The ability to store and interconnect all available information on proteins is crucial to modern biological research. Accordingly, the Universal Protein Resource (UniProt) plays an increasingly important role by providing a stable, comprehensive, freely accessible central resource on protein sequences and functional annotation. UniProt is produced by the UniProt Consortium, formed in 2002 by the European Bioinformatics Institute (EBI), the Protein Information Resource (PIR) and the Swiss Institute of Bioinformatics (SIB). The core activities include manual curation of protein sequences assisted by computational analysis, sequence archiving, development of a user-friendly UniProt web site and the provision of additional value-added information through cross-references to other databases. UniProt is comprised of three major components, each optimized for different uses: the UniProt Archive, the UniProt Knowledgebase and the UniProt Reference Clusters. An additional component consisting of metagenomic and environmental sequences has recently been added to UniProt to ensure availability of such sequences in a timely fashion. UniProt is updated and distributed on a bi-weekly basis and can be accessed online for searches or download at http://www.uniprot.org.