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Reviewed, UniProtKB/Swiss-Prot P33302 (PDR5_YEAST)

Last modified November 25, 2008. Version 97. Feed History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended 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
OrganismSaccharomyces cerevisiae (Baker's yeast) [Complete proteome]
Taxonomic identifier4932 [NCBI]
Taxonomic lineageEukaryota › Fungi › Dikarya › Ascomycota › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces

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Protein attributes

Sequence length1511 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

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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: help@uniprot.org.

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.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 15111511Pleiotropic ABC efflux transporter of multiple drugs
PRO_0000093442

Regions

Topological domain1 – 517517Cytoplasmic Potential
Transmembrane518 – 54225 Potential
Topological domain543 – 55816Extracellular Potential
Transmembrane559 – 57921 Potential
Topological domain580 – 61132Cytoplasmic Potential
Transmembrane612 – 62817 Potential
Topological domain629 – 6313Extracellular Potential
Transmembrane632 – 65019 Potential
Topological domain651 – 66515Cytoplasmic Potential
Transmembrane666 – 68520 Potential
Topological domain686 – 77489Extracellular Potential
Transmembrane775 – 79319 Potential
Topological domain794 – 1237444Cytoplasmic Potential
Transmembrane1238 – 126023 Potential
Topological domain1261 – 129131Extracellular Potential
Transmembrane1292 – 131322 Potential
Topological domain1314 – 132411Cytoplasmic Potential
Transmembrane1325 – 134925 Potential
Topological domain1350 – 13545Extracellular Potential
Transmembrane1355 – 137925 Potential
Topological domain1380 – 13889Cytoplasmic Potential
Transmembrane1389 – 140719 Potential
Topological domain1408 – 147669Extracellular Potential
Transmembrane1477 – 149923 Potential
Topological domain1500 – 151112Cytoplasmic Potential
Domain161 – 410250ABC transporter 1
Domain869 – 1112244ABC transporter 2
Nucleotide binding905 – 9128ATP Potential
Compositional bias784 – 7874Poly-Phe

Amino acid modifications

Modified residue491Phosphothreonine
Modified residue541Phosphoserine
Modified residue581Phosphoserine
Modified residue591Phosphothreonine
Modified residue611Phosphoserine
Modified residue8371Phosphoserine
Modified residue8401Phosphoserine
Modified residue8411Phosphoserine
Modified residue8491Phosphoserine
Modified residue8501Phosphoserine
Modified residue8541Phosphoserine
Modified residue8571Phosphotyrosine
Modified residue8631Phosphoserine
Glycosylation7341N-linked (GlcNAc...) Potential
Glycosylation14471N-linked (GlcNAc...) Potential
Cross-link825Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)

Experimental info

Mutagenesis1831L → P: Activates ER-associated degradation
Mutagenesis2571T → I: Alters drug specificity
Mutagenesis3021G → D: Confers generalized drug resistance
Mutagenesis6481S → F: Alters drug specificity
Mutagenesis9051G → S: Inactivates drug transport
Mutagenesis9081G → S: Inactivates drug transport
Mutagenesis10091G → C: Confers generalized drug resistance
Mutagenesis10401G → D: Alters drug specificity
Mutagenesis10481S → V: Alters drug specificity
Mutagenesis12891E → K: Alters drug specificity
Mutagenesis13111Y → S: Alters drug specificity
Mutagenesis13601S → F: Alters drug specificity
Mutagenesis13931T → I: Alters drug specificity
Mutagenesis14271C → Y: Activates ER-associated degradation
Sequence conflict1711N → L in BAA05547. Ref.1
Sequence conflict1901V → I in BAA05547. Ref.1
Sequence conflict2141D → T in BAA05547. Ref.1
Sequence conflict3081G → V in BAA05547. Ref.1
Sequence conflict340 – 3456Missing in BAA05547. Ref.1
Sequence conflict4761R → H in BAA05547. Ref.1
Sequence conflict6481Missing in BAA05547. Ref.1
Sequence conflict7701D → H in BAA05547. Ref.1

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Sequences

Sequence LengthMass (Da)Tools
P33302-1 [UniParc].

Last modified February 1, 1994. Version 1.
Checksum: 4540DC0BF04744BA

FASTA1,511170,438
        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

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References

« Hide 'large scale' references
[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. expand/collapse author list , 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.