Nuclear receptors (NRs) are ligand-inducible transcription factors that regulate processes, such as homeostasis, differentiation, embryonic development and organ physiology. A total of 49 human NRs have been identified (¹). Their ligands are lipophilic compounds such as steroids, thyroid hormone, vitamin D3 and retinoids (²). The endogenous ligands are not yet known for 30% of the NRs (³). As nuclear receptors are involved in almost all aspects of human physiology and are implicated in many important diseases including cancer, diabetes and osteoporosis, understanding of these receptors has major implications for human biology and for the development of new drug treatments. Nuclear receptors are targets for pharmaceutical industries with similar importance (⁴), as the G protein-coupled receptors (GPCRs), ion channels and kinases.

Due to the increasing amounts of experimental and computational data buried in numerous databases and scientific articles, the task of extracting, combining and validating this data is becoming an increasingly large hurdle for the individual scientist. Databases that revolve around a single protein family can help researchers in using all data needed for their research, while relieving them of the onerous tasks related to the retrieval of many data from different sources (⁵).

The NucleaRDB is a data source that holds many different data types (Table 1) in a well organized and easily accessible form (⁶). The data are validated, internally consistent and updated regularly. The NucleaRDB provides access to the data via various interfaces, which depending on the users’ needs, are suited either for automated access or interactive usage.

All data in the NucleaRDB web interface are extensively connected, allowing for easy navigation between different data types. The main way of accessing the NucleaRDB’s contents is via the hierarchical family tree. For each family, users can access the individual receptors, multiple sequence alignments (and all derived data and analyses such as correlation scores and protein distance networks), mutations, structures and models (Figure 1). All pages contain links to all related data and information. Extensive search facilities are available, allowing the search for proteins, sequences, structures, families and mutations using various search criteria and filters. A BLAST service is available that allows users to run their own sequences against the NucleaRDB.

All data types and search facilities are accessible from the web pages as well as from the web service endpoints, allowing users to write workflows or in-house software that uses the NucleaRDB.

The data in the NucleaRDB is stored in a PostgreSQL (www.postgresql.org) relational database. The web service interface is developed with the Apache CXF (cxf.apache.org) web services framework. We offer both Simple Object Access Protocol and Representational state transfer endpoints. The web interface is built using the Apache Wicket (wicket.apache.org) web application framework. The database is accessed via a Hibernate (www.hibernate.org) object-relational mapping layer. The server is running within Sun’s Glassfish (www.glassfish.org) application server.

The NucleaRDB provides researchers with a single point of access for nuclear receptor-related data. Not only does the NucleaRDB hold a large amount of information, it also provides a broad scope of tools and dissemination facilities, relieving scientist of many of the tasks that come with collecting, validating and integrating many diverse data.

BioRange program of the Netherlands Bioinformatics Centre (NBIC); BSIK grant through the Netherlands Genomics Initiative (NGI); EMBRACE project that is funded by the European Commission within its FP6 Programme, under the thematic area ‘Life sciences, genomics and biotechnology for health’ (contract number LHSG-CT-2004-512092); and TIPharma. Funding for open access charge: RUNMC.

Conflict of interest statement. None declared.

We thank Maarten Hekkelman, Wilmar Teunissen and Tim teBeek for their support with computer science issues. We thank TIPharma for financial support.