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Protein

Insulin receptor substrate 1

Gene

Irs1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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).By similarity

GO - Molecular functioni

GO - Biological processi

  • cellular response to insulin stimulus Source: MGI
  • insulin-like growth factor receptor signaling pathway Source: UniProtKB
  • insulin receptor signaling pathway Source: MGI
  • lipid catabolic process Source: MGI
  • mammary gland development Source: MGI
  • negative regulation of insulin secretion Source: MGI
  • phosphatidylinositol 3-kinase signaling Source: MGI
  • phosphatidylinositol-mediated signaling Source: Reactome
  • positive regulation of cell migration Source: MGI
  • positive regulation of fatty acid beta-oxidation Source: MGI
  • positive regulation of glucose import Source: MGI
  • positive regulation of glucose import in response to insulin stimulus Source: MGI
  • positive regulation of glucose metabolic process Source: MGI
  • positive regulation of glycogen biosynthetic process Source: MGI
  • positive regulation of mesenchymal cell proliferation Source: MGI
  • positive regulation of phosphatidylinositol 3-kinase activity Source: MGI
  • protein kinase B signaling Source: MGI
  • protein localization to nucleus Source: MGI
  • regulation of gene expression Source: MGI
  • response to insulin Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Transducer

Enzyme and pathway databases

ReactomeiR-MMU-198203. PI3K/AKT activation.
R-MMU-2586551. Signaling by Leptin.

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
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:99454. Irs1.

Subcellular locationi

GO - Cellular componenti

  • caveola Source: MGI
  • ciliary basal body Source: MGI
  • cytoplasm Source: MGI
  • cytosol Source: GO_Central
  • nucleus Source: MGI
  • plasma membrane Source: MGI
Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000842371 – 1233Insulin receptor substrate 1Add BLAST1233

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei3PhosphoserineBy similarity1
Modified residuei99Phosphoserine; by CK2By similarity1
Modified residuei265Phosphoserine; by RPS6KB1By similarity1
Modified residuei302Phosphoserine; by RPS6KB1By similarity1
Modified residuei307Phosphoserine; by IKKB, MAPK8 and RPS6KB1By similarity1
Modified residuei318PhosphoserineBy similarity1
Modified residuei325PhosphoserineCombined sources1
Modified residuei340PhosphoserineCombined sources1
Modified residuei343PhosphoserineBy similarity1
Modified residuei414PhosphoserineCombined sources1
Modified residuei441PhosphothreonineBy similarity1
Modified residuei448PhosphothreonineBy similarity1
Modified residuei460Phosphotyrosine; by INSRBy similarity1
Modified residuei522Phosphoserine; by RPS6KB1By similarity1
Modified residuei608Phosphotyrosine; by INSRBy similarity1
Modified residuei628Phosphotyrosine; by INSRBy similarity1
Modified residuei632Phosphoserine; by RPS6KB1 and ROCK21 Publication1
Modified residuei658PhosphotyrosineBy similarity1
Modified residuei789Phosphoserine; by AMPK and SIK21 Publication1
Modified residuei887PhosphoserineCombined sources1
Modified residuei891Phosphotyrosine; by INSRBy similarity1
Modified residuei935Phosphotyrosine; by INSRBy similarity1
Modified residuei983Phosphotyrosine; by INSRBy similarity1
Modified residuei1096PhosphoserineCombined sources1
Modified residuei1097PhosphoserineCombined sources1
Modified residuei1173Phosphotyrosine; by INSRBy similarity1
Modified residuei1220Phosphotyrosine; by INSRBy similarity1

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

MaxQBiP35569.
PaxDbiP35569.
PeptideAtlasiP35569.
PRIDEiP35569.

PTM databases

iPTMnetiP35569.
PhosphoSitePlusiP35569.
SwissPalmiP35569.

Expressioni

Tissue specificityi

Expressed in osteoblasts, but not in osteoclasts.1 Publication

Gene expression databases

CleanExiMM_IRS1.

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.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi200788. 10 interactors.
DIPiDIP-32456N.
IntActiP35569. 47 interactors.
MINTiMINT-1540686.
STRINGi10090.ENSMUSP00000063795.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AYBX-ray3.00P887-898[»]
5AXIX-ray2.50E606-610[»]
ProteinModelPortaliP35569.
SMRiP35569.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP35569.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini12 – 115PHPROSITE-ProRule annotationAdd BLAST104
Domaini155 – 259IRS-type PTBPROSITE-ProRule annotationAdd BLAST105

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni3 – 133Mediates interaction with PHIPBy similarityAdd BLAST131
Regioni891 – 893GRB2-bindingBy similarity3

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi460 – 463YXXM motif 14
Motifi546 – 549YXXM motif 24
Motifi608 – 611YXXM motif 34
Motifi628 – 631YXXM motif 44
Motifi658 – 661YXXM motif 54
Motifi727 – 730YXXM motif 64
Motifi935 – 938YXXM motif 74
Motifi983 – 986YXXM motif 84
Motifi1006 – 1009YXXM motif 94

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi675 – 680Poly-Ser6
Compositional biasi872 – 877Poly-Gln6
Compositional biasi1119 – 1128Poly-Gly10
Compositional biasi1194 – 1198Poly-Pro5

Sequence similaritiesi

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

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410IXEK. Eukaryota.
ENOG410Z9EP. LUCA.
HOGENOMiHOG000113103.
HOVERGENiHBG000542.
InParanoidiP35569.
KOiK16172.
PhylomeDBiP35569.

Family and domain databases

CDDicd01204. PTB_IRS. 1 hit.
Gene3Di2.30.29.30. 2 hits.
InterProiIPR002404. IRS_PTB.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
[Graphical view]
PfamiPF02174. IRS. 1 hit.
PF00169. PH. 1 hit.
[Graphical view]
PRINTSiPR00628. INSULINRSI.
SMARTiSM00233. PH. 1 hit.
SM00310. PTBI. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 2 hits.
PROSITEiPS51064. IRS_PTB. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P35569-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASPPDTDGF SDVRKVGYLR KPKSMHKRFF VLRAASEAGG PARLEYYENE
60 70 80 90 100
KKWRHKSSAP KRSIPLESCF NINKRADSKN KHLVALYTRD EHFAIAADSE
110 120 130 140 150
AEQDSWYQAL LQLHNRAKAH HDGAGGGCGG SCSGSSGVGE AGEDLSYDTG
160 170 180 190 200
PGPAFKEVWQ VILKPKGLGQ TKNLIGIYRL CLTSKTISFV KLNSEAAAVV
210 220 230 240 250
LQLMNIRRCG HSENFFFIEV GRSAVTGPGE FWMQVDDSVV AQNMHETILE
260 270 280 290 300
AMRAMSDEFR PRSKSQSSSS CSNPISVPLR RHHLNNPPPS QVGLTRRSRT
310 320 330 340 350
ESITATSPAS MVGGKPGSFR VRASSDGEGT MSRPASVDGS PVSPSTNRTH
360 370 380 390 400
AHRHRGSSRL HPPLNHSRSI PMPSSRCSPS ATSPVSLSSS STSGHGSTSD
410 420 430 440 450
CLFPRRSSAS VSGSPSDGGF ISSDEYGSSP CDFRSSFRSV TPDSLGHTPP
460 470 480 490 500
ARGEEELSNY ICMGGKGAST LAAPNGHYIL SRGGNGHRYI PGANLGTSPA
510 520 530 540 550
LPGDEAAGAA DLDNRFRKRT HSAGTSPTIS HQKTPSQSSV ASIEEYTEMM
560 570 580 590 600
PAAYPPGGGS GGRLPGYRHS AFVPTHSYPE EGLEMHHLER RGGHHRPDTS
610 620 630 640 650
NLHTDDGYMP MSPGVAPVPS NRKGNGDYMP MSPKSVSAPQ QIINPIRRHP
660 670 680 690 700
QRVDPNGYMM MSPSGSCSPD IGGGSSSSSS ISAAPSGSSY GKPWTNGVGG
710 720 730 740 750
HHTHALPHAK PPVESGGGKL LPCTGDYMNM SPVGDSNTSS PSECYYGPED
760 770 780 790 800
PQHKPVLSYY SLPRSFKHTQ RPGEPEEGAR HQHLRLSSSS GRLRYTATAE
810 820 830 840 850
DSSSSTSSDS LGGGYCGARP ESSLTHPHHH VLQPHLPRKV DTAAQTNSRL
860 870 880 890 900
ARPTRLSLGD PKASTLPRVR EQQQQQQSSL HPPEPKSPGE YVNIEFGSGQ
910 920 930 940 950
PGYLAGPATS RSSPSVRCPP QLHPAPREET GSEEYMNMDL GPGRRATWQE
960 970 980 990 1000
SGGVELGRIG PAPPGSATVC RPTRSVPNSR GDYMTMQIGC PRQSYVDTSP
1010 1020 1030 1040 1050
VAPVSYADMR TGIAAEKASL PRPTGAAPPP SSTASSSASV TPQGATAEQA
1060 1070 1080 1090 1100
THSSLLGGPQ GPGGMSAFTR VNLSPNHNQS AKVIRADTQG CRRRHSSETF
1110 1120 1130 1140 1150
SAPTRAGNTV PFGAGAAVGG SGGGGGGGSE DVKRHSSASF ENVWLRPGDL
1160 1170 1180 1190 1200
GGVSKESAPV CGAAGGLEKS LNYIDLDLAK EHSQDCPSQQ QSLPPPPPHQ
1210 1220 1230
PLGSNEGNSP RRSSEDLSNY ASISFQKQPE DRQ
Length:1,233
Mass (Da):130,723
Last modified:June 1, 1994 - v1
Checksum:iC0E9B2D890DADD87
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1038 – 1039Missing (PubMed:8448209).Curated2
Sequence conflicti1182H → R in CAA49378 (PubMed:8448209).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L24563 mRNA. Translation: AAA39335.1.
X69722 mRNA. Translation: CAA49378.1.
PIRiS30185.
RefSeqiNP_034700.2. NM_010570.4.
UniGeneiMm.4952.

Genome annotation databases

GeneIDi16367.
KEGGimmu:16367.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L24563 mRNA. Translation: AAA39335.1.
X69722 mRNA. Translation: CAA49378.1.
PIRiS30185.
RefSeqiNP_034700.2. NM_010570.4.
UniGeneiMm.4952.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AYBX-ray3.00P887-898[»]
5AXIX-ray2.50E606-610[»]
ProteinModelPortaliP35569.
SMRiP35569.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200788. 10 interactors.
DIPiDIP-32456N.
IntActiP35569. 47 interactors.
MINTiMINT-1540686.
STRINGi10090.ENSMUSP00000063795.

PTM databases

iPTMnetiP35569.
PhosphoSitePlusiP35569.
SwissPalmiP35569.

Proteomic databases

MaxQBiP35569.
PaxDbiP35569.
PeptideAtlasiP35569.
PRIDEiP35569.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi16367.
KEGGimmu:16367.

Organism-specific databases

CTDi3667.
MGIiMGI:99454. Irs1.

Phylogenomic databases

eggNOGiENOG410IXEK. Eukaryota.
ENOG410Z9EP. LUCA.
HOGENOMiHOG000113103.
HOVERGENiHBG000542.
InParanoidiP35569.
KOiK16172.
PhylomeDBiP35569.

Enzyme and pathway databases

ReactomeiR-MMU-198203. PI3K/AKT activation.
R-MMU-2586551. Signaling by Leptin.

Miscellaneous databases

ChiTaRSiIrs1. mouse.
EvolutionaryTraceiP35569.
PROiP35569.
SOURCEiSearch...

Gene expression databases

CleanExiMM_IRS1.

Family and domain databases

CDDicd01204. PTB_IRS. 1 hit.
Gene3Di2.30.29.30. 2 hits.
InterProiIPR002404. IRS_PTB.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
[Graphical view]
PfamiPF02174. IRS. 1 hit.
PF00169. PH. 1 hit.
[Graphical view]
PRINTSiPR00628. INSULINRSI.
SMARTiSM00233. PH. 1 hit.
SM00310. PTBI. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 2 hits.
PROSITEiPS51064. IRS_PTB. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: November 2, 2016
This is version 154 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.