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 SOCS Box Domain | |
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Structure:
 The SOCS/VHLalpha domain consists of three alpha-helices that pack in a manner reminiscent of the so-called "folded-leaf" four helix cluster, except that the fourth helix is absent. A helix from Elongin C fits into this gap and completes the four helix cluster creating an arrangement of two pairs of helices that pack perpendicular to one another.
Structure Reference:
Stebbins, CE. et al. (1999) Science. 284(5413): 455-461. PDB: 1VCB.
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Domain binding and function:
The SOCS box is an approximately 40 amino acid region of homology that is invariably located at the C-terminus of the proteins in which it is present. Initially identified in the SOCS, or supressors 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/VHLalpha 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. These include SH2 domains (SOCS proteins), WD40 repeats (WSB proteins), a SPRY domain (SSB proteins), Ankyrin repeats (ASB proteins), and a GTPase domain (RAR family).
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Examples of Proteins:
| SOCS BOX Domain Proteins |
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Binding Partners |
| Socs-1 |  |
Elongin B/C |
| Socs-3 | |
Elongin B/C |
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Referenced in part on Cell Signaling Technology Website, Reference Section on Protein Domains. We gratefully acknowledge the following contributors:
Piers Nash1, Dan Lin3, Kathleen Binns2, Clark Wells2, Rob Ingham2, Terry Kubiseski2, Bernard Liu1, Matt Smith2,3, Ivan Blasutig2,3, Maria Sierra1, Caesar Lim2,3, Michael Arc1, Jim Fawcett2 and Tony Pawson2,3.
1. Ben May Institute for Cancer Research, The University of Chicago, Chicago, Illinois, 60637, USA
2. Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada
3. Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, M5S 1A8, Canada
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