Death Domain database

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Death Domain Database
Content
Descriptionprotein-protein interaction database for the Death Domain superfamily.
Contact
AuthorsDongseop Kwon
Primary citation PMID   22135292
Release date2011
Access
Website www.deathdomain.org

The Death Domain database is a secondary database of protein-protein interactions (PPI) of the death domain superfamily. [1] Members of this superfamily are key players in apoptosis, inflammation, necrosis, and immune cell signaling pathways. Negative death domain superfamily-mediated signaling events result in various human diseases which include, cancers, neurodegenerative diseases, and immunological disorders. Creating death domain databases are of particular interest to researchers in the biomedical field as it enables a further understanding of the molecular mechanisms involved in death domain interactions while also providing easy access to tools such as an interaction map that illustrates the protein-protein interaction network and information. There is currently only one database that exclusively looks at death domains but there are other databases and resources that have information on this superfamily. [1] According to PubMed, [2] this database has been cited by seven peer-reviewed articles to date because of its extensive and specific information on the death domains and their PPI summaries.

Contents

The Death Domain superfamily

The evolutionarily conserved Death Domain superfamily is defined by a death fold motif which is formed by several protein-interaction domains. [3] The domains consist of six-seven tightly coiled alpha-helices arranged in a "Greek-key fold". [1] [3] This superfamily is considered one of the largest and most studied protein-protein interaction (PPI) network.

There are four types of death domain subfamilies: death effector domain (DED), [4] caspase recruitment domain (CARD), [5] pyrin domain (PYD), and death domain (DD). [1] [6] These subfamily domains are grouped together because of similarity in their sequence and structure. [7] However, while similar, each domain has its own defining structural feature: a RxDL-motif in the DEDs, an interrupted, first helix in the CARDs, a smaller (or sometimes ambiguous) third helix in PYDs, and a more exposed, flexible third helix in the DDs. [1] Members of this subfamily only form homotypic bonds with the same type of subfamily domain. For example, DED will only bind with DED, CARD-CARD, PYD-PYD and DD-DD. These homotypic interactions are with only two members of the same domain (or on rare occasions with more) and there has been no evidence to suggest that these domains have heterotypic interactions with one another. [3]

Death Domain subfamilies

Death effector domain (DED)

DED domains are highly conserved in the Chordata phylum and can also be found in smaller percentages in the Echinodermata phylum and viruses. [8] DED-containing proteins are associated with apoptosis regulation with caspase protein interaction and have been notably documented in mammals. [3] [9] DED domains have been known to interact with other domains and include: nuclear localization sequences (in DEDD), transmembrane domains (in Bap31 and Bar), nucleotide-binding domains (in Dap3), SAM domains (in Bar), coiled-coil domains (in Hip and Hippi), and E2-binding RING domains (in Bar). [10]

Caspase recruitment domain (CARD)

CARD domains are primarily found in chordates, with many being from the animal kingdom, and are found in smaller percentages in Nematoda and Echinodermata phyla. [11] Protein modules containing the CARD domain are associated with apoptosis, through the regulation of caspases that they are interacting with, as well in inflammation processes through its participation in NF-kappaB signaling pathways. [12]

Pyrin domain (PYD)

The PYD domain, also known as the Domain in Apoptosis and INterferon response (DAPIN) domain, is typically found in vertebrates and viral proteins and are involved in apoptosis, cancer, and inflammation. [13] The functions of this group are the least understood among the 4 members of the death domain superfamily. [3]

Death domain (DD)

This domain is predominantly found in the animal kingdom, especially among mammals, who have many different types of PPI's containing death domains. [7] According to SMART's non-redundant database, mammals have about 61% of known DD-domains. [14] DD-containing proteins are associated with apoptosis and inflammation, similar to the CARD domain. It has also been linked with innate immunity. [15] DDs can also be found with other types of domains including Ankyrin repeats, caspase-like folds, kinase domains, leucine zippers, leucine-rich repeats (LRR), TIR domains, and ZU5 domains. [7]

Overview

Deathdomain.org was initially created by Kwon et al. (2012) to stimulate further research into the death domain superfamily mediated signaling pathway. Their database is manually curated and focuses on providing detailed information on the death domain superfamily and its protein-protein interactions. Kwon and his team started by researching, compiling and curating 295 published peer-reviewed studies that focused on PPI modules and their associated death domains. The database now provides users with information from 311 peer-reviewed studies, a slight increase from the original publication. [1]

This database provides:

Constructing the database

PubMed database [2] was the primary source used for data collection in the DeathDomain.org database. The authors for the site started by finding synonyms for the 99 death domain superfamily proteins from UniProtKB [16] and Entrez Gene. [17] Along with the protein name, synonyms were used to search for articles in the PudMed database for death domain proteins that were involved in physical binding to other proteins. Further searches were done on DIP, [18] IntAct, [19] MINT [20] and STRING [21] databases to ensure that all relevant articles were included in the study. The authors were able to find and manually curate 295 peer-reviewed articles that discussed 175 PPI pairs among 99 DD superfamily proteins. These numbers have increased since the original publication to 311 peer-reviewed papers discussing 181 PPI pairs among 99 DD superfamily proteins. [1]

To curate data in the literature, the authors chose to focus on the analytical methods, experimental results, resources, and nomenclature. If there was insufficient data in the papers, users will see "Not specified" in these sections. [1]

Features

DD superfamily and PPI summaries

This feature can be accessed by picking a death domain of interest and using the subtab to pick a protein containing this domain. It will take the user to a wealth of information that can be seen in great detail ("In detail" tab) or in lesser detail ("At a glance" tab) on top (Fig. 1D and 1C, respectively). The data is further broken down into three categories: interaction, characterization, and functional role. These categories were chosen because they were used in similar studies. [22] In most cases, for each PPI, users can learn more about them by clicking the PubMed ID, giving details including the title, abstract, authors, interactions mentioned in the article, and a link to the publication. [23]

Other subheading tabs give access to protein information including the proteins full name, alternative names, function, and death domain subfamily and boundary region. The latter conveniently allows users to obtain the amino acid sequences and domain boundaries from UniProtKB/Swiss-Prot and UniProtKB/TrEMBL databases in either embl, genbank or fasta format. [16] By clicking the external database link, users can get this information for the domain-containing protein found in other species. They can also access more information on similar databases (Uniprot, DIP, STRING, KEGG, IntAct, and MINT) by clicking the appropriate identifier number. The last two tabs will provide users with downloadable 3-D structure images under the "3-D structure" tab and the natural mutations and related diseases they are involved in under the "Disease" tab (Fig. 1E). [23]

Statistics

The statistics page consists of a list of publications (separated by year of publication) used in the database and can be accessed via a hyperlink. The page also presents tabulated summaries of the number of PPIs per domain and are also hyperlinked to their PPI summary page. Another tabulated feature is a comparison of the DD superfamily mediated PPI pairs found on the Death Domain database to other PPI databases. This page illustrates to users that their database has more PPI pairs than Deathbase.org and the same number as IntAct and Mint. [24]

Other resources

Database NameType of DatabaseFeaturesOrganisms in Database
Deathbase [25] Database of proteins involved in cell death-Data on function, structure, and evolution of proteins involved in apoptosis/ other forms of cell death

-Manually curated data

-Easy searches based on species, protein, pathway, family, and domain names

Human

Mouse

Zebrafish

Fly

Worm

IntActMolecular interaction database-Open source database system and includes analysis tools for molecular interaction data

-Manually curated data (from EMBL-EBI)

-Comprehensive search options: Gene, Protein, RNA, Chemical name, UniProtKB, ChEBI AC, UniProtKB ID, RNACentral ID, PMID, and IMEx ID

Cellular organisms

Viruses

Many others

MINT [20] Molecular interaction database-Experimentally verified protein-protein interaction data

-Manually curated data

-Easy search options: species, protein, gene name, UniProt Protein Accession Number, and PubMed id/D.O.I

Human

Yeast

Fruit Fly

Worm

STRING [21] Protein-protein interaction network database-Data on known and predicted protein-protein interactions: direct (physical) and indirect (functional) association

-Manually curated data

-Easy search options: Species, protein name, and Identifier

2031 total organisms
DIP [18] Protein-protein interaction network database-Data on experimentally determined interactions between proteins

-Manually curated data

-Easy search options: protein, sequence, motif, article, IMEx, and pathBLAST

Human

Yeast

Fruit Fly

Many others

Related Research Articles

<span class="mw-page-title-main">CATH database</span>

The CATH Protein Structure Classification database is a free, publicly available online resource that provides information on the evolutionary relationships of protein domains. It was created in the mid-1990s by Professor Christine Orengo and colleagues including Janet Thornton and David Jones, and continues to be developed by the Orengo group at University College London. CATH shares many broad features with the SCOP resource, however there are also many areas in which the detailed classification differs greatly.

<span class="mw-page-title-main">UniProt</span> Database of protein sequences and functional information

UniProt is a freely accessible database of protein sequence and functional information, many entries being derived from genome sequencing projects. It contains a large amount of information about the biological function of proteins derived from the research literature. It is maintained by the UniProt consortium, which consists of several European bioinformatics organisations and a foundation from Washington, DC, USA.

<span class="mw-page-title-main">Fas ligand</span> Protein-coding gene in the species Homo sapiens

Fas ligand is a type-II transmembrane protein expressed on various types of cells, including cytotoxic T lymphocytes, monocytes, neutrophils, breast epithelial cells, vascular endothelial cells and natural killer (NK) cells. It binds with its receptor, called FAS receptor and plays a crucial role in the regulation of the immune system and in induction of apoptosis, a programmed cell death.

<span class="mw-page-title-main">Death effector domain</span> InterPro Domain

The death-effector domain (DED) is a protein interaction domain found only in eukaryotes that regulates a variety of cellular signalling pathways. The DED domain is found in inactive procaspases and proteins that regulate caspase activation in the apoptosis cascade such as FAS-associating death domain-containing protein (FADD). FADD recruits procaspase 8 and procaspase 10 into a death induced signaling complex (DISC). This recruitment is mediated by a homotypic interaction between the procaspase DED and a second DED that is death effector domain in an adaptor protein that is directly associated with activated TNF receptors. Complex formation allows proteolytic activation of procaspase into the active caspase form which results in the initiation of apoptosis. Structurally the DED domain are a subclass of protein motif known as the death fold and contains 6 alpha helices, that closely resemble the structure of the Death domain (DD).

The DrugBank database is a comprehensive, freely accessible, online database containing information on drugs and drug targets created and maintained by the University of Alberta and The Metabolomics Innovation Centre located in Alberta, Canada. As both a bioinformatics and a cheminformatics resource, DrugBank combines detailed drug data with comprehensive drug target information. DrugBank has used content from Wikipedia; Wikipedia also often links to Drugbank, posing potential circular reporting issues.

<span class="mw-page-title-main">Amos Bairoch</span> Swiss bioinformatician

Amos Bairoch is a Swiss bioinformatician and Professor of Bioinformatics at the Department of Human Protein Sciences of the University of Geneva where he leads the CALIPHO group at the Swiss Institute of Bioinformatics (SIB) combining bioinformatics, curation, and experimental efforts to functionally characterize human proteins.

InterPro is a database of protein families, protein domains and functional sites in which identifiable features found in known proteins can be applied to new protein sequences in order to functionally characterise them.

<span class="mw-page-title-main">CARD (domain)</span> Interaction motifs found in a wide array of proteins

Caspase recruitment domains, or caspase activation and recruitment domains (CARDs), are interaction motifs found in a wide array of proteins, typically those involved in processes relating to inflammation and apoptosis. These domains mediate the formation of larger protein complexes via direct interactions between individual CARDs. CARDs are found on a strikingly wide range of proteins, including helicases, kinases, mitochondrial proteins, caspases, and other cytoplasmic factors.

<span class="mw-page-title-main">Death fold</span> Tertiary protein structure motif

The death fold is a tertiary structure motif commonly found in proteins involved in apoptosis or inflammation-related processes. This motif is commonly found in domains that participate in protein–protein interactions leading to the formation of large functional complexes. Examples of death fold domains include the death domain (DD), death effector domain (DED), caspase recruitment domain (CARD), and pyrin domain (PYD).

<span class="mw-page-title-main">Fas receptor</span> Protein found in humans

The Fas receptor, also known as Fas, FasR, apoptosis antigen 1, cluster of differentiation 95 (CD95) or tumor necrosis factor receptor superfamily member 6 (TNFRSF6), is a protein that in humans is encoded by the FAS gene. Fas was first identified using a monoclonal antibody generated by immunizing mice with the FS-7 cell line. Thus, the name Fas is derived from FS-7-associated surface antigen.

<span class="mw-page-title-main">FADD</span> Human protein and coding gene

FAS-associated death domain protein, also called MORT1, is encoded by the FADD gene on the 11q13.3 region of chromosome 11 in humans.

<span class="mw-page-title-main">Protein domain</span> Self-stable region of a proteins chain that folds independently from the rest

In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist of several domains, and a domain may appear in a variety of different proteins. Molecular evolution uses domains as building blocks and these may be recombined in different arrangements to create proteins with different functions. In general, domains vary in length from between about 50 amino acids up to 250 amino acids in length. The shortest domains, such as zinc fingers, are stabilized by metal ions or disulfide bridges. Domains often form functional units, such as the calcium-binding EF hand domain of calmodulin. Because they are independently stable, domains can be "swapped" by genetic engineering between one protein and another to make chimeric proteins.

<span class="mw-page-title-main">Caspase 2</span> Enzyme found in humans

Caspase 2 also known as CASP2 is an enzyme that, in humans, is encoded by the CASP2 gene. CASP2 orthologs have been identified in nearly all mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts.

<span class="mw-page-title-main">MicrobesOnline</span>

MicrobesOnline is a publicly and freely accessible website that hosts multiple comparative genomic tools for comparing microbial species at the genomic, transcriptomic and functional levels. MicrobesOnline was developed by the Virtual Institute for Microbial Stress and Survival, which is based at the Lawrence Berkeley National Laboratory in Berkeley, California. The site was launched in 2005, with regular updates until 2011.

<span class="mw-page-title-main">PYCARD</span> Human protein and coding gene

PYCARD, often referred to as ASC, is a protein that in humans is encoded by the PYCARD gene. It is localized mainly in the nucleus of monocytes and macrophages. In case of pathogen infection, however, it relocalizes rapidly to the cytoplasm, perinuclear space, endoplasmic reticulum and mitochondria and it is a key adaptor protein in activation of the inflammasome.

SUPERFAMILY is a database and search platform of structural and functional annotation for all proteins and genomes. It classifies amino acid sequences into known structural domains, especially into SCOP superfamilies. Domains are functional, structural, and evolutionary units that form proteins. Domains of common Ancestry are grouped into superfamilies. The domains and domain superfamilies are defined and described in SCOP. Superfamilies are groups of proteins which have structural evidence to support a common evolutionary ancestor but may not have detectable sequence homology.

<span class="mw-page-title-main">Death domain</span>

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.

<span class="mw-page-title-main">Pyrin domain</span>

A pyrin domain is a protein domain and a subclass of protein motif known as the death fold, the 4th and most recently discovered member of the death domain superfamily (DDF). It was originally discovered in the pyrin protein, or marenostrin, encoded by MEFV. The mutation of the MEFV gene is the cause of the disease known as Familial Mediterranean Fever. The domain is encoded in 23 human proteins and at least 31 mouse genes.

TopFIND is the Termini oriented protein Function Inferred Database (TopFIND) is an integrated knowledgebase focused on protein termini, their formation by proteases and functional implications. It contains information about the processing and the processing state of proteins and functional implications thereof derived from research literature, contributions by the scientific community and biological databases.

In bioinformatics, the PANTHER classification system is a large curated biological database of gene/protein families and their functionally related subfamilies that can be used to classify and identify the function of gene products. PANTHER is part of the Gene Ontology Reference Genome Project designed to classify proteins and their genes for high-throughput analysis.

References

  1. 1 2 3 4 5 6 7 8 Kwon, Dongseop; Yoon Jong Hwan; Shin Soo-Yong; Jang Tae-Ho; Kim Hong-Gee; So Insuk; Jeon Ju-Hong; Park Hyun Ho (Jan 2012). "A comprehensive manually curated protein-protein interaction database for the Death Domain superfamily". Nucleic Acids Research. 40 (D1): D331–D336. doi:10.1093/nar/gkr1149. PMC   3245059 . PMID   22135292.
  2. 1 2 Sayers, EW; Barrett, T; Benson, DA; Bolton, E; Bryant, SH; Canese, K; Chetvernin, V; Church, DM; Dicuccio, M; Federhen, S; et al. (2011). "Database resources of the National Center for Biotechnology Information". Nucleic Acids Res. 39 (Database issue): D38–D51. doi:10.1093/nar/gkq1172. PMC   3013733 . PMID   21097890.
  3. 1 2 3 4 5 Lahm, A; Paradiso, A; Green, D. R.; Melino, G (2003). "Death fold domain interaction in apoptosis". Cell Death and Differentiation. 10 (1): 10–12. doi:10.1038/sj.cdd.4401203. ISSN   1350-9047. PMID   12655289. S2CID   32593733.
  4. Chinnaiyan, AM; O'Rourke, K; Tewari, M; Dixit, VM (1995). "FADD, a novel death domain-containing protein, interacts with the death domain of fas and initiates apoptosis". Cell. 81 (4): 505–512. doi: 10.1016/0092-8674(95)90071-3 . PMID   7538907. S2CID   16906755.
  5. Hofmann, K; Bucher, P; Tschopp, J (1997). "The CARD domain: A new apoptotic signalling motif". Trends in Biochemical Sciences. 22 (5): 155–156. doi:10.1016/S0968-0004(97)01043-8. ISSN   0968-0004. PMID   9175472.
  6. Tartaglia, LA; Ayres, TM; Wong, GHW; Goeddel, DV (1993), "A novel domain within the 55 kd TNF receptor signals cell death", Cell, 74 (5): 845–53, doi:10.1016/0092-8674(93)90464-2, PMID   8397073, S2CID   38732043
  7. 1 2 3 Death domain (IPR000488) , retrieved 3 November 2016
  8. Thomas, L; Henson, A; Reed, JC; Salsbury, FR; Thorburn, A (2004). "Direct binding of Fas-associated death domain (FADD) to the tumor necrosis factor-related apoptosis-inducing ligand receptor DR5 is regulated by the death effector domain of FADD". The Journal of Biological Chemistry. 279 (31): 32780–5. doi: 10.1074/jbc.M401680200 . PMID   15173180.
  9. DED: Death effector domain , retrieved 3 November 2016
  10. Reed, JC; Doctor, KS; Godsik, A (2004). "The domains of apoptosis: A genomics perspective". Science's STKE. 2004 (239): re9. doi:10.1126/stke.2392004re9. PMID   15226512. S2CID   40047696.
  11. CARD: Caspase recruitment domain , retrieved 3 November 2016
  12. Bouchier-Hayes, L; Martin, SJ (2002). "CARD games in apoptosis and immunity". EMBO Reports. 3 (7): 616–621. doi:10.1093/embo-reports/kvf139. PMC   1084193 . PMID   12101092.
  13. Staub, E.; Dahl, E; Rosenthal, A (2001). "The DAPIN family: A novel domain links apoptotic and interferon response proteins". Trends in Biochemical Sciences. 26 (2): 83–85. doi:10.1016/S0968-0004(00)01717-5. PMID   11166557.
  14. DEATH: DEATH domain, found in proteins involved in cell death (apoptosis). , retrieved 3 November 2016
  15. 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", Journal of Endotoxin Research, 9 (1): 55–59, doi: 10.1177/09680519030090010701 , ISSN   0968-0519, PMID   12691620
  16. 1 2 The UniProt Consortium (2010). "The Universal Protein Resource (UniProt) in 2010". Nucleic Acids Res. 38 (Database issue): D142–D148. doi:10.1093/nar/gkp846. PMC   2808944 . PMID   19843607.
  17. Maglott, D; Ostell, J; Pruitt, KD; Tatusova, T (2011). "Entrez Gene: gene-centered information at NCBI". Nucleic Acids Res. 39 (Database issue): D52–D57. doi:10.1093/nar/gkq1237. PMC   3013746 . PMID   21115458.
  18. 1 2 Salwinski, L; Miller, CL; Smith, AJ; Pettit, FK; Bowie, JU; Eisenberg, D (2004). "The Database of Interacting Proteins: 2004 update". Nucleic Acids Res. 32 (90001): D449–D451. doi:10.1093/nar/gkh086. PMC   308820 . PMID   14681454.
  19. Aranda, B; Achuthan, P; Alam-Faruque, Y; Armean, I; Bridge, A; Derow, C; Feuermann, M; Ghanbarian, AT; Kerrien, S; Khadake, J; et al. (2010). "The IntAct molecular interaction database in 2010". Nucleic Acids Res. 38 (Database issue): D525–D531. doi:10.1093/nar/gkp878. PMC   2808934 . PMID   19850723.
  20. 1 2 Ceol, A; Chatr Aryamontri, A; Licata, L; Peluso, D; Briquanti, L; Perfetto, L; Castagnoli, L; Cesareni, G (2010). "MINT, the molecular interaction database: 2009 update". Nucleic Acids Res. 38 (Database issue): D532–D539. doi:10.1093/nar/gkp983. PMC   2808973 . PMID   19897547.
  21. 1 2 Szklarcyk, D; Francheschini, A; Kuhn, M; Simonovic, M; Roth, A; Minquez, P; Doerks, T; Stark, M; Muller, J; Bork, P; et al. (2011). "The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored". Nucleic Acids Res. 39 (Database issue): D561–D568. doi:10.1093/nar/gkq973. PMC   3013807 . PMID   21045058.
  22. Xenarios, I; Eisenberg, D (2001). "Protein interaction databases" (PDF). Curr. Opin. Biotechnol. 12 (4): 334–339. doi:10.1016/s0958-1669(00)00224-x. PMID   11551460.
  23. 1 2 "Detailed Information on The Death Domain Superfamily and PPIs". Deathdomain. Retrieved 3 November 2016.
  24. "Statistics". Deathdomain. Retrieved 3 November 2016.
  25. "Cell Death / Apoptosis Database". Deathbase.org. Retrieved 1 December 2016.