A Database and Interactive Web Service for Dissecting the Bcl-2 Interactome

Before running Bcl-2-Ome, please make sure you have an up-to-date Java installation on your computer, as Bcl-2-Ome is provided as Java Web Start application.
Check here which Java version is installed on your computer.

Important information for Mac Users: you have to follow the guidelines to open an app from an unidentified developer to run Bcl-2-Ome, more information regarding this can be found on the Apple Support page.
We also show here how to do this.

See examples on how the GUI of Bcl-2-Ome can be used.

Bcl-2-Ome will open in a separate window. If you are using a QHD+ display, you may have to change your resolution settings to visualize the database in an optimal way.

1 Contents of Bcl-2-Ome and Data Submission

The entries of the database can also be downloaded as xml file: Bcl-2-Ome contents

Submit additional data for review and addition to the database or obtain details regarding the reviewing process.

2 Description and Contact

Bcl-2-Ome contains published data describing interactions within the Bcl-2 protein family.

It aims at facilitating research on the Bcl-2 family by providing an overview of the multiple interactions taking place within the family and the numerous studies that have been performed to uncover these. Quantitative as well as qualitative studies were added to the database.

All data were manually collected from the respective research articles. Every added experiment was supplemented with detailed information about the experimental conditions, such as cell line, antibodies or detergents. Additionally, Bcl-2-Ome lists experimental details about (Bcl-2 family specific) factors potentially influencing their interactions, such as the use of nonionic detergents in coimmunoprecipitation studies [1] or peptide length in in vitro binding assays [2-3].

Moreover, further review of the included experiments is facilitated by providing the exact references including figure numbers and links to the primary literature.

The software uses the JUNG 2.0.1 libraries, which are licensed under the BSD open-source license [4]. For details on licenses, see bottom of this page.

Feedback is welcome, please contact
annika [dot] hantusch (at) uni-konstanz [dot] de

2.1 General

A graph illustrates Bcl-2 family members as nodes and experiments defining interactions within the Bcl-2 family as edges connecting the nodes. Each edge constitutes one experimental outcome. In the right panel multiple possibilities to select a subset of edges are provided. The lower part of the panel contains areas to display detailed information about selected interactions, select experiments by reference or retrieve protein sequences.

2.2 Toolbar

When the mouse button is selected, edges can be selected to show experimental details and single or multiple proteins can be highlighted and moved within the white are. Only in the mouse button mode edges can be selected by a single click and protein sequences will be shown by double clicking on a selected node. For more information, read sections 'Experiment Info' or 'Protein Sequence'.

The button showing an arrow that points in four ways provides a tool to relocate the whole graph within in the white area. Zooming of the graph is enabled by clicking on the "+" or "-" buttons on the right, or by using the mouse wheel.

2.3 Select Experiment Types

In the left half of the experiment type panel the color code of the different experiment types can be seen. Experiments can be selected or deselected to make them (un-)visible in the graph. The integer in brackets behind each experiment type denotes the number of available experiments in Bcl-2-Ome.
Additionally, another color mode is available: it colors all interactions according to true (black) and false (gray) values (see section 'Experiment Info').

The right half of the panel provides further possibilities to show a selection of experiments in the graph. 'Interactions' denote affinities between proteins, 'Effector activations' denote a measured conformational change, dimer- or multimerization of Bax or Bak in response to incubation with a protein of the Bcl-2 family. Edges defining effector activation are shown as directed edges in the graph, whereas interactions are presented as undirected edges.

Qualitative and quantitative experimental outcomes can be selected for analysis in the lower right part of the 'Experiment Types' panel.

2.4 Select Proteins

It is possible to show only those edges connecting certain proteins of interest. For this purpose, two different options are provided. The 'AND' option will show interactions in between the selected proteins. The 'OR' option will show all interactions of the selected protein(s) to all other proteins, no matter if those other proteins are selected or not.

2.5 Experiment Info

By clicking on an edge (the mouse button on top has to be selected for this purpose), the edge is highlighted and detailed information about the experiment are shown in the 'Experiment Info' tab. Provided information define the two proteins, their relation as discovered in this experiment and the experiment type. A boolean value (true or false) is given, which defines whether this interaction / effector activation was observed in the respective experiment or not.

A short description gives a summary of the experiment and details further defining the experimental setup, if needed. Depending on the experiment type and the data provided in the respective publication, different additional information are given. In all cases a complete reference including figure number and a link to the respective publication is provided. The link can be opened with a single click on the blue marked DOI. Further information define the organism a cell line was derived from (e.g. human/mouse) and the cell line (e.g. 293T) or label an in vitro experiment and define the used detergent (e.g. Triton X-100/CHAPS) or instrument (e.g. Biacore 3000 biosensor).

Below, all proteins that were involved in this experiment are listed, with information about the sequence origin of their protein sequence, the use of chimeras, truncated protein versions or BH3 peptides and, if available, the used concentration.

If the corresponding edge, to which the experimental information are shown, is not highlighted any more, it can be highlighted again by moving the mouse into the experiment info field.

By clicking on another edge, the information of the former experiment is deleted from the tab.

2.6 References of Bcl-2-Ome Entries

All references are listed in the references tab, showing year of publication and first author. By double clicking on an entry, the publication will be opened in a new tab / window of the browser.

The table can be sorted by clicking on the respective header columns.

2.7 Protein Sequence

In this tab, protein sequences for either human or mouse can be shown. By double clicking on a protein in the graph, the canonical protein sequence as defined by Uniprot (state March 18, 2016) is added to the text field. By clicking somewhere in the white space next to the graph and dragging the mouse, multiple proteins can be selected. By clicking on either one of the selected proteins, all protein sequences are added to the text field.

Whether the mouse or the human protein sequence is shown in response to a double click depends on the item that is marked in the upper right corner. By clicking on the "clear" button, all sequences are deleted from the text field.

2.8 Abbreviations

  • DOI: Digital object identifier
  • FRET: Fluorescence resonance energy transfer
  • FPA: Fluorescence polarization assay
  • SPR: Surface plasmon resonance
  • ITC: Isothermal titration calorimetry
  • FPLC: Fast protein liquid chromatography
  • FCCS: Fluorescence cross-correlation spectroscopy
  • Kd: Dissociation constant (nM)
  • kon: Rate constant defining association
  • koff: Rate constant defining dissociation
  • IC50: Half maximal inhibitory concentration (nM)
  • MEF: Mouse embryonic fibroblasts
  • DKO: Double knockout
  • MLM: Mouse liver mitochondria
  • Antibody1: Used for immunoprecipitation (in case of coimmunoprecipitations)
  • Antibody2: Used for immunoblotting (in case of coimmunoprecipitations)
  • wt: Wild type
  • TM: Transmembrane

3 References

[1] Hsu, Y. T. & Youle, R. J. Nonionic detergents induce dimerization among members of the Bcl-2 family. J. Biol. Chem. 272, 13829–13834 (1997).
doi: 10.1074/jbc.272.21.13829

[2] Kelekar, A., Chang, B. S., Harlan, J. E., Fesik, S. W. & Thompson, C. B. Bad is a BH3 domain-containing protein that forms an inactivating dimer with Bcl-XL. Mol. Cell. Biol. 17, 7040–7046 (1997).
PMID: 9372935

[3] Petros, A. M. et al. Rationale for Bcl-XL/Bad peptide complex formation from structure, mutagenesis, and biophysical studies. Protein Sci. 9, 2528–2534 (2000).
doi: 10.1110/ps.9.12.2528

[4] The JUNG Development Team. JUNG: The Java Universal Network/Graph Framework. (2010).
at http://jung.sourceforge.net

The JUNG license can be accessed at http://jung.sourceforge.net/license.txt or here: JUNG license

The JUNG library uses Apache's collections-generic library, which is published under the Apache License: Apache license

4 Related resources

Other resources that the interested Bcl-2-Ome user might find useful:

The STRING database

BCL2DB: database of BCL-2 family members and BH3-only proteins

The IntAct molecular interaction database