<p>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 <db_xref db="INTERPRO" dbkey="IPR001875"/>) and the caspase recruitment domain (CARD, see <db_xref db="INTERPRO" dbkey="IPR001315"/>), which work in similar pathways and show similar interaction properties [<cite idref="PUB00015013"/>]. DD bind each other forming oligomers. Mammals have numerous and diverse DD-containing proteins [<cite idref="PUB00005444"/>]. Within these proteins, the DD domains can be found in combination with other domains, including: CARDs, DEDs, ankyrin repeats (<db_xref db="INTERPRO" dbkey="IPR002110"/>), caspase-like folds, kinase domains, leucine zippers (<db_xref db="INTERPRO" dbkey="IPR002158"/>), leucine-rich repeats (LRR) (<db_xref db="INTERPRO" dbkey="IPR001611"/>), TIR domains (<db_xref db="INTERPRO" dbkey="IPR000157"/>), and ZU5 domains (<db_xref db="INTERPRO" dbkey="IPR000906"/>) [<cite idref="PUB00015057"/>].</p><p>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 [<cite idref="PUB00015011"/>, <cite idref="PUB00015012"/>]. 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 [<cite idref="PUB00015014"/>].</p>