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NCI: The SOCS box is an approximately 40 amino acid region of homology invariably located at the C-terminus of the proteins in which it is present. Initially identified in the SOCS, or suppressors of cytokine signaling family of proteins, the SOCS box appears to be involved in targeting proteins for ubiquitination. The SOCS box contains a sub-domain known as the BC-box that is also found in the VHLa domain. The BC box in both SOCS box and VHLa domain facilitates binding to the Elongin BC complex. Elongin BC, in turn, interacts with the von-Hippel Lindau (VHL) tumor suppressor protein to form the core of the larger VCB E3 ubiquitin protein ligase complex. Thus, the SOCS box/VHLa domain may serve a function analogous to the structurally related F-box protein linking substrates to E3 complexes to allow ubiquitination. Five classes of N-terminal regions are found associated with the C-terminal SOCS box. (Pawson Lab, SLRI, Mount Sinai Hospital, 2003)
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