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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)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 12511251Insulin receptor substrate 1PRO_0000084234Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei3 – 31PhosphoserineBy similarity
Modified residuei99 – 991Phosphoserine; by CK2By similarity
Modified residuei270 – 2701PhosphoserineBy similarity
Modified residuei307 – 3071Phosphoserine; by RPS6KB1By similarity
Modified residuei312 – 3121Phosphoserine; by IKKB, MAPK8 and RPS6KB1By similarity
Modified residuei323 – 3231PhosphoserineBy similarity
Modified residuei330 – 3301PhosphoserineBy similarity
Modified residuei345 – 3451PhosphoserineBy similarity
Modified residuei348 – 3481PhosphoserineBy similarity
Modified residuei419 – 4191PhosphoserineBy similarity
Modified residuei446 – 4461PhosphothreonineBy similarity
Modified residuei453 – 4531PhosphothreonineBy similarity
Modified residuei465 – 4651Phosphotyrosine; by INSRBy similarity
Modified residuei527 – 5271Phosphoserine; by RPS6KB1By similarity
Modified residuei612 – 6121Phosphotyrosine; by INSRBy similarity
Modified residuei629 – 6291PhosphoserineBy similarity
Modified residuei632 – 6321Phosphotyrosine; by INSRBy similarity
Modified residuei636 – 6361Phosphoserine; by RPS6KB1By similarity
Modified residuei662 – 6621PhosphotyrosineBy similarity
Modified residuei792 – 7921Phosphoserine; by AMPK and SIK2By similarity
Modified residuei901 – 9011PhosphoserineBy similarity
Modified residuei905 – 9051Phosphotyrosine; by INSRBy similarity
Modified residuei950 – 9501Phosphotyrosine; by INSRBy similarity
Modified residuei998 – 9981Phosphotyrosine; by INSRBy similarity
Modified residuei1109 – 11091PhosphoserineBy similarity
Modified residuei1110 – 11101PhosphoserineBy similarity
Modified residuei1188 – 11881Phosphotyrosine; by INSRBy similarity
Modified residuei1238 – 12381Phosphotyrosine; by INSRBy similarity

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 interaction.

Structurei

3D structure databases

ProteinModelPortaliQ28224.
SMRiQ28224. Positions 11-267.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini12 – 115104PHPROSITE-ProRule annotationAdd
BLAST
Domaini160 – 264105IRS-type PTBPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni3 – 137135Mediates interaction with PHIPBy similarityAdd
BLAST
Regioni905 – 9073GRB2-bindingBy similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi465 – 4684YXXM motif 1
Motifi551 – 5544YXXM motif 2
Motifi612 – 6154YXXM motif 3
Motifi632 – 6354YXXM motif 4
Motifi662 – 6654YXXM motif 5
Motifi730 – 7334YXXM motif 6
Motifi950 – 9534YXXM motif 7
Motifi998 – 10014YXXM motif 8
Motifi1021 – 10244YXXM motif 9

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi128 – 1347Poly-Gly
Compositional biasi268 – 444177Ser-richAdd
BLAST
Compositional biasi391 – 3988Poly-Ser
Compositional biasi680 – 6856Poly-Ser
Compositional biasi805 – 8139Poly-Ser
Compositional biasi875 – 89117Gln-richAdd
BLAST
Compositional biasi1201 – 121919Pro-richAdd
BLAST

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

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.
SMRiQ28224. Positions 11-267.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ28224. 1 interaction.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

HOVERGENiHBG000542.

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 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: January 20, 2016
This is version 82 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.