Summary: Death domain
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Death domain Edit Wikipedia article
Structure of the Fas (APO-1/CD95) death domain.
The death domain (DD) is a protein interaction module composed of a bundle of six alpha-helices. DD is a subclass of protein motif known as the death fold and is related in sequence and structure to the death effector domain (DED) and the caspase recruitment domain (CARD), which work in similar pathways and show similar interaction properties. DD bind each other forming oligomers. Mammals have numerous and diverse DD-containing proteins. Within these proteins, the DD domains can be found in combination with other domains, including: CARDs, DEDs, ankyrin repeats, caspase-like folds, kinase domains, leucine zippers, leucine-rich repeats (LRR), TIR domains, and ZU5 domains.
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. 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 signaling 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-like receptors through bipartite adapter proteins such as MyD88.
- Huang B, Eberstadt M, Olejniczak ET, Meadows RP, Fesik SW (1996). "NMR structure and mutagenesis of the Fas (APO-1/CD95) death domain". Nature 384 (6610): 638–41. doi:10.1038/384638a0. PMID 8967952.
- Weber CH, Vincenz C (August 2001). "The death domain superfamily: a tale of two interfaces?". Trends Biochem. Sci. 26 (8): 475–81. doi:10.1016/S0968-0004(01)01905-3. PMID 11504623.
- Feinstein E, Kimchi A, Wallach D, Boldin M, Varfolomeev E (September 1995). "The death domain: a module shared by proteins with diverse cellular functions". Trends Biochem. Sci. 20 (9): 342–4. doi:10.1016/S0968-0004(00)89070-2. PMID 7482697.
- Reed JC, Doctor KS, Godzik A (June 2004). "The domains of apoptosis: a genomics perspective". Sci. STKE 2004 (239): re9. doi:10.1126/stke.2392004re9. PMID 15226512.
- Wajant H (2003). "Death receptors". Essays Biochem. 39: 53–71. PMID 14585074.
- Bhardwaj A, Aggarwal BB (September 2003). "Receptor-mediated choreography of life and death". J. Clin. Immunol. 23 (5): 317–32. doi:10.1023/A:1025319031417. PMID 14601641.
- O'Neill LA, Dunne A, Edjeback M, Gray P, Jefferies C, Wietek C (2003). "Mal and MyD88: adapter proteins involved in signal transduction by Toll-like receptors". J. Endotoxin Res. 9 (1): 55–9. doi:10.1179/096805103125001351. PMID 12691620.
This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
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Hofmann K, Tschopp J; , FEBS lett 1995;371:321-323.: The death domain motif found in Fas (Apo-1) and Tnf receptor is Present in proteins involved in apoptosis and axonal guidance. PUBMED:7556620 EPMC:7556620
Feinstein E, Kimchi A, Wallach D, Boldin M, Varfolomeev E; , Trends Biochem Sci 1995;20:342-344.: The death domain - A module shared by proteins with diverse cellular functions. PUBMED:7482697 EPMC:7482697
Internal database links
|SCOOP:||Thiol_cytolysin Cloacin_immun BRK Mg296 Nrf1_activ_bdg DUF3723 HTH_25 HTH_26 HTH_37 DUF4447 mit_SMPDase HopW1-1 Zwint Ad_Cy_reg|
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR000488
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 INTERPRO) and the caspase recruitment domain (CARD, see INTERPRO), which work in similar pathways and show similar interaction properties [PUBMED:11504623]. DD bind each other forming oligomers. Mammals have numerous and diverse DD-containing proteins [PUBMED:7482697]. Within these proteins, the DD domains can be found in combination with other domains, including: CARDs, DEDs, ankyrin repeats (INTERPRO), caspase-like folds, kinase domains, leucine zippers (INTERPRO), leucine-rich repeats (LRR) (INTERPRO), TIR domains (INTERPRO), and ZU5 domains (INTERPRO) [PUBMED: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 [PUBMED:14585074, PUBMED: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 [PUBMED:12691620].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||protein binding (GO:0005515)|
|Biological process||signal transduction (GO:0007165)|
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The death domain superfamily is composed of three families: the death domain (DD); the death effector domain (DED) and the caspase recruitment domain (CARD). All of the members perform a pivotal role in signalling events that regulate apoptosis. Protein-protein interactions are mediated by self-self associations, in which CARD-CARD, DD-DD and DED-DED contacts are formed exclusively The three families possess remarkably similar structures, each comprising an antiparallel six helical bundle in the Greek Key topology. Structurally, the DD and CARD families are the most dissimilar. The former is comprised of two perpendicular three-helix bundles, whereas the latter CARD domain contains six helices that are almost parallel with each other. Interestingly, the interactions in CARD or DD containing heterodimers are quite different .
The clan contains the following 6 members:CARD CARD_2 Death Death_2 DED PYRIN
We make a range of alignments for each Pfam-A family:
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Curation and family details
|Seed source:||Reference  and .|
|Author:||Bateman A, Griffiths-Jones SR|
|Number in seed:||60|
|Number in full:||3980|
|Average length of the domain:||80.40 aa|
|Average identity of full alignment:||20 %|
|Average coverage of the sequence by the domain:||9.69 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 80369284 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||18|
|Download:||download the raw HMM for this family|
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There are 8 interactions for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Death domain has been found. There are 81 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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