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TC-DB is a comprehensive relational database containing structural, functional and evolutionary information about transmembrane transport proteins. The database contains factual material extracted from more than 9000 references, covering approximately 3000 representative proteins, classified into over 400 families. TC-DB is the primary resource allowing access to the data upon which the TC system is based. The TC system has been adopted by the international union of biochemistry and molecular biology (IUBMB). The functional ontology developed for TC-DB provides an infrastructure to develop powerful queries that yield biological insight. The TC-DB website offers a number of software tools that facilitate the analysis of membrane transporters. Multiple avenues of access are supported by the web interface including classification drill-down, parametric searching, and full-text searching. TC-DB has been used for the annotation of transport proteins in newly sequenced genomes and provides tools to trace evolutionary pathways. The database as well as web services are accessible free of charge at http://tcdb. ucsd. edu.