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IRS2_MOUSE Reviewed; 1321 AA.
P81122; B9EJW3;
15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
27-JUL-2011, sequence version 2.
02-DEC-2020, entry version 166.
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; 339 antibodies.
Ensembl; ENSMUST00000040514; ENSMUSP00000038514; ENSMUSG00000038894.
GeneID; 384783; -.
KEGG; mmu:384783; -.
UCSC; uc009kuz.1; mouse.
CTD; 8660; -.
MGI; MGI:109334; Irs2.
eggNOG; ENOG502QUNU; Eukaryota.
GeneTree; ENSGT00940000161407; -.
HOGENOM; CLU_004902_1_0_1; -.
InParanoid; P81122; -.
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 18 CRISPR screens.
ChiTaRS; Irs2; mouse.
EvolutionaryTrace; P81122; -.
PRO; PR:P81122; -.
Proteomes; UP000000589; Chromosome 8.
RNAct; P81122; protein.
Bgee; ENSMUSG00000038894; Expressed in blood and 191 other tissues.
Genevisible; P81122; MM.
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