Domain

Death domain (IPR000488)

Short name: Death_domain

Domain relationships

Description

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 [PMID: 11504623]. DD bind each other forming oligomers. Mammals have numerous and diverse DD-containing proteins [PMID: 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 (IPR002158), leucine-rich repeats (LRR) (IPR001611), TIR domains (IPR000157), and ZU5 domains (IPR000906) [PMID: 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 [PMID: 14585074, PMID: 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 [PMID: 12691620].

GO terms

Biological Process

GO:0007165 signal transduction

Molecular Function

GO:0005515 protein binding

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
Pfam
SMART
PROSITE profiles