title: AQR1 gene (ORF YNL065w) encodes a plasma membrane transporter of the major facilitator superfamily that confers resistance to short-chain monocarboxylic acids and quinidine in Saccharomyces cerevisiae.
abstract: We report results on the functional analysis of Saccharomyces cerevisiae ORF YNL065w, predicted to code for a protein belonging to the poorly characterized major facilitator superfamily (MFS) of transporters that are involved in multidrug resistance (MDR). YNL065w is important for a moderate increase of yeast tolerance to ketoconazole and to the cationic dye crystal violet; it protects the cell against short-chain monocarboxylic acids (C(2)-C(6)), but not against highly liposoluble acids such as octanoic acid or the phenoxyacetic-acid herbicides 2,4-D and MCPA; it is also a determinant of resistance to the antiarrhytmic and antimalarial drug quinidine. The encoding ORF was, thus, denominated the AQR1 gene. Results obtained using an AQR1-lacZ fusion indicate that gene expression is very low and it is not stimulated under weak acid stress. The encoded putative transporter was localized in the plasma membrane by fluorescence microscopy observation of the overproduced Aqr1-GFP fusion protein distribution.
authors.affiliation: Centro de Engenharia Biológica e Química, Instituto Superior Técnico, Avenida Rovisco Pais, 1049-001 Lisbon, Portugal.
authors.forename: Sandra
authors.initials: S
authors.lastname: Tenreiro
authors.forename: Patrícia A
authors.initials: PA
authors.lastname: Nunes
authors.forename: Cristina A
authors.initials: CA
authors.lastname: Viegas
authors.forename: Mónica S
authors.initials: MS
authors.lastname: Neves
authors.forename: Miguel C
authors.initials: MC
authors.lastname: Teixeira
authors.forename: M Guadalupe
authors.initials: MG
authors.lastname: Cabral
authors.forename: Isabel
authors.initials: I
authors.lastname: Sá-Correia
mesh_terms: D002264:Carboxylic Acids / Q000494:pharmacology*; D026141:Drug Resistance, Multiple, Fungal / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D027501:Monocarboxylic Acid Transporters; D016366:Open Reading Frames / Q000235:genetics; D011802:Quinidine / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C454200:AQR1 protein, S cerevisiae; D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D026901:Membrane Transport Proteins; D027501:Monocarboxylic Acid Transporters; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D011802:Quinidine