SOCS/VHL/BC-box represents a family that comprises SOCS proteins, VHL proteins and only BC-box containing proteins. The BC-box is a sub-domain that exists in both the SOCS and VHL domains and facilitates binding to the Elongin-B/C complex. SOCS is an ~80-residue domain named "Supressors Of Cytokine Signaling", which is located in the C-terminus and specifically recognize and bind a substrate. VHL is named "Von-Hippel Lindau", which forms the core of a large BCR E3 ubiquitin ligase complex. Compared to the SOCS domain, VHL lacks a C-terminal sequence (downstream of the BC-box) of the SOCS. VHL protein specifically interacts with endogenous Cul2-Rbx1 in mammalian cells. VHL or SOCS can serve as a substrate recognition subunit and form a BCR ubiquitin ligase complex, which targets the substrates for proteasome degradation (1).
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