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| http://www.biopax.org/relea... | |
| http://www.biopax.org/relea... |
Pleiotropic ABC efflux transporter of multiple drugs
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| http://www.biopax.org/relea... |
PDR5_YEAST
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| http://www.biopax.org/relea... | |
| http://www.biopax.org/relea... |
Pleiotropic drug resistance protein 5,
Suppressor of toxicity of sporidesmin
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| http://www.biopax.org/relea... |
FUNCTION: Active efflux of weakly charged organic compounds of 90 cubic Angstroms to 300 cubic Angstroms surface volume. Confers resistance to numerous chemicals including cycloheximide, sulfomethuron methyl, steroids, antiseptics, antibiotics, anticancer, herbicides, mycotoxins, insecticides, ionophores, alkaloids, flavonoids, phenothiazines, organotin compounds, carbazoles, lysosomotropic aminoesters, detergents, rhodamines and other fluorophores, azoles and other antifungals. Exhibits nucleoside triphosphatase activity. ENZYME REGULATION: FK506, isonitrile, enniatin, RU49953, kitasatospora E420, staurosporine CGP42700, prenyl-flavonoids, D- octapeptides were found to be inhibitors in vivo. Vanadate and oligomycin were found to be inhibitors in vitro. BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.5 mM for MgATP; Vmax=2.5 umol/min/mg enzyme; Note=Activity measured in plasma membranes; pH dependence: Optimum pH is 7.0; SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. Note=The ERAD mutants 'Pro-183' and 'Tyr-1427' fail to reach the plasma membrane. The mutant 'Pro-183' accumulates into ER- associated compartments. INDUCTION: Expressed during exponential growth. Transcription is transiently activated within 40 min after induction by benomyl and other toxic chemicals. Multidrug resistance and PDR5 mRNA level are activated by the transcription regulators PDR1, PDR3, YAP1, YAP2, STB5 and by the mitochondrial rho zero mutation. Mutations or deletion in the PDR1 or PDR3 transcription factors strongly activate PDR5 mRNA and PDR5 translation. The transcription regulator RDR1 represses PDR5 expression. DOMAIN: The N-terminal ABC transporter domain (positions 161 to 410) contains degenerated Walker A and B ATP-binding motifs, suggesting that it may be less efficient in ATP binding or not functional at all. This is a distinctive feature of the PDR subfamily. DOMAIN: The unusual length of the two extracellular loops at positions 686 to 774 and 1408 to 1476 is another specific feature of the PDR subfamily which may have an important role for function. PTM: Ubiquitinylation mediates endocytosis and vacuolar degradation. Phosphorylation by casein kinase I stabilizes the protein half-life. BIOTECHNOLOGY: Strains lacking PDR5 are used for toxicity tests. Strains overexpressing PDR5 are used for screening antifungal sensitizers. MISCELLANEOUS: Present with 42000 molecules/cell in log phase SD medium in log phase SD medium. MISCELLANEOUS: Full-sized PDR5 orthologs are found only in fungi and plants. Their topology and substrate specificity are distinct from mammalian MDR transporters. MISCELLANEOUS: This protein has been 'adopted' by Andre Goffeau from the Catholic University of Louvain (Belgium). The above- mentioned scientist has agreed to help us to curate information available on this protein. We are grateful to that person for committing precious time to help producing annotation useful to the whole community. However that person is not responsible for any errors or omissions in this UniProtKB/Swiss-Prot entry. If you have found something wrong or missing in this entry you should submit an update report to: help@uniprot.org. SIMILARITY: Belongs to the ABC transporter superfamily. ABCG family. PDR (TC 3.A.1.205) subfamily. SIMILARITY: Contains 2 ABC transporter domains. SEQUENCE CAUTION: Sequence=BAA05547.1; Type=Frameshift; Positions=61; GENE SYNONYMS: LEM1 STS1 YDR1. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License.
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