TRAF6 protein

The TRAF6 protein (TRAF6 stands for "TNF Receptor Associated Factor 6") is encoded by the gene of the same name, which is located on chromosome 11p12. TRAF proteins belong to the family of TNF receptor-associated factors (TRAF proteins).

TRAF proteins are associated with members of the TNF receptor superfamily and mediate their signal transduction. The TRAF-6 protein has an amino-terminal RING domain followed by four zinc finger motifs, a central coiled-coil region, and a highly conserved carboxyl-terminal domain known as the TRAF-C domain, which mediates signaling from members of the TNF receptor superfamily as well as the Toll/IL-1 family.

Signals from receptors such as CD40, TNFSF11/RANCE and interleukin-1 have been shown to be mediated by this protein (Cao Z et al. 1996). The encoded protein also interacts with various protein kinases, including IRAK1/IRAK, SRC and PKCzeta, providing a link between different signaling pathways. TRAF6 protein as a signal transducer in the NF-kappaB signaling pathway, which activates IkappaB kinase (IKK) in response to proinflammatory cytokines (Shembade N et al. 2007). Its interaction with UBE2N/UBC13 and UBE2V1/UEV1A, which are ubiquitin-conjugating enzymes that catalyze the formation of polyubiquitin chains, has been shown to be required for IKK activation.

The TRAF6 protein also interacts with the transforming growth factor (TGF) beta receptor complex and is required for Smad-independent activation of JNK and p38 kinases. It is a key molecule in antiviral innate and antigen-specific immune responses.

The encoded protein acts as an adapter protein that appears to play a role in signal transduction initiated via TNF receptor, TLR-1 receptor, IL-1 and IL-17 receptors (Ye H et al. 2002). Among other things, regulates osteoclast differentiation by mediating the activation of adapter protein complex 1 (AP-1) and NF-kappa-B in response to stimulation by RANK-L.