SOCS3
entrez
9021
canonical
uniprot
O14543
canonical
ensembl
ENSG00000184557
resolver
ensp
ENSP00000330341
resolver
ensp
ENSP00000577785
resolver
ensp
ENSP00000582466
resolver
enst
ENST00000330871
resolver
enst
ENST00000907726
resolver
enst
ENST00000912407
resolver
genesymbol
SOCS3
resolver
genesymbol_syn
CIS3
resolver
genesymbol_syn
SSI3
resolver
hgnc
HGNC:19391
resolver
uniprot
O14509
resolver
uniprot
Q6FI39
resolver
uniprot_entry
Q6FI39_HUMAN
resolver
uniprot_entry
SOCS3_HUMAN
resolver
uniprot_sec
O14509
resolver
amino_acid_sequence
MVTHSKFPAAGMSRPLDTSLRLKTFSSKSEYQLVVNAVRKLQESGFYWSAVTGGEANLLLSAEPAGTFLIRDSSDQRHFFTLSVKTQSGTKNLRIQCEGGSFSLQSDPRSTQPVPRFDCVLKLVHHYMPPPGAPSFPSPPTEPSSEVPEQPSAQPLPGSPPRRAYYIYSGGEKIPLVLSRPLSSNVATLQHLCRKTVNGHLDSYEKVTQLPGPIREFLDQYDAPL
uniprot
proteins
disease_involvement
DISEASE: Note=There is some evidence that SOCS3 may be a susceptibility gene for atopic dermatitis linked to 17q25. SOCS3 messenger RNA is significantly more highly expressed in skin from patients with atopic dermatitis than in skin from healthy controls. Furthermore, a genetic association between atopic dermatitis and a haplotype in the SOCS3 gene has been found in two independent groups of patients. {ECO:0000269|PubMed:16685656}.
uniprot
proteins
function
FUNCTION: SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS3 is involved in negative regulation of cytokines that signal through the JAK/STAT pathway (PubMed:16459330). Inhibits signal transduction by binding to transmembrane signaling receptors including IL6ST/gp130, LIFR, EPOR, INSR, IL12RB2, CSF3R/G-CSF-R and LEPR. Binding to JAK2 inhibits its kinase activity and regulates IL6 signaling. Suppresses fetal liver erythropoiesis. Regulates onset and maintenance of allergic responses mediated by T-helper type 2 cells (By similarity). Probable substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15601820). Upon OSM stimulation, negatively regulates the JAK-STAT signaling mediated through type II OSM receptor complex by interacting directly with JAK1 (PubMed:16459330). {ECO:0000250|UniProtKB:O35718, ECO:0000269|PubMed:15601820, ECO:0000269|PubMed:16459330}.
uniprot
proteins
mass_dalton
24770
uniprot
proteins
mutagenesis
MUTAGEN 22; /note="L->A,F: Little effect on EPO-induced STAT5 signaling suppression."; /evidence="ECO:0000269|PubMed:10421843"; MUTAGEN 22; /note="L->D: Complete loss of EPO-induced STAT5 signaling suppression. No suppression of JAK2 phosphorylation."; /evidence="ECO:0000269|PubMed:10421843"; MUTAGEN 25; /note="F->A: Complete loss of EPO-induced STAT5 signaling suppression. Abolishes binding to JH1."; /evidence="ECO:0000269|PubMed:10421843"; MUTAGEN 30; /note="E->R: Partial loss of EPO-induced STAT5 signaling suppression. No effect on LIF-induced signaling suppression. Abolishes binding to JH1. Inhibits JAK2 phosphorylation."; /evidence="ECO:0000269|PubMed:10421843"; MUTAGEN 31; /note="Y->A: Complete loss of EPO-induced STAT5 signaling suppression. No effect on LIF-induced STAT3 signaling. Abolishes binding to JH1."; /evidence="ECO:0000269|PubMed:10421843"; MUTAGEN 31; /note="Y->F: Little effect on EPO-induced signaling suppression."; /evidence="ECO:0000269|PubMed:10421843"; MUTAGEN 34; /note="V->E: Complete loss of EPO/LIF-induced signaling suppression."; /evidence="ECO:0000269|PubMed:10421843"; MUTAGEN 41; /note="L->R: Complete loss of EPO/LIF-induced signaling inhibition. Abolishes binding to JH1."; /evidence="ECO:0000269|PubMed:10421843"; MUTAGEN 45; /note="G->A: Little effect on EPO/LIF signaling."; /evidence="ECO:0000269|PubMed:10421843"; MUTAGEN 53; /note="G->V: No effect on binding to Y429/Y431 phosphorylated EPOR."; /evidence="ECO:0000269|PubMed:12027890"; MUTAGEN 58; /note="L->A: Impaired binding to Y429/Y431 phosphorylated EPOR."; /evidence="ECO:0000269|PubMed:12027890"; MUTAGEN 71; /note="R->E: Complete loss of EPO/LIF-induced signaling suppression. No inhibition of JAK2 phosphorylation."; /evidence="ECO:0000269|PubMed:10421843, ECO:0000269|PubMed:14559241"; MUTAGEN 71; /note="R->K: No effect on EPO/LIF-induced signaling suppression. Partial suppression of JAK2 phosphorylation. No effect on binding to JH1. Loss of binding to IL12RB2."; /evidence="ECO:0000269|PubMed:10421843, ECO:0000269|PubMed:14559241"; MUTAGEN 93; /note="L->A: Impaired binding to Y429/Y431 phosphorylated EPOR."; /evidence="ECO:0000269|PubMed:12027890"; MUTAGEN 94; /note="R->E: Greatly impaired binding to Y429/Y431 phosphorylated EPOR."; /evidence="ECO:0000269|PubMed:12027890
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination.
uniprot
proteins
post_translational_modification
PTM: Phosphorylated on tyrosine residues after stimulation by the cytokines, IL-2, EPO or IGF1.
uniprot
proteins
pubmed
10421843
uniprot
proteins
pubmed
11071852
uniprot
proteins
pubmed
12027890
uniprot
proteins
pubmed
14559241
uniprot
proteins
pubmed
15070676
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15601820
uniprot
proteins
pubmed
16410555
uniprot
proteins
pubmed
16459330
uniprot
proteins
pubmed
16685656
uniprot
proteins
pubmed
23019338
uniprot
proteins
pubmed
9266833
uniprot
proteins
pubmed
9344848
uniprot
proteins
sequence_length
225
uniprot
proteins