18673-18681(1990).
[12]
PROTEIN SEQUENCE OF 28-45 AND 763-782, FUNCTION, AND FORMATION OF A HYBRID
RECEPTOR WITH IGF1R.
TISSUE=Placenta;
PubMed=8257688; DOI=10.1021/bi00212a019;
Kasuya J., Paz I.B., Maddux B.A., Goldfine I.D., Hefta S.A.,
Fujita-Yamaguchi Y.;
"Characterization of human placental insulin-like growth factor-I/insulin
hybrid receptors by protein microsequencing and purification.";
Biochemistry 32:13531-13536(1993).
[13]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 538-1382 (ISOFORM SHORT).
TISSUE=Brain;
Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
Ohara O., Nagase T., Kikuno R.F.;
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
[14]
NUCLEOTIDE SEQUENCE [MRNA] OF 728-772 (ISOFORM LONG), AND ALTERNATIVE
SPLICING.
PubMed=2538124; DOI=10.1016/0006-291x(89)92439-x;
Seino S., Bell G.I.;
"Alternative splicing of human insulin receptor messenger RNA.";
Biochem. Biophys. Res. Commun. 159:312-316(1989).
[15]
NUCLEOTIDE SEQUENCE [MRNA] OF 744-823 (ISOFORM LONG), TISSUE SPECIFICITY,
LIGAND-BINDING, AND AUTOPHOSPHORYLATION.
PubMed=2369896; DOI=10.1002/j.1460-2075.1990.tb07416.x;
Mosthaf L., Grako K., Dull T.J., Coussens L., Ullrich A., McClain D.A.;
"Functionally distinct insulin receptors generated by tissue-specific
alternative splicing.";
EMBO J. 9:2409-2413(1990).
[16]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 895-1085.
PubMed=2566545; DOI=10.2337/diab.38.6.737;
Elbein S.C.;
"Molecular and clinical characterization of an insertional polymorphism of
the insulin-receptor gene.";
Diabetes 38:737-743(1989).
[17]
PROTEIN SEQUENCE OF 927-956; 981-1019; 1182-1194 AND 1352-1369, AND
PHOSPHORYLATION AT TYR-999; TYR-1355 AND TYR-1361.
TISSUE=Placenta;
PubMed=3166375; DOI=10.1042/bj2520607;
Tavare J.M., Denton R.M.;
"Studies on the autophosphorylation of the insulin receptor from human
placenta. Analysis of the sites phosphorylated by two-dimensional peptide
mapping.";
Biochem. J. 252:607-615(1988).
[18]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1006-1123.
PubMed=2544997; DOI=10.1126/science.2544997;
Taira M., Taira M., Hashimoto N., Shimada F., Suzuki Y., Kanatsuka A.,
Nakamura F., Ebina Y., Tatibana M., Makino H.;
"Human diabetes associated with a deletion of the tyrosine kinase domain of
the insulin receptor.";
Science 245:63-66(1989).
[19]
PARTIAL PROTEIN SEQUENCE.
PubMed=3447155;
Fujita-Yamaguchi Y., Hawke D., Shively J.E., Choi S.;
"Partial amino acid sequence analyses of human placental insulin
receptor.";
Protein Seq. Data Anal. 1:3-6(1987).
[20]
MUTAGENESIS OF LYS-1057.
PubMed=3101064; DOI=10.1073/pnas.84.3.704;
Ebina Y., Araki E., Taira M., Shimada F., Mori M., Craik C.S., Siddle K.,
Pierce S.B., Roth R.A., Rutter W.J.;
"Replacement of lysine residue 1030 in the putative ATP-binding region of
the insulin receptor abolishes insulin- and antibody-stimulated glucose
uptake and receptor kinase activity.";
Proc. Natl. Acad. Sci. U.S.A. 84:704-708(1987).
[21]
MUTAGENESIS OF TYR-999.
PubMed=2842060; DOI=10.1016/s0092-8674(88)80008-4;
White M.F., Livingston J.N., Backer J.M., Lauris V., Dull T.J., Ullrich A.,
Kahn C.R.;
"Mutation of the insulin receptor at tyrosine 960 inhibits signal
transmission but does not affect its tyrosine kinase activity.";
Cell 54:641-649(1988).
[22]
AUTOPHOSPHORYLATION.
PubMed=1321605; DOI=10.1016/s0006-291x(05)80799-5;
Dickens M., Tavare J.M.;
"Analysis of the order of autophosphorylation of human insulin receptor
tyrosines 1158, 1162 and 1163.";
Biochem. Biophys. Res. Commun. 186:244-250(1992).
[23]
DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-541.
PubMed=1472036; DOI=10.1016/0006-291x(92)92250-2;
Schaeffer L., Ljungqvist L.;
"Identification of a disulfide bridge connecting the alpha-subunits of the
extracellular domain of the insulin receptor.";
Biochem. Biophys. Res. Commun. 189:650-653(1992).
[24]
FUNCTION, AND FORMATION OF A HYBRID RECEPTOR WITH IGF1R.
PubMed=8452530; DOI=10.1042/bj2900419;
Soos M.A., Field C.E., Siddle K.;
"Purified hybrid insulin/insulin-like growth factor-I receptors bind
insulin-like growth factor-I, but not insulin, with high affinity.";
Biochem. J. 290:419-426(1993).
[25]
FUNCTION, AND INTERACTION WITH PIK3R1.
PubMed=8276809;
Van Horn D.J., Myers M.G. Jr., Backer J.M.;
"Direct activation of the phosphatidylinositol 3'-kinase by the insulin
receptor.";
J. Biol. Chem. 269:29-32(1994).
[26]
INTERACTION WITH IRS1 AND SHC1, AND MUTAGENESIS OF LEU-991; TYR-992;
ASN-996; 996-ASN-PRO-997; PRO-997; TYR-999; LEU-1000 AND ALA-1002.
PubMed=7559478; DOI=10.1074/jbc.270.40.23258;
He W., O'Neill T.J., Gustafson T.A.;
"Distinct modes of interaction of SHC and insulin receptor substrate-1 with
the insulin receptor NPEY region via non-SH2 domains.";
J. Biol. Chem. 270:23258-23262(1995).
[27]
INTERACTION WITH IRS1; SHC1 AND PIK3R1, AND MUTAGENESIS OF ASN-996;
PRO-997; GLU-998; TYR-999 AND LYS-1057.
PubMed=7537849; DOI=10.1128/mcb.15.5.2500;
Gustafson T.A., He W., Craparo A., Schaub C.D., O'Neill T.J.;
"Phosphotyrosine-dependent interaction of SHC and insulin receptor
substrate 1 with the NPEY motif of the insulin receptor via a novel non-SH2
domain.";
Mol. Cell. Biol. 15:2500-2508(1995).
[28]
FORMATION OF A HYBRID RECEPTOR WITH IGF1R, AND TISSUE SPECIFICITY.
PubMed=9355755; DOI=10.1042/bj3270209;
Bailyes E.M., Nave B.T., Soos M.A., Orr S.R., Hayward A.C., Siddle K.;
"Insulin receptor/IGF-I receptor hybrids are widely distributed in
mammalian tissues: quantification of individual receptor species by
selective immunoprecipitation and immunoblotting.";
Biochem. J. 327:209-215(1997).
[29]
FUNCTION IN PHOSPHORYLATION OF STAT5B, MUTAGENESIS OF TYR-999, AND
INTERACTION WITH STAT5B; IRS1 AND IRS2.
PubMed=9428692; DOI=10.1111/j.1432-1033.1997.0411a.x;
Sawka-Verhelle D., Filloux C., Tartare-Deckert S., Mothe I.,
Van Obberghen E.;
"Identification of Stat 5B as a substrate of the insulin receptor.";
Eur. J. Biochem. 250:411-417(1997).
[30]
INTERACTION WITH PTPRF.
PubMed=8995282; DOI=10.1074/jbc.272.11.7519;
Ahmad F., Goldstein B.J.;
"Functional association between the insulin receptor and the transmembrane
protein-tyrosine phosphatase LAR in intact cells.";
J. Biol. Chem. 272:448-457(1997).
[31]
INTERACTION WITH PTPRE, AND DEPHOSPHORYLATION BY PTPRE.
PubMed=8999839; DOI=10.1074/jbc.272.3.1639;
Bandyopadhyay D., Kusari A., Kenner K.A., Liu F., Chernoff J.,
Gustafson T.A., Kusari J.;
"Protein-tyrosine phosphatase 1B complexes with the insulin receptor in
vivo and is tyrosine-phosphorylated in the presence of insulin.";
J. Biol. Chem. 272:1639-1645(1997).
[32]
FORMATION OF A HYBRID RECEPTOR WITH IGF1R, AND TISSUE SPECIFICITY.
PubMed=9202395; DOI=10.1016/s0303-7207(97)04050-1;
Federici M., Porzio O., Zucaro L., Fusco A., Borboni P., Lauro D.,
Sesti G.;
"Distribution of insulin/insulin-like growth factor-I hybrid receptors in
human tissues.";
Mol. Cell. Endocrinol. 129:121-126(1997).
[33]
TISSUE SPECIFICITY, AND FUNCTION AS RECEPTOR FOR IGFII (ISOFORM SHORT).
PubMed=10207053; DOI=10.1128/mcb.19.5.3278;
Frasca F., Pandini G., Scalia P., Sciacca L., Mineo R., Costantino A.,
Goldfine I.D., Belfiore A., Vigneri R.;
"Insulin receptor isoform A, a newly recognized, high-affinity insulin-like
growth factor II receptor in fetal and cancer cells.";
Mol. Cell. Biol. 19:3278-3288(1999).
[34]
INTERACTION WITH ENPP1, AND ACTIVITY REGULATION.
PubMed=10615944; DOI=10.2337/diabetes.49.1.13;
Maddux B.A., Goldfine I.D.;
"Membrane glycoprotein PC-1 inhibition of insulin receptor function occurs
via direct interaction with the receptor alpha-subunit.";
Diabetes 49:13-19(2000).
[35]
PHOSPHORYLATION, AND DEPHOSPHORYLATION BY PTPN1 AND PTPN2.
PubMed=10734133; DOI=10.1074/jbc.275.13.9792;
Waelchli S., Curchod M.L., Gobert R.P., Arkinstall S.,
Hooft van Huijsduijnen R.;
"Identification of tyrosine phosphatases that dephosphorylate the insulin
receptor. A brute force approach based on 'substrate-trapping' mutants.";
J. Biol. Chem. 275:9792-9796(2000).
[36]
INTERACTION WITH GRB7, AND MUTAGENESIS OF LYS-1057; TYR-1189 AND TYR-1190.
PubMed=10803466; DOI=10.1038/sj.onc.1203469;
Kasus-Jacobi A., Bereziat V., Perdereau D., Girard J., Burnol A.F.;
"Evidence for an interaction between the insulin receptor and Grb7. A role
for two of its binding domains, PIR and SH2.";
Oncogene 19:2052-2059(2000).
[37]
INTERACTION WITH SORBS1.
PubMed=11374898; DOI=10.1006/geno.2001.6541;
Lin W.-H., Huang C.-J., Liu M.-W., Chang H.-M., Chen Y.-J., Tai T.-Y.,
Chuang L.-M.;
"Cloning, mapping, and characterization of the human sorbin and SH3 domain
containing 1 (SORBS1) gene: a protein associated with c-Abl during insulin
signaling in the hepatoma cell line Hep3B.";
Genomics 74:12-20(2001).
[38]
CATALYTIC ACTIVITY, MUTAGENESIS OF ASP-1159 AND ARG-1163, AND ACTIVITY
REGULATION.
PubMed=11598120; DOI=10.1074/jbc.m107236200;
Ablooglu A.J., Frankel M., Rusinova E., Ross J.B., Kohanski R.A.;
"Multiple activation loop conformations and their regulatory properties in
the insulin receptor's kinase domain.";
J. Biol. Chem. 276:46933-46940(2001).
[39]
INTERACTION WITH GRB14, AND ACTIVITY REGULATION.
PubMed=11726652; DOI=10.1074/jbc.m106574200;
Bereziat V., Kasus-Jacobi A., Perdereau D., Cariou B., Girard J.,
Burnol A.F.;
"Inhibition of insulin receptor catalytic activity by the molecular adapter
Grb14.";
J. Biol. Chem. 277:4845-4852(2002).
[40]
FUNCTION, AND FORMATION OF A HYBRID RECEPTOR WITH IGF1R.
PubMed=12138094; DOI=10.1074/jbc.m202766200;
Pandini G., Frasca F., Mineo R., Sciacca L., Vigneri R., Belfiore A.;
"Insulin/insulin-like growth factor I hybrid receptors have different
biological characteristics depending on the insulin receptor isoform
involved.";
J. Biol. Chem. 277:39684-39695(2002).
[41]
INTERACTION WITH GRB10, AND ACTIVITY REGULATION.
PubMed=12493740; DOI=10.1074/jbc.m208518200;
Wick K.R., Werner E.D., Langlais P., Ramos F.J., Dong L.Q., Shoelson S.E.,
Liu F.;
"Grb10 inhibits insulin-stimulated insulin receptor substrate (IRS)-
phosphatidylinositol 3-kinase/Akt signaling pathway by disrupting the
association of IRS-1/IRS-2 with the insulin receptor.";
J. Biol. Chem. 278:8460-8467(2003).
[42]
PHOSPHORYLATION, AND DEPHOSPHORYLATION BY PTPN2.
PubMed=12612081; DOI=10.1128/mcb.23.6.2096-2108.2003;
Galic S., Klingler-Hoffmann M., Fodero-Tavoletti M.T., Puryer M.A.,
Meng T.C., Tonks N.K., Tiganis T.;
"Regulation of insulin receptor signaling by the protein tyrosine
phosphatase TCPTP.";
Mol. Cell. Biol. 23:2096-2108(2003).
[43]
INTERACTION WITH SOCS7.
PubMed=16127460; DOI=10.1172/jci23853;
Banks A.S., Li J., McKeag L., Hribal M.L., Kashiwada M., Accili D.,
Rothman P.B.;
"Deletion of SOCS7 leads to enhanced insulin action and enlarged islets of
Langerhans.";
J. Clin. Invest. 115:2462-2471(2005).
[44]
FUNCTION IN PHOSPHORYLATION OF PDPK1, AND INTERACTION WITH PDPK1.
PubMed=16314505; DOI=10.1128/mcb.25.24.10803-10814.2005;
Fiory F., Alberobello A.T., Miele C., Oriente F., Esposito I., Corbo V.,
Ruvo M., Tizzano B., Rasmussen T.E., Gammeltoft S., Formisano P.,
Beguinot F.;
"Tyrosine phosphorylation of phosphoinositide-dependent kinase 1 by the
insulin receptor is necessary for insulin metabolic signaling.";
Mol. Cell. Biol. 25:10803-10814(2005).
[45]
DEPHOSPHORYLATION BY PTPRE.
PubMed=15738637; DOI=10.2108/zsj.22.169;
Nakagawa Y., Aoki N., Aoyama K., Shimizu H., Shimano H., Yamada N.,
Miyazaki H.;
"Receptor-type protein tyrosine phosphatase epsilon (PTPepsilonM) is a
negative regulator of insulin signaling in primary hepatocytes and liver.";
Zool. Sci. 22:169-175(2005).
[46]
FUNCTION, AND FORMATION OF A HYBRID RECEPTOR WITH IGF1R.
PubMed=16831875; DOI=10.1074/jbc.m605189200;
Slaaby R., Schaeffer L., Lautrup-Larsen I., Andersen A.S., Shaw A.C.,
Mathiasen I.S., Brandt J.;
"Hybrid receptors formed by insulin receptor (IR) and insulin-like growth
factor I receptor (IGF-IR) have low insulin and high IGF-1 affinity
irrespective of the IR splice variant.";
J. Biol. Chem. 281:25869-25874(2006).
[47]
REVIEW ON SIGNALING PATHWAYS.
PubMed=16493415; DOI=10.1038/nrm1837;
Taniguchi C.M., Emanuelli B., Kahn C.R.;
"Critical nodes in signalling pathways: insights into insulin action.";
Nat. Rev. Mol. Cell Biol. 7:85-96(2006).
[48]
REVIEW ON REGULATION OF INSR FUNCTION.
PubMed=17347799; DOI=10.1007/s00018-007-6359-9;
Youngren J.F.;
"Regulation of insulin receptor function.";
Cell. Mol. Life Sci. 64:873-891(2007).
[49]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-400; TYR-401 AND SER-407, AND
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma;
PubMed=18669648; DOI=10.1073/pnas.0805139105;
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
Elledge S.J., Gygi S.P.;
"A quantitative atlas of mitotic phosphorylation.";
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
[50]
DOMAIN, AND INSULIN-BINDING SITE.
PubMed=19459609; DOI=10.1021/bi900261q;
Menting J.G., Ward C.W., Margetts M.B., Lawrence M.C.;
"A thermodynamic study of ligand binding to the first three domains of the
human insulin receptor: relationship between the receptor alpha-chain C-
terminal peptide and the site 1 insulin mimetic peptides.";
Biochemistry 48:5492-5500(2009).
[51]
GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-242 AND ASN-541.
TISSUE=Liver;
PubMed=19159218; DOI=10.1021/pr8008012;
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
"Glycoproteomics analysis of human liver tissue by combination of multiple
enzyme digestion and hydrazide chemistry.";
J. Proteome Res. 8:651-661(2009).
[52]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
Mann M., Daub H.;
"Large-scale proteomics analysis of the human kinome.";
Mol. Cell. Proteomics 8:1751-1764(2009).
[53]
GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-445 AND ASN-920.
TISSUE=Leukemic T-cell;
PubMed=19349973; DOI=10.1038/nbt.1532;
Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
Schiess R., Aebersold R., Watts J.D.;
"Mass-spectrometric identification and relative quantification of N-linked
cell surface glycoproteins.";
Nat. Biotechnol. 27:378-386(2009).
[54]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Liver;
PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
Ye M., Zou H.;
"An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
phosphoproteome.";
J. Proteomics 96:253-262(2014).
[55]
INTERACTION WITH CCDC88A AND GNAI3.
PubMed=25187647; DOI=10.1091/mbc.e14-05-0978;
Lin C., Ear J., Midde K., Lopez-Sanchez I., Aznar N., Garcia-Marcos M.,
Kufareva I., Abagyan R., Ghosh P.;
"Structural basis for activation of trimeric Gi proteins by multiple growth
factor receptors via GIV/Girdin.";
Mol. Biol. Cell 25:3654-3671(2014).
[56]
INTERACTION WITH SORL1.
PubMed=27322061; DOI=10.1172/jci84708;
Schmidt V., Schulz N., Yan X., Schuermann A., Kempa S., Kern M.,
Blueher M., Poy M.N., Olivecrona G., Willnow T.E.;
"SORLA facilitates insulin receptor signaling in adipocytes and exacerbates
obesity.";
J. Clin. Invest. 126:2706-2720(2016).
[57]
SUBUNIT.
PubMed=27617429; DOI=10.1038/nsmb.3292;
Menting J.G., Gajewiak J., MacRaild C.A., Chou D.H., Disotuar M.M.,
Smith N.A., Miller C., Erchegyi J., Rivier J.E., Olivera B.M., Forbes B.E.,
Smith B.J., Norton R.S., Safavi-Hemami H., Lawrence M.C.;
"A minimized human insulin-receptor-binding motif revealed in a Conus
geographus venom insulin.";
Nat. Struct. Mol. Biol. 23:916-920(2016).
[58]
X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1005-1310.
PubMed=7997262; DOI=10.1038/372746a0;
Hubbard S.R., Wei L., Ellis L., Hendrickson W.A.;
"Crystal structure of the tyrosine kinase domain of the human insulin
receptor.";
Nature 372:746-754(1994).
[59]
X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 1005-1310 IN COMPLEX WITH ATP
ANALOG AND IRS1 PEPTIDE, CATALYTIC ACTIVITY, ACTIVE SITE,
AUTOPHOSPHORYLATION, AND PHOSPHORYLATION AT TYR-1185; TYR-1189 AND
TYR-1190.
PubMed=9312016; DOI=10.1093/emboj/16.18.5572;
Hubbard S.R.;
"Crystal structure of the activated insulin receptor tyrosine kinase in
complex with peptide substrate and ATP analog.";
EMBO J. 16:5572-5581(1997).
[60]
X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 1005-1310 IN COMPLEX WITH ATP
ANALOG, AND CATALYTIC ACTIVITY.
PubMed=11124964; DOI=10.1074/jbc.m010161200;
Till J.H., Ablooglu A.J., Frankel M., Bishop S.M., Kohanski R.A.,
Hubbard S.R.;
"Crystallographic and solution studies of an activation loop mutant of the
insulin receptor tyrosine kinase: insights into kinase mechanism.";
J. Biol. Chem. 276:10049-10055(2001).
[61]
X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 1005-1298 OF MUTANT ASN-1159,
CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, AND MUTAGENESIS OF TYR-1011.
PubMed=12707268; DOI=10.1074/jbc.m302425200;
Li S., Covino N.D., Stein E.G., Till J.H., Hubbard S.R.;
"Structural and biochemical evidence for an autoinhibitory role for
tyrosine 984 in the juxtamembrane region of the insulin receptor.";
J. Biol. Chem. 278:26007-26014(2003).
[62]
X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1005-1310 IN COMPLEX WITH ATP
ANALOG AND SH2B2, AND PHOSPHORYLATION AT TYR-1185; TYR-1189 AND TYR-1190.
PubMed=14690593; DOI=10.1016/s1097-2765(03)00487-8;
Hu J., Liu J., Ghirlando R., Saltiel A.R., Hubbard S.R.;
"Structural basis for recruitment of the adaptor protein APS to the
activated insulin receptor.";
Mol. Cell 12:1379-1389(2003).
[63]
X-RAY CRYSTALLOGRAPHY (3.20 ANGSTROMS) OF 1005-1310 IN COMPLEX WITH GRB14,
INTERACTION WITH GRB14, AUTOPHOSPHORYLATION, AND PHOSPHORYLATION AT
TYR-1185; TYR-1189 AND TYR-1190.
PubMed=16246733; DOI=10.1016/j.molcel.2005.09.001;
Depetris R.S., Hu J., Gimpelevich I., Holt L.J., Daly R.J., Hubbard S.R.;
"Structural basis for inhibition of the insulin receptor by the adaptor
protein Grb14.";
Mol. Cell 20:325-333(2005).
[64]
X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 1005-1310 IN COMPLEX WITH PTPN1,
AND PHOSPHORYLATION AT TYR-1185; TYR-1189 AND TYR-1190.
PubMed=16271887; DOI=10.1016/j.str.2005.07.019;
Li S., Depetris R.S., Barford D., Chernoff J., Hubbard S.R.;
"Crystal structure of a complex between protein tyrosine phosphatase 1B and
the insulin receptor tyrosine kinase.";
Structure 13:1643-1651(2005).
[65]
X-RAY CRYSTALLOGRAPHY (3.8 ANGSTROMS) OF 28-943 IN COMPLEX WITH INSULIN
ANALOG, DOMAIN, AND DISULFIDE BONDS.
PubMed=16957736; DOI=10.1038/nature05106;
McKern N.M., Lawrence M.C., Streltsov V.A., Lou M.Z., Adams T.E.,
Lovrecz G.O., Elleman T.C., Richards K.M., Bentley J.D., Pilling P.A.,
Hoyne P.A., Cartledge K.A., Pham T.M., Lewis J.L., Sankovich S.E.,
Stoichevska V., Da Silva E., Robinson C.P., Frenkel M.J., Sparrow L.G.,
Fernley R.T., Epa V.C., Ward C.W.;
"Structure of the insulin receptor ectodomain reveals a folded-over
conformation.";
Nature 443:218-221(2006).
[66]
X-RAY CRYSTALLOGRAPHY (2.32 ANGSTROMS) OF 28-512, GLYCOSYLATION AT ASN-43;
ASN-52; ASN-138; ASN-242; ASN-282; ASN-364; ASN-424 AND ASN-445, AND
DISULFIDE BONDS.
PubMed=16894147; DOI=10.1073/pnas.0605395103;
Lou M., Garrett T.P., McKern N.M., Hoyne P.A., Epa V.C., Bentley J.D.,
Lovrecz G.O., Cosgrove L.J., Frenkel M.J., Ward C.W.;
"The first three domains of the insulin receptor differ structurally from
the insulin-like growth factor 1 receptor in the regions governing ligand
specificity.";
Proc. Natl. Acad. Sci. U.S.A. 103:12429-12434(2006).
[67]
X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 1005-1310 IN COMPLEX WITH ATP AND
IRS2, CATALYTIC ACTIVITY, PHOSPHORYLATION AT TYR-1185; TYR-1189 AND
TYR-1190, AND INTERACTION WITH IRS2.
PubMed=18278056; DOI=10.1038/nsmb.1388;
Wu J., Tseng Y.D., Xu C.F., Neubert T.A., White M.F., Hubbard S.R.;
"Structural and biochemical characterization of the KRLB region in insulin
receptor substrate-2.";
Nat. Struct. Mol. Biol. 15:251-258(2008).
[68]
X-RAY CRYSTALLOGRAPHY (3.25 ANGSTROMS) OF 1009-1310 IN COMPLEX WITH
INHIBITORY PEPTIDE, AND PHOSPHORYLATION AT TYR-1185; TYR-1189 AND TYR-1190.
PubMed=18767165; DOI=10.1002/prot.22207;
Katayama N., Orita M., Yamaguchi T., Hisamichi H., Kuromitsu S.,
Kurihara H., Sakashita H., Matsumoto Y., Fujita S., Niimi T.;
"Identification of a key element for hydrogen-bonding patterns between
protein kinases and their inhibitors.";
Proteins 73:795-801(2008).
[69]
X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 1005-1310 IN COMPLEX WITH
SYNTHETIC INHIBITOR, AND CATALYTIC ACTIVITY.
PubMed=19071018; DOI=10.1016/j.bmcl.2008.11.077;
Chamberlain S.D., Redman A.M., Wilson J.W., Deanda F., Shotwell J.B.,
Gerding R., Lei H., Yang B., Stevens K.L., Hassell A.M., Shewchuk L.M.,
Leesnitzer M.A., Smith J.L., Sabbatini P., Atkins C., Groy A., Rowand J.L.,
Kumar R., Mook R.A. Jr., Moorthy G., Patnaik S.;
"Optimization of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine IGF-1R
tyrosine kinase inhibitors towards JNK selectivity.";
Bioorg. Med. Chem. Lett. 19:360-364(2009).
[70]
X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1005-1310 IN COMPLEX WITH
SYNTHETIC INHIBITOR, AND CATALYTIC ACTIVITY.
PubMed=19056263; DOI=10.1016/j.bmcl.2008.11.046;
Chamberlain S.D., Wilson J.W., Deanda F., Patnaik S., Redman A.M., Yang B.,
Shewchuk L., Sabbatini P., Leesnitzer M.A., Groy A., Atkins C., Gerding R.,
Hassell A.M., Lei H., Mook R.A. Jr., Moorthy G., Rowand J.L., Stevens K.L.,
Kumar R., Shotwell J.B.;
"Discovery of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines: potent
inhibitors of the IGF-1R receptor tyrosine kinase.";
Bioorg. Med. Chem. Lett. 19:469-473(2009).
[71]
X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 1017-1322 IN COMPLEX WITH
SYNTHETIC INHIBITOR, AND CATALYTIC ACTIVITY.
PubMed=19394223; DOI=10.1016/j.bmcl.2008.12.110;
Patnaik S., Stevens K.L., Gerding R., Deanda F., Shotwell J.B., Tang J.,
Hamajima T., Nakamura H., Leesnitzer M.A., Hassell A.M., Shewchuck L.M.,
Kumar R., Lei H., Chamberlain S.D.;
"Discovery of 3,5-disubstituted-1H-pyrrolo[2,3-b]pyridines as potent
inhibitors of the insulin-like growth factor-1 receptor (IGF-1R) tyrosine
kinase.";
Bioorg. Med. Chem. Lett. 19:3136-3140(2009).
[72]
X-RAY CRYSTALLOGRAPHY (3.80 ANGSTROMS) OF 28-956, INSULIN-BINDING REGION,
AND DISULFIDE BONDS.
PubMed=20348418; DOI=10.1073/pnas.1001813107;
Smith B.J., Huang K., Kong G., Chan S.J., Nakagawa S., Menting J.G.,
Hu S.Q., Whittaker J., Steiner D.F., Katsoyannis P.G., Ward C.W.,
Weiss M.A., Lawrence M.C.;
"Structural resolution of a tandem hormone-binding element in the insulin
receptor and its implications for design of peptide agonists.";
Proc. Natl. Acad. Sci. U.S.A. 107:6771-6776(2010).
[73]
X-RAY CRYSTALLOGRAPHY (3.9 ANGSTROMS) OF 28-620 IN COMPLEX WITH INSULIN,
DOMAIN, GLYCOSYLATION AT ASN-43; ASN-52; ASN-138; ASN-242 AND ASN-282, AND
DISULFIDE BONDS.
PubMed=23302862; DOI=10.1038/nature11781;
Menting J.G., Whittaker J., Margetts M.B., Whittaker L.J., Kong G.K.,
Smith B.J., Watson C.J., Zakova L., Kletvikova E., Jiracek J., Chan S.J.,
Steiner D.F., Dodson G.G., Brzozowski A.M., Weiss M.A., Ward C.W.,
Lawrence M.C.;
"How insulin engages its primary binding site on the insulin receptor.";
Nature 493:241-245(2013).
[74]
VARIANT IRAN TYPE A SER-762.
PubMed=3283938; DOI=10.1126/science.3283938;
Yoshimasa Y., Seino S., Whittaker J., Kakehi T., Kosaki A., Kuzuya H.,
Imura H., Bell G.I., Steiner D.F.;
"Insulin-resistant diabetes due to a point mutation that prevents insulin
proreceptor processing.";
Science 240:784-787(1988).
[75]
VARIANT LEPRCH GLU-487.
PubMed=2834824; DOI=10.1126/science.2834824;
Kadowaki T., Bevins C., Cama A., Ojamaa K., Marcus-Samuels B., Kadowaki H.,
Beitz L., McKeon C., Taylor S.I.;
"Two mutant alleles of the insulin receptor gene in a patient with extreme
insulin resistance.";
Science 240:787-790(1988).
[76]
VARIANT LEPRCH PRO-260.
PubMed=2479553; DOI=10.1002/j.1460-2075.1989.tb08387.x;
Klinkhamer M.P., Groen N.A., van der Zon G.C.M., Lindhout D.,
Sandkuyl L.A., Krans H.M.J., Moeller W., Maassen J.A.;
"A leucine-to-proline mutation in the insulin receptor in a family with
insulin resistance.";
EMBO J. 8:2503-2507(1989).
[77]
VARIANT IRAN TYPE A VAL-1035.
PubMed=2544998; DOI=10.1126/science.2544998;
Odawara M., Kadowaki T., Yamamoto R., Shibasaki Y., Tobe K., Accili D.,
Bevins C., Mikami Y., Matsuura N., Akanuma Y., Takaku F., Taylor S.I.,
Kasuga M.;
"Human diabetes associated with a mutation in the tyrosine kinase domain of
the insulin receptor.";
Science 245:66-68(1989).
[78]
VARIANT IRAN TYPE A THR-1161.
PubMed=2168397;
Moller D.E., Yokota A., White M.F., Pazianos A.G., Flier J.S.;
"A naturally occurring mutation of insulin receptor alanine 1134 impairs
tyrosine kinase function and is associated with dominantly inherited
insulin resistance.";
J. Biol. Chem. 265:14979-14985(1990).
[79]
CHARACTERIZATION OF VARIANT RMS LYS-42.
PubMed=2121734;
Kadowaki T., Kadowaki H., Accili D., Taylor S.I.;
"Substitution of lysine for asparagine at position 15 in the alpha-subunit
of the human insulin receptor. A mutation that impairs transport of
receptors to the cell surface and decreases the affinity of insulin
binding.";
J. Biol. Chem. 265:19143-19150(1990).
[80]
VARIANT RMS LYS-42, VARIANT LEPRCH ARG-236, AND VARIANT IRAN TYPE A
SER-489.
PubMed=2365819; DOI=10.1172/jci114693;
Kadowaki T., Kadowaki H., Rechler M.M., Serrano-Rios M., Roth J.,
Gorden P., Taylor S.I.;
"Five mutant alleles of the insulin receptor gene in patients with genetic
forms of insulin resistance.";
J. Clin. Invest. 86:254-264(1990).
[81]
VARIANT IRAN TYPE A SER-1227.
PubMed=1963473; DOI=10.1210/mend-4-8-1183;
Moller D.E., Yokota A., Ginsberg-Fellner F., Flier J.S.;
"Functional properties of a naturally occurring Trp1200-->Ser1200 mutation
of the insulin receptor.";
Mol. Endocrinol. 4:1183-1191(1990).
[82]
VARIANT GLU-1095.
PubMed=2040394; DOI=10.2337/diab.40.6.777;
O'Rahilly S., Choi W.H., Patel P., Turner R.C., Flier J.S., Moller D.E.;
"Detection of mutations in insulin-receptor gene in NIDDM patients by
analysis of single-stranded conformation polymorphisms.";
Diabetes 40:777-782(1991).
[83]
VARIANT IRAN TYPE A GLN-1020.
PubMed=2002058;
Kusari J., Takata Y., Hatada E., Freidenberg G., Kolterman O.,
Olefsky J.M.;
"Insulin resistance and diabetes due to different mutations in the tyrosine
kinase domain of both insulin receptor gene alleles.";
J. Biol. Chem. 266:5260-5267(1991).
[84]
VARIANT INS RESISTANCE ILE-1180.
PubMed=1890161; DOI=10.1210/jcem-73-4-894;
Cama A., de la Luz Sierra M., Ottini L., Kadowaki T., Gorden P.,
Imperato-Mcginley J., Taylor S.I.;
"A mutation in the tyrosine kinase domain of the insulin receptor
associated with insulin resistance in an obese woman.";
J. Clin. Endocrinol. Metab. 73:894-901(1991).
[85]
VARIANTS LEPRCH ALA-55 AND ARG-393.
PubMed=1607067; DOI=10.2337/diab.41.4.408;
Barbetti F., Gejman P.V., Taylor S.I., Raben N., Cama A., Bonora E.,
Pizzo P., Moghetti P., Muggeo M., Roth J.;
"Detection of mutations in insulin receptor gene by denaturing gradient gel
electrophoresis.";
Diabetes 41:408-415(1992).
[86]
VARIANT NIDDM GLN-1191.
PubMed=1607076; DOI=10.2337/diab.41.4.521;
Cocozza S., Porcellini A., Riccardi G., Monticelli A., Condorelli G.,
Ferrara A., Pianese L., Miele C., Capaldo B., Beguinot F., Varrone S.;
"NIDDM associated with mutation in tyrosine kinase domain of insulin
receptor gene.";
Diabetes 41:521-526(1992).
[87]
VARIANT IRAN TYPE A LEU-1205.
PubMed=1563582; DOI=10.1007/bf00400927;
Kim H., Kadowaki H., Sakura H., Odawara M., Momomura K., Takahashi Y.,
Miyazaki Y., Ohtani T., Akanuma Y., Yazaki Y., Kasuga M., Taylor S.I.,
Kadowaki T.;
"Detection of mutations in the insulin receptor gene in patients with
insulin resistance by analysis of single-stranded conformational
polymorphisms.";
Diabetologia 35:261-266(1992).
[88]
VARIANT LEPRCH ARG-58.
PubMed=1730625;
van der Vorm E.R., van der Zon G.C.M., Moeller W., Krans H.M.J.,
Lindhout D., Maassen J.A.;
"An Arg for Gly substitution at position 31 in the insulin receptor, linked
to insulin resistance, inhibits receptor processing and transport.";
J. Biol. Chem. 267:66-71(1992).
[89]
VARIANT NIDDM GLN-1158.
PubMed=1470163;
Kasuga M., Kishimoto M., Hashiramoto M., Yonezawa K., Kazumi T., Hagino H.,
Shii K.;
"Insulin receptor Arg1131-->Gln: a novel mutation in the catalytic loop of
insulin receptor observed in insulin resistant diabetes.";
Nihon Geka Gakkai Zasshi 93:968-971(1992).
[90]
VARIANT MET-1012.
PubMed=8432414; DOI=10.2337/diab.42.3.429;
Elbein S.C., Sorensen L.K., Schumacher M.C.;
"Methionine for valine substitution in exon 17 of the insulin receptor gene
in a pedigree with familial NIDDM.";
Diabetes 42:429-434(1993).
[91]
VARIANT IRAN TYPE A ASP-1075.
PubMed=8243830; DOI=10.2337/diab.42.12.1837;
Haruta T., Takata Y., Iwanishi M., Maegawa H., Imamura T., Egawa K.,
Itazu T., Kobayashi M.;
"Ala1048-->Asp mutation in the kinase domain of insulin receptor causes
defective kinase activity and insulin resistance.";
Diabetes 42:1837-1844(1993).
[92]
VARIANT MET-1012.
PubMed=8458533; DOI=10.1007/bf00400701;
van der Vorm E.R., Kuipers A., Bonenkamp J.W., Kleijer W.J.,
van Maldergem L., Herwig J., Maassen J.A.;
"Patients with lipodystrophic diabetes mellitus of the Seip-Berardinelli
type, express normal insulin receptors.";
Diabetologia 36:172-174(1993).
[93]
VARIANT INS RESISTANCE LEU-1220.
PubMed=8390949; DOI=10.1007/bf00402277;
Iwanishi M., Haruta T., Takata Y., Ishibashi O., Sasaoka T., Egawa K.,
Imamura T., Naitou K., Itazu T., Kobayashi M.;
"A mutation (Trp1193-->Leu1193) in the tyrosine kinase domain of the
insulin receptor associated with type A syndrome of insulin resistance.";
Diabetologia 36:414-422(1993).
[94]
VARIANT INS RESISTANCE LEU-220.
PubMed=8242067; DOI=10.1093/hmg/2.9.1437;
Carrera P., Cordera R., Ferrari M., Cremonesi L., Taramelli R.,
Andraghetti G., Carducci C., Dozio N., Pozza G., Taylor S.I., Micossi P.,
Barbetti F.;
"Substitution of Leu for Pro-193 in the insulin receptor in a patient with
a genetic form of severe insulin resistance.";
Hum. Mol. Genet. 2:1437-1441(1993).
[95]
CHARACTERIZATION OF VARIANT IRAN TYPE A GLU-1162.
PubMed=8096518;
Cama A., de la Luz Sierra M., Quon M.J., Ottini L., Gorden P., Taylor S.I.;
"Substitution of glutamic acid for alanine 1135 in the putative 'catalytic
loop' of the tyrosine kinase domain of the human insulin receptor. A
mutation that impairs proteolytic processing into subunits and inhibits
receptor tyrosine kinase activity.";
J. Biol. Chem. 268:8060-8069(1993).
[96]
VARIANT IRAN TYPE A VAL-409.
PubMed=8388389;
Lebrun C., Baron V., Kaliman P., Gautier N., Dolais-Kitabgi J.,
Taylor S.I., Accili D., van Obberghen E.;
"Antibodies to the extracellular receptor domain restore the hormone-
insensitive kinase and conformation of the mutant insulin receptor valine
382.";
J. Biol. Chem. 268:11272-11277(1993).
[97]
VARIANT LEPRCH MET-146.
PubMed=8326490; DOI=10.1136/jmg.30.6.470;
Al-Gazali L.I., Khalil M., Devadas K.;
"A syndrome of insulin resistance resembling leprechaunism in five sibs of
consanguineous parents.";
J. Med. Genet. 30:470-475(1993).
[98]
VARIANT LEPRCH PRO-113.
PubMed=8419945; DOI=10.1073/pnas.90.1.60;
Longo N., Langley S.D., Griffin L.D., Elsas L.J.;
"Activation of glucose transport by a natural mutation in the human insulin
receptor.";
Proc. Natl. Acad. Sci. U.S.A. 90:60-64(1993).
[99]
VARIANT IRAN TYPE A GLN-1201.
PubMed=8288049; DOI=10.2337/diab.43.2.247;
Moller D.E., Cohen O., Yamaguchi Y., Assiz R., Grigorescu F., Eberle A.,
Morrow L.A., Moses A.C., Flier J.S.;
"Prevalence of mutations in the insulin receptor gene in subjects with
features of the type A syndrome of insulin resistance.";
Diabetes 43:247-255(1994).
[100]
VARIANT RMS SYNDROME LEU-350, VARIANTS IRAN TYPE A LEU-1205 AND GLN-1378,
AND VARIANT MET-1012.
PubMed=8314008; DOI=10.2337/diab.43.3.357;
Krook A., Kumar S., Laing I., Boulton A.J., Wass J.A., O'Rahilly S.;
"Molecular scanning of the insulin receptor gene in syndromes of insulin
resistance.";
Diabetes 43:357-368(1994).
[101]
CHARACTERIZATION OF VARIANT IRAN TYPE A GLN-1201.
PubMed=8082780; DOI=10.1016/0014-5793(94)00876-0;
Moritz W., Froesch E.R., Boeni-Schnetzler M.;
"Functional properties of a heterozygous mutation (Arg1174-->Gln) in the
tyrosine kinase domain of the insulin receptor from a type A insulin
resistant patient.";
FEBS Lett. 351:276-280(1994).
[102]
VARIANT LEPRCH SER-439.
PubMed=8188715;
van der Vorm E.R., Kuipers A., Kielkopf-Renner S., Krans H.M.J., Moller W.,
Maassen J.A.;
"A mutation in the insulin receptor that impairs proreceptor processing but
not insulin binding.";
J. Biol. Chem. 269:14297-14302(1994).
[103]
CHARACTERIZATION OF VARIANTS IRAN TYPE A ASP-1206 AND LEU-1220.
PubMed=7983039;
Imamura T., Takata Y., Sasaoka T., Takada Y., Morioka H., Haruta T.,
Sawa T., Iwanishi M., Hu Y.G., Suzuki Y., Hamada J., Kobayashi M.;
"Two naturally occurring mutations in the kinase domain of insulin receptor
accelerate degradation of the insulin receptor and impair the kinase
activity.";
J. Biol. Chem. 269:31019-31027(1994).
[104]
VARIANT LEPRCH MET-146.
PubMed=7815442; DOI=10.1136/jmg.31.9.715;
Hone J., Accili D., al-Gazali L.I., Lestringant G., Orban T., Taylor S.I.;
"Homozygosity for a new mutation (Ile119-->Met) in the insulin receptor
gene in five sibs with familial insulin resistance.";
J. Med. Genet. 31:715-716(1994).
[105]
VARIANT NIDDM ALA-858, AND VARIANT CYS-1361.
PubMed=7657032; DOI=10.2337/diab.44.9.1081;
Kan M., Kanai F., Iida M., Jinnouchi H., Todaka M., Imanaka T., Ito K.,
Nishioka Y., Ohnishi T., Kamohara S., Hayashi H., Murakami T., Kagawa S.,
Sano H., Hashimoto N., Yoshida S., Makino H., Ebina Y.;
"Frequency of mutations of insulin receptor gene in Japanese patients with
NIDDM.";
Diabetes 44:1081-1086(1995).
[106]
VARIANT LEPRCH ASN-308 DEL.
PubMed=7538143; DOI=10.1210/jcem.80.5.7538143;
Longo N., Langley S.D., Griffin L.D., Elsas L.J.;
"Two mutations in the insulin receptor gene of a patient with
leprechaunism: application to prenatal diagnosis.";
J. Clin. Endocrinol. Metab. 80:1496-1501(1995).
[107]
VARIANT PHE-1023.
PubMed=8890729; DOI=10.1530/eje.0.1350357;
Moritz W., Boeni-Schnetzler M., Stevens W., Froesch E.R., Levy J.R.;
"In-frame exon 2 deletion in insulin receptor RNA in a family with extreme
insulin resistance in association with defective insulin binding: a case
report.";
Eur. J. Endocrinol. 135:357-363(1996).
[108]
VARIANT LEPRCH ASN-308 DEL.
PubMed=8636294; DOI=10.1210/jcem.81.2.8636294;
Desbois-Mouthon C., Sert-Langeron C., Magre J., Oreal E., Blivet M.J.,
Flori E., Besmond C., Capeau J., Caron M.;
"Deletion of Asn281 in the alpha-subunit of the human insulin receptor
causes constitutive activation of the receptor and insulin
desensitization.";
J. Clin. Endocrinol. Metab. 81:719-727(1996).
[109]
VARIANT MET-1012.
PubMed=9199575; DOI=10.1086/515464;
Hansen L., Hansen T., Clausen J.O., Echwald S.M., Urhammer S.A.,
Rasmussen S.K., Pedersen O.;
"The Val985Met insulin-receptor variant in the Danish Caucasian population:
lack of associations with non-insulin-dependent diabetes mellitus or
insulin resistance.";
Am. J. Hum. Genet. 60:1532-1535(1997).
[110]
VARIANTS IRAN TYPE A GLY-86 AND PRO-89.
PubMed=9175790; DOI=10.1006/bbrc.1997.6695;
Rouard M., Macari F., Bouix O., Lautier C., Brun J.F., Lefebvre P.,
Renard E., Bringer J., Jaffiol C., Grigorescu F.;
"Identification of two novel insulin receptor mutations, Asp59Gly and
Leu62Pro, in type A syndrome of extreme insulin resistance.";
Biochem. Biophys. Res. Commun. 234:764-768(1997).
[111]
CHARACTERIZATION OF VARIANT LEPRCH MET-937.
PubMed=9299395; DOI=10.1006/bbrc.1997.7181;
Kadowaki H., Takahashi Y., Ando A., Momomura K., Kaburagi Y., Quin J.D.,
MacCuish A.C., Koda N., Fukushima Y., Taylor S.I., Akanuma Y., Yazaki Y.,
Kadowaki T.;
"Four mutant alleles of the insulin receptor gene associated with genetic
syndromes of extreme insulin resistance.";
Biochem. Biophys. Res. Commun. 237:516-520(1997).
[112]
VARIANTS LEPRCH TRP-1119 AND LYS-1206.
PubMed=9249867;
DOI=10.1002/(sici)1097-0223(199707)17:7<657::aid-pd132>3.0.co;2-8;
Desbois-Mouthon C., Girodon E., Ghanem N., Caron M., Pennerath A.,
Conteville P., Magre J., Besmond C., Goossens M., Capeau J., Amselem S.;
"Molecular analysis of the insulin receptor gene for prenatal diagnosis of
leprechaunism in two families.";
Prenat. Diagn. 17:657-663(1997).
[113]
VARIANTS LEPRCH TYR-301 AND TRP-1201.
PubMed=9703342; DOI=10.2337/diab.47.8.1362;
Whitehead J.P., Soos M.A., Jackson R., Tasic V., Kocova M., O'Rahilly S.;
"Multiple molecular mechanisms of insulin receptor dysfunction in a patient
with Donohue syndrome.";
Diabetes 47:1362-1364(1998).
[114]
VARIANTS RMS THR-1143 AND TRP-1158.
PubMed=10443650; DOI=10.1210/jcem.84.8.5902;
Longo N., Wang Y., Pasquali M.;
"Progressive decline in insulin levels in Rabson-Mendenhall syndrome.";
J. Clin. Endocrinol. Metab. 84:2623-2629(1999).
[115]
VARIANTS IRAN TYPE A LEU-167 AND VAL-1055.
PubMed=10733238; DOI=10.1034/j.1399-0004.2000.570110.x;
Rique S., Nogues C., Ibanez L., Marcos M.V., Ferragut J., Carrascosa A.,
Potau N.;
"Identification of three novel mutations in the insulin receptor gene in
type A insulin resistant patients.";
Clin. Genet. 57:67-69(2000).
[116]
VARIANT IRAN TYPE A TYR-280.
PubMed=11260230; DOI=10.1034/j.1399-0004.2001.590309.x;
Osawa H., Nishimiya T., Ochi M., Niiya T., Onuma H., Kitamuro F., Kaino Y.,
Kida K., Makino H.;
"Identification of novel C253Y missense and Y864X nonsense mutations in the
insulin receptor gene in type A insulin-resistant patients.";
Clin. Genet. 59:194-197(2001).
[117]
VARIANT IRAN TYPE A CYS-279.
PubMed=12107746; DOI=10.1007/s00125-002-0798-5;
Hamer I., Foti M., Emkey R., Cordier-Bussat M., Philippe J., De Meyts P.,
Maeder C., Kahn C.R., Carpentier J.-L.;
"An arginine to cysteine(252) mutation in insulin receptors from a patient
with severe insulin resistance inhibits receptor internalisation but
preserves signalling events.";
Diabetologia 45:657-667(2002).
[118]
CHARACTERIZATION OF VARIANTS LEPRCH PRO-113; VAL-119; ASN-308 DEL; THR-925
AND TRP-926, AND VARIANTS RMS THR-997; THR-1143; TRP-1158 AND TRP-1201.
PubMed=12023989; DOI=10.1093/hmg/11.12.1465;
Longo N., Wang Y., Smith S.A., Langley S.D., DiMeglio L.A.,
Giannella-Neto D.;
"Genotype-phenotype correlation in inherited severe insulin resistance.";
Hum. Mol. Genet. 11:1465-1475(2002).
[119]
VARIANT LEPRCH VAL-362 DEL.
PubMed=12538626; DOI=10.1210/en.2002-220815;
George S., Johansen A., Soos M.A., Mortensen H., Gammeltoft S., Saudek V.,
Siddle K., Hansen L., O'Rahilly S.;
"Deletion of V335 from the L2 domain of the insulin receptor results in a
conformationally abnormal receptor that is unable to bind insulin and
causes Donohue's syndrome in a human subject.";
Endocrinology 144:631-637(2003).
[120]
VARIANT IRAN TYPE A HIS-279, VARIANTS LEPRCH GLN-120; LEU-350; ASP-458 AND
TRP-1119, CHARACTERIZATION OF VARIANT IRAN TYPE A HIS-279, AND
CHARACTERIZATION OF VARIANTS LEPRCH GLN-120 AND ASP-458.
PubMed=12970295; DOI=10.1210/jc.2003-030034;
Maassen J.A., Tobias E.S., Kayserilli H., Tukel T., Yuksel-Apak M.,
D'Haens E., Kleijer W.J., Fery F., van der Zon G.C.M.;
"Identification and functional assessment of novel and known insulin
receptor mutations in five patients with syndromes of severe insulin
resistance.";
J. Clin. Endocrinol. Metab. 88:4251-4257(2003).
[121]
VARIANT HHF5 GLN-1201.
PubMed=15161766; DOI=10.2337/diabetes.53.6.1592;
Hoejlund K., Hansen T., Lajer M., Henriksen J.E., Levin K., Lindholm J.,
Pedersen O., Bech-Nielsen H.;
"A novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia
linked to a mutation in the human insulin receptor gene.";
Diabetes 53:1592-1598(2004).
[122]
VARIANTS RMS ARG-236 AND SER-386, AND CHARACTERIZATION OF VARIANTS RMS
ARG-236 AND SER-386.
PubMed=17201797; DOI=10.1111/j.1365-2265.2006.02678.x;
Tuthill A., Semple R.K., Day R., Soos M.A., Sweeney E., Seymour P.J.,
Didi M., O'Rahilly S.;
"Functional characterization of a novel insulin receptor mutation
contributing to Rabson-Mendenhall syndrome.";
Clin. Endocrinol. (Oxf.) 66:21-26(2007).
[123]
VARIANTS [LARGE SCALE ANALYSIS] ARG-228; ARG-695; SER-811; MET-1012;
VAL-1065 AND ALA-1282.
PubMed=17344846; DOI=10.1038/nature05610;
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
Futreal P.A., Stratton M.R.;
"Patterns of somatic mutation in human cancer genomes.";
Nature 446:153-158(2007).
[124]
VARIANTS LEPRCH CYS-818 AND 890-ARG--SER-1382 DEL.
PubMed=22768670; DOI=10.1515/jpem-2011-0448;
Nobile S., Semple R.K., Carnielli V.P.;
"A novel mutation of the insulin receptor gene in a preterm infant with
Donohue syndrome and heart failure.";
J. Pediatr. Endocrinol. Metab. 25:363-366(2012).
[125]
VARIANTS LEPRCH THR-56 AND TYR-286, AND CHARACTERIZATION OF VARIANTS LEPRCH
THR-56 AND TYR-286.
PubMed=24498630; DOI=10.1002/mgg3.43;
Falik Zaccai T.C., Kalfon L., Klar A., Elisha M.B., Hurvitz H.,
Weingarten G., Chechik E., Fleisher Sheffer V., Haj Yahya R., Meidan G.,
Gross-Kieselstein E., Bauman D., Hershkovitz S., Yaron Y., Orr-Urtreger A.,
Wertheimer E.;
"Two novel mutations identified in familial cases with Donohue syndrome.";
Mol. Genet. Genomic Med. 2:64-72(2014).
[126]
VARIANTS RMS CYS-256; LEU-635; ILE-835; VAL-842; LEU-874; SER-878 AND
999-TYR--SER-1382 DEL, VARIANTS IRAN TYPE A ASP-489 AND MET-1054, VARIANTS
LEPRCH PHE-657; ARG-659 AND CYS-818, CHARACTERIZATION OF VARIANTS LEPRCH
PHE-657; ARG-659; CYS-818; THR-925; TRP-926 AND MET-937, AND
CHARACTERIZATION OF VARIANTS RMS LEU-635; ILE-835; VAL-842; LEU-874 AND
SER-878.
PubMed=28765322; DOI=10.2337/db17-0301;
Hosoe J., Kadowaki H., Miya F., Aizu K., Kawamura T., Miyata I.,
Satomura K., Ito T., Hara K., Tanaka M., Ishiura H., Tsuji S., Suzuki K.,
Takakura M., Boroevich K.A., Tsunoda T., Yamauchi T., Shojima N.,
Kadowaki T.;
"Structural Basis and Genotype-Phenotype Correlations of INSR Mutations
Causing Severe Insulin Resistance.";
Diabetes 66:2713-2723(2017).
-!- FUNCTION: Receptor tyrosine kinase which mediates the pleiotropic
actions of insulin. Binding of insulin leads to phosphorylation of
several intracellular substrates, including, insulin receptor
substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling
intermediates. Each of these phosphorylated proteins serve as docking
proteins for other signaling proteins that contain Src-homology-2
domains (SH2 domain) that specifically recognize different
phosphotyrosine residues, including the p85 regulatory subunit of PI3K
and SHP2. Phosphorylation of IRSs proteins lead to the activation of
two main signaling pathways: the PI3K-AKT/PKB pathway, which is
responsible for most of the metabolic actions of insulin, and the Ras-
MAPK pathway, which regulates expression of some genes and cooperates
with the PI3K pathway to control cell growth and differentiation.
Binding of the SH2 domains of PI3K to phosphotyrosines on IRS1 leads to
the activation of PI3K and the generation of phosphatidylinositol-(3,
4, 5)-triphosphate (PIP3), a lipid second messenger, which activates
several PIP3-dependent serine/threonine kinases, such as PDPK1 and
subsequently AKT/PKB. The net effect of this pathway is to produce a
translocation of the glucose transporter SLC2A4/GLUT4 from cytoplasmic
vesicles to the cell membrane to facilitate glucose transport.
Moreover, upon insulin stimulation, activated AKT/PKB is responsible
for: anti-apoptotic effect of insulin by inducing phosphorylation of
BAD; regulates the expression of gluconeogenic and lipogenic enzymes by
controlling the activity of the winged helix or forkhead (FOX) class of
transcription factors. Another pathway regulated by PI3K-AKT/PKB
activation is mTORC1 signaling pathway which regulates cell growth and
metabolism and integrates signals from insulin. AKT mediates insulin-
stimulated protein synthesis by phosphorylating TSC2 thereby activating
mTORC1 pathway. The Ras/RAF/MAP2K/MAPK pathway is mainly involved in
mediating cell growth, survival and cellular differentiation of
insulin. Phosphorylated IRS1 recruits GRB2/SOS complex, which triggers
the activation of the Ras/RAF/MAP2K/MAPK pathway. In addition to
binding insulin, the insulin receptor can bind insulin-like growth
factors (IGFI and IGFII). Isoform Short has a higher affinity for IGFII
binding. When present in a hybrid receptor with IGF1R, binds IGF1.
PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR
isoform Long are activated with a high affinity by IGF1, with low
affinity by IGF2 and not significantly activated by insulin, and that
hybrid receptors composed of IGF1R and INSR isoform Short are activated
by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that
hybrid receptors composed of IGF1R and INSR isoform Long and hybrid
receptors composed of IGF1R and INSR isoform Short have similar binding
characteristics, both bind IGF1 and have a low affinity for insulin. In
adipocytes, inhibits lipolysis (By similarity).
{ECO:0000250|UniProtKB:P15208, ECO:0000269|PubMed:12138094,
ECO:0000269|PubMed:16314505, ECO:0000269|PubMed:16831875,
ECO:0000269|PubMed:8257688, ECO:0000269|PubMed:8276809,
ECO:0000269|PubMed:8452530, ECO:0000269|PubMed:9428692}.
-!- CATALYTIC ACTIVITY:
Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
[protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
Evidence={ECO:0000255|PROSITE-ProRule:PRU10028,
ECO:0000269|PubMed:11124964, ECO:0000269|PubMed:11598120,
ECO:0000269|PubMed:12707268, ECO:0000269|PubMed:18278056,
ECO:0000269|PubMed:19056263, ECO:0000269|PubMed:19071018,
ECO:0000269|PubMed:19394223, ECO:0000269|PubMed:9312016};
-!- ACTIVITY REGULATION: Activated in response to insulin.
Autophosphorylation activates the kinase activity. PTPN1, PTPRE and
PTPRF dephosphorylate important tyrosine residues, thereby reducing
INSR activity. Inhibited by ENPP1. GRB10 and GRB14 inhibit the
catalytic activity of the INSR, they block access of substrates to the
activated receptor. SOCS1 and SOCS3 act as negative regulators of INSR
activity, they bind to the activated INRS and interfere with the
phosphorylation of INSR substrates. {ECO:0000269|PubMed:10615944,
ECO:0000269|PubMed:11598120, ECO:0000269|PubMed:11726652,
ECO:0000269|PubMed:12493740, ECO:0000269|PubMed:2211730}.
-!- SUBUNIT: Tetramer of 2 alpha and 2 beta chains linked by disulfide
bonds. The alpha chains carry the insulin-binding regions, while the
beta chains carry the kinase domain. Forms a hybrid receptor with
IGF1R, the hybrid is a tetramer consisting of 1 alpha chain and 1 beta
chain of INSR and 1 alpha chain and 1 beta chain of IGF1R. Interacts
with SORBS1 but dissociates from it following insulin stimulation.
Binds SH2B2. Activated form of INSR interacts (via Tyr-999) with the
PTB/PID domains of IRS1 and SHC1. The sequences surrounding the
phosphorylated NPXY motif contribute differentially to either IRS1 or
SHC1 recognition. Interacts (via tyrosines in the C-terminus) with IRS2
(via PTB domain and 591-786 AA); the 591-786 would be the primary
anchor of IRS2 to INSR while the PTB domain would have a stabilizing
action on the interaction with INSR. Interacts with the SH2 domains of
the 85 kDa regulatory subunit of PI3K (PIK3R1) in vitro, when
autophosphorylated on tyrosine residues. Interacts with SOCS7.
Interacts (via the phosphorylated Tyr-999), with SOCS3. Interacts (via
the phosphorylated Tyr-1185, Tyr-1189, Tyr-1190) with SOCS1. Interacts
with CAV2 (tyrosine-phosphorylated form); the interaction is increased
with 'Tyr-27'phosphorylation of CAV2 (By similarity). Interacts with
ARRB2 (By similarity). Interacts with GRB10; this interaction blocks
the association between IRS1/IRS2 and INSR, significantly reduces
insulin-stimulated tyrosine phosphorylation of IRS1 and IRS2 and thus
decreases insulin signaling. Interacts with GRB7. Interacts with PDPK1.
Interacts (via Tyr-1190) with GRB14 (via BPS domain); this interaction
protects the tyrosines in the activation loop from dephosphorylation,
but promotes dephosphorylation of Tyr-999, this results in decreased
interaction with, and phosphorylation of, IRS1. Interacts (via subunit
alpha) with ENPP1 (via 485-599 AA); this interaction blocks
autophosphorylation. Interacts with PTPRE; this interaction is
dependent of Tyr-1185, Tyr-1189 and Tyr-1190 of the INSR. Interacts
with STAT5B (via SH2 domain). Interacts with PTPRF. Interacts with
ATIC; ATIC together with PRKAA2/AMPK2 and HACD3/PTPLAD1 is proposed to
be part of a signaling netwok regulating INSR autophosphorylation and
endocytosis (By similarity). Interacts with the cone snail venom
insulin Con-Ins G1 (PubMed:27617429). Interacts with the insulin
receptor SORL1; this interaction strongly increases its surface
exposure, hence strengthens insulin signal reception (PubMed:27322061).
Interacts (tyrosine phosphorylated) with CCDC88A/GIV (via SH2-like
region); binding requires autophosphorylation of the INSR C-terminal
region (PubMed:25187647). Interacts with GNAI3; the interaction is
probably mediated by CCDC88A/GIV (PubMed:25187647). {ECO:0000250,
ECO:0000250|UniProtKB:P15127, ECO:0000269|PubMed:10615944,
ECO:0000269|PubMed:10803466, ECO:0000269|PubMed:11124964,
ECO:0000269|PubMed:11374898, ECO:0000269|PubMed:11726652,
ECO:0000269|PubMed:12493740, ECO:0000269|PubMed:14690593,
ECO:0000269|PubMed:16127460, ECO:0000269|PubMed:16246733,
ECO:0000269|PubMed:16271887, ECO:0000269|PubMed:16314505,
ECO:0000269|PubMed:16957736, ECO:0000269|PubMed:18278056,
ECO:0000269|PubMed:18767165, ECO:0000269|PubMed:19056263,
ECO:0000269|PubMed:19071018, ECO:0000269|PubMed:19394223,
ECO:0000269|PubMed:2211730, ECO:0000269|PubMed:23302862,
ECO:0000269|PubMed:25187647, ECO:0000269|PubMed:27322061,
ECO:0000269|PubMed:27617429, ECO:0000269|PubMed:7537849,
ECO:0000269|PubMed:7559478, ECO:0000269|PubMed:8276809,
ECO:0000269|PubMed:8995282, ECO:0000269|PubMed:8999839,
ECO:0000269|PubMed:9312016, ECO:0000269|PubMed:9428692}.
-!- INTERACTION:
P06213; Q99490: AGAP2; NbExp=2; IntAct=EBI-475899, EBI-2361824;
P06213; Q8NEJ0: DUSP18; NbExp=2; IntAct=EBI-475899, EBI-10698945;
P06213; P22413: ENPP1; NbExp=2; IntAct=EBI-475899, EBI-3197846;
P06213; Q13322: GRB10; NbExp=3; IntAct=EBI-475899, EBI-80275;
P06213; P05019: IGF1; NbExp=4; IntAct=EBI-475899, EBI-7902275;
P06213; P35568: IRS1; NbExp=3; IntAct=EBI-475899, EBI-517592;
P06213; Q15323: KRT31; NbExp=3; IntAct=EBI-475899, EBI-948001;
P06213; P27986: PIK3R1; NbExp=3; IntAct=EBI-475899, EBI-79464;
P06213; P19174: PLCG1; NbExp=9; IntAct=EBI-475899, EBI-79387;
P06213; P18031: PTPN1; NbExp=32; IntAct=EBI-475899, EBI-968788;
P06213; Q06124: PTPN11; NbExp=2; IntAct=EBI-475899, EBI-297779;
P06213; Q15256: PTPRR; NbExp=2; IntAct=EBI-475899, EBI-2265659;
P06213; Q9NRF2: SH2B1; NbExp=6; IntAct=EBI-475899, EBI-310491;
P06213; P29353: SHC1; NbExp=2; IntAct=EBI-475899, EBI-78835;
P06213; P01317: INS; Xeno; NbExp=5; IntAct=EBI-475899, EBI-3989070;
P06213; P35570: Irs1; Xeno; NbExp=5; IntAct=EBI-475899, EBI-520230;
P06213-1; P32121: ARRB2; NbExp=2; IntAct=EBI-15558981, EBI-714559;
P06213-1; P06213-1: INSR; NbExp=4; IntAct=EBI-15558981, EBI-15558981;
P06213-1; P18031: PTPN1; NbExp=2; IntAct=EBI-15558981, EBI-968788;
P06213-1; Q92485-2: SMPDL3B; NbExp=2; IntAct=EBI-15558981, EBI-21501656;
P06213-1; P81122: Irs2; Xeno; NbExp=8; IntAct=EBI-15558981, EBI-1369862;
P06213-1; Q1XH17: Trim72; Xeno; NbExp=2; IntAct=EBI-15558981, EBI-16034016;
P06213-2; P01308: INS; NbExp=6; IntAct=EBI-9984921, EBI-7090529;
P06213-2; Q13257: MAD2L1; NbExp=3; IntAct=EBI-9984921, EBI-78203;
P06213-2; Q92485-2: SMPDL3B; NbExp=2; IntAct=EBI-9984921, EBI-21501656;
P06213-2; P01317: INS; Xeno; NbExp=2; IntAct=EBI-9984921, EBI-3989070;
-!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P15208};
Single-pass type I membrane protein {ECO:0000305}. Late endosome
{ECO:0000250|UniProtKB:P15208}. Lysosome
{ECO:0000250|UniProtKB:P15208}. Note=Binding of insulin to INSR induces
internalization and lysosomal degradation of the receptor, a means for
downregulating this signaling pathway after stimulation. In the
presence of SORL1, internalized INSR molecules are redirected back to
the cell surface, thereby preventing their lysosomal catabolism and
strengthening insulin signal reception. {ECO:0000250|UniProtKB:P15208}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=Long; Synonyms=HIR-B;
IsoId=P06213-1; Sequence=Displayed;
Name=Short; Synonyms=HIR-A;
IsoId=P06213-2; Sequence=VSP_002898;
-!- TISSUE SPECIFICITY: Isoform Long and isoform Short are predominantly
expressed in tissue targets of insulin metabolic effects: liver,
adipose tissue and skeletal muscle but are also expressed in the
peripheral nerve, kidney, pulmonary alveoli, pancreatic acini, placenta
vascular endothelium, fibroblasts, monocytes, granulocytes,
erythrocytes and skin. Isoform Short is preferentially expressed in
fetal cells such as fetal fibroblasts, muscle, liver and kidney. Found
as a hybrid receptor with IGF1R in muscle, heart, kidney, adipose
tissue, skeletal muscle, hepatoma, fibroblasts, spleen and placenta (at
protein level). Overexpressed in several tumors, including breast,
colon, lung, ovary, and thyroid carcinomas.
{ECO:0000269|PubMed:10207053, ECO:0000269|PubMed:2369896,
ECO:0000269|PubMed:9202395, ECO:0000269|PubMed:9355755}.
-!- DOMAIN: The tetrameric insulin receptor binds insulin via non-identical
regions from two alpha chains, primarily via the C-terminal region of
the first INSR alpha chain. Residues from the leucine-rich N-terminus
of the other INSR alpha chain also contribute to this insulin binding
site. A secondary insulin-binding site is formed by residues at the
junction of fibronectin type-III domain 1 and 2.
{ECO:0000269|PubMed:16957736, ECO:0000269|PubMed:19459609,
ECO:0000269|PubMed:23302862}.
-!- PTM: After being transported from the endoplasmic reticulum to the
Golgi apparatus, the single glycosylated precursor is further
glycosylated and then cleaved, followed by its transport to the plasma
membrane. {ECO:0000269|PubMed:1472036, ECO:0000269|PubMed:16894147,
ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19349973,
ECO:0000269|PubMed:23302862, ECO:0000269|PubMed:2983222}.
-!- PTM: Autophosphorylated on tyrosine residues in response to insulin.
Phosphorylation of Tyr-999 is required for binding to IRS1, SHC1 and
STAT5B. Dephosphorylated by PTPRE at Tyr-999, Tyr-1185, Tyr-1189 and
Tyr-1190. Dephosphorylated by PTPRF and PTPN1. Dephosphorylated by
PTPN2; down-regulates insulin-induced signaling.
{ECO:0000269|PubMed:10734133, ECO:0000269|PubMed:12612081,
ECO:0000269|PubMed:14690593, ECO:0000269|PubMed:16246733,
ECO:0000269|PubMed:16271887, ECO:0000269|PubMed:18278056,
ECO:0000269|PubMed:18767165, ECO:0000269|PubMed:3166375,
ECO:0000269|PubMed:9312016}.
-!- DISEASE: Rabson-Mendenhall syndrome (RMS) [MIM:262190]: Severe insulin
resistance syndrome characterized by insulin-resistant diabetes
mellitus with pineal hyperplasia and somatic abnormalities. Typical
features include coarse, senile-appearing facies, dental and skin
abnormalities, abdominal distension, and phallic enlargement.
Inheritance is autosomal recessive. {ECO:0000269|PubMed:10443650,
ECO:0000269|PubMed:12023989, ECO:0000269|PubMed:17201797,
ECO:0000269|PubMed:2121734, ECO:0000269|PubMed:2365819,
ECO:0000269|PubMed:28765322, ECO:0000269|PubMed:8314008}. Note=The
disease is caused by variants affecting the gene represented in this
entry.
-!- DISEASE: Leprechaunism (LEPRCH) [MIM:246200]: Represents the most
severe form of insulin resistance syndrome, characterized by
intrauterine and postnatal growth retardation and death in early
infancy. Inheritance is autosomal recessive.
{ECO:0000269|PubMed:12023989, ECO:0000269|PubMed:12538626,
ECO:0000269|PubMed:12970295, ECO:0000269|PubMed:1607067,
ECO:0000269|PubMed:1730625, ECO:0000269|PubMed:22768670,
ECO:0000269|PubMed:2365819, ECO:0000269|PubMed:24498630,
ECO:0000269|PubMed:2479553, ECO:0000269|PubMed:2834824,
ECO:0000269|PubMed:28765322, ECO:0000269|PubMed:7538143,
ECO:0000269|PubMed:7815442, ECO:0000269|PubMed:8188715,
ECO:0000269|PubMed:8326490, ECO:0000269|PubMed:8419945,
ECO:0000269|PubMed:8636294, ECO:0000269|PubMed:9249867,
ECO:0000269|PubMed:9299395, ECO:0000269|PubMed:9703342}. Note=The
disease is caused by variants affecting the gene represented in this
entry.
-!- DISEASE: Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]:
A multifactorial disorder of glucose homeostasis caused by a lack of
sensitivity to the body's own insulin. Affected individuals usually
have an obese body habitus and manifestations of a metabolic syndrome
characterized by diabetes, insulin resistance, hypertension and
hypertriglyceridemia. The disease results in long-term complications
that affect the eyes, kidneys, nerves, and blood vessels.
{ECO:0000269|PubMed:1470163, ECO:0000269|PubMed:1607076,
ECO:0000269|PubMed:7657032}. Note=The gene represented in this entry
may be involved in disease pathogenesis.
-!- DISEASE: Familial hyperinsulinemic hypoglycemia 5 (HHF5) [MIM:609968]:
Familial hyperinsulinemic hypoglycemia [MIM:256450], also referred to
as congenital hyperinsulinism, nesidioblastosis, or persistent
hyperinsulinemic hypoglycemia of infancy (PPHI), is the most common
cause of persistent hypoglycemia in infancy and is due to defective
negative feedback regulation of insulin secretion by low glucose
levels. {ECO:0000269|PubMed:15161766}. Note=The disease is caused by
variants affecting the gene represented in this entry.
-!- DISEASE: Insulin-resistant diabetes mellitus with acanthosis nigricans
type A (IRAN type A) [MIM:610549]: Characterized by the association of
severe insulin resistance (manifested by marked hyperinsulinemia and a
failure to respond to exogenous insulin) with the skin lesion
acanthosis nigricans and ovarian hyperandrogenism in adolescent female
subjects. Women frequently present with hirsutism, acne, amenorrhea or
oligomenorrhea, and virilization. This syndrome is different from the
type B that has been demonstrated to be secondary to the presence of
circulating autoantibodies against the insulin receptor.
{ECO:0000269|PubMed:10733238, ECO:0000269|PubMed:11260230,
ECO:0000269|PubMed:12107746, ECO:0000269|PubMed:12970295,
ECO:0000269|PubMed:1563582, ECO:0000269|PubMed:1963473,
ECO:0000269|PubMed:2002058, ECO:0000269|PubMed:2168397,
ECO:0000269|PubMed:2365819, ECO:0000269|PubMed:2544998,
ECO:0000269|PubMed:28765322, ECO:0000269|PubMed:3283938,
ECO:0000269|PubMed:8243830, ECO:0000269|PubMed:8288049,
ECO:0000269|PubMed:8314008, ECO:0000269|PubMed:8388389,
ECO:0000269|PubMed:9175790}. Note=The disease is caused by variants
affecting the gene represented in this entry.
-!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
kinase family. Insulin receptor subfamily. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
-!- WEB RESOURCE: Name=Wikipedia; Note=Insulin receptor entry;
URL="https://en.wikipedia.org/wiki/Insulin_receptor";
---------------------------------------------------------------------------
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---------------------------------------------------------------------------
EMBL; M10051; AAA59174.1; -; mRNA.
EMBL; X02160; CAA26096.1; -; mRNA.
EMBL; M32972; AAA59452.1; -; Genomic_DNA.
EMBL; M23100; AAA59452.1; JOINED; Genomic_DNA.
EMBL; M32823; AAA59452.1; JOINED; Genomic_DNA.
EMBL; M32824; AAA59452.1; JOINED; Genomic_DNA.
EMBL; M32825; AAA59452.1; JOINED; Genomic_DNA.
EMBL; M32826; AAA59452.1; JOINED; Genomic_DNA.
EMBL; M32827; AAA59452.1; JOINED; Genomic_DNA.
EMBL; M32828; AAA59452.1; JOINED; Genomic_DNA.
EMBL; M32829; AAA59452.1; JOINED; Genomic_DNA.
EMBL; M32830; AAA59452.1; JOINED; Genomic_DNA.
EMBL; M32831; AAA59452.1; JOINED; Genomic_DNA.
EMBL; M32832; AAA59452.1; JOINED; Genomic_DNA.
EMBL; M32833; AAA59452.1; JOINED; Genomic_DNA.
EMBL; M32834; AAA59452.1; JOINED; Genomic_DNA.
EMBL; M32835; AAA59452.1; JOINED; Genomic_DNA.
EMBL; M32836; AAA59452.1; JOINED; Genomic_DNA.
EMBL; M32837; AAA59452.1; JOINED; Genomic_DNA.
EMBL; M32838; AAA59452.1; JOINED; Genomic_DNA.
EMBL; M32839; AAA59452.1; JOINED; Genomic_DNA.
EMBL; M32840; AAA59452.1; JOINED; Genomic_DNA.
EMBL; M32841; AAA59452.1; JOINED; Genomic_DNA.
EMBL; M32842; AAA59452.1; JOINED; Genomic_DNA.
EMBL; AC010311; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AC010526; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AC010606; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AC125387; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; BC117172; AAI17173.1; -; mRNA.
EMBL; J03466; AAA59175.1; -; Genomic_DNA.
EMBL; J05043; AAA59190.1; -; Genomic_DNA.
EMBL; M76592; AAC37604.1; -; Genomic_DNA.
EMBL; AB208861; BAD92098.1; -; mRNA.
EMBL; M24555; AAA59178.1; -; mRNA.
EMBL; M29929; AAA59176.1; -; Genomic_DNA.
EMBL; M29930; AAA59177.1; -; Genomic_DNA.
EMBL; M27197; AAA86791.1; -; Genomic_DNA.
EMBL; M27195; AAA86791.1; JOINED; Genomic_DNA.
CCDS; CCDS12176.1; -. [P06213-1]
CCDS; CCDS42487.1; -. [P06213-2]
PIR; A37348; INHUR.
RefSeq; NP_000199.2; NM_000208.3. [P06213-1]
RefSeq; NP_001073285.1; NM_001079817.2. [P06213-2]
PDB; 1GAG; X-ray; 2.70 A; A=1005-1310.
PDB; 1I44; X-ray; 2.40 A; A=1005-1310.
PDB; 1IR3; X-ray; 1.90 A; A=1005-1310.
PDB; 1IRK; X-ray; 2.10 A; A=1005-1310.
PDB; 1P14; X-ray; 1.90 A; A=1005-1310.
PDB; 1RQQ; X-ray; 2.60 A; A/B=1005-1310.
PDB; 2AUH; X-ray; 3.20 A; A=1005-1310.
PDB; 2B4S; X-ray; 2.30 A; B/D=1005-1310.
PDB; 2HR7; X-ray; 2.32 A; A/B=28-512.
PDB; 2MFR; NMR; -; A=940-988.
PDB; 2Z8C; X-ray; 3.25 A; A=1008-1310.
PDB; 3BU3; X-ray; 1.65 A; A=1005-1310.
PDB; 3BU5; X-ray; 2.10 A; A=1005-1310.
PDB; 3BU6; X-ray; 1.95 A; A=1005-1310.
PDB; 3EKK; X-ray; 2.10 A; A=1005-1310.
PDB; 3EKN; X-ray; 2.20 A; A=1005-1310.
PDB; 3ETA; X-ray; 2.60 A; A/B=1017-1322.
PDB; 3W11; X-ray; 3.90 A; E=28-337, F=731-744.
PDB; 3W12; X-ray; 4.30 A; E=28-337, F=731-744.
PDB; 3W13; X-ray; 4.30 A; E=28-337, F=724-744.
PDB; 4IBM; X-ray; 1.80 A; A/B=1005-1310.
PDB; 4OGA; X-ray; 3.50 A; E=28-337, F=731-744.
PDB; 4XLV; X-ray; 2.30 A; A=983-1310.
PDB; 4XSS; X-ray; 3.00 A; E=28-337.
PDB; 4XST; X-ray; 3.00 A; E=28-337.
PDB; 4ZXB; X-ray; 3.30 A; E=28-956.
PDB; 5E1S; X-ray; 2.26 A; A=1005-1310.
PDB; 5HHW; X-ray; 1.79 A; A=1005-1310.
PDB; 5J3H; X-ray; 3.27 A; E=28-337.
PDB; 5KQV; X-ray; 4.40 A; E/F=28-746.
PDB; 5U1M; X-ray; 1.80 A; B=991-999.
PDB; 6HN4; EM; 4.20 A; E/F=28-955.
PDB; 6HN5; EM; 3.20 A; E/F=28-955.
PDB; 6PXV; EM; 3.20 A; A/C=28-1382.
PDB; 6PXW; EM; 3.10 A; A/B=28-1382.
PDB; 6SOF; EM; 4.30 A; A/C=28-746, B/D=795-956.
PDB; 6VEP; X-ray; 2.90 A; E/K/Q/W=28-337, F/L/R/X=731-746.
PDB; 6VEQ; X-ray; 3.25 A; E/K=28-337, F/L=731-746.
PDBsum; 1GAG; -.
PDBsum; 1I44; -.
PDBsum; 1IR3; -.
PDBsum; 1IRK; -.
PDBsum; 1P14; -.
PDBsum; 1RQQ; -.
PDBsum; 2AUH; -.
PDBsum; 2B4S; -.
PDBsum; 2HR7; -.
PDBsum; 2MFR; -.
PDBsum; 2Z8C; -.
PDBsum; 3BU3; -.
PDBsum; 3BU5; -.
PDBsum; 3BU6; -.
PDBsum; 3EKK; -.
PDBsum; 3EKN; -.
PDBsum; 3ETA; -.
PDBsum; 3W11; -.
PDBsum; 3W12; -.
PDBsum; 3W13; -.
PDBsum; 4IBM; -.
PDBsum; 4OGA; -.
PDBsum; 4XLV; -.
PDBsum; 4XSS; -.
PDBsum; 4XST; -.
PDBsum; 4ZXB; -.
PDBsum; 5E1S; -.
PDBsum; 5HHW; -.
PDBsum; 5J3H; -.
PDBsum; 5KQV; -.
PDBsum; 5U1M; -.
PDBsum; 6HN4; -.
PDBsum; 6HN5; -.
PDBsum; 6PXV; -.
PDBsum; 6PXW; -.
PDBsum; 6SOF; -.
PDBsum; 6VEP; -.
PDBsum; 6VEQ; -.
BMRB; P06213; -.
SASBDB; P06213; -.
SMR; P06213; -.
BioGRID; 109854; 119.
CORUM; P06213; -.
DIP; DIP-480N; -.
ELM; P06213; -.
IntAct; P06213; 81.
MINT; P06213; -.
STRING; 9606.ENSP00000303830; -.
BindingDB; P06213; -.
ChEMBL; CHEMBL1981; -.
DrugBank; DB08513; [4-({5-(AMINOCARBONYL)-4-[(3-METHYLPHENYL)AMINO]PYRIMIDIN-2-YL}AMINO)PHENYL]ACETIC ACID.
DrugBank; DB03909; Adenosine-5'-[Beta, Gamma-Methylene]Triphosphate.
DrugBank; DB05120; AT1391.
DrugBank; DB12267; Brigatinib.
DrugBank; DB09129; Chromic chloride.
DrugBank; DB12010; Fostamatinib.
DrugBank; DB01306; Insulin aspart.
DrugBank; DB09564; Insulin degludec.
DrugBank; DB01307; Insulin detemir.
DrugBank; DB00047; Insulin glargine.
DrugBank; DB01309; Insulin glulisine.
DrugBank; DB00030; Insulin human.
DrugBank; DB00046; Insulin lispro.
DrugBank; DB00071; Insulin pork.
DrugBank; DB01277; Mecasermin.
DrugBank; DB14751; Mecasermin rinfabate.
DrugBank; DB05115; NN344.
DrugCentral; P06213; -.
GuidetoPHARMACOLOGY; 1800; -.
GlyConnect; 1402; 8 N-Linked glycans (6 sites).
GlyGen; P06213; 21 sites, 3 O-linked glycans (3 sites).
iPTMnet; P06213; -.
PhosphoSitePlus; P06213; -.
BioMuta; INSR; -.
DMDM; 308153655; -.
CPTAC; CPTAC-1771; -.
CPTAC; CPTAC-1772; -.
EPD; P06213; -.
jPOST; P06213; -.
MassIVE; P06213; -.
MaxQB; P06213; -.
PaxDb; P06213; -.
PeptideAtlas; P06213; -.
PRIDE; P06213; -.
ProteomicsDB; 51872; -. [P06213-1]
ProteomicsDB; 51873; -. [P06213-2]
ABCD; P06213; 3 sequenced antibodies.
Antibodypedia; 3403; 2025 antibodies.
DNASU; 3643; -.
Ensembl; ENST00000302850; ENSP00000303830; ENSG00000171105. [P06213-1]
Ensembl; ENST00000341500; ENSP00000342838; ENSG00000171105. [P06213-2]
GeneID; 3643; -.
KEGG; hsa:3643; -.
UCSC; uc002mgd.2; human. [P06213-1]
CTD; 3643; -.
DisGeNET; 3643; -.
GeneCards; INSR; -.
GeneReviews; INSR; -.
HGNC; HGNC:6091; INSR.
HPA; ENSG00000171105; Tissue enhanced (pancreas).
MalaCards; INSR; -.
MIM; 125853; phenotype.
MIM; 147670; gene.
MIM; 246200; phenotype.
MIM; 262190; phenotype.
MIM; 609968; phenotype.
MIM; 610549; phenotype.
neXtProt; NX_P06213; -.
OpenTargets; ENSG00000171105; -.
Orphanet; 263458; Hyperinsulinism due to INSR deficiency.
Orphanet; 2297; Insulin-resistance syndrome type A.
Orphanet; 508; Leprechaunism.
Orphanet; 769; Rabson-Mendenhall syndrome.
PharmGKB; PA202; -.
VEuPathDB; HostDB:ENSG00000171105.13; -.
eggNOG; KOG4258; Eukaryota.
GeneTree; ENSGT00940000155404; -.
HOGENOM; CLU_000288_166_0_1; -.
InParanoid; P06213; -.
OMA; SDGQCCH; -.
OrthoDB; 1567781at2759; -.
PhylomeDB; P06213; -.
TreeFam; TF351636; -.
BRENDA; 2.7.10.1; 2681.
PathwayCommons; P06213; -.
Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
Reactome; R-HSA-74713; IRS activation.
Reactome; R-HSA-74749; Signal attenuation.
Reactome; R-HSA-74751; Insulin receptor signalling cascade.
Reactome; R-HSA-74752; Signaling by Insulin receptor.
Reactome; R-HSA-77387; Insulin receptor recycling.
SABIO-RK; P06213; -.
SignaLink; P06213; -.
SIGNOR; P06213; -.
BioGRID-ORCS; 3643; 7 hits in 905 CRISPR screens.
ChiTaRS; INSR; human.
EvolutionaryTrace; P06213; -.
GeneWiki; Insulin_receptor; -.
GenomeRNAi; 3643; -.
Pharos; P06213; Tclin.
PRO; PR:P06213; -.
Proteomes; UP000005640; Chromosome 19.
RNAct; P06213; protein.
Bgee; ENSG00000171105; Expressed in oviduct epithelium and 250 other tissues.
ExpressionAtlas; P06213; baseline and differential.
Genevisible; P06213; HS.
GO; GO:0030424; C:axon; IBA:GO_Central.
GO; GO:0005901; C:caveola; IDA:BHF-UCL.
GO; GO:0032590; C:dendrite membrane; ISS:ARUK-UCL.
GO; GO:0010008; C:endosome membrane; TAS:Reactome.
GO; GO:0009897; C:external side of plasma membrane; ISS:ARUK-UCL.
GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
GO; GO:0005899; C:insulin receptor complex; IDA:UniProtKB.
GO; GO:0005887; C:integral component of plasma membrane; IDA:BHF-UCL.
GO; GO:0005770; C:late endosome; IEA:UniProtKB-SubCell.
GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
GO; GO:0016020; C:membrane; IDA:BHF-UCL.
GO; GO:0032809; C:neuronal cell body membrane; ISS:ARUK-UCL.
GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL.
GO; GO:0043235; C:receptor complex; IDA:MGI.
GO; GO:0001540; F:amyloid-beta binding; IPI:ARUK-UCL.
GO; GO:0005524; F:ATP binding; IDA:BHF-UCL.
GO; GO:0038024; F:cargo receptor activity; ISS:ARUK-UCL.
GO; GO:0005525; F:GTP binding; IDA:BHF-UCL.
GO; GO:0042802; F:identical protein binding; IPI:IntAct.
GO; GO:0043559; F:insulin binding; IDA:UniProtKB.
GO; GO:0043560; F:insulin receptor substrate binding; IPI:UniProtKB.
GO; GO:0005009; F:insulin-activated receptor activity; IDA:UniProtKB.
GO; GO:0031994; F:insulin-like growth factor I binding; IPI:BHF-UCL.
GO; GO:0031995; F:insulin-like growth factor II binding; IPI:BHF-UCL.
GO; GO:0005159; F:insulin-like growth factor receptor binding; IDA:BHF-UCL.
GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; IPI:UniProtKB.
GO; GO:0019904; F:protein domain specific binding; IPI:CAFA.
GO; GO:0004713; F:protein tyrosine kinase activity; IDA:BHF-UCL.
GO; GO:0044877; F:protein-containing complex binding; IPI:ARUK-UCL.
GO; GO:0051425; F:PTB domain binding; IPI:UniProtKB.
GO; GO:0005198; F:structural molecule activity; IDA:UniProtKB.
GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
GO; GO:0000187; P:activation of MAPK activity; IMP:BHF-UCL.
GO; GO:0032147; P:activation of protein kinase activity; IMP:BHF-UCL.
GO; GO:0032148; P:activation of protein kinase B activity; IDA:BHF-UCL.
GO; GO:0030325; P:adrenal gland development; IEA:Ensembl.
GO; GO:0097242; P:amyloid-beta clearance; ISS:ARUK-UCL.
GO; GO:0005975; P:carbohydrate metabolic process; IEA:UniProtKB-KW.
GO; GO:0071363; P:cellular response to growth factor stimulus; IEA:Ensembl.
GO; GO:0032869; P:cellular response to insulin stimulus; IDA:BHF-UCL.
GO; GO:0097062; P:dendritic spine maintenance; ISS:ARUK-UCL.
GO; GO:0008544; P:epidermis development; IEA:Ensembl.
GO; GO:0031017; P:exocrine pancreas development; IEA:Ensembl.
GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:BHF-UCL.
GO; GO:0042593; P:glucose homeostasis; IMP:BHF-UCL.
GO; GO:0003007; P:heart morphogenesis; IMP:BHF-UCL.
GO; GO:0008286; P:insulin receptor signaling pathway; IDA:UniProtKB.
GO; GO:0007612; P:learning; TAS:ARUK-UCL.
GO; GO:0008584; P:male gonad development; IEA:Ensembl.
GO; GO:0030238; P:male sex determination; IEA:Ensembl.
GO; GO:0007613; P:memory; TAS:ARUK-UCL.
GO; GO:0007275; P:multicellular organism development; IBA:GO_Central.
GO; GO:1990535; P:neuron projection maintenance; ISS:ARUK-UCL.
GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; IEA:Ensembl.
GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:BHF-UCL.
GO; GO:0030335; P:positive regulation of cell migration; IMP:BHF-UCL.
GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:BHF-UCL.
GO; GO:0048639; P:positive regulation of developmental growth; IMP:BHF-UCL.
GO; GO:0046326; P:positive regulation of glucose import; IDA:BHF-UCL.
GO; GO:0045725; P:positive regulation of glycogen biosynthetic process; IDA:BHF-UCL.
GO; GO:0045821; P:positive regulation of glycolytic process; IMP:BHF-UCL.
GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:BHF-UCL.
GO; GO:0051446; P:positive regulation of meiotic cell cycle; IEA:Ensembl.
GO; GO:0045840; P:positive regulation of mitotic nuclear division; IMP:BHF-UCL.
GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IMP:BHF-UCL.
GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IBA:GO_Central.
GO; GO:0051897; P:positive regulation of protein kinase B signaling; IMP:BHF-UCL.
GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:BHF-UCL.
GO; GO:0043243; P:positive regulation of protein-containing complex disassembly; ISS:ARUK-UCL.
GO; GO:0002092; P:positive regulation of receptor internalization; IDA:CACAO.
GO; GO:0060267; P:positive regulation of respiratory burst; IDA:BHF-UCL.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IEA:Ensembl.
GO; GO:0046777; P:protein autophosphorylation; IDA:BHF-UCL.
GO; GO:0006468; P:protein phosphorylation; TAS:ARUK-UCL.
GO; GO:0006898; P:receptor-mediated endocytosis; ISS:ARUK-UCL.
GO; GO:0045995; P:regulation of embryonic development; IMP:BHF-UCL.
GO; GO:2000194; P:regulation of female gonad development; IEA:Ensembl.
GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:BHF-UCL.
GO; GO:0019087; P:transformation of host cell by virus; IMP:BHF-UCL.
GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
GO; GO:0150104; P:transport across blood-brain barrier; NAS:ARUK-UCL.
CDD; cd00063; FN3; 2.
CDD; cd00064; FU; 1.
Gene3D; 2.60.40.10; -; 4.
Gene3D; 3.80.20.20; -; 2.
InterPro; IPR003961; FN3_dom.
InterPro; IPR036116; FN3_sf.
InterPro; IPR006211; Furin-like_Cys-rich_dom.
InterPro; IPR006212; Furin_repeat.
InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
InterPro; IPR013783; Ig-like_fold.
InterPro; IPR040969; Insulin_TMD.
InterPro; IPR011009; Kinase-like_dom_sf.
InterPro; IPR000719; Prot_kinase_dom.
InterPro; IPR017441; Protein_kinase_ATP_BS.
InterPro; IPR000494; Rcpt_L-dom.
InterPro; IPR036941; Rcpt_L-dom_sf.
InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
InterPro; IPR008266; Tyr_kinase_AS.
InterPro; IPR020635; Tyr_kinase_cat_dom.
InterPro; IPR016246; Tyr_kinase_insulin-like_rcpt.
InterPro; IPR002011; Tyr_kinase_rcpt_2_CS.
Pfam; PF00757; Furin-like; 1.
Pfam; PF17870; Insulin_TMD; 1.
Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
Pfam; PF01030; Recep_L_domain; 2.
PIRSF; PIRSF000620; Insulin_receptor; 1.
PRINTS; PR00109; TYRKINASE.
SMART; SM00060; FN3; 3.
SMART; SM00261; FU; 2.
SMART; SM00219; TyrKc; 1.
SUPFAM; SSF49265; SSF49265; 3.
SUPFAM; SSF56112; SSF56112; 1.
SUPFAM; SSF57184; SSF57184; 1.
PROSITE; PS50853; FN3; 2.
PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PROSITE; PS00239; RECEPTOR_TYR_KIN_II; 1.
1: Evidence at protein level;
3D-structure; Alternative splicing; ATP-binding; Carbohydrate metabolism;
Cell membrane; Cleavage on pair of basic residues; Diabetes mellitus;
Direct protein sequencing; Disease variant; Disulfide bond; Endosome;
Glycoprotein; Kinase; Lysosome; Membrane; Nucleotide-binding;
Phosphoprotein; Receptor; Reference proteome; Repeat; Signal; Transferase;
Transmembrane; Transmembrane helix; Tyrosine-protein kinase.
SIGNAL 1..27
/evidence="ECO:0000269|PubMed:2211730,
ECO:0000269|PubMed:2983222, ECO:0000269|PubMed:8257688"
CHAIN 28..758
/note="Insulin receptor subunit alpha"
/id="PRO_0000016687"
CHAIN 763..1382
/note="Insulin receptor subunit beta"
/id="PRO_0000016689"
TOPO_DOM 28..758
/note="Extracellular"
/evidence="ECO:0000305"
TOPO_DOM 763..956
/note="Extracellular"
/evidence="ECO:0000305"
TRANSMEM 957..979
/note="Helical"
/evidence="ECO:0000255"
TOPO_DOM 980..1382
/note="Cytoplasmic"
/evidence="ECO:0000305"
DOMAIN 624..726
/note="Fibronectin type-III 1"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
DOMAIN 757..842
/note="Fibronectin type-III 2"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
DOMAIN 853..947
/note="Fibronectin type-III 3"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
DOMAIN 1023..1298
/note="Protein kinase"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
NP_BIND 1104..1110
/note="ATP"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
ECO:0000269|PubMed:18278056"
NP_BIND 1163..1164
/note="ATP"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
ECO:0000269|PubMed:18278056"
REGION 733..741
/note="Insulin-binding"
REGION 999
/note="Important for interaction with IRS1, SHC1 and
STAT5B"
/evidence="ECO:0000269|PubMed:9428692"
REGION 1361..1364
/note="PIK3R1-binding"
COMPBIAS 28..174
/note="Leu-rich"
COMPBIAS 182..339
/note="Cys-rich"
ACT_SITE 1159
/note="Proton donor/acceptor"
/evidence="ECO:0000269|PubMed:9312016"
BINDING 1033
/note="ATP"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
ECO:0000269|PubMed:18278056"
BINDING 1057
/note="ATP"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
ECO:0000269|PubMed:18278056"
BINDING 1177
/note="ATP"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
ECO:0000269|PubMed:18278056"
SITE 66
/note="Insulin-binding"
/evidence="ECO:0000305"
MOD_RES 400
/note="Phosphoserine"
/evidence="ECO:0000244|PubMed:18669648"
MOD_RES 401
/note="Phosphotyrosine"
/evidence="ECO:0000244|PubMed:18669648"
MOD_RES 407
/note="Phosphoserine"
/evidence="ECO:0000244|PubMed:18669648"
MOD_RES 992
/note="Phosphotyrosine; by autocatalysis"
/evidence="ECO:0000305"
MOD_RES 999
/note="Phosphotyrosine; by autocatalysis"
/evidence="ECO:0000305|PubMed:3166375"
MOD_RES 1011
/note="Phosphotyrosine; by autocatalysis"
/evidence="ECO:0000305"
MOD_RES 1185
/note="Phosphotyrosine; by autocatalysis"
/evidence="ECO:0000269|PubMed:14690593,
ECO:0000269|PubMed:16246733, ECO:0000269|PubMed:16271887,
ECO:0000269|PubMed:18278056, ECO:0000269|PubMed:18767165,
ECO:0000269|PubMed:3166375, ECO:0000269|PubMed:9312016"
MOD_RES 1189
/note="Phosphotyrosine; by autocatalysis"
/evidence="ECO:0000269|PubMed:14690593,
ECO:0000269|PubMed:16246733, ECO:0000269|PubMed:16271887,
ECO:0000269|PubMed:18278056, ECO:0000269|PubMed:18767165,
ECO:0000269|PubMed:3166375, ECO:0000269|PubMed:9312016"
MOD_RES 1190
/note="Phosphotyrosine; by autocatalysis"
/evidence="ECO:0000269|PubMed:14690593,
ECO:0000269|PubMed:16246733, ECO:0000269|PubMed:16271887,
ECO:0000269|PubMed:18278056, ECO:0000269|PubMed:18767165,
ECO:0000269|PubMed:3166375, ECO:0000269|PubMed:9312016"
MOD_RES 1355
/note="Phosphotyrosine; by autocatalysis"
/evidence="ECO:0000305|PubMed:3166375"
MOD_RES 1361
/note="Phosphotyrosine; by autocatalysis"
/evidence="ECO:0000305|PubMed:3166375"
CARBOHYD 43
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000269|PubMed:16894147,
ECO:0000269|PubMed:23302862, ECO:0000269|PubMed:2983222"
CARBOHYD 52
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000269|PubMed:16894147,
ECO:0000269|PubMed:23302862"
CARBOHYD 105
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 138
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000269|PubMed:16894147,
ECO:0000269|PubMed:23302862"
CARBOHYD 242
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000269|PubMed:16894147,
ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:23302862"
CARBOHYD 282
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000269|PubMed:16894147,
ECO:0000269|PubMed:23302862"
CARBOHYD 322
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 364
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000269|PubMed:16894147"
CARBOHYD 424
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000269|PubMed:16894147"
CARBOHYD 445
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000269|PubMed:16894147,
ECO:0000269|PubMed:19349973"
CARBOHYD 541
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000269|PubMed:1472036,
ECO:0000269|PubMed:19159218"
CARBOHYD 633
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 651
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 698
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 769
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000269|PubMed:2983222"
CARBOHYD 782
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 920
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000269|PubMed:19349973"
CARBOHYD 933
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
DISULFID 35..53
DISULFID 153..182
DISULFID 186..209
DISULFID 196..215
DISULFID 219..228
DISULFID 223..234
DISULFID 235..243
DISULFID 239..252
DISULFID 255..264
DISULFID 268..280
DISULFID 286..311
DISULFID 293..301
DISULFID 315..328
DISULFID 331..335
DISULFID 339..360
DISULFID 462..495
/evidence="ECO:0000269|PubMed:1472036"
DISULFID 551
/note="Interchain"
/evidence="ECO:0000269|PubMed:1472036"
DISULFID 674..899
DISULFID 825..834
VAR_SEQ 745..756
/note="Missing (in isoform Short)"
/evidence="ECO:0000303|PubMed:15489334,
ECO:0000303|PubMed:2983222, ECO:0000303|Ref.13"
/id="VSP_002898"
VARIANT 2
/note="A -> G (in dbSNP:rs7508518)"
/evidence="ECO:0000269|PubMed:15489334,
ECO:0000269|PubMed:2210055, ECO:0000269|PubMed:2280779,
ECO:0000269|PubMed:2777789, ECO:0000269|PubMed:2806055,
ECO:0000269|PubMed:2859121, ECO:0000269|PubMed:2983222,
ECO:0000269|PubMed:3680248"
/id="VAR_058395"
VARIANT 42
/note="N -> K (in RMS; impairs transport to the plasma
membrane and reduces the affinity to bind insulin;
dbSNP:rs121913143)"
/evidence="ECO:0000269|PubMed:2121734,
ECO:0000269|PubMed:2365819"
/id="VAR_004079"
VARIANT 55
/note="V -> A (in LEPRCH; Verona-1; dbSNP:rs121913152)"
/evidence="ECO:0000269|PubMed:1607067"
/id="VAR_004080"
VARIANT 56
/note="I -> T (in LEPRCH; abolishes post-translational
processing; dbSNP:rs1555689937)"
/evidence="ECO:0000269|PubMed:24498630"
/id="VAR_079535"
VARIANT 58
/note="G -> R (in LEPRCH; Helmond; inhibits processing and
transport; dbSNP:rs52836744)"
/evidence="ECO:0000269|PubMed:1730625"
/id="VAR_004081"
VARIANT 86
/note="D -> G (in IRAN type A)"
/evidence="ECO:0000269|PubMed:9175790"
/id="VAR_015907"
VARIANT 89
/note="L -> P (in IRAN type A)"
/evidence="ECO:0000269|PubMed:9175790"
/id="VAR_015908"
VARIANT 113
/note="R -> P (in LEPRCH; Atlanta-1; abolishes insulin
binding; dbSNP:rs121913153)"
/evidence="ECO:0000269|PubMed:12023989,
ECO:0000269|PubMed:8419945"
/id="VAR_004082"
VARIANT 119
/note="A -> V (in LEPRCH; markedly impairs insulin binding;
dbSNP:rs1347473020)"
/evidence="ECO:0000269|PubMed:12023989"
/id="VAR_015909"
VARIANT 120
/note="L -> Q (in LEPRCH; inhibits receptor processing)"
/evidence="ECO:0000269|PubMed:12970295"
/id="VAR_031518"
VARIANT 146
/note="I -> M (in LEPRCH; mild; dbSNP:rs121913159)"
/evidence="ECO:0000269|PubMed:7815442,
ECO:0000269|PubMed:8326490"
/id="VAR_015539"
VARIANT 167
/note="V -> L (in IRAN type A; dbSNP:rs938519025)"
/evidence="ECO:0000269|PubMed:10733238"
/id="VAR_015910"
VARIANT 171
/note="Y -> H (in dbSNP:rs1051692)"
/evidence="ECO:0000269|PubMed:2859121"
/id="VAR_058396"
VARIANT 220
/note="P -> L (in Ins resistance; severe;
dbSNP:rs749094324)"
/evidence="ECO:0000269|PubMed:8242067"
/id="VAR_004083"
VARIANT 228
/note="C -> R (in a gastric adenocarcinoma sample; somatic
mutation)"
/evidence="ECO:0000269|PubMed:17344846"
/id="VAR_041429"
VARIANT 236
/note="H -> R (in RMS and LEPRCH; Winnipeg; may impair
receptor processing; dbSNP:rs121913145)"
/evidence="ECO:0000269|PubMed:17201797,
ECO:0000269|PubMed:2365819"
/id="VAR_004084"
VARIANT 256
/note="R -> C (in RMS; dbSNP:rs781007453)"
/evidence="ECO:0000269|PubMed:28765322"
/id="VAR_079536"
VARIANT 260
/note="L -> P (in LEPRCH; Geldeimalsen; dbSNP:rs121913141)"
/evidence="ECO:0000269|PubMed:2479553"
/id="VAR_004085"
VARIANT 279
/note="R -> C (in IRAN type A; inhibits receptor
internalization; dbSNP:rs1568470274)"
/evidence="ECO:0000269|PubMed:12107746"
/id="VAR_015540"
VARIANT 279
/note="R -> H (in IRAN type A; interferes with receptor
processing; dbSNP:rs1329693158)"
/evidence="ECO:0000269|PubMed:12970295"
/id="VAR_031519"
VARIANT 280
/note="C -> Y (in IRAN type A)"
/evidence="ECO:0000269|PubMed:11260230"
/id="VAR_015911"
VARIANT 286
/note="C -> Y (in LEPRCH; abolishes post-translational
processing)"
/evidence="ECO:0000269|PubMed:24498630"
/id="VAR_079537"
VARIANT 301
/note="C -> Y (in LEPRCH)"
/evidence="ECO:0000269|PubMed:9703342"
/id="VAR_015912"
VARIANT 308
/note="Missing (in LEPRCH; abolishes insulin binding)"
/evidence="ECO:0000269|PubMed:12023989,
ECO:0000269|PubMed:7538143, ECO:0000269|PubMed:8636294"
/id="VAR_015913"
VARIANT 350
/note="S -> L (in RMS and LEPRCH)"
/evidence="ECO:0000269|PubMed:12970295,
ECO:0000269|PubMed:8314008"
/id="VAR_015914"
VARIANT 362
/note="Missing (in LEPRCH)"
/evidence="ECO:0000269|PubMed:12538626"
/id="VAR_015541"
VARIANT 386
/note="G -> S (in RMS; may impair receptor processing;
dbSNP:rs764221583)"
/evidence="ECO:0000269|PubMed:17201797"
/id="VAR_031520"
VARIANT 393
/note="G -> R (in LEPRCH; Verona-1; dbSNP:rs267607184)"
/evidence="ECO:0000269|PubMed:1607067"
/id="VAR_004086"
VARIANT 409
/note="F -> V (in IRAN type A; dbSNP:rs121913142)"
/evidence="ECO:0000269|PubMed:8388389"
/id="VAR_004087"
VARIANT 439
/note="W -> S (in LEPRCH; impairs transport of the receptor
to the cell surface; dbSNP:rs121913158)"
/evidence="ECO:0000269|PubMed:8188715"
/id="VAR_015542"
VARIANT 448
/note="I -> T (in dbSNP:rs1051691)"
/evidence="ECO:0000269|PubMed:2859121"
/id="VAR_015915"
VARIANT 458
/note="N -> D (in LEPRCH; partially inhibits receptor
processing and autophosphorylation; strongly impairs ERK
phosphorylation; induces wild-type levels of IRS-1
phosphorylation; dbSNP:rs121913160)"
/evidence="ECO:0000269|PubMed:12970295"
/id="VAR_031521"
VARIANT 487
/note="K -> E (in LEPRCH; ARK-1; dbSNP:rs121913136)"
/evidence="ECO:0000269|PubMed:2834824"
/id="VAR_004088"
VARIANT 489
/note="N -> D (in IRAN type A; unknown pathological
significance; dbSNP:rs1135401742)"
/evidence="ECO:0000269|PubMed:28765322"
/id="VAR_079538"
VARIANT 489
/note="N -> S (in IRAN type A; dbSNP:rs121913147)"
/evidence="ECO:0000269|PubMed:2365819"
/id="VAR_004089"
VARIANT 492
/note="Q -> K"
/evidence="ECO:0000269|PubMed:2859121"
/id="VAR_015916"
VARIANT 635
/note="S -> L (in RMS; decreases post-translational
processing)"
/evidence="ECO:0000269|PubMed:28765322"
/id="VAR_079539"
VARIANT 657
/note="V -> F (in LEPRCH; impairs post-translational
processing; dbSNP:rs1135401737)"
/evidence="ECO:0000269|PubMed:28765322"
/id="VAR_079540"
VARIANT 659
/note="W -> R (in LEPRCH; impairs post-translational
processing)"
/evidence="ECO:0000269|PubMed:28765322"
/id="VAR_079541"
VARIANT 695
/note="Q -> R (in dbSNP:rs55906835)"
/evidence="ECO:0000269|PubMed:17344846"
/id="VAR_041430"
VARIANT 762
/note="R -> S (in IRAN type A; dbSNP:rs121913138)"
/evidence="ECO:0000269|PubMed:3283938"
/id="VAR_004090"
VARIANT 811
/note="G -> S (in dbSNP:rs35045353)"
/evidence="ECO:0000269|PubMed:17344846"
/id="VAR_041431"
VARIANT 818
/note="Y -> C (in LEPRCH; abolishes post-translational
processing)"
/evidence="ECO:0000269|PubMed:22768670,
ECO:0000269|PubMed:28765322"
/id="VAR_079542"
VARIANT 830
/note="P -> L (in dbSNP:rs2162771)"
/id="VAR_055986"
VARIANT 835
/note="S -> I (in RMS; impairs post-translational
processing; dbSNP:rs1135401739)"
/evidence="ECO:0000269|PubMed:28765322"
/id="VAR_079543"
VARIANT 842
/note="A -> V (in RMS; decreases post-translational
processing; dbSNP:rs1135401738)"
/evidence="ECO:0000269|PubMed:28765322"
/id="VAR_079544"
VARIANT 858
/note="T -> A (in NIDDM; dbSNP:rs182552223)"
/evidence="ECO:0000269|PubMed:7657032"
/id="VAR_015917"
VARIANT 874
/note="P -> L (in RMS; impairs post-translational
processing)"
/evidence="ECO:0000269|PubMed:28765322"
/id="VAR_079545"
VARIANT 878
/note="N -> S (in RMS; impairs post-translational
processing; dbSNP:rs887190835)"
/evidence="ECO:0000269|PubMed:28765322"
/id="VAR_079546"
VARIANT 890..1382
/note="Missing (in LEPRCH)"
/evidence="ECO:0000269|PubMed:22768670"
/id="VAR_079547"
VARIANT 925
/note="I -> T (in LEPRCH; abolishes post-translational
processing; abolishes insulin binding)"
/evidence="ECO:0000269|PubMed:12023989,
ECO:0000269|PubMed:28765322"
/id="VAR_015918"
VARIANT 926
/note="R -> W (in LEPRCH; markedly impairs insulin
binding;impairs post-translational processing;
dbSNP:rs911929963)"
/evidence="ECO:0000269|PubMed:12023989,
ECO:0000269|PubMed:28765322"
/id="VAR_015919"
VARIANT 937
/note="T -> M (in LEPRCH; impaired receptor processing;
impairs post-translational processing)"
/evidence="ECO:0000269|PubMed:28765322,
ECO:0000269|PubMed:9299395"
/id="VAR_015920"
VARIANT 997
/note="P -> T (in RMS; reduces insulin binding)"
/evidence="ECO:0000269|PubMed:12023989"
/id="VAR_015921"
VARIANT 999..1382
/note="Missing (in RMS)"
/evidence="ECO:0000269|PubMed:28765322"
/id="VAR_079548"
VARIANT 1012
/note="V -> M (in dbSNP:rs1799816)"
/evidence="ECO:0000269|PubMed:17344846,
ECO:0000269|PubMed:8314008, ECO:0000269|PubMed:8432414,
ECO:0000269|PubMed:8458533, ECO:0000269|PubMed:9199575"
/id="VAR_004091"
VARIANT 1020
/note="R -> Q (in IRAN type A; dbSNP:rs121913148)"
/evidence="ECO:0000269|PubMed:2002058"
/id="VAR_004092"
VARIANT 1023
/note="I -> F"
/evidence="ECO:0000269|PubMed:8890729"
/id="VAR_015922"
VARIANT 1035
/note="G -> V (in IRAN type A; dbSNP:rs121913135)"
/evidence="ECO:0000269|PubMed:2544998"
/id="VAR_004093"
VARIANT 1054
/note="V -> M (in IRAN type A; unknown pathological
significance; dbSNP:rs1135401741)"
/evidence="ECO:0000269|PubMed:28765322"
/id="VAR_079549"
VARIANT 1055
/note="A -> V (in IRAN type A)"
/evidence="ECO:0000269|PubMed:10733238"
/id="VAR_015923"
VARIANT 1065
/note="L -> V (in dbSNP:rs56395521)"
/evidence="ECO:0000269|PubMed:17344846"
/id="VAR_041432"
VARIANT 1075
/note="A -> D (in IRAN type A)"
/evidence="ECO:0000269|PubMed:8243830"
/id="VAR_004094"
VARIANT 1095
/note="K -> E (in a NIDDM subject; dbSNP:rs909008899)"
/evidence="ECO:0000269|PubMed:2040394"
/id="VAR_015924"
VARIANT 1119
/note="R -> W (in LEPRCH; dbSNP:rs1229730671)"
/evidence="ECO:0000269|PubMed:12970295,
ECO:0000269|PubMed:9249867"
/id="VAR_015925"
VARIANT 1143
/note="I -> T (in RMS; reduces insulin binding)"
/evidence="ECO:0000269|PubMed:10443650,
ECO:0000269|PubMed:12023989"
/id="VAR_015926"
VARIANT 1158
/note="R -> Q (in NIDDM)"
/evidence="ECO:0000269|PubMed:1470163"
/id="VAR_015927"
VARIANT 1158
/note="R -> W (in RMS; abolishes insulin binding;
dbSNP:rs111993466)"
/evidence="ECO:0000269|PubMed:10443650,
ECO:0000269|PubMed:12023989"
/id="VAR_015928"
VARIANT 1161
/note="A -> T (in IRAN type A; dbSNP:rs121913139)"
/evidence="ECO:0000269|PubMed:2168397"
/id="VAR_004095"
VARIANT 1162
/note="A -> E (in IRAN type A; impairs proteolytic
processing; dbSNP:rs121913154)"
/evidence="ECO:0000269|PubMed:8096518"
/id="VAR_004096"
VARIANT 1180
/note="M -> I (in a patient with insulin resistance;
dbSNP:rs121913157)"
/evidence="ECO:0000269|PubMed:1890161"
/id="VAR_004097"
VARIANT 1191
/note="R -> Q (in NIDDM; dbSNP:rs121913150)"
/evidence="ECO:0000269|PubMed:1607076"
/id="VAR_004098"
VARIANT 1201
/note="R -> Q (in HHF5 and IRAN type A; interferes with
kinase activation by insulin; dbSNP:rs121913156)"
/evidence="ECO:0000269|PubMed:15161766,
ECO:0000269|PubMed:8082780, ECO:0000269|PubMed:8288049"
/id="VAR_015929"
VARIANT 1201
/note="R -> W (in LEPRCH and RMS; reduces insulin binding
possibly due to reduced receptor levels on the cell
surface; dbSNP:rs1568426700)"
/evidence="ECO:0000269|PubMed:12023989,
ECO:0000269|PubMed:9703342"
/id="VAR_015930"
VARIANT 1205
/note="P -> L (in IRAN type A; moderate;
dbSNP:rs1295645322)"
/evidence="ECO:0000269|PubMed:1563582,
ECO:0000269|PubMed:8314008"
/id="VAR_004099"
VARIANT 1206
/note="E -> D (in IRAN type A; accelerates degradation of
the protein and impairs kinase activity)"
/evidence="ECO:0000269|PubMed:7983039"
/id="VAR_015931"
VARIANT 1206
/note="E -> K (in LEPRCH)"
/evidence="ECO:0000269|PubMed:9249867"
/id="VAR_015932"
VARIANT 1220
/note="W -> L (in IRAN type A; accelerates degradation of
the protein and impairs kinase activity; dbSNP:rs52800171)"
/evidence="ECO:0000269|PubMed:7983039,
ECO:0000269|PubMed:8390949"
/id="VAR_004100"
VARIANT 1227
/note="W -> S (in IRAN type A; dbSNP:rs121913140)"
/evidence="ECO:0000269|PubMed:1963473"
/id="VAR_004101"
VARIANT 1282
/note="T -> A (in dbSNP:rs55875349)"
/evidence="ECO:0000269|PubMed:17344846"
/id="VAR_041433"
VARIANT 1361
/note="Y -> C (in dbSNP:rs13306449)"
/evidence="ECO:0000269|PubMed:7657032"
/id="VAR_015933"
VARIANT 1378
/note="R -> Q (in IRAN type A; dbSNP:rs52826008)"
/evidence="ECO:0000269|PubMed:8314008"
/id="VAR_015934"
MUTAGEN 991
/note="L->A: Reduces interaction with IRS1 but has no
effect on interaction with SHC1."
/evidence="ECO:0000269|PubMed:7559478"
MUTAGEN 992
/note="Y->A: Reduces interaction with IRS1 but has no
effect on interaction with SHC1."
/evidence="ECO:0000269|PubMed:7559478"
MUTAGEN 996..997
/note="NP->AA: Abolishes interaction with IRS1. Severely
disrupts, but does not abolish interaction with SHC1."
/evidence="ECO:0000269|PubMed:7559478"
MUTAGEN 996
/note="N->A: Abolishes interaction with IRS1 and
significantly reduces interaction with SHC1. Has no effect
on interaction with PIK3R1."
/evidence="ECO:0000269|PubMed:7537849,
ECO:0000269|PubMed:7559478"
MUTAGEN 997
/note="P->A: Abolishes interaction with IRS1 and
significantly reduces interaction with SHC1. Has no effect
on interaction with PIK3R1."
/evidence="ECO:0000269|PubMed:7537849,
ECO:0000269|PubMed:7559478"
MUTAGEN 998
/note="E->A: Does not affect interaction with IRS1, SHC1 or
PIK3R1."
/evidence="ECO:0000269|PubMed:7537849"
MUTAGEN 999
/note="Y->E: Abolishes interaction with IRS1 and SHC1."
/evidence="ECO:0000269|PubMed:2842060,
ECO:0000269|PubMed:7537849, ECO:0000269|PubMed:7559478,
ECO:0000269|PubMed:9428692"
MUTAGEN 999
/note="Y->F: Has no effect on insulin-stimulated
autophosphorylation, but inhibits the biological activity
of the receptor. Abolishes interaction with IRS1 and almost
completely prevents interaction with SHC1. Has no effect on
interaction with PIK3R1. Abolishes interaction with
STAT5B."
/evidence="ECO:0000269|PubMed:2842060,
ECO:0000269|PubMed:7537849, ECO:0000269|PubMed:7559478,
ECO:0000269|PubMed:9428692"
MUTAGEN 1000
/note="L->A,R: Severely reduces interaction with SHC1. Has
no effect on interaction with IRS1."
/evidence="ECO:0000269|PubMed:7559478"
MUTAGEN 1002
/note="A->D: Reduces interaction with IRS1 but has no
effect on interaction with SHC1."
/evidence="ECO:0000269|PubMed:7559478"
MUTAGEN 1011
/note="Y->A: Increases kinase activity."
/evidence="ECO:0000269|PubMed:12707268"
MUTAGEN 1057
/note="K->A: Abolishes the kinase activity and abolishes
interaction with IRS1, SHC1, GRB7 and PIK3R1."
/evidence="ECO:0000269|PubMed:10803466,
ECO:0000269|PubMed:3101064, ECO:0000269|PubMed:7537849"
MUTAGEN 1057
/note="K->M,R: Abolishes the kinase activity."
/evidence="ECO:0000269|PubMed:10803466,
ECO:0000269|PubMed:3101064, ECO:0000269|PubMed:7537849"
MUTAGEN 1159
/note="D->N: Loss of kinase activity."
/evidence="ECO:0000269|PubMed:11598120"
MUTAGEN 1163
/note="R->Q: Loss of kinase activity."
/evidence="ECO:0000269|PubMed:11598120"
MUTAGEN 1189
/note="Y->F: Reduced interaction with GRB7."
/evidence="ECO:0000269|PubMed:10803466"
MUTAGEN 1190
/note="Y->F: Strongly reduced interaction with GRB7."
/evidence="ECO:0000269|PubMed:10803466"
CONFLICT 601
/note="D -> N (in Ref. 19; AA sequence)"
/evidence="ECO:0000305"
CONFLICT 830
/note="P -> E (in Ref. 19; AA sequence)"
/evidence="ECO:0000305"
CONFLICT 1278
/note="K -> N (in Ref. 2; CAA26096)"
/evidence="ECO:0000305"
STRAND 33..42
/evidence="ECO:0000244|PDB:2HR7"
HELIX 45..50
/evidence="ECO:0000244|PDB:2HR7"
STRAND 53..65
/evidence="ECO:0000244|PDB:2HR7"
HELIX 70..72
/evidence="ECO:0000244|PDB:2HR7"
TURN 73..75
/evidence="ECO:0000244|PDB:2HR7"
STRAND 83..86
/evidence="ECO:0000244|PDB:2HR7"
STRAND 88..93
/evidence="ECO:0000244|PDB:2HR7"
TURN 100..102
/evidence="ECO:0000244|PDB:2HR7"
STRAND 115..117
/evidence="ECO:0000244|PDB:6PXW"
STRAND 118..124
/evidence="ECO:0000244|PDB:2HR7"
STRAND 141..149
/evidence="ECO:0000244|PDB:2HR7"
HELIX 160..162
/evidence="ECO:0000244|PDB:2HR7"
STRAND 171..175
/evidence="ECO:0000244|PDB:2HR7"
HELIX 176..178
/evidence="ECO:0000244|PDB:2HR7"
TURN 187..192
/evidence="ECO:0000244|PDB:2HR7"
STRAND 199..201
/evidence="ECO:0000244|PDB:2HR7"
STRAND 204..206
/evidence="ECO:0000244|PDB:2HR7"
STRAND 209..211
/evidence="ECO:0000244|PDB:2HR7"
HELIX 221..223
/evidence="ECO:0000244|PDB:2HR7"
STRAND 243..247
/evidence="ECO:0000244|PDB:2HR7"
STRAND 251..260
/evidence="ECO:0000244|PDB:2HR7"
STRAND 263..267
/evidence="ECO:0000244|PDB:2HR7"
STRAND 273..275
/evidence="ECO:0000244|PDB:2HR7"
TURN 276..278
/evidence="ECO:0000244|PDB:2HR7"
STRAND 279..281
/evidence="ECO:0000244|PDB:2HR7"
HELIX 283..295
/evidence="ECO:0000244|PDB:2HR7"
STRAND 298..300
/evidence="ECO:0000244|PDB:2HR7"
STRAND 305..307
/evidence="ECO:0000244|PDB:2HR7"
STRAND 310..314
/evidence="ECO:0000244|PDB:2HR7"
STRAND 319..321
/evidence="ECO:0000244|PDB:2HR7"
TURN 323..325
/evidence="ECO:0000244|PDB:6VEP"
STRAND 327..330
/evidence="ECO:0000244|PDB:2HR7"
STRAND 332..334
/evidence="ECO:0000244|PDB:2HR7"
STRAND 338..348
/evidence="ECO:0000244|PDB:2HR7"
HELIX 351..355
/evidence="ECO:0000244|PDB:2HR7"
TURN 356..359
/evidence="ECO:0000244|PDB:2HR7"
STRAND 361..369
/evidence="ECO:0000244|PDB:2HR7"
STRAND 373..375
/evidence="ECO:0000244|PDB:6HN5"
HELIX 377..385
/evidence="ECO:0000244|PDB:2HR7"
STRAND 390..393
/evidence="ECO:0000244|PDB:2HR7"
STRAND 395..399
/evidence="ECO:0000244|PDB:2HR7"
STRAND 404..406
/evidence="ECO:0000244|PDB:2HR7"
TURN 422..424
/evidence="ECO:0000244|PDB:2HR7"
STRAND 425..430
/evidence="ECO:0000244|PDB:2HR7"
STRAND 437..439
/evidence="ECO:0000244|PDB:4ZXB"
TURN 441..443
/evidence="ECO:0000244|PDB:2HR7"
STRAND 447..450
/evidence="ECO:0000244|PDB:6HN5"
STRAND 452..458
/evidence="ECO:0000244|PDB:2HR7"
HELIX 463..472
/evidence="ECO:0000244|PDB:2HR7"
TURN 476..478
/evidence="ECO:0000244|PDB:2HR7"
TURN 481..483
/evidence="ECO:0000244|PDB:2HR7"
STRAND 486..490
/evidence="ECO:0000244|PDB:2HR7"
STRAND 498..500
/evidence="ECO:0000244|PDB:6PXW"
STRAND 502..507
/evidence="ECO:0000244|PDB:6PXW"
STRAND 512..516
/evidence="ECO:0000244|PDB:6PXW"
HELIX 524..526
/evidence="ECO:0000244|PDB:6PXW"
STRAND 527..534
/evidence="ECO:0000244|PDB:6PXW"
STRAND 538..540
/evidence="ECO:0000244|PDB:6PXW"
STRAND 552..554
/evidence="ECO:0000244|PDB:6HN5"
STRAND 557..561
/evidence="ECO:0000244|PDB:6PXW"
STRAND 570..573
/evidence="ECO:0000244|PDB:6HN5"
STRAND 578..580
/evidence="ECO:0000244|PDB:6PXW"
STRAND 588..597
/evidence="ECO:0000244|PDB:6PXW"
STRAND 601..603
/evidence="ECO:0000244|PDB:6PXW"
STRAND 608..610
/evidence="ECO:0000244|PDB:4ZXB"
STRAND 613..616
/evidence="ECO:0000244|PDB:6PXW"
STRAND 626..631
/evidence="ECO:0000244|PDB:6PXV"
STRAND 633..636
/evidence="ECO:0000244|PDB:6PXV"
STRAND 638..643
/evidence="ECO:0000244|PDB:6PXV"
STRAND 654..658
/evidence="ECO:0000244|PDB:6PXV"
HELIX 666..669
/evidence="ECO:0000244|PDB:6PXV"
HELIX 732..740
/evidence="ECO:0000244|PDB:6VEP"
STRAND 798..803
/evidence="ECO:0000244|PDB:6PXV"
STRAND 805..809
/evidence="ECO:0000244|PDB:6PXV"
STRAND 817..827
/evidence="ECO:0000244|PDB:6PXV"
STRAND 838..843
/evidence="ECO:0000244|PDB:6PXV"
STRAND 858..861
/evidence="ECO:0000244|PDB:6PXV"
STRAND 867..870
/evidence="ECO:0000244|PDB:6PXV"
STRAND 881..890
/evidence="ECO:0000244|PDB:6PXV"
STRAND 896..901
/evidence="ECO:0000244|PDB:6PXV"
HELIX 902..908
/evidence="ECO:0000244|PDB:6PXV"
STRAND 910..913
/evidence="ECO:0000244|PDB:6PXV"
STRAND 918..931
/evidence="ECO:0000244|PDB:6PXV"
STRAND 940..944
/evidence="ECO:0000244|PDB:6PXV"
HELIX 953..979
/evidence="ECO:0000244|PDB:2MFR"
STRAND 992..995
/evidence="ECO:0000244|PDB:5U1M"
TURN 1003..1005
/evidence="ECO:0000244|PDB:4XLV"
HELIX 1009..1011
/evidence="ECO:0000244|PDB:1IR3"
HELIX 1014..1016
/evidence="ECO:0000244|PDB:1IRK"
HELIX 1020..1022
/evidence="ECO:0000244|PDB:3BU3"
STRAND 1023..1031
/evidence="ECO:0000244|PDB:3BU3"
STRAND 1033..1043
/evidence="ECO:0000244|PDB:3BU3"
STRAND 1046..1048
/evidence="ECO:0000244|PDB:2Z8C"
STRAND 1050..1057
/evidence="ECO:0000244|PDB:3BU3"
HELIX 1065..1078
/evidence="ECO:0000244|PDB:3BU3"
STRAND 1089..1093
/evidence="ECO:0000244|PDB:3BU3"
STRAND 1095..1098
/evidence="ECO:0000244|PDB:3BU3"
STRAND 1100..1104
/evidence="ECO:0000244|PDB:3BU3"
HELIX 1111..1117
/evidence="ECO:0000244|PDB:3BU3"
STRAND 1119..1121
/evidence="ECO:0000244|PDB:3ETA"
HELIX 1133..1152
/evidence="ECO:0000244|PDB:3BU3"
STRAND 1154..1156
/evidence="ECO:0000244|PDB:2AUH"
HELIX 1162..1164
/evidence="ECO:0000244|PDB:3BU3"
STRAND 1165..1167
/evidence="ECO:0000244|PDB:3BU3"
STRAND 1173..1175
/evidence="ECO:0000244|PDB:3BU3"
STRAND 1181..1183
/evidence="ECO:0000244|PDB:1IRK"
TURN 1185..1187
/evidence="ECO:0000244|PDB:3BU3"
STRAND 1190..1192
/evidence="ECO:0000244|PDB:5HHW"
STRAND 1194..1198
/evidence="ECO:0000244|PDB:3BU3"
HELIX 1200..1202
/evidence="ECO:0000244|PDB:3BU3"
HELIX 1205..1210
/evidence="ECO:0000244|PDB:3BU3"
HELIX 1215..1230
/evidence="ECO:0000244|PDB:3BU3"
TURN 1236..1239
/evidence="ECO:0000244|PDB:3BU3"
HELIX 1242..1250
/evidence="ECO:0000244|PDB:3BU3"
HELIX 1263..1272
/evidence="ECO:0000244|PDB:3BU3"
HELIX 1277..1279
/evidence="ECO:0000244|PDB:3BU3"
HELIX 1283..1290
/evidence="ECO:0000244|PDB:3BU3"
HELIX 1291..1293
/evidence="ECO:0000244|PDB:5HHW"
HELIX 1298..1301
/evidence="ECO:0000244|PDB:3BU3"
TURN 1303..1305
/evidence="ECO:0000244|PDB:4XLV"
HELIX 1307..1309
/evidence="ECO:0000244|PDB:1I44"
SEQUENCE 1382 AA; 156333 MW; 709A955660739066 CRC64;
MATGGRRGAA AAPLLVAVAA LLLGAAGHLY PGEVCPGMDI RNNLTRLHEL ENCSVIEGHL
QILLMFKTRP EDFRDLSFPK LIMITDYLLL FRVYGLESLK DLFPNLTVIR GSRLFFNYAL
VIFEMVHLKE LGLYNLMNIT RGSVRIEKNN ELCYLATIDW SRILDSVEDN YIVLNKDDNE
ECGDICPGTA KGKTNCPATV INGQFVERCW THSHCQKVCP TICKSHGCTA EGLCCHSECL
GNCSQPDDPT KCVACRNFYL DGRCVETCPP PYYHFQDWRC VNFSFCQDLH HKCKNSRRQG
CHQYVIHNNK CIPECPSGYT MNSSNLLCTP CLGPCPKVCH LLEGEKTIDS VTSAQELRGC
TVINGSLIIN IRGGNNLAAE LEANLGLIEE ISGYLKIRRS YALVSLSFFR KLRLIRGETL
EIGNYSFYAL DNQNLRQLWD WSKHNLTITQ GKLFFHYNPK LCLSEIHKME EVSGTKGRQE
RNDIALKTNG DQASCENELL KFSYIRTSFD KILLRWEPYW PPDFRDLLGF MLFYKEAPYQ
NVTEFDGQDA CGSNSWTVVD IDPPLRSNDP KSQNHPGWLM RGLKPWTQYA IFVKTLVTFS
DERRTYGAKS DIIYVQTDAT NPSVPLDPIS VSNSSSQIIL KWKPPSDPNG NITHYLVFWE
RQAEDSELFE LDYCLKGLKL PSRTWSPPFE SEDSQKHNQS EYEDSAGECC SCPKTDSQIL
KELEESSFRK TFEDYLHNVV FVPRKTSSGT GAEDPRPSRK RRSLGDVGNV TVAVPTVAAF
PNTSSTSVPT SPEEHRPFEK VVNKESLVIS GLRHFTGYRI ELQACNQDTP EERCSVAAYV
SARTMPEAKA DDIVGPVTHE IFENNVVHLM WQEPKEPNGL IVLYEVSYRR YGDEELHLCV
SRKHFALERG CRLRGLSPGN YSVRIRATSL AGNGSWTEPT YFYVTDYLDV PSNIAKIIIG
PLIFVFLFSV VIGSIYLFLR KRQPDGPLGP LYASSNPEYL SASDVFPCSV YVPDEWEVSR
EKITLLRELG QGSFGMVYEG NARDIIKGEA ETRVAVKTVN ESASLRERIE FLNEASVMKG
FTCHHVVRLL GVVSKGQPTL VVMELMAHGD LKSYLRSLRP EAENNPGRPP PTLQEMIQMA
AEIADGMAYL NAKKFVHRDL AARNCMVAHD FTVKIGDFGM TRDIYETDYY RKGGKGLLPV
RWMAPESLKD GVFTTSSDMW SFGVVLWEIT SLAEQPYQGL SNEQVLKFVM DGGYLDQPDN
CPERVTDLMR MCWQFNPKMR PTFLEIVNLL KDDLHPSFPE VSFFHSEENK APESEELEME
FEDMENVPLD RSSHCQREEA GGRDGGSSLG FKRSYEEHIP YTHMNGGKKN GRILTLPRSN
PS


Related products :

Catalog number Product name Quantity
18-783-75598 RABBIT ANTI HUMAN CD220 - INSULIN RECEPTOR; EC 2.7.10.1; IR; CD220 antigen Polyclonal 0.05 mg
BMMS-636-R1 Insulin Receptor (Beta-Subunit ) 1mL
BMMS-636-B Insulin Receptor (Beta-Subunit ) 1mL
BMMS-636-BCS Insulin Receptor (Beta-Subunit ) 5sld
BMMS-636-MX Insulin Receptor (Beta-Subunit ) MTO
BMMS-635-X Insulin Receptor (Beta-Subunit ) 0.2mL
BMMS-635-B1X Insulin Receptor (Beta-Subunit ) 0.1mL
BMMS-635-B1 Insulin Receptor (Beta-Subunit ) 0.5mL
BMMS-635-B0 Insulin Receptor (Beta-Subunit ) 0.1mL
BMMS-635-B Insulin Receptor (Beta-Subunit ) 1mL
BMMS-635-MX Insulin Receptor (Beta-Subunit ) MTO
BMMS-636-X Insulin Receptor (Beta-Subunit) 0.2mL
BMMS-636-BCL Insulin Receptor (Beta-Subunit) 0.1mL
BMMS-636-R1 Insulin Receptor (Beta-Subunit) 1mL
BMMS-636-R7 Insulin Receptor (Beta-Subunit) 7mL
BMMS-636-B0 Insulin Receptor (Beta-Subunit ) 0.1mL
BMMS-636-B1X Insulin Receptor (Beta-Subunit) 0.1mL
BMMS-636-BCL Insulin Receptor (Beta-Subunit ) 0.1mL
BMMS-636-R7 Insulin Receptor (Beta-Subunit ) 7mL
BMMS-635-X Insulin Receptor (Beta-Subunit) 0.2mL
BMMS-636-X Insulin Receptor (Beta-Subunit ) 0.2mL
BMMS-635-B1X Insulin Receptor (Beta-Subunit) 0.1mL
BMMS-636-MX Insulin Receptor (Beta-Subunit) MTO
BMMS-635-B1 Insulin Receptor (Beta-Subunit) 0.5mL
BMMS-635-B0 Insulin Receptor (Beta-Subunit) 0.1mL
Pathways :
WP1913: Signaling by Insulin receptor
WP2292: Chemokine signaling pathway
WP566: canonical wnt - zebrafish
WP2272: Pathogenic Escherichia coli infection
WP1367: TGF-beta Receptor Signaling Pathway
WP809: TGF-beta Receptor Signaling Pathway
WP2328: Allograft rejection
WP926: TGF-beta Receptor Signaling Pathway
WP258: TGF-beta Receptor Signaling Pathway
WP1045: TGF-beta Receptor Signaling Pathway
WP362: TGF-beta Receptor Signaling Pathway
WP1566: Citrate cycle (TCA cycle)
WP1614: 1- and 2-Methylnaphthalene degradation
WP1963: The effect of Glucocorticoids on target gene expression
WP1161: TGF-beta Receptor Signaling Pathway
WP1655: Geraniol degradation
WP768: EPO Receptor Signaling
WP1112: EPO Receptor Signaling
WP1345: T Cell Receptor Signaling Pathway
WP94: Signaling of Hepatocyte Growth Factor Receptor
WP352: T Cell Receptor Signaling Pathway
WP578: Leptin Insulin Overlap
WP1235: Signaling of Hepatocyte Growth Factor Receptor
WP847: Insulin Signaling
WP26: Signal Transduction of S1P Receptor

Related Genes :
[INSR] Insulin receptor (IR) (EC 2.7.10.1) (CD antigen CD220) [Cleaved into: Insulin receptor subunit alpha; Insulin receptor subunit beta]
[Insr] Insulin receptor (IR) (EC 2.7.10.1) (CD antigen CD220) [Cleaved into: Insulin receptor subunit alpha; Insulin receptor subunit beta]
[Insr] Insulin receptor (IR) (EC 2.7.10.1) (CD antigen CD220) [Cleaved into: Insulin receptor subunit alpha; Insulin receptor subunit beta]
[daf-2 Y55D5A.5] Insulin-like receptor (IR) (EC 2.7.10.1) (Abnormal dauer formation protein 2) [Cleaved into: Insulin-like receptor subunit alpha; Insulin-like receptor subunit beta]
[Igf1r] Insulin-like growth factor 1 receptor (EC 2.7.10.1) (Insulin-like growth factor I receptor) (IGF-I receptor) (CD antigen CD221) [Cleaved into: Insulin-like growth factor 1 receptor alpha chain; Insulin-like growth factor 1 receptor beta chain]
[IGF1R] Insulin-like growth factor 1 receptor (EC 2.7.10.1) (Insulin-like growth factor I receptor) (IGF-I receptor) (CD antigen CD221) [Cleaved into: Insulin-like growth factor 1 receptor alpha chain; Insulin-like growth factor 1 receptor beta chain]
[INSR] Insulin receptor (IR) (EC 2.7.10.1) (CD antigen CD220) [Cleaved into: Insulin receptor subunit alpha; Insulin receptor subunit beta] (Fragment)
[InR dinr Dir-a Inr-a CG18402] Insulin-like receptor (dIR) (dInr) (EC 2.7.10.1) (dIRH) [Cleaved into: Insulin-like receptor subunit alpha; Insulin-like receptor subunit beta 1; Insulin-like receptor subunit beta 2]
[Igf1r] Insulin-like growth factor 1 receptor (EC 2.7.10.1) (Insulin-like growth factor I receptor) (IGF-I receptor) (CD antigen CD221) [Cleaved into: Insulin-like growth factor 1 receptor alpha chain; Insulin-like growth factor 1 receptor beta chain]
[IGF1R] Insulin-like growth factor 1 receptor (EC 2.7.10.1) (Insulin-like growth factor I receptor) (IGF-I receptor) (CD antigen CD221) [Cleaved into: Insulin-like growth factor 1 receptor alpha chain; Insulin-like growth factor 1 receptor beta chain] (Fragment)
[IGF2R MPRI] Cation-independent mannose-6-phosphate receptor (CI Man-6-P receptor) (CI-MPR) (M6PR) (300 kDa mannose 6-phosphate receptor) (MPR 300) (Insulin-like growth factor 2 receptor) (Insulin-like growth factor II receptor) (IGF-II receptor) (M6P/IGF2 receptor) (M6P/IGF2R) (CD antigen CD222)
[Igf2r] Cation-independent mannose-6-phosphate receptor (CI Man-6-P receptor) (CI-MPR) (M6PR) (300 kDa mannose 6-phosphate receptor) (MPR 300) (Insulin-like growth factor 2 receptor) (Insulin-like growth factor II receptor) (IGF-II receptor) (M6P/IGF2 receptor) (M6P/IGF2R) (CD antigen CD222)
[IGF2R M6P] Cation-independent mannose-6-phosphate receptor (CI Man-6-P receptor) (CI-MPR) (M6PR) (300 kDa mannose 6-phosphate receptor) (MPR 300) (Insulin-like growth factor 2 receptor) (Insulin-like growth factor II receptor) (IGF-II receptor) (CD antigen CD222)
[BAIAP2] Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAI-associated protein 2) (BAI1-associated protein 2) (Protein BAP2) (Fas ligand-associated factor 3) (FLAF3) (Insulin receptor substrate p53/p58) (IRS-58) (IRSp53/58) (Insulin receptor substrate protein of 53 kDa) (IRSp53) (Insulin receptor substrate p53)
[Baiap2] Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAI-associated protein 2) (BAI1-associated protein 2) (Insulin receptor substrate protein of 53 kDa) (IRSp53) (Insulin receptor substrate p53) (Insulin receptor tyrosine kinase 53 kDa substrate)
[Znf106 H3a Sh3bp3 Sirm Zfp106 Znf474] Zinc finger protein 106 (Zfp-106) (H3a minor histocompatibility antigen) (Son of insulin receptor mutant) (Zinc finger protein 474)
[Baiap2] Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAI-associated protein 2) (BAI1-associated protein 2) (Insulin receptor substrate protein of 53 kDa) (IRSp53) (Insulin receptor substrate p53) (Insulin receptor tyrosine kinase substrate protein p53)
[PDGFRB PDGFR PDGFR1] Platelet-derived growth factor receptor beta (PDGF-R-beta) (PDGFR-beta) (EC 2.7.10.1) (Beta platelet-derived growth factor receptor) (Beta-type platelet-derived growth factor receptor) (CD140 antigen-like family member B) (Platelet-derived growth factor receptor 1) (PDGFR-1) (CD antigen CD140b)
[Pdgfrb Pdgfr Pdgfr1] Platelet-derived growth factor receptor beta (PDGF-R-beta) (PDGFR-beta) (EC 2.7.10.1) (Beta platelet-derived growth factor receptor) (Beta-type platelet-derived growth factor receptor) (CD140 antigen-like family member B) (Platelet-derived growth factor receptor 1) (PDGFR-1) (CD antigen CD140b)
[Ceacam1 Bgp Bgp1] Carcinoembryonic antigen-related cell adhesion molecule 1 (Biliary glycoprotein 1) (BGP-1) (Biliary glycoprotein D) (MHVR1) (Murine hepatitis virus receptor) (MHV-R) (CD antigen CD66a)
[IRS1] Insulin receptor substrate 1 (IRS-1)
[Irs1 Irs-1] Insulin receptor substrate 1 (IRS-1) (pp185)
[SIRPA BIT MFR MYD1 PTPNS1 SHPS1 SIRP] Tyrosine-protein phosphatase non-receptor type substrate 1 (SHP substrate 1) (SHPS-1) (Brain Ig-like molecule with tyrosine-based activation motifs) (Bit) (CD172 antigen-like family member A) (Inhibitory receptor SHPS-1) (Macrophage fusion receptor) (MyD-1 antigen) (Signal-regulatory protein alpha-1) (Sirp-alpha-1) (Signal-regulatory protein alpha-2) (Sirp-alpha-2) (Signal-regulatory protein alpha-3) (Sirp-alpha-3) (p84) (CD antigen CD172a)
[ITGAV MSK8 VNRA VTNR] Integrin alpha-V (Vitronectin receptor) (Vitronectin receptor subunit alpha) (CD antigen CD51) [Cleaved into: Integrin alpha-V heavy chain; Integrin alpha-V light chain]
[Irs1 Irs-1] Insulin receptor substrate 1 (IRS-1)
[LRP1 A2MR APR] Prolow-density lipoprotein receptor-related protein 1 (LRP-1) (Alpha-2-macroglobulin receptor) (A2MR) (Apolipoprotein E receptor) (APOER) (CD antigen CD91) [Cleaved into: Low-density lipoprotein receptor-related protein 1 85 kDa subunit (LRP-85); Low-density lipoprotein receptor-related protein 1 515 kDa subunit (LRP-515); Low-density lipoprotein receptor-related protein 1 intracellular domain (LRPICD)]
[Lrp1 A2mr] Prolow-density lipoprotein receptor-related protein 1 (LRP-1) (Alpha-2-macroglobulin receptor) (A2MR) (CD antigen CD91) [Cleaved into: Low-density lipoprotein receptor-related protein 1 85 kDa subunit (LRP-85); Low-density lipoprotein receptor-related protein 1 515 kDa subunit (LRP-515); Low-density lipoprotein receptor-related protein 1 intracellular domain (LRPICD)]
[DDR1 CAK EDDR1 NEP NTRK4 PTK3A RTK6 TRKE] Epithelial discoidin domain-containing receptor 1 (Epithelial discoidin domain receptor 1) (EC 2.7.10.1) (CD167 antigen-like family member A) (Cell adhesion kinase) (Discoidin receptor tyrosine kinase) (HGK2) (Mammary carcinoma kinase 10) (MCK-10) (Protein-tyrosine kinase 3A) (Protein-tyrosine kinase RTK-6) (TRK E) (Tyrosine kinase DDR) (Tyrosine-protein kinase CAK) (CD antigen CD167a)
[Fgfr4 Fgfr-4 Mpk-11] Fibroblast growth factor receptor 4 (FGFR-4) (EC 2.7.10.1) (Protein-tyrosine kinase receptor MPK-11) (CD antigen CD334)
[INS] Insulin [Cleaved into: Insulin B chain; Insulin A chain]

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