TRAF6
Description
The TRAF6 (TNF receptor associated factor 6) is a protein-coding gene located on chromosome 11.
TRAF6 is a TRAF human protein. The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins are associated with, and mediate signal transduction from members of the TNF receptor superfamily. This protein mediates the signaling not only from the members of the TNF receptor superfamily, but also from the members of the Toll/IL-1 family. Signals from receptors such as CD40, TNFSF11/TRANCE/RANKL and IL-1 have been shown to be mediated by this protein. This protein also interacts with various protein kinases including IRAK1/IRAK, SRC and PKCzeta, which provides a link between distinct signaling pathways. This protein functions as a signal transducer in the NF-kappaB pathway that activates IkappaB kinase (IKK) in response to proinflammatory cytokines. The interaction of this protein with UBE2N/UBC13, and UBE2V1/UEV1A, which are ubiquitin conjugating enzymes catalyzing the formation of polyubiquitin chains, has been found to be required for IKK activation by this protein. Two alternatively spliced transcript variants encoding identical proteins have been reported.
TRAF6 is an E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of 'Lys-63'-linked-polyubiquitin chains conjugated to proteins, such as ECSIT, IKBKG, IRAK1, AKT1 and AKT2. It also mediates ubiquitination of free/unanchored polyubiquitin chain that leads to MAP3K7 activation. TRAF6 leads to the activation of NF-kappa-B and JUN. TRAF6 appears to play a role in dendritic cells (DCs) maturation and/or activation. It represses c-Myb-mediated transactivation, in B-lymphocytes. TRAF6 is an adapter protein that appears to play a role in signal transduction initiated via TNF receptor, IL-1 receptor and IL-17 receptor. It regulates osteoclast differentiation by mediating the activation of adapter protein complex 1 (AP-1) and NF-kappa-B, in response to RANK-L stimulation. Together with MAP3K8, TRAF6 mediates CD40 signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. TRAF6 participates also in the TCR signaling by ubiquitinating LAT.
TRAF6 is also known as MGC:3310, RNF85.
