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Insulin receptor substrate 1 (IRS-1)

 IRS1_HUMAN              Reviewed;        1242 AA.
P35568;
01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
01-JUN-1994, sequence version 1.
17-JUN-2020, entry version 218.
RecName: Full=Insulin receptor substrate 1;
Short=IRS-1;
Name=IRS1;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Skeletal muscle;
PubMed=8513971; DOI=10.2337/diab.42.7.1041;
Araki E., Sun X.J., Haag B.L. III, Chuang L.M., Zhang Y., Yang-Feng T.L.,
White M.F., Kahn C.R.;
"Human skeletal muscle insulin receptor substrate-1. Characterization of
the cDNA, gene, and chromosomal localization.";
Diabetes 42:1041-1054(1993).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=1311924; DOI=10.1016/0006-291x(92)91640-c;
Nishiyama M., Wands J.R.;
"Cloning and increased expression of an insulin receptor substrate-1-like
gene in human hepatocellular carcinoma.";
Biochem. Biophys. Res. Commun. 183:280-285(1992).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Eye;
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).
[4]
TURNOVER.
PubMed=8240352; DOI=10.1006/bbrc.1993.2315;
Smith L.K., Bradshaw M., Croall D.E., Garner C.W.;
"The insulin receptor substrate (IRS-1) is a PEST protein that is
susceptible to calpain degradation in vitro.";
Biochem. Biophys. Res. Commun. 196:767-772(1993).
[5]
INTERACTION WITH IGF1R.
PubMed=7541045; DOI=10.1074/jbc.270.26.15639;
Craparo A., O'Neill T.J., Gustafson T.A.;
"Non-SH2 domains within insulin receptor substrate-1 and SHC mediate their
phosphotyrosine-dependent interaction with the NPEY motif of the insulin-
like growth factor I receptor.";
J. Biol. Chem. 270:15639-15643(1995).
[6]
INTERACTION WITH INSR.
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).
[7]
INTERACTION WITH INSR.
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).
[8]
MUTAGENESIS OF SER-794, AND PHOSPHORYLATION AT SER-794.
PubMed=12624099; DOI=10.1074/jbc.m211770200;
Horike N., Takemori H., Katoh Y., Doi J., Min L., Asano T., Sun X.J.,
Yamamoto H., Kasayama S., Muraoka M., Nonaka Y., Okamoto M.;
"Adipose-specific expression, phosphorylation of Ser794 in insulin receptor
substrate-1, and activation in diabetic animals of salt-inducible kinase-
2.";
J. Biol. Chem. 278:18440-18447(2003).
[9]
PHOSPHORYLATION AT SER-1101.
PubMed=15364919; DOI=10.1074/jbc.c400186200;
Li Y., Soos T.J., Li X., Wu J., Degennaro M., Sun X., Littman D.R.,
Birnbaum M.J., Polakiewicz R.D.;
"Protein kinase C Theta inhibits insulin signaling by phosphorylating IRS1
at Ser(1101).";
J. Biol. Chem. 279:45304-45307(2004).
[10]
PHOSPHORYLATION BY ALK, AND INTERACTION WITH ALK.
PubMed=15226403; DOI=10.1242/jcs.01183;
Motegi A., Fujimoto J., Kotani M., Sakuraba H., Yamamoto T.;
"ALK receptor tyrosine kinase promotes cell growth and neurite outgrowth.";
J. Cell Sci. 117:3319-3329(2004).
[11]
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).
[12]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-662, AND IDENTIFICATION BY
MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=15592455; DOI=10.1038/nbt1046;
Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
Zha X.-M., Polakiewicz R.D., Comb M.J.;
"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
Nat. Biotechnol. 23:94-101(2005).
[13]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-629 AND SER-636, AND
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma;
PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
"Global, in vivo, and site-specific phosphorylation dynamics in signaling
networks.";
Cell 127:635-648(2006).
[14]
INTERACTION WITH ALK, AND FUNCTION.
PubMed=16878150; DOI=10.1038/sj.onc.1209840;
Kuo A.H., Stoica G.E., Riegel A.T., Wellstein A.;
"Recruitment of insulin receptor substrate-1 and activation of NF-kappaB
essential for midkine growth signaling through anaplastic lymphoma
kinase.";
Oncogene 26:859-869(2007).
[15]
PHOSPHORYLATION AT SER-270; SER-307; SER-636 AND SER-1101.
PubMed=18952604; DOI=10.1074/jbc.m806480200;
Zhang J., Gao Z., Yin J., Quon M.J., Ye J.;
"S6K directly phosphorylates IRS-1 on Ser-270 to promote insulin resistance
in response to TNF-(alpha) signaling through IKK2.";
J. Biol. Chem. 283:35375-35382(2008).
[16]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma;
PubMed=18220336; DOI=10.1021/pr0705441;
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
phosphoproteomic analysis.";
J. Proteome Res. 7:1346-1351(2008).
[17]
UBIQUITINATION, PHOSPHORYLATION AT SER-307; SER-312; SER-527 AND SER-636,
AND MUTAGENESIS OF SER-307; SER-312; SER-527; SER-636 AND SER-639.
PubMed=18498745; DOI=10.1016/j.molcel.2008.03.009;
Xu X., Sarikas A., Dias-Santagata D.C., Dolios G., Lafontant P.J.,
Tsai S.C., Zhu W., Nakajima H., Nakajima H.O., Field L.J., Wang R.,
Pan Z.Q.;
"The CUL7 E3 ubiquitin ligase targets insulin receptor substrate 1 for
ubiquitin-dependent degradation.";
Mol. Cell 30:403-414(2008).
[18]
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).
[19]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-348, AND IDENTIFICATION BY
MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Leukemic T-cell;
PubMed=19690332; DOI=10.1126/scisignal.2000007;
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
Rodionov V., Han D.K.;
"Quantitative phosphoproteomic analysis of T cell receptor signaling
reveals system-wide modulation of protein-protein interactions.";
Sci. Signal. 2:RA46-RA46(2009).
[20]
PHOSPHORYLATION AT SER-312 AND TYR-941.
PubMed=20685959; DOI=10.1091/mbc.e10-06-0481;
Yang X., Nath A., Opperman M.J., Chan C.;
"The double-stranded RNA-dependent protein kinase differentially regulates
insulin receptor substrates 1 and 2 in HepG2 cells.";
Mol. Biol. Cell 21:3449-3458(2010).
[21]
PHOSPHORYLATION AT TYR-612; TYR-632 AND TYR-896, AND MUTAGENESIS OF TYR-612
AND TYR-632.
PubMed=23401856; DOI=10.1128/mcb.01447-12;
Koh A., Lee M.N., Yang Y.R., Jeong H., Ghim J., Noh J., Kim J., Ryu D.,
Park S., Song P., Koo S.H., Leslie N.R., Berggren P.O., Choi J.H.,
Suh P.G., Ryu S.H.;
"C1-Ten is a protein tyrosine phosphatase of insulin receptor substrate 1
(IRS-1), regulating IRS-1 stability and muscle atrophy.";
Mol. Cell. Biol. 33:1608-1620(2013).
[22]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-323; THR-453; SER-527 AND
SER-629, AND 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).
[23]
STRUCTURE BY NMR OF 157-267.
PubMed=8599766; DOI=10.1038/nsb0496-388;
Zhou M.-M., Huang B., Olejniczak E.T., Meadows R.P., Shuker S.B.,
Miyazaki M., Trueb T., Shoelson S.E., Fesik S.W.;
"Structural basis for IL-4 receptor phosphopeptide recognition by the IRS-1
PTB domain.";
Nat. Struct. Biol. 3:388-393(1996).
[24]
X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 4-267.
PubMed=10411883; DOI=10.1073/pnas.96.15.8378;
Dhe-Paganon S., Ottinger E.A., Nolte R.T., Eck M.J., Shoelson S.E.;
"Crystal structure of the pleckstrin homology-phosphotyrosine binding (PH-
PTB) targeting region of insulin receptor substrate 1.";
Proc. Natl. Acad. Sci. U.S.A. 96:8378-8383(1999).
[25]
X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 889-902 IN COMPLEX WITH IGF1R.
PubMed=11694888; DOI=10.1038/nsb721;
Favelyukis S., Till J.H., Hubbard S.R., Miller W.T.;
"Structure and autoregulation of the insulin-like growth factor 1 receptor
kinase.";
Nat. Struct. Biol. 8:1058-1063(2001).
[26]
VARIANTS PRO-512 AND ARG-971.
PubMed=8104271; DOI=10.1016/0140-6736(93)92694-o;
Almind K., Bjoerbaek C., Vestergaard H., Hansen T., Echwald S.,
Pedersen O.;
"Aminoacid polymorphisms of insulin receptor substrate-1 in non-insulin-
dependent diabetes mellitus.";
Lancet 342:828-832(1993).
[27]
VARIANT NIDDM GLY-723 DEL.
PubMed=8723689;
DOI=10.1002/(sici)1098-1004(1996)7:4<364::aid-humu13>3.0.co;2-0;
Esposito D.L., Mammarella S., Ranieri A., della Loggia F., Capani F.,
Consoli A., Mariani-Costantini R., Caramia F.G., Cama A., Battista P.;
"Deletion of Gly723 in the insulin receptor substrate-1 of a patient with
noninsulin-dependent diabetes mellitus.";
Hum. Mutat. 7:364-366(1996).
[28]
VARIANTS NIDDM TYR-1043 AND TYR-1095.
PubMed=10206679;
DOI=10.1002/(sici)1098-1004(1998)11:5<411::aid-humu12>3.0.co;2-#;
Mammarella S., Creati B., Esposito D.L., Arcuri P., della Loggia F.,
Capani F., Mariani-Costantini R., Caramia F.G., Battista P., Cama A.;
"Novel allele of the insulin receptor substrate-1 bearing two non-
conservative amino acid substitutions in a patient with noninsulin-
dependent diabetes mellitus.";
Hum. Mutat. 11:411-411(1998).
[29]
CHARACTERIZATION OF VARIANT ARG-971.
PubMed=10843189; DOI=10.1210/jcem.85.5.6608;
Hribal M.L., Federici M., Porzio O., Lauro D., Borboni P., Accili D.,
Lauro R., Sesti G.;
"The Gly-->Arg(972) amino acid polymorphism in insulin receptor substrate-1
affects glucose metabolism in skeletal muscle cells.";
J. Clin. Endocrinol. Metab. 85:2004-2013(2000).
[30]
ASSOCIATION OF VARIANT ARG-971 WITH NIDDM.
PubMed=12843189; DOI=10.1210/jc.2002-021716;
Marini M.A., Frontoni S., Mineo D., Bracaglia D., Cardellini M.,
De Nicolais P., Baroni A., D'Alfonso R., Perna M., Lauro D., Federici M.,
Gambardella S., Lauro R., Sesti G.;
"The Arg(972) variant in insulin receptor substrate-1 is associated with an
atherogenic profile in offspring of type 2 diabetic patients.";
J. Clin. Endocrinol. Metab. 88:3368-3371(2003).
[31]
VARIANT ARG-971.
PubMed=14671192; DOI=10.1210/jc.2003-030453;
Abate N., Carulli L., Cabo-Chan A. Jr., Chandalia M., Snell P.G.,
Grundy S.M.;
"Genetic polymorphism PC-1 K121Q and ethnic susceptibility to insulin
resistance.";
J. Clin. Endocrinol. Metab. 88:5927-5934(2003).
[32]
VARIANT ARG-608, AND CHARACTERIZATION OF VARIANT ARG-608.
PubMed=12679424; DOI=10.1210/jc.2002-020933;
Esposito D.L., Li Y., Vanni C., Mammarella S., Veschi S., Della Loggia F.,
Mariani-Costantini R., Battista P., Quon M.J., Cama A.;
"A novel T608R missense mutation in insulin receptor substrate-1 identified
in a subject with type 2 diabetes impairs metabolic insulin signaling.";
J. Clin. Endocrinol. Metab. 88:1468-1475(2003).
[33]
VARIANT ARG-971, ASSOCIATION WITH ENDOTHELIAL DYSFUNCTION, AND
CARDIOVASCULAR DISEASE.
PubMed=14707024; DOI=10.1161/01.cir.0000109498.77895.6f;
Federici M., Pandolfi A., De Filippis E.A., Pellegrini G., Menghini R.,
Lauro D., Cardellini M., Romano M., Sesti G., Lauro R., Consoli A.;
"G972R IRS-1 variant impairs insulin regulation of endothelial nitric oxide
synthase in cultured human endothelial cells.";
Circulation 109:399-405(2004).
[34]
VARIANT ARG-971, AND MOLECULAR MECHANISM OF LINKAGE TO NIDDM.
PubMed=15590636; DOI=10.1074/jbc.m412300200;
McGettrick A.J., Feener E.P., Kahn C.R.;
"Human insulin receptor substrate-1 (IRS-1) polymorphism G972R causes IRS-1
to associate with the insulin receptor and inhibit receptor
autophosphorylation.";
J. Biol. Chem. 280:6441-6446(2005).
-!- FUNCTION: May mediate the control of various cellular processes by
insulin. When phosphorylated by the insulin receptor binds specifically
to various cellular proteins containing SH2 domains such as
phosphatidylinositol 3-kinase p85 subunit or GRB2. Activates
phosphatidylinositol 3-kinase when bound to the regulatory p85 subunit
(By similarity). {ECO:0000250, ECO:0000269|PubMed:16878150}.
-!- SUBUNIT: Interacts with UBTF and PIK3CA (By similarity). Interacts (via
phosphorylated YXXM motifs) with PIK3R1 (By similarity). Interacts with
ROCK1 and FER (By similarity). Interacts (via PH domain) with PHIP (By
similarity). Interacts with GRB2 (By similarity). Interacts with SOCS7
(PubMed:16127460). Interacts (via IRS-type PTB domain) with IGF1R and
INSR (via the tyrosine-phosphorylated NPXY motif) (PubMed:7541045,
PubMed:7559478, PubMed:7537849). Interacts with ALK (PubMed:15226403,
PubMed:16878150). Interacts with EIF2AK2/PKR (By similarity). Interacts
with GKAP1 (By similarity). Interacts with DGKZ in the absence of
insulin; insulin stimulation decreases this interaction (By
similarity). Found in a ternary complex with DGKZ and PIP5K1A in the
absence of insulin stimulation (By similarity).
{ECO:0000250|UniProtKB:P35569, ECO:0000250|UniProtKB:P35570,
ECO:0000269|PubMed:15226403, ECO:0000269|PubMed:16127460,
ECO:0000269|PubMed:16878150, ECO:0000269|PubMed:7537849,
ECO:0000269|PubMed:7541045, ECO:0000269|PubMed:7559478}.
-!- INTERACTION:
P35568; O75815: BCAR3; NbExp=3; IntAct=EBI-517592, EBI-702336;
P35568; P04626: ERBB2; NbExp=2; IntAct=EBI-517592, EBI-641062;
P35568; P06213: INSR; NbExp=3; IntAct=EBI-517592, EBI-475899;
P35568; P11940: PABPC1; NbExp=2; IntAct=EBI-517592, EBI-81531;
P35568; P42336: PIK3CA; NbExp=20; IntAct=EBI-517592, EBI-2116585;
P35568; P27986: PIK3R1; NbExp=12; IntAct=EBI-517592, EBI-79464;
P35568; P27986-2: PIK3R1; NbExp=3; IntAct=EBI-517592, EBI-9090282;
P35568; Q92569: PIK3R3; NbExp=4; IntAct=EBI-517592, EBI-79893;
P35568; Q06124: PTPN11; NbExp=3; IntAct=EBI-517592, EBI-297779;
P35568; P03495: NS; Xeno; NbExp=2; IntAct=EBI-517592, EBI-2548993;
P35568; P03070; Xeno; NbExp=2; IntAct=EBI-517592, EBI-617698;
-!- PTM: Serine phosphorylation of IRS1 is a mechanism for insulin
resistance. Ser-312 phosphorylation inhibits insulin action through
disruption of IRS1 interaction with the insulin receptor (By
similarity). Phosphorylation of Tyr-896 is required for GRB2-binding
(By similarity). Phosphorylated by ALK. Phosphorylated at Ser-270, Ser-
307, Ser-636 and Ser-1101 by RPS6KB1; phosphorylation induces
accelerated degradation of IRS1 (PubMed:18952604). Phosphorylated on
tyrosine residues in response to insulin (PubMed:23401856). In skeletal
muscles, dephosphorylated on Tyr-612 by TNS2 under anabolic conditions;
dephosphorylation results in the proteasomal degradation of IRS1
(PubMed:23401856). {ECO:0000250|UniProtKB:P35569,
ECO:0000250|UniProtKB:P35570, ECO:0000269|PubMed:15364919,
ECO:0000269|PubMed:18498745, ECO:0000269|PubMed:18952604,
ECO:0000269|PubMed:20685959, ECO:0000269|PubMed:23401856}.
-!- PTM: Ubiquitinated by the Cul7-RING(FBXW8) complex in a mTOR-dependent
manner, leading to its degradation: the Cul7-RING(FBXW8) complex
recognizes and binds IRS1 previously phosphorylated by S6 kinase
(RPS6KB1 or RPS6KB2). {ECO:0000269|PubMed:18498745}.
-!- POLYMORPHISM: The Arg-971 polymorphism impairs the ability of insulin
to stimulate glucose transport, glucose transporter translocation, and
glycogen synthesis by affecting the PI3K/AKT1/GSK3 signaling pathway.
The polymorphism at Arg-971 may contribute to the in vivo insulin
resistance observed in carriers of this variant. Arg-971 could
contribute to the risk for atherosclerotic cardiovascular diseases
associated with non-insulin-dependent diabetes mellitus (NIDDM) by
producing a cluster of insulin resistance-related metabolic
abnormalities. In insulin-stimulated human endothelial cells from
carriers of the Arg-971 polymorphism, genetic impairment of the
IRS1/PI3K/PDPK1/AKT1 insulin signaling cascade results in impaired
insulin-stimulated nitric oxide (NO) release and suggested that this
may be a mechanism through which the Arg-971 polymorphism contributes
to the genetic predisposition to develop endothelial dysfunction and
cardiovascular disease. The Arg-971 polymorphism not only reduces
phosphorylation of the substrate but allows IRS1 to act as an inhibitor
of PI3K, producing global insulin resistance.
-!- 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:10206679, ECO:0000269|PubMed:12843189,
ECO:0000269|PubMed:8723689}. Note=The gene represented in this entry
may be involved in disease pathogenesis.
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EMBL; S85963; AAB21608.1; -; Genomic_DNA.
EMBL; S62539; AAB27175.1; -; mRNA.
EMBL; BC053895; AAH53895.1; -; mRNA.
CCDS; CCDS2463.1; -.
PIR; I53160; JS0670.
RefSeq; NP_005535.1; NM_005544.2.
PDB; 1IRS; NMR; -; A=157-267.
PDB; 1K3A; X-ray; 2.10 A; B=891-902.
PDB; 1QQG; X-ray; 2.30 A; A/B=4-267.
PDB; 2Z8C; X-ray; 3.25 A; B=731-736.
PDB; 5U1M; X-ray; 1.80 A; A=161-265.
PDB; 6BNT; X-ray; 3.20 A; B=607-620.
PDBsum; 1IRS; -.
PDBsum; 1K3A; -.
PDBsum; 1QQG; -.
PDBsum; 2Z8C; -.
PDBsum; 5U1M; -.
PDBsum; 6BNT; -.
SMR; P35568; -.
BioGRID; 109874; 95.
CORUM; P35568; -.
DIP; DIP-523N; -.
ELM; P35568; -.
IntAct; P35568; 33.
MINT; P35568; -.
STRING; 9606.ENSP00000304895; -.
DrugBank; DB08513; [4-({5-(AMINOCARBONYL)-4-[(3-METHYLPHENYL)AMINO]PYRIMIDIN-2-YL}AMINO)PHENYL]ACETIC ACID.
iPTMnet; P35568; -.
PhosphoSitePlus; P35568; -.
BioMuta; IRS1; -.
DMDM; 547738; -.
EPD; P35568; -.
jPOST; P35568; -.
MassIVE; P35568; -.
MaxQB; P35568; -.
PaxDb; P35568; -.
PeptideAtlas; P35568; -.
PRIDE; P35568; -.
ProteomicsDB; 55088; -.
Antibodypedia; 3935; 2451 antibodies.
DNASU; 3667; -.
Ensembl; ENST00000305123; ENSP00000304895; ENSG00000169047.
GeneID; 3667; -.
KEGG; hsa:3667; -.
UCSC; uc002voh.5; human.
CTD; 3667; -.
DisGeNET; 3667; -.
EuPathDB; HostDB:ENSG00000169047.5; -.
GeneCards; IRS1; -.
HGNC; HGNC:6125; IRS1.
HPA; ENSG00000169047; Low tissue specificity.
MalaCards; IRS1; -.
MIM; 125853; phenotype.
MIM; 147545; gene.
neXtProt; NX_P35568; -.
OpenTargets; ENSG00000169047; -.
PharmGKB; PA203; -.
eggNOG; ENOG410IXEK; Eukaryota.
eggNOG; ENOG410Z9EP; LUCA.
GeneTree; ENSGT00940000161579; -.
HOGENOM; CLU_004902_2_0_1; -.
InParanoid; P35568; -.
KO; K16172; -.
OMA; YGKLWTN; -.
OrthoDB; 298675at2759; -.
PhylomeDB; P35568; -.
TreeFam; TF325994; -.
Reactome; R-HSA-109704; PI3K Cascade.
Reactome; R-HSA-112399; IRS-mediated signalling.
Reactome; R-HSA-112412; SOS-mediated signalling.
Reactome; R-HSA-1257604; PIP3 activates AKT signaling.
Reactome; R-HSA-1266695; Interleukin-7 signaling.
Reactome; R-HSA-198203; PI3K/AKT activation.
Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer.
Reactome; R-HSA-2428928; IRS-related events triggered by IGF1R.
Reactome; R-HSA-2586552; Signaling by Leptin.
Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
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-9603381; Activated NTRK3 signals through PI3K.
Reactome; R-HSA-982772; Growth hormone receptor signaling.
SignaLink; P35568; -.
SIGNOR; P35568; -.
BioGRID-ORCS; 3667; 18 hits in 791 CRISPR screens.
ChiTaRS; IRS1; human.
EvolutionaryTrace; P35568; -.
GeneWiki; IRS1; -.
GenomeRNAi; 3667; -.
Pharos; P35568; Tbio.
PRO; PR:P35568; -.
Proteomes; UP000005640; Chromosome 2.
RNAct; P35568; protein.
Bgee; ENSG00000169047; Expressed in endometrium and 236 other tissues.
ExpressionAtlas; P35568; baseline and differential.
Genevisible; P35568; HS.
GO; GO:0005901; C:caveola; IDA:BHF-UCL.
GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
GO; GO:0005829; C:cytosol; IDA:HPA.
GO; GO:0005899; C:insulin receptor complex; ISS:BHF-UCL.
GO; GO:0043231; C:intracellular membrane-bounded organelle; ISS:UniProtKB.
GO; GO:0005654; C:nucleoplasm; IDA:HPA.
GO; GO:0005634; C:nucleus; ISS:UniProtKB.
GO; GO:0005886; C:plasma membrane; IDA:HPA.
GO; GO:0005158; F:insulin receptor binding; IPI:UniProtKB.
GO; GO:0005159; F:insulin-like growth factor receptor binding; IPI:UniProtKB.
GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; IPI:UniProtKB.
GO; GO:0001784; F:phosphotyrosine residue binding; IPI:CAFA.
GO; GO:0005080; F:protein kinase C binding; ISS:BHF-UCL.
GO; GO:0042169; F:SH2 domain binding; ISS:UniProtKB.
GO; GO:0005070; F:SH3/SH2 adaptor activity; IDA:BHF-UCL.
GO; GO:0005068; F:transmembrane receptor protein tyrosine kinase adaptor activity; ISS:BHF-UCL.
GO; GO:0071398; P:cellular response to fatty acid; ISS:ARUK-UCL.
GO; GO:0032869; P:cellular response to insulin stimulus; IMP:BHF-UCL.
GO; GO:0042593; P:glucose homeostasis; TAS:BHF-UCL.
GO; GO:0008286; P:insulin receptor signaling pathway; IDA:UniProtKB.
GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; IPI:UniProtKB.
GO; GO:0038111; P:interleukin-7-mediated signaling pathway; TAS:Reactome.
GO; GO:0000165; P:MAPK cascade; TAS:Reactome.
GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; ISS:BHF-UCL.
GO; GO:0046676; P:negative regulation of insulin secretion; IDA:BHF-UCL.
GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; IDA:BHF-UCL.
GO; GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome.
GO; GO:0008284; P:positive regulation of cell population proliferation; NAS:BHF-UCL.
GO; GO:0032000; P:positive regulation of fatty acid beta-oxidation; IMP:BHF-UCL.
GO; GO:0046326; P:positive regulation of glucose import; IDA:BHF-UCL.
GO; GO:0010907; P:positive regulation of glucose metabolic process; IMP:BHF-UCL.
GO; GO:0045725; P:positive regulation of glycogen biosynthetic process; IMP:BHF-UCL.
GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; IDA:BHF-UCL.
GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; ISS:BHF-UCL.
GO; GO:0051897; P:positive regulation of protein kinase B signaling; TAS:Reactome.
GO; GO:0032868; P:response to insulin; IDA:BHF-UCL.
GO; GO:0043434; P:response to peptide hormone; ISS:BHF-UCL.
GO; GO:0007165; P:signal transduction; TAS:ProtInc.
CDD; cd01204; PTB_IRS; 1.
Gene3D; 2.30.29.30; -; 2.
IDEAL; IID00657; -.
InterPro; IPR039011; IRS.
InterPro; IPR002404; IRS_PTB.
InterPro; IPR011993; PH-like_dom_sf.
InterPro; IPR001849; PH_domain.
PANTHER; PTHR10614; PTHR10614; 1.
Pfam; PF02174; IRS; 1.
Pfam; PF00169; PH; 1.
PRINTS; PR00628; INSULINRSI.
SMART; SM00233; PH; 1.
SMART; SM00310; PTBI; 1.
PROSITE; PS51064; IRS_PTB; 1.
PROSITE; PS50003; PH_DOMAIN; 1.
1: Evidence at protein level;
3D-structure; Diabetes mellitus; Disease mutation; Phosphoprotein;
Polymorphism; Reference proteome; Repeat; Transducer; Ubl conjugation.
CHAIN 1..1242
/note="Insulin receptor substrate 1"
/id="PRO_0000084236"
DOMAIN 12..115
/note="PH"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
DOMAIN 160..264
/note="IRS-type PTB"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00389"
REGION 3..137
/note="Mediates interaction with PHIP"
/evidence="ECO:0000250"
REGION 896..898
/note="GRB2-binding"
/evidence="ECO:0000250"
MOTIF 465..468
/note="YXXM motif 1"
MOTIF 551..554
/note="YXXM motif 2"
MOTIF 612..615
/note="YXXM motif 3"
MOTIF 632..635
/note="YXXM motif 4"
MOTIF 662..665
/note="YXXM motif 5"
MOTIF 732..735
/note="YXXM motif 6"
MOTIF 941..944
/note="YXXM motif 7"
MOTIF 989..992
/note="YXXM motif 8"
MOTIF 1012..1015
/note="YXXM motif 9"
COMPBIAS 128..134
/note="Poly-Gly"
COMPBIAS 268..444
/note="Ser-rich"
COMPBIAS 680..686
/note="Poly-Ser"
COMPBIAS 807..815
/note="Poly-Ser"
COMPBIAS 877..882
/note="Poly-Gln"
COMPBIAS 1192..1210
/note="Pro-rich"
MOD_RES 3
/note="Phosphoserine"
/evidence="ECO:0000250|UniProtKB:P35570"
MOD_RES 99
/note="Phosphoserine; by CK2"
/evidence="ECO:0000250|UniProtKB:P35570"
MOD_RES 270
/note="Phosphoserine; by RPS6KB1"
/evidence="ECO:0000269|PubMed:18952604"
MOD_RES 307
/note="Phosphoserine; by RPS6KB1"
/evidence="ECO:0000269|PubMed:18498745,
ECO:0000269|PubMed:18952604"
MOD_RES 312
/note="Phosphoserine; by IKKB, MAPK8 and RPS6KB1"
/evidence="ECO:0000269|PubMed:18498745,
ECO:0000269|PubMed:20685959"
MOD_RES 323
/note="Phosphoserine"
/evidence="ECO:0000244|PubMed:24275569"
MOD_RES 330
/note="Phosphoserine"
/evidence="ECO:0000250|UniProtKB:P35569"
MOD_RES 345
/note="Phosphoserine"
/evidence="ECO:0000250|UniProtKB:P35569"
MOD_RES 348
/note="Phosphoserine"
/evidence="ECO:0000244|PubMed:19690332"
MOD_RES 419
/note="Phosphoserine"
/evidence="ECO:0000250|UniProtKB:P35569"
MOD_RES 446
/note="Phosphothreonine"
/evidence="ECO:0000250|UniProtKB:P35570"
MOD_RES 453
/note="Phosphothreonine"
/evidence="ECO:0000244|PubMed:24275569"
MOD_RES 465
/note="Phosphotyrosine; by INSR"
/evidence="ECO:0000250|UniProtKB:P35570"
MOD_RES 527
/note="Phosphoserine; by RPS6KB1"
/evidence="ECO:0000244|PubMed:24275569,
ECO:0000269|PubMed:18498745"
MOD_RES 612
/note="Phosphotyrosine; by INSR"
/evidence="ECO:0000269|PubMed:23401856"
MOD_RES 629
/note="Phosphoserine"
/evidence="ECO:0000244|PubMed:17081983,
ECO:0000244|PubMed:24275569"
MOD_RES 632
/note="Phosphotyrosine; by INSR"
/evidence="ECO:0000269|PubMed:23401856"
MOD_RES 636
/note="Phosphoserine; by RPS6KB1"
/evidence="ECO:0000244|PubMed:17081983,
ECO:0000269|PubMed:18498745, ECO:0000269|PubMed:18952604"
MOD_RES 662
/note="Phosphotyrosine"
/evidence="ECO:0000244|PubMed:15592455"
MOD_RES 794
/note="Phosphoserine; by AMPK and SIK2"
/evidence="ECO:0000269|PubMed:12624099"
MOD_RES 892
/note="Phosphoserine"
/evidence="ECO:0000250|UniProtKB:P35569"
MOD_RES 896
/note="Phosphotyrosine; by INSR"
/evidence="ECO:0000269|PubMed:23401856"
MOD_RES 941
/note="Phosphotyrosine; by INSR"
/evidence="ECO:0000269|PubMed:20685959"
MOD_RES 989
/note="Phosphotyrosine; by INSR"
/evidence="ECO:0000250|UniProtKB:P35570"
MOD_RES 1100
/note="Phosphoserine"
/evidence="ECO:0000250|UniProtKB:P35569"
MOD_RES 1101
/note="Phosphoserine; by RPS6KB1 and PKC/PRKCQ"
/evidence="ECO:0000269|PubMed:15364919,
ECO:0000269|PubMed:18952604"
MOD_RES 1179
/note="Phosphotyrosine; by INSR"
/evidence="ECO:0000250|UniProtKB:P35570"
MOD_RES 1229
/note="Phosphotyrosine; by INSR"
/evidence="ECO:0000250|UniProtKB:P35570"
VARIANT 158
/note="P -> R (in dbSNP:rs1801108)"
/id="VAR_014853"
VARIANT 209
/note="M -> T (in dbSNP:rs1801118)"
/id="VAR_014854"
VARIANT 512
/note="A -> P (in dbSNP:rs1801276)"
/evidence="ECO:0000269|PubMed:8104271"
/id="VAR_005299"
VARIANT 608
/note="T -> R (may contribute to insulin resistance by
impairing metabolic signaling through PI3K-dependent
pathways; dbSNP:rs104893642)"
/evidence="ECO:0000269|PubMed:12679424"
/id="VAR_025320"
VARIANT 723
/note="Missing (in NIDDM)"
/evidence="ECO:0000269|PubMed:8723689"
/id="VAR_005301"
VARIANT 809
/note="S -> F (in dbSNP:rs1801120)"
/id="VAR_014855"
VARIANT 892
/note="S -> G (in dbSNP:rs1801277)"
/id="VAR_014856"
VARIANT 971
/note="G -> R (in dbSNP:rs1801278)"
/evidence="ECO:0000269|PubMed:10843189,
ECO:0000269|PubMed:14671192, ECO:0000269|PubMed:14707024,
ECO:0000269|PubMed:15590636, ECO:0000269|PubMed:8104271"
/id="VAR_005300"
VARIANT 1043
/note="S -> Y (in NIDDM)"
/evidence="ECO:0000269|PubMed:10206679"
/id="VAR_005302"
VARIANT 1095
/note="C -> Y (in NIDDM)"
/evidence="ECO:0000269|PubMed:10206679"
/id="VAR_005303"
VARIANT 1137
/note="D -> N (in dbSNP:rs3731594)"
/id="VAR_021837"
MUTAGEN 307
/note="S->A: Impaired degradation by the Cul7-RING(FBXW8)
complex; when associated with A-312; A-527; A-636 and A-
639."
/evidence="ECO:0000269|PubMed:18498745"
MUTAGEN 312
/note="S->A: Impaired degradation by the Cul7-RING(FBXW8)
complex; when associated with A-307; A-527; A-636 and A-
639."
/evidence="ECO:0000269|PubMed:18498745"
MUTAGEN 527
/note="S->A: Impaired degradation by the Cul7-RING(FBXW8)
complex; when associated with A-307; A-312; A-636 and A-
639."
/evidence="ECO:0000269|PubMed:18498745"
MUTAGEN 612
/note="Y->F: Induces IRS1 degradation."
/evidence="ECO:0000269|PubMed:23401856"
MUTAGEN 632
/note="Y->F: Does not affect IRS1 stability."
/evidence="ECO:0000269|PubMed:23401856"
MUTAGEN 636
/note="S->A: Impaired degradation by the Cul7-RING(FBXW8)
complex; when associated with A-307; A-312; A-527 and A-
639."
/evidence="ECO:0000269|PubMed:18498745"
MUTAGEN 639
/note="S->A: Impaired degradation by the Cul7-RING(FBXW8)
complex; when associated with A-307; A-312; A-527 and A-
636."
/evidence="ECO:0000269|PubMed:18498745"
MUTAGEN 794
/note="S->A: Loss of phosphorylation by SIK2."
/evidence="ECO:0000269|PubMed:12624099"
CONFLICT 134
/note="G -> GG (in Ref. 2; AAB21608)"
/evidence="ECO:0000305"
CONFLICT 362
/note="S -> R (in Ref. 2; AAB21608)"
/evidence="ECO:0000305"
CONFLICT 384
/note="P -> R (in Ref. 2; AAB21608)"
/evidence="ECO:0000305"
STRAND 13..20
/evidence="ECO:0000244|PDB:1QQG"
TURN 22..24
/evidence="ECO:0000244|PDB:1QQG"
STRAND 27..33
/evidence="ECO:0000244|PDB:1QQG"
TURN 37..39
/evidence="ECO:0000244|PDB:1QQG"
STRAND 40..49
/evidence="ECO:0000244|PDB:1QQG"
HELIX 50..54
/evidence="ECO:0000244|PDB:1QQG"
STRAND 61..65
/evidence="ECO:0000244|PDB:1QQG"
HELIX 66..68
/evidence="ECO:0000244|PDB:1QQG"
STRAND 69..75
/evidence="ECO:0000244|PDB:1QQG"
STRAND 81..90
/evidence="ECO:0000244|PDB:1QQG"
STRAND 92..96
/evidence="ECO:0000244|PDB:1QQG"
HELIX 100..113
/evidence="ECO:0000244|PDB:1QQG"
STRAND 162..172
/evidence="ECO:0000244|PDB:5U1M"
HELIX 173..176
/evidence="ECO:0000244|PDB:5U1M"
STRAND 181..187
/evidence="ECO:0000244|PDB:5U1M"
STRAND 189..196
/evidence="ECO:0000244|PDB:5U1M"
STRAND 203..207
/evidence="ECO:0000244|PDB:5U1M"
HELIX 208..210
/evidence="ECO:0000244|PDB:5U1M"
STRAND 211..217
/evidence="ECO:0000244|PDB:5U1M"
STRAND 220..225
/evidence="ECO:0000244|PDB:5U1M"
STRAND 233..239
/evidence="ECO:0000244|PDB:5U1M"
HELIX 243..262
/evidence="ECO:0000244|PDB:5U1M"
STRAND 897..901
/evidence="ECO:0000244|PDB:1K3A"
SEQUENCE 1242 AA; 131591 MW; 3C0EFD9E32B3E64A CRC64;
MASPPESDGF SDVRKVGYLR KPKSMHKRFF VLRAASEAGG PARLEYYENE KKWRHKSSAP
KRSIPLESCF NINKRADSKN KHLVALYTRD EHFAIAADSE AEQDSWYQAL LQLHNRAKGH
HDGAAALGAG GGGGSCSGSS GLGEAGEDLS YGDVPPGPAF KEVWQVILKP KGLGQTKNLI
GIYRLCLTSK TISFVKLNSE AAAVVLQLMN IRRCGHSENF FFIEVGRSAV TGPGEFWMQV
DDSVVAQNMH ETILEAMRAM SDEFRPRSKS QSSSNCSNPI SVPLRRHHLN NPPPSQVGLT
RRSRTESITA TSPASMVGGK PGSFRVRASS DGEGTMSRPA SVDGSPVSPS TNRTHAHRHR
GSARLHPPLN HSRSIPMPAS RCSPSATSPV SLSSSSTSGH GSTSDCLFPR RSSASVSGSP
SDGGFISSDE YGSSPCDFRS SFRSVTPDSL GHTPPARGEE ELSNYICMGG KGPSTLTAPN
GHYILSRGGN GHRCTPGTGL GTSPALAGDE AASAADLDNR FRKRTHSAGT SPTITHQKTP
SQSSVASIEE YTEMMPAYPP GGGSGGRLPG HRHSAFVPTR SYPEEGLEMH PLERRGGHHR
PDSSTLHTDD GYMPMSPGVA PVPSGRKGSG DYMPMSPKSV SAPQQIINPI RRHPQRVDPN
GYMMMSPSGG CSPDIGGGPS SSSSSSNAVP SGTSYGKLWT NGVGGHHSHV LPHPKPPVES
SGGKLLPCTG DYMNMSPVGD SNTSSPSDCY YGPEDPQHKP VLSYYSLPRS FKHTQRPGEP
EEGARHQHLR LSTSSGRLLY AATADDSSSS TSSDSLGGGY CGARLEPSLP HPHHQVLQPH
LPRKVDTAAQ TNSRLARPTR LSLGDPKAST LPRAREQQQQ QQPLLHPPEP KSPGEYVNIE
FGSDQSGYLS GPVAFHSSPS VRCPSQLQPA PREEETGTEE YMKMDLGPGR RAAWQESTGV
EMGRLGPAPP GAASICRPTR AVPSSRGDYM TMQMSCPRQS YVDTSPAAPV SYADMRTGIA
AEEVSLPRAT MAAASSSSAA SASPTGPQGA AELAAHSSLL GGPQGPGGMS AFTRVNLSPN
RNQSAKVIRA DPQGCRRRHS SETFSSTPSA TRVGNTVPFG AGAAVGGGGG SSSSSEDVKR
HSSASFENVW LRPGELGGAP KEPAKLCGAA GGLENGLNYI DLDLVKDFKQ CPQECTPEPQ
PPPPPPPHQP LGSGESSSTR RSSEDLSAYA SISFQKQPED RQ


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Related Genes :
[Irs1 Irs-1] Insulin receptor substrate 1 (IRS-1) (pp185)
[Irs1 Irs-1] Insulin receptor substrate 1 (IRS-1)
[IRS1] Insulin receptor substrate 1 (IRS-1)
[IRS4] Insulin receptor substrate 4 (IRS-4) (160 kDa phosphotyrosine protein) (py160) (Phosphoprotein of 160 kDa) (pp160)
[BAIAP2] Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAI-associated protein 2) (BAI1-associated protein 2) (Protein BAP2) (Fas ligand-associated factor 3) (FLAF3) (Insulin receptor substrate p53/p58) (IRS-58) (IRSp53/58) (Insulin receptor substrate protein of 53 kDa) (IRSp53) (Insulin receptor substrate p53)
[Igf1r] Insulin-like growth factor 1 receptor (EC 2.7.10.1) (Insulin-like growth factor I receptor) (IGF-I receptor) (CD antigen CD221) [Cleaved into: Insulin-like growth factor 1 receptor alpha chain; Insulin-like growth factor 1 receptor beta chain]
[Baiap2] Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAI-associated protein 2) (BAI1-associated protein 2) (Insulin receptor substrate protein of 53 kDa) (IRSp53) (Insulin receptor substrate p53) (Insulin receptor tyrosine kinase substrate protein p53)
[IGF1R] Insulin-like growth factor 1 receptor (EC 2.7.10.1) (Insulin-like growth factor I receptor) (IGF-I receptor) (CD antigen CD221) [Cleaved into: Insulin-like growth factor 1 receptor alpha chain; Insulin-like growth factor 1 receptor beta chain]
[Irs4] Insulin receptor substrate 4 (IRS-4) (Phosphoprotein of 160 kDa) (pp160)
[Igf1r] Insulin-like growth factor 1 receptor (EC 2.7.10.1) (Insulin-like growth factor I receptor) (IGF-I receptor) (CD antigen CD221) [Cleaved into: Insulin-like growth factor 1 receptor alpha chain; Insulin-like growth factor 1 receptor beta chain]
[IGF1R] Insulin-like growth factor 1 receptor (EC 2.7.10.1) (Insulin-like growth factor I receptor) (IGF-I receptor) (CD antigen CD221) [Cleaved into: Insulin-like growth factor 1 receptor alpha chain; Insulin-like growth factor 1 receptor beta chain] (Fragment)
[INSR] Insulin receptor (IR) (EC 2.7.10.1) (CD antigen CD220) [Cleaved into: Insulin receptor subunit alpha; Insulin receptor subunit beta]
[Insr] Insulin receptor (IR) (EC 2.7.10.1) (CD antigen CD220) [Cleaved into: Insulin receptor subunit alpha; Insulin receptor subunit beta]
[Insr] Insulin receptor (IR) (EC 2.7.10.1) (CD antigen CD220) [Cleaved into: Insulin receptor subunit alpha; Insulin receptor subunit beta]
[InR dinr Dir-a Inr-a CG18402] Insulin-like receptor (dIR) (dInr) (EC 2.7.10.1) (dIRH) [Cleaved into: Insulin-like receptor subunit alpha; Insulin-like receptor subunit beta 1; Insulin-like receptor subunit beta 2]
[IGF1R] Insulin-like growth factor 1 receptor (EC 2.7.10.1) (Insulin-like growth factor I receptor) (IGF-I receptor) (CD antigen CD221) (Fragments)
[Baiap2] Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAI-associated protein 2) (BAI1-associated protein 2) (Insulin receptor substrate protein of 53 kDa) (IRSp53) (Insulin receptor substrate p53) (Insulin receptor tyrosine kinase 53 kDa substrate)
[DOK4] Docking protein 4 (Downstream of tyrosine kinase 4) (Insulin receptor substrate 5) (IRS-5) (IRS5)
[DOK5 C20orf180] Docking protein 5 (Downstream of tyrosine kinase 5) (Insulin receptor substrate 6) (IRS-6) (IRS6)
[irs1-a] Insulin receptor substrate 1-A (IRS1-A) (xIRS-1-A) (XIRS-L)
[daf-2 Y55D5A.5] Insulin-like receptor (IR) (EC 2.7.10.1) (Abnormal dauer formation protein 2) [Cleaved into: Insulin-like receptor subunit alpha; Insulin-like receptor subunit beta]
[Ros1 Ros Ros-1] Proto-oncogene tyrosine-protein kinase ROS (EC 2.7.10.1) (Proto-oncogene c-Ros) (Proto-oncogene c-Ros-1) (Receptor tyrosine kinase c-ros oncogene 1) (c-Ros receptor tyrosine kinase)
[Igf1 Igf-1] Insulin-like growth factor I (IGF-I) (Somatomedin)
[Igf1 Igf-1] Insulin-like growth factor I (IGF-I) (Somatomedin)
[NISCH IRAS KIAA0975] Nischarin (Imidazoline receptor 1) (I-1) (IR1) (Imidazoline receptor antisera-selected protein) (hIRAS) (Imidazoline-1 receptor) (I1R) (Imidazoline-1 receptor candidate protein) (I-1 receptor candidate protein) (I1R candidate protein)
[Sirpa Bit Mfr Ptpns1 Shps1 Sirp] Tyrosine-protein phosphatase non-receptor type substrate 1 (SHP substrate 1) (SHPS-1) (Brain Ig-like molecule with tyrosine-based activation motifs) (Bit) (CD172 antigen-like family member A) (Inhibitory receptor SHPS-1) (Macrophage fusion receptor) (Macrophage membrane protein MFP150) (Signal-regulatory protein alpha-1) (Sirp-alpha-1) (CD antigen CD172a)
[INSR] Insulin receptor (IR) (EC 2.7.10.1) (CD antigen CD220) [Cleaved into: Insulin receptor subunit alpha; Insulin receptor subunit beta] (Fragment)
[Frs2 Frs2a] Fibroblast growth factor receptor substrate 2 (FGFR substrate 2) (FGFR-signaling adaptor SNT) (FRS2-alpha) (Suc1-associated neurotrophic factor target 1) (SNT-1)
[BAIAP2] Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAI-associated protein 2) (BAI1-associated protein 2) (Insulin receptor substrate protein of 53 kDa) (IRSp53) (Insulin receptor substrate p53) (Insulin receptor tyrosine kinase 53 kDa substrate) (p58/p53)
[FRS2] Fibroblast growth factor receptor substrate 2 (FGFR substrate 2) (FGFR-signaling adaptor SNT) (Suc1-associated neurotrophic factor target 1) (SNT-1)

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