MOAT-E (ARA) is a full-length MRP cMOAT subfamily transporter expressed inkidney and liver

Multidrug resistance-associated protein (MRP) and the canalicular multispec ific organic anion transporter (cMOAT) are organic anion pumps that have be en linked to cytotoxic drug resistance. We previously reported the isolatio n of three human MRP/cMOAT-related transporters, MOAT-B (MRP4), MOAT-C (MRP 5) and MOAT-D (MRP3). In the present study we describe the fourth MRP/cMOAT -related transporter. We analysed ARA, a human cDNA reported to encode a 45 3 residue MRP-related transporter and found that it represents a fused tran script composed of MRP sequences and partial sequences of a novel transport er. The complete coding sequence of this novel transporter, which we design ated MOAT-E, was isolated. MOAT-E encodes a 1503 residue transporter that i s most closely related to MRP (45%), MOAT-D (44%) and cMOAT (39%), both in terms of amino acid identity and sharing a common topology in which similar to 17 transmembrane spanning helices are distributed within three membrane spanning domains. RNA blot analysis indicated that MOAT-E expression is re stricted to kidney and liver. These observations suggest that MOAT-E may fu nction as an organic anion transporter involved in cellular detoxification and possibly in the hepatobiliary and renal excretion of xenobiotics and/or endogenous metabolites. Isolation of MOAT-E helps to define the MRP/cMOAT subfamily of transporters.