IRS2_HUMAN
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 03-AUG-2022, entry version 189.
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; Q96EB6: SIRT1; NbExp=2; IntAct=EBI-1049582, EBI-1802965;
CC Q9Y4H2; P63104: YWHAZ; NbExp=3; 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; 65.
DR ELM; Q9Y4H2; -.
DR IntAct; Q9Y4H2; 21.
DR MINT; Q9Y4H2; -.
DR STRING; 9606.ENSP00000365016; -.
DR GlyGen; Q9Y4H2; 1 site, 1 O-linked glycan (1 site).
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; Q9Y4H2; -.
DR PeptideAtlas; Q9Y4H2; -.
DR PRIDE; Q9Y4H2; -.
DR ProteomicsDB; 86205; -.
DR Antibodypedia; 25473; 376 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 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; LCYRPCP; -.
DR OrthoDB; 298675at2759; -.
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; 154 hits in 1082 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 205 other tissues.
DR Genevisible; Q9Y4H2; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl.
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:0043548; F:phosphatidylinositol 3-kinase binding; IBA:GO_Central.
DR GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0019903; F:protein phosphatase binding; 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:2000648; P:positive regulation of stem cell proliferation; 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:0072089; P:stem cell proliferation; IEA:Ensembl.
DR GO; GO:0044342; P:type B pancreatic cell proliferation; IEA:Ensembl.
DR CDD; cd01204; PTB_IRS; 1.
DR Gene3D; 2.30.29.30; -; 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; PTHR10614; 1.
DR Pfam; PF02174; IRS; 1.
DR Pfam; PF00169; PH; 1.
DR PRINTS; PR00628; INSULINRSI.
DR SMART; SM00233; PH; 1.
DR SMART; SM00310; PTBI; 1.
DR PROSITE; PS51064; IRS_PTB; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
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
