IRS1
entrez
3667
canonical
uniprot
P35568
canonical
ensembl
ENSG00000169047
resolver
ensp
ENSP00000304895
resolver
ensp
ENSP00000588888
resolver
enst
ENST00000305123
resolver
enst
ENST00000918829
resolver
genesymbol
IRS1
resolver
hgnc
HGNC:6125
resolver
uniprot_entry
IRS1_HUMAN
resolver
amino_acid_sequence
MASPPESDGFSDVRKVGYLRKPKSMHKRFFVLRAASEAGGPARLEYYENEKKWRHKSSAPKRSIPLESCFNINKRADSKNKHLVALYTRDEHFAIAADSEAEQDSWYQALLQLHNRAKGHHDGAAALGAGGGGGSCSGSSGLGEAGEDLSYGDVPPGPAFKEVWQVILKPKGLGQTKNLIGIYRLCLTSKTISFVKLNSEAAAVVLQLMNIRRCGHSENFFFIEVGRSAVTGPGEFWMQVDDSVVAQNMHETILEAMRAMSDEFRPRSKSQSSSNCSNPISVPLRRHHLNNPPPSQVGLTRRSRTESITATSPASMVGGKPGSFRVRASSDGEGTMSRPASVDGSPVSPSTNRTHAHRHRGSARLHPPLNHSRSIPMPASRCSPSATSPVSLSSSSTSGHGSTSDCLFPRRSSASVSGSPSDGGFISSDEYGSSPCDFRSSFRSVTPDSLGHTPPARGEEELSNYICMGGKGPSTLTAPNGHYILSRGGNGHRCTPGTGLGTSPALAGDEAASAADLDNRFRKRTHSAGTSPTITHQKTPSQSSVASIEEYTEMMPAYPPGGGSGGRLPGHRHSAFVPTRSYPEEGLEMHPLERRGGHHRPDSSTLHTDDGYMPMSPGVAPVPSGRKGSGDYMPMSPKSVSAPQQIINPIRRHPQRVDPNGYMMMSPSGGCSPDIGGGPSSSSSSSNAVPSGTSYGKLWTNGVGGHHSHVLPHPKPPVESSGGKLLPCTGDYMNMSPVGDSNTSSPSDCYYGPEDPQHKPVLSYYSLPRSFKHTQRPGEPEEGARHQHLRLSTSSGRLLYAATADDSSSSTSSDSLGGGYCGARLEPSLPHPHHQVLQPHLPRKVDTAAQTNSRLARPTRLSLGDPKASTLPRAREQQQQQQPLLHPPEPKSPGEYVNIEFGSDQSGYLSGPVAFHSSPSVRCPSQLQPAPREEETGTEEYMKMDLGPGRRAAWQESTGVEMGRLGPAPPGAASICRPTRAVPSSRGDYMTMQMSCPRQSYVDTSPAAPVSYADMRTGIAAEEVSLPRATMAAASSSSAASASPTGPQGAAELAAHSSLLGGPQGPGGMSAFTRVNLSPNRNQSAKVIRADPQGCRRRHSSETFSSTPSATRVGNTVPFGAGAAVGGGGGSSSSSEDVKRHSSASFENVWLRPGELGGAPKEPAKLCGAAGGLENGLNYIDLDLVKDFKQCPQECTPEPQPPPPPPPHQPLGSGESSSTRRSSEDLSAYASISFQKQPEDRQ
uniprot
proteins
disease_involvement
DISEASE: Type 2 diabetes mellitus (T2D) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. {ECO:0000269|PubMed:10206679, ECO:0000269|PubMed:12843189, ECO:0000269|PubMed:8723689}. Note=The gene represented in this entry may be involved in disease pathogenesis.
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:7541045, PubMed:33991522, PubMed:38625937). Plays therefore an important role in development, growth, glucose homeostasis as well as lipid metabolism (PubMed:19639489). 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:11171109, PubMed:8265614). 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 (By similarity). 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. Acts a positive regulator of the Wnt/beta-catenin signaling pathway through suppression of DVL2 autophagy-mediated degradation leading to cell proliferation (PubMed:24616100). {ECO:0000250|UniProtKB:P35570, ECO:0000269|PubMed:11171109, ECO:0000269|PubMed:16878150, ECO:0000269|PubMed:19639489, ECO:0000269|PubMed:38625937, ECO:0000269|PubMed:7541045, ECO:0000269|PubMed:8265614}.
uniprot
proteins
mass_dalton
131591
uniprot
proteins
mutagenesis
MUTAGEN 307; /note="S->A: Impaired degradation by the Cul7-RING(FBXW8) complex; when associated with A-312; A-527; A-636 and A-639."; /evidence="ECO:0000269|PubMed:18498745"; MUTAGEN 312; /note="S->A: Impaired degradation by the Cul7-RING(FBXW8) complex; when associated with A-307; A-527; A-636 and A-639."; /evidence="ECO:0000269|PubMed:18498745"; MUTAGEN 527; /note="S->A: Impaired degradation by the Cul7-RING(FBXW8) complex; when associated with A-307; A-312; A-636 and A-639."; /evidence="ECO:0000269|PubMed:18498745"; MUTAGEN 612; /note="Y->F: Induces IRS1 degradation."; /evidence="ECO:0000269|PubMed:23401856"; MUTAGEN 632; /note="Y->F: Does not affect IRS1 stability."; /evidence="ECO:0000269|PubMed:23401856"; MUTAGEN 636; /note="S->A: Impaired degradation by the Cul7-RING(FBXW8) complex; when associated with A-307; A-312; A-527 and A-639."; /evidence="ECO:0000269|PubMed:18498745"; MUTAGEN 639; /note="S->A: Impaired degradation by the Cul7-RING(FBXW8) complex; when associated with A-307; A-312; A-527 and A-636."; /evidence="ECO:0000269|PubMed:18498745"; MUTAGEN 794; /note="S->A: Loss of phosphorylation by SIK2."; /evidence="ECO:0000269|PubMed:12624099"; MUTAGEN 1186; /note="K->R: Significantly reduced TRAF4-mediated ubiquitination; when associated with R-1189."; /evidence="ECO:0000269|PubMed:33991522"; MUTAGEN 1189; /note="K->R: Significantly reduced TRAF4-mediated ubiquitination; when associated with R-1186."; /evidence="ECO:0000269|PubMed:33991522
uniprot
proteins
post_translational_modification
PTM: Serine phosphorylation of IRS1 is a mechanism for insulin resistance. Ser-307, Ser-312, Ser-315, and Ser-323 phosphorylations inhibit insulin action through disruption of IRS1 interaction with the insulin receptor INSR (PubMed:38625937). Phosphorylation of Tyr-896 is required for GRB2-binding (By similarity). Phosphorylated by ALK. Phosphorylated at Ser-270, Ser-307, Ser-636 and Ser-1101 by RPS6KB1; phosphorylation induces accelerated degradation of IRS1 (PubMed:18952604). Phosphorylated on tyrosine residues in response to insulin (PubMed:23401856). In skeletal muscles, dephosphorylated on Tyr-612 by TNS2 under anabolic conditions; dephosphorylation results in the proteasomal degradation of IRS1 (PubMed:23401856). {ECO:0000250|UniProtKB:P35569, ECO:0000250|UniProtKB:P35570, ECO:0000269|PubMed:15364919, ECO:0000269|PubMed:18498745, ECO:0000269|PubMed:18952604, ECO:0000269|PubMed:20685959, ECO:0000269|PubMed:23401856, ECO:0000269|PubMed:38625937}.; 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) (PubMed:18498745). Ubiquitinated by TRAF4 through 'Lys-29' linkage; this ubiquitination regulates the interaction of IRS1 with IGFR and IRS1 tyrosine phosphorylation upon IGF1 stimulation (PubMed:33991522). {ECO:0000269|PubMed:18498745, ECO:0000269|PubMed:33991522}.; PTM: S-nitrosylation at by BLVRB inhibits its activity. {ECO:0000269|PubMed:38056462}.
uniprot
proteins
pubmed
10206679
uniprot
proteins
pubmed
10411883
uniprot
proteins
pubmed
10843189
uniprot
proteins
pubmed
11171109
uniprot
proteins
pubmed
11694888
uniprot
proteins
pubmed
12624099
uniprot
proteins
pubmed
12679424
uniprot
proteins
pubmed
12843189
uniprot
proteins
pubmed
1311924
uniprot
proteins
pubmed
14671192
uniprot
proteins
pubmed
14707024
uniprot
proteins
pubmed
15226403
uniprot
proteins
pubmed
15364919
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15590636
uniprot
proteins
pubmed
15592455
uniprot
proteins
pubmed
16127460
uniprot
proteins
pubmed
16878150
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
18220336
uniprot
proteins
pubmed
18498745
uniprot
proteins
pubmed
18952604
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19639489
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20685959
uniprot
proteins
pubmed
23401856
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24616100
uniprot
proteins
pubmed
25101860
uniprot
proteins
pubmed
30092354
uniprot
proteins
pubmed
33991522
uniprot
proteins
pubmed
38056462
uniprot
proteins
pubmed
38625937
uniprot
proteins
pubmed
7537849
uniprot
proteins
pubmed
7541045
uniprot
proteins
pubmed
7559478
uniprot
proteins
pubmed
8104271
uniprot
proteins
pubmed
8240352
uniprot
proteins
pubmed
8265614
uniprot
proteins
pubmed
8513971
uniprot
proteins
pubmed
8599766
uniprot
proteins
pubmed
8723689
uniprot
proteins
sequence_length
1242
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19639489}. Nucleus {ECO:0000269|PubMed:19639489}. Note=Nuclear or cytoplasmic localization of IRS1 correlates with the transition from proliferation to chondrogenic differentiation. {ECO:0000269|PubMed:19639489}.
uniprot
proteins