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P35569

- IRS1_MOUSE

UniProt

P35569 - IRS1_MOUSE

Protein

Insulin receptor substrate 1

Gene

Irs1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 134 (01 Oct 2014)
      Sequence version 1 (01 Jun 1994)
      Previous versions | rss
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    Functioni

    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.By similarity

    GO - Molecular functioni

    1. insulin-like growth factor receptor binding Source: UniProtKB
    2. insulin receptor binding Source: UniProtKB
    3. phosphatidylinositol 3-kinase binding Source: UniProtKB
    4. protein binding Source: IntAct
    5. protein kinase binding Source: MGI
    6. SH2 domain binding Source: UniProtKB
    7. signal transducer activity Source: UniProtKB-KW

    GO - Biological processi

    1. cellular response to insulin stimulus Source: MGI
    2. insulin-like growth factor receptor signaling pathway Source: UniProtKB
    3. lipid catabolic process Source: MGI
    4. mammary gland development Source: MGI
    5. positive regulation of cell migration Source: MGI
    6. positive regulation of mesenchymal cell proliferation Source: MGI
    7. positive regulation of phosphatidylinositol 3-kinase activity Source: MGI
    8. protein kinase B signaling Source: MGI
    9. protein localization to nucleus Source: MGI
    10. regulation of gene expression Source: MGI

    Keywords - Molecular functioni

    Transducer

    Enzyme and pathway databases

    ReactomeiREACT_169390. Signaling by Leptin.
    REACT_205300. PI3K/AKT activation.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Insulin receptor substrate 1
    Short name:
    IRS-1
    Gene namesi
    Name:Irs1
    Synonyms:Irs-1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Unplaced

    Organism-specific databases

    MGIiMGI:99454. Irs1.

    Subcellular locationi

    GO - Cellular componenti

    1. ciliary basal body Source: MGI
    2. cytoplasm Source: MGI
    3. cytosol Source: Reactome
    4. nucleus Source: MGI
    5. plasma membrane Source: MGI

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 12331233Insulin receptor substrate 1PRO_0000084237Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei99 – 991Phosphoserine; by CK2By similarity
    Modified residuei265 – 2651Phosphoserine; by RPS6KB1By similarity
    Modified residuei302 – 3021Phosphoserine; by RPS6KB1By similarity
    Modified residuei307 – 3071Phosphoserine; by IKKB, MAPK8 and RPS6KB1By similarity
    Modified residuei340 – 3401Phosphoserine1 Publication
    Modified residuei343 – 3431PhosphoserineBy similarity
    Modified residuei460 – 4601Phosphotyrosine; by INSRBy similarity
    Modified residuei522 – 5221Phosphoserine; by RPS6KB1By similarity
    Modified residuei608 – 6081Phosphotyrosine; by INSRBy similarity
    Modified residuei628 – 6281Phosphotyrosine; by INSRBy similarity
    Modified residuei632 – 6321Phosphoserine; by RPS6KB1 and ROCK21 Publication
    Modified residuei658 – 6581PhosphotyrosineBy similarity
    Modified residuei789 – 7891Phosphoserine; by AMPK and SIK21 Publication
    Modified residuei891 – 8911Phosphotyrosine; by INSRBy similarity
    Modified residuei935 – 9351Phosphotyrosine; by INSRBy similarity
    Modified residuei983 – 9831Phosphotyrosine; by INSRBy similarity
    Modified residuei1097 – 10971Phosphoserine; alternate1 Publication
    Modified residuei1097 – 10971Phosphoserine; by RPS6KB1 and PKC/PRKCQ; alternateBy similarity
    Modified residuei1173 – 11731Phosphotyrosine; by INSRBy similarity
    Modified residuei1220 – 12201Phosphotyrosine; by INSRBy similarity

    Post-translational modificationi

    Serine phosphorylation of IRS1 is a mechanism for insulin resistance. Ser-307 phosphorylation inhibits insulin action through disruption of IRS1 interaction with the insulin receptor By similarity. Phosphorylation of Tyr-891 is required for GRB2-binding By similarity. Phosphorylated by ALK. Phosphorylated at Ser-265, Ser-302, Ser-632 and Ser-1097 by RPS6KB1; phosphorylation induces accelerated degradation of IRS1 By similarity.By similarity
    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).By similarity

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    PRIDEiP35569.

    PTM databases

    PhosphoSiteiP35569.

    Expressioni

    Tissue specificityi

    Expressed in osteoblasts, but not in osteoclasts.1 Publication

    Gene expression databases

    CleanExiMM_IRS1.
    GenevestigatoriP35569.

    Interactioni

    Subunit structurei

    Interacts (via phosphorylated YXXM motifs) with PIK3R1 By similarity. Interacts with ROCK1 By similarity. Interacts with GRB2 By similarity. Interacts with SOCS7 By similarity. Interacts (via IRS-type PTB domain) with IGF1R and INSR (via the tyrosine-phosphorylated NPXY motif) By similarity. Interacts with UBTF and PIK3CA. Interacts (via PH domain) with PHIP. Interacts with FER. Interacts with ALK By similarity. Interacts with EIF2AK2/PKR.By similarity4 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Eif2ak2Q039632EBI-400825,EBI-2603444
    Pik3r1P264502EBI-400825,EBI-641764
    TP53BP2Q13625-22EBI-400825,EBI-287091From a different organism.

    Protein-protein interaction databases

    BioGridi200788. 8 interactions.
    DIPiDIP-32456N.
    IntActiP35569. 45 interactions.
    MINTiMINT-1540686.
    STRINGi10090.ENSMUSP00000063795.

    Structurei

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1AYBX-ray3.00P887-898[»]
    ProteinModelPortaliP35569.
    SMRiP35569. Positions 11-262.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP35569.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini12 – 115104PHPROSITE-ProRule annotationAdd
    BLAST
    Domaini155 – 259105IRS-type PTBPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni3 – 133131Mediates interaction with PHIPBy similarityAdd
    BLAST
    Regioni891 – 8933GRB2-bindingBy similarity

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi460 – 4634YXXM motif 1
    Motifi546 – 5494YXXM motif 2
    Motifi608 – 6114YXXM motif 3
    Motifi628 – 6314YXXM motif 4
    Motifi658 – 6614YXXM motif 5
    Motifi727 – 7304YXXM motif 6
    Motifi935 – 9384YXXM motif 7
    Motifi983 – 9864YXXM motif 8
    Motifi1006 – 10094YXXM motif 9

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi675 – 6806Poly-Ser
    Compositional biasi872 – 8776Poly-Gln
    Compositional biasi1119 – 112810Poly-Gly
    Compositional biasi1194 – 11985Poly-Pro

    Sequence similaritiesi

    Contains 1 IRS-type PTB domain.PROSITE-ProRule annotation
    Contains 1 PH domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiNOG81285.
    HOGENOMiHOG000113103.
    HOVERGENiHBG000542.
    InParanoidiP35569.
    KOiK16172.
    PhylomeDBiP35569.

    Family and domain databases

    Gene3Di2.30.29.30. 2 hits.
    InterProiIPR002404. Insln_rcpt_S1.
    IPR001849. PH_domain.
    IPR011993. PH_like_dom.
    [Graphical view]
    PfamiPF02174. IRS. 1 hit.
    PF00169. PH. 1 hit.
    [Graphical view]
    PRINTSiPR00628. INSULINRSI.
    SMARTiSM00233. PH. 1 hit.
    SM00310. PTBI. 1 hit.
    [Graphical view]
    PROSITEiPS51064. IRS_PTB. 1 hit.
    PS50003. PH_DOMAIN. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P35569-1 [UniParc]FASTAAdd to Basket

    « Hide

    MASPPDTDGF SDVRKVGYLR KPKSMHKRFF VLRAASEAGG PARLEYYENE     50
    KKWRHKSSAP KRSIPLESCF NINKRADSKN KHLVALYTRD EHFAIAADSE 100
    AEQDSWYQAL LQLHNRAKAH HDGAGGGCGG SCSGSSGVGE AGEDLSYDTG 150
    PGPAFKEVWQ VILKPKGLGQ TKNLIGIYRL CLTSKTISFV KLNSEAAAVV 200
    LQLMNIRRCG HSENFFFIEV GRSAVTGPGE FWMQVDDSVV AQNMHETILE 250
    AMRAMSDEFR PRSKSQSSSS CSNPISVPLR RHHLNNPPPS QVGLTRRSRT 300
    ESITATSPAS MVGGKPGSFR VRASSDGEGT MSRPASVDGS PVSPSTNRTH 350
    AHRHRGSSRL HPPLNHSRSI PMPSSRCSPS ATSPVSLSSS STSGHGSTSD 400
    CLFPRRSSAS VSGSPSDGGF ISSDEYGSSP CDFRSSFRSV TPDSLGHTPP 450
    ARGEEELSNY ICMGGKGAST LAAPNGHYIL SRGGNGHRYI PGANLGTSPA 500
    LPGDEAAGAA DLDNRFRKRT HSAGTSPTIS HQKTPSQSSV ASIEEYTEMM 550
    PAAYPPGGGS GGRLPGYRHS AFVPTHSYPE EGLEMHHLER RGGHHRPDTS 600
    NLHTDDGYMP MSPGVAPVPS NRKGNGDYMP MSPKSVSAPQ QIINPIRRHP 650
    QRVDPNGYMM MSPSGSCSPD IGGGSSSSSS ISAAPSGSSY GKPWTNGVGG 700
    HHTHALPHAK PPVESGGGKL LPCTGDYMNM SPVGDSNTSS PSECYYGPED 750
    PQHKPVLSYY SLPRSFKHTQ RPGEPEEGAR HQHLRLSSSS GRLRYTATAE 800
    DSSSSTSSDS LGGGYCGARP ESSLTHPHHH VLQPHLPRKV DTAAQTNSRL 850
    ARPTRLSLGD PKASTLPRVR EQQQQQQSSL HPPEPKSPGE YVNIEFGSGQ 900
    PGYLAGPATS RSSPSVRCPP QLHPAPREET GSEEYMNMDL GPGRRATWQE 950
    SGGVELGRIG PAPPGSATVC RPTRSVPNSR GDYMTMQIGC PRQSYVDTSP 1000
    VAPVSYADMR TGIAAEKASL PRPTGAAPPP SSTASSSASV TPQGATAEQA 1050
    THSSLLGGPQ GPGGMSAFTR VNLSPNHNQS AKVIRADTQG CRRRHSSETF 1100
    SAPTRAGNTV PFGAGAAVGG SGGGGGGGSE DVKRHSSASF ENVWLRPGDL 1150
    GGVSKESAPV CGAAGGLEKS LNYIDLDLAK EHSQDCPSQQ QSLPPPPPHQ 1200
    PLGSNEGNSP RRSSEDLSNY ASISFQKQPE DRQ 1233
    Length:1,233
    Mass (Da):130,723
    Last modified:June 1, 1994 - v1
    Checksum:iC0E9B2D890DADD87
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti1038 – 10392Missing(PubMed:8448209)Curated
    Sequence conflicti1182 – 11821H → R in CAA49378. (PubMed:8448209)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L24563 mRNA. Translation: AAA39335.1.
    X69722 mRNA. Translation: CAA49378.1.
    PIRiS30185.
    RefSeqiNP_034700.2. NM_010570.4.
    XP_006496504.1. XM_006496441.1.
    UniGeneiMm.4952.

    Genome annotation databases

    GeneIDi16367.
    KEGGimmu:16367.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L24563 mRNA. Translation: AAA39335.1 .
    X69722 mRNA. Translation: CAA49378.1 .
    PIRi S30185.
    RefSeqi NP_034700.2. NM_010570.4.
    XP_006496504.1. XM_006496441.1.
    UniGenei Mm.4952.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1AYB X-ray 3.00 P 887-898 [» ]
    ProteinModelPortali P35569.
    SMRi P35569. Positions 11-262.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 200788. 8 interactions.
    DIPi DIP-32456N.
    IntActi P35569. 45 interactions.
    MINTi MINT-1540686.
    STRINGi 10090.ENSMUSP00000063795.

    PTM databases

    PhosphoSitei P35569.

    Proteomic databases

    PRIDEi P35569.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 16367.
    KEGGi mmu:16367.

    Organism-specific databases

    CTDi 3667.
    MGIi MGI:99454. Irs1.

    Phylogenomic databases

    eggNOGi NOG81285.
    HOGENOMi HOG000113103.
    HOVERGENi HBG000542.
    InParanoidi P35569.
    KOi K16172.
    PhylomeDBi P35569.

    Enzyme and pathway databases

    Reactomei REACT_169390. Signaling by Leptin.
    REACT_205300. PI3K/AKT activation.

    Miscellaneous databases

    EvolutionaryTracei P35569.
    NextBioi 289484.
    PROi P35569.
    SOURCEi Search...

    Gene expression databases

    CleanExi MM_IRS1.
    Genevestigatori P35569.

    Family and domain databases

    Gene3Di 2.30.29.30. 2 hits.
    InterProi IPR002404. Insln_rcpt_S1.
    IPR001849. PH_domain.
    IPR011993. PH_like_dom.
    [Graphical view ]
    Pfami PF02174. IRS. 1 hit.
    PF00169. PH. 1 hit.
    [Graphical view ]
    PRINTSi PR00628. INSULINRSI.
    SMARTi SM00233. PH. 1 hit.
    SM00310. PTBI. 1 hit.
    [Graphical view ]
    PROSITEi PS51064. IRS_PTB. 1 hit.
    PS50003. PH_DOMAIN. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Cloning of the mouse insulin receptor substrate-1 (IRS-1) gene and complete sequence of mouse IRS-1."
      Araki E., Haag B.L. III, Kahn C.R.
      Biochim. Biophys. Acta 1221:353-356(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "The insulin-elicited 160 kDa phosphotyrosine protein in mouse adipocytes is an insulin receptor substrate 1: identification by cloning."
      Keller S.R., Aebersold R., Garner C.W., Lienhard G.E.
      Biochim. Biophys. Acta 1172:323-326(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. "The protein-tyrosine kinase fer associates with signaling complexes containing insulin receptor substrate-1 and phosphatidylinositol 3-kinase."
      Iwanishi M., Czech M.P., Cherniack A.D.
      J. Biol. Chem. 275:38995-39000(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH FER.
    4. "Cloning and characterization of PHIP, a novel insulin receptor substrate-1 pleckstrin homology domain interacting protein."
      Farhang-Fallah J., Yin X., Trentin G., Cheng A.M., Rozakis-Adcock M.
      J. Biol. Chem. 275:40492-40497(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PHIP.
    5. "Insulin receptor substrate-1 in osteoblast is indispensable for maintaining bone turnover."
      Ogata N., Chikazu D., Kubota N., Terauchi Y., Tobe K., Azuma Y., Ohta T., Kadowaki T., Nakamura K., Kawaguchi H.
      J. Clin. Invest. 105:935-943(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    6. "5'-AMP-activated protein kinase phosphorylates IRS-1 on Ser-789 in mouse C2C12 myotubes in response to 5-aminoimidazole-4-carboxamide riboside."
      Jakobsen S.N., Hardie D.G., Morrice N., Tornqvist H.E.
      J. Biol. Chem. 276:46912-46916(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-789.
    7. "Control of cell size through phosphorylation of upstream binding factor 1 by nuclear phosphatidylinositol 3-kinase."
      Drakas R., Tu X., Baserga R.
      Proc. Natl. Acad. Sci. U.S.A. 101:9272-9276(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH UBTF AND PIK3CA, EFFECT ON CELL AND BODY SIZE.
    8. Cited for: PHOSPHORYLATION AT SER-632.
    9. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-340 AND SER-1097, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    10. "Double-stranded RNA-activated protein kinase is a key modulator of insulin sensitivity in physiological conditions and in obesity in mice."
      Carvalho-Filho M.A., Carvalho B.M., Oliveira A.G., Guadagnini D., Ueno M., Dias M.M., Tsukumo D.M., Hirabara S.M., Reis L.F., Curi R., Carvalheira J.B., Saad M.J.
      Endocrinology 153:5261-5274(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH EIF2AK2.

    Entry informationi

    Entry nameiIRS1_MOUSE
    AccessioniPrimary (citable) accession number: P35569
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 1, 1994
    Last sequence update: June 1, 1994
    Last modified: October 1, 2014
    This is version 134 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3