| Primary Identifier | IPR000488 | Type | Domain |
| Short Name | Death_domain |
| description | The death domain (DD) is a homotypic protein interaction module composed of a bundle of six α-helices. DD is related in sequence and structure to the death effector domain (DED, see ) and the caspase recruitment domain (CARD, see ), which work in similar pathways and show similar interaction properties []. DD bind each other forming oligomers. Mammals have numerous and diverse DD-containing proteins []. Within these proteins, the DD domains can be found in combination with other domains, including: CARDs, DEDs, ankyrin repeats (), caspase-like folds, kinase domains, leucine zippers, leucine-rich repeats (LRR) (), TIR domains (), and ZU5 domains () [].Some DD-containing proteins are involved in the regulation of apoptosis and inflammation through their activation of caspases and NF-kappaB, which typically involves interactions with TNF (tumour necrosis factor) cytokine receptors [, ]. In humans, eight of the over 30 known TNF receptors contain DD in their cytoplasmic tails; several of these TNF receptors use caspase activation as a signalling mechanism. The DD mediates self-association of these receptors, thus giving the signal to downstream events that lead to apoptosis. Other DD-containing proteins, such as ankyrin, MyD88 and pelle, are probably not directly involved in cell death signalling. DD-containing proteins also have links to innate immunity, communicating with Toll family receptors through bipartite adapter proteins such as MyD88 []. |
