Tumor necrosis factor receptor-associated factor 6 (TRAF6) regulates adaptive immunity, innate immunity and bone metabolism. TRAF6 is a ubiquitin (Ub) ligase that mediates the activation of protein kinases, such as transforming growth factor beta-activated kinase (TAK1) and IκB kinase (IKK), by catalyzing the formation of a unique polyubiquitin chain linked through Lys 63 of Ub. TRAF6 is essential for activating NFκB signaling pathway in response to interleukin-1 and Toll-like receptor ligands. The coiled-coil domain of TRAF6 is essential for its auto-ubiquitination and activating NFκB signaling pathway.
