SOCS3
This gene encodes a member of the STAT-induced STAT inhibitor (SSI), also known as suppressor of cytokine signaling (SOCS), family. SSI family members are cytokine-inducible negative regulators of cytokine signaling. The expression of this gene is induced by various cytokines, including IL6, IL10, and interferon (IFN)-gamma. The protein encoded by this gene can bind to JAK2 kinase, and inhibit the activity of JAK2 kinase. Studies of the mouse counterpart of this gene suggested the roles of this gene in the negative regulation of fetal liver hematopoiesis, and placental development. [provided by RefSeq, Jul 2008]
Full Name
Suppressor Of Cytokine Signaling 3
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 IL6ST/gp130, LIF, erythropoietin, insulin, IL12, GCSF and leptin receptors. 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).
Biological Process
Biological Process branching involved in labyrinthine layer morphogenesisIEA:Ensembl
Biological Process cell differentiationIEA:Ensembl
Biological Process cellular response to interleukin-17IEA:Ensembl
Biological Process cellular response to leukemia inhibitory factorIEA:Ensembl
Biological Process intracellular signal transductionIEA:InterPro
Biological Process negative regulation of apoptotic processManual Assertion Based On ExperimentTAS:ProtInc
Biological Process negative regulation of inflammatory responseIEA:Ensembl
Biological Process negative regulation of insulin receptor signaling pathwayIEA:Ensembl
Biological Process negative regulation of receptor signaling pathway via JAK-STATManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process negative regulation of tyrosine phosphorylation of STAT proteinManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process phosphatidylinositol phosphate biosynthetic processManual Assertion Based On ExperimentIBA:GO_Central
Biological Process placenta blood vessel developmentIEA:Ensembl
Biological Process positive regulation of cell differentiationIEA:Ensembl
Biological Process protein ubiquitinationIEA:UniProtKB-UniPathway
Biological Process receptor signaling pathway via JAK-STATIEA:InterPro
Cellular Location
cytosol
phosphatidylinositol 3-kinase complex
Involvement in disease
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.
PTM
Phosphorylated on tyrosine residues after stimulation by the cytokines, IL-2, EPO or IGF1.
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