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Protein

Insulin receptor substrate 1

Gene

IRS1

Organism
Chlorocebus aethiops (Green monkey) (Cercopithecus aethiops)
Status
Reviewed-Annotation score: Annotation score: 3 out of 5-Experimental evidence at transcript 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

Complete GO annotation...

Keywords - Molecular functioni

Transducer

Names & Taxonomyi

Protein namesi
Recommended name:
Insulin receptor substrate 1
Short name:
IRS-1
Gene namesi
Name:IRS1
OrganismiChlorocebus aethiops (Green monkey) (Cercopithecus aethiops)
Taxonomic identifieri9534 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniCercopithecidaeCercopithecinaeChlorocebus

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000842341 – 1251Insulin receptor substrate 1Add BLAST1251

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei3PhosphoserineBy similarity1
Modified residuei99Phosphoserine; by CK2By similarity1
Modified residuei270PhosphoserineBy similarity1
Modified residuei307Phosphoserine; by RPS6KB1By similarity1
Modified residuei312Phosphoserine; by IKKB, MAPK8 and RPS6KB1By similarity1
Modified residuei323PhosphoserineBy similarity1
Modified residuei330PhosphoserineBy similarity1
Modified residuei345PhosphoserineBy similarity1
Modified residuei348PhosphoserineBy similarity1
Modified residuei419PhosphoserineBy similarity1
Modified residuei446PhosphothreonineBy similarity1
Modified residuei453PhosphothreonineBy similarity1
Modified residuei465Phosphotyrosine; by INSRBy similarity1
Modified residuei527Phosphoserine; by RPS6KB1By similarity1
Modified residuei612Phosphotyrosine; by INSRBy similarity1
Modified residuei629PhosphoserineBy similarity1
Modified residuei632Phosphotyrosine; by INSRBy similarity1
Modified residuei636Phosphoserine; by RPS6KB1By similarity1
Modified residuei662PhosphotyrosineBy similarity1
Modified residuei792Phosphoserine; by AMPK and SIK2By similarity1
Modified residuei901PhosphoserineBy similarity1
Modified residuei905Phosphotyrosine; by INSRBy similarity1
Modified residuei950Phosphotyrosine; by INSRBy similarity1
Modified residuei998Phosphotyrosine; by INSRBy similarity1
Modified residuei1109PhosphoserineBy similarity1
Modified residuei1110PhosphoserineBy similarity1
Modified residuei1188Phosphotyrosine; by INSRBy similarity1
Modified residuei1238Phosphotyrosine; by INSRBy similarity1

Post-translational modificationi

Serine phosphorylation of IRS1 is a mechanism for insulin resistance. Ser-312 phosphorylation inhibits insulin action through disruption of IRS1 interaction with the insulin receptor, and Ser-792 phosphorylation is increased in the liver of insulin-resistant rats (By similarity). Phosphorylation of Tyr-905 is required for GRB2-binding (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

Interactioni

Subunit structurei

Interacts with SOCS7. Interacts (via phosphorylated YXXM motifs) with PIK3R1. Interacts with ROCK1. Interacts with GRB2. Interacts with SOCS7. Interacts (via IRS-type PTB domain) with IGF1R and INSR (via the tyrosine-phosphorylated NPXY motif). Interacts with UBTF and PIK3CA. Interacts (via PH domain) with PHIP. Interacts with FER (By similarity). Interacts with EIF2AK2/PKR (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ28224. 1 interactor.

Structurei

3D structure databases

ProteinModelPortaliQ28224.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini12 – 115PHPROSITE-ProRule annotationAdd BLAST104
Domaini160 – 264IRS-type PTBPROSITE-ProRule annotationAdd BLAST105

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni3 – 137Mediates interaction with PHIPBy similarityAdd BLAST135
Regioni905 – 907GRB2-bindingBy similarity3

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi465 – 468YXXM motif 14
Motifi551 – 554YXXM motif 24
Motifi612 – 615YXXM motif 34
Motifi632 – 635YXXM motif 44
Motifi662 – 665YXXM motif 54
Motifi730 – 733YXXM motif 64
Motifi950 – 953YXXM motif 74
Motifi998 – 1001YXXM motif 84
Motifi1021 – 1024YXXM motif 94

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi128 – 134Poly-Gly7
Compositional biasi268 – 444Ser-richAdd BLAST177
Compositional biasi391 – 398Poly-Ser8
Compositional biasi680 – 685Poly-Ser6
Compositional biasi805 – 813Poly-Ser9
Compositional biasi875 – 891Gln-richAdd BLAST17
Compositional biasi1201 – 1219Pro-richAdd BLAST19

Sequence similaritiesi

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

Keywords - Domaini

Repeat

Phylogenomic databases

HOVERGENiHBG000542.

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.

Q28224-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASPPESDGF SDVRKVGYLR KPKSMHKRFF VLRAASETGD PARLEYYENE
60 70 80 90 100
KKWRHKSSAP KRSIPLESCF NINKRADSKN KHLVALYTRD EHFAIAADSE
110 120 130 140 150
AEQDSWYQAL LQLHNRAKGH HDGAAALGAG GGGGSCSGSS GLGEAGEDLS
160 170 180 190 200
YGDVPPGPAF KEVWQVILKP KGLGQTKNLI GIYRLCLTSK TISFVKLNSE
210 220 230 240 250
AAAVVLQLMN IRRCGHSENF FFIEVGRSAV TGPGEFWMQV DDSVVAQNMH
260 270 280 290 300
ETILEAMRAM SDEFRPRSKS QSSSNCSNPI SVPLRRHHLN NPPPSQVGLT
310 320 330 340 350
RRSRTESITA TSPASMVGGK PGSFRVRASS DGEGTMSRPA SVDGSPVSPS
360 370 380 390 400
TNRTHAHRHR GSARLHPPLN HSRSIPMPAS RCSPSATSPV SLSSSSTSGH
410 420 430 440 450
GSTSDCLFPR RSSASVSGSP SDGGFISSDE YGSSPCDFRS SFRSVTPDSL
460 470 480 490 500
GHTPPARGEE ELSNYICMGG KGPSTLTAPN GHYILSRGGN GHRYTPGTGL
510 520 530 540 550
GTSPALAGDE ASSAADLDNR FRKRTHSAGT SPTITHQKTP SQSSVASIEE
560 570 580 590 600
YTEMMPAYPP GGGSGGRLPG HRHSAFVPTH SYPEEGLEMH PLERRGGHHR
610 620 630 640 650
PDSSTLHTDD GYMPMSPGVA PVPSSRKGSG DYMPMSPKSV SAPQQIINPI
660 670 680 690 700
RRHPQRVDPN GYMMMSPSGG CSPDIGGGPS SSSSSTVPSG SSYGKLWTKG
710 720 730 740 750
VGAHNSQVLL HPKPPVESSG GKLLPCTGDY MNMSPVGDSN TSSPSDCYYG
760 770 780 790 800
PEDPQHKPVL SYYSLPRSFK HTQRPGEPEE GARHQHLRLS TSSGRLLYAA
810 820 830 840 850
TADDSSSSTS SDSLGGGYCG ARLEPSLPHP HHQVLQPHLP RKVDTAAQTN
860 870 880 890 900
SRLARPTRLS LGDPKASTLP RAREQQQQQQ QQQQQQQQQQ QPLLHPPEPK
910 920 930 940 950
SPGEYVNIEF GSDQPGYLSG PVASRSSPSV RCPSQLQPAP REEETGTEEY
960 970 980 990 1000
MKMDLGPGRR AAWQESTGVE MGRLGPAPPG AASICRPTRA VPSSRGDYMT
1010 1020 1030 1040 1050
MQMSCPRQSY VDTSPIAPVS YADMRTGIAA EEVSLPRATM AAAASSSAAS
1060 1070 1080 1090 1100
ASPTGPQGAA ELAAHSSLLG GAQGPGGMSA FTRVNLSPNR NQSAKVIRAD
1110 1120 1130 1140 1150
PQGCRRRHSS ETFSSTPSAT RVGNTVPFGA GAAIGGSGGS SSSSEDVKRH
1160 1170 1180 1190 1200
SSASFENVWL RPGELGGAPK EPAQLCGAAG GLENGLNYID LDLVKDFKQR
1210 1220 1230 1240 1250
PQECTPQPQP PPPPPPHQPL GSSESSSTRR SSEDLSAYAS ISFQKQPEDL

Q
Length:1,251
Mass (Da):133,054
Last modified:November 1, 1996 - v1
Checksum:i924CCAC3BE68EB98
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D64157 mRNA. Translation: BAA11026.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D64157 mRNA. Translation: BAA11026.1.

3D structure databases

ProteinModelPortaliQ28224.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ28224. 1 interactor.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

HOVERGENiHBG000542.

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_CHLAE
AccessioniPrimary (citable) accession number: Q28224
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 29, 2005
Last sequence update: November 1, 1996
Last modified: October 5, 2016
This is version 83 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Documents

  1. 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.