The death effector domain (DED) is a homotypic protein interaction module composed of a bundle of six alpha-helices. DED is related in sequence and structure to the death domain (DD, see IPR000488 ) and the caspase recruitment domain (CARD, see IPR001315 ), which work in similar pathways and show similar interaction properties [ (PUBMED:11504623) ]. The dimerisation of DED domains is mediated primarily by electrostatic interactions. DED domains can be found in isolation, or in combination with other domains. Domains associated with DED include: caspase catalytic domains (in caspase-8, -10), death domains (in FADD), nuclear localisation sequences (in DEDD), transmembrane domains (in Bap31 and Bar), nucleotide-binding domains (in Dap3), coiled-coil domains (in Hip and Hippi), SAM domains (in Bar), and E2-binding RING domains (in Bar) [ (PUBMED:15226512) ].
Several DED-containing proteins are involved in the regulation of apoptosis through their interactions with DED-containing caspases, such as caspases 8 and 10 in humans, both of which contain tandem pairs of DEDs. There are many DED-containing modulators of apoptosis, which can either enhance or inhibit caspase activation [ (PUBMED:15173180) ].
Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death.
Cell. 1996; 85: 803-15
Display abstract
Fas/APO-1 and p55 tumor necrosis factor (TNF) receptor (p55-R) activate cellular mechanisms that result in cell death. Upon activation of these receptors, Fas/APO-1 binds a protein called MORT1 (or FADD) and p55-R binds a protein called TRADD. MORT1 and TRADD can also bind to each other. We have cloned a novel protein, MACH, that binds to MORT1. This protein exists in multiple isoforms, some of which contain a region that has proteolytic activity and shows marked sequence homology to proteases of the ICE/CED-3 family. Cellular expression of the proteolytic MACH isoforms results in cell death. Expression of MACH isoforms that contain an incomplete ICE/CED-3 region provides effective protection against the cytotoxicity induced by Fas/APO-1 or p55-R triggering. These findings suggest that MACH is the most upstream enzymatic component in the Fas/APO-1- and p55-R-induced cell death signaling cascades.
Metabolism (metabolic pathways involving proteins which contain this domain)
This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with DED domain which could be assigned to a KEGG orthologous group, and not all proteins containing DED domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
