Death domain of tumor necrosis factor receptor superfamily member 21
Death domain (DD) found in tumor necrosis factor receptor superfamily member 21 (TNFRSF21), also called death receptor-6, DR6. DR6 is an orphan receptor that is expressed ubiquitously, but shows high expression in lymphoid organs, heart, brain and pancreas. Results from DR6(-/-) mice indicate that DR6 plays an important regulatory role for the generation of adaptive immunity. It may also be involved in tumor cell survival and immune evasion. In neuronal cells, it binds beta-amyloid precursor protein (APP) and activates caspase-dependent cell death. It may contribute to the pathogenesis of Alzheimer's disease. In general, 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 CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.
Jiyao W et al.(2023). "The conserved domain database in 2023.",