EC 3.6.3.44 - Xenobiotic-transporting ATPase

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IntEnz Enzyme Nomenclature
EC 3.6.3.44

Names

Accepted name:
xenobiotic-transporting ATPase
Other names:
P-glycoprotein
multidrug-resistance protein
MDR protein
pleiotropic-drug-resistance protein
PDR protein
steroid-transporting ATPase
ATP phosphohydrolase (steroid-exporting)
Systematic name:
ATP phosphohydrolase (xenobiotic-exporting)

Reaction

Comments:

ABC-type (ATP-binding cassette-type) ATPase, characterized by the presence of two similar ATP-binding domains. Does not undergo phosphorylation during the transport process. The enzyme 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 transport glutathione—drug conjugates. Some also show some 'flippase' (phospholipid-translocating ATPase; EC 3.6.3.1) activity.

Links to other databases

Enzymes and pathways: NC-IUBMB , BRENDA , ExplorEnz , ENZYME@ExPASy , KEGG , MetaCyc , UniPathway
Protein domains and families: PROSITE:PDOC00185
Structural data: CSA , EC2PDB
Gene Ontology: GO:0008559
UniProtKB/Swiss-Prot: (46) [show] [UniProt]

References

  1. Bellamy, W.T.
    P-glycoproteins and multidrug resistance.
    Annu. Rev. Pharmac. Toxicol. 36: 161-183 (1996). [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. Enzym. Regul. 36: 351-363 (1996). [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: 321-333 (1997). [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: 5130-5136 (1998). [PMID: 9823323]
  5. van Veen, H.W. and Konings, W.N.
    The ABC family of multidrug transporters in microorganisms.
    Biochim. Biophys. Acta 1365: 31-36 (1998). [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: 320-329 (1995). [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: 1536-1543 (1995). [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: 25167-25172 (1996). [PMID: 8810273]

[EC 3.6.3.44 created 2000 (EC 3.6.3.45 incorporated 2006), modified 2006]