Insulin receptor substrate 2 (IRS-2) (4PS)

 IRS2_MOUSE              Reviewed;        1321 AA.
 P81122; B9EJW3;
 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
 27-JUL-2011, sequence version 2.
 17-JUN-2020, entry version 164.
 RecName: Full=Insulin receptor substrate 2;
          Short=IRS-2;
 AltName: Full=4PS;
 Name=Irs2;
 Mus musculus (Mouse).
 Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
 Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
 Murinae; Mus; Mus.
 NCBI_TaxID=10090;
 [1]
 NUCLEOTIDE SEQUENCE, AND PARTIAL PROTEIN SEQUENCE.
 PubMed=7675087; DOI=10.1038/377173a0;
 Sun X.J., Wang L.-M., Zhang Y., Yenush L., Myers M.G. Jr., Glasheen E.,
 Lane W.S., Pierce J.H., White M.F.;
 "Role of IRS-2 in insulin and cytokine signalling.";
 Nature 377:173-177(1995).
 [2]
 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
 TISSUE=Brain;
 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).
 [3]
 INTERACTION WITH PHIP.
 PubMed=11018022; DOI=10.1074/jbc.c000611200;
 Farhang-Fallah J., Yin X., Trentin G., Cheng A.M., Rozakis-Adcock M.;
 "Cloning and characterization of PHIP, a novel insulin receptor substrate-1
 pleckstrin homology domain interacting protein.";
 J. Biol. Chem. 275:40492-40497(2000).
 [4]
 SUBCELLULAR LOCATION.
 PubMed=17636024; DOI=10.1128/mcb.02409-06;
 Podcheko A., Northcott P., Bikopoulos G., Lee A., Bommareddi S.R.,
 Kushner J.A., Farhang-Fallah J., Rozakis-Adcock M.;
 "Identification of a WD40 repeat-containing isoform of PHIP as a novel
 regulator of beta-cell growth and survival.";
 Mol. Cell. Biol. 27:6484-6496(2007).
 [5]
 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-649, AND IDENTIFICATION BY
 MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
 TISSUE=Brain;
 PubMed=18034455; DOI=10.1021/pr0701254;
 Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
 "Large-scale identification and evolution indexing of tyrosine
 phosphorylation sites from murine brain.";
 J. Proteome Res. 7:311-318(2008).
 [6]
 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-385; SER-388; THR-524;
 SER-728; SER-907; SER-1151 AND SER-1165, AND IDENTIFICATION BY MASS
 SPECTROMETRY [LARGE SCALE ANALYSIS].
 TISSUE=Brain, Kidney, Lung, Spleen, and Testis;
 PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
 Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
 Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
 "A tissue-specific atlas of mouse protein phosphorylation and expression.";
 Cell 143:1174-1189(2010).
 -!- FUNCTION: May mediate the control of various cellular processes by
     insulin.
 -!- SUBUNIT: Interacts with PHIP. {ECO:0000269|PubMed:11018022}.
 -!- INTERACTION:
     P81122; Q923E4: Sirt1; NbExp=2; IntAct=EBI-1369862, EBI-1802585;
     P81122; P06213-1: INSR; Xeno; NbExp=8; IntAct=EBI-1369862, EBI-15558981;
 -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:17636024}.
 -!- TISSUE SPECIFICITY: Skeletal muscle, lung, brain, liver, kidney, heart
     and spleen.
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 EMBL; BC147580; AAI47581.1; -; mRNA.
 CCDS; CCDS52477.1; -.
 RefSeq; NP_001074681.1; NM_001081212.1.
 PDB; 3BU3; X-ray; 1.65 A; B=620-634.
 PDB; 3BU5; X-ray; 2.10 A; B=620-634.
 PDB; 3BU6; X-ray; 1.95 A; B=620-634.
 PDBsum; 3BU3; -.
 PDBsum; 3BU5; -.
 PDBsum; 3BU6; -.
 SMR; P81122; -.
 BioGRID; 239306; 3.
 DIP; DIP-39500N; -.
 IntAct; P81122; 7.
 MINT; P81122; -.
 STRING; 10090.ENSMUSP00000038514; -.
 iPTMnet; P81122; -.
 PhosphoSitePlus; P81122; -.
 EPD; P81122; -.
 jPOST; P81122; -.
 MaxQB; P81122; -.
 PaxDb; P81122; -.
 PeptideAtlas; P81122; -.
 PRIDE; P81122; -.
 Antibodypedia; 25473; 338 antibodies.
 Ensembl; ENSMUST00000040514; ENSMUSP00000038514; ENSMUSG00000038894.
 GeneID; 384783; -.
 KEGG; mmu:384783; -.
 UCSC; uc009kuz.1; mouse.
 CTD; 8660; -.
 MGI; MGI:109334; Irs2.
 eggNOG; ENOG410IXEK; Eukaryota.
 eggNOG; ENOG410Z9EP; LUCA.
 GeneTree; ENSGT00940000161407; -.
 HOGENOM; CLU_004902_1_0_1; -.
 InParanoid; P81122; -.
 KO; K07187; -.
 OMA; YKAPYTC; -.
 OrthoDB; 298675at2759; -.
 TreeFam; TF325994; -.
 Reactome; R-MMU-109704; PI3K Cascade.
 Reactome; R-MMU-112399; IRS-mediated signalling.
 Reactome; R-MMU-112412; SOS-mediated signalling.
 Reactome; R-MMU-1257604; PIP3 activates AKT signaling.
 Reactome; R-MMU-1266695; Interleukin-7 signaling.
 Reactome; R-MMU-198203; PI3K/AKT activation.
 Reactome; R-MMU-2428928; IRS-related events triggered by IGF1R.
 Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
 Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
 Reactome; R-MMU-74713; IRS activation.
 Reactome; R-MMU-74749; Signal attenuation.
 Reactome; R-MMU-8853659; RET signaling.
 Reactome; R-MMU-9027276; Erythropoietin activates Phosphoinositide-3-kinase (PI3K).
 Reactome; R-MMU-9027284; Erythropoietin activates RAS.
 BioGRID-ORCS; 384783; 2 hits in 13 CRISPR screens.
 ChiTaRS; Irs2; mouse.
 EvolutionaryTrace; P81122; -.
 PRO; PR:P81122; -.
 Proteomes; UP000000589; Chromosome 8.
 RNAct; P81122; protein.
 Bgee; ENSMUSG00000038894; Expressed in blood and 172 other tissues.
 Genevisible; P81122; MM.
 GO; GO:0005623; C:cell; IEA:GOC.
 GO; GO:0005829; C:cytosol; IDA:MGI.
 GO; GO:0005886; C:plasma membrane; IDA:MGI.
 GO; GO:0032991; C:protein-containing complex; IDA:MGI.
 GO; GO:0071889; F:14-3-3 protein binding; ISO:MGI.
 GO; GO:0005158; F:insulin receptor binding; ISO:MGI.
 GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; IDA:MGI.
 GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
 GO; GO:0019901; F:protein kinase binding; IDA:MGI.
 GO; GO:0019903; F:protein phosphatase binding; ISO:MGI.
 GO; GO:0007420; P:brain development; IMP:MGI.
 GO; GO:0071333; P:cellular response to glucose stimulus; IEA:Ensembl.
 GO; GO:0032869; P:cellular response to insulin stimulus; IDA:MGI.
 GO; GO:0008286; P:insulin receptor signaling pathway; IMP:MGI.
 GO; GO:0030879; P:mammary gland development; IGI:MGI.
 GO; GO:0002903; P:negative regulation of B cell apoptotic process; IMP:BHF-UCL.
 GO; GO:0033673; P:negative regulation of kinase activity; IMP:BHF-UCL.
 GO; GO:0010748; P:negative regulation of long-chain fatty acid import across plasma membrane; ISO:MGI.
 GO; GO:0030890; P:positive regulation of B cell proliferation; IDA:BHF-UCL.
 GO; GO:0030335; P:positive regulation of cell migration; IGI:MGI.
 GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:MGI.
 GO; GO:0032000; P:positive regulation of fatty acid beta-oxidation; ISO:MGI.
 GO; GO:0046326; P:positive regulation of glucose import; ISO:MGI.
 GO; GO:0010907; P:positive regulation of glucose metabolic process; ISO:MGI.
 GO; GO:0045725; P:positive regulation of glycogen biosynthetic process; ISO:MGI.
 GO; GO:0032024; P:positive regulation of insulin secretion; IMP:BHF-UCL.
 GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; IGI:MGI.
 GO; GO:0009749; P:response to glucose; IDA:BHF-UCL.
 CDD; cd01204; PTB_IRS; 1.
 Gene3D; 2.30.29.30; -; 2.
 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; Cytoplasm; Direct protein sequencing; Methylation;
 Phosphoprotein; Reference proteome; Transducer.
 CHAIN           1..1321
                 /note="Insulin receptor substrate 2"
                 /id="PRO_0000084240"
 DOMAIN          16..144
                 /note="PH"
                 /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
 DOMAIN          191..295
                 /note="IRS-type PTB"
                 /evidence="ECO:0000255|PROSITE-ProRule:PRU00389"
 MOTIF           536..539
                 /note="YXXM motif 1"
 MOTIF           594..597
                 /note="YXXM motif 2"
 MOTIF           649..652
                 /note="YXXM motif 3"
 MOTIF           671..674
                 /note="YXXM motif 4"
 MOTIF           734..737
                 /note="YXXM motif 5"
 MOTIF           814..817
                 /note="YXXM motif 6"
 MOTIF           1061..1064
                 /note="YXXM motif 7"
 COMPBIAS        19..28
                 /note="Poly-Asn"
 COMPBIAS        444..449
                 /note="Poly-Ser"
 COMPBIAS        638..641
                 /note="Poly-Ser"
 COMPBIAS        936..939
                 /note="Poly-Ser"
 MOD_RES         303
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q9Y4H2"
 MOD_RES         343
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q9Y4H2"
 MOD_RES         347
                 /note="Phosphothreonine"
                 /evidence="ECO:0000250|UniProtKB:Q9Y4H2"
 MOD_RES         362
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q9Y4H2"
 MOD_RES         381
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q9Y4H2"
 MOD_RES         385
                 /note="Phosphoserine"
                 /evidence="ECO:0000244|PubMed:21183079"
 MOD_RES         388
                 /note="Phosphoserine"
                 /evidence="ECO:0000244|PubMed:21183079"
 MOD_RES         409
                 /note="Omega-N-methylarginine"
                 /evidence="ECO:0000250|UniProtKB:Q9Y4H2"
 MOD_RES         517
                 /note="Phosphothreonine"
                 /evidence="ECO:0000250|UniProtKB:Q9Y4H2"
 MOD_RES         520
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q9Y4H2"
 MOD_RES         524
                 /note="Phosphothreonine"
                 /evidence="ECO:0000244|PubMed:21183079"
 MOD_RES         536
                 /note="Phosphotyrosine; by INSR"
                 /evidence="ECO:0000250"
 MOD_RES         556
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q9Y4H2"
 MOD_RES         573
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q9Y4H2"
 MOD_RES         575
                 /note="Phosphothreonine"
                 /evidence="ECO:0000250|UniProtKB:Q9Y4H2"
 MOD_RES         576
                 /note="Phosphothreonine"
                 /evidence="ECO:0000250|UniProtKB:Q9Y4H2"
 MOD_RES         590
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q9Y4H2"
 MOD_RES         604
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q9Y4H2"
 MOD_RES         616
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q9Y4H2"
 MOD_RES         649
                 /note="Phosphotyrosine"
                 /evidence="ECO:0000244|PubMed:18034455"
 MOD_RES         671
                 /note="Phosphotyrosine; by INSR"
                 /evidence="ECO:0000250|UniProtKB:Q9Y4H2"
 MOD_RES         675
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q9Y4H2"
 MOD_RES         678
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q9Y4H2"
 MOD_RES         727
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q9Y4H2"
 MOD_RES         728
                 /note="Phosphoserine"
                 /evidence="ECO:0000244|PubMed:21183079"
 MOD_RES         762
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q9Y4H2"
 MOD_RES         771
                 /note="Phosphothreonine"
                 /evidence="ECO:0000250|UniProtKB:Q9Y4H2"
 MOD_RES         796
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q9Y4H2"
 MOD_RES         819
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q9Y4H2"
 MOD_RES         907
                 /note="Phosphoserine"
                 /evidence="ECO:0000244|PubMed:21183079"
 MOD_RES         911
                 /note="Phosphotyrosine; by INSR"
                 /evidence="ECO:0000250"
 MOD_RES         965
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q9Y4H2"
 MOD_RES         970
                 /note="Phosphotyrosine; by INSR"
                 /evidence="ECO:0000250"
 MOD_RES         1071
                 /note="Phosphothreonine"
                 /evidence="ECO:0000250|UniProtKB:Q9Y4H2"
 MOD_RES         1089
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q9Y4H2"
 MOD_RES         1148
                 /note="Phosphothreonine"
                 /evidence="ECO:0000250|UniProtKB:Q9Y4H2"
 MOD_RES         1151
                 /note="Phosphoserine"
                 /evidence="ECO:0000244|PubMed:21183079"
 MOD_RES         1163
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q9Y4H2"
 MOD_RES         1165
                 /note="Phosphoserine"
                 /evidence="ECO:0000244|PubMed:21183079"
 MOD_RES         1175
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q9Y4H2"
 MOD_RES         1190
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q9Y4H2"
 MOD_RES         1242
                 /note="Phosphotyrosine; by INSR"
                 /evidence="ECO:0000250"
 MOD_RES         1303
                 /note="Phosphotyrosine; by INSR"
                 /evidence="ECO:0000250"
 CONFLICT        13
                 /note="A -> G (in Ref. 1; no nucleotide entry)"
                 /evidence="ECO:0000305"
 CONFLICT        232
                 /note="Q -> G (in Ref. 1; no nucleotide entry)"
                 /evidence="ECO:0000305"
 CONFLICT        240
                 /note="M -> N (in Ref. 1; no nucleotide entry)"
                 /evidence="ECO:0000305"
 CONFLICT        428
                 /note="M -> N (in Ref. 1; no nucleotide entry)"
                 /evidence="ECO:0000305"
 CONFLICT        761
                 /note="M -> K (in Ref. 1; no nucleotide entry)"
                 /evidence="ECO:0000305"
 CONFLICT        916
                 /note="F -> P (in Ref. 1; no nucleotide entry)"
                 /evidence="ECO:0000305"
 CONFLICT        975
                 /note="F -> P (in Ref. 1; no nucleotide entry)"
                 /evidence="ECO:0000305"
 CONFLICT        1062
                 /note="T -> S (in Ref. 1; no nucleotide entry)"
                 /evidence="ECO:0000305"
 HELIX           625..627
                 /evidence="ECO:0000244|PDB:3BU3"
 STRAND          629..633
                 /evidence="ECO:0000244|PDB:3BU3"
 SEQUENCE   1321 AA;  136763 MW;  823A5458DA21C9C7 CRC64;
 MASAPLPGPP ASAGGDGPNL NNNNNNNNHS VRKCGYLRKQ KHGHKRFFVL RGPGTGGDEA
 SAAGGSPPQP PRLEYYESEK KWRSKAGAPK RVIALDCCLN INKRADAKHK YLIALYTKDE
 YFAVAAENEQ EQEGWYRALT DLVSEGRSGE GGSGTTGGSC SASLPGVLGG SAGAAGCDDN
 YGLVTPATAV YREVWQVNLK PKGLGQSKNL TGVYRLCLSA RTIGFVKLNC EQPSVTLQLM
 NIRRCGHSDS FFFIEVGRSA VTGPGELWMQ ADDSVVAQNI HETILEAMKA LKELFEFRPR
 SKSQSSGSSA THPISVPGAR RHHHLVNLPP SQTGLVRRSR TDSLAATPPA AKCTSCRVRT
 ASEGDGGAAG GAGTAGGRPM SVAGSPLSPG PVRAPLSRSH TLSAGCGGRP SKVTLAPAGG
 ALQHSRSMSM PVAHSPPAAT SPGSLSSSSG HGSGSYPLPP GSHPHLPHPL HHPQGQRPSS
 GSASASGSPS DPGFMSLDEY GSSPGDLRAF SSHRSNTPES IAETPPARDG SGGELYGYMS
 MDRPLSHCGR PYRRVSGDGA QDLDRGLRKR TYSLTTPARQ RQVPQPSSAS LDEYTLMRAT
 FSGSSGRLCP SFPASSPKVA YNPYPEDYGD IEIGSHKSSS SNLGADDGYM PMTPGAALRS
 GGPNSCKSDD YMPMSPTSVS APKQILQPRL AAALPPSGAA VPAPPSGVGR TFPVNGGGYK
 ASSPAESSPE DSGYMRMWCG SKLSMENPDP KLLPNGDYLN MSPSEAGTAG TPPDFSAALR
 GGSEGLKGIP GHCYSSLPRS YKAPCSCSGD NDQYVLMSSP VGRILEEERL EPQATPGAGT
 FGAAGGSHTQ PHHSAVPSSM RPSAIGGRPE GFLGQRCRAV RPTRLSLEGL QTLPSMQEYP
 LPTEPKSPGE YINIDFGEAG TRLSPPAPPL LASAASSSSL LSASSPASSL GSGTPGTSSD
 SRQRSPLSDY MNLDFSSPKS PKPSTRSGDT VGSMDGLLSP EASSPYPPLP PRPSTSPSSL
 QQPLPPAPGD LYRLPPASAA TSQGPTAGSS MSSEPGDNGD YTEMAFGVAA TPPQPIVAPP
 KPEGARVASP TSGLKRLSLM DQVSGVEAFL QVSQPPDPHR GAKVIRADPQ GGRRRHSSET
 FSSTTTVTPV SPSFAHNSKR HNSASVENVS LRKSSEGSST LGGGDEPPTS PGQAQPLVAV
 PPVPQARPWN PGQPGALIGC PGGSSSPMRR ETSVGFQNGL NYIAIDVRGE QGSLAQSQPQ
 PGDKNSWSRT RSLGGLLGTV GGSGASGVCG GPGTGALPSA STYASIDFLS HHLKEATVVK
 E

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