Insulin receptor substrate 1 - Mus musculus (Mouse)

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Reviewed, UniProtKB/Swiss-Prot P35569 (IRS1_MOUSE)

Last modified October 13, 2009. Version 90. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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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)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

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

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Protein attributes

Sequence length	1233 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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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. Interacts with SOCS7 By similarity.
Subunit structure	Interacts with the NPXY motif of tyrosine-phosphorylated IGF1R and INSR via the PTB domain. Binds to phosphatidylinositol 3-kinase p85 subunit via the phosphorylated YXXM motifs. Binds ROCK1 By similarity. Binds to UBTF and PIK3CA in nuclear extracts.
Tissue specificity	Expressed in osteoblasts, but not in osteoclasts. Ref.3
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.
Sequence similarities	Contains 1 IRS-type PTB domain. Contains 1 PH domain.

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Ontologies

Keywords
Domain	Repeat
Molecular function	Transducer
PTM	Phosphoprotein
Technical term	3D-structure
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 mammary gland development Inferred from genetic interaction. Source: MGI positive regulation of cell migration Inferred from genetic interaction. Source: MGI positive regulation of mesenchymal cell proliferation Inferred from genetic interaction. Source: MGI protein kinase B signaling cascade Inferred from genetic interaction. Source: MGI
Cellular component	cytosol Inferred from Experiment. Source: Reactome microsome Inferred from direct assay. Source: MGI nucleus Inferred from direct assay. 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 phosphoinositide 3-kinase binding Inferred from sequence or structural similarity. Source: UniProtKB protein kinase binding Inferred from direct assay. Source: MGI signal transducer activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
Phip	Q8VDD9	1	EBI-400825,EBI-1369766
TP53BP2	Q13625-2	2	EBI-400825,EBI-287091	From a different organism.
Tp53bp2	Q8CG79	1	EBI-400825,EBI-645416

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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

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.5

Modified residue

Phosphotyrosine By similarity

Modified residue

Phosphoserine; by CK2 By similarity

Modified residue

307

Phosphoserine By similarity

Modified residue

324

Phosphoserine Ref.5

Modified residue

340

Phosphoserine Ref.5

Modified residue

460

Phosphotyrosine; by INSR By similarity

Modified residue

526

Phosphoserine By similarity

Modified residue

608

Phosphotyrosine; by INSR By similarity

Modified residue

628

Phosphotyrosine; by INSR By similarity

Modified residue

632

Phosphoserine By similarity

Modified residue

658

Phosphotyrosine By similarity

Modified residue

789

Phosphoserine; by SNF1LK2 By similarity

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 similarity

Modified residue

1139

Phosphoserine Ref.5

Modified residue

1173

Phosphotyrosine; by INSR By similarity

Modified residue

1214

Phosphoserine Ref.5

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

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Sequences

Sequence

Length

Mass (Da)

Tools

P35569-1 [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

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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: 8167159] [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: 8448209] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"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: 10749573] [Abstract] Cited for: TISSUE SPECIFICITY.
[4]	"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: 15197263] [Abstract] Cited for: INTERACTION WITH UBTF AND PIK3CA, EFFECT ON CELL AND BODY SIZE.
[5]	"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: 17242355] [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.

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Cross-references

Sequence databases

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

IPI

IPI00119627.

PIR

S30185.

RefSeq

NP_034700.2.

UniGene

Mm.4952

3D structure databases

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

ModBase

Search...

Protein-protein interaction databases

IntAct

P35569. 37 interactions.

STRING

P35569.

PTM databases

PhosphoSite

P35569.

Proteomic databases

PRIDE

P35569.

Genome annotation databases

Ensembl

ENSMUST00000069799; ENSMUSP00000063795; ENSMUSG00000055980; Mus musculus. [Genome view]

GeneID

16367.

KEGG

mmu:16367.

UCSC

R11A8.6. c. elegans.

Organism-specific databases

MGI

MGI:99454. Irs1.

Phylogenomic databases

HOGENOM

P35569.

HOVERGEN

P35569.

Gene expression databases

ArrayExpress

P35569.

Bgee

P35569.

CleanEx

MM_IRS1.

Genevestigator

P35569.

GermOnline

ENSMUSG00000055980. Mus musculus.

Family and domain databases

InterPro

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

Gene3D

G3DSA:2.30.29.30. PH_type. 2 hits.

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 Resources

SOURCE

Search...

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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:	October 13, 2009
This is version 90 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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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 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

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents