PathLocdb: a comprehensive database for the subcellular localization of metabolic pathways and its application to multiple localization analysis

BACKGROUND: In eukaryotes, the cell is divided into several compartments enclosed by unitary membranes. Such compartmentalization is critical for cells to restrict different pathways to be carried out in different subcellular regions. The summary and classification of subcellular localizations of metabolic pathways are the first steps towards understanding their roles in spatial differentiation and the specialization of metabolic pathways in different organisms. RESULTS: Integrating the subcellular localization of enzymes and their pathways from UniProt Knowledgebase and KEGG pathway databases, we present the first database for subcellular localization of 43014 pathways from 80676 UniProt entries and their pathway annotations from UniProt and KEGG pathway databases. To extract pathway localization across organisms, we defined 889 superpathways as clusters of basic pathways with the same pathway annotations from different organisms. Over eighty-eight percent of superpathways in the Swiss-Prot dataset occur in cytoplasm and mitochondria. And over seventy percent of UniProt superpathways have multiple localization annotations. We summarized four common reasons for the multiple localization of superpathways. Based on this database, we also discovered 88 potential transport systems between different steps of multiply localized pathways and 45 duplicated genes from 17 pathways, occurring in parallel in several locations in humans. CONCLUSIONS: PathLocdb is a free web-accessible database that enables biochemical researchers to quickly access summarized subcellular localization of pathways from UniProt and KEGG pathway databases. As the first effort to systematically integrate pathway localization, this database is very useful in discovering the variation of localization of pathways between organisms and also cross-talk between different organelles within a pathway. The Pathlocdb database is available at http://pathloc.cbi.pku.edu.cn.