PABC11 (also known as MOAT-C and MRP5), a member of the ABC family of proteins, has anion transporter activity but does not confer multidrug resistance when overexpressed in human embryonic kidney 293 cells

Several members of the ABC family of proteins have been implicated in multi drug resistance associated with cancer therapies. A novel member of this ge ne family, designated pABC11, has been identified using degenerate polymera se chain reaction. The full-length cDNA spans 5881 base pairs and encodes a n open reading frame of 1437 amino acids predicted to contain two sets of t ransmembrane domains and two nucleotide binding domains characteristic of A BC proteins. The nucleotide sequence described herein extends that of three recently reported sequences, MRP5 (Kool, M., de Haas, M., Scheffer, G., Sc heper, R., van Eijk, M., Juijn, J., Baas, F., and Borst, P. (1997) Cancer R es. 57, 3537-3547), SMRP (Suzuki, T., Nishio, K., Sasaki, H., Kurokawa, H,, Saito-Ohara, F., Ikeuchi, T., Tanabe, S., Terada, M., and Saijo, N. (1997) Biochem. Biophys. Res. Commun. 238, 790-794), and MOAT-C (Belinsky, M., Ba in, L., Balsara, B., Testa, J., and Kruh, G. (1998) J. Natl. Cancer Inst. 9 0, 1735-1741), in the 5' direction. Northern blot analysis detected five tr anscripts that were differentially expressed in several tissue types, and t he gene encoding pABC11 was mapped to chromosome 3. Confocal imaging of HEK 293 cells expressing a green fluorescent protein-pABC11 construct confirmed plasma membrane localization of the fusion protein. Overexpression of pABC 11 resulted in reduced labeling with the fluorochromes 5-chloromethylfluore scein diacetate, fluorescein diacetate, and 2',7'-bis-(2-carboxyethyl)-5 (a nd-6)carboxyfluorescein acetoxymethyl ester but not with calcein or rhodami ne derivatives, consistent with pABC11 being an anion transporter. Fluoroch rome export was ATP-dependent but glutathione-independent. We also show tha t this export pump does not confer resistance to various classes of cytotox ic drugs but does provide small but significant resistance to CdCl2 and pot assium antimonyl tartrate.