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).

1. Kamura, T., Maenaka, K., Kotoshiba, S., Matsumoto, M., Kohda, D., Conaway, R.C., Conaway, J.W. and Nakayama, K.I. (2004). VHL-box and SOCS-box domains determine binding specificity for Cul2-Rbx1 and Cul5-Rbx2 modules of ubiquitin ligases. Genes Dev., 18, 3055-3065. PMID: 15601820