Death domain of Nuclear Factor-KappaB precursor proteins
Death Domain (DD) of Nuclear Factor-KappaB (NF-kB) precursor proteins. The NF-kB family of transcription factors play a central role in cardiovascular growth, stress response, and inflammation by controlling the expression of a network of different genes. There are five NF-kB proteins, all containing an N-terminal REL Homology Domain (RHD). Two of these, NF-kB1 and NF-kB2 are produced from the processing of the precursor proteins p105 and p100, respectively. In addition to RHD, p105 and p100 contain ANK repeats and a C-terminal DD. NF-kBs are regulated by the Inhibitor of NF-kB (IkB) Kinase (IKK) complex through classical and non-canonical pathways, which differ in the IKK subunits involved and downstream targets. IKKs facilitate the release of NF-kB dimers from an inactive state, allowing them to migrate to the nucleus where they regulate gene transcription. The precursor proteins p105 and p100 function as IkBs and as NF-kB proteins after being processed by the proteasome. 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.",