Death Effector Domain: a protein-protein interaction domain
Death Effector Domains comprise a subfamily of the Death Domain (DD) superfamily. DED-containing proteins include Fas-Associated via Death Domain (FADD), Astrocyte phosphoprotein PEA-15, the initiator caspases (caspase-8 and -10), and FLICE-inhibitory protein (FLIP), among others. These proteins are prominent components of the programmed cell death (apoptosis) pathway. Some members also have non-apoptotic functions such as regulation of insulin signaling (DEDD and PEA15) and cell cycle progression (DEDD). 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.