AIM AND SCOPE
This database is a collection of sequence, structural and functional information about the Bcl-2 family of apoptotic regulators.
It will enable researchers to readily retrieve Bcl-2 family sequences, their related information and obtain data of relevance to them.
DEVELOPMENT AND CONSTRUCTION
Seed sequences of Bcl-2 family members and initial homology groups were from Aouacheria et al. Mol Biol Evol, 2005
For each seed sequence, BLAST searches were performed (against GenBank
, and the Ensembl Trace Archive
) and the resulting hits were checked manually.
Sometimes final sequences were obtained by the fusion of several clones in order to obtain the longest piece.
For each relevant hit, annotations, sequence and functional features and the source organism were extracted and loaded by automated retrieval systems into an in-house developed relational database (consisting of more than 27 tables).
Tables were created with different data types to hold dissimilar data.
BCL-2-DB resides on a postgreSQL server at PBIL
Release 1.0 (August 2008) of BCL-2-DB contains 896 Bcl-2 family entries from 149 metazoan species.
BCL-2-DB was developed and applied for the 'helical bundle' class of Bcl-2 family members (multi-BH region proteins plus BH3-only protein Bid).
The members of this subfamily are homologous (i.e. the genes coding these Bcl-2 family members presumably descend from a common ancestor gene).
However, BCL-2-DB has been designed in such a way that it can be easily adapted to incorporate the other Bcl-2-related subfamilies (BH3-only, BNip1-3 proteins and viral Bcl-2 family members).
Future developments also include expression data from ESTs, SAGE and microarrays, and a unified interface to query literature references as well as evolutionary, chromosomal, functional and structural information about all subgroups of Bcl-2 family proteins.
Last, all BCL-2-DB entries will be given a specific accession number and files will be converted to GenBank formatted records.
A text-based string search for any text within the Bcl-2-DB can be performed using the 'Quick Search' option.
This option enables the user to browse BCL-2-DB through all fields of the database files and returns a 'Result' page.
The hits are linked to their respective 'entry card'.
The 'Advanced Search' form allows searches of Bcl-2 family members based on their name, homology group and species. Up to four different criteria can be searched simultaneously.
Bcl-2 family entries not present in Ensembl were extracted from GenBank (Annotated and CoreNucleotide) or from dbEST and the Ensembl Trace Server through BLAST searches.
The database in which a Bcl-2 family sequence has been identified is provided since it indicates the reliability of the information given. Assignment of the 'homology' category is based on multiple alignments and phylogenetic analyses.
Search results are returned as by a common web-search engine, providing links to individual Bcl-2 family protein/gene pages. On these pages, selected information about the specific Bcl-2 family member is compiled.
An archive can be downloaded comprising FASTA sequences grouped by name or homology group.
The formatted text file will list all mRNA or protein sequences. Use the checkboxes if you want to select specific Bcl-2 family members.
On each 'entry card', selected information about a specific Bcl-2 family member is compiled. The web page provides information divided into several sections.
The first section ('Infos') gives general information such as common protein/gene names and the organism of origin. The name corresponds to the HUGO nomenclature and to the most common acronym otherwise. Links are supplied to view pre-calculated Homolens
phylogenetic trees and to predict protein features such as presence of a TM motif (TM prediction with TMPRED
) or domain composition (using InterProScan
The function category (Pro or Anti-apoptotic) is also given. In case of missing information (no experimental data), functional information available for one particular Bcl-2 family member was transferred to all other sequences of its homology group.
In the next section ('Sequences'), available transcript and protein sequences can be obtained. Where available, genomic sequences (exonic and intronic sequences, as well as upstream and downstream regions) are provided.
Archives can be downloaded comprising FASTA sequences grouped by name, organism or homology group. The formatted text files will list all mRNA or protein sequences. Structure files in PDB format ('Download') can also be downloaded.
The third section ('Identifiers') contains the Bcl2DB ID and respective accession numbers for the protein/gene. The last section ('Protein features') provides links to other databases where further and complementary information can be accessed. Since numerous Bcl-2 family members are known proteins/genes, the page provides links to other public-domain databases that keep information on them (such as Pubmed references, data about the size and isoelectric point as well as information concerning structural and functional features).
BROWSE BCL-2-DB BY ORGANISM
This registry lists all species for which at least one Bcl-2 family sequence is available. Further information (common name and TaxID of the source organism according to the NCBI Taxonomy Browser
is displayed upon moving the cursor over the respective species name.
BROWSE BY HOMOLOGY GROUP
The protein entries are assigned to 17 homologous subfamilies (homology groups) which are grouped into 6 families. Entries were assigned to homology subfamilies according to sequence similarity by performing multisequence alignments and phylogenetic analyses (from Aouacheria et al. Mol Biol Evol, 2005
). Some proteins within the database could not be classified by sequence similarity and were grouped in the 'OTHER' group. They will be reassigned during a database update in case of the classification procedure evolves.
A table permits browsing of the database by homology group ('List'). Protein names contain links to their respective GeneCards
A browsable tree which allows the retrieval of entries by homology is also available ('Hierarchic tree'), at present manually constructed based on sequence and phylogenetic analyses.
Clicking on names allows selection of homology subfamilies (corresponding to the well-known family members) while clicking on branches allows selection of homologous families regrouping several family members (Bcl-2 family member'-LIKE').
BROWSE BY STRUCTURE
Helix-bundled Bcl-2 family members form a group of phylogenetically related proteins, which share a common structural organization. For 15 proteins of 9 different homology groups, crystal or NMR structures were deposited (by August 2008). The user can visualize the 3D structures interactively within the web browser by using the Java applet JMOL
('Display 3D Structure') or download the structure files in PDB format ('Download'). BCL-2-DB contains hyperlinked cross-references to Pubmed and to the RCSB Protein Data Bank. Coordinates coming from 3D-modelling will be added in a future release.
BROWSE BY DOMAIN
Because BCL-2-DB is intended for the study of Bcl-2 family proteins, only Interpro
entries related to BH domains are retained. By using the data held in Interpro, users have information incorporating Pfam, TIGRFams, SmartHMM, Prosite, Prints, and ProDom algorithms. In future versions, the results will be viewed with a graphical representation of domain architecture. Moreover, Bcl-2 family alignments will be analyzed using the hmmbuild program of the HMMER
package to generate profile hidden Markov models (pHMMs) describing the alignments. This work will help to improve the definition of Bcl-2 family domains.
BROWSE THE BCL-2 FAMILY INTERACTOME
An important paradigm for Bcl-2 family proteins is their molecular interaction network. Moreover, numerous proteins from outside the Bcl-2 family have been reported to interact with and modulate the function of all three subfamilies of Bcl-2 proteins. This page includes external links to several online interactome databases.
In addition, to get a global portrait of the BCL-2 family interactome in humans, we integrated data of ten main PPI databases (including published interactions) unifying them in a common platform.
BCL-2-DB is developing to feature important information such as a 'Who's who?' in the field, meeting advertisements, educational resources and so on. In order to keep BCL-2-DB as up-to-date and useful as possible, we strongly encourage all the experts in the field to directly submit relevant data through the Internet. HTML-based forms that enable electronic submission are currently under development.