The TRAF-C domain is involved in homotypic and heterotypic aggregation of TRAFs and in interaction of the TNF-receptor superfamily. TRAF6 cDNA has been identified as sequences homologous to the TRAF-C domain of TRAF2 and as binding the cytoplasmic tail of CD40 using the yeast two hybrid system. TRAF6 has a TRAF domain in its carboxyl terminus and has a RING finger domain, a cluster of zinc fingers and a coiled-coil domain. TRAF6 interacts strongly with itself, and weakly with both TRAF2 and TRAF3. Overexpression of TRAF6 activates NF-?B. TRAF6 is likely to be a component of the signaling cascade that starts at the IL-1? receptor and results in the activation of NF-?B.