MOAT-E (ARA) is a full-length MRP/cMOAT subfamily transporter expressed in kidney and liver.
Multidrug resistance-associated protein (MRP) and the canalicular multispecific organic anion transporter (cMOAT) are organic anion pumps that have been linked to cytotoxic drug resistance. We previously reported the isolation of three human MRP/cMOAT-related transporters, MOAT-B (MRP4), MOAT-C (MRP5) 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 453 residue MRP-related transporter, and found that it represents a fused transcript composed of MRP sequences and partial sequences of a novel transporter. The complete coding sequence of this novel transporter, which we designated MOAT-E, was isolated. MOAT-E encodes a 1503 residue transporter that is 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 approximately 17 transmembrane spanning helices are distributed within three membrane spanning domains. RNA blot analysis indicated that MOAT-E expression is restricted to kidney and liver. These observations suggest that MOAT-E may function 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.
Belinsky
M G
MG
Division of Medical Sciences, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Kruh
G D
GD
D018528:ATP-Binding Cassette Transporters / Q000032:analysis* / Q000737:chemistry / Q000235:genetics; D000595:Amino Acid Sequence; D027321:Anion Transport Proteins; D002352:Carrier Proteins / Q000032:analysis* / Q000737:chemistry / Q000235:genetics; D018076:DNA, Complementary / Q000302:isolation & purification; D006801:Humans; D007668:Kidney / Q000737:chemistry*; D008099:Liver / Q000737:chemistry*; D008969:Molecular Sequence Data; D027425:ATP-Binding Cassette, Sub-Family C Proteins
D018528:ATP-Binding Cassette Transporters; D027321:Anion Transport Proteins; D002352:Carrier Proteins; D018076:DNA, Complementary; D027425:ATP-Binding Cassette, Sub-Family C Proteins