Reviewed, UniProtKB/Swiss-Prot P33302 (PDR5_YEAST)

Names and origin

Protein names

Recommended name:
    Pleiotropic ABC efflux transporter of multiple drugs
Alternative name(s):
    Pleiotropic drug resistance protein 5
    Suppressor of toxicity of sporidesmin

Gene names

Name:	PDR5
Synonyms:	LEM1, STS1, YDR1
Ordered Locus Names:	YOR153W

Organism

Saccharomyces cerevisiae (Baker's yeast) [Complete proteome]

Taxonomic identifier

4932 [NCBI]

Taxonomic lineage

Eukaryota › Fungi › Dikarya › Ascomycota › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces

Protein attributes

Sequence length	1511 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Active efflux of weakly charged organic compounds of 90 cubic Angstroms to 300 cubic Angstroms surface volume. Confers resistance to numerous chemicals including cycloheximide, sulfomethuron methyl, steroids, antiseptics, antibiotics, anticancer, herbicides, mycotoxins, insecticides, ionophores, alkaloids, flavonoids, phenothiazines, organotin compounds, carbazoles, lysosomotropic aminoesters, detergents, rhodamines and other fluorophores, azoles and other antifungals. Exhibits nucleoside triphosphatase activity.
Enzyme regulation	FK506, isonitrile, enniatin, RU49953, kitasatospora E420, staurosporine CGP42700, prenyl-flavonoids, D-octapeptides were found to be inhibitors in vivo. Vanadate and oligomycin were found to be inhibitors in vitro.
Subcellular location	Cell membrane; Multi-pass membrane protein. Note= The ERAD mutants 'Pro-183' and 'Tyr-1427' fail to reach the plasma membrane. The mutant 'Pro-183' accumulates into ER-associated compartments.
Induction	Expressed during exponential growth. Transcription is transiently activated within 40 min after induction by benomyl and other toxic chemicals. Multidrug resistance and PDR5 mRNA level are activated by the transcription regulators PDR1, PDR3, YAP1, YAP2, STB5 and by the mitochondrial rho zero mutation. Mutations or deletion in the PDR1 or PDR3 transcription factors strongly activate PDR5 mRNA and PDR5 translation. The transcription regulator RDR1 represses PDR5 expression.
Domain	The N-terminal ABC transporter domain (positions 161 to 410) contains degenerated Walker A and B ATP-binding motifs, suggesting that it may be less efficient in ATP binding or not functional at all. This is a distinctive feature of the PDR subfamily. The unusual length of the two extracellular loops at positions 686 to 774 and 1408 to 1476 is another specific feature of the PDR subfamily which may have an important role for function.
Post-translational modification	Ubiquitinylation mediates endocytosis and vacuolar degradation. Phosphorylation by casein kinase I stabilizes the protein half-life.
Biotechnological use	Strains lacking PDR5 are used for toxicity tests. Strains overexpressing PDR5 are used for screening antifungal sensitizers.
Miscellaneous	Present with 42000 molecules/cell in log phase SD medium in log phase SD medium. Full-sized PDR5 orthologs are found only in fungi and plants. Their topology and substrate specificity are distinct from mammalian MDR transporters. This protein has been 'adopted' by Andre Goffeau from the Catholic University of Louvain (Belgium). The above-mentioned scientist has agreed to help us to curate information available on this protein. We are grateful to that person for committing precious time to help producing annotation useful to the whole community. However that person is not responsible for any errors or omissions in this UniProtKB/Swiss-Prot entry. If you have found something wrong or missing in this entry you should submit an update report to: [e-mail].
Sequence similarities	Belongs to the ABC transporter family. PDR subfamily. Contains 2 ABC transporter domains.
Biophysicochemical properties	Kinetic parameters: Activity measured in plasma membranes. KM=0.5 mM for MgATP Vmax=2.5 µmol/min/mg enzyme pH dependence: Optimum pH is 7.0.
Sequence caution	The sequence BAA05547.1 differs from that shown. Reason: Frameshift at position 61.

Ontologies

Keywords
Biological process	Antibiotic resistance Cycloheximide resistance Transport
Cellular component	Cell membrane Membrane
Domain	Repeat Transmembrane
Ligand	ATP-binding Nucleotide-binding
PTM	Glycoprotein Phosphoprotein Ubl conjugation
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	drug transport Traceable author statement. Source: SGD response to toxin Inferred from expression pattern. Source: SGD
Cellular component	mitochondrion Inferred from direct assay. Source: SGD plasma membrane Ref.18 Ref.43 Inferred from direct assay. Source: SGD
Molecular function	xenobiotic-transporting ATPase activity Traceable author statement. Source: SGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 1511	1511	Pleiotropic ABC efflux transporter of multiple drugs
Regions
	Topological domain	1 – 517	517	Cytoplasmic Potential
	Transmembrane	518 – 542	25	Potential
	Topological domain	543 – 558	16	Extracellular Potential
	Transmembrane	559 – 579	21	Potential
	Topological domain	580 – 611	32	Cytoplasmic Potential
	Transmembrane	612 – 628	17	Potential
	Topological domain	629 – 631	3	Extracellular Potential
	Transmembrane	632 – 650	19	Potential
	Topological domain	651 – 665	15	Cytoplasmic Potential
	Transmembrane	666 – 685	20	Potential
	Topological domain	686 – 774	89	Extracellular Potential
	Transmembrane	775 – 793	19	Potential
	Topological domain	794 – 1237	444	Cytoplasmic Potential
	Transmembrane	1238 – 1260	23	Potential
	Topological domain	1261 – 1291	31	Extracellular Potential
	Transmembrane	1292 – 1313	22	Potential
	Topological domain	1314 – 1324	11	Cytoplasmic Potential
	Transmembrane	1325 – 1349	25	Potential
	Topological domain	1350 – 1354	5	Extracellular Potential
	Transmembrane	1355 – 1379	25	Potential
	Topological domain	1380 – 1388	9	Cytoplasmic Potential
	Transmembrane	1389 – 1407	19	Potential
	Topological domain	1408 – 1476	69	Extracellular Potential
	Transmembrane	1477 – 1499	23	Potential
	Topological domain	1500 – 1511	12	Cytoplasmic Potential
	Domain	161 – 410	250	ABC transporter 1
	Domain	869 – 1112	244	ABC transporter 2
	Nucleotide binding	905 – 912	8	ATP Potential
	Compositional bias	784 – 787	4	Poly-Phe
Amino acid modifications
	Modified residue	49	1	Phosphothreonine
	Modified residue	54	1	Phosphoserine
	Modified residue	58	1	Phosphoserine
	Modified residue	59	1	Phosphothreonine
	Modified residue	61	1	Phosphoserine
	Modified residue	837	1	Phosphoserine
	Modified residue	840	1	Phosphoserine
	Modified residue	841	1	Phosphoserine
	Modified residue	849	1	Phosphoserine
	Modified residue	850	1	Phosphoserine
	Modified residue	854	1	Phosphoserine
	Modified residue	857	1	Phosphotyrosine
	Modified residue	863	1	Phosphoserine
	Glycosylation	734	1	N-linked (GlcNAc...) Potential
	Glycosylation	1447	1	N-linked (GlcNAc...) Potential
	Cross-link	825		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Experimental info
	Mutagenesis	183	1	L → P: Activates ER-associated degradation
	Mutagenesis	257	1	T → I: Alters drug specificity
	Mutagenesis	302	1	G → D: Confers generalized drug resistance
	Mutagenesis	648	1	S → F: Alters drug specificity
	Mutagenesis	905	1	G → S: Inactivates drug transport
	Mutagenesis	908	1	G → S: Inactivates drug transport
	Mutagenesis	1009	1	G → C: Confers generalized drug resistance
	Mutagenesis	1040	1	G → D: Alters drug specificity
	Mutagenesis	1048	1	S → V: Alters drug specificity
	Mutagenesis	1289	1	E → K: Alters drug specificity
	Mutagenesis	1311	1	Y → S: Alters drug specificity
	Mutagenesis	1360	1	S → F: Alters drug specificity
	Mutagenesis	1393	1	T → I: Alters drug specificity
	Mutagenesis	1427	1	C → Y: Activates ER-associated degradation
	Sequence conflict	171	1	N → L in BAA05547. Ref.1
	Sequence conflict	190	1	V → I in BAA05547. Ref.1
	Sequence conflict	214	1	D → T in BAA05547. Ref.1
	Sequence conflict	308	1	G → V in BAA05547. Ref.1
	Sequence conflict	340 – 345	6	Missing in BAA05547. Ref.1
	Sequence conflict	476	1	R → H in BAA05547. Ref.1
	Sequence conflict	648	1	Missing in BAA05547. Ref.1
	Sequence conflict	770	1	D → H in BAA05547. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P33302-1 [UniParc]. Last modified February 1, 1994. Version 1. Checksum: 4540DC0BF04744BA	FASTA	1,511	170,438
	10 20 30 40 50 60 MPEAKLNNNV NDVTSYSSAS SSTENAADLH NYNGFDEHTE ARIQKLARTL TAQSMQNSTQ 70 80 90 100 110 120 SAPNKSDAQS IFSSGVEGVN PIFSDPEAPG YDPKLDPNSE NFSSAAWVKN MAHLSAADPD 130 140 150 160 170 180 FYKPYSLGCA WKNLSASGAS ADVAYQSTVV NIPYKILKSG LRKFQRSKET NTFQILKPMD 190 200 210 220 230 240 GCLNPGELLV VLGRPGSGCT TLLKSISSNT HGFDLGADTK ISYSGYSGDD IKKHFRGEVV 250 260 270 280 290 300 YNAEADVHLP HLTVFETLVT VARLKTPQNR IKGVDRESYA NHLAEVAMAT YGLSHTRNTK 310 320 330 340 350 360 VGNDIVRGVS GGERKRVSIA EVSICGSKFQ CWDNATRGLD SATALEFIRA LKTQADISNT 370 380 390 400 410 420 SATVAIYQCS QDAYDLFNKV CVLDDGYQIY YGPADKAKKY FEDMGYVCPS RQTTADFLTS 430 440 450 460 470 480 VTSPSERTLN KDMLKKGIHI PQTPKEMNDY WVKSPNYKEL MKEVDQRLLN DDEASREAIK 490 500 510 520 530 540 EAHIAKQSKR ARPSSPYTVS YMMQVKYLLI RNMWRLRNNI GFTLFMILGN CSMALILGSM 550 560 570 580 590 600 FFKIMKKGDT STFYFRGSAM FFAILFNAFS SLLEIFSLYE ARPITEKHRT YSLYHPSADA 610 620 630 640 650 660 FASVLSEIPS KLIIAVCFNI IFYFLVDFRR NGGVFFFYLL INIVAVFSMS HLFRCVGSLT 670 680 690 700 710 720 KTLSEAMVPA SMLLLALSMY TGFAIPKKKI LRWSKWIWYI NPLAYLFESL LINEFHGIKF 730 740 750 760 770 780 PCAEYVPRGP AYANISSTES VCTVVGAVPG QDYVLGDDFI RGTYQYYHKD KWRGFGIGMA 790 800 810 820 830 840 YVVFFFFVYL FLCEYNEGAK QKGEILVFPR SIVKRMKKRG VLTEKNANDP ENVGERSDLS 850 860 870 880 890 900 SDRKMLQESS EEESDTYGEI GLSKSEAIFH WRNLCYEVQI KAETRRILNN VDGWVKPGTL 910 920 930 940 950 960 TALMGASGAG KTTLLDCLAE RVTMGVITGD ILVNGIPRDK SFPRSIGYCQ QQDLHLKTAT 970 980 990 1000 1010 1020 VRESLRFSAY LRQPAEVSIE EKNRYVEEVI KILEMEKYAD AVVGVAGEGL NVEQRKRLTI 1030 1040 1050 1060 1070 1080 GVELTAKPKL LVFLDEPTSG LDSQTAWSIC QLMKKLANHG QAILCTIHQP SAILMQEFDR 1090 1100 1110 1120 1130 1140 LLFMQRGGKT VYFGDLGEGC KTMIDYFESH GAHKCPADAN PAEWMLEVVG AAPGSHANQD 1150 1160 1170 1180 1190 1200 YYEVWRNSEE YRAVQSELDW MERELPKKGS ITAAEDKHEF SQSIIYQTKL VSIRLFQQYW 1210 1220 1230 1240 1250 1260 RSPDYLWSKF ILTIFNQLFI GFTFFKAGTS LQGLQNQMLA VFMFTVIFNP ILQQYLPSFV 1270 1280 1290 1300 1310 1320 QQRDLYEARE RPSRTFSWIS FIFAQIFVEV PWNILAGTIA YFIYYYPIGF YSNASAAGQL 1330 1340 1350 1360 1370 1380 HERGALFWLF SCAFYVYVGS MGLLVISFNQ VAESAANLAS LLFTMSLSFC GVMTTPSAMP 1390 1400 1410 1420 1430 1440 RFWIFMYRVS PLTYFIQALL AVGVANVDVK CADYELLEFT PPSGMTCGQY MEPYLQLAKT 1450 1460 1470 1480 1490 1500 GYLTDENATD TCSFCQISTT NDYLANVNSF YSERWRNYGI FICYIAFNYI AGVFFYWLAR 1510 VPKKNGKLSK K

References

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[1]	"Saccharomyces cerevisiae YDR1, which encodes a member of the ATP-binding cassette (ABC) superfamily, is required for multidrug resistance." Hirata D., Yano K., Miyahara K., Miyakawa T. Curr. Genet. 26:285-294(1994) [PubMed: 7882421] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 38626 / AH22 / NRRL Y-12843.
[2]	"PDR5, a novel yeast multidrug resistance conferring transporter controlled by the transcription regulator PDR1." Balzi E., Wang M., Leterme S., van Dyck L., Goffeau A. J. Biol. Chem. 269:2206-2214(1994) [PubMed: 8294477] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PARTIAL PROTEIN SEQUENCE, TOPOLOGY, DOMAINS. Strain: ATCC 204508 / S288c.
[3]	"Molecular cloning and expression of the Saccharomyces cerevisiae STS1 gene product. A yeast ABC transporter conferring mycotoxin resistance." Bissinger P.H., Kuchler K. J. Biol. Chem. 269:4180-4186(1994) [PubMed: 8307980] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 204510 / AB320.
[4]	"Analysis of a 35.6 kb region on the right arm of Saccharomyces cerevisiae chromosome XV." Bordonne R., Camasses A., Madania A., Poch O., Tarassov I.A., Winsor B., Martin R.P. Yeast 13:73-83(1997) [PubMed: 9046089] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: S288c / FY1678.
[5]	"The nucleotide sequence of Saccharomyces cerevisiae chromosome XV." Dujon B., Albermann K., Aldea M., Alexandraki D., Ansorge W., Arino J., Benes V., Bohn C., Bolotin-Fukuhara M., Bordonne R., Boyer J., Camasses A., Casamayor A., Casas C., Cheret G., Cziepluch C., Daignan-Fornier B., Dang V.-D. , de Haan M., Delius H., Durand P., Fairhead C., Feldmann H., Gaillon L., Galisson F., Gamo F.-J., Gancedo C., Goffeau A., Goulding S.E., Grivell L.A., Habbig B., Hand N.J., Hani J., Hattenhorst U., Hebling U., Hernando Y., Herrero E., Heumann K., Hiesel R., Hilger F., Hofmann B., Hollenberg C.P., Hughes B., Jauniaux J.-C., Kalogeropoulos A., Katsoulou C., Kordes E., Lafuente M.J., Landt O., Louis E.J., Maarse A.C., Madania A., Mannhaupt G., Marck C., Martin R.P., Mewes H.-W., Michaux G., Paces V., Parle-McDermott A.G., Pearson B.M., Perrin A., Pettersson B., Poch O., Pohl T.M., Poirey R., Portetelle D., Pujol A., Purnelle B., Ramezani Rad M., Rechmann S., Schwager C., Schweizer M., Sor F., Sterky F., Tarassov I.A., Teodoru C., Tettelin H., Thierry A., Tobiasch E., Tzermia M., Uhlen M., Unseld M., Valens M., Vandenbol M., Vetter I., Vlcek C., Voet M., Volckaert G., Voss H., Wambutt R., Wedler H., Wiemann S., Winsor B., Wolfe K.H., Zollner A., Zumstein E., Kleine K. Nature 387:98-102(1997) [PubMed: 9169874] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: S288c / FY1678.
[6]	"The multidrug resistance gene PDR1 from Saccharomyces cerevisiae." Balzi E., Chen W., Ulaszewski S., Capieaux E., Goffeau A. J. Biol. Chem. 262:16871-16879(1987) [PubMed: 3316228] [Abstract] Cited for: TRANSCRIPTION REGULATION.
[7]	"Interaction of the yeast pleiotropic drug resistance genes PDR1 and PDR5." Meyers S., Schauer W., Balzi E., Wagner M., Goffeau A., Golin J. Curr. Genet. 21:431-436(1992) [PubMed: 1319843] [Abstract] Cited for: TRANSCRIPTION REGULATION.
[8]	"Loss of function mutation in the yeast multiple drug resistance gene PDR5 causes a reduction in chloramphenicol efflux." Leonard P.J., Rathod P.K., Golin J. Antimicrob. Agents Chemother. 38:2492-2494(1994) [