Death Effector Domain, repeat 2, of cellular FLICE-Inhibitory Protein
Death Effector Domain (DED), repeat 2, similar to that found in cellular FLICE-inhibitory protein (c-FLIP/CASH, also known as Casper/iFLICE/FLAME-1/CLARP/MRIT/usurpin). c-FLIP is a catalytically inactive homolog of the initator procaspases-8 and -10. It negatively influences apoptotic signaling by interfering with the efficient formation of the Death Inducing Signalling Complex (DISC). At low levels, c-FLIP has been shown to enhance apoptotic signaling by allosterically activating caspase-8. As a modulator of the initiator caspases, c-FLIP regulates life and death in various types of cells and tissues. All members contain two N-terminal DEDs and a C-terminal pseudo-caspase domain. 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 can recruit other proteins into signaling complexes.
Comment:The tandem DED domains, DED1 and DED2, in FLIP are associated rigidly to form a single compact structure, with each domain playing a unique structural role and is not interchangeable with the other. This explains why both domains are required for FLIP function.
Structure:2BBZ_A; Interface between DED1 and DED2 in Molluscum contagiosum virus MC159 (v-FLIP); contacts at 4A.
Jiyao W et al.(2023). "The conserved domain database in 2023.",