ExplorEnz: EC 7.6.2.2

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7.6.2.2

Accepted name:

ABC-type xenobiotic transporter

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 (cf. EC 7.6.2.1, P-type phospholipid transporter).

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, MetaCyc, PDB

References:

1.	Bellamy, W.T. P-glycoproteins and multidrug resistance. Annu. Rev. Pharmacol. Toxicol. 36 (1996) 161–183. [DOI] [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. [DOI] [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. [DOI] [PMID: 9381978]
4.	Loe, D.W., Deeley, R.G. and Cole, S.P. Characterization of vincristine transport by the M_r 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. [DOI] [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. [DOI] [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. [DOI] [PMID: 8810273]

[EC 7.6.2.2 created 2000 as EC 3.6.3.44 (EC 3.6.3.45 incorporated 2006), modified 2006, transferred 2018 to EC 7.6.2.2]