SOCS box

Kamuea, T., et al.. The Elongin BC complex interacts with the conserved SOCS-box motif present in members of the SOCS, ras, WD-40 repeat, and ankyrin repeat families. Genes Dev,... 

Kamizono, S., et al.. The SOCS box of SOCS-1 accelerates ubiquitin-dependent proteolysis ofTEL-JAK2./ Biol Chem, 2001, 276(16), 12530-8. 

Zhang, J. G., et al.. The conserved SOCS box motif in suppressors of cytokine signaling binds to elongins B and C and may couple bound proteins to proteasomal degradation. Proc Nad Acad Sci USA, 1999, 96(5), 2071-6. 

Fig. 7.7. Comparison of the Skp2-Skpl and VHL-ElonginC-ElonginB complexes reveals the structural similarity between the E-box and SOCS-box (VHL a-domain) and similarity of the assembly of the intact SI

They do this in at least two ways. First, because they contain SH2 domains, they can bind to the phosphotyrosine residues of proteins involved in the pathway. In doing this they act as competitive inhibitors of the pathway proteins that are activated by binding to these residues. Second, they contain a domain called a SOCS box. The SOCS box forms part of an 3 Ub ligase. Therefore, binding of SOCS proteins to proteins in the pathway targets them for ubiquitinylation and subsequent degradation. 

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