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Protein

Insulin receptor substrate 2

Gene

IRS2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

May mediate the control of various cellular processes by insulin.

GO - Molecular functioni

GO - Biological processi

  • axon guidance Source: Reactome
  • brain development Source: Ensembl
  • cell proliferation Source: Ensembl
  • cellular response to glucose stimulus Source: Ensembl
  • cellular response to insulin stimulus Source: BHF-UCL
  • glucose metabolic process Source: ProtInc
  • insulin receptor signaling pathway Source: BHF-UCL
  • interleukin-7-mediated signaling pathway Source: Reactome
  • lipid homeostasis Source: BHF-UCL
  • mammary gland development Source: Ensembl
  • MAPK cascade Source: Reactome
  • 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: BHF-UCL
  • phosphatidylinositol-mediated signaling Source: Reactome
  • positive regulation of B cell proliferation Source: BHF-UCL
  • positive regulation of cell migration Source: Ensembl
  • positive regulation of cell proliferation Source: BHF-UCL
  • positive regulation of fatty acid beta-oxidation Source: BHF-UCL
  • positive regulation of glucose import Source: BHF-UCL
  • positive regulation of glucose metabolic process Source: BHF-UCL
  • positive regulation of glycogen biosynthetic process Source: BHF-UCL
  • positive regulation of insulin secretion Source: BHF-UCL
  • positive regulation of mesenchymal cell proliferation Source: Ensembl
  • positive regulation of protein kinase B signaling Source: Reactome
  • regulation of lipid metabolic process Source: BHF-UCL
  • response to glucose Source: BHF-UCL
  • signal transduction Source: ProtInc

Keywordsi

Molecular functionTransducer

Enzyme and pathway databases

ReactomeiR-HSA-109704 PI3K Cascade
R-HSA-112412 SOS-mediated signalling
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-1266695 Interleukin-7 signaling
R-HSA-198203 PI3K/AKT activation
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-2428928 IRS-related events triggered by IGF1R
R-HSA-2586552 Signaling by Leptin
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-74713 IRS activation
R-HSA-74749 Signal attenuation
R-HSA-8853659 RET signaling
R-HSA-982772 Growth hormone receptor signaling
SignaLinkiQ9Y4H2
SIGNORiQ9Y4H2

Names & Taxonomyi

Protein namesi
Recommended name:
Insulin receptor substrate 2
Short name:
IRS-2
Gene namesi
Name:IRS2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

EuPathDBiHostDB:ENSG00000185950.8
HGNCiHGNC:6126 IRS2
MIMi600797 gene
neXtProtiNX_Q9Y4H2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

DisGeNETi8660
MalaCardsiIRS2
OpenTargetsiENSG00000185950
PharmGKBiPA375

Polymorphism and mutation databases

BioMutaiIRS2
DMDMi62298062

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000842391 – 1338Insulin receptor substrate 2Add BLAST1338

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei306PhosphoserineCombined sources1
Modified residuei346PhosphoserineCombined sources1
Modified residuei350PhosphothreonineCombined sources1
Modified residuei365PhosphoserineCombined sources1
Modified residuei384PhosphoserineCombined sources1
Modified residuei388PhosphoserineCombined sources1
Modified residuei391PhosphoserineCombined sources1
Modified residuei412Omega-N-methylarginineCombined sources1
Modified residuei520PhosphothreonineCombined sources1
Modified residuei523PhosphoserineCombined sources1
Modified residuei527PhosphothreonineCombined sources1
Modified residuei540Phosphotyrosine; by INSRBy similarity1
Modified residuei560PhosphoserineCombined sources1
Modified residuei577PhosphoserineCombined sources1
Modified residuei579PhosphothreonineCombined sources1
Modified residuei580PhosphothreonineCombined sources1
Modified residuei594PhosphoserineCombined sources1
Modified residuei608PhosphoserineCombined sources1
Modified residuei620PhosphoserineCombined sources1
Modified residuei653Phosphotyrosine; by INSRBy similarity1
Modified residuei675Phosphotyrosine; by INSRCombined sources1
Modified residuei679PhosphoserineCombined sources1
Modified residuei682PhosphoserineCombined sources1
Modified residuei735PhosphoserineCombined sources1
Modified residuei736PhosphoserineCombined sources1
Modified residuei770PhosphoserineCombined sources1
Modified residuei779PhosphothreonineCombined sources1
Modified residuei805PhosphoserineCombined sources1
Modified residuei828PhosphoserineCombined sources1
Modified residuei915PhosphoserineCombined sources1
Modified residuei919Phosphotyrosine; by INSRBy similarity1
Modified residuei973PhosphoserineCombined sources1
Modified residuei978Phosphotyrosine; by INSRBy similarity1
Modified residuei1082PhosphothreonineCombined sources1
Modified residuei1100PhosphoserineCombined sources1
Modified residuei1159PhosphothreonineCombined sources1
Modified residuei1162PhosphoserineCombined sources1
Modified residuei1174PhosphoserineCombined sources1
Modified residuei1176PhosphoserineCombined sources1
Modified residuei1186PhosphoserineCombined sources1
Modified residuei1203PhosphoserineCombined sources1
Modified residuei1253Phosphotyrosine; by INSRBy similarity1

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

EPDiQ9Y4H2
MaxQBiQ9Y4H2
PaxDbiQ9Y4H2
PeptideAtlasiQ9Y4H2
PRIDEiQ9Y4H2

PTM databases

iPTMnetiQ9Y4H2
PhosphoSitePlusiQ9Y4H2

Miscellaneous databases

PMAP-CutDBQ9Y4H2

Expressioni

Gene expression databases

BgeeiENSG00000185950
CleanExiHS_IRS2
GenevisibleiQ9Y4H2 HS

Organism-specific databases

HPAiCAB016944
HPA054664

Interactioni

Subunit structurei

Interacts with PHIP.By similarity

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114209, 43 interactors
ELMiQ9Y4H2
IntActiQ9Y4H2, 15 interactors
MINTiQ9Y4H2
STRINGi9606.ENSP00000365016

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3FQWX-ray1.93C1097-1105[»]
3FQXX-ray1.70C1097-1105[»]
ProteinModelPortaliQ9Y4H2
SMRiQ9Y4H2
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Y4H2

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini16 – 144PHPROSITE-ProRule annotationAdd BLAST129
Domaini194 – 298IRS-type PTBPROSITE-ProRule annotationAdd BLAST105

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi540 – 543YXXM motif 14
Motifi598 – 601YXXM motif 24
Motifi653 – 656YXXM motif 34
Motifi675 – 678YXXM motif 44
Motifi742 – 745YXXM motif 54
Motifi823 – 826YXXM motif 64
Motifi1072 – 1075YXXM motif 74

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi19 – 28Poly-Asn10
Compositional biasi371 – 380Poly-Ala10
Compositional biasi447 – 452Poly-Ser6
Compositional biasi460 – 467Poly-Pro8
Compositional biasi533 – 537Poly-Gly5
Compositional biasi642 – 645Poly-Ser4
Compositional biasi694 – 701Poly-Ala8
Compositional biasi944 – 947Poly-Ser4
Compositional biasi1031 – 1038Poly-Pro8
Compositional biasi1265 – 1278Poly-ProAdd BLAST14

Phylogenomic databases

eggNOGiENOG410IXEK Eukaryota
ENOG410Z9EP LUCA
GeneTreeiENSGT00530000063420
HOVERGENiHBG000542
InParanoidiQ9Y4H2
KOiK07187
OMAiMHEYPLP
OrthoDBiEOG091G02EF
PhylomeDBiQ9Y4H2
TreeFamiTF325994

Family and domain databases

CDDicd01204 PTB_IRS, 1 hit
Gene3Di2.30.29.30, 2 hits
InterProiView protein in InterPro
IPR002404 IRS_PTB
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
PfamiView protein in Pfam
PF02174 IRS, 1 hit
PF00169 PH, 1 hit
PRINTSiPR00628 INSULINRSI
SMARTiView protein in SMART
SM00233 PH, 1 hit
SM00310 PTBI, 1 hit
PROSITEiView protein in PROSITE
PS51064 IRS_PTB, 1 hit
PS50003 PH_DOMAIN, 1 hit

Sequencei

Sequence statusi: Complete.

Q9Y4H2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASPPRHGPP GPASGDGPNL NNNNNNNNHS VRKCGYLRKQ KHGHKRFFVL
60 70 80 90 100
RGPGAGGDEA TAGGGSAPQP PRLEYYESEK KWRSKAGAPK RVIALDCCLN
110 120 130 140 150
INKRADAKHK YLIALYTKDE YFAVAAENEQ EQEGWYRALT DLVSEGRAAA
160 170 180 190 200
GDAPPAAAPA ASCSASLPGA LGGSAGAAGA EDSYGLVAPA TAAYREVWQV
210 220 230 240 250
NLKPKGLGQS KNLTGVYRLC LSARTIGFVK LNCEQPSVTL QLMNIRRCGH
260 270 280 290 300
SDSFFFIEVG RSAVTGPGEL WMQADDSVVA QNIHETILEA MKALKELFEF
310 320 330 340 350
RPRSKSQSSG SSATHPISVP GARRHHHLVN LPPSQTGLVR RSRTDSLAAT
360 370 380 390 400
PPAAKCSSCR VRTASEGDGG AAAGAAAAGA RPVSVAGSPL SPGPVRAPLS
410 420 430 440 450
RSHTLSGGCG GRGSKVALLP AGGALQHSRS MSMPVAHSPP AATSPGSLSS
460 470 480 490 500
SSGHGSGSYP PPPGPHPPLP HPLHHGPGQR PSSGSASASG SPSDPGFMSL
510 520 530 540 550
DEYGSSPGDL RAFCSHRSNT PESIAETPPA RDGGGGGEFY GYMTMDRPLS
560 570 580 590 600
HCGRSYRRVS GDAAQDLDRG LRKRTYSLTT PARQRPVPQP SSASLDEYTL
610 620 630 640 650
MRATFSGSAG RLCPSCPASS PKVAYHPYPE DYGDIEIGSH RSSSSNLGAD
660 670 680 690 700
DGYMPMTPGA ALAGSGSGSC RSDDYMPMSP ASVSAPKQIL QPRAAAAAAA
710 720 730 740 750
AVPSAGPAGP APTSAAGRTF PASGGGYKAS SPAESSPEDS GYMRMWCGSK
760 770 780 790 800
LSMEHADGKL LPNGDYLNVS PSDAVTTGTP PDFFSAALHP GGEPLRGVPG
810 820 830 840 850
CCYSSLPRSY KAPYTCGGDS DQYVLMSSPV GRILEEERLE PQATPGPSQA
860 870 880 890 900
ASAFGAGPTQ PPHPVVPSPV RPSGGRPEGF LGQRGRAVRP TRLSLEGLPS
910 920 930 940 950
LPSMHEYPLP PEPKSPGEYI NIDFGEPGAR LSPPAPPLLA SAASSSSLLS
960 970 980 990 1000
ASSPASSLGS GTPGTSSDSR QRSPLSDYMN LDFSSPKSPK PGAPSGHPVG
1010 1020 1030 1040 1050
SLDGLLSPEA SSPYPPLPPR PSASPSSSLQ PPPPPPAPGE LYRLPPASAV
1060 1070 1080 1090 1100
ATAQGPGAAS SLSSDTGDNG DYTEMAFGVA ATPPQPIAAP PKPEAARVAS
1110 1120 1130 1140 1150
PTSGVKRLSL MEQVSGVEAF LQASQPPDPH RGAKVIRADP QGGRRRHSSE
1160 1170 1180 1190 1200
TFSSTTTVTP VSPSFAHNPK RHNSASVENV SLRKSSEGGV GVGPGGGDEP
1210 1220 1230 1240 1250
PTSPRQLQPA PPLAPQGRPW TPGQPGGLVG CPGSGGSPMR RETSAGFQNG
1260 1270 1280 1290 1300
LNYIAIDVRE EPGLPPQPQP PPPPLPQPGD KSSWGRTRSL GGLISAVGVG
1310 1320 1330
STGGGCGGPG PGALPPANTY ASIDFLSHHL KEATIVKE
Length:1,338
Mass (Da):137,334
Last modified:March 29, 2005 - v2
Checksum:i58E569E8BDBAF3D7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti28N → NN in AAD21531 (PubMed:10077005).Curated1
Sequence conflicti39 – 41KQK → NEE in AAD21531 (PubMed:10077005).Curated3
Sequence conflicti59E → K in BAA24500 (PubMed:9312143).Curated1
Sequence conflicti81K → N in BAA24500 (PubMed:9312143).Curated1
Sequence conflicti107A → P in BAA24500 (PubMed:9312143).Curated1
Sequence conflicti171L → V in BAA24500 (PubMed:9312143).Curated1
Sequence conflicti371A → R in AAD21531 (PubMed:10077005).Curated1
Sequence conflicti379 – 382GARP → AQRL in AAD21531 (PubMed:10077005).Curated4
Sequence conflicti406S → I in BAA24500 (PubMed:9312143).Curated1
Sequence conflicti410 – 419GGRGSKVALL → RAAGTKWHCF in BAA24500 (PubMed:9312143).Curated10
Sequence conflicti424A → G in BAA24500 (PubMed:9312143).Curated1
Sequence conflicti436 – 438AHS → EHL in BAA24500 (PubMed:9312143).Curated3
Sequence conflicti453G → D in BAA24500 (PubMed:9312143).Curated1
Sequence conflicti456S → W in BAA24500 (PubMed:9312143).Curated1
Sequence conflicti468P → L in BAA24500 (PubMed:9312143).Curated1
Sequence conflicti662L → F in AAD21531 (PubMed:10077005).Curated1
Sequence conflicti704S → F in BAA24500 (PubMed:9312143).Curated1
Sequence conflicti714S → F in BAA24500 (PubMed:9312143).Curated1
Sequence conflicti848S → T in BAA24500 (PubMed:9312143).Curated1
Sequence conflicti872P → R in AAD21531 (PubMed:10077005).Curated1
Sequence conflicti875 – 878GRPE → RRS in AAD21531 (PubMed:10077005).Curated4
Sequence conflicti956S → L in BAA24500 (PubMed:9312143).Curated1
Sequence conflicti1252N → K in BAA24500 (PubMed:9312143).Curated1
Sequence conflicti1303G → R in BAA24500 (PubMed:9312143).Curated1
Sequence conflicti1314 – 1338LPPAN…TIVKE → PAPCPTTYAQH in BAA24500 (PubMed:9312143).CuratedAdd BLAST25

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_033992789H → Y. Corresponds to variant dbSNP:rs35223808Ensembl.1
Natural variantiVAR_021557879G → S1 PublicationCorresponds to variant dbSNP:rs549588978Ensembl.1
Natural variantiVAR_021558882G → A1 PublicationCorresponds to variant dbSNP:rs201499247Ensembl.1
Natural variantiVAR_033993999V → M. Corresponds to variant dbSNP:rs35927012Ensembl.1
Natural variantiVAR_0148571057G → D1 PublicationCorresponds to variant dbSNP:rs1805097EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB000732 Genomic DNA Translation: BAA24500.1
AF073310 mRNA Translation: AAD21531.1
AF322115, AF322114 Genomic DNA Translation: AAG50013.1
AL162497 Genomic DNA No translation available.
AF288517 Genomic DNA Translation: AAK83053.1
CCDSiCCDS9510.1
RefSeqiNP_003740.2, NM_003749.2
UniGeneiHs.442344

Genome annotation databases

EnsembliENST00000375856; ENSP00000365016; ENSG00000185950
GeneIDi8660
KEGGihsa:8660
UCSCiuc001vqv.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiIRS2_HUMAN
AccessioniPrimary (citable) accession number: Q9Y4H2
Secondary accession number(s): Q96RR2, Q9BZG0, Q9Y6I5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: March 29, 2005
Last modified: May 23, 2018
This is version 165 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

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