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MGP Database

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MGP003770

UniProt Annotations

Entry Information

Gene Name	suppressor of cytokine signaling 3
Protein Entry	SOCS3_HUMAN
UniProt ID	O14543
Species	Human

Comments

Comment type	Description
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.
Domain	The ESS and SH2 domains are required for JAK phosphotyrosine binding. Further interaction with the KIR domain is necessary for signal and kinase inhibition.
Domain	The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes. {ECO:0000250}.
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. Inhibits cytokine signal transduction by binding to tyrosine kinase receptors including gp130, LIF, erythropoietin, insulin, IL12, GCSF and leptin receptors. Binding to JAK2 inhibits its kinase activity. Suppresses fetal liver erythropoiesis. Regulates onset and maintenance of allergic responses mediated by T-helper type 2 cells. Regulates IL-6 signaling in vivo (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. Seems to recognize IL6ST (By similarity). {ECO:0000250}.
Interaction	Q13480:GAB1; NbExp=4; IntAct=EBI-714146, EBI-517684; P10721:KIT; NbExp=3; IntAct=EBI-714146, EBI-1379503; Q66K74:MAP1S; NbExp=6; IntAct=EBI-714146, EBI-2133734;
Pathway	Protein modification; protein ubiquitination.
Ptm	Phosphorylated on tyrosine residues after stimulation by the cytokines, IL-2, EPO or IGF1.
Similarity	Contains 1 SH2 domain. {ECO:0000255\|PROSITE- ProRule:PRU00191}.
Similarity	Contains 1 SOCS box domain. {ECO:0000255\|PROSITE- ProRule:PRU00194}.
Subunit	Interacts with multiple activated proteins of the tyrosine kinase signaling pathway including IGF1 receptor, insulin receptor and JAK2. Binding to JAK2 is mediated through the KIR and SH2 domains to a phosphorylated tyrosine residue within the JAK2 JH1 domain. Binds specific activated tyrosine residues of the leptin, EPO, IL12, GSCF and gp130 receptors. Interaction with CSNK1E stabilizes SOCS3 protein. Component of the probable ECS(SOCS3) E3 ubiquitin-protein ligase complex which contains CUL5, RNF7/RBX2, Elongin BC complex and SOCS3. Interacts with CUL5, RNF7, TCEB1 and TCEB2. Interacts with CUL2. Interacts with FGFR3. Interacts with INSR (By similarity). Interacts with BCL10; this interaction may interfere with BCL10-binding with PELI2 (By similarity). {ECO:0000250}.
Tissue Specificity	Widely expressed with high expression in heart, placenta, skeletal muscle, peripheral blood leukocytes, fetal and adult lung, and fetal liver and kidney. Lower levels in thymus.
Web Resource	Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/SOCS3ID44124ch17q25.html";