GENE NAMETNF receptor associated factor 6
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 signaling from members of the TNF receptor superfamily as well as the Toll/IL-1 family. Sigls from receptors such as CD40, TNFSF11/RANCE 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. This protein also interacts with the transforming growth factor (TGF) beta receptor complex and is required for Smad-independent activation of the JNK and p38 kinases. This protein has an amino termil RING domain which is followed by four zinc-finger motifs, a central coiled-coil region and a highly conserved carboxyl termil domain, known as the TRAF-C domain. Two altertively spliced transcript variants, encoding an identical protein, have been reported. [provided by RefSeq, Feb 2012]


Complication Evidence PMID
Neuropathy1. Treatment of diabetic peripheral neuropathy with sildefil, a phosphodiesterase type 5 inhibitor, augmentedMiRNA-146a expression and decreased levels of IRAK1 and TRAF6 in the DRG neurons. In vitro, blockage of MiRNA-146a in DRG neurons abolished the effect of sildefil on DRG neuron protection and downregulation of IRAK1 and TRAF6 proteins under hyperglycemia. Our data provide the first evidence showing that MiRNA-146a plays an important role in mediating DRG neuron apoptosis under hyperglycemic conditions.24316060
Nephropathy1. Significant association was also found between rs16928973 in TRAF6 gene and diabetic nephropathy (DN) under the allelic model.27062898