Death-like domain superfamily (IPR011029)
Short name: DEATH-like_dom_sf
- Death domain (IPR000488)
- CARD domain (IPR001315)
- Death effector domain (IPR001875)
- DAPIN domain (IPR004020)
- FADD (IPR016729)
- Apoptosis regulator, Ced-4 (IPR016854)
- Apoptotic protease-activating factor 1 (IPR017251)
- Myeloid differentiation primary response protein MyD88 (IPR017281)
- Receptor-interacting serine/threonine-protein kinase 2 (IPR017322)
- Interleukin-1 receptor-associated kinase 4 (IPR017428)
- Tube, Death domain (IPR029397)
- Astrocytic phosphoprotein PEA-15 (IPR029546)
- Caspase-9 (IPR033171)
- B-cell lymphoma/leukemia 10/E10 (IPR033238)
- Caspase recruitment domain-containing protein 11 (IPR033538)
- Interleukin-1 receptor-associated kinase 3 (IPR033610)
- Interleukin-1 receptor-associated kinase-like 2 (IPR033611)
- Tumor necrosis factor receptor 1A, death domain (IPR033994)
- Fas receptor, death domain (IPR033998)
- Tumour necrosis factor receptor 10A/B, death domain (IPR034029)
- Tumor necrosis factor receptor 21, death domain (IPR034037)
- MyD88, death domain (IPR034249)
- Interleukin-1 receptor-associated kinase 1, death domain (IPR035533)
- Caspase-10 (IPR035701)
- Caspase-2 (IPR035702)
- TRADD (IPR035712)
- Pelle, death domain (IPR037924)
- RIP1, Death domain (IPR037934)
- Death domain-containing protein CRADD (IPR037939)
- MALT1, death domain (IPR037940)
- Apoptotic Protease-Activating Factor 1, CARD domain (IPR037963)
- IRAK4, Death domain (IPR037970)
- Ankyrin-3, death domain (IPR037971)
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 [PMID: 11828422, PMID: 12655292]. 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 [PMID: 15226512].
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 [PMID: 12719729]. 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 [PMID: 12101092]. 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.
This superfamily represents the death domain and other structurally similar domains, including DED, CARD and the DAPIN domain.
- SSF47986 (SSF47986)