Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
79  structures 171  species 2  interactions 3125  sequences 542  architectures

Family: Death (PF00531)

Summary: Death domain

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Death domain". More...

Death domain Edit Wikipedia article

Death domain
PDB 1ddf EBI.jpg
Structure of the Fas (APO-1/CD95) death domain.[1]
Identifiers
Symbol Death
Pfam PF00531
InterPro IPR000488
SMART DEATH
PROSITE PDOC50017
SCOP 1ddf
SUPERFAMILY 1ddf
CDD cd01670

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.[2] DD bind each other forming oligomers. Mammals have numerous and diverse DD-containing proteins.[3] 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.[4]

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.[5][6] 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.[7]

See also[edit]

References[edit]

  1. ^ 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. 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ 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. 
  5. ^ Wajant H (2003). "Death receptors". Essays Biochem. 39: 53–71. PMID 14585074. 
  6. ^ 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. 
  7. ^ 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 article incorporates text from the public domain Pfam and InterPro IPR000488

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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.

Death domain Provide feedback

No Pfam abstract.

Literature references

  1. 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

  2. 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

  3. Huang BH, Eberstadt M, Olejniczak ET, Meadows RP, Fesik SW; , Nature 1996;384:638-641.: NMR structure and mutagenesis of the Fas (Apo-1/CD95) death domain. PUBMED:8967952 EPMC:8967952


Internal database links

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].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...

Pfam Clan

This family is a member of clan Death (CL0041), which contains the following 5 members:

CARD Death Death_2 DED PYRIN

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(88)
Full
(3125)
Representative proteomes NCBI
(2836)
Meta
(0)
RP15
(804)
RP35
(885)
RP55
(1205)
RP75
(1743)
Jalview View  View  View  View  View  View  View   
HTML View  View  View  View  View  View     
PP/heatmap 1 View  View  View  View  View     
Pfam viewer View  View             

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(88)
Full
(3125)
Representative proteomes NCBI
(2836)
Meta
(0)
RP15
(804)
RP35
(885)
RP55
(1205)
RP75
(1743)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(88)
Full
(3125)
Representative proteomes NCBI
(2836)
Meta
(0)
RP15
(804)
RP35
(885)
RP55
(1205)
RP75
(1743)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download    
Gzipped Download   Download   Download   Download   Download   Download   Download    

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Reference [1] and [2].
Previous IDs: death;
Type: Domain
Author: Bateman A, Griffiths-Jones SR
Number in seed: 88
Number in full: 3125
Average length of the domain: 80.60 aa
Average identity of full alignment: 19 %
Average coverage of the sequence by the domain: 10.09 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.6 21.6
Trusted cut-off 21.6 21.6
Noise cut-off 21.5 21.5
Model length: 83
Family (HMM) version: 17
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Show

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

Interactions

There are 2 interactions for this family. More...

DED Death

Structures

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 79 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.

Loading structure mapping...