RINGdb: An integrated database for G protein-coupled receptors and regulators of G protein signaling

RINGdb contains information on mutations, tissue distributions, protein-protein interactions, diseases/disorders and other features, which has been automatically collected from the Internet and manually extracted from the literature. In addition, RINGdb offers various user-friendly query functions to answer different questions about RGS proteins and GPCRs such as their possible contribution to disease processes, the putative direct or indirect relationship between RGS proteins and GPCRs. RINGdb also integrates organized database cross-references to allow users direct access to detailed information. The database is now available at http://ringdb.csie.ncu.edu.tw/ringdb/ webcite.RINGdb is the only integrated database on the Internet to provide comprehensive RGS protein and GPCR information. This knowledgebase will be useful for clinical research, drug discovery and GPCR signaling pathway research.G protein-coupled receptors (GPCRs), which represent the largest family of cell-surface receptors, mediate a variety of extracellular signals, modulating many intracellular responses [1]. A wide variety of GPCRs control the activity of enzymes, ion channels and transport of vesicles via the catalysis of the GDP-GTP exchange on heterotrimeric G proteins (Gα-βγ), the key players in transmembrane signaling [2,3]. Signal-induced conformational changes enhance the guanine-nucleotide-exchange activity of the receptor, leading to the release of GDP (and subsequent binding of GTP) by the Gα subunit [2]. On binding GTP, conformational changes of Gα allow the release of Gβγ and the subsequent engagement of effectors that are specific to each Gα subtype [2]. GPCRs are extremely important because 50% of all currently marketed drugs have action on specific GPCRs [4]. However, only 10% of GPCRs are targeted by these drugs, emphasizing the potential of the remaining 90% of the members of the GPCR superfamily for the treatment of human diseases [5]. Tissue-specific expression coupled with the