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TRAFs (TNF receptor-associated factors) are a family of multifunctional adaptor proteins that bind to surface receptors and recruit additional proteins to form multiprotein signaling complexes capable of promoting cellular responses. 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.TRAF6 plays a critical role in innate and adaptive immunity, bone metabolism, and development of certain tissues including the nervous system. TRAF6 also activates Src family nonreceptor tyrosine kinases leading to Akt activation.