Insulin receptor substrate 1 - Mus musculus (Mouse)

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P35569 (IRS1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 122. History...

Clusters with 100%, 90%, 50% identity |

Documents (3) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Insulin receptor substrate 1
Short name=IRS-1

Gene names

Name:	Irs1
Synonyms:	Irs-1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1233 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Ref.3 Ref.4 Ref.7
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. Phospsphorylated 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
Domain	Repeat
Molecular function	Transducer
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	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 cascade 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_component	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_function	SH2 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 phospholipid binding Inferred from electronic annotation. Source: InterPro 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
Eif2ak2	Q03963	2	EBI-400825,EBI-2603444
TP53BP2	Q13625-2	2	EBI-400825,EBI-287091	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1233

1233

Insulin receptor substrate 1

PRO_0000084237

Regions

Domain

12 – 115

104

Domain

155 – 259

105

IRS-type PTB

Region

3 – 133

131

Mediates interaction with PHIP By similarity

Region

891 – 893

GRB2-binding By similarity

Motif

460 – 463

YXXM motif 1

Motif

546 – 549

YXXM motif 2

Motif

608 – 611

YXXM motif 3

Motif

628 – 631

YXXM motif 4

Motif

658 – 661

YXXM motif 5

Motif

727 – 730

YXXM motif 6

Motif

935 – 938

YXXM motif 7

Motif

983 – 986

YXXM motif 8

Motif

1006 – 1009

YXXM motif 9

Compositional bias

675 – 680

Poly-Ser

Compositional bias

872 – 877

Poly-Gln

Compositional bias

1119 – 1128

Poly-Gly

Compositional bias

1194 – 1198

Poly-Pro

Amino acid modifications

Modified residue

Phosphoserine Ref.9

Modified residue

Phosphoserine; by CK2 By similarity

Modified residue

265

Phosphoserine; by RPS6KB1 By similarity

Modified residue

302

Phosphoserine; by RPS6KB1 By similarity

Modified residue

307

Phosphoserine By similarity

Modified residue

324

Phosphoserine Ref.9

Modified residue

340

Phosphoserine Ref.9

Modified residue

343

Phosphoserine By similarity

Modified residue

460

Phosphotyrosine; by INSR By similarity

Modified residue

608

Phosphotyrosine; by INSR By similarity

Modified residue

628

Phosphotyrosine; by INSR By similarity

Modified residue

632

Phosphoserine; by RPS6KB1 and ROCK2 Probable

Modified residue

658

Phosphotyrosine By similarity

Modified residue

789

Phosphoserine; by AMPK and SIK2 Ref.6

Modified residue

891

Phosphotyrosine; by INSR By similarity

Modified residue

935

Phosphotyrosine; by INSR By similarity

Modified residue

983

Phosphotyrosine; by INSR By similarity

Modified residue

1097

Phosphoserine; by RPS6KB1 and PKC/PRKCQ By similarity

Modified residue

1139

Phosphoserine Ref.9

Modified residue

1173

Phosphotyrosine; by INSR By similarity

Modified residue

1214

Phosphoserine Ref.9

Modified residue

1220

Phosphotyrosine; by INSR By similarity

Experimental info

Sequence conflict

1038 – 1039

Missing Ref.2

Sequence conflict

1182

H → R in CAA49378. Ref.2

Sequences

Sequence

Length

Mass (Da)

Tools

P35569 [UniParc].

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

FASTA

1,233

130,723

        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' referencesShow '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-3; SER-324; SER-340; SER-1139 AND SER-1214, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L24563 mRNA. Translation: AAA39335.1.
X69722 mRNA. Translation: CAA49378.1.

IPI

IPI00119627.

PIR

S30185.

RefSeq

NP_034700.2. NM_010570.4.

UniGene

Mm.4952.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AYB	X-ray	3.00	P	887-898	[»]

ProteinModelPortal

P35569.

SMR

P35569. Positions 11-262.

ModBase

Search...

Protein-protein interaction databases

IntAct

P35569. 39 interactions.

MINT

MINT-1540686.

STRING

10090.ENSMUSP00000063795.

PTM databases

PhosphoSite

P35569.

Proteomic databases

PRIDE

P35569.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

16367.

KEGG

mmu:16367.

Organism-specific databases

CTD

3667.

MGI

MGI:99454. Irs1.

Phylogenomic databases

eggNOG

NOG81285.

HOGENOM

HOG000113103.

HOVERGEN

HBG000542.

InParanoid

P35569.

K16172.

OrthoDB

EOG4J6RQG.

Enzyme and pathway databases

Reactome

REACT_115202. Signal Transduction.

Gene expression databases

CleanEx

MM_IRS1.

Genevestigator

P35569.

GermOnline

ENSMUSG00000055980. Mus musculus.

Family and domain databases

Gene3D

2.30.29.30. 2 hits.

InterPro

IPR002404. Insln_rcpt_S1.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
[Graphical view]

Pfam

PF02174. IRS. 1 hit.
PF00169. PH. 1 hit.
[Graphical view]

PRINTS

PR00628. INSULINRSI.

SMART

SM00233. PH. 1 hit.
SM00310. PTBI. 1 hit.
[Graphical view]

PROSITE

PS51064. IRS_PTB. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P35569.

NextBio

289484.

SOURCE

Search...

Entry information

Entry name

IRS1_MOUSE

Accession

Primary (citable) accession number: P35569

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	June 1, 1994
Last modified:	April 3, 2013
This is version 122 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

MGD cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents