SSF47986

DEATH domain

SUPERFAMILY entry
Member databaseSUPERFAMILY
SUPERFAMILY typehomologous superfamily

Description
Imported from IPR011029

This superfamily represents the death domain and other structurally similar domains, including DED, CARD and the DAPIN domain.

The death domain (DD) is a conserved region of about 80 residues found on death receptors, and which is required for death signalling, as well as a variety of non-apoptotic functions
[1, 2]
. Proteins containing this domain include the low affinity neurotrophin receptor p73, Fas, FADD (Fas-associated death domain protein), TNF-1 (tumour necrosis factor receptor-1), Pelle protein kinase, and the Tube adaptor protein
[5]
.

The induction of apoptosis also relies on the presence of a second domain, called the death effector domain. The death effector domain (DED) occurs in proteins that regulate programmed cell death, including both pro- and anti-apoptotic proteins; many of these proteins are also involved in controlling cellular activation and proliferation pathways
[3]
. Proteins containing this domain include FADD (DED N-terminal, DD C-terminal), PEA-15 (phosphoproteins enriched in astrocytes 15kDa), caspases and FLIP.

The induction of apoptosis results in the activation of caspases, a family of aspartyl-specific cysteine proteases that are the main executioners of apoptosis. For example, the DED of FADD recruits two DED-containing caspases, caspase-8 and caspase-10, to form the death-inducing signal complex, which initiates apoptosis. Proteins containing the caspase recruitment domain (CARD) are involved in the recruitment and activation of caspases during apoptosis
[4]
. Other CARD proteins participate in NF-kappaB signalling pathways associated with innate or adaptive immune responses. Proteins containing CARD include Raidd, APAF-1 (apoptotic protease activating factor 1), procaspase 9 and iceberg (inhibitor of interleukin-1-beta generation).

The DD shows strong structural similarity to both DED and CARD. They all display a 6-helical closed bundle fold, with greek key topology and an internal psuedo two-fold symmetry. However, despite their overall similarity in topology, each domain forms specialised interactions, typically only with members of its own subfamily, for example DED with DED.

References
Imported from IPR011029

1.Molecular mechanisms of death-receptor-mediated apoptosis. Sartorius U, Schmitz I, Krammer PH. Chembiochem 2, 20-9, (2001). View articlePMID: 11828422

2.All in the family: evolutionary and functional relationships among death receptors. Bridgham JT, Wilder JA, Hollocher H, Johnson AL. Cell Death Differ. 10, 19-25, (2003). View articlePMID: 12655292

3.The death effector domain protein family: regulators of cellular homeostasis. Tibbetts MD, Zheng L, Lenardo MJ. Nat. Immunol. 4, 404-9, (2003). View articlePMID: 12719729

4.CARD games in apoptosis and immunity. Bouchier-Hayes L, Martin SJ. EMBO Rep. 3, 616-21, (2002). View articlePMID: 12101092

5.The domains of apoptosis: a genomics perspective. Reed JC, Doctor KS, Godzik A. Sci. STKE 2004, re9, (2004). View articlePMID: 15226512

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