DEATH

DEATH domain, found in proteins involved in cell death (apoptosis).
DEATH
SMART accession number:SM00005
Description: Alpha-helical domain present in a variety of proteins with apoptotic functions. Some (but not all) of these domains form homotypic and heterotypic dimers.
Interpro abstract (IPR000488):

The death domain (DD) is a homotypic protein interaction module composed of a bundle of six alpha-helices. DD is related in sequence and structure to the death effector domain (DED, see IPR001875 ) and the caspase recruitment domain (CARD, see IPR001315 ), which work in similar pathways and show similar interaction properties [ (PUBMED:11504623) ]. DD bind each other forming oligomers. Mammals have numerous and diverse DD-containing proteins [ (PUBMED:7482697) ]. Within these proteins, the DD domains can be found in combination with other domains, including: CARDs, DEDs, ankyrin repeats ( IPR002110 ), caspase-like folds, kinase domains, leucine zippers, leucine-rich repeats (LRR) ( IPR001611 ), TIR domains ( IPR000157 ), and ZU5 domains ( IPR000906 ) [ (PUBMED:15226512) ].

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 [ (PUBMED:14585074) (PUBMED:14601641) ]. 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 [ (PUBMED:12691620) ].

GO process:signal transduction (GO:0007165)
GO function:protein binding (GO:0005515)
Family alignment:
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There are 10756 DEATH domains in 10503 proteins in SMART's nrdb database.

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