PDR1/YGL013C Summary Help

Standard Name PDR1
Systematic Name YGL013C
Alias AMY1 , ANT1 , BOR2 , CYH3 , NRA2 , SMR2 , TIL1 , TPE1 , TPE3
Feature Type ORF, Verified
Description Transcription factor that regulates the pleiotropic drug response; zinc cluster protein that is a master regulator involved in recruiting other zinc cluster proteins to pleiotropic drug response elements (PDREs) to fine tune the regulation of multidrug resistance genes; relocalizes to the cytosol in response to hypoxia; PDR1 has a paralog, PDR3, that arose from the whole genome duplication (1, 2, 3 and see Summary Paragraph)
Name Description Pleiotropic Drug Resistance
Chromosomal Location
ChrVII:472298 to 469092 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Genetic position: -8 cM
Gene Ontology Annotations All PDR1 GO evidence and references
  View Computational GO annotations for PDR1
Molecular Function
Manually curated
High-throughput
Biological Process
Manually curated
Cellular Component
Manually curated
Targets 44 genes
Regulators 8 genes
Resources
Classical genetics
gain of function
null
unspecified
Large-scale survey
null
overexpression
unspecified
Resources
171 total interaction(s) for 130 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 14
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 7
  • Biochemical Activity: 1
  • Co-crystal Structure: 1
  • Co-fractionation: 1
  • Reconstituted Complex: 3
  • Two-hybrid: 6

Genetic Interactions
  • Dosage Rescue: 1
  • Negative Genetic: 73
  • Phenotypic Enhancement: 33
  • Phenotypic Suppression: 5
  • Positive Genetic: 4
  • Synthetic Growth Defect: 20
  • Synthetic Rescue: 1

Resources
Expression Summary
histogram
Resources
Length (a.a.) 1,068
Molecular Weight (Da) 121,793
Isoelectric Point (pI) 6.91
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrVII:472298 to 469092 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Genetic position: -8 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..3207 472298..469092 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) | UniProtKB
Primary SGDIDS000002981
SUMMARY PARAGRAPH for PDR1

PDR1 and PDR3 encode zinc finger transcription factors that are regulators of the pleiotropic drug response in S. cerevisiae. Pdr1p and Pdr3p are 36% identical in amino acid composition (4) and can form homodimers or heterodimers (5). Pdr1p and Pdr3p serve as both transcriptional activators and repressors by binding to pleiotropic drug response elements (PDREs) present in the promoters of target genes involved in multidrug resistance (reviewed in 6, 7, and 8). A key feature of the PDRE consensus sequence, 5'-TCCGCGGA-3', is the presence of CGG triplets in an everted repeat orientation (9) and both Pdr1p and Pdr3p constitutively occupy both perfect and degenerate PDREs (5). These two factors have overlapping but not identical sets of target genes and the individual effect on any given shared target gene can also differ (10, 11 and references therein). This variation in regulatory ability may be due either to differences in post-translational modification or heterodimer formation with other transcriptional factors such as Rdr1p and Stb5p (12, 1). Targets include the ABC transporters encoded by PDR5, PDR10, PDR15, SNQ2, and YOR1, the hexose transporter genes HXT9 and HXT11, and sphingolipid biosynthetic genes such as IPT1 (13, and reviewed in 8). Pdr3p also participates in other processes that do not involve Pdr1p, such as retrograde response signaling (14, 15), as well as regulating the DNA damage-inducible genes MAG1 and DDI1 (16).

Loss of either PDR1 or PDR3 results in differential drug tolerance, and loss of both pdr1 and pdr3 results in severe drug hypersensitivity. Single pdr1 null mutants are markedly decreased in their resistance to different drugs while the affect of a single pdr3 null mutation is less severe (4 and 17). Hyperactive mutants of Pdr1p and Pdr3p often lead to enhanced drug resistance due to an increase in drug transporters (reviewed in 6), but only about 10% of the roughly 200 genes containing a PDRE-like element in their promoters respond transcriptionally to the hyperactive forms of Pdr1p and Pdr3p, indicating that factors beyond the presence of a PDRE may be necessary for transcriptional activation by Pdr1p and Pdr3p (reviewed in 7).

Last updated: 2007-09-28 Contact SGD

References cited on this page View Complete Literature Guide for PDR1
1) Akache B, et al.  (2004) Complex interplay among regulators of drug resistance genes in Saccharomyces cerevisiae. J Biol Chem 279(27):27855-60
2) 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
3) Ghosh Dastidar R, et al.  (2012) The nuclear localization of SWI/SNF proteins is subjected to oxygen regulation. Cell Biosci 2(1):30
4) Delaveau T, et al.  (1994) PDR3, a new yeast regulatory gene, is homologous to PDR1 and controls the multidrug resistance phenomenon. Mol Gen Genet 244(5):501-11
5) Mamnun YM, et al.  (2002) The yeast zinc finger regulators Pdr1p and Pdr3p control pleiotropic drug resistance (PDR) as homo- and heterodimers in vivo. Mol Microbiol 46(5):1429-40
6) MacPherson S, et al.  (2006) A fungal family of transcriptional regulators: the zinc cluster proteins. Microbiol Mol Biol Rev 70(3):583-604
7) Moye-Rowley WS  (2003) Transcriptional control of multidrug resistance in the yeast Saccharomyces. Prog Nucleic Acid Res Mol Biol 73():251-79
8) Jungwirth H and Kuchler K  (2006) Yeast ABC transporters-- a tale of sex, stress, drugs and aging. FEBS Lett 580(4):1131-8
9) Hellauer K, et al.  (1996) A novel DNA binding motif for yeast zinc cluster proteins: the Leu3p and Pdr3p transcriptional activators recognize everted repeats. Mol Cell Biol 16(11):6096-102
10) DeRisi J, et al.  (2000) Genome microarray analysis of transcriptional activation in multidrug resistance yeast mutants. FEBS Lett 470(2):156-60
11) Sidorova M, et al.  (2007) Loss-of-function pdr3 mutations convert the Pdr3p transcription activator to a protein suppressing multidrug resistance in Saccharomyces cerevisiae. FEMS Yeast Res 7(2):254-64
12) 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
13) Hallstrom TC, et al.  (2001) Coordinate control of sphingolipid biosynthesis and multidrug resistance in Saccharomyces cerevisiae. J Biol Chem 276(26):23674-80
14) Panwar SL and Moye-Rowley WS  (2006) Long Chain Base Tolerance in Saccharomyces cerevisiae Is Induced by Retrograde Signals from the Mitochondria. J Biol Chem 281(10):6376-84
15) Devaux F, et al.  (2002) Genome-wide studies on the nuclear PDR3-controlled response to mitochondrial dysfunction in yeast. FEBS Lett 515(1-3):25-8
16) Zhu Y and Xiao W  (2004) Pdr3 is required for DNA damage induction of MAG1 and DDI1 via a bi-directional promoter element. Nucleic Acids Res 32(17):5066-75
17) Katzmann DJ, et al.  (1994) Transcriptional control of the yeast PDR5 gene by the PDR3 gene product. Mol Cell Biol 14(7):4653-61
18) Badis G, et al.  (2008) A library of yeast transcription factor motifs reveals a widespread function for Rsc3 in targeting nucleosome exclusion at promoters. Mol Cell 32(6):878-87
19) Harbison CT, et al.  (2004) Transcriptional regulatory code of a eukaryotic genome. Nature 431(7004):99-104
20) Zhu C, et al.  (2009) High-resolution DNA-binding specificity analysis of yeast transcription factors. Genome Res 19(4):556-66