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Protein

Insulin receptor substrate 1

Gene

Irs1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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: RGD
  • insulin receptor binding Source: RGD
  • 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

Keywordsi

Molecular functionTransducer

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2922 Irs1

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

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 (PubMed:11606564, PubMed:12006586, PubMed:7504175). 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). Phosphorylated on tyrosine residues in response to insulin (By similarity).By similarity3 Publications
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 (PubMed:1380456). Interacts with ROCK1 (PubMed:11739394). Interacts (via PH domain) with PHIP (PubMed:11018022). Interacts with GRB2 (PubMed:8491186). Interacts with ALK (By similarity). Interacts with EIF2AK2/PKR (By similarity). Interacts with GKAP1 (PubMed:25586176). Interacts with DGKZ in the absence of insulin; insulin stimulation decreases this interaction (PubMed:27739494). Found in a ternary complex with DGKZ and PIP5K1A in the absence of insulin stimulation (By similarity).By similarity6 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi247500, 13 interactors
CORUMiP35570
DIPiDIP-664N
ELMiP35570
IntActiP35570, 21 interactors
MINTiP35570
STRINGi10116.ENSRNOP00000019579

Chemistry databases

BindingDBiP35570

Structurei

3D structure databases

ProteinModelPortaliP35570
SMRiP35570
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

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
InterProiView protein in InterPro
IPR039011 IRS
IPR002404 IRS_PTB
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
PANTHERiPTHR10614 PTHR10614, 1 hit
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

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
G3V7V7G3V7V7_RAT
Insulin receptor substrate 1
Irs1 rCG_24010
1,235Annotation score:

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

Similar proteinsi

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

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5WRKX-ray2.62P607-614[»]
5WRLX-ray3.10P627-634[»]
5WRMX-ray2.60P657-664[»]
ProteinModelPortaliP35570
SMRiP35570
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247500, 13 interactors
CORUMiP35570
DIPiDIP-664N
ELMiP35570
IntActiP35570, 21 interactors
MINTiP35570
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

Miscellaneous databases

PROiPR:P35570

Family and domain databases

CDDicd01204 PTB_IRS, 1 hit
Gene3Di2.30.29.30, 2 hits
InterProiView protein in InterPro
IPR039011 IRS
IPR002404 IRS_PTB
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
PANTHERiPTHR10614 PTHR10614, 1 hit
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
ProtoNetiSearch...

Entry informationi

Entry nameiIRS1_RAT
AccessioniPrimary (citable) accession number: P35570
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: October 10, 2018
This is version 159 of the entry and version 1 of the sequence. See 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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