ID   IRS2_HUMAN              Reviewed;        1338 AA.
AC   Q9Y4H2; Q96RR2; Q9BZG0; Q9Y6I5;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   29-MAR-2005, sequence version 2.
DT   27-MAR-2024, entry version 198.
DE   RecName: Full=Insulin receptor substrate 2;
DE            Short=IRS-2;
GN   Name=IRS2;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=9312143; DOI=10.1074/jbc.272.40.25267;
RA   Ogihara T., Isobe T., Ichimura T., Taoka M., Funaki M., Sakoda H.,
RA   Onishi Y., Inukai K., Anai M., Fukushima Y., Kikuchi M., Yazaki Y., Oka Y.,
RA   Asano T.;
RT   "14-3-3 protein binds to insulin receptor substrate-1, one of the binding
RT   sites of which is in the phosphotyrosine binding domain.";
RL   J. Biol. Chem. 272:25267-25274(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=10077005; DOI=10.1210/mend.13.3.0256;
RA   Vassen L., Wegrzyn W., Klein-Hitpass L.;
RT   "Human insulin receptor substrate-2 (IRS-2) is a primary progesterone
RT   response gene.";
RL   Mol. Endocrinol. 13:485-494(1999).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Heyne B.;
RT   "Insulin receptor substrate 2 gene sequence.";
RL   Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15057823; DOI=10.1038/nature02379;
RA   Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA   Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA   Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA   Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA   Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA   Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA   Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA   Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA   Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA   Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA   Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA   Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA   Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA   Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA   Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA   Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA   Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA   Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA   Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA   Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA   Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA   Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA   Rogers J., Ross M.T.;
RT   "The DNA sequence and analysis of human chromosome 13.";
RL   Nature 428:522-528(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE OF 1-1337, AND VARIANTS SER-879 AND ALA-882.
RA   Heyne B., Gehrisch S., Jaross W.;
RT   "Two missense mutations in insulin receptor substrate 2 (G879S and
RT   G882A).";
RL   Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-388; SER-391 AND SER-560, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA   Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT   "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT   networks.";
RL   Cell 127:635-648(2006).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-350 AND THR-527, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=16964243; DOI=10.1038/nbt1240;
RA   Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT   "A probability-based approach for high-throughput protein phosphorylation
RT   analysis and site localization.";
RL   Nat. Biotechnol. 24:1285-1292(2006).
RN   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-915, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18220336; DOI=10.1021/pr0705441;
RA   Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT   "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT   phosphoproteomic analysis.";
RL   J. Proteome Res. 7:1346-1351(2008).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-388; SER-391 AND SER-915, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Platelet;
RX   PubMed=18088087; DOI=10.1021/pr0704130;
RA   Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA   Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT   "Phosphoproteome of resting human platelets.";
RL   J. Proteome Res. 7:526-534(2008).
RN   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-306; SER-346; THR-350;
RP   SER-365; SER-384; SER-388; SER-391; SER-523; THR-527; SER-577; THR-579;
RP   THR-580; SER-594; SER-608; SER-620; SER-679; SER-735; SER-736; SER-770;
RP   THR-779; SER-828; SER-915; SER-973; SER-1100; THR-1159; SER-1162; SER-1174;
RP   SER-1176 AND SER-1203, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [11]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19413330; DOI=10.1021/ac9004309;
RA   Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT   "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT   refined SCX-based approach.";
RL   Anal. Chem. 81:4493-4501(2009).
RN   [12]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-391, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA   Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA   Mann M., Daub H.;
RT   "Large-scale proteomics analysis of the human kinome.";
RL   Mol. Cell. Proteomics 8:1751-1764(2009).
RN   [13]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-306; SER-388; SER-391;
RP   SER-560; SER-594; TYR-675; SER-736; SER-915 AND SER-1176, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA   Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA   Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT   "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT   site occupancy during mitosis.";
RL   Sci. Signal. 3:RA3-RA3(2010).
RN   [14]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [15]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-306; SER-560; SER-915 AND
RP   SER-1176, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA   Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA   Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT   "System-wide temporal characterization of the proteome and phosphoproteome
RT   of human embryonic stem cell differentiation.";
RL   Sci. Signal. 4:RS3-RS3(2011).
RN   [16]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-306; THR-350; THR-520;
RP   THR-527; SER-560; SER-577; THR-579; SER-594; TYR-675; SER-679; SER-682;
RP   SER-736; SER-805; SER-915; SER-973; SER-1100; SER-1174; SER-1176; SER-1186
RP   AND SER-1203, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   ANALYSIS].
RC   TISSUE=Cervix carcinoma, and Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [17]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-594; SER-915; SER-973;
RP   THR-1082 AND SER-1100, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [18]
RP   METHYLATION [LARGE SCALE ANALYSIS] AT ARG-412, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Colon carcinoma;
RX   PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA   Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA   Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA   Bedford M.T., Comb M.J.;
RT   "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT   methylation.";
RL   Mol. Cell. Proteomics 13:372-387(2014).
RN   [19]
RP   VARIANT ASP-1057.
RX   PubMed=12687350; DOI=10.1007/s00439-003-0935-3;
RA   Lautier C., El Mkadem S.A., Renard E., Brun J.F., Gris J.-C., Bringer J.,
RA   Grigorescu F.;
RT   "Complex haplotypes of IRS2 gene are associated with severe obesity and
RT   reveal heterogeneity in the effect of Gly1057Asp mutation.";
RL   Hum. Genet. 113:34-43(2003).
CC   -!- FUNCTION: May mediate the control of various cellular processes by
CC       insulin.
CC   -!- SUBUNIT: Interacts with PHIP. {ECO:0000250}.
CC   -!- INTERACTION:
CC       Q9Y4H2; P27986: PIK3R1; NbExp=3; IntAct=EBI-1049582, EBI-79464;
CC       Q9Y4H2; P31947: SFN; NbExp=4; IntAct=EBI-1049582, EBI-476295;
CC       Q9Y4H2; Q96EB6: SIRT1; NbExp=2; IntAct=EBI-1049582, EBI-1802965;
CC       Q9Y4H2; P63104: YWHAZ; NbExp=5; IntAct=EBI-1049582, EBI-347088;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250}.
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DR   EMBL; AB000732; BAA24500.1; -; Genomic_DNA.
DR   EMBL; AF073310; AAD21531.1; -; mRNA.
DR   EMBL; AF322115; AAG50013.1; -; Genomic_DNA.
DR   EMBL; AF322114; AAG50013.1; JOINED; Genomic_DNA.
DR   EMBL; AL162497; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AF288517; AAK83053.1; -; Genomic_DNA.
DR   CCDS; CCDS9510.1; -.
DR   RefSeq; NP_003740.2; NM_003749.2.
DR   PDB; 3FQW; X-ray; 1.93 A; C=1097-1105.
DR   PDB; 3FQX; X-ray; 1.70 A; C=1097-1105.
DR   PDBsum; 3FQW; -.
DR   PDBsum; 3FQX; -.
DR   AlphaFoldDB; Q9Y4H2; -.
DR   SMR; Q9Y4H2; -.
DR   BioGRID; 114209; 75.
DR   ELM; Q9Y4H2; -.
DR   IntAct; Q9Y4H2; 23.
DR   MINT; Q9Y4H2; -.
DR   STRING; 9606.ENSP00000365016; -.
DR   GlyCosmos; Q9Y4H2; 1 site, 1 glycan.
DR   GlyGen; Q9Y4H2; 11 sites, 1 O-linked glycan (11 sites).
DR   iPTMnet; Q9Y4H2; -.
DR   PhosphoSitePlus; Q9Y4H2; -.
DR   BioMuta; IRS2; -.
DR   DMDM; 62298062; -.
DR   EPD; Q9Y4H2; -.
DR   jPOST; Q9Y4H2; -.
DR   MassIVE; Q9Y4H2; -.
DR   MaxQB; Q9Y4H2; -.
DR   PaxDb; 9606-ENSP00000365016; -.
DR   PeptideAtlas; Q9Y4H2; -.
DR   ProteomicsDB; 86205; -.
DR   Pumba; Q9Y4H2; -.
DR   Antibodypedia; 25473; 535 antibodies from 37 providers.
DR   DNASU; 8660; -.
DR   Ensembl; ENST00000375856.5; ENSP00000365016.3; ENSG00000185950.9.
DR   GeneID; 8660; -.
DR   KEGG; hsa:8660; -.
DR   MANE-Select; ENST00000375856.5; ENSP00000365016.3; NM_003749.3; NP_003740.2.
DR   UCSC; uc001vqv.4; human.
DR   AGR; HGNC:6126; -.
DR   CTD; 8660; -.
DR   DisGeNET; 8660; -.
DR   GeneCards; IRS2; -.
DR   HGNC; HGNC:6126; IRS2.
DR   HPA; ENSG00000185950; Tissue enhanced (bone).
DR   MalaCards; IRS2; -.
DR   MIM; 600797; gene.
DR   neXtProt; NX_Q9Y4H2; -.
DR   OpenTargets; ENSG00000185950; -.
DR   PharmGKB; PA375; -.
DR   VEuPathDB; HostDB:ENSG00000185950; -.
DR   eggNOG; ENOG502QUNU; Eukaryota.
DR   GeneTree; ENSGT00940000161407; -.
DR   HOGENOM; CLU_004902_1_0_1; -.
DR   InParanoid; Q9Y4H2; -.
DR   OMA; CHRKRTY; -.
DR   OrthoDB; 4212441at2759; -.
DR   PhylomeDB; Q9Y4H2; -.
DR   TreeFam; TF325994; -.
DR   PathwayCommons; Q9Y4H2; -.
DR   Reactome; R-HSA-109704; PI3K Cascade.
DR   Reactome; R-HSA-112399; IRS-mediated signalling.
DR   Reactome; R-HSA-112412; SOS-mediated signalling.
DR   Reactome; R-HSA-1257604; PIP3 activates AKT signaling.
DR   Reactome; R-HSA-1266695; Interleukin-7 signaling.
DR   Reactome; R-HSA-198203; PI3K/AKT activation.
DR   Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer.
DR   Reactome; R-HSA-2428928; IRS-related events triggered by IGF1R.
DR   Reactome; R-HSA-2586552; Signaling by Leptin.
DR   Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR   Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR   Reactome; R-HSA-74713; IRS activation.
DR   Reactome; R-HSA-74749; Signal attenuation.
DR   Reactome; R-HSA-8853659; RET signaling.
DR   Reactome; R-HSA-9006335; Signaling by Erythropoietin.
DR   Reactome; R-HSA-9027276; Erythropoietin activates Phosphoinositide-3-kinase (PI3K).
DR   Reactome; R-HSA-9027277; Erythropoietin activates Phospholipase C gamma (PLCG).
DR   Reactome; R-HSA-9027283; Erythropoietin activates STAT5.
DR   Reactome; R-HSA-9027284; Erythropoietin activates RAS.
DR   Reactome; R-HSA-982772; Growth hormone receptor signaling.
DR   SignaLink; Q9Y4H2; -.
DR   SIGNOR; Q9Y4H2; -.
DR   BioGRID-ORCS; 8660; 172 hits in 1176 CRISPR screens.
DR   ChiTaRS; IRS2; human.
DR   EvolutionaryTrace; Q9Y4H2; -.
DR   GeneWiki; IRS2; -.
DR   GenomeRNAi; 8660; -.
DR   Pharos; Q9Y4H2; Tbio.
DR   PRO; PR:Q9Y4H2; -.
DR   Proteomes; UP000005640; Chromosome 13.
DR   RNAct; Q9Y4H2; Protein.
DR   Bgee; ENSG00000185950; Expressed in decidua and 207 other cell types or tissues.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0071889; F:14-3-3 protein binding; IEA:Ensembl.
DR   GO; GO:0005158; F:insulin receptor binding; IBA:GO_Central.
DR   GO; GO:0141038; F:phosphatidylinositol 3-kinase activator activity; IEA:Ensembl.
DR   GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; IBA:GO_Central.
DR   GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl.
DR   GO; GO:0019903; F:protein phosphatase binding; IEA:Ensembl.
DR   GO; GO:0005068; F:transmembrane receptor protein tyrosine kinase adaptor activity; IEA:Ensembl.
DR   GO; GO:0007420; P:brain development; IEA:Ensembl.
DR   GO; GO:0071333; P:cellular response to glucose stimulus; IEA:Ensembl.
DR   GO; GO:0032869; P:cellular response to insulin stimulus; IMP:BHF-UCL.
DR   GO; GO:0010631; P:epithelial cell migration; IEA:Ensembl.
DR   GO; GO:0006006; P:glucose metabolic process; TAS:ProtInc.
DR   GO; GO:0008286; P:insulin receptor signaling pathway; ISS:BHF-UCL.
DR   GO; GO:0055088; P:lipid homeostasis; TAS:BHF-UCL.
DR   GO; GO:0030879; P:mammary gland development; IEA:Ensembl.
DR   GO; GO:0002903; P:negative regulation of B cell apoptotic process; ISS:BHF-UCL.
DR   GO; GO:0033673; P:negative regulation of kinase activity; ISS:BHF-UCL.
DR   GO; GO:0010748; P:negative regulation of long-chain fatty acid import across plasma membrane; IMP:BHF-UCL.
DR   GO; GO:0030890; P:positive regulation of B cell proliferation; ISS:BHF-UCL.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; NAS:BHF-UCL.
DR   GO; GO:0010634; P:positive regulation of epithelial cell migration; IEA:Ensembl.
DR   GO; GO:0032000; P:positive regulation of fatty acid beta-oxidation; IMP:BHF-UCL.
DR   GO; GO:0046326; P:positive regulation of glucose import; IMP:BHF-UCL.
DR   GO; GO:0010907; P:positive regulation of glucose metabolic process; IMP:BHF-UCL.
DR   GO; GO:0045725; P:positive regulation of glycogen biosynthetic process; IMP:BHF-UCL.
DR   GO; GO:0032024; P:positive regulation of insulin secretion; ISS:BHF-UCL.
DR   GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; IEA:Ensembl.
DR   GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IEA:Ensembl.
DR   GO; GO:1904692; P:positive regulation of type B pancreatic cell proliferation; IEA:Ensembl.
DR   GO; GO:0019216; P:regulation of lipid metabolic process; TAS:BHF-UCL.
DR   GO; GO:0009749; P:response to glucose; ISS:BHF-UCL.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR   GO; GO:0044342; P:type B pancreatic cell proliferation; IEA:Ensembl.
DR   CDD; cd01257; PH_IRS; 1.
DR   CDD; cd01204; PTB_IRS; 1.
DR   Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 2.
DR   InterPro; IPR039011; IRS.
DR   InterPro; IPR002404; IRS_PTB.
DR   InterPro; IPR011993; PH-like_dom_sf.
DR   InterPro; IPR001849; PH_domain.
DR   PANTHER; PTHR10614; INSULIN RECEPTOR SUBSTRATE; 1.
DR   PANTHER; PTHR10614:SF7; INSULIN RECEPTOR SUBSTRATE 2; 1.
DR   Pfam; PF02174; IRS; 1.
DR   Pfam; PF00169; PH; 1.
DR   PRINTS; PR00628; INSULINRSI.
DR   SMART; SM01244; IRS; 1.
DR   SMART; SM00233; PH; 1.
DR   SMART; SM00310; PTBI; 1.
DR   SUPFAM; SSF50729; PH domain-like; 2.
DR   PROSITE; PS51064; IRS_PTB; 1.
DR   PROSITE; PS50003; PH_DOMAIN; 1.
DR   Genevisible; Q9Y4H2; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Cytoplasm; Methylation; Phosphoprotein; Reference proteome;
KW   Transducer.
FT   CHAIN           1..1338
FT                   /note="Insulin receptor substrate 2"
FT                   /id="PRO_0000084239"
FT   DOMAIN          16..144
FT                   /note="PH"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT   DOMAIN          194..298
FT                   /note="IRS-type PTB"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00389"
FT   REGION          1..31
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          49..72
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          303..411
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          428..537
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          703..739
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          840..1101
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1121..1296
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           540..543
FT                   /note="YXXM motif 1"
FT   MOTIF           598..601
FT                   /note="YXXM motif 2"
FT   MOTIF           653..656
FT                   /note="YXXM motif 3"
FT   MOTIF           675..678
FT                   /note="YXXM motif 4"
FT   MOTIF           742..745
FT                   /note="YXXM motif 5"
FT   MOTIF           823..826
FT                   /note="YXXM motif 6"
FT   MOTIF           1072..1075
FT                   /note="YXXM motif 7"
FT   COMPBIAS        16..31
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        442..457
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        458..475
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        480..494
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        939..983
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1011..1042
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1054..1070
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1132..1146
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1147..1183
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1204..1219
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1263..1279
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         306
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         346
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648"
FT   MOD_RES         350
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:16964243,
FT                   ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163"
FT   MOD_RES         365
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648"
FT   MOD_RES         384
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648"
FT   MOD_RES         388
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:17081983,
FT                   ECO:0007744|PubMed:18088087, ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:20068231"
FT   MOD_RES         391
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:17081983,
FT                   ECO:0007744|PubMed:18088087, ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:20068231"
FT   MOD_RES         412
FT                   /note="Omega-N-methylarginine"
FT                   /evidence="ECO:0007744|PubMed:24129315"
FT   MOD_RES         520
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         523
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648"
FT   MOD_RES         527
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:16964243,
FT                   ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163"
FT   MOD_RES         540
FT                   /note="Phosphotyrosine; by INSR"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         560
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:17081983,
FT                   ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         577
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         579
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         580
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:18669648"
FT   MOD_RES         594
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163,
FT                   ECO:0007744|PubMed:24275569"
FT   MOD_RES         608
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648"
FT   MOD_RES         620
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648"
FT   MOD_RES         653
FT                   /note="Phosphotyrosine; by INSR"
FT                   /evidence="ECO:0000250|UniProtKB:P81122"
FT   MOD_RES         675
FT                   /note="Phosphotyrosine; by INSR"
FT                   /evidence="ECO:0007744|PubMed:20068231,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         679
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         682
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         735
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648"
FT   MOD_RES         736
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT   MOD_RES         770
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648"
FT   MOD_RES         779
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:18669648"
FT   MOD_RES         805
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         828
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648"
FT   MOD_RES         915
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18088087,
FT                   ECO:0007744|PubMed:18220336, ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT                   ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT   MOD_RES         919
FT                   /note="Phosphotyrosine; by INSR"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         973
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT   MOD_RES         978
FT                   /note="Phosphotyrosine; by INSR"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         1082
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         1100
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT   MOD_RES         1159
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:18669648"
FT   MOD_RES         1162
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648"
FT   MOD_RES         1174
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         1176
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         1186
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         1203
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         1253
FT                   /note="Phosphotyrosine; by INSR"
FT                   /evidence="ECO:0000250"
FT   VARIANT         789
FT                   /note="H -> Y (in dbSNP:rs35223808)"
FT                   /id="VAR_033992"
FT   VARIANT         879
FT                   /note="G -> S (in dbSNP:rs549588978)"
FT                   /evidence="ECO:0000269|Ref.5"
FT                   /id="VAR_021557"
FT   VARIANT         882
FT                   /note="G -> A (in dbSNP:rs201499247)"
FT                   /evidence="ECO:0000269|Ref.5"
FT                   /id="VAR_021558"
FT   VARIANT         999
FT                   /note="V -> M (in dbSNP:rs35927012)"
FT                   /id="VAR_033993"
FT   VARIANT         1057
FT                   /note="G -> D (in dbSNP:rs1805097)"
FT                   /evidence="ECO:0000269|PubMed:12687350"
FT                   /id="VAR_014857"
FT   CONFLICT        28
FT                   /note="N -> NN (in Ref. 2; AAD21531)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        39..41
FT                   /note="KQK -> NEE (in Ref. 2; AAD21531)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        59
FT                   /note="E -> K (in Ref. 1; BAA24500)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        81
FT                   /note="K -> N (in Ref. 1; BAA24500)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        107
FT                   /note="A -> P (in Ref. 1; BAA24500)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        171
FT                   /note="L -> V (in Ref. 1; BAA24500)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        371
FT                   /note="A -> R (in Ref. 2; AAD21531)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        379..382
FT                   /note="GARP -> AQRL (in Ref. 2; AAD21531)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        406
FT                   /note="S -> I (in Ref. 1; BAA24500)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        410..419
FT                   /note="GGRGSKVALL -> RAAGTKWHCF (in Ref. 1; BAA24500)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        424
FT                   /note="A -> G (in Ref. 1; BAA24500)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        436..438
FT                   /note="AHS -> EHL (in Ref. 1; BAA24500)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        453
FT                   /note="G -> D (in Ref. 1; BAA24500)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        456
FT                   /note="S -> W (in Ref. 1; BAA24500)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        468
FT                   /note="P -> L (in Ref. 1; BAA24500)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        662
FT                   /note="L -> F (in Ref. 2; AAD21531)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        704
FT                   /note="S -> F (in Ref. 1; BAA24500)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        714
FT                   /note="S -> F (in Ref. 1; BAA24500)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        848
FT                   /note="S -> T (in Ref. 1; BAA24500)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        872
FT                   /note="P -> R (in Ref. 2; AAD21531)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        875..878
FT                   /note="GRPE -> RRS (in Ref. 2; AAD21531)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        956
FT                   /note="S -> L (in Ref. 1; BAA24500)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1252
FT                   /note="N -> K (in Ref. 1; BAA24500)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1303
FT                   /note="G -> R (in Ref. 1; BAA24500)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1314..1338
FT                   /note="LPPANTYASIDFLSHHLKEATIVKE -> PAPCPTTYAQH (in Ref. 1;
FT                   BAA24500)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1338 AA;  137334 MW;  58E569E8BDBAF3D7 CRC64;
     MASPPRHGPP GPASGDGPNL NNNNNNNNHS VRKCGYLRKQ KHGHKRFFVL RGPGAGGDEA
     TAGGGSAPQP PRLEYYESEK KWRSKAGAPK RVIALDCCLN INKRADAKHK YLIALYTKDE
     YFAVAAENEQ EQEGWYRALT DLVSEGRAAA GDAPPAAAPA ASCSASLPGA LGGSAGAAGA
     EDSYGLVAPA TAAYREVWQV NLKPKGLGQS KNLTGVYRLC LSARTIGFVK LNCEQPSVTL
     QLMNIRRCGH SDSFFFIEVG RSAVTGPGEL WMQADDSVVA QNIHETILEA MKALKELFEF
     RPRSKSQSSG SSATHPISVP GARRHHHLVN LPPSQTGLVR RSRTDSLAAT PPAAKCSSCR
     VRTASEGDGG AAAGAAAAGA RPVSVAGSPL SPGPVRAPLS RSHTLSGGCG GRGSKVALLP
     AGGALQHSRS MSMPVAHSPP AATSPGSLSS SSGHGSGSYP PPPGPHPPLP HPLHHGPGQR
     PSSGSASASG SPSDPGFMSL DEYGSSPGDL RAFCSHRSNT PESIAETPPA RDGGGGGEFY
     GYMTMDRPLS HCGRSYRRVS GDAAQDLDRG LRKRTYSLTT PARQRPVPQP SSASLDEYTL
     MRATFSGSAG RLCPSCPASS PKVAYHPYPE DYGDIEIGSH RSSSSNLGAD DGYMPMTPGA
     ALAGSGSGSC RSDDYMPMSP ASVSAPKQIL QPRAAAAAAA AVPSAGPAGP APTSAAGRTF
     PASGGGYKAS SPAESSPEDS GYMRMWCGSK LSMEHADGKL LPNGDYLNVS PSDAVTTGTP
     PDFFSAALHP GGEPLRGVPG CCYSSLPRSY KAPYTCGGDS DQYVLMSSPV GRILEEERLE
     PQATPGPSQA ASAFGAGPTQ PPHPVVPSPV RPSGGRPEGF LGQRGRAVRP TRLSLEGLPS
     LPSMHEYPLP PEPKSPGEYI NIDFGEPGAR LSPPAPPLLA SAASSSSLLS ASSPASSLGS
     GTPGTSSDSR QRSPLSDYMN LDFSSPKSPK PGAPSGHPVG SLDGLLSPEA SSPYPPLPPR
     PSASPSSSLQ PPPPPPAPGE LYRLPPASAV ATAQGPGAAS SLSSDTGDNG DYTEMAFGVA
     ATPPQPIAAP PKPEAARVAS PTSGVKRLSL MEQVSGVEAF LQASQPPDPH RGAKVIRADP
     QGGRRRHSSE TFSSTTTVTP VSPSFAHNPK RHNSASVENV SLRKSSEGGV GVGPGGGDEP
     PTSPRQLQPA PPLAPQGRPW TPGQPGGLVG CPGSGGSPMR RETSAGFQNG LNYIAIDVRE
     EPGLPPQPQP PPPPLPQPGD KSSWGRTRSL GGLISAVGVG STGGGCGGPG PGALPPANTY
     ASIDFLSHHL KEATIVKE
//