ISOLATION OF MOAT-B, A WIDELY EXPRESSED MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN CANALICULAR MULTISPECIFIC ORGANIC ANION TRANSPORTER-RELATEDTRANSPORTER

Multidrug resistance-associated protein (MRP) and canalicular multispe cific organic anion transporter (cMOAT) are closely related mammalian ATP-binding cassette transporters that export organic anions from cell s. Transfection studies have established that MRP confers resistance t o natural product cytotoxic agents, and recent evidence suggests the p ossibility that cMOAT may contribute to cytotoxic drug resistance as w ell. Based upon the potential importance of these transporters in clin ical drug resistance and their important physiological roles in the ex port of the amphiphilic products of phase I and phase ZI metabolism, w e sought to identify other MRP-related transporters, Using a degenerat e PCR approach, we isolated a cDNA that encodes a novel ATP-binding ca ssette transporter, which we designated MOAT-B. The MOAT-B gene was ma pped using fluorescence in situ hybridization to chromosome band 13q32 . Comparison of the MOAT-B predicted protein with other transporters r evealed that it is most closely related to MRP, cMOAT, and the yeast o rganic anion transporter YCF1, Although MOAT-B is closely related to t hese transporters, it is distinguished by the absence of a similar to 200 amino acid NH2-terminal hydrophobic extension that is present in M RP and cMOAT and which is predicted to encode several transmembrane sp anning segments. In addition, the MOAT-B tissue distribution is distin ct from MRP and cMOAT, In contrast to MRP, which is widely expressed i n tissues, including liver, and cMOAT, the expression of which is larg ely restricted to liver, the MOAT-B transcript is widely expressed, wi th particularly high levels in prostate, but is barely detectable in l iver, These data indicate that MOAT-B is a ubiquitously expressed tran sporter that is closely related to MRP and cMOAT and raise the possibi lity that it may be an organic anion pump relevant to cellular detoxif ication.