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P35569 (IRS1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Insulin receptor substrate 1

Short name=IRS-1
Gene names
Name:Irs1
Synonyms:Irs-1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1233 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

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. Ref.3 Ref.4 Ref.7 Ref.10

Tissue specificity

Expressed in osteoblasts, but not in osteoclasts. Ref.5

Post-translational modification

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. Ref.6 Ref.8

Sequence similarities

Contains 1 IRS-type PTB domain.

Contains 1 PH domain.

Ontologies

Keywords
   DomainRepeat
   Molecular functionTransducer
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular response to insulin stimulus

Inferred from direct assay PubMed 11375348. Source: MGI

insulin receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

insulin-like growth factor receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

lipid catabolic process

Inferred from mutant phenotype PubMed 11375348. Source: MGI

mammary gland development

Inferred from genetic interaction PubMed 17662267. Source: MGI

positive regulation of cell migration

Inferred from genetic interaction PubMed 17662267. Source: MGI

positive regulation of mesenchymal cell proliferation

Inferred from genetic interaction PubMed 17662267. Source: MGI

positive regulation of phosphatidylinositol 3-kinase activity

Inferred from mutant phenotype PubMed 11375348. Source: MGI

protein kinase B signaling

Inferred from genetic interaction PubMed 15249583. Source: MGI

protein localization to nucleus

Inferred from direct assay PubMed 19952108. Source: MGI

regulation of gene expression

Inferred from mutant phenotype PubMed 11375348. Source: MGI

   Cellular_componentciliary basal body

Inferred from direct assay PubMed 19596798. Source: MGI

cytoplasm

Inferred from direct assay PubMed 12878164. Source: MGI

cytosol

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay PubMed 12878164. Source: MGI

plasma membrane

Inferred from direct assay PubMed 11375348. Source: MGI

   Molecular_functionSH2 domain binding

Inferred from sequence or structural similarity. Source: UniProtKB

insulin receptor binding

Inferred from sequence or structural similarity. Source: UniProtKB

insulin-like growth factor receptor binding

Inferred from sequence or structural similarity. Source: UniProtKB

phosphatidylinositol 3-kinase binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 17965023PubMed 18059474PubMed 20144759PubMed 20804756. Source: IntAct

protein kinase binding

Inferred from direct assay PubMed 14733908. Source: MGI

signal transducer activity

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 12331233Insulin receptor substrate 1
PRO_0000084237

Regions

Domain12 – 115104PH
Domain155 – 259105IRS-type PTB
Region3 – 133131Mediates interaction with PHIP By similarity
Region891 – 8933GRB2-binding By similarity
Motif460 – 4634YXXM motif 1
Motif546 – 5494YXXM motif 2
Motif608 – 6114YXXM motif 3
Motif628 – 6314YXXM motif 4
Motif658 – 6614YXXM motif 5
Motif727 – 7304YXXM motif 6
Motif935 – 9384YXXM motif 7
Motif983 – 9864YXXM motif 8
Motif1006 – 10094YXXM motif 9
Compositional bias675 – 6806Poly-Ser
Compositional bias872 – 8776Poly-Gln
Compositional bias1119 – 112810Poly-Gly
Compositional bias1194 – 11985Poly-Pro

Amino acid modifications

Modified residue991Phosphoserine; by CK2 By similarity
Modified residue2651Phosphoserine; by RPS6KB1 By similarity
Modified residue3021Phosphoserine; by RPS6KB1 By similarity
Modified residue3071Phosphoserine; by IKKB and MAPK8 By similarity
Modified residue3401Phosphoserine Ref.9
Modified residue3431Phosphoserine By similarity
Modified residue4601Phosphotyrosine; by INSR By similarity
Modified residue6081Phosphotyrosine; by INSR By similarity
Modified residue6281Phosphotyrosine; by INSR By similarity
Modified residue6321Phosphoserine; by RPS6KB1 and ROCK2 Probable
Modified residue6581Phosphotyrosine By similarity
Modified residue7891Phosphoserine; by AMPK and SIK2 Ref.6
Modified residue8911Phosphotyrosine; by INSR By similarity
Modified residue9351Phosphotyrosine; by INSR By similarity
Modified residue9831Phosphotyrosine; by INSR By similarity
Modified residue10971Phosphoserine; alternate Ref.9
Modified residue10971Phosphoserine; by RPS6KB1 and PKC/PRKCQ; alternate By similarity
Modified residue11731Phosphotyrosine; by INSR By similarity
Modified residue12201Phosphotyrosine; by INSR By similarity

Experimental info

Sequence conflict1038 – 10392Missing Ref.2
Sequence conflict11821H → R in CAA49378. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P35569 [UniParc].

Last modified June 1, 1994. Version 1.
Checksum: C0E9B2D890DADD87

FASTA1,233130,723
        10         20         30         40         50         60 
MASPPDTDGF SDVRKVGYLR KPKSMHKRFF VLRAASEAGG PARLEYYENE KKWRHKSSAP 

        70         80         90        100        110        120 
KRSIPLESCF NINKRADSKN KHLVALYTRD EHFAIAADSE AEQDSWYQAL LQLHNRAKAH 

       130        140        150        160        170        180 
HDGAGGGCGG SCSGSSGVGE AGEDLSYDTG PGPAFKEVWQ VILKPKGLGQ TKNLIGIYRL 

       190        200        210        220        230        240 
CLTSKTISFV KLNSEAAAVV LQLMNIRRCG HSENFFFIEV GRSAVTGPGE FWMQVDDSVV 

       250        260        270        280        290        300 
AQNMHETILE AMRAMSDEFR PRSKSQSSSS CSNPISVPLR RHHLNNPPPS QVGLTRRSRT 

       310        320        330        340        350        360 
ESITATSPAS MVGGKPGSFR VRASSDGEGT MSRPASVDGS PVSPSTNRTH AHRHRGSSRL 

       370        380        390        400        410        420 
HPPLNHSRSI PMPSSRCSPS ATSPVSLSSS STSGHGSTSD CLFPRRSSAS VSGSPSDGGF 

       430        440        450        460        470        480 
ISSDEYGSSP CDFRSSFRSV TPDSLGHTPP ARGEEELSNY ICMGGKGAST LAAPNGHYIL 

       490        500        510        520        530        540 
SRGGNGHRYI PGANLGTSPA LPGDEAAGAA DLDNRFRKRT HSAGTSPTIS HQKTPSQSSV 

       550        560        570        580        590        600 
ASIEEYTEMM PAAYPPGGGS GGRLPGYRHS AFVPTHSYPE EGLEMHHLER RGGHHRPDTS 

       610        620        630        640        650        660 
NLHTDDGYMP MSPGVAPVPS NRKGNGDYMP MSPKSVSAPQ QIINPIRRHP QRVDPNGYMM 

       670        680        690        700        710        720 
MSPSGSCSPD IGGGSSSSSS ISAAPSGSSY GKPWTNGVGG HHTHALPHAK PPVESGGGKL 

       730        740        750        760        770        780 
LPCTGDYMNM SPVGDSNTSS PSECYYGPED PQHKPVLSYY SLPRSFKHTQ RPGEPEEGAR 

       790        800        810        820        830        840 
HQHLRLSSSS GRLRYTATAE DSSSSTSSDS LGGGYCGARP ESSLTHPHHH VLQPHLPRKV 

       850        860        870        880        890        900 
DTAAQTNSRL ARPTRLSLGD PKASTLPRVR EQQQQQQSSL HPPEPKSPGE YVNIEFGSGQ 

       910        920        930        940        950        960 
PGYLAGPATS RSSPSVRCPP QLHPAPREET GSEEYMNMDL GPGRRATWQE SGGVELGRIG 

       970        980        990       1000       1010       1020 
PAPPGSATVC RPTRSVPNSR GDYMTMQIGC PRQSYVDTSP VAPVSYADMR TGIAAEKASL 

      1030       1040       1050       1060       1070       1080 
PRPTGAAPPP SSTASSSASV TPQGATAEQA THSSLLGGPQ GPGGMSAFTR VNLSPNHNQS 

      1090       1100       1110       1120       1130       1140 
AKVIRADTQG CRRRHSSETF SAPTRAGNTV PFGAGAAVGG SGGGGGGGSE DVKRHSSASF 

      1150       1160       1170       1180       1190       1200 
ENVWLRPGDL GGVSKESAPV CGAAGGLEKS LNYIDLDLAK EHSQDCPSQQ QSLPPPPPHQ 

      1210       1220       1230 
PLGSNEGNSP RRSSEDLSNY ASISFQKQPE DRQ 

« Hide

References

« Hide 'large scale' references
[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]"Role of Rho-kinase in regulation of insulin action and glucose homeostasis."
Furukawa N., Ongusaha P., Jahng W.J., Araki K., Choi C.S., Kim H.J., Lee Y.H., Kaibuchi K., Kahn B.B., Masuzaki H., Kim J.K., Lee S.W., Kim Y.B.
Cell Metab. 2:119-129(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-632.
[9]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L24563 mRNA. Translation: AAA39335.1.
X69722 mRNA. Translation: CAA49378.1.
PIRS30185.
RefSeqNP_034700.2. NM_010570.4.
XP_006496504.1. XM_006496441.1.
UniGeneMm.4952.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1AYBX-ray3.00P887-898[»]
ProteinModelPortalP35569.
SMRP35569. Positions 11-262.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid200788. 8 interactions.
DIPDIP-32456N.
IntActP35569. 45 interactions.
MINTMINT-1540686.
STRING10090.ENSMUSP00000063795.

PTM databases

PhosphoSiteP35569.

Proteomic databases

PRIDEP35569.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID16367.
KEGGmmu:16367.

Organism-specific databases

CTD3667.
MGIMGI:99454. Irs1.

Phylogenomic databases

eggNOGNOG81285.
HOGENOMHOG000113103.
HOVERGENHBG000542.
InParanoidP35569.
KOK16172.
PhylomeDBP35569.

Enzyme and pathway databases

ReactomeREACT_188257. Signal Transduction.
REACT_200794. Mus musculus biological processes.

Gene expression databases

CleanExMM_IRS1.
GenevestigatorP35569.

Family and domain databases

Gene3D2.30.29.30. 2 hits.
InterProIPR002404. Insln_rcpt_S1.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
[Graphical view]
PfamPF02174. IRS. 1 hit.
PF00169. PH. 1 hit.
[Graphical view]
PRINTSPR00628. INSULINRSI.
SMARTSM00233. PH. 1 hit.
SM00310. PTBI. 1 hit.
[Graphical view]
PROSITEPS51064. IRS_PTB. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP35569.
NextBio289484.
PROP35569.
SOURCESearch...

Entry information

Entry nameIRS1_MOUSE
AccessionPrimary (citable) accession number: P35569
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: June 11, 2014
This is version 132 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot