PDR5/YOR153W Summary Help

Standard Name PDR5 1
Systematic Name YOR153W
Alias LEM1 , YDR1 , STS1
Feature Type ORF, Verified
Description Plasma membrane ATP-binding cassette (ABC) transporter; multidrug transporter actively regulated by Pdr1p; also involved in steroid transport, cation resistance, and cellular detoxification during exponential growth; PDR5 has a paralog, PDR15, that arose from the whole genome duplication (2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and see Summary Paragraph)
Name Description Pleiotropic Drug Resistance 1
Chromosomal Location
ChrXV:619840 to 624375 | ORF Map | GBrowse
Gbrowse
Genetic position: 85 cM
Gene Ontology Annotations All PDR5 GO evidence and references
  View Computational GO annotations for PDR5
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 13 genes
Resources
Classical genetics
null
overexpression
reduction of function
Large-scale survey
null
Resources
135 total interaction(s) for 102 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 17
  • Affinity Capture-RNA: 5
  • Affinity Capture-Western: 2
  • Biochemical Activity: 2
  • Co-fractionation: 10
  • PCA: 44
  • Two-hybrid: 11

Genetic Interactions
  • Dosage Rescue: 3
  • Negative Genetic: 6
  • Phenotypic Enhancement: 12
  • Phenotypic Suppression: 4
  • Synthetic Growth Defect: 15
  • Synthetic Rescue: 4

Resources
Expression Summary
histogram
Resources
Length (a.a.) 1,511
Molecular Weight (Da) 170,437
Isoelectric Point (pI) 7.75
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXV:619840 to 624375 | ORF Map | GBrowse
SGD ORF map
Genetic position: 85 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..4536 619840..624375 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | TCDB | UniProtKB
Primary SGDIDS000005679
SUMMARY PARAGRAPH for PDR5

PDR5 encodes a multidrug transporter that is involved in the pleiotropic drug response (reviewed in 12, 13, and 14). Pdr5p efflux pump activity is NTP-dependent (15) and mediates resistance to many xenobiotic compounds including mutagens, fungicides, steroids, and anticancer drugs (reviewed in 12 and 14). In addition to drug response, Pdr5p is also involved in cation resistance (4), lipid translocation (16, 17), and in quorum sensing for yeast populations growing in liquid culture (18). Null mutations of pdr5 are not lethal but do confer a drug- and salt-hypersensitive phenotype (1, 4).

Pdr5p, a proposed homodimer, functions at the plasma membrane and has a half life of 45-90 minutes (19, 6). Pdr5p is monoubiquitnated, which serves as a signal for endocytosis and eventual degradation in the vacuole (6, 7 and reviewed in 12). Countering ubiquitination, Pdr5p phosphorylation by serine/threonine kinase (encoded by YCK1 and YCK2) stabilizes the protein (20, 21). Pdr5p levels are highest during exponential growth and are greatly reduced when cells enter diauxic growth or when nutrients are depleted (10, 22). PDR5 expression is positively regulated by Pdr1p and Pdr3p (3, 23) and negatively regulated by Rdr1p (24) through the binding of these transcription factors to pleiotropic drug response elements (PDREs) present in the PDR5 promoter (25). PDR5 expression is also heat-shock-induced by the AP-1 transcription factors Yap1p and Cad1p (26).

Pdr5p is a member of the ATP-binding cassette (ABC) family of proteins, a large group that are conserved from bacteria to humans (3 and references therein). Overexpression of the human ABC transporter ABCB1/MDR1 (OMIM) is a factor in tumor resistance to drug therapy, and deficient ABC transporter function has been implicated in other human diseases as well (reviewed in 27). S. cerevisiae ABC proteins are often used as a model to study the clinical problem of drug resistance in infectious disease and cancer as well as in pharmaceutical screens for novel drugs (28 and reviewed in 29).

Last updated: 2011-01-13 Contact SGD

References cited on this page View Complete Literature Guide for PDR5
1) Leppert G, et al.  (1990) Cloning by gene amplification of two loci conferring multiple drug resistance in Saccharomyces. Genetics 125(1):13-20
2) Mahe Y, et al.  (1996) The ATP binding cassette transporters Pdr5 and Snq2 of Saccharomyces cerevisiae can mediate transport of steroids in vivo. J Biol Chem 271(41):25167-72
3) Balzi E, et al.  (1994) PDR5, a novel yeast multidrug resistance conferring transporter controlled by the transcription regulator PDR1. J Biol Chem 269(3):2206-14
4) Miyahara K, et al.  (1996) The involvement of the Saccharomyces cerevisiae multidrug resistance transporters Pdr5p and Snq2p in cation resistance. FEBS Lett 399(3):317-20
5) Bissinger PH and Kuchler K  (1994) Molecular cloning and expression of the Saccharomyces cerevisiae STS1 gene product. A yeast ABC transporter conferring mycotoxin resistance. J Biol Chem 269(6):4180-6
6) Egner R, et al.  (1995) Endocytosis and vacuolar degradation of the plasma membrane-localized Pdr5 ATP-binding cassette multidrug transporter in Saccharomyces cerevisiae. Mol Cell Biol 15(11):5879-87
7) Egner R and Kuchler K  (1996) The yeast multidrug transporter Pdr5 of the plasma membrane is ubiquitinated prior to endocytosis and degradation in the vacuole. FEBS Lett 378(2):177-81
8) Rogers B, et al.  (2001) The pleitropic drug ABC transporters from Saccharomyces cerevisiae. J Mol Microbiol Biotechnol 3(2):207-14
9) Emter R, et al.  (2002) ERG6 and PDR5 regulate small lipophilic drug accumulation in yeast cells via distinct mechanisms. FEBS Lett 521(1-3):57-61
10) Mamnun YM, et al.  (2004) Expression regulation of the yeast PDR5 ATP-binding cassette (ABC) transporter suggests a role in cellular detoxification during the exponential growth phase. FEBS Lett 559(1-3):111-7
11) Byrne KP and Wolfe KH  (2005) The Yeast Gene Order Browser: combining curated homology and syntenic context reveals gene fate in polyploid species. Genome Res 15(10):1456-61
12) Ernst R, et al.  (2005) Yeast ATP-binding cassette transporters: cellular cleaning pumps. Methods Enzymol 400:460-84
13) Golin J, et al.  (2007) The yeast Pdr5p multidrug transporter: how does it recognize so many substrates? Biochem Biophys Res Commun 356(1):1-5
14) Bauer BE, et al.  (1999) Inventory and function of yeast ABC proteins: about sex, stress, pleiotropic drug and heavy metal resistance. Biochim Biophys Acta 1461(2):217-36
15) Decottignies A, et al.  (1994) Solubilization and characterization of the overexpressed PDR5 multidrug resistance nucleotide triphosphatase of yeast. J Biol Chem 269(17):12797-803
16) Decottignies A, et al.  (1998) ATPase and multidrug transport activities of the overexpressed yeast ABC protein Yor1p. J Biol Chem 273(20):12612-22
17) Kihara A and Igarashi Y  (2004) Cross talk between sphingolipids and glycerophospholipids in the establishment of plasma membrane asymmetry. Mol Biol Cell 15(11):4949-59
18) Hlavacek O, et al.  (2009) Putative role for ABC multidrug exporters in yeast quorum sensing. FEBS Lett 583(7):1107-13
19) Ferreira-Pereira A, et al.  (2003) Three-dimensional reconstruction of the Saccharomyces cerevisiae multidrug resistance protein Pdr5p. J Biol Chem 278(14):11995-9
20) Decottignies A, et al.  (1999) Casein kinase I-dependent phosphorylation and stability of the yeast multidrug transporter Pdr5p. J Biol Chem 274(52):37139-46
21) de Thozee CP, et al.  (2007) Subcellular trafficking of the yeast plasma membrane ABC transporter, Pdr5, is impaired by a mutation in the N-terminal nucleotide-binding fold. Mol Microbiol 63(3):811-25
22) Malac J, et al.  (2005) Glucose-induced MDR pump resynthesis in respiring yeast cells depends on nutrient level. Biochem Biophys Res Commun 337(1):138-41
23) Katzmann DJ, et al.  (1994) Transcriptional control of the yeast PDR5 gene by the PDR3 gene product. Mol Cell Biol 14(7):4653-61
24) Hellauer K, et al.  (2002) Zinc cluster protein Rdr1p is a transcriptional repressor of the PDR5 gene encoding a multidrug transporter. J Biol Chem 277(20):17671-6
25) Katzmann DJ, et al.  (1996) Multiple Pdr1p/Pdr3p binding sites are essential for normal expression of the ATP binding cassette transporter protein-encoding gene PDR5. J Biol Chem 271(38):23049-54
26) Miyahara K, et al.  (1996) yAP-1- and yAP-2-mediated, heat shock-induced transcriptional activation of the multidrug resistance ABC transporter genes in Saccharomyces cerevisiae. Curr Genet 29(2):103-5
27) Decottignies A and Goffeau A  (1997) Complete inventory of the yeast ABC proteins. Nat Genet 15(2):137-45
28) Lamping E, et al.  (2007) Characterization of three classes of membrane proteins involved in fungal azole resistance by functional hyperexpression in Saccharomyces cerevisiae. Eukaryot Cell 6(7):1150-65
29) Sipos G and Kuchler K  (2006) Fungal ATP-binding cassette (ABC) transporters in drug resistance & detoxification. Curr Drug Targets 7(4):471-81