Death Effector Domain found in Fas-Associated via Death Domain
Death Effector Domain (DED) found in Fas-Associated via Death Domain (FADD). DEDs comprise a subfamily of the Death Domain (DD) superfamily. FADD is a component of the death-inducing signaling complex (DISC) and serves as an adaptor in the signaling pathway of death receptor proteins. It modulates apoptosis as well as non-apoptotic processes such as cell cycle progression, survival, innate immune signaling, and hematopoiesis. FADD contains an N-terminal DED and a C-terminal DD. Its DD interacts with the DD of the activated death receptor and its DED recruits the initiator caspases 8 and 10 to the DISC complex via a homotypic interaction with the N-terminal DED of the caspase. 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.
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