TRAFs (TNF receptor associated proteins) form a family of cytoplasmic adapter proteins that mediate signal transduction from many members of the TNF-receptor superfamily and the interleukin-1 receptor. The carboxy-terminal region of TRAFs is required for self-association and interaction with receptor cytoplasmic domains following ligand-induced oligomerization. Recent molecular cloning studies have lead to identification of six TRAFs (TRAF1-TRAF6). TRAF3, originally named CRAF1, interacts directly with the CD40 cytoplasmic tail throμgh a region of similarity to the tumor necrosis factor-alpha (TNF-alpha) receptor-associated factors. TRAF3 binds only a single site, which contains the sequence PEQET, whereas TRAF1 and TRAF2 are capable of binding to either the PEQET site or an additional downstream domain.