Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Insulin receptor substrate 2

Gene

Irs2

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.

GO - Molecular functioni

  • insulin receptor binding Source: GO_Central
  • phosphatidylinositol 3-kinase binding Source: MGI
  • protein kinase binding Source: MGI
  • signal transducer activity Source: GO_Central

GO - Biological processi

  • brain development Source: MGI
  • cell proliferation Source: MGI
  • cellular response to glucose stimulus Source: Ensembl
  • cellular response to insulin stimulus Source: MGI
  • insulin receptor signaling pathway Source: MGI
  • mammary gland development Source: MGI
  • negative regulation of B cell apoptotic process Source: BHF-UCL
  • negative regulation of kinase activity Source: BHF-UCL
  • negative regulation of plasma membrane long-chain fatty acid transport Source: MGI
  • phosphatidylinositol-mediated signaling Source: Reactome
  • positive regulation of B cell proliferation Source: BHF-UCL
  • positive regulation of cell migration Source: MGI
  • positive regulation of cell proliferation Source: MGI
  • positive regulation of fatty acid beta-oxidation Source: MGI
  • positive regulation of glucose import Source: MGI
  • positive regulation of glucose metabolic process Source: MGI
  • positive regulation of glycogen biosynthetic process Source: MGI
  • positive regulation of insulin secretion Source: BHF-UCL
  • positive regulation of mesenchymal cell proliferation Source: MGI
  • regulation of lipid metabolic process Source: GO_Central
  • response to glucose Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Transducer

Enzyme and pathway databases

ReactomeiR-MMU-109704. PI3K Cascade.
R-MMU-112412. SOS-mediated signalling.
R-MMU-1257604. PIP3 activates AKT signaling.
R-MMU-198203. PI3K/AKT activation.
R-MMU-2428928. IRS-related events triggered by IGF1R.
R-MMU-2586551. Signaling by Leptin.
R-MMU-2586552. Signaling by Leptin.
R-MMU-5673001. RAF/MAP kinase cascade.
R-MMU-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
R-MMU-74713. IRS activation.
R-MMU-74749. Signal attenuation.
R-MMU-8853659. RET signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Insulin receptor substrate 2
Short name:
IRS-2
Alternative name(s):
4PS
Gene namesi
Name:Irs2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:109334. Irs2.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: MGI
  • plasma membrane Source: MGI
  • protein complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000842401 – 1321Insulin receptor substrate 2Add BLAST1321

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei303PhosphoserineBy similarity1
Modified residuei343PhosphoserineBy similarity1
Modified residuei347PhosphothreonineBy similarity1
Modified residuei362PhosphoserineBy similarity1
Modified residuei381PhosphoserineBy similarity1
Modified residuei385PhosphoserineCombined sources1
Modified residuei388PhosphoserineCombined sources1
Modified residuei409Omega-N-methylarginineBy similarity1
Modified residuei517PhosphothreonineBy similarity1
Modified residuei520PhosphoserineBy similarity1
Modified residuei524PhosphothreonineCombined sources1
Modified residuei536Phosphotyrosine; by INSRBy similarity1
Modified residuei556PhosphoserineBy similarity1
Modified residuei573PhosphoserineBy similarity1
Modified residuei575PhosphothreonineBy similarity1
Modified residuei576PhosphothreonineBy similarity1
Modified residuei590PhosphoserineBy similarity1
Modified residuei604PhosphoserineBy similarity1
Modified residuei616PhosphoserineBy similarity1
Modified residuei649PhosphotyrosineCombined sources1
Modified residuei671Phosphotyrosine; by INSRBy similarity1
Modified residuei675PhosphoserineBy similarity1
Modified residuei678PhosphoserineBy similarity1
Modified residuei727PhosphoserineBy similarity1
Modified residuei728PhosphoserineCombined sources1
Modified residuei762PhosphoserineBy similarity1
Modified residuei771PhosphothreonineBy similarity1
Modified residuei796PhosphoserineBy similarity1
Modified residuei819PhosphoserineBy similarity1
Modified residuei907PhosphoserineCombined sources1
Modified residuei911Phosphotyrosine; by INSRBy similarity1
Modified residuei965PhosphoserineBy similarity1
Modified residuei970Phosphotyrosine; by INSRBy similarity1
Modified residuei1071PhosphothreonineBy similarity1
Modified residuei1089PhosphoserineBy similarity1
Modified residuei1148PhosphothreonineBy similarity1
Modified residuei1151PhosphoserineCombined sources1
Modified residuei1163PhosphoserineBy similarity1
Modified residuei1165PhosphoserineCombined sources1
Modified residuei1175PhosphoserineBy similarity1
Modified residuei1190PhosphoserineBy similarity1
Modified residuei1242Phosphotyrosine; by INSRBy similarity1
Modified residuei1303Phosphotyrosine; by INSRBy similarity1

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

EPDiP81122.
MaxQBiP81122.
PaxDbiP81122.
PeptideAtlasiP81122.
PRIDEiP81122.

PTM databases

iPTMnetiP81122.
PhosphoSitePlusiP81122.

Expressioni

Tissue specificityi

Skeletal muscle, lung, brain, liver, kidney, heart and spleen.

Gene expression databases

BgeeiENSMUSG00000038894.
CleanExiMM_IRS2.
GenevisibleiP81122. MM.

Interactioni

Subunit structurei

Interacts with PHIP.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
Sirt1Q923E42EBI-1369862,EBI-1802585

GO - Molecular functioni

  • insulin receptor binding Source: GO_Central
  • phosphatidylinositol 3-kinase binding Source: MGI
  • protein kinase binding Source: MGI

Protein-protein interaction databases

BioGridi239306. 3 interactors.
DIPiDIP-39500N.
IntActiP81122. 4 interactors.
MINTiMINT-100745.
STRINGi10090.ENSMUSP00000038514.

Structurei

Secondary structure

11321
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi625 – 627Combined sources3
Beta strandi629 – 633Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3BU3X-ray1.65B620-634[»]
3BU5X-ray2.10B620-634[»]
3BU6X-ray1.95B620-634[»]
ProteinModelPortaliP81122.
SMRiP81122.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP81122.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini16 – 144PHPROSITE-ProRule annotationAdd BLAST129
Domaini191 – 295IRS-type PTBPROSITE-ProRule annotationAdd BLAST105

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi536 – 539YXXM motif 14
Motifi594 – 597YXXM motif 24
Motifi649 – 652YXXM motif 34
Motifi671 – 674YXXM motif 44
Motifi734 – 737YXXM motif 54
Motifi814 – 817YXXM motif 64
Motifi1061 – 1064YXXM motif 74

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi19 – 28Poly-Asn10
Compositional biasi444 – 449Poly-Ser6
Compositional biasi638 – 641Poly-Ser4
Compositional biasi936 – 939Poly-Ser4

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiENOG410IXEK. Eukaryota.
ENOG410Z9EP. LUCA.
GeneTreeiENSGT00530000063420.
HOGENOMiHOG000113103.
HOVERGENiHBG000542.
InParanoidiP81122.
KOiK07187.
OMAiWYRALTD.
OrthoDBiEOG091G02EF.
TreeFamiTF325994.

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.

P81122-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASAPLPGPP ASAGGDGPNL NNNNNNNNHS VRKCGYLRKQ KHGHKRFFVL
60 70 80 90 100
RGPGTGGDEA SAAGGSPPQP PRLEYYESEK KWRSKAGAPK RVIALDCCLN
110 120 130 140 150
INKRADAKHK YLIALYTKDE YFAVAAENEQ EQEGWYRALT DLVSEGRSGE
160 170 180 190 200
GGSGTTGGSC SASLPGVLGG SAGAAGCDDN YGLVTPATAV YREVWQVNLK
210 220 230 240 250
PKGLGQSKNL TGVYRLCLSA RTIGFVKLNC EQPSVTLQLM NIRRCGHSDS
260 270 280 290 300
FFFIEVGRSA VTGPGELWMQ ADDSVVAQNI HETILEAMKA LKELFEFRPR
310 320 330 340 350
SKSQSSGSSA THPISVPGAR RHHHLVNLPP SQTGLVRRSR TDSLAATPPA
360 370 380 390 400
AKCTSCRVRT ASEGDGGAAG GAGTAGGRPM SVAGSPLSPG PVRAPLSRSH
410 420 430 440 450
TLSAGCGGRP SKVTLAPAGG ALQHSRSMSM PVAHSPPAAT SPGSLSSSSG
460 470 480 490 500
HGSGSYPLPP GSHPHLPHPL HHPQGQRPSS GSASASGSPS DPGFMSLDEY
510 520 530 540 550
GSSPGDLRAF SSHRSNTPES IAETPPARDG SGGELYGYMS MDRPLSHCGR
560 570 580 590 600
PYRRVSGDGA QDLDRGLRKR TYSLTTPARQ RQVPQPSSAS LDEYTLMRAT
610 620 630 640 650
FSGSSGRLCP SFPASSPKVA YNPYPEDYGD IEIGSHKSSS SNLGADDGYM
660 670 680 690 700
PMTPGAALRS GGPNSCKSDD YMPMSPTSVS APKQILQPRL AAALPPSGAA
710 720 730 740 750
VPAPPSGVGR TFPVNGGGYK ASSPAESSPE DSGYMRMWCG SKLSMENPDP
760 770 780 790 800
KLLPNGDYLN MSPSEAGTAG TPPDFSAALR GGSEGLKGIP GHCYSSLPRS
810 820 830 840 850
YKAPCSCSGD NDQYVLMSSP VGRILEEERL EPQATPGAGT FGAAGGSHTQ
860 870 880 890 900
PHHSAVPSSM RPSAIGGRPE GFLGQRCRAV RPTRLSLEGL QTLPSMQEYP
910 920 930 940 950
LPTEPKSPGE YINIDFGEAG TRLSPPAPPL LASAASSSSL LSASSPASSL
960 970 980 990 1000
GSGTPGTSSD SRQRSPLSDY MNLDFSSPKS PKPSTRSGDT VGSMDGLLSP
1010 1020 1030 1040 1050
EASSPYPPLP PRPSTSPSSL QQPLPPAPGD LYRLPPASAA TSQGPTAGSS
1060 1070 1080 1090 1100
MSSEPGDNGD YTEMAFGVAA TPPQPIVAPP KPEGARVASP TSGLKRLSLM
1110 1120 1130 1140 1150
DQVSGVEAFL QVSQPPDPHR GAKVIRADPQ GGRRRHSSET FSSTTTVTPV
1160 1170 1180 1190 1200
SPSFAHNSKR HNSASVENVS LRKSSEGSST LGGGDEPPTS PGQAQPLVAV
1210 1220 1230 1240 1250
PPVPQARPWN PGQPGALIGC PGGSSSPMRR ETSVGFQNGL NYIAIDVRGE
1260 1270 1280 1290 1300
QGSLAQSQPQ PGDKNSWSRT RSLGGLLGTV GGSGASGVCG GPGTGALPSA
1310 1320
STYASIDFLS HHLKEATVVK E
Length:1,321
Mass (Da):136,763
Last modified:July 27, 2011 - v2
Checksum:i823A5458DA21C9C7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti13A → G no nucleotide entry (PubMed:7675087).Curated1
Sequence conflicti232Q → G no nucleotide entry (PubMed:7675087).Curated1
Sequence conflicti240M → N no nucleotide entry (PubMed:7675087).Curated1
Sequence conflicti428M → N no nucleotide entry (PubMed:7675087).Curated1
Sequence conflicti761M → K no nucleotide entry (PubMed:7675087).Curated1
Sequence conflicti916F → P no nucleotide entry (PubMed:7675087).Curated1
Sequence conflicti975F → P no nucleotide entry (PubMed:7675087).Curated1
Sequence conflicti1062T → S no nucleotide entry (PubMed:7675087).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC147580 mRNA. Translation: AAI47581.1.
CCDSiCCDS52477.1.
RefSeqiNP_001074681.1. NM_001081212.1.
UniGeneiMm.407207.

Genome annotation databases

EnsembliENSMUST00000040514; ENSMUSP00000038514; ENSMUSG00000038894.
GeneIDi384783.
KEGGimmu:384783.
UCSCiuc009kuz.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC147580 mRNA. Translation: AAI47581.1.
CCDSiCCDS52477.1.
RefSeqiNP_001074681.1. NM_001081212.1.
UniGeneiMm.407207.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3BU3X-ray1.65B620-634[»]
3BU5X-ray2.10B620-634[»]
3BU6X-ray1.95B620-634[»]
ProteinModelPortaliP81122.
SMRiP81122.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi239306. 3 interactors.
DIPiDIP-39500N.
IntActiP81122. 4 interactors.
MINTiMINT-100745.
STRINGi10090.ENSMUSP00000038514.

PTM databases

iPTMnetiP81122.
PhosphoSitePlusiP81122.

Proteomic databases

EPDiP81122.
MaxQBiP81122.
PaxDbiP81122.
PeptideAtlasiP81122.
PRIDEiP81122.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000040514; ENSMUSP00000038514; ENSMUSG00000038894.
GeneIDi384783.
KEGGimmu:384783.
UCSCiuc009kuz.1. mouse.

Organism-specific databases

CTDi8660.
MGIiMGI:109334. Irs2.

Phylogenomic databases

eggNOGiENOG410IXEK. Eukaryota.
ENOG410Z9EP. LUCA.
GeneTreeiENSGT00530000063420.
HOGENOMiHOG000113103.
HOVERGENiHBG000542.
InParanoidiP81122.
KOiK07187.
OMAiWYRALTD.
OrthoDBiEOG091G02EF.
TreeFamiTF325994.

Enzyme and pathway databases

ReactomeiR-MMU-109704. PI3K Cascade.
R-MMU-112412. SOS-mediated signalling.
R-MMU-1257604. PIP3 activates AKT signaling.
R-MMU-198203. PI3K/AKT activation.
R-MMU-2428928. IRS-related events triggered by IGF1R.
R-MMU-2586551. Signaling by Leptin.
R-MMU-2586552. Signaling by Leptin.
R-MMU-5673001. RAF/MAP kinase cascade.
R-MMU-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
R-MMU-74713. IRS activation.
R-MMU-74749. Signal attenuation.
R-MMU-8853659. RET signaling.

Miscellaneous databases

EvolutionaryTraceiP81122.
PROiP81122.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000038894.
CleanExiMM_IRS2.
GenevisibleiP81122. MM.

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 nameiIRS2_MOUSE
AccessioniPrimary (citable) accession number: P81122
Secondary accession number(s): B9EJW3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 27, 2011
Last modified: November 2, 2016
This is version 135 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, 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.