Irs1
entrez
25467
canonical
uniprot
P35570
canonical
ensembl
ENSRNOG00000014597
resolver
ensp
ENSRNOP00000019579
resolver
ensp
ENSRNOP00000101528
resolver
enst
ENSRNOT00000019579
resolver
enst
ENSRNOT00000144395
resolver
genesymbol
Irs1
resolver
genesymbol_syn
Irs-1
resolver
uniprot
G3V7V7
resolver
uniprot_entry
G3V7V7_RAT
resolver
uniprot_entry
IRS1_RAT
resolver
amino_acid_sequence
MASPPDTDGFSDVRKVGYLRKPKSMHKRFFVLRAASEAGGPARLEYYENEKKWRHKSSAPKRSIPLESCFNINKRADSKNKHLVALYTRDEHFAIAADSEAEQDSWYQALLQLHNRAKAHHDGAGGGCGGSCSGSSGVGEAGEDLSYDTGPGPAFKEVWQVILKPKGLGQTKNLIGIYRLCLTSKTISFVKLNSEAAAVVLQLMNIRRCGHSENFFFIEVGRSAVTGPGEFWMQVDDSVVAQNMHETILEAMRAMSDEFRPRTKSQSSSSCSNPISVPLRRHHLNNPPPSQVGLTRRSRTESITATSPASMVGGKPGSFRVRASSDGEGTMSRPASVDGSPVSPSTNRTHAHRHRGSSRLHPPLNHSRSIPMPSSRCSPSATSPVSLSSSSTSGHGSTSDCLFPRRSSASVSGSPSDGGFISSDEYGSSPCDFRSSFRSVTPDSLGHTPPARGEEELSNYICMGGKGASTLTAPNGHYILSRGGNGHRYIPGATMGTSPALTGDEAAGAADLDNRFRKRTHSAGTSPTISHQKTPSQSSVVSIEEYTEMMPAAYPPGGGSGGRLPGYRHSAFVPTHSYPEEGLEMHHLERRGGHHRPDSSNLHTDDGYMPMSPGVAPVPSNRKGNGDYMPMSPKSVSAPQQIINPIRRHPQRVDPNGYMMMSPSGSCSPDIGGGSCSSSSISAAPSGSSYGKPWTNGVGGHHTHALPHAKPPVESGGGKLLPCTGDYMNMSPVGDSNTSSPSECYYGPEDPQHKPVLSYYSLPRSFKHTQRPGEPEEGARHQHLRLSSSSGRLRYTATAEDSSSSTSSDSLGGGYCGARPESSVTHPHHHALQPHLPRKVDTAAQTNSRLARPTRLSLGDPKASTLPRVREQQQQQQQQQQSSLHPPEPKSPGEYVNIEFGSGQPGYLAGPATSRSSPSVRCLPQLHPAPREETGSEEYMNMDLGPGRRATWQESGGVELGRVGPAPPGAASICRPTRSVPNSRGDYMTMQIGCPRQSYVDTSPVAPVSYADMRTGIAAEKVSLPRTTGAAPPPSSTASASASVTPQGAAEQAAHSSLLGGPQGPGGMSAFTRVNLSPNHNQSAKVIRADTQGCRRRHSSETFSAPTRAANTVSFGAGAAGGGSGGGSEDVKRHSSASFENVWLRPGDLGGASKESAPGCGAAGGLEKSLNYIDLDLVKDVKQHPQDCPSQQQSLPPPPPHQPLGSNEGSSPRRSSEDLSTYASINFQKQPEDRQ
uniprot
proteins
function
FUNCTION: Signaling adapter protein that participates in the signal transduction from two prominent receptor tyrosine kinases, insulin receptor/INSR and insulin-like growth factor I receptor/IGF1R (PubMed:12399410). Plays therefore an important role in development, growth, glucose homeostasis as well as lipid metabolism. Upon phosphorylation by the insulin receptor, functions as a signaling scaffold that propagates insulin action through binding to SH2 domain-containing proteins including the p85 regulatory subunit of PI3K, NCK1, NCK2, GRB2 or SHP2 (PubMed:1380456). Recruitment of GRB2 leads to the activation of the guanine nucleotide exchange factor SOS1 which in turn triggers the Ras/Raf/MEK/MAPK signaling cascade (PubMed:8491186). Activation of the PI3K/AKT pathway is responsible for most of insulin metabolic effects in the cell, and the Ras/Raf/MEK/MAPK is involved in the regulation of gene expression and in cooperation with the PI3K pathway regulates cell growth and differentiation (By similarity). Acts a positive regulator of the Wnt/beta-catenin signaling pathway through suppression of DVL2 autophagy-mediated degradation leading to cell proliferation (By similarity). {ECO:0000250|UniProtKB:P35568, ECO:0000269|PubMed:12399410, ECO:0000269|PubMed:1380456, ECO:0000269|PubMed:8491186}.
uniprot
proteins
mass_dalton
131178
uniprot
proteins
mutagenesis
MUTAGEN 106; /note="W->A: Loss of interaction with PHIP."; /evidence="ECO:0000269|PubMed:11018022
uniprot
proteins
post_translational_modification
PTM: 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). In skeletal muscles, dephosphorylated on Tyr-608 by TNS2 under anabolic conditions; dephosphorylation results in the proteasomal degradation of IRS1 (By similarity). {ECO:0000250|UniProtKB:P35568, ECO:0000250|UniProtKB:P35569, ECO:0000269|PubMed:11606564, ECO:0000269|PubMed:12006586, ECO:0000269|PubMed:7504175}.; PTM: 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). Ubiquitinated by TRAF4 through 'Lys-29' linkage; this ubiquitination regulates the interaction of IRS1 with IGFR and IRS1 tyrosine phosphorylation upon IGF1 stimulation (By similarity). {ECO:0000250|UniProtKB:P35568}.; PTM: S-nitrosylation at by BLVRB inhibits its activity. {ECO:0000250|UniProtKB:P35568}.
uniprot
proteins
pubmed
11018022
uniprot
proteins
pubmed
11606564
uniprot
proteins
pubmed
11739394
uniprot
proteins
pubmed
12006586
uniprot
proteins
pubmed
12399410
uniprot
proteins
pubmed
1380456
uniprot
proteins
pubmed
1648180
uniprot
proteins
pubmed
2022647
uniprot
proteins
pubmed
22673903
uniprot
proteins
pubmed
24187137
uniprot
proteins
pubmed
25586176
uniprot
proteins
pubmed
27739494
uniprot
proteins
pubmed
7504175
uniprot
proteins
pubmed
8349691
uniprot
proteins
pubmed
8491186
uniprot
proteins
sequence_length
1235
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P35568}. Nucleus {ECO:0000250|UniProtKB:P35568}. Note=Nuclear or cytoplasmic localization of IRS1 correlates with the transition from proliferation to chondrogenic differentiation. {ECO:0000250|UniProtKB:P35568}.
uniprot
proteins