FLR1/YBR008C Summary Help

Standard Name FLR1 1
Systematic Name YBR008C
Feature Type ORF, Verified
Description Plasma membrane transporter of the major facilitator superfamily; member of the 12-spanner drug:H(+) antiporter DHA1 family; involved in efflux of fluconazole, diazaborine, benomyl, methotrexate, and other drugs; expression induced in cells treated with the mycotoxin patulin; relocalizes from nucleus to plasma membrane upon DNA replication stress (1, 2, 3, 4, 5, 6 and see Summary Paragraph)
Name Description FLuconazole Resistance 1
Chromosomal Location
ChrII:254209 to 252563 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gene Ontology Annotations All FLR1 GO evidence and references
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 4 genes
Classical genetics
Large-scale survey
7 total interaction(s) for 6 unique genes/features.
Physical Interactions
  • Affinity Capture-RNA: 1

Genetic Interactions
  • Negative Genetic: 4
  • Synthetic Growth Defect: 2

Expression Summary
Length (a.a.) 548
Molecular Weight (Da) 61,628
Isoelectric Point (pI) 6.31
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrII:254209 to 252563 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Last Update Coordinates: 2011-02-03 | Sequence: 1997-01-28
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..1647 254209..252563 2011-02-03 1997-01-28
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | TCDB | UniProtKB
Primary SGDIDS000000212

The widespread biological phenomenon of multidrug resistance (MDR) poses serious challenges for the treatment of human cancers, and also of bacterial and fungal infections. MDR is typically associated with transport systems that catalyze the efflux of various compounds out of the cell. Among the most important MDR transporters are those belonging to the major facilitator superfamily (MFS). MFS-MDR transporters are found in Eucarya, Bacteria, and Archaea, and have been classified into two families based on the number of predicted transmembrane spans: The Drug:H+ Antiporter-1 (12-Spanner; DHA1) Family, TC 2.A.1.2, and the Drug:H+ Antiporter-2 (14-Spanner; DHA2) Family, TC 2.A.1.3 (7).

In S. cerevisiae, the DHA1 family comprises 12 genes involved in various biological processes: AQR1, QDR1, QDR2, QDR3, FLR1, DTR1, TPO1, TPO2, TPO3, TPO4, HOL1, and YHK8 (7). Aqr1p, Qdr1-3p, and Flr1p are plasma membrane proteins that serve as multidrug transporters (8, 9, 10, 11, 12, 1, 2). Aqr1p has also been implicated in the excretion of excess amino acids, and Qdr2p in the import of potassium ions (13, 14). Dtr1p, a putative dityrosine transporter, resides in the prospore membrane and functions in spore wall synthesis (15, 16). Tpo1-4p are membrane proteins involved in the export of polyamines, including spermine, spermidine, and putrescine (17, 18). Hol1p participates in cation and alcohol transport (19, 20), and Yhk8p is a putative drug transporter requiring further experimental characterization (12, 21).

The 12 DHA1 family genes of S. cerevisiae are similar to several ion and amine transporters in human, including SLC22A5, SLC22A11, SLC22A13, SLC22A14, and SLC22A3, which function primarily in the elimination of drugs and other xenobiotics from various tissues. Mutations in the human genes have been implicated in Crohn's disease, hypoglycemia, and various myopathies.

Last updated: 2008-02-08 Contact SGD

References cited on this page View Complete Literature Guide for FLR1
1) Alarco AM, et al.  (1997) AP1-mediated multidrug resistance in Saccharomyces cerevisiae requires FLR1 encoding a transporter of the major facilitator superfamily. J Biol Chem 272(31):19304-13
2) Broco N, et al.  (1999) FLR1 gene (ORF YBR008c) is required for benomyl and methotrexate resistance in Saccharomyces cerevisiae and its benomyl-induced expression is dependent on pdr3 transcriptional regulator. Yeast 15(15):1595-608
3) Jungwirth H, et al.  (2000) Diazaborine resistance in yeast involves the efflux pumps Ycf1p and Flr1p and is enhanced by a gain-of-function allele of gene YAP1. Eur J Biochem 267(15):4809-16
4) Iwahashi Y, et al.  (2006) Mechanisms of patulin toxicity under conditions that inhibit yeast growth. J Agric Food Chem 54(5):1936-42
5) Dias PJ, et al.  (2010) Evolution of the 12-Spanner Drug:H+ Antiporter DHA1 Family in Hemiascomycetous Yeasts. OMICS 14(6):701-10
6) Tkach JM, et al.  (2012) Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress. Nat Cell Biol 14(9):966-76
7) Gbelska Y, et al.  (2006) Evolution of gene families: the multidrug resistance transporter genes in five related yeast species. FEMS Yeast Res 6(3):345-55
8) Tenreiro S, et al.  (2002) 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. Biochem Biophys Res Commun 292(3):741-8
9) Nunes PA, et al.  (2001) Resistance and adaptation to quinidine in Saccharomyces cerevisiae: role of QDR1 (YIL120w), encoding a plasma membrane transporter of the major facilitator superfamily required for multidrug resistance. Antimicrob Agents Chemother 45(5):1528-34
10) Tenreiro S, et al.  (2005) The yeast multidrug transporter Qdr3 (Ybr043c): localization and role as a determinant of resistance to quinidine, barban, cisplatin, and bleomycin. Biochem Biophys Res Commun 327(3):952-9
11) Vargas RC, et al.  (2004) Saccharomyces cerevisiae multidrug transporter Qdr2p (Yil121wp): localization and function as a quinidine resistance determinant. Antimicrob Agents Chemother 48(7):2531-7
12) Goffeau A, et al.  (1997) Multidrug-resistant transport proteins in yeast: complete inventory and phylogenetic characterization of yeast open reading frames with the major facilitator superfamily. Yeast 13(1):43-54
13) Velasco I, et al.  (2004) Saccharomyces cerevisiae Aqr1 is an internal-membrane transporter involved in excretion of amino acids. Eukaryot Cell 3(6):1492-503
14) Vargas RC, et al.  (2007) Saccharomyces cerevisiae Multidrug Resistance Transporter Qdr2 Is Implicated in Potassium Uptake, Providing a Physiological Advantage to Quinidine-Stressed Cells. Eukaryot Cell 6(2):134-42
15) Felder T, et al.  (2002) Dtrlp, a multidrug resistance transporter of the major facilitator superfamily, plays an essential role in spore wall maturation in Saccharomyces cerevisiae. Eukaryot Cell 1(5):799-810
16) Iwamoto MA, et al.  (2005) Saccharomyces cerevisiae Sps1p regulates trafficking of enzymes required for spore wall synthesis. Eukaryot Cell 4(3):536-44
17) Tomitori H, et al.  (2001) Multiple polyamine transport systems on the vacuolar membrane in yeast. Biochem J 353(Pt 3):681-8
18) Albertsen M, et al.  (2003) Localization and function of the yeast multidrug transporter Tpo1p. J Biol Chem 278(15):12820-5
19) Gaber RF, et al.  (1990) HOL1 mutations confer novel ion transport in Saccharomyces cerevisiae. Mol Cell Biol 10(2):643-52
20) Wright MB, et al.  (1996) Amino acid substitutions in membrane-spanning domains of Hol1, a member of the major facilitator superfamily of transporters, confer nonselective cation uptake in Saccharomyces cerevisiae. J Bacteriol 178(24):7197-205
21) Barker KS, et al.  (2003) Identification of genes differentially expressed in association with reduced azole susceptibility in Saccharomyces cerevisiae. J Antimicrob Chemother 51(5):1131-40