PDR5/YOR153W Summary Help

PDR5 BASIC INFORMATION

Standard Name PDR5
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 (1, 2, 3, 4, 5, 6, 7, 8, 9 and see Summary Paragraph)
Name Description Pleiotropic Drug Resistance
GO 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
Mutant Phenotype All PDR5 Phenotype details and references
Classical genetics
null
Large-scale survey
null
Interactions PDR5 All interactions details and references
60 total interaction(s) for 51 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 6
  • Affinity Capture-RNA: 1
  • Co-fractionation: 10
  • PCA: 12
  • Two-hybrid: 11
Genetic Interactions
  • Dosage Rescue: 1
  • Phenotypic Enhancement: 8
  • Phenotypic Suppression: 2
  • Synthetic Growth Defect: 7
  • Synthetic Rescue: 2
Sequence Information
ChrXV:619841 to 624376 | ORF Map | GBrowse
Gbrowse
Genetic position: 85 cM
Last Update Coordinates: 2006-01-05 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates		 Chromosomal
Coordinates		 Most Recent Updates
Coordinates Sequence
CDS 1..4536 619841..624376 2006-01-05 1996-07-31
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | TCDB | UniProtKB
Primary SGDIDS000005679

PDR5 RESOURCES

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Expression Summary histogram

ADDITIONAL INFORMATION for PDR5

NOMENCLATURE CONFLICT NOTE

NameRelevanceDescription
NCB2Nomenclature conflictYDR1 has been used in the literature to refer to both PDR5/YOR153W, which encodes a multi drug transporter, and NCB2/YDR397C, which encodes the beta subunit of a negative regulator of RNA Polymerase II holoenzyme.
STS1Nomenclature conflictThe name STS1 has been used to describe both PDR5/YOR153W, a transporting ATPase involved in multidrug resistance, and STS1/YIR011C, a protein involved in ubiquitin-dependent protein catabolism.

SUMMARY PARAGRAPH for PDR5

PDR5 encodes a multidrug transporter that is involved in the pleiotropic drug response (reviewed in 10, 11, and 12). Pdr5p efflux pump activity is NTP-dependent (13) and mediates resistance to many xenobiotic compounds including mutagens, fungicides, steroids, and anticancer drugs (reviewed in 10 and 12). In addition to drug response, Pdr5p is also involved in cation resistance (3) and lipid translocation (14, 15). Null mutations of pdr5 are not lethal but do confer a drug- and salt-hypersensitive phenotype (16, 3).

Pdr5p, a proposed homodimer, functions at the plasma membrane and has a half life of 45-90 minutes (17, 5). Pdr5p is monoubiquitnated, which serves as a signal for endocytosis and eventual degradation in the vacuole (5, 6 and reviewed in 10). Countering ubiquitination, Pdr5p phosphorylation by serine/threonine kinase (encoded by YCK1 and YCK2) stabilizes the protein (18, 19). Pdr5p levels are highest during exponential growth and are greatly reduced when cells enter diauxic growth or when nutrients are depleted (9, 20). PDR5 expression is positively regulated by Pdr1p and Pdr3p (2, 21) and negatively regulated by Rdr1p (22) through the binding of these transcription factors to pleiotropic drug response elements (PDREs) present in the PDR5 promoter (23).

Pdr5p is a member of the ATP-binding cassette (ABC) family of proteins, a large group that conserved from bacteria to humans (2 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 24). 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 (25 and reviewed in 26).

Last updated: 2007-11-06

REFERENCES CITED ON THIS PAGE [View Complete Literature Guide for PDR5]

1) 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
2) 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
3) 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
4) 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
5) 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
6) 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
7) Rogers B, et al.  (2001) The pleitropic drug ABC transporters from Saccharomyces cerevisiae. J Mol Microbiol Biotechnol 3(2):207-14
8) 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
9) 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
10) Ernst R, et al.  (2005) Yeast ATP-binding cassette transporters: cellular cleaning pumps. Methods Enzymol 400:460-84
11) 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
12) 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
13) 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
14) Decottignies A, et al.  (1998) ATPase and multidrug transport activities of the overexpressed yeast ABC protein Yor1p. J Biol Chem 273(20):12612-22
15) 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
16) Leppert G, et al.  (1990) Cloning by gene amplification of two loci conferring multiple drug resistance in Saccharomyces. Genetics 125(1):13-20
17) Ferreira-Pereira A, et al.  (2003) Three-dimensional reconstruction of the Saccharomyces cerevisiae multidrug resistance protein Pdr5p. J Biol Chem 278(14):11995-9
18) 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
19) 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
20) 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
21) Katzmann DJ, et al.  (1994) Transcriptional control of the yeast PDR5 gene by the PDR3 gene product. Mol Cell Biol 14(7):4653-61
22) 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
23) 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
24) Decottignies A and Goffeau A  (1997) Complete inventory of the yeast ABC proteins. Nat Genet 15(2):137-45
25) 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
26) Sipos G and Kuchler K  (2006) Fungal ATP-binding cassette (ABC) transporters in drug resistance & detoxification. Curr Drug Targets 7(4):471-81