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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.
30-AUG-2017, entry version 239.
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,
ENZYME 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;
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 ENZYME 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 ENZYME
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 ENZYME 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 ENZYME 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/nrg1767;
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]
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).
[56]
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).
[57]
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).
[58]
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).
[59]
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).
[60]
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).
[61]
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).
[62]
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).
[63]
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).
[64]
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).
[65]
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).
[66]
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).
[67]
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).
[68]
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).
[69]
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).
[70]
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).
[71]
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).
[72]
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).
[73]
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).
[74]
VARIANT LEPRCH PRO-260.
PubMed=2479553;
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).
[75]
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).
[76]
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).
[77]
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).
[78]
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).
[79]
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).
[80]
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).
[81]
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).
[82]
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).
[83]
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).
[84]
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).
[85]
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).
[86]
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).
[87]
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).
[88]
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).
[89]
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).
[90]
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).
[91]
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).
[92]
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).
[93]
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).
[94]
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).
[95]
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).
[96]
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).
[97]
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).
[98]
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).
[99]
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).
[100]
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).
[101]
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).
[102]
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).
[103]
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).
[104]
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).
[105]
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).
[106]
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).
[107]
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).
[108]
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).
[109]
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).
[110]
VARIANTS LEPRCH TRP-1119 AND LYS-1206.
PubMed=9249867;
DOI=10.1002/(SICI)1097-0223(199707)17:7<657::AID-PD132>3.3.CO;2-#;
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).
[111]
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).
[112]
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).
[113]
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).
[114]
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).
[115]
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).
[116]
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).
[117]
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).
[118]
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).
[119]
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).
[120]
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).
[121]
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).
-!- 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.
{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: ATP + a [protein]-L-tyrosine = ADP + a
[protein]-L-tyrosine phosphate. {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}.
-!- ENZYME 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). {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: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:
Q99490:AGAP2; NbExp=2; IntAct=EBI-475899, EBI-2361824;
P22413:ENPP1; NbExp=2; IntAct=EBI-475899, EBI-3197846;
Q13322:GRB10; NbExp=3; IntAct=EBI-475899, EBI-80275;
P05019:IGF1; NbExp=4; IntAct=EBI-475899, EBI-7902275;
P01317:INS (xeno); NbExp=5; IntAct=EBI-475899, EBI-3989070;
P35568:IRS1; NbExp=3; IntAct=EBI-475899, EBI-517592;
P35570:Irs1 (xeno); NbExp=5; IntAct=EBI-475899, EBI-520230;
Q15323:KRT31; NbExp=3; IntAct=EBI-475899, EBI-948001;
P27986:PIK3R1; NbExp=3; IntAct=EBI-475899, EBI-79464;
P19174:PLCG1; NbExp=9; IntAct=EBI-475899, EBI-79387;
P18031:PTPN1; NbExp=33; IntAct=EBI-475899, EBI-968788;
Q06124:PTPN11; NbExp=2; IntAct=EBI-475899, EBI-297779;
Q9NRF2:SH2B1; NbExp=6; IntAct=EBI-475899, EBI-310491;
P29353:SHC1; NbExp=2; IntAct=EBI-475899, EBI-78835;
-!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
protein.
-!- 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:8314008}. Note=The
disease is caused by mutations 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:2365819,
ECO:0000269|PubMed:2479553, ECO:0000269|PubMed:2834824,
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
mutations 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 mutations 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: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 mutations 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";
-----------------------------------------------------------------------
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
Distributed under the Creative Commons Attribution-NoDerivs License
-----------------------------------------------------------------------
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]
UniGene; Hs.465744; -.
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; 3W14; X-ray; 4.40 A; E/F=28-746.
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.
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; 3W14; -.
PDBsum; 4IBM; -.
PDBsum; 4OGA; -.
PDBsum; 4XLV; -.
PDBsum; 4XSS; -.
PDBsum; 4XST; -.
PDBsum; 4ZXB; -.
PDBsum; 5E1S; -.
PDBsum; 5HHW; -.
PDBsum; 5J3H; -.
ProteinModelPortal; P06213; -.
SMR; P06213; -.
BioGrid; 109854; 87.
DIP; DIP-480N; -.
ELM; P06213; -.
IntAct; P06213; 50.
MINT; MINT-1516246; -.
STRING; 9606.ENSP00000303830; -.
BindingDB; P06213; -.
ChEMBL; CHEMBL1981; -.
DrugBank; DB08513; [4-({5-(AMINOCARBONYL)-4-[(3-METHYLPHENYL)AMINO]PYRIMIDIN-2-YL}AMINO)PHENYL]ACETIC ACID.
DrugBank; DB05120; AT1391.
DrugBank; DB09129; Chromic chloride.
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; DB05115; NN344.
GuidetoPHARMACOLOGY; 1800; -.
iPTMnet; P06213; -.
PhosphoSitePlus; P06213; -.
BioMuta; INSR; -.
DMDM; 308153655; -.
EPD; P06213; -.
MaxQB; P06213; -.
PaxDb; P06213; -.
PeptideAtlas; P06213; -.
PRIDE; P06213; -.
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; -.
H-InvDB; HIX0040111; -.
HGNC; HGNC:6091; INSR.
HPA; HPA036302; -.
HPA; HPA036303; -.
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; -.
eggNOG; KOG4258; Eukaryota.
eggNOG; COG0515; LUCA.
GeneTree; ENSGT00760000118818; -.
HOGENOM; HOG000038045; -.
HOVERGEN; HBG006134; -.
InParanoid; P06213; -.
KO; K04527; -.
OMA; ESAGECC; -.
OrthoDB; EOG091G00GE; -.
PhylomeDB; P06213; -.
TreeFam; TF351636; -.
BRENDA; 2.7.10.1; 2681.
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; -.
ChiTaRS; INSR; human.
EvolutionaryTrace; P06213; -.
GeneWiki; Insulin_receptor; -.
GenomeRNAi; 3643; -.
PRO; PR:P06213; -.
Proteomes; UP000005640; Chromosome 19.
Bgee; ENSG00000171105; -.
CleanEx; HS_INSR; -.
ExpressionAtlas; P06213; baseline and differential.
Genevisible; P06213; HS.
GO; GO:0005901; C:caveola; IDA:BHF-UCL.
GO; GO:0010008; C:endosome membrane; TAS:Reactome.
GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB.
GO; GO:0005899; C:insulin receptor complex; IMP:BHF-UCL.
GO; GO:0005887; C:integral component of plasma membrane; IDA:BHF-UCL.
GO; GO:0016020; C:membrane; IDA:BHF-UCL.
GO; GO:0005886; C:plasma membrane; TAS:Reactome.
GO; GO:0043235; C:receptor complex; IDA:MGI.
GO; GO:0005524; F:ATP binding; IDA:BHF-UCL.
GO; GO:0005525; F:GTP binding; IDA:BHF-UCL.
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:0051425; F:PTB domain binding; IPI:UniProtKB.
GO; GO:0004716; F:signal transducer, downstream of receptor, with protein tyrosine kinase activity; IDA:BHF-UCL.
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: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: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: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 proliferation; IDA:BHF-UCL.
GO; GO:0048639; P:positive regulation of developmental growth; IMP:BHF-UCL.
GO; GO:0045740; P:positive regulation of DNA replication; 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: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: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: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:0051290; P:protein heterotetramerization; IDA:UniProtKB.
GO; GO:0006468; P:protein phosphorylation; TAS: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.
CDD; cd00063; FN3; 2.
Gene3D; 2.60.40.10; -; 3.
Gene3D; 3.80.20.20; -; 3.
InterPro; IPR003961; FN3_dom.
InterPro; IPR006211; Furin-like_Cys-rich_dom.
InterPro; IPR006212; Furin_repeat.
InterPro; IPR009030; Growth_fac_rcpt_.
InterPro; IPR013783; Ig-like_fold.
InterPro; IPR011009; Kinase-like_dom.
InterPro; IPR032675; L_dom-like.
InterPro; IPR000719; Prot_kinase_dom.
InterPro; IPR017441; Protein_kinase_ATP_BS.
InterPro; IPR000494; Rcpt_L-dom.
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; PF07714; Pkinase_Tyr; 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; 4.
SUPFAM; SSF52058; SSF52058; 2.
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; Complete proteome;
Diabetes mellitus; Direct protein sequencing; Disease mutation;
Disulfide bond; Glycoprotein; Kinase; Membrane; Nucleotide-binding;
Phosphoprotein; Polymorphism; Receptor; Reference proteome; Repeat;
Signal; Transferase; Transmembrane; Transmembrane helix;
Tyrosine-protein kinase.
SIGNAL 1 27 {ECO:0000269|PubMed:2211730,
ECO:0000269|PubMed:2983222,
ECO:0000269|PubMed:8257688}.
CHAIN 28 758 Insulin receptor subunit alpha.
/FTId=PRO_0000016687.
CHAIN 763 1382 Insulin receptor subunit beta.
/FTId=PRO_0000016689.
TOPO_DOM 28 758 Extracellular. {ECO:0000305}.
TOPO_DOM 763 956 Extracellular. {ECO:0000305}.
TRANSMEM 957 979 Helical. {ECO:0000255}.
TOPO_DOM 980 1382 Cytoplasmic. {ECO:0000305}.
DOMAIN 624 726 Fibronectin type-III 1.
{ECO:0000255|PROSITE-ProRule:PRU00316}.
DOMAIN 757 842 Fibronectin type-III 2.
{ECO:0000255|PROSITE-ProRule:PRU00316}.
DOMAIN 853 947 Fibronectin type-III 3.
{ECO:0000255|PROSITE-ProRule:PRU00316}.
DOMAIN 1023 1298 Protein kinase. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
NP_BIND 1104 1110 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159,
ECO:0000269|PubMed:18278056}.
NP_BIND 1163 1164 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159,
ECO:0000269|PubMed:18278056}.
REGION 733 741 Insulin-binding.
REGION 999 999 Important for interaction with IRS1, SHC1
and STAT5B. {ECO:0000269|PubMed:9428692}.
REGION 1361 1364 PIK3R1-binding.
COMPBIAS 28 174 Leu-rich.
COMPBIAS 182 339 Cys-rich.
ACT_SITE 1159 1159 Proton donor/acceptor.
{ECO:0000269|PubMed:9312016}.
BINDING 1033 1033 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159,
ECO:0000269|PubMed:18278056}.
BINDING 1057 1057 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159,
ECO:0000269|PubMed:18278056}.
BINDING 1177 1177 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159,
ECO:0000269|PubMed:18278056}.
SITE 66 66 Insulin-binding. {ECO:0000305}.
MOD_RES 400 400 Phosphoserine.
{ECO:0000244|PubMed:18669648}.
MOD_RES 401 401 Phosphotyrosine.
{ECO:0000244|PubMed:18669648}.
MOD_RES 407 407 Phosphoserine.
{ECO:0000244|PubMed:18669648}.
MOD_RES 992 992 Phosphotyrosine; by autocatalysis.
{ECO:0000305}.
MOD_RES 999 999 Phosphotyrosine; by autocatalysis.
{ECO:0000305|PubMed:3166375}.
MOD_RES 1011 1011 Phosphotyrosine; by autocatalysis.
{ECO:0000305}.
MOD_RES 1185 1185 Phosphotyrosine; by autocatalysis.
{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 1189 Phosphotyrosine; by autocatalysis.
{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 1190 Phosphotyrosine; by autocatalysis.
{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 1355 Phosphotyrosine; by autocatalysis.
{ECO:0000305|PubMed:3166375}.
MOD_RES 1361 1361 Phosphotyrosine; by autocatalysis.
{ECO:0000305|PubMed:3166375}.
CARBOHYD 43 43 N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:16894147,
ECO:0000269|PubMed:23302862,
ECO:0000269|PubMed:2983222}.
CARBOHYD 52 52 N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:16894147,
ECO:0000269|PubMed:23302862}.
CARBOHYD 105 105 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 138 138 N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:16894147,
ECO:0000269|PubMed:23302862}.
CARBOHYD 242 242 N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:16894147,
ECO:0000269|PubMed:19159218,
ECO:0000269|PubMed:23302862}.
CARBOHYD 282 282 N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:16894147,
ECO:0000269|PubMed:23302862}.
CARBOHYD 322 322 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 364 364 N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:16894147}.
CARBOHYD 424 424 N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:16894147}.
CARBOHYD 445 445 N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:16894147,
ECO:0000269|PubMed:19349973}.
CARBOHYD 541 541 N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:1472036,
ECO:0000269|PubMed:19159218}.
CARBOHYD 633 633 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 651 651 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 698 698 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 769 769 N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:2983222}.
CARBOHYD 782 782 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 920 920 N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:19349973}.
CARBOHYD 933 933 N-linked (GlcNAc...) asparagine.
{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 {ECO:0000269|PubMed:1472036}.
DISULFID 551 551 Interchain. {ECO:0000269|PubMed:1472036}.
DISULFID 674 899
DISULFID 825 834
VAR_SEQ 745 756 Missing (in isoform Short).
{ECO:0000303|PubMed:15489334,
ECO:0000303|PubMed:2983222,
ECO:0000303|Ref.13}.
/FTId=VSP_002898.
VARIANT 2 2 A -> G (in dbSNP:rs7508518).
{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}.
/FTId=VAR_058395.
VARIANT 42 42 N -> K (in RMS; impairs transport to the
plasma membrane and reduces the affinity
to bind insulin; dbSNP:rs121913143).
{ECO:0000269|PubMed:2121734,
ECO:0000269|PubMed:2365819}.
/FTId=VAR_004079.
VARIANT 55 55 V -> A (in LEPRCH; Verona-1;
dbSNP:rs121913152).
{ECO:0000269|PubMed:1607067}.
/FTId=VAR_004080.
VARIANT 58 58 G -> R (in LEPRCH; Helmond; inhibits
processing and transport;
dbSNP:rs52836744).
{ECO:0000269|PubMed:1730625}.
/FTId=VAR_004081.
VARIANT 86 86 D -> G (in IRAN type A).
{ECO:0000269|PubMed:9175790}.
/FTId=VAR_015907.
VARIANT 89 89 L -> P (in IRAN type A).
{ECO:0000269|PubMed:9175790}.
/FTId=VAR_015908.
VARIANT 113 113 R -> P (in LEPRCH; Atlanta-1; abolishes
insulin binding; dbSNP:rs121913153).
{ECO:0000269|PubMed:12023989,
ECO:0000269|PubMed:8419945}.
/FTId=VAR_004082.
VARIANT 119 119 A -> V (in LEPRCH; markedly impairs
insulin binding).
{ECO:0000269|PubMed:12023989}.
/FTId=VAR_015909.
VARIANT 120 120 L -> Q (in LEPRCH; inhibits receptor
processing).
{ECO:0000269|PubMed:12970295}.
/FTId=VAR_031518.
VARIANT 146 146 I -> M (in LEPRCH; mild;
dbSNP:rs121913159).
{ECO:0000269|PubMed:7815442,
ECO:0000269|PubMed:8326490}.
/FTId=VAR_015539.
VARIANT 167 167 V -> L (in IRAN type A).
{ECO:0000269|PubMed:10733238}.
/FTId=VAR_015910.
VARIANT 171 171 Y -> H (in dbSNP:rs1051692).
{ECO:0000269|PubMed:2859121}.
/FTId=VAR_058396.
VARIANT 220 220 P -> L (in Ins resistance; severe;
dbSNP:rs749094324).
{ECO:0000269|PubMed:8242067}.
/FTId=VAR_004083.
VARIANT 228 228 C -> R (in a gastric adenocarcinoma
sample; somatic mutation).
{ECO:0000269|PubMed:17344846}.
/FTId=VAR_041429.
VARIANT 236 236 H -> R (in RMS and LEPRCH; Winnipeg; may
impair receptor processing;
dbSNP:rs121913145).
{ECO:0000269|PubMed:17201797,
ECO:0000269|PubMed:2365819}.
/FTId=VAR_004084.
VARIANT 260 260 L -> P (in LEPRCH; Geldeimalsen;
dbSNP:rs121913141).
{ECO:0000269|PubMed:2479553}.
/FTId=VAR_004085.
VARIANT 279 279 R -> C (in IRAN type A; inhibits receptor
internalization).
{ECO:0000269|PubMed:12107746}.
/FTId=VAR_015540.
VARIANT 279 279 R -> H (in IRAN type A; interferes with
receptor processing).
{ECO:0000269|PubMed:12970295}.
/FTId=VAR_031519.
VARIANT 280 280 C -> Y (in IRAN type A).
{ECO:0000269|PubMed:11260230}.
/FTId=VAR_015911.
VARIANT 301 301 C -> Y (in LEPRCH).
{ECO:0000269|PubMed:9703342}.
/FTId=VAR_015912.
VARIANT 308 308 Missing (in LEPRCH; abolishes insulin
binding). {ECO:0000269|PubMed:12023989,
ECO:0000269|PubMed:7538143,
ECO:0000269|PubMed:8636294}.
/FTId=VAR_015913.
VARIANT 350 350 S -> L (in RMS and LEPRCH).
{ECO:0000269|PubMed:12970295,
ECO:0000269|PubMed:8314008}.
/FTId=VAR_015914.
VARIANT 362 362 Missing (in LEPRCH).
{ECO:0000269|PubMed:12538626}.
/FTId=VAR_015541.
VARIANT 386 386 G -> S (in RMS; may impair receptor
processing; dbSNP:rs764221583).
{ECO:0000269|PubMed:17201797}.
/FTId=VAR_031520.
VARIANT 393 393 G -> R (in LEPRCH; Verona-1;
dbSNP:rs267607184).
{ECO:0000269|PubMed:1607067}.
/FTId=VAR_004086.
VARIANT 409 409 F -> V (in IRAN type A;
dbSNP:rs121913142).
{ECO:0000269|PubMed:8388389}.
/FTId=VAR_004087.
VARIANT 439 439 W -> S (in LEPRCH; impairs transport of
the receptor to the cell surface;
dbSNP:rs121913158).
{ECO:0000269|PubMed:8188715}.
/FTId=VAR_015542.
VARIANT 448 448 I -> T (in dbSNP:rs1051691).
{ECO:0000269|PubMed:2859121}.
/FTId=VAR_015915.
VARIANT 458 458 N -> D (in LEPRCH; partially inhibits
receptor processing and
autophosphorylation; strongly impairs ERK
phosphorylation; induces wild-type levels
of IRS-1 phosphorylation;
dbSNP:rs121913160).
{ECO:0000269|PubMed:12970295}.
/FTId=VAR_031521.
VARIANT 487 487 K -> E (in LEPRCH; ARK-1;
dbSNP:rs28933083).
{ECO:0000269|PubMed:2834824}.
/FTId=VAR_004088.
VARIANT 489 489 N -> S (in IRAN type A;
dbSNP:rs28933085).
{ECO:0000269|PubMed:2365819}.
/FTId=VAR_004089.
VARIANT 492 492 Q -> K (in dbSNP:rs1131851).
{ECO:0000269|PubMed:2859121}.
/FTId=VAR_015916.
VARIANT 695 695 Q -> R (in dbSNP:rs55906835).
{ECO:0000269|PubMed:17344846}.
/FTId=VAR_041430.
VARIANT 762 762 R -> S (in IRAN type A;
dbSNP:rs121913138).
{ECO:0000269|PubMed:3283938}.
/FTId=VAR_004090.
VARIANT 811 811 G -> S (in dbSNP:rs35045353).
{ECO:0000269|PubMed:17344846}.
/FTId=VAR_041431.
VARIANT 830 830 P -> L (in dbSNP:rs2162771).
/FTId=VAR_055986.
VARIANT 858 858 T -> A (in NIDDM; dbSNP:rs182552223).
{ECO:0000269|PubMed:7657032}.
/FTId=VAR_015917.
VARIANT 925 925 I -> T (in LEPRCH; abolishes insulin
binding). {ECO:0000269|PubMed:12023989}.
/FTId=VAR_015918.
VARIANT 926 926 R -> W (in LEPRCH; markedly impairs
insulin binding).
{ECO:0000269|PubMed:12023989}.
/FTId=VAR_015919.
VARIANT 937 937 T -> M (in LEPRCH; impaired receptor
processing).
{ECO:0000269|PubMed:9299395}.
/FTId=VAR_015920.
VARIANT 997 997 P -> T (in RMS; reduces insulin binding).
{ECO:0000269|PubMed:12023989}.
/FTId=VAR_015921.
VARIANT 1012 1012 V -> M (rare polymorphism;
dbSNP:rs1799816).
{ECO:0000269|PubMed:17344846,
ECO:0000269|PubMed:8314008,
ECO:0000269|PubMed:8432414,
ECO:0000269|PubMed:8458533,
ECO:0000269|PubMed:9199575}.
/FTId=VAR_004091.
VARIANT 1020 1020 R -> Q (in IRAN type A;
dbSNP:rs121913148).
{ECO:0000269|PubMed:2002058}.
/FTId=VAR_004092.
VARIANT 1023 1023 I -> F. {ECO:0000269|PubMed:8890729}.
/FTId=VAR_015922.
VARIANT 1035 1035 G -> V (in IRAN type A;
dbSNP:rs121913135).
{ECO:0000269|PubMed:2544998}.
/FTId=VAR_004093.
VARIANT 1055 1055 A -> V (in IRAN type A).
{ECO:0000269|PubMed:10733238}.
/FTId=VAR_015923.
VARIANT 1065 1065 L -> V (in dbSNP:rs56395521).
{ECO:0000269|PubMed:17344846}.
/FTId=VAR_041432.
VARIANT 1075 1075 A -> D (in IRAN type A).
{ECO:0000269|PubMed:8243830}.
/FTId=VAR_004094.
VARIANT 1095 1095 K -> E (in a NIDDM subject).
{ECO:0000269|PubMed:2040394}.
/FTId=VAR_015924.
VARIANT 1119 1119 R -> W (in LEPRCH).
{ECO:0000269|PubMed:12970295,
ECO:0000269|PubMed:9249867}.
/FTId=VAR_015925.
VARIANT 1143 1143 I -> T (in RMS; reduces insulin binding).
{ECO:0000269|PubMed:10443650,
ECO:0000269|PubMed:12023989}.
/FTId=VAR_015926.
VARIANT 1158 1158 R -> Q (in NIDDM).
{ECO:0000269|PubMed:1470163}.
/FTId=VAR_015927.
VARIANT 1158 1158 R -> W (in RMS; abolishes insulin
binding; dbSNP:rs111993466).
{ECO:0000269|PubMed:10443650,
ECO:0000269|PubMed:12023989}.
/FTId=VAR_015928.
VARIANT 1161 1161 A -> T (in IRAN type A;
dbSNP:rs28933084).
{ECO:0000269|PubMed:2168397}.
/FTId=VAR_004095.
VARIANT 1162 1162 A -> E (in IRAN type A; impairs
proteolytic processing;
dbSNP:rs121913154).
{ECO:0000269|PubMed:8096518}.
/FTId=VAR_004096.
VARIANT 1180 1180 M -> I (in a patient with insulin
resistance; dbSNP:rs121913157).
{ECO:0000269|PubMed:1890161}.
/FTId=VAR_004097.
VARIANT 1191 1191 R -> Q (in NIDDM; dbSNP:rs121913150).
{ECO:0000269|PubMed:1607076}.
/FTId=VAR_004098.
VARIANT 1201 1201 R -> Q (in HHF5 and IRAN type A;
interferes with kinase activation by
insulin; dbSNP:rs28933086).
{ECO:0000269|PubMed:15161766,
ECO:0000269|PubMed:8082780,
ECO:0000269|PubMed:8288049}.
/FTId=VAR_015929.
VARIANT 1201 1201 R -> W (in LEPRCH and RMS; reduces
insulin binding possibly due to reduced
receptor levels on the cell surface).
{ECO:0000269|PubMed:12023989,
ECO:0000269|PubMed:9703342}.
/FTId=VAR_015930.
VARIANT 1205 1205 P -> L (in IRAN type A; moderate).
{ECO:0000269|PubMed:1563582,
ECO:0000269|PubMed:8314008}.
/FTId=VAR_004099.
VARIANT 1206 1206 E -> D (in IRAN type A; accelerates
degradation of the protein and impairs
kinase activity).
{ECO:0000269|PubMed:7983039}.
/FTId=VAR_015931.
VARIANT 1206 1206 E -> K (in LEPRCH).
{ECO:0000269|PubMed:9249867}.
/FTId=VAR_015932.
VARIANT 1220 1220 W -> L (in IRAN type A; accelerates
degradation of the protein and impairs
kinase activity; dbSNP:rs52800171).
{ECO:0000269|PubMed:7983039,
ECO:0000269|PubMed:8390949}.
/FTId=VAR_004100.
VARIANT 1227 1227 W -> S (in IRAN type A;
dbSNP:rs121913140).
{ECO:0000269|PubMed:1963473}.
/FTId=VAR_004101.
VARIANT 1282 1282 T -> A (in dbSNP:rs55875349).
{ECO:0000269|PubMed:17344846}.
/FTId=VAR_041433.
VARIANT 1361 1361 Y -> C (in dbSNP:rs13306449).
{ECO:0000269|PubMed:7657032}.
/FTId=VAR_015933.
VARIANT 1378 1378 R -> Q (in IRAN type A;
dbSNP:rs52826008).
{ECO:0000269|PubMed:8314008}.
/FTId=VAR_015934.
MUTAGEN 991 991 L->A: Reduces interaction with IRS1 but
has no effect on interaction with SHC1.
{ECO:0000269|PubMed:7559478}.
MUTAGEN 992 992 Y->A: Reduces interaction with IRS1 but
has no effect on interaction with SHC1.
{ECO:0000269|PubMed:7559478}.
MUTAGEN 996 997 NP->AA: Abolishes interaction with IRS1.
Severely disrupts, but does not abolish
interaction with SHC1.
{ECO:0000269|PubMed:7559478}.
MUTAGEN 996 996 N->A: Abolishes interaction with IRS1 and
significantly reduces interaction with
SHC1. Has no effect on interaction with
PIK3R1. {ECO:0000269|PubMed:7537849,
ECO:0000269|PubMed:7559478}.
MUTAGEN 997 997 P->A: Abolishes interaction with IRS1 and
significantly reduces interaction with
SHC1. Has no effect on interaction with
PIK3R1. {ECO:0000269|PubMed:7537849,
ECO:0000269|PubMed:7559478}.
MUTAGEN 998 998 E->A: Does not affect interaction with
IRS1, SHC1 or PIK3R1.
{ECO:0000269|PubMed:7537849}.
MUTAGEN 999 999 Y->E: Abolishes interaction with IRS1 and
SHC1. {ECO:0000269|PubMed:2842060,
ECO:0000269|PubMed:7537849,
ECO:0000269|PubMed:7559478,
ECO:0000269|PubMed:9428692}.
MUTAGEN 999 999 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. {ECO:0000269|PubMed:2842060,
ECO:0000269|PubMed:7537849,
ECO:0000269|PubMed:7559478,
ECO:0000269|PubMed:9428692}.
MUTAGEN 1000 1000 L->A,R: Severely reduces interaction with
SHC1. Has no effect on interaction with
IRS1. {ECO:0000269|PubMed:7559478}.
MUTAGEN 1002 1002 A->D: Reduces interaction with IRS1 but
has no effect on interaction with SHC1.
{ECO:0000269|PubMed:7559478}.
MUTAGEN 1011 1011 Y->A: Increases kinase activity.
{ECO:0000269|PubMed:12707268}.
MUTAGEN 1057 1057 K->A: Abolishes the kinase activity and
abolishes interaction with IRS1, SHC1,
GRB7 and PIK3R1.
{ECO:0000269|PubMed:10803466,
ECO:0000269|PubMed:3101064,
ECO:0000269|PubMed:7537849}.
MUTAGEN 1057 1057 K->M,R: Abolishes the kinase activity.
{ECO:0000269|PubMed:10803466,
ECO:0000269|PubMed:3101064,
ECO:0000269|PubMed:7537849}.
MUTAGEN 1159 1159 D->N: Loss of kinase activity.
{ECO:0000269|PubMed:11598120}.
MUTAGEN 1163 1163 R->Q: Loss of kinase activity.
{ECO:0000269|PubMed:11598120}.
MUTAGEN 1189 1189 Y->F: Reduced interaction with GRB7.
{ECO:0000269|PubMed:10803466}.
MUTAGEN 1190 1190 Y->F: Strongly reduced interaction with
GRB7. {ECO:0000269|PubMed:10803466}.
CONFLICT 601 601 D -> N (in Ref. 19; AA sequence).
{ECO:0000305}.
CONFLICT 830 830 P -> E (in Ref. 19; AA sequence).
{ECO:0000305}.
CONFLICT 1278 1278 K -> N (in Ref. 2; CAA26096).
{ECO:0000305}.
STRAND 33 42 {ECO:0000244|PDB:2HR7}.
HELIX 45 50 {ECO:0000244|PDB:2HR7}.
STRAND 53 65 {ECO:0000244|PDB:2HR7}.
HELIX 70 72 {ECO:0000244|PDB:2HR7}.
TURN 73 75 {ECO:0000244|PDB:2HR7}.
STRAND 83 86 {ECO:0000244|PDB:2HR7}.
STRAND 88 93 {ECO:0000244|PDB:2HR7}.
TURN 100 102 {ECO:0000244|PDB:2HR7}.
STRAND 118 124 {ECO:0000244|PDB:2HR7}.
STRAND 141 149 {ECO:0000244|PDB:2HR7}.
HELIX 160 162 {ECO:0000244|PDB:2HR7}.
STRAND 171 175 {ECO:0000244|PDB:2HR7}.
HELIX 176 178 {ECO:0000244|PDB:2HR7}.
TURN 187 192 {ECO:0000244|PDB:2HR7}.
STRAND 199 201 {ECO:0000244|PDB:2HR7}.
STRAND 204 206 {ECO:0000244|PDB:2HR7}.
STRAND 209 211 {ECO:0000244|PDB:2HR7}.
HELIX 221 223 {ECO:0000244|PDB:2HR7}.
STRAND 243 247 {ECO:0000244|PDB:2HR7}.
STRAND 251 260 {ECO:0000244|PDB:2HR7}.
STRAND 263 267 {ECO:0000244|PDB:2HR7}.
STRAND 273 275 {ECO:0000244|PDB:2HR7}.
TURN 276 278 {ECO:0000244|PDB:2HR7}.
STRAND 279 281 {ECO:0000244|PDB:2HR7}.
HELIX 283 295 {ECO:0000244|PDB:2HR7}.
STRAND 298 300 {ECO:0000244|PDB:2HR7}.
STRAND 305 307 {ECO:0000244|PDB:2HR7}.
STRAND 310 314 {ECO:0000244|PDB:2HR7}.
STRAND 319 321 {ECO:0000244|PDB:2HR7}.
TURN 323 325 {ECO:0000244|PDB:4ZXB}.
STRAND 327 330 {ECO:0000244|PDB:2HR7}.
STRAND 332 334 {ECO:0000244|PDB:2HR7}.
STRAND 338 348 {ECO:0000244|PDB:2HR7}.
HELIX 351 355 {ECO:0000244|PDB:2HR7}.
TURN 356 359 {ECO:0000244|PDB:2HR7}.
STRAND 361 369 {ECO:0000244|PDB:2HR7}.
HELIX 377 385 {ECO:0000244|PDB:2HR7}.
STRAND 390 393 {ECO:0000244|PDB:2HR7}.
STRAND 395 399 {ECO:0000244|PDB:2HR7}.
STRAND 404 406 {ECO:0000244|PDB:2HR7}.
TURN 422 424 {ECO:0000244|PDB:2HR7}.
STRAND 425 430 {ECO:0000244|PDB:2HR7}.
STRAND 437 439 {ECO:0000244|PDB:4ZXB}.
TURN 441 443 {ECO:0000244|PDB:2HR7}.
STRAND 452 458 {ECO:0000244|PDB:2HR7}.
HELIX 463 472 {ECO:0000244|PDB:2HR7}.
TURN 476 478 {ECO:0000244|PDB:2HR7}.
TURN 481 483 {ECO:0000244|PDB:2HR7}.
STRAND 486 490 {ECO:0000244|PDB:2HR7}.
STRAND 498 500 {ECO:0000244|PDB:4ZXB}.
STRAND 502 507 {ECO:0000244|PDB:4ZXB}.
STRAND 512 516 {ECO:0000244|PDB:4ZXB}.
HELIX 524 526 {ECO:0000244|PDB:4ZXB}.
STRAND 527 536 {ECO:0000244|PDB:4ZXB}.
STRAND 538 540 {ECO:0000244|PDB:4ZXB}.
STRAND 559 561 {ECO:0000244|PDB:4ZXB}.
STRAND 577 580 {ECO:0000244|PDB:4ZXB}.
STRAND 588 597 {ECO:0000244|PDB:4ZXB}.
STRAND 601 603 {ECO:0000244|PDB:4ZXB}.
STRAND 608 610 {ECO:0000244|PDB:4ZXB}.
STRAND 613 616 {ECO:0000244|PDB:4ZXB}.
STRAND 626 631 {ECO:0000244|PDB:4ZXB}.
STRAND 633 636 {ECO:0000244|PDB:4ZXB}.
STRAND 638 643 {ECO:0000244|PDB:4ZXB}.
STRAND 654 658 {ECO:0000244|PDB:4ZXB}.
HELIX 666 669 {ECO:0000244|PDB:4ZXB}.
HELIX 722 735 {ECO:0000244|PDB:4ZXB}.
STRAND 798 803 {ECO:0000244|PDB:4ZXB}.
STRAND 805 809 {ECO:0000244|PDB:4ZXB}.
STRAND 817 827 {ECO:0000244|PDB:4ZXB}.
STRAND 838 843 {ECO:0000244|PDB:4ZXB}.
STRAND 858 861 {ECO:0000244|PDB:4ZXB}.
STRAND 867 870 {ECO:0000244|PDB:4ZXB}.
STRAND 881 890 {ECO:0000244|PDB:4ZXB}.
STRAND 896 901 {ECO:0000244|PDB:4ZXB}.
HELIX 902 908 {ECO:0000244|PDB:4ZXB}.
STRAND 910 913 {ECO:0000244|PDB:4ZXB}.
STRAND 918 931 {ECO:0000244|PDB:4ZXB}.
STRAND 940 944 {ECO:0000244|PDB:4ZXB}.
HELIX 953 979 {ECO:0000244|PDB:2MFR}.
TURN 1003 1005 {ECO:0000244|PDB:4XLV}.
HELIX 1009 1011 {ECO:0000244|PDB:1IR3}.
HELIX 1014 1016 {ECO:0000244|PDB:1IRK}.
HELIX 1020 1022 {ECO:0000244|PDB:3BU3}.
STRAND 1023 1031 {ECO:0000244|PDB:3BU3}.
STRAND 1033 1043 {ECO:0000244|PDB:3BU3}.
STRAND 1046 1048 {ECO:0000244|PDB:2Z8C}.
STRAND 1050 1057 {ECO:0000244|PDB:3BU3}.
HELIX 1065 1078 {ECO:0000244|PDB:3BU3}.
STRAND 1089 1093 {ECO:0000244|PDB:3BU3}.
STRAND 1095 1098 {ECO:0000244|PDB:3BU3}.
STRAND 1100 1104 {ECO:0000244|PDB:3BU3}.
HELIX 1111 1117 {ECO:0000244|PDB:3BU3}.
STRAND 1119 1121 {ECO:0000244|PDB:3ETA}.
HELIX 1133 1152 {ECO:0000244|PDB:3BU3}.
STRAND 1154 1156 {ECO:0000244|PDB:2AUH}.
HELIX 1162 1164 {ECO:0000244|PDB:3BU3}.
STRAND 1165 1167 {ECO:0000244|PDB:3BU3}.
STRAND 1173 1175 {ECO:0000244|PDB:3BU3}.
STRAND 1181 1183 {ECO:0000244|PDB:1IRK}.
TURN 1185 1187 {ECO:0000244|PDB:3BU3}.
STRAND 1190 1192 {ECO:0000244|PDB:5HHW}.
STRAND 1194 1198 {ECO:0000244|PDB:3BU3}.
HELIX 1200 1202 {ECO:0000244|PDB:3BU3}.
HELIX 1205 1210 {ECO:0000244|PDB:3BU3}.
HELIX 1215 1230 {ECO:0000244|PDB:3BU3}.
TURN 1236 1239 {ECO:0000244|PDB:3BU3}.
HELIX 1242 1250 {ECO:0000244|PDB:3BU3}.
HELIX 1263 1272 {ECO:0000244|PDB:3BU3}.
HELIX 1277 1279 {ECO:0000244|PDB:3BU3}.
HELIX 1283 1290 {ECO:0000244|PDB:3BU3}.
HELIX 1291 1293 {ECO:0000244|PDB:5HHW}.
HELIX 1298 1301 {ECO:0000244|PDB:3BU3}.
TURN 1303 1305 {ECO:0000244|PDB:4XLV}.
HELIX 1307 1309 {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


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BMMS-635-B1 Insulin Receptor (Beta-Subunit) 0.5mL
BMMS-635-B0 Insulin Receptor (Beta-Subunit) 0.1mL


 

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