SOCS4 complex: Human SOCS4-ElonginC-ElonginB complex
PDB Code: 2IZV
The suppressor of cytokine signalling (SOCS) family comprises in human SOCS1-7 and CIS1. In general SOCS 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 SOCS4 in vivo is not clear and so far no substrates have been unambiguously identified. SOCS4 shares significant sequence homology with SOCS5 and the lack of an obvious lymphoid phenotype in SOCS5-deficient mice may reflect functional redundancy between these two SOCS family members. Both SOCS proteins are induced by EGF and are reported to target EGFR for proteasomal degradation. The structure of human SOCS4 in complex with ElonginC and ElonginB was refined at 2.55 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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