SOCS2 complex

SOCS2 complex

SOCS2 complex: Human SOCS2-ElonginC-ElonginB complex
PDB Code: 2C9W
The suppressor of cytokine signalling (SOCS) family comprises SOCS1-7 and CIS1. Members of this family have been shown to be negative regulators of cytokine receptor signalling via the JAK/STAT pathway. The proteins contain a variable N-terminal domain, a central SH2 domain and a C-terminal SOCS box. The SOCS box shows weak sequence similarity with the alpha domain of the von Hippel Lindau (VHL) tumour suppressor which binds ElonginC/B to target hypoxia-inducible factor (HIF-1 a ) for proteasomal degradation. By analogy it has been speculated that many, if not all, SOCS box-containing proteins act as part of an E3 ubiquitin ligase complex.
The role of SOCS2 in growth hormone (GH) signalling in vivo has been convincingly demonstrated by the phenotype of SOCS2 deficient mice, which are 30-40% larger than normal littermates. This phenotype is similar to mice overexpressing GH and human patients with gigantism. The specific linkage of the SOCS2 -/- phenotype to the JAK/STAT pathway has been demonstrated by STAT5b/SOCS2 double knockout mice which have no overgrowth phenotype. Further studies have demonstrated specific binding of SOCS2 to the phosphorylated GH receptor and regulation of its signalling in vitro.
The structure of human SOCS2 in complex with ElonginC and ElonginB was refined at 1.9 Å resolution and includes a central SH2 domain flanked by an N-terminal extended SH2 subdomain and a C-terminal SOCS box.

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