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3.A.1.205.1
Pleiotropic drug resistance (PDR; Pdr5) exporter; steroid exporter; sporidesmin toxicity suppressor (Sts1); MDR; cyclic nucleotide exporter; amphipathic anion exporter. Its ATPase activity is inhibited by its substrate, clotrimazole; can use ATP, GTP and maybe UTP to drive efflux (Golin et al., 2007).  Molecular modeling revealed aspects of the binding pocket and mechanism of action (Rutledge et al. 2011).  Charged residues at the end of TMS2 affect transport (Dou et al. 2016). The 23-membered-ring macrolide tacrolimus, a commonly used immunosuppressant, also known as FK506, is a broad-spectrum inhibitor and an efflux pump substrate, and mutations that minimize its export have been isolated (Tanabe et al. 2018).

Accession Number:P33302
Protein Name:Pdr5 aka Sts1 aka Ydr1 aka LEM1 aka YOR153W
Length:1511
Molecular Weight:170438.00
Species:Saccharomyces cerevisiae (Baker's yeast) [4932]
Number of TMSs:15
Location1 / Topology2 / Orientation3: Cell membrane1 / Multi-pass membrane protein2
Substrate drugs, Cyclic nucleotides, Amphipathic anions

Cross database links:

Genevestigator: P33302
eggNOG: fuNOG04532
HEGENOM: HBG323792
DIP: DIP-6776N
RefSeq: NP_014796.1   
Entrez Gene ID: 854324   
Pfam: PF01061    PF00005    PF06422   
KEGG: sce:YOR153W   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0005739 C:mitochondrion
GO:0005886 C:plasma membrane
GO:0005524 F:ATP binding
GO:0042802 F:identical protein binding
GO:0008559 F:xenobiotic-transporting ATPase activity
GO:0015893 P:drug transport
GO:0046677 P:response to antibiotic
GO:0046898 P:response to cycloheximide

References (76)

[1] “Saccharomyces cerevisiae YDR1, which encodes a member of the ATP-binding cassette (ABC) superfamily, is required for multidrug resistance.”  Hirata D.et.al.   7882421
[2] “PDR5, a novel yeast multidrug resistance conferring transporter controlled by the transcription regulator PDR1.”  Balzi E.et.al.   8294477
[3] “Molecular cloning and expression of the Saccharomyces cerevisiae STS1 gene product. A yeast ABC transporter conferring mycotoxin resistance.”  Bissinger P.H.et.al.   8307980
[4] “Analysis of a 35.6 kb region on the right arm of Saccharomyces cerevisiae chromosome XV.”  Bordonne R.et.al.   9046089
[5] “The nucleotide sequence of Saccharomyces cerevisiae chromosome XV.”  Dujon B.et.al.   9169874
[6] “The multidrug resistance gene PDR1 from Saccharomyces cerevisiae.”  Balzi E.et.al.   3316228
[7] “Interaction of the yeast pleiotropic drug resistance genes PDR1 and PDR5.”  Meyers S.et.al.   1319843
[8] “Loss of function mutation in the yeast multiple drug resistance gene PDR5 causes a reduction in chloramphenicol efflux.”  Leonard P.J.et.al.   7840595
[9] “Solubilization and characterization of the overexpressed PDR5 multidrug resistance nucleotide triphosphatase of yeast.”  Decottignies A.et.al.   8175692
[10] “Transcriptional control of the yeast PDR5 gene by the PDR3 gene product.”  Katzmann D.J.et.al.   8007969
[11] “Positive autoregulation of the yeast transcription factor Pdr3p, which is involved in control of drug resistance.”  Delahodde A.et.al.   7623800
[12] “Endocytosis and vacuolar degradation of the plasma membrane-localized Pdr5 ATP-binding cassette multidrug transporter in Saccharomyces cerevisiae.”  Egner R.et.al.   7565740
[13] “LEM1, an ATP-binding-cassette transporter, selectively modulates the biological potency of steroid hormones.”  Kralli A.et.al.   7753868
[14] “yAP-1- and yAP-2-mediated, heat shock-induced transcriptional activation of the multidrug resistance ABC transporter genes in Saccharomyces cerevisiae.”  Miyahara K.et.al.   8821655
[15] “The yeast multidrug transporter Pdr5 of the plasma membrane is ubiquitinated prior to endocytosis and degradation in the vacuole.”  Egner R.et.al.   8549828
[16] “The involvement of the Saccharomyces cerevisiae multidrug resistance transporters Pdr5p and Snq2p in cation resistance.”  Miyahara K.et.al.   8985171
[17] “An FK506-sensitive transporter selectively decreases intracellular levels and potency of steroid hormones.”  Kralli A.et.al.   8663352
[18] “The ATP binding cassette transporters Pdr5 and Snq2 of Saccharomyces cerevisiae can mediate transport of steroids in vivo.”  Mahe Y.et.al.   8810273
[19] “Anticancer drugs, ionophoric peptides, and steroids as substrates of the yeast multidrug transporter Pdr5p.”  Kolaczkowski M.et.al.   8940170
[20] “Camptothecin sensitivity is mediated by the pleiotropic drug resistance network in yeast.”  Reid R.J.D.et.al.   9115278
[21] “Clustered amino acid substitutions in the yeast transcription regulator Pdr3p increase pleiotropic drug resistance and identify a new central regulatory domain.”  Nourani A.et.al.   9393437
[22] “Molecular and phenotypic characterization of yeast PDR1 mutants that show hyperactive transcription of various ABC multidrug transporter genes.”  Carvajal E.et.al.   9393438
[23] “Complete inventory of the yeast ABC proteins.”  Decottignies A.et.al.   9020838
[24] “Role of ABC transporters in aureobasidin A resistance.”  Ogawa A.et.al.   9559778
[25] “Endoplasmic reticulum degradation of a mutated ATP-binding cassette transporter Pdr5 proceeds in a concerted action of Sec61 and the proteasome.”  Plemper R.K.et.al.   9830032
[26] “Genetic separation of FK506 susceptibility and drug transport in the yeast Pdr5 ATP-binding cassette multidrug resistance transporter.”  Egner R.et.al.   9450972
[27] “In vivo characterization of the drug resistance profile of the major ABC transporters and other components of the yeast pleiotropic drug resistance network.”  Kolaczkowski M.et.al.   9818966
[28] “Casein kinase I-dependent phosphorylation and stability of the yeast multidrug transporter Pdr5p.”  Decottignies A.et.al.   10601275
[29] “Chemical specificity of the PDR5 multidrug resistance gene product of Saccharomyces cerevisiae based on studies with tri-n-alkyltin chlorides.”  Golin J.et.al.   10602734
[30] “Role of the PDR gene network in yeast susceptibility to the antifungal antibiotic mucidin.”  Michalkova-Papajova D.et.al.   10639374
[31] “The transmembrane domain 10 of the yeast Pdr5p ABC antifungal efflux pump determines both substrate specificity and inhibitor susceptibility.”  Egner R.et.al.   10712705
[32] “Genome microarray analysis of transcriptional activation in multidrug resistance yeast mutants.”  DeRisi J.et.al.   10734226
[33] “Prenyl-flavonoids as potent inhibitors of the Pdr5p multidrug ABC transporter from Saccharomyces cerevisiae.”  Conseil G.et.al.   10841772
[34] “Protein kinase C effectors bind to multidrug ABC transporters and inhibit their activity.”  Conseil G.et.al.   11327879
[35] “A novel screening for inhibitors of a pleiotropic drug resistant pump, Pdr5, in Saccharomyces cerevisiae.”  Hiraga K.et.al.   11515543
[36] “Purification and some properties of an inhibitor for a yeast pleiotropic drug resistant pump from Kitasatospora sp. E-420.”  Wanigasekera A.et.al.   11758940
[37] “The ABC transporter Pdr5p mediates the efflux of nonsteroidal ecdysone agonists in Saccharomyces cerevisiae.”  Hu W.et.al.   11422371
[38] “Saccharomyces cerevisiae multidrug resistance gene expression inversely correlates with the status of the F(0) component of the mitochondrial ATPase.”  Zhang X.et.al.   11602584
[39] “The pleitropic drug ABC transporters from Saccharomyces cerevisiae.”  Rogers B.et.al.   11321575
[40] “Zinc cluster protein Rdr1p is a transcriptional repressor of the PDR5 gene encoding a multidrug transporter.”  Hellauer K.et.al.   11882665
[41] “New regulators of drug sensitivity in the family of yeast zinc cluster proteins.”  Akache B.et.al.   11943786
[42] “Phosphoproteome analysis by mass spectrometry and its application to Saccharomyces cerevisiae.”  Ficarro S.B.et.al.   11875433
[43] “Subproteomics: identification of plasma membrane proteins from the yeast Saccharomyces cerevisiae.”  Navarre C.et.al.   12469340
[44] “Potent competitive inhibition of drug binding to the Saccharomyces cerevisiae ABC exporter Pdr5p by the hydrophobic estradiol-derivative RU49953.”  Conseil G.et.al.   12896805
[45] “Phenothiazines as potent modulators of yeast multidrug resistance.”  Kolaczkowski M.et.al.   13678835
[46] “Studies with novel Pdr5p substrates demonstrate a strong size dependence for xenobiotic efflux.”  Golin J.et.al.   12496287
[47] “A general strategy to uncover transcription factor properties identifies a new regulator of drug resistance in yeast.”  Hikkel I.et.al.   12529331
[48] “Three-dimensional reconstruction of the Saccharomyces cerevisiae multidrug resistance protein Pdr5p.”  Ferreira-Pereira A.et.al.   12551908
[49] “Antifungal activity of amiodarone is mediated by disruption of calcium homeostasis.”  Gupta S.S.et.al.   12754197
[50] “Global analysis of protein expression in yeast.”  Ghaemmaghami S.et.al.   14562106
[51] “A proteomics approach to understanding protein ubiquitination.”  Peng J.et.al.   12872131
[52] “A subset of membrane-associated proteins is ubiquitinated in response to mutations in the endoplasmic reticulum degradation machinery.”  Hitchcock A.L.et.al.   14557538
[53] “A yeast-based method for the detection of cyto and genotoxicity.”  Lichtenberg-Frate H.et.al.   14599467
[54] “Chemosensitization of fluconazole resistance in Saccharomyces cerevisiae and pathogenic fungi by a D-octapeptide derivative.”  Niimi K.et.al.   15047528
[55] “The transporters Pdr5p and Snq2p mediate diazaborine resistance and are under the control of the gain-of-function allele PDR1-12.”  Wehrschutz-Sigl E.et.al.   15009193
[56] “Expression regulation of the yeast PDR5 ATP-binding cassette (ABC) transporter suggests a role in cellular detoxification during the exponential growth phase.”  Mamnun Y.M.et.al.   14960317
[57] “On the mechanism of constitutive Pdr1 activator-mediated PDR5 transcription in Saccharomyces cerevisiae: evidence for enhanced recruitment of coactivators and altered nucleosome structures.”  Gao C.et.al.   15294907
[58] “Enniatin has a new function as an inhibitor of Pdr5p, one of the ABC transporters in Saccharomyces cerevisiae.”  Hiraga K.et.al.   15707993
[59] “A new function of isonitrile as an inhibitor of the Pdr5p multidrug ABC transporter in Saccharomyces cerevisiae.”  Yamamoto S.et.al.   15796929
[60] “The role of hydrogen bond acceptor groups in the interaction of substrates with Pdr5p, a major yeast drug transporter.”  Hanson L.et.al.   16008355
[61] “Retrograde regulation of multidrug resistance in Saccharomyces cerevisiae.”  Moye-Rowley W.S.et.al.   15896930
[62] “Mutational analysis of the yeast multidrug resistance ABC transporter Pdr5p with altered drug specificity.”  Tutulan-Cunita A.C.et.al.   15836770
[63] “Activity of yeast multidrug resistance pumps during growth is controlled by carbon source and the composition of growth-depleted medium: DiS-C3(3) fluorescence assay.”  Malac J.et.al.   16061415
[64] “Regulation of the sphingoid long-chain base kinase Lcb4p by ergosterol and heme: studies in phytosphingosine-resistant mutants.”  Sano T.et.al.   16141212
[65] “Early expression of yeast genes affected by chemical stress.”  Lucau-Danila A.et.al.   15713640
[66] “Early transcriptional response of Saccharomyces cerevisiae to stress imposed by the herbicide 2,4-dichlorophenoxyacetic acid.”  Teixeira M.C.et.al.   16487346
[67] “Adaptive response to the antimalarial drug artesunate in yeast involves Pdr1p/Pdr3p-mediated transcriptional activation of the resistance determinants TPO1 and PDR5.”  Alenquer M.et.al.   17156010
[68] “ELM1 is required for multidrug resistance in Saccharomyces cerevisiae.”  Souid A.K.et.al.   16751665
[69] “A global topology map of the Saccharomyces cerevisiae membrane proteome.”  Kim H.et.al.   16847258
[70] “The yeast Pdr5p multidrug transporter: how does it recognize so many substrates?”  Golin J.et.al.   17316560
[71] “The central role of PDR1 in the foundation of yeast drug resistance.”  Fardeau V.et.al.   17158869
[72] “Large-scale phosphorylation analysis of alpha-factor-arrested Saccharomyces cerevisiae.”  Li X.et.al.   17330950
[73] “Subcellular trafficking of the yeast plasma membrane ABC transporter, Pdr5, is impaired by a mutation in the N-terminal nucleotide-binding fold.”  de Thozee C.P.et.al.   17302805
[74] “Analysis of phosphorylation sites on proteins from Saccharomyces cerevisiae by electron transfer dissociation (ETD) mass spectrometry.”  Chi A.et.al.   17287358
[75] “Proteome-wide identification of in vivo targets of DNA damage checkpoint kinases.”  Smolka M.B.et.al.   17563356
[76] “A multidimensional chromatography technology for in-depth phosphoproteome analysis.”  Albuquerque C.P.et.al.   18407956

External Searches:

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MPEAKLNNNV NDVTSYSSAS SSTENAADLH NYNGFDEHTE ARIQKLARTL TAQSMQNSTQ 
61:	SAPNKSDAQS IFSSGVEGVN PIFSDPEAPG YDPKLDPNSE NFSSAAWVKN MAHLSAADPD 
121:	FYKPYSLGCA WKNLSASGAS ADVAYQSTVV NIPYKILKSG LRKFQRSKET NTFQILKPMD 
181:	GCLNPGELLV VLGRPGSGCT TLLKSISSNT HGFDLGADTK ISYSGYSGDD IKKHFRGEVV 
241:	YNAEADVHLP HLTVFETLVT VARLKTPQNR IKGVDRESYA NHLAEVAMAT YGLSHTRNTK 
301:	VGNDIVRGVS GGERKRVSIA EVSICGSKFQ CWDNATRGLD SATALEFIRA LKTQADISNT 
361:	SATVAIYQCS QDAYDLFNKV CVLDDGYQIY YGPADKAKKY FEDMGYVCPS RQTTADFLTS 
421:	VTSPSERTLN KDMLKKGIHI PQTPKEMNDY WVKSPNYKEL MKEVDQRLLN DDEASREAIK 
481:	EAHIAKQSKR ARPSSPYTVS YMMQVKYLLI RNMWRLRNNI GFTLFMILGN CSMALILGSM 
541:	FFKIMKKGDT STFYFRGSAM FFAILFNAFS SLLEIFSLYE ARPITEKHRT YSLYHPSADA 
601:	FASVLSEIPS KLIIAVCFNI IFYFLVDFRR NGGVFFFYLL INIVAVFSMS HLFRCVGSLT 
661:	KTLSEAMVPA SMLLLALSMY TGFAIPKKKI LRWSKWIWYI NPLAYLFESL LINEFHGIKF 
721:	PCAEYVPRGP AYANISSTES VCTVVGAVPG QDYVLGDDFI RGTYQYYHKD KWRGFGIGMA 
781:	YVVFFFFVYL FLCEYNEGAK QKGEILVFPR SIVKRMKKRG VLTEKNANDP ENVGERSDLS 
841:	SDRKMLQESS EEESDTYGEI GLSKSEAIFH WRNLCYEVQI KAETRRILNN VDGWVKPGTL 
901:	TALMGASGAG KTTLLDCLAE RVTMGVITGD ILVNGIPRDK SFPRSIGYCQ QQDLHLKTAT 
961:	VRESLRFSAY LRQPAEVSIE EKNRYVEEVI KILEMEKYAD AVVGVAGEGL NVEQRKRLTI 
1021:	GVELTAKPKL LVFLDEPTSG LDSQTAWSIC QLMKKLANHG QAILCTIHQP SAILMQEFDR 
1081:	LLFMQRGGKT VYFGDLGEGC KTMIDYFESH GAHKCPADAN PAEWMLEVVG AAPGSHANQD 
1141:	YYEVWRNSEE YRAVQSELDW MERELPKKGS ITAAEDKHEF SQSIIYQTKL VSIRLFQQYW 
1201:	RSPDYLWSKF ILTIFNQLFI GFTFFKAGTS LQGLQNQMLA VFMFTVIFNP ILQQYLPSFV 
1261:	QQRDLYEARE RPSRTFSWIS FIFAQIFVEV PWNILAGTIA YFIYYYPIGF YSNASAAGQL 
1321:	HERGALFWLF SCAFYVYVGS MGLLVISFNQ VAESAANLAS LLFTMSLSFC GVMTTPSAMP 
1381:	RFWIFMYRVS PLTYFIQALL AVGVANVDVK CADYELLEFT PPSGMTCGQY MEPYLQLAKT 
1441:	GYLTDENATD TCSFCQISTT NDYLANVNSF YSERWRNYGI FICYIAFNYI AGVFFYWLAR 
1501:	VPKKNGKLSK K