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SOCS3

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.

The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes.

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).

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.

Pathway

Protein modification; protein ubiquitination.

Post-translational modifications

Phosphorylated on tyrosine residues after stimulation by the cytokines, IL-2, EPO or IGF1.

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.

Alternative names

  • Suppressor of cytokine signaling 3
  • SOCS-3
  • Cytokine-inducible SH2 protein 3
  • STAT-induced STAT inhibitor 3
  • CIS-3
  • SSI-3
  • SSI3
  • CIS3
  • SOCS3

Target type

Proteins

Primary research area

Immunology & Infectious Disease

Molecular weight

24770Da