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UniProtKB/Swiss-Prot entry Q9Y4H2


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name IRS2_HUMAN
Primary accession number Q9Y4H2
Secondary accession numbers Q96RR2 Q9BZG0 Q9Y6I5
Integrated into Swiss-Prot on May 30, 2000
Sequence was last modified on March 29, 2005 (Sequence version 2)
Annotations were last modified on    June 10, 2008 (Entry version 61)
Name and origin of the protein
Protein name Insulin receptor substrate 2
Synonym IRS-2
Gene name
Name: IRS2
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
DOI=10.1074/jbc.272.40.25267; PubMed=9312143 [NCBI, ExPASy, EBI, Israel, Japan]
Ogihara T., Isobe T., Ichimura T., Taoka M., Funaki M., Sakoda H., Onishi Y., Inukai K., Anai M., Fukushima Y., Kikuchi M., Yazaki Y., Oka Y., Asano T.;
"14-3-3 protein binds to insulin receptor substrate-1, one of the binding sites of which is in the phosphotyrosine binding domain.";
J. Biol. Chem. 272:25267-25274(1997).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
DOI=10.1210/me.13.3.485; PubMed=10077005 [NCBI, ExPASy, EBI, Israel, Japan]
Vassen L., Wegrzyn W., Klein-Hitpass L.;
"Human insulin receptor substrate-2 (IRS-2) is a primary progesterone response gene.";
Mol. Endocrinol. 13:485-494(1999).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Heyne B.;
"Insulin receptor substrate 2 gene sequence.";
Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/nature02379; PubMed=15057823 [NCBI, ExPASy, EBI, Israel, Japan]
Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T.;
"The DNA sequence and analysis of human chromosome 13.";
Nature 428:522-528(2004).
[5]
NUCLEOTIDE SEQUENCE OF 1-1337, AND VARIANTS SER-879 AND ALA-882.
Heyne B., Gehrisch S., Jaross W.;
"Two missense mutations in insulin receptor substrate 2 (G879S and G882A).";
Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
[6]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-520; SER-915; SER-1100 AND SER-1203, AND MASS SPECTROMETRY.
TISSUE=Epithelium;
DOI=10.1073/pnas.0404720101; PubMed=15302935 [NCBI, ExPASy, EBI, Israel, Japan]
Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P.;
"Large-scale characterization of HeLa cell nuclear phosphoproteins.";
Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004).
[7]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-309; SER-388; SER-391; SER-560 AND SER-1176, AND MASS SPECTROMETRY.
TISSUE=Epithelium;
DOI=10.1016/j.cell.2006.09.026; PubMed=17081983 [NCBI, ExPASy, EBI, Israel, Japan]
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).
[8]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-346; THR-350; THR-527; SER-577; THR-580 AND SER-1100, AND MASS SPECTROMETRY.
TISSUE=Epithelium;
DOI=10.1038/nbt1240; PubMed=16964243 [NCBI, ExPASy, EBI, Israel, Japan]
Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
"A probability-based approach for high-throughput protein phosphorylation analysis and site localization.";
Nat. Biotechnol. 24:1285-1292(2006).
[9]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-334, AND MASS SPECTROMETRY.
DOI=10.1126/science.1140321; PubMed=17525332 [NCBI, ExPASy, EBI, Israel, Japan]
Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.";
Science 316:1160-1166(2007).
[10]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-388; SER-391; SER-608; SER-915 AND SER-1100, AND MASS SPECTROMETRY.
TISSUE=Platelet;
DOI=10.1021/pr0704130; PubMed=18088087 [NCBI, ExPASy, EBI, Israel, Japan]
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.;
"Phosphoproteome of resting human platelets.";
J. Proteome Res. 7:526-534(2008).
[11]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-713; SER-770; SER-772; SER-915 AND SER-1176, AND MASS SPECTROMETRY.
DOI=10.1021/pr0705441; PubMed=18220336 [NCBI, ExPASy, EBI, Israel, Japan]
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).
[12]
VARIANT ASP-1057.
DOI=10.1007/s00439-003-0935-3; PubMed=12687350 [NCBI, ExPASy, EBI, Israel, Japan]
Lautier C., El Mkadem S.A., Renard E., Brun J.F., Gris J.-C., Bringer J., Grigorescu F.;
"Complex haplotypes of IRS2 gene are associated with severe obesity and reveal heterogeneity in the effect of Gly1057Asp mutation.";
Hum. Genet. 113:34-43(2003).
Comments
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
AB000732; BAA24500.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF073310; AAD21531.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF322115; AAG50013.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF322114; AAG50013.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AL162497; CAH72369.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF288517; AAK83053.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
RefSeq NP_003740.2; -.
UniGene Hs.442344
3D structure databases
HSSP P35568; 1IRS. [HSSP ENTRY / PDB]
ModBase Q9Y4H2.
Protein-protein interaction databases
IntAct Q9Y4H2; -.
PTM databases
PhosphoSite Q9Y4H2; -.
Enzyme and pathway databases
Reactome REACT_498; Signaling by insulin receptor.
REACT_508; Signal attenuation.
Organism-specific databases
HGNC HGNC:6126; IRS2.
GeneLynx IRS2; Homo sapiens.
GenAtlas IRS2.
MIM 600797; gene. [NCBI / EBI]
PharmGKB PA375; -.
GeneCards Q9Y4H2.
Gene expression databases
ArrayExpress Q9Y4H2; -.
CleanEx HS_IRS2; -.
GermOnline ENSG00000185950; Homo sapiens.
Ontologies
GO
GO:0005886; Cellular component: plasma membrane (inferred from experiment from Reactome).
GO:0005515; Molecular function: protein binding (inferred from physical interaction from IntAct).
GO:0004871; Molecular function: signal transducer activity (traceable author statement from ProtInc).
GO:0006006; Biological process: glucose metabolic process (traceable author statement from ProtInc).
GO:0007165; Biological process: signal transduction (traceable author statement from ProtInc).
QuickGo view.
Family and domain databases
InterPro IPR002404; Insln_rcpt_S1.
IPR001849; PH.
IPR011993; PH_type.
Graphical view of domain structure.
Gene3D G3DSA:2.30.29.30; PH_type; 2.
Pfam PF02174; IRS; 1.
PF00169; PH; 1.
Pfam graphical view of domain structure.
PRINTS PR00628; INSULINRSI.
SMART SM00233; PH; 1.
SM00310; PTBI; 1.
SMART graphical view of domain structure.
PROSITE PS51064; IRS_PTB; 1.
PS50003; PH_DOMAIN; 1.
PROSITE graphical view of domain structure (profiles).
BLOCKS Q9Y4H2.
Genome annotation databases
Ensembl ENSG00000185950; Homo sapiens. [Contig view]
GeneID 8660; -.
KEGG hsa:8660; -.
Phylogenomic databases
HOVERGEN Q9Y4H2; -.
Other
SOURCE IRS2; Homo sapiens.
ProtoNet Q9Y4H2.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
Phosphoprotein; Polymorphism; Transducer.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom    To Length Description FTId
CHAIN   1   1338  1338     Insulin receptor substrate 2. PRO_0000084239
DOMAIN   16    144  129     PH. 
DOMAIN   194    298  105     IRS-type PTB. 
MOTIF   540    543  4     YXXM motif 1. 
MOTIF   598    601  4     YXXM motif 2. 
MOTIF   653    656  4     YXXM motif 3. 
MOTIF   675    678  4     YXXM motif 4. 
MOTIF   742    745  4     YXXM motif 5. 
MOTIF   823    826  4     YXXM motif 6. 
MOTIF   1072   1075  4     YXXM motif 7. 
COMPBIAS   19     28  10     Poly-Asn. 
COMPBIAS   371    380  10     Poly-Ala. 
COMPBIAS   447    452  6     Poly-Ser. 
COMPBIAS   460    467  8     Poly-Pro. 
COMPBIAS   533    537  5     Poly-Gly. 
COMPBIAS   642    645  4     Poly-Ser. 
COMPBIAS   694    701  8     Poly-Ala. 
COMPBIAS   944    947  4     Poly-Ser. 
COMPBIAS   1031   1038  8     Poly-Pro. 
COMPBIAS   1265   1278  14     Poly-Pro. 
MOD_RES   309    309        Phosphoserine. 
MOD_RES   334    334        Phosphoserine. 
MOD_RES   346    346        Phosphoserine. 
MOD_RES   350    350        Phosphothreonine. 
MOD_RES   388    388        Phosphoserine. 
MOD_RES   391    391        Phosphoserine. 
MOD_RES   520    520        Phosphothreonine. 
MOD_RES   527    527        Phosphothreonine. 
MOD_RES   540    540        Phosphotyrosine; by INSR (By similarity). 
MOD_RES   560    560        Phosphoserine. 
MOD_RES   577    577        Phosphoserine. 
MOD_RES   580    580        Phosphothreonine. 
MOD_RES   608    608        Phosphoserine. 
MOD_RES   653    653        Phosphotyrosine; by INSR (By similarity). 
MOD_RES   675    675        Phosphotyrosine; by INSR (By similarity). 
MOD_RES   713    713        Phosphothreonine. 
MOD_RES   770    770        Phosphoserine. 
MOD_RES   772    772        Phosphoserine. 
MOD_RES   915    915        Phosphoserine. 
MOD_RES   919    919        Phosphotyrosine; by INSR (By similarity). 
MOD_RES   978    978        Phosphotyrosine; by INSR (By similarity). 
MOD_RES   1100   1100        Phosphoserine. 
MOD_RES   1176   1176        Phosphoserine. 
MOD_RES   1203   1203        Phosphoserine. 
MOD_RES   1253   1253        Phosphotyrosine; by INSR (By similarity). 
VARIANT   789    789  1     H -> Y (in dbSNP:rs35223808 [NCBI]). VAR_033992 
VARIANT   879    879  1     G -> S. VAR_021557 
VARIANT   882    882  1     G -> A. VAR_021558 
VARIANT   999    999  1     V -> M (in dbSNP:rs35927012 [NCBI]). VAR_033993 
VARIANT   1057   1057  1     G -> D (in dbSNP:rs1805097 [NCBI]). VAR_014857 
CONFLICT   28     28        N -> NN (in Ref. 2; AAD21531). 
CONFLICT   39     41        KQK -> NEE (in Ref. 2; AAD21531). 
CONFLICT   59     59        E -> K (in Ref. 1; BAA24500). 
CONFLICT   81     81        K -> N (in Ref. 1; BAA24500). 
CONFLICT   107    107        A -> P (in Ref. 1; BAA24500). 
CONFLICT   171    171        L -> V (in Ref. 1; BAA24500). 
CONFLICT   371    371        A -> R (in Ref. 2; AAD21531). 
CONFLICT   379    382        GARP -> AQRL (in Ref. 2; AAD21531). 
CONFLICT   406    406        S -> I (in Ref. 1; BAA24500). 
CONFLICT   410    419        GGRGSKVALL -> RAAGTKWHCF (in Ref. 1; BAA24500). 
CONFLICT   424    424        A -> G (in Ref. 1; BAA24500). 
CONFLICT   436    438        AHS -> EHL (in Ref. 1; BAA24500). 
CONFLICT   453    453        G -> D (in Ref. 1; BAA24500). 
CONFLICT   456    456        S -> W (in Ref. 1; BAA24500). 
CONFLICT   468    468        P -> L (in Ref. 1; BAA24500). 
CONFLICT   662    662        L -> F (in Ref. 2; AAD21531). 
CONFLICT   704    704        S -> F (in Ref. 1; BAA24500). 
CONFLICT   714    714        S -> F (in Ref. 1; BAA24500). 
CONFLICT   848    848        S -> T (in Ref. 1; BAA24500). 
CONFLICT   872    872        P -> R (in Ref. 2). 
CONFLICT   875    878        GRPE -> RRS (in Ref. 2). 
CONFLICT   956    956        S -> L (in Ref. 1; BAA24500). 
CONFLICT   1252   1252        N -> K (in Ref. 1; BAA24500). 
CONFLICT   1303   1303        G -> R (in Ref. 1; BAA24500). 
CONFLICT   1314   1338        LPPANTYASIDFLSHHLKEATIVKE -> PAPCPTTYAQH (in Ref. 1; BAA24500). 
Sequence information
Length: 1338 AA [This is the length of the unprocessed precursor] Molecular weight: 137334 Da [This is the MW of the unprocessed precursor] CRC64: 58E569E8BDBAF3D7 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MASPPRHGPP GPASGDGPNL NNNNNNNNHS VRKCGYLRKQ KHGHKRFFVL RGPGAGGDEA 

        70         80         90        100        110        120 
TAGGGSAPQP PRLEYYESEK KWRSKAGAPK RVIALDCCLN INKRADAKHK YLIALYTKDE 

       130        140        150        160        170        180 
YFAVAAENEQ EQEGWYRALT DLVSEGRAAA GDAPPAAAPA ASCSASLPGA LGGSAGAAGA 

       190        200        210        220        230        240 
EDSYGLVAPA TAAYREVWQV NLKPKGLGQS KNLTGVYRLC LSARTIGFVK LNCEQPSVTL 

       250        260        270        280        290        300 
QLMNIRRCGH SDSFFFIEVG RSAVTGPGEL WMQADDSVVA QNIHETILEA MKALKELFEF 

       310        320        330        340        350        360 
RPRSKSQSSG SSATHPISVP GARRHHHLVN LPPSQTGLVR RSRTDSLAAT PPAAKCSSCR 

       370        380        390        400        410        420 
VRTASEGDGG AAAGAAAAGA RPVSVAGSPL SPGPVRAPLS RSHTLSGGCG GRGSKVALLP 

       430        440        450        460        470        480 
AGGALQHSRS MSMPVAHSPP AATSPGSLSS SSGHGSGSYP PPPGPHPPLP HPLHHGPGQR 

       490        500        510        520        530        540 
PSSGSASASG SPSDPGFMSL DEYGSSPGDL RAFCSHRSNT PESIAETPPA RDGGGGGEFY 

       550        560        570        580        590        600 
GYMTMDRPLS HCGRSYRRVS GDAAQDLDRG LRKRTYSLTT PARQRPVPQP SSASLDEYTL 

       610        620        630        640        650        660 
MRATFSGSAG RLCPSCPASS PKVAYHPYPE DYGDIEIGSH RSSSSNLGAD DGYMPMTPGA 

       670        680        690        700        710        720 
ALAGSGSGSC RSDDYMPMSP ASVSAPKQIL QPRAAAAAAA AVPSAGPAGP APTSAAGRTF 

       730        740        750        760        770        780 
PASGGGYKAS SPAESSPEDS GYMRMWCGSK LSMEHADGKL LPNGDYLNVS PSDAVTTGTP 

       790        800        810        820        830        840 
PDFFSAALHP GGEPLRGVPG CCYSSLPRSY KAPYTCGGDS DQYVLMSSPV GRILEEERLE 

       850        860        870        880        890        900 
PQATPGPSQA ASAFGAGPTQ PPHPVVPSPV RPSGGRPEGF LGQRGRAVRP TRLSLEGLPS 

       910        920        930        940        950        960 
LPSMHEYPLP PEPKSPGEYI NIDFGEPGAR LSPPAPPLLA SAASSSSLLS ASSPASSLGS 

       970        980        990       1000       1010       1020 
GTPGTSSDSR QRSPLSDYMN LDFSSPKSPK PGAPSGHPVG SLDGLLSPEA SSPYPPLPPR 

      1030       1040       1050       1060       1070       1080 
PSASPSSSLQ PPPPPPAPGE LYRLPPASAV ATAQGPGAAS SLSSDTGDNG DYTEMAFGVA 

      1090       1100       1110       1120       1130       1140 
ATPPQPIAAP PKPEAARVAS PTSGVKRLSL MEQVSGVEAF LQASQPPDPH RGAKVIRADP 

      1150       1160       1170       1180       1190       1200 
QGGRRRHSSE TFSSTTTVTP VSPSFAHNPK RHNSASVENV SLRKSSEGGV GVGPGGGDEP 

      1210       1220       1230       1240       1250       1260 
PTSPRQLQPA PPLAPQGRPW TPGQPGGLVG CPGSGGSPMR RETSAGFQNG LNYIAIDVRE 

      1270       1280       1290       1300       1310       1320 
EPGLPPQPQP PPPPLPQPGD KSSWGRTRSL GGLISAVGVG STGGGCGGPG PGALPPANTY 

      1330 
ASIDFLSHHL KEATIVKE 

Q9Y4H2 in FASTA format

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