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.

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
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 13211321Insulin receptor substrate 2PRO_0000084240Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei303 – 3031PhosphoserineBy similarity
Modified residuei343 – 3431PhosphoserineBy similarity
Modified residuei347 – 3471PhosphothreonineBy similarity
Modified residuei362 – 3621PhosphoserineBy similarity
Modified residuei381 – 3811PhosphoserineBy similarity
Modified residuei385 – 3851PhosphoserineCombined sources
Modified residuei388 – 3881PhosphoserineCombined sources
Modified residuei517 – 5171PhosphothreonineBy similarity
Modified residuei520 – 5201PhosphoserineBy similarity
Modified residuei524 – 5241PhosphothreonineCombined sources
Modified residuei536 – 5361Phosphotyrosine; by INSRBy similarity
Modified residuei556 – 5561PhosphoserineBy similarity
Modified residuei573 – 5731PhosphoserineBy similarity
Modified residuei575 – 5751PhosphothreonineBy similarity
Modified residuei576 – 5761PhosphothreonineBy similarity
Modified residuei590 – 5901PhosphoserineBy similarity
Modified residuei604 – 6041PhosphoserineBy similarity
Modified residuei616 – 6161PhosphoserineBy similarity
Modified residuei649 – 6491PhosphotyrosineCombined sources
Modified residuei671 – 6711Phosphotyrosine; by INSRBy similarity
Modified residuei675 – 6751PhosphoserineBy similarity
Modified residuei678 – 6781PhosphoserineBy similarity
Modified residuei727 – 7271PhosphoserineBy similarity
Modified residuei728 – 7281PhosphoserineCombined sources
Modified residuei762 – 7621PhosphoserineBy similarity
Modified residuei771 – 7711PhosphothreonineBy similarity
Modified residuei796 – 7961PhosphoserineBy similarity
Modified residuei819 – 8191PhosphoserineBy similarity
Modified residuei907 – 9071PhosphoserineCombined sources
Modified residuei911 – 9111Phosphotyrosine; by INSRBy similarity
Modified residuei965 – 9651PhosphoserineBy similarity
Modified residuei970 – 9701Phosphotyrosine; by INSRBy similarity
Modified residuei1071 – 10711PhosphothreonineBy similarity
Modified residuei1089 – 10891PhosphoserineBy similarity
Modified residuei1148 – 11481PhosphothreonineBy similarity
Modified residuei1151 – 11511PhosphoserineCombined sources
Modified residuei1163 – 11631PhosphoserineBy similarity
Modified residuei1165 – 11651PhosphoserineCombined sources
Modified residuei1175 – 11751PhosphoserineBy similarity
Modified residuei1190 – 11901PhosphoserineBy similarity
Modified residuei1242 – 12421Phosphotyrosine; by INSRBy similarity
Modified residuei1303 – 13031Phosphotyrosine; by INSRBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP81122.
MaxQBiP81122.
PaxDbiP81122.
PeptideAtlasiP81122.
PRIDEiP81122.

PTM databases

iPTMnetiP81122.
PhosphoSiteiP81122.

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 interactions.
DIPiDIP-39500N.
IntActiP81122. 4 interactions.
MINTiMINT-100745.
STRINGi10090.ENSMUSP00000038514.

Structurei

Secondary structure

1
1321
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi625 – 6273Combined sources
Beta strandi629 – 6335Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3BU3X-ray1.65B620-634[»]
3BU5X-ray2.10B620-634[»]
3BU6X-ray1.95B620-634[»]
ProteinModelPortaliP81122.
SMRiP81122. Positions 31-300.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP81122.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini16 – 144129PHPROSITE-ProRule annotationAdd
BLAST
Domaini191 – 295105IRS-type PTBPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi536 – 5394YXXM motif 1
Motifi594 – 5974YXXM motif 2
Motifi649 – 6524YXXM motif 3
Motifi671 – 6744YXXM motif 4
Motifi734 – 7374YXXM motif 5
Motifi814 – 8174YXXM motif 6
Motifi1061 – 10644YXXM motif 7

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi19 – 2810Poly-Asn
Compositional biasi444 – 4496Poly-Ser
Compositional biasi638 – 6414Poly-Ser
Compositional biasi936 – 9394Poly-Ser

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

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti13 – 131A → G no nucleotide entry (PubMed:7675087).Curated
Sequence conflicti232 – 2321Q → G no nucleotide entry (PubMed:7675087).Curated
Sequence conflicti240 – 2401M → N no nucleotide entry (PubMed:7675087).Curated
Sequence conflicti428 – 4281M → N no nucleotide entry (PubMed:7675087).Curated
Sequence conflicti761 – 7611M → K no nucleotide entry (PubMed:7675087).Curated
Sequence conflicti916 – 9161F → P no nucleotide entry (PubMed:7675087).Curated
Sequence conflicti975 – 9751F → P no nucleotide entry (PubMed:7675087).Curated
Sequence conflicti1062 – 10621T → S no nucleotide entry (PubMed:7675087).Curated

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
EntryMethodResolution (Å)ChainPositionsPDBsum
3BU3X-ray1.65B620-634[»]
3BU5X-ray2.10B620-634[»]
3BU6X-ray1.95B620-634[»]
ProteinModelPortaliP81122.
SMRiP81122. Positions 31-300.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

PTM databases

iPTMnetiP81122.
PhosphoSiteiP81122.

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.

Miscellaneous databases

EvolutionaryTraceiP81122.
PROiP81122.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000038894.
CleanExiMM_IRS2.
GenevisibleiP81122. MM.

Family and domain databases

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: September 7, 2016
This is version 133 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.