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P35569

- IRS1_MOUSE

UniProt

P35569 - IRS1_MOUSE

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Protein
Insulin receptor substrate 1
Gene
Irs1, Irs-1
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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.

GO - Molecular functioni

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

GO - Biological processi

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

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
Complete GO annotation...

PTM / Processingi

Molecule processing

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

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei99 – 991Phosphoserine; by CK2 By similarity
Modified residuei265 – 2651Phosphoserine; by RPS6KB1 By similarity
Modified residuei302 – 3021Phosphoserine; by RPS6KB1 By similarity
Modified residuei307 – 3071Phosphoserine; by IKKB, MAPK8 and RPS6KB1 By similarity
Modified residuei340 – 3401Phosphoserine1 Publication
Modified residuei343 – 3431Phosphoserine By similarity
Modified residuei460 – 4601Phosphotyrosine; by INSR By similarity
Modified residuei522 – 5221Phosphoserine; by RPS6KB1 By similarity
Modified residuei608 – 6081Phosphotyrosine; by INSR By similarity
Modified residuei628 – 6281Phosphotyrosine; by INSR By similarity
Modified residuei632 – 6321Phosphoserine; by RPS6KB1 and ROCK2 Inferred
Modified residuei658 – 6581Phosphotyrosine By similarity
Modified residuei789 – 7891Phosphoserine; by AMPK and SIK21 Publication
Modified residuei891 – 8911Phosphotyrosine; by INSR By similarity
Modified residuei935 – 9351Phosphotyrosine; by INSR By similarity
Modified residuei983 – 9831Phosphotyrosine; by INSR By similarity
Modified residuei1097 – 10971Phosphoserine; alternate1 Publication
Modified residuei1097 – 10971Phosphoserine; by RPS6KB1 and PKC/PRKCQ; alternate By similarity
Modified residuei1173 – 11731Phosphotyrosine; by INSR By similarity
Modified residuei1220 – 12201Phosphotyrosine; by INSR By 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.2 Publications
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.4 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.

Miscellaneous databases

EvolutionaryTraceiP35569.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini12 – 115104PH
Add
BLAST
Domaini155 – 259105IRS-type PTB
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni3 – 133131Mediates interaction with PHIP By similarity
Add
BLAST
Regioni891 – 8933GRB2-binding By 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 PH domain.

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

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti1038 – 10392Missing1 Publication
Sequence conflicti1182 – 11821H → R in CAA49378. 1 Publication

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...

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

« Hide 'large scale' publications
  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: September 3, 2014
This is version 133 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

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