Death Effector Domain (DED) found in DEDD and DEDD2. Both proteins have a single N-terminal DED and a long C-terminal portion with no known domains. DEDD has been shown to block mitotic progression by inhibiting Cdk1 and to be involved in regulating the insulin signaling cascade. DEDD and DEDD2 can bind to themselves, to each other, and to the two tandem DED-containing caspases, caspase-8 and -10. In general, DEDs comprise a subfamily of the Death Domain (DD) superfamily. DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including PYRIN and CARD (Caspase activation and recruitment domain). They serve as adaptors in signaling pathways and they can recruit other proteins into signaling complexes.
Comment:The charge triad is part of a signature motif (E/D-RxDL) that is present in the DED family but not in other families of death domains (DD, CARD or Pyrin).
Comment:The charge triad is essential for the function of some DED-containing proteins. In FLIP, it is involved in the interaction with FADD to block apoptosis. In PEA15, the triad is necessary for interaction with ERK MAP kinase.