Reaction: ATP + H2O + xenobiotic[side 1] = ADP + phosphate + xenobiotic[side 2]
Other name(s): xenobiotic-transporting ATPase; multidrug-resistance protein; MDR protein; P-glycoprotein; pleiotropic-drug-resistance protein; PDR protein; steroid-transporting ATPase; ATP phosphohydrolase (steroid-exporting)
Systematic name: ATP phosphohydrolase (ABC-type, xenobiotic-exporting)
Comments: An ATP-binding cassette (ABC) type transporter, characterized by the presence of two similar ATP-binding domains/proteins and two integral membrane domains/proteins. Does not undergo phosphorylation during the transport process. The enzymes from Gram-positive bacteria and eukaryotic cells export a number of drugs with unusual specificity, covering various groups of unrelated substances while ignoring some that are closely related structurally. Several distinct enzymes may be present in a single eukaryotic cell. Many of them also transport glutathione—drug conjugates (see EC 7.6.2.3, ABC-type glutathione-S-conjugate transporter) while others also show some ‘flippase’ activity (redundant, but not identical, to EC 7.6.2.1, P-type phospholipid transporter).
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Bellamy, W.T. P-glycoproteins and multidrug resistance. Annu. Rev. Pharmacol. Toxicol. 36 (1996) 161-183. [PMID: 8725386]
2. Frijters, C.M., Ottenhoff, R., Van Wijland, M.J., Van Nieuwkerk, C., Groen, A.K. and Oude-Elferink, R.P. Influence of bile salts on hepatic mdr2 P-glycoprotein expression. Adv. Enzyme Regul. 36 (1996) 351-363. [PMID: 8869755]
3. Keppler, D., König, J. and Buchler, M. The canalicular multidrug resistance protein, cMRP/MRP2, a novel conjugate export pump expressed in the apical membrane of hepatocytes. Adv. Enzyme Regul. 37 (1997) 321-333. [PMID: 9381978]
4. Loe, D.W., Deeley, R.G. and Cole, S.P. Characterization of vincristine transport by the Mr 190,000 multidrug resistance protein (MRP): evidence for cotransport with reduced glutathione. Cancer Res. 58 (1998) 5130-5136. [PMID: 9823323]
5. van Veen, H.W. and Konings, W.N. The ABC family of multidrug transporters in microorganisms. Biochim. Biophys. Acta 1365 (1998) 31-36. [PMID: 9693718]
6. Griffiths, J.K. and Sansom, C.E. The Transporter Factsbook, Academic Press, San Diego, 1998.
7. Prasad, R., De Wergifosse, P., Goffeau, A. and Balzi, E. Molecular cloning and characterization of a novel gene of Candida albicans, CDR1, conferring multiple resistance to drugs and antifungals. Curr. Genet. 27 (1995) 320-329. [PMID: 7614555]
8. Nagao, K., Taguchi, Y., Arioka, M., Kadokura, H., Takatsuki, A., Yoda, K. and Yamasaki, M. bfr1+, a novel gene of Schizosaccharomyces pombe which confers brefeldin A resistance, is structurally related to the ATP-binding cassette superfamily. J. Bacteriol. 177 (1995) 1536-1543. [PMID: 7883711]
9. Mahé, Y., Lemoine, Y. and Kuchler, K. The ATP-binding cassette transporters Pdr5 and Snq2 of Saccharomyces cerevisiae can mediate transport of steroids in vivo. J. Biol. Chem. 271 (1996) 25167-25172. [PMID: 8810273]