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Protein

Insulin receptor substrate 1

Gene

Irs1

Organism
Rattus norvegicus (Rat)
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. 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.1 Publication

GO - Molecular functioni

  • insulin-like growth factor receptor binding Source: UniProtKB
  • insulin receptor binding Source: UniProtKB
  • phosphatidylinositol 3-kinase binding Source: UniProtKB
  • protein domain specific binding Source: RGD
  • protein kinase binding Source: RGD
  • protein kinase C binding Source: BHF-UCL
  • SH2 domain binding Source: UniProtKB
  • transmembrane receptor protein tyrosine kinase adaptor activity Source: BHF-UCL

GO - Biological processi

  • aging Source: RGD
  • cellular response to angiotensin Source: RGD
  • cellular response to brain-derived neurotrophic factor stimulus Source: RGD
  • cellular response to radiation Source: RGD
  • insulin-like growth factor receptor signaling pathway Source: UniProtKB
  • insulin receptor signaling pathway Source: BHF-UCL
  • JAK-STAT cascade involved in growth hormone signaling pathway Source: Reactome
  • negative regulation of insulin receptor signaling pathway Source: BHF-UCL
  • negative regulation of insulin secretion Source: BHF-UCL
  • negative regulation of somatostatin secretion Source: BHF-UCL
  • positive regulation of glucagon secretion Source: BHF-UCL
  • positive regulation of insulin receptor signaling pathway Source: BHF-UCL
  • positive regulation of phosphatidylinositol 3-kinase activity Source: UniProtKB
  • positive regulation of phosphorylation Source: BHF-UCL
  • protein heterooligomerization Source: RGD
  • response to activity Source: RGD
  • response to caffeine Source: RGD
  • response to peptide hormone Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Transducer

Enzyme and pathway databases

ReactomeiR-RNO-112412. SOS-mediated signalling.
R-RNO-982772. Growth hormone receptor signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Insulin receptor substrate 1
Short name:
IRS-1
Alternative name(s):
pp185
Gene namesi
Name:Irs1
Synonyms:Irs-1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2922. Irs1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: RGD
  • insulin receptor complex Source: BHF-UCL
  • intracellular membrane-bounded organelle Source: UniProtKB
  • nucleus Source: UniProtKB
  • plasma membrane Source: RGD
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi106W → A: Loss of interaction with PHIP. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL1163110.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000842381 – 1235Insulin receptor substrate 1Add BLAST1235

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei3PhosphoserineCombined sources1
Modified residuei99Phosphoserine; by CK21 Publication1
Modified residuei265Phosphoserine; by RPS6KB1By similarity1
Modified residuei302Phosphoserine; by RPS6KB1By similarity1
Modified residuei307Phosphoserine; by IKKB, MAPK8 and RPS6KB1By similarity1
Modified residuei318PhosphoserineBy similarity1
Modified residuei325PhosphoserineBy similarity1
Modified residuei340PhosphoserineBy similarity1
Modified residuei343PhosphoserineCombined sources1
Modified residuei414PhosphoserineBy similarity1
Modified residuei441PhosphothreonineCombined sources1
Modified residuei448PhosphothreonineCombined sources1
Modified residuei460Phosphotyrosine; by INSR1 Publication1
Modified residuei502Phosphothreonine; by CK21 Publication1
Modified residuei522Phosphoserine; by RPS6KB1By similarity1
Modified residuei608Phosphotyrosine; by INSR1 Publication1
Modified residuei628Phosphotyrosine; by INSR1 Publication1
Modified residuei632Phosphoserine; by RPS6KB1 and ROCK2By similarity1
Modified residuei658PhosphotyrosineBy similarity1
Modified residuei789Phosphoserine; by AMPK and SIK21 Publication1
Modified residuei891PhosphoserineCombined sources1
Modified residuei895Phosphotyrosine; by INSR1 Publication1
Modified residuei939Phosphotyrosine; by INSR1 Publication1
Modified residuei987Phosphotyrosine; by INSR1 Publication1
Modified residuei1099PhosphoserineBy similarity1
Modified residuei1100Phosphoserine; by RPS6KB1By similarity1
Modified residuei1172Phosphotyrosine; by INSR1 Publication1
Modified residuei1222Phosphotyrosine; by INSR1 Publication1

Post-translational modificationi

Serine phosphorylation of IRS1 is a mechanism for insulin resistance. Ser-307 phosphorylation inhibits insulin action through disruption of IRS1 interaction with the insulin receptor, and Ser-789 phosphorylation is increased in the liver of insulin-resistant rats. Phosphorylation of Tyr-895 is required for GRB2-binding. Phosphorylated by ALK. Phosphorylated at Ser-265, Ser-302, Ser-632 and Ser-1100 by RPS6KB1; phosphorylation induces accelerated degradation of IRS1 (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

Proteomic databases

PaxDbiP35570.
PRIDEiP35570.

PTM databases

iPTMnetiP35570.
PhosphoSitePlusiP35570.

Interactioni

Subunit structurei

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

Binary interactionsi

WithEntry#Exp.IntActNotes
FynP396884EBI-520230,EBI-524514From a different organism.
GRB2P629935EBI-520230,EBI-401755From a different organism.
INSRP062135EBI-520230,EBI-475899From a different organism.
Pabpc1Q9EPH82EBI-520230,EBI-919825
PhipQ8VDD92EBI-520230,EBI-1369766From a different organism.
PIK3R1P279862EBI-520230,EBI-79464From a different organism.
Pik3r1Q637873EBI-520230,EBI-518443
PRKCQQ047592EBI-520230,EBI-374762From a different organism.
PTPN1P180313EBI-520230,EBI-968788From a different organism.
PTPN11Q061243EBI-520230,EBI-297779From a different organism.
TP53BP2Q13625-24EBI-520230,EBI-287091From a different organism.

GO - Molecular functioni

  • insulin-like growth factor receptor binding Source: UniProtKB
  • insulin receptor binding Source: UniProtKB
  • phosphatidylinositol 3-kinase binding Source: UniProtKB
  • protein domain specific binding Source: RGD
  • protein kinase binding Source: RGD
  • protein kinase C binding Source: BHF-UCL
  • SH2 domain binding Source: UniProtKB
  • transmembrane receptor protein tyrosine kinase adaptor activity Source: BHF-UCL

Protein-protein interaction databases

BioGridi247500. 13 interactors.
DIPiDIP-664N.
IntActiP35570. 21 interactors.
MINTiMINT-259238.
STRINGi10116.ENSRNOP00000019579.

Chemistry databases

BindingDBiP35570.

Structurei

3D structure databases

ProteinModelPortaliP35570.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini12 – 115PHPROSITE-ProRule annotationAdd BLAST104
Domaini155 – 259IRS-type PTBPROSITE-ProRule annotationAdd BLAST105

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni3 – 133Mediates interaction with PHIP1 PublicationAdd BLAST131
Regioni895 – 897GRB2-binding3

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi460 – 463YXXM motif 14
Motifi546 – 549YXXM motif 24
Motifi608 – 611YXXM motif 34
Motifi628 – 631YXXM motif 44
Motifi658 – 661YXXM motif 54
Motifi727 – 730YXXM motif 64
Motifi939 – 942YXXM motif 74
Motifi987 – 990YXXM motif 84
Motifi1010 – 1013YXXM motif 94

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi872 – 881Poly-Gln10
Compositional biasi1196 – 1200Poly-Pro5

Sequence similaritiesi

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

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410IXEK. Eukaryota.
ENOG410Z9EP. LUCA.
HOGENOMiHOG000113103.
HOVERGENiHBG000542.
InParanoidiP35570.
KOiK16172.
PhylomeDBiP35570.

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.

P35570-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASPPDTDGF SDVRKVGYLR KPKSMHKRFF VLRAASEAGG PARLEYYENE
60 70 80 90 100
KKWRHKSSAP KRSIPLESCF NINKRADSKN KHLVALYTRD EHFAIAADSE
110 120 130 140 150
AEQDSWYQAL LQLHNRAKAH HDGAGGGCGG SCSGSSGVGE AGEDLSYDTG
160 170 180 190 200
PGPAFKEVWQ VILKPKGLGQ TKNLIGIYRL CLTSKTISFV KLNSEAAAVV
210 220 230 240 250
LQLMNIRRCG HSENFFFIEV GRSAVTGPGE FWMQVDDSVV AQNMHETILE
260 270 280 290 300
AMRAMSDEFR PRTKSQSSSS CSNPISVPLR RHHLNNPPPS QVGLTRRSRT
310 320 330 340 350
ESITATSPAS MVGGKPGSFR VRASSDGEGT MSRPASVDGS PVSPSTNRTH
360 370 380 390 400
AHRHRGSSRL HPPLNHSRSI PMPSSRCSPS ATSPVSLSSS STSGHGSTSD
410 420 430 440 450
CLFPRRSSAS VSGSPSDGGF ISSDEYGSSP CDFRSSFRSV TPDSLGHTPP
460 470 480 490 500
ARGEEELSNY ICMGGKGAST LTAPNGHYIL SRGGNGHRYI PGATMGTSPA
510 520 530 540 550
LTGDEAAGAA DLDNRFRKRT HSAGTSPTIS HQKTPSQSSV VSIEEYTEMM
560 570 580 590 600
PAAYPPGGGS GGRLPGYRHS AFVPTHSYPE EGLEMHHLER RGGHHRPDSS
610 620 630 640 650
NLHTDDGYMP MSPGVAPVPS NRKGNGDYMP MSPKSVSAPQ QIINPIRRHP
660 670 680 690 700
QRVDPNGYMM MSPSGSCSPD IGGGSCSSSS ISAAPSGSSY GKPWTNGVGG
710 720 730 740 750
HHTHALPHAK PPVESGGGKL LPCTGDYMNM SPVGDSNTSS PSECYYGPED
760 770 780 790 800
PQHKPVLSYY SLPRSFKHTQ RPGEPEEGAR HQHLRLSSSS GRLRYTATAE
810 820 830 840 850
DSSSSTSSDS LGGGYCGARP ESSVTHPHHH ALQPHLPRKV DTAAQTNSRL
860 870 880 890 900
ARPTRLSLGD PKASTLPRVR EQQQQQQQQQ QSSLHPPEPK SPGEYVNIEF
910 920 930 940 950
GSGQPGYLAG PATSRSSPSV RCLPQLHPAP REETGSEEYM NMDLGPGRRA
960 970 980 990 1000
TWQESGGVEL GRVGPAPPGA ASICRPTRSV PNSRGDYMTM QIGCPRQSYV
1010 1020 1030 1040 1050
DTSPVAPVSY ADMRTGIAAE KVSLPRTTGA APPPSSTASA SASVTPQGAA
1060 1070 1080 1090 1100
EQAAHSSLLG GPQGPGGMSA FTRVNLSPNH NQSAKVIRAD TQGCRRRHSS
1110 1120 1130 1140 1150
ETFSAPTRAA NTVSFGAGAA GGGSGGGSED VKRHSSASFE NVWLRPGDLG
1160 1170 1180 1190 1200
GASKESAPGC GAAGGLEKSL NYIDLDLVKD VKQHPQDCPS QQQSLPPPPP
1210 1220 1230
HQPLGSNEGS SPRRSSEDLS TYASINFQKQ PEDRQ
Length:1,235
Mass (Da):131,178
Last modified:June 1, 1994 - v1
Checksum:iA274BC7540CA85C5
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1098H → L AA sequence (PubMed:2022647).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X58375 mRNA. Translation: CAA41264.1.
PIRiS16948.
RefSeqiNP_037101.1. NM_012969.1.
UniGeneiRn.10476.

Genome annotation databases

GeneIDi25467.
KEGGirno:25467.
UCSCiRGD:2922. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X58375 mRNA. Translation: CAA41264.1.
PIRiS16948.
RefSeqiNP_037101.1. NM_012969.1.
UniGeneiRn.10476.

3D structure databases

ProteinModelPortaliP35570.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247500. 13 interactors.
DIPiDIP-664N.
IntActiP35570. 21 interactors.
MINTiMINT-259238.
STRINGi10116.ENSRNOP00000019579.

Chemistry databases

BindingDBiP35570.
ChEMBLiCHEMBL1163110.

PTM databases

iPTMnetiP35570.
PhosphoSitePlusiP35570.

Proteomic databases

PaxDbiP35570.
PRIDEiP35570.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi25467.
KEGGirno:25467.
UCSCiRGD:2922. rat.

Organism-specific databases

CTDi3667.
RGDi2922. Irs1.

Phylogenomic databases

eggNOGiENOG410IXEK. Eukaryota.
ENOG410Z9EP. LUCA.
HOGENOMiHOG000113103.
HOVERGENiHBG000542.
InParanoidiP35570.
KOiK16172.
PhylomeDBiP35570.

Enzyme and pathway databases

ReactomeiR-RNO-112412. SOS-mediated signalling.
R-RNO-982772. Growth hormone receptor signaling.

Miscellaneous databases

PROiP35570.

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_RAT
AccessioniPrimary (citable) accession number: P35570
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: November 2, 2016
This is version 144 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

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.