The Death-domain

A heterodimerization domain present in several proteins involved in apoptotic signal transduction and the NFkB pathway.

This page is based on the publication:
Hofmann K. and Tschopp J. (1995), The death domain motif found in Fas(Apo-1) and TNF receptor is present in proteins involved in apoptosis and axonal guidance FEBS Lett. 371:321-323

Short description

The death domain has initially been characterized as a intracellular homology domain of FAS (Apo-1) and the TNF-receptor, which is important for apoptotic signaling in both receptors [1]. Subsequently, a number of other proteins have been found to interact with the cytoplasmic part of either FAS or the TNF receptor in the region of the death domain. Overexpression of these proteins usually leads to cell death. By profile analysis, we have shown that a number of other proteins contain regions with significant similarity to the death domain. Interestingly, several of these proteins also work in the context of cell death signaling. The list of death domain containing proteins comprises the FAS, TNF-receptor, NGF-receptor, several receptor-interacting proteins( MORT1/FADD, TRADD, RIP) all isoforms of ankyrin, the human 'death-associated protein kinase' (DAP-kinase), MyD88, the axonal guidance molecule unc-5, and the protein kinase pelle, acting in the drosophila toll/dorsal/cactus pathway which has analogies to the mammalian NFkB pathway. In a related paper, Feinstein et al. also reported death domains in NFkB and tube. These domains have borderline significance in our profile analysis.

[1] Cleveland J., Ihle J.N., Cell 81:479-482 (1995).
[2] Feinstein E., Kimchi A., Wallach D., Boldin M., Varfolomeev E., Trends Biochem. Sci. 20:342-344 (1995).

PROSITE

The death domain is included in PROSITE under the accession numbers PS50017 for the data entry, and PDOC50017 for the documentation entry. The alignment used for construction of the profile is available in MSF format. There is also an updated list of database sequences containing death domains.

Domain cartoons

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Abbreviations: TR: TNFR-family Cys-rich repeat; A: Ankyrin-repeat; DD: death domain; Ig: Immunoglobulin domain; toll: IL1R/toll domain.
Links to WWW-pages describing some of these domains can be found near the bottom of this page.

Alignment of representative sequences

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Note: You can check your sequence for the occurence of this and other domains by using the ProfileScan server.
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