SOCS6 Gene - Suppressor of Cytokine Signaling 6 | Function, Mutations & Disease

SOCS6 (Suppressor of Cytokine Signaling 6) encodes a member of the SOCS family of proteins that act as negative regulators of cytokine receptor signaling via the JAK-STAT pathway. The protein contains a central SH2 domain and a C-terminal SOCS box, mediating interactions with phosphorylated tyrosine residues and targeting signaling proteins for ubiquitination. SOCS6 is involved in insulin signaling, cell growth, and apoptosis, and has been implicated in various cancers and metabolic disorders.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• JAK-STAT signaling pathway (KEGG: hsa04630)

• Cytokine-cytokine receptor interaction (KEGG: hsa04060)

• Insulin signaling pathway (KEGG: hsa04910)

• SOCS-mediated negative regulation of cytokine signaling (Reactome: R-HSA-912526)

SOCS6 is a 535-amino acid protein (UniProt O14544) containing an N-terminal region, a central SH2 domain that binds phosphorylated tyrosines, and a C-terminal SOCS box that recruits E3 ubiquitin ligase components. It negatively regulates cytokine signaling by inhibiting JAK kinase activity and targeting signaling intermediates for proteasomal degradation. SOCS6 also modulates insulin receptor signaling by promoting IRS1/2 ubiquitination. Expression is widespread, with highest levels in heart, liver, and kidney. Altered expression or mutations are linked to cancer and metabolic diseases.