ID PDR5_YEAST Reviewed; 1511 AA. AC P33302; D6W2L0; DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1994, sequence version 1. DT 02-SEP-2026, entry version 235. DE RecName: Full=Pleiotropic ABC efflux transporter of multiple drugs; DE AltName: Full=Pleiotropic drug resistance protein 5; DE AltName: Full=Suppressor of toxicity of sporidesmin; GN Name=PDR5; Synonyms=LEM1, STS1, YDR1; OrderedLocusNames=YOR153W; OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast). OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; OC Saccharomycetales; Saccharomycetaceae; Saccharomyces. OX NCBI_TaxID=559292; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 38626 / AH22 / NRRL Y-12843; RX PubMed=7882421; DOI=10.1007/bf00310491; RA Hirata D., Yano K., Miyahara K., Miyakawa T.; RT "Saccharomyces cerevisiae YDR1, which encodes a member of the ATP-binding RT cassette (ABC) superfamily, is required for multidrug resistance."; RL Curr. Genet. 26:285-294(1994). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PARTIAL PROTEIN SEQUENCE, TOPOLOGY, AND RP DOMAINS. RC STRAIN=ATCC 204508 / S288c; RX PubMed=8294477; DOI=10.1016/s0021-9258(17)42155-7; RA Balzi E., Wang M., Leterme S., van Dyck L., Goffeau A.; RT "PDR5, a novel yeast multidrug resistance conferring transporter controlled RT by the transcription regulator PDR1."; RL J. Biol. Chem. 269:2206-2214(1994). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 204510 / AB320; RX PubMed=8307980; DOI=10.1016/s0021-9258(17)41760-1; RA Bissinger P.H., Kuchler K.; RT "Molecular cloning and expression of the Saccharomyces cerevisiae STS1 gene RT product. A yeast ABC transporter conferring mycotoxin resistance."; RL J. Biol. Chem. 269:4180-4186(1994). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=S288c / FY1678; RX PubMed=9046089; RX DOI=10.1002/(sici)1097-0061(199701)13:1<73::aid-yea52>3.0.co;2-m; RA Bordonne R., Camasses A., Madania A., Poch O., Tarassov I.A., Winsor B., RA Martin R.P.; RT "Analysis of a 35.6 kb region on the right arm of Saccharomyces cerevisiae RT chromosome XV."; RL Yeast 13:73-83(1997). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=9169874; DOI=10.1038/387s098; RA Dujon B., Albermann K., Aldea M., Alexandraki D., Ansorge W., Arino J., RA Benes V., Bohn C., Bolotin-Fukuhara M., Bordonne R., Boyer J., Camasses A., RA Casamayor A., Casas C., Cheret G., Cziepluch C., Daignan-Fornier B., RA Dang V.-D., de Haan M., Delius H., Durand P., Fairhead C., Feldmann H., RA Gaillon L., Galisson F., Gamo F.-J., Gancedo C., Goffeau A., Goulding S.E., RA Grivell L.A., Habbig B., Hand N.J., Hani J., Hattenhorst U., Hebling U., RA Hernando Y., Herrero E., Heumann K., Hiesel R., Hilger F., Hofmann B., RA Hollenberg C.P., Hughes B., Jauniaux J.-C., Kalogeropoulos A., RA Katsoulou C., Kordes E., Lafuente M.J., Landt O., Louis E.J., Maarse A.C., RA Madania A., Mannhaupt G., Marck C., Martin R.P., Mewes H.-W., Michaux G., RA Paces V., Parle-McDermott A.G., Pearson B.M., Perrin A., Pettersson B., RA Poch O., Pohl T.M., Poirey R., Portetelle D., Pujol A., Purnelle B., RA Ramezani Rad M., Rechmann S., Schwager C., Schweizer M., Sor F., Sterky F., RA Tarassov I.A., Teodoru C., Tettelin H., Thierry A., Tobiasch E., RA Tzermia M., Uhlen M., Unseld M., Valens M., Vandenbol M., Vetter I., RA Vlcek C., Voet M., Volckaert G., Voss H., Wambutt R., Wedler H., RA Wiemann S., Winsor B., Wolfe K.H., Zollner A., Zumstein E., Kleine K.; RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XV."; RL Nature 387:98-102(1997). RN [6] RP GENOME REANNOTATION. RC STRAIN=ATCC 204508 / S288c; RX PubMed=24374639; DOI=10.1534/g3.113.008995; RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R., RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S., RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.; RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now."; RL G3 (Bethesda) 4:389-398(2014). RN [7] RP TRANSCRIPTION REGULATION. RX PubMed=3316228; DOI=10.1016/s0021-9258(18)45464-6; RA Balzi E., Chen W., Ulaszewski S., Capieaux E., Goffeau A.; RT "The multidrug resistance gene PDR1 from Saccharomyces cerevisiae."; RL J. Biol. Chem. 262:16871-16879(1987). RN [8] RP TRANSCRIPTION REGULATION. RX PubMed=1319843; DOI=10.1007/bf00351651; RA Meyers S., Schauer W., Balzi E., Wagner M., Goffeau A., Golin J.; RT "Interaction of the yeast pleiotropic drug resistance genes PDR1 and RT PDR5."; RL Curr. Genet. 21:431-436(1992). RN [9] RP SUBSTRATES. RX PubMed=7840595; DOI=10.1128/aac.38.10.2492; RA Leonard P.J., Rathod P.K., Golin J.; RT "Loss of function mutation in the yeast multiple drug resistance gene PDR5 RT causes a reduction in chloramphenicol efflux."; RL Antimicrob. Agents Chemother. 38:2492-2494(1994). RN [10] RP PURIFICATION, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=8175692; DOI=10.1016/s0021-9258(18)99946-1; RA Decottignies A., Kolaczkowski M., Balzi E., Goffeau A.; RT "Solubilization and characterization of the overexpressed PDR5 multidrug RT resistance nucleotide triphosphatase of yeast."; RL J. Biol. Chem. 269:12797-12803(1994). RN [11] RP TRANSCRIPTION REGULATION. RX PubMed=8007969; DOI=10.1128/mcb.14.7.4653-4661.1994; RA Katzmann D.J., Burnett P.E., Golin J., Mahe Y., Moye-Rowley W.S.; RT "Transcriptional control of the yeast PDR5 gene by the PDR3 gene product."; RL Mol. Cell. Biol. 14:4653-4661(1994). RN [12] RP TRANSCRIPTION REGULATION. RX PubMed=7623800; DOI=10.1128/mcb.15.8.4043; RA Delahodde A., Delaveau T., Jacq C.; RT "Positive autoregulation of the yeast transcription factor Pdr3p, which is RT involved in control of drug resistance."; RL Mol. Cell. Biol. 15:4043-4051(1995). RN [13] RP DEGRADATION. RX PubMed=7565740; DOI=10.1128/mcb.15.11.5879; RA Egner R., Mahe Y., Pandjaitan R., Kuchler K.; RT "Endocytosis and vacuolar degradation of the plasma membrane-localized Pdr5 RT ATP-binding cassette multidrug transporter in Saccharomyces cerevisiae."; RL Mol. Cell. Biol. 15:5879-5887(1995). RN [14] RP FUNCTION. RX PubMed=7753868; DOI=10.1073/pnas.92.10.4701; RA Kralli A., Bohen S.P., Yamamoto K.R.; RT "LEM1, an ATP-binding-cassette transporter, selectively modulates the RT biological potency of steroid hormones."; RL Proc. Natl. Acad. Sci. U.S.A. 92:4701-4705(1995). RN [15] RP TRANSCRIPTION REGULATION. RX PubMed=8821655; DOI=10.1007/bf02221572; RA Miyahara K., Hirata D., Miyakawa T.; RT "yAP-1- and yAP-2-mediated, heat shock-induced transcriptional activation RT of the multidrug resistance ABC transporter genes in Saccharomyces RT cerevisiae."; RL Curr. Genet. 29:103-105(1996). RN [16] RP DEGRADATION. RX PubMed=8549828; DOI=10.1016/0014-5793(95)01450-0; RA Egner R., Kuchler K.; RT "The yeast multidrug transporter Pdr5 of the plasma membrane is RT ubiquitinated prior to endocytosis and degradation in the vacuole."; RL FEBS Lett. 378:177-181(1996). RN [17] RP FUNCTION. RX PubMed=8985171; DOI=10.1016/s0014-5793(96)01353-1; RA Miyahara K., Mizunuma M., Hirata D., Tsuchiya E., Miyakawa T.; RT "The involvement of the Saccharomyces cerevisiae multidrug resistance RT transporters Pdr5p and Snq2p in cation resistance."; RL FEBS Lett. 399:317-320(1996). RN [18] RP INHIBITORS. RX PubMed=8663352; DOI=10.1074/jbc.271.29.17152; RA Kralli A., Yamamoto K.R.; RT "An FK506-sensitive transporter selectively decreases intracellular levels RT and potency of steroid hormones."; RL J. Biol. Chem. 271:17152-17156(1996). RN [19] RP FUNCTION. RX PubMed=8810273; DOI=10.1074/jbc.271.41.25167; RA Mahe Y., Lemoine Y., Kuchler K.; RT "The ATP binding cassette transporters Pdr5 and Snq2 of Saccharomyces RT cerevisiae can mediate transport of steroids in vivo."; RL J. Biol. Chem. 271:25167-25172(1996). RN [20] RP FUNCTION. RX PubMed=8940170; DOI=10.1074/jbc.271.49.31543; RA Kolaczkowski M., van der Rest M., Cybularz-Kolaczkowska A., RA Soumillion J.P., Konings W.N., Goffeau A.; RT "Anticancer drugs, ionophoric peptides, and steroids as substrates of the RT yeast multidrug transporter Pdr5p."; RL J. Biol. Chem. 271:31543-31548(1996). RN [21] RP SUBSTRATES. RX PubMed=9115278; DOI=10.1074/jbc.272.18.12091; RA Reid R.J.D., Kauh E.A., Bjornsti M.-A.; RT "Camptothecin sensitivity is mediated by the pleiotropic drug resistance RT network in yeast."; RL J. Biol. Chem. 272:12091-12099(1997). RN [22] RP TRANSCRIPTION REGULATION. RX PubMed=9393437; DOI=10.1007/s004380050583; RA Nourani A., Papajova D., Delahodde A., Jacq C., Subik J.; RT "Clustered amino acid substitutions in the yeast transcription regulator RT Pdr3p increase pleiotropic drug resistance and identify a new central RT regulatory domain."; RL Mol. Gen. Genet. 256:397-405(1997). RN [23] RP INDUCTION. RX PubMed=9393438; DOI=10.1007/s004380050584; RA Carvajal E., van den Hazel H.B., Cybularz-Kolaczkowska A., Balzi E., RA Goffeau A.; RT "Molecular and phenotypic characterization of yeast PDR1 mutants that show RT hyperactive transcription of various ABC multidrug transporter genes."; RL Mol. Gen. Genet. 256:406-415(1997). RN [24] RP PROTEIN FAMILY. RX PubMed=9020838; DOI=10.1038/ng0297-137; RA Decottignies A., Goffeau A.; RT "Complete inventory of the yeast ABC proteins."; RL Nat. Genet. 15:137-145(1997). RN [25] RP SUBSTRATES. RX PubMed=9559778; DOI=10.1128/aac.42.4.755; RA Ogawa A., Hashida-Okado T., Endo M., Yoshioka H., Tsuruo T., Takesako K., RA Kato I.; RT "Role of ABC transporters in aureobasidin A resistance."; RL Antimicrob. Agents Chemother. 42:755-761(1998). RN [26] RP TRAFFICKING. RX PubMed=9830032; DOI=10.1074/jbc.273.49.32848; RA Plemper R.K., Egner R., Kuchler K., Wolf D.H.; RT "Endoplasmic reticulum degradation of a mutated ATP-binding cassette RT transporter Pdr5 proceeds in a concerted action of Sec61 and the RT proteasome."; RL J. Biol. Chem. 273:32848-32856(1998). RN [27] RP FUNCTION, AND MUTAGENESIS. RX PubMed=9450972; DOI=10.1091/mbc.9.2.523; RA Egner R., Rosenthal F.E., Kralli A., Sanglard D., Kuchler K.; RT "Genetic separation of FK506 susceptibility and drug transport in the yeast RT Pdr5 ATP-binding cassette multidrug resistance transporter."; RL Mol. Biol. Cell 9:523-543(1998). RN [28] RP FUNCTION. RX PubMed=9818966; DOI=10.1089/mdr.1998.4.143; RA Kolaczkowski M., Kolaczowska A., Luczynski J., Witek S., Goffeau A.; RT "In vivo characterization of the drug resistance profile of the major ABC RT transporters and other components of the yeast pleiotropic drug resistance RT network."; RL Microb. Drug Resist. 4:143-158(1998). RN [29] RP PHOSPHORYLATION BY CK1. RX PubMed=10601275; DOI=10.1074/jbc.274.52.37139; RA Decottignies A., Owsianik G., Ghislain M.; RT "Casein kinase I-dependent phosphorylation and stability of the yeast RT multidrug transporter Pdr5p."; RL J. Biol. Chem. 274:37139-37146(1999). RN [30] RP SUBSTRATES. RX PubMed=10602734; DOI=10.1128/aac.44.1.134-138.2000; RA Golin J., Barkatt A., Cronin S., Eng G., May L.; RT "Chemical specificity of the PDR5 multidrug resistance gene product of RT Saccharomyces cerevisiae based on studies with tri-n-alkyltin chlorides."; RL Antimicrob. Agents Chemother. 44:134-138(2000). RN [31] RP SUBSTRATES. RX PubMed=10639374; DOI=10.1128/aac.44.2.418-420.2000; RA Michalkova-Papajova D., Obernauerova M., Subik J.; RT "Role of the PDR gene network in yeast susceptibility to the antifungal RT antibiotic mucidin."; RL Antimicrob. Agents Chemother. 44:418-420(2000). RN [32] RP TOPOLOGY, AND MUTAGENESIS. RX PubMed=10712705; DOI=10.1046/j.1365-2958.2000.01798.x; RA Egner R., Bauer B.E., Kuchler K.; RT "The transmembrane domain 10 of the yeast Pdr5p ABC antifungal efflux pump RT determines both substrate specificity and inhibitor susceptibility."; RL Mol. Microbiol. 35:1255-1263(2000). RN [33] RP TRANSCRIPTION REGULATION. RX PubMed=10734226; DOI=10.1016/s0014-5793(00)01294-1; RA DeRisi J., van den Hazel B., Marc P., Balzi E., Brown P., Jacq C., RA Goffeau A.; RT "Genome microarray analysis of transcriptional activation in multidrug RT resistance yeast mutants."; RL FEBS Lett. 470:156-160(2000). RN [34] RP FUNCTION, AND INHIBITORS. RX PubMed=10841772; DOI=10.1021/bi000040f; RA Conseil G., Decottignies A., Jault J.-M., Comte G., Barron D., Goffeau A., RA Di Pietro A.; RT "Prenyl-flavonoids as potent inhibitors of the Pdr5p multidrug ABC RT transporter from Saccharomyces cerevisiae."; RL Biochemistry 39:6910-6917(2000). RN [35] RP INHIBITORS. RX PubMed=11327879; DOI=10.1021/bi002453m; RA Conseil G., Perez-Victoria J.M., Jault J.-M., Gamarro F., Goffeau A., RA Hofmann J., Di Pietro A.; RT "Protein kinase C effectors bind to multidrug ABC transporters and inhibit RT their activity."; RL Biochemistry 40:2564-2571(2001). RN [36] RP BIOTECHNOLOGY. RX PubMed=11515543; DOI=10.1271/bbb.65.1589; RA Hiraga K., Wanigasekera A., Sugi H., Hamanaka N., Oda K.; RT "A novel screening for inhibitors of a pleiotropic drug resistant pump, RT Pdr5, in Saccharomyces cerevisiae."; RL Biosci. Biotechnol. Biochem. 65:1589-1595(2001). RN [37] RP INHIBITORS. RX PubMed=11758940; DOI=10.1271/bbb.65.2353; RA Wanigasekera A., Hiraga K., Hamanaka N., Oda K.; RT "Purification and some properties of an inhibitor for a yeast pleiotropic RT drug resistant pump from Kitasatospora sp. E-420."; RL Biosci. Biotechnol. Biochem. 65:2353-2357(2001). RN [38] RP SUBSTRATES. RX PubMed=11422371; DOI=10.1046/j.1432-1327.2001.02245.x; RA Hu W., Feng Q., Palli S.R., Krell P.J., Arif B.M., Retnakaran A.; RT "The ABC transporter Pdr5p mediates the efflux of nonsteroidal ecdysone RT agonists in Saccharomyces cerevisiae."; RL Eur. J. Biochem. 268:3416-3422(2001). RN [39] RP METABOLIC REGULATION. RX PubMed=11602584; DOI=10.1074/jbc.m106285200; RA Zhang X., Moye-Rowley W.S.; RT "Saccharomyces cerevisiae multidrug resistance gene expression inversely RT correlates with the status of the F(0) component of the mitochondrial RT ATPase."; RL J. Biol. Chem. 276:47844-47852(2001). RN [40] RP FUNCTION. RX PubMed=11321575; RA Rogers B., Decottignies A., Kolaczkowski M., Carvajal E., Balzi E., RA Goffeau A.; RT "The pleitropic drug ABC transporters from Saccharomyces cerevisiae."; RL J. Mol. Microbiol. Biotechnol. 3:207-214(2001). RN [41] RP TRANSCRIPTION REGULATION. RX PubMed=11882665; DOI=10.1074/jbc.m201637200; RA Hellauer K., Akache B., MacPherson S., Sirard E., Turcotte B.; RT "Zinc cluster protein Rdr1p is a transcriptional repressor of the PDR5 gene RT encoding a multidrug transporter."; RL J. Biol. Chem. 277:17671-17676(2002). RN [42] RP TRANSCRIPTION REGULATION. RX PubMed=11943786; DOI=10.1074/jbc.m202566200; RA Akache B., Turcotte B.; RT "New regulators of drug sensitivity in the family of yeast zinc cluster RT proteins."; RL J. Biol. Chem. 277:21254-21260(2002). RN [43] RP SUBCELLULAR LOCATION. RX PubMed=12469340; RX DOI=10.1002/1615-9861(200212)2:12<1706::aid-prot1706>3.0.co;2-k; RA Navarre C., Degand H., Bennett K.L., Crawford J.S., Moertz E., Boutry M.; RT "Subproteomics: identification of plasma membrane proteins from the yeast RT Saccharomyces cerevisiae."; RL Proteomics 2:1706-1714(2002). RN [44] RP FUNCTION, AND INHIBITORS. RX PubMed=12896805; DOI=10.1016/s0005-2736(03)00193-7; RA Conseil G., Perez-Victoria J.M., Renoir J.M., Goffeau A., Di Pietro A.; RT "Potent competitive inhibition of drug binding to the Saccharomyces RT cerevisiae ABC exporter Pdr5p by the hydrophobic estradiol-derivative RT RU49953."; RL Biochim. Biophys. Acta 1614:131-134(2003). RN [45] RP FUNCTION, AND INHIBITORS. RX PubMed=13678835; DOI=10.1016/s0924-8579(03)00214-0; RA Kolaczkowski M., Michalak K., Motohashi N.; RT "Phenothiazines as potent modulators of yeast multidrug resistance."; RL Int. J. Antimicrob. Agents 22:279-283(2003). RN [46] RP SUBSTRATES. RX PubMed=12496287; DOI=10.1074/jbc.m210908200; RA Golin J., Ambudkar S.V., Gottesman M.M., Habib A.D., Sczepanski J., RA Ziccardi W., May L.; RT "Studies with novel Pdr5p substrates demonstrate a strong size dependence RT for xenobiotic efflux."; RL J. Biol. Chem. 278:5963-5969(2003). RN [47] RP TRANSCRIPTION REGULATION. RX PubMed=12529331; DOI=10.1074/jbc.m208549200; RA Hikkel I., Lucau-Danila A., Delaveau T., Marc P., Devaux F., Jacq C.; RT "A general strategy to uncover transcription factor properties identifies a RT new regulator of drug resistance in yeast."; RL J. Biol. Chem. 278:11427-11432(2003). RN [48] RP PURIFICATION, AND ELECTRON MICROSCOPY. RX PubMed=12551908; DOI=10.1074/jbc.m212198200; RA Ferreira-Pereira A., Marco S., Decottignies A., Nader J., Goffeau A., RA Rigaud J.L.; RT "Three-dimensional reconstruction of the Saccharomyces cerevisiae multidrug RT resistance protein Pdr5p."; RL J. Biol. Chem. 278:11995-11999(2003). RN [49] RP SUBSTRATES. RX PubMed=12754197; DOI=10.1074/jbc.m303300200; RA Gupta S.S., Ton V.-K., Beaudry V., Rulli S., Cunningham K., Rao R.; RT "Antifungal activity of amiodarone is mediated by disruption of calcium RT homeostasis."; RL J. Biol. Chem. 278:28831-28839(2003). RN [50] RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS]. RX PubMed=14562106; DOI=10.1038/nature02046; RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., RA O'Shea E.K., Weissman J.S.; RT "Global analysis of protein expression in yeast."; RL Nature 425:737-741(2003). RN [51] RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-825, AND IDENTIFICATION BY RP MASS SPECTROMETRY. RC STRAIN=SUB592; RX PubMed=12872131; DOI=10.1038/nbt849; RA Peng J., Schwartz D., Elias J.E., Thoreen C.C., Cheng D., Marsischky G., RA Roelofs J., Finley D., Gygi S.P.; RT "A proteomics approach to understanding protein ubiquitination."; RL Nat. Biotechnol. 21:921-926(2003). RN [52] RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-825, AND IDENTIFICATION BY RP MASS SPECTROMETRY. RX PubMed=14557538; DOI=10.1073/pnas.2135500100; RA Hitchcock A.L., Auld K., Gygi S.P., Silver P.A.; RT "A subset of membrane-associated proteins is ubiquitinated in response to RT mutations in the endoplasmic reticulum degradation machinery."; RL Proc. Natl. Acad. Sci. U.S.A. 100:12735-12740(2003). RN [53] RP BIOTECHNOLOGY. RX PubMed=14599467; DOI=10.1016/s0887-2333(03)00129-2; RA Lichtenberg-Frate H., Schmitt M., Gellert G., Ludwig J.; RT "A yeast-based method for the detection of cyto and genotoxicity."; RL Toxicol. in Vitro 17:709-716(2003). RN [54] RP BIOTECHNOLOGY. RX PubMed=15047528; DOI=10.1128/aac.48.4.1256-1271.2004; RA Niimi K., Harding D.R., Parshot R., King A., Lun D.J., Decottignies A., RA Niimi M., Lin S., Cannon R.D., Goffeau A., Monk B.C.; RT "Chemosensitization of fluconazole resistance in Saccharomyces cerevisiae RT and pathogenic fungi by a D-octapeptide derivative."; RL Antimicrob. Agents Chemother. 48:1256-1271(2004). RN [55] RP SUBSTRATES. RX PubMed=15009193; DOI=10.1111/j.1432-1033.2004.04018.x; RA Wehrschutz-Sigl E., Jungwirth H., Bergler H., Hogenauer G.; RT "The transporters Pdr5p and Snq2p mediate diazaborine resistance and are RT under the control of the gain-of-function allele PDR1-12."; RL Eur. J. Biochem. 271:1145-1152(2004). RN [56] RP FUNCTION. RX PubMed=14960317; DOI=10.1016/s0014-5793(04)00046-8; RA Mamnun Y.M., Schuller C., Kuchler K.; RT "Expression regulation of the yeast PDR5 ATP-binding cassette (ABC) RT transporter suggests a role in cellular detoxification during the RT exponential growth phase."; RL FEBS Lett. 559:111-117(2004). RN [57] RP INDUCTION. RX PubMed=15294907; DOI=10.1074/jbc.m406363200; RA Gao C., Wang L., Milgrom E., Shen W.C.; RT "On the mechanism of constitutive Pdr1 activator-mediated PDR5 RT transcription in Saccharomyces cerevisiae: evidence for enhanced RT recruitment of coactivators and altered nucleosome structures."; RL J. Biol. Chem. 279:42677-42686(2004). RN [58] RP INHIBITORS. RX PubMed=15707993; DOI=10.1016/j.bbrc.2005.01.075; RA Hiraga K., Yamamoto S., Fukuda H., Hamanaka N., Oda K.; RT "Enniatin has a new function as an inhibitor of Pdr5p, one of the ABC RT transporters in Saccharomyces cerevisiae."; RL Biochem. Biophys. Res. Commun. 328:1119-1125(2005). RN [59] RP INHIBITORS. RX PubMed=15796929; DOI=10.1016/j.bbrc.2005.03.009; RA Yamamoto S., Hiraga K., Abiko A., Hamanaka N., Oda K.; RT "A new function of isonitrile as an inhibitor of the Pdr5p multidrug ABC RT transporter in Saccharomyces cerevisiae."; RL Biochem. Biophys. Res. Commun. 330:622-628(2005). RN [60] RP SUBSTRATES. RX PubMed=16008355; DOI=10.1021/bi0502994; RA Hanson L., May L., Tuma P., Keeven J., Mehl P., Ferenz M., Ambudkar S.V., RA Golin J.; RT "The role of hydrogen bond acceptor groups in the interaction of substrates RT with Pdr5p, a major yeast drug transporter."; RL Biochemistry 44:9703-9713(2005). RN [61] RP METABOLIC REGULATION. RX PubMed=15896930; DOI=10.1016/j.gene.2005.03.019; RA Moye-Rowley W.S.; RT "Retrograde regulation of multidrug resistance in Saccharomyces RT cerevisiae."; RL Gene 354:15-21(2005). RN [62] RP FUNCTION, AND MUTAGENESIS. RX PubMed=15836770; DOI=10.1111/j.1365-2443.2005.00847.x; RA Tutulan-Cunita A.C., Mikoshi M., Mizunuma M., Hirata D., Miyakawa T.; RT "Mutational analysis of the yeast multidrug resistance ABC transporter RT Pdr5p with altered drug specificity."; RL Genes Cells 10:409-420(2005). RN [63] RP INDUCTION. RX PubMed=16061415; DOI=10.1016/j.biocel.2005.06.005; RA Malac J., Urbankova E., Sigler K., Gaskova D.; RT "Activity of yeast multidrug resistance pumps during growth is controlled RT by carbon source and the composition of growth-depleted medium: DiS-C3(3) RT fluorescence assay."; RL Int. J. Biochem. Cell Biol. 37:2536-2543(2005). RN [64] RP SUBSTRATES. RX PubMed=16141212; DOI=10.1074/jbc.m503147200; RA Sano T., Kihara A., Kurotsu F., Iwaki S., Igarashi Y.; RT "Regulation of the sphingoid long-chain base kinase Lcb4p by ergosterol and RT heme: studies in phytosphingosine-resistant mutants."; RL J. Biol. Chem. 280:36674-36682(2005). RN [65] RP INDUCTION. RX PubMed=15713640; DOI=10.1128/mcb.25.5.1860-1868.2005; RA Lucau-Danila A., Lelandais G., Kozovska Z., Tanty V., Delaveau T., RA Devaux F., Jacq C.; RT "Early expression of yeast genes affected by chemical stress."; RL Mol. Cell. Biol. 25:1860-1868(2005). RN [66] RP INDUCTION. RX PubMed=16487346; DOI=10.1111/j.1567-1364.2006.00041.x; RA Teixeira M.C., Fernandes A.R., Mira N.P., Becker J.D., Sa-Correia I.; RT "Early transcriptional response of Saccharomyces cerevisiae to stress RT imposed by the herbicide 2,4-dichlorophenoxyacetic acid."; RL FEMS Yeast Res. 6:230-248(2006). RN [67] RP INDUCTION. RX PubMed=17156010; DOI=10.1111/j.1567-1364.2006.00095.x; RA Alenquer M., Tenreiro S., Sa-Correia I.; RT "Adaptive response to the antimalarial drug artesunate in yeast involves RT Pdr1p/Pdr3p-mediated transcriptional activation of the resistance RT determinants TPO1 and PDR5."; RL FEMS Yeast Res. 6:1130-1139(2006). RN [68] RP METABOLIC REGULATION, AND FUNCTION. RX PubMed=16751665; DOI=10.1534/genetics.106.057596; RA Souid A.K., Gao C., Wang L., Milgrom E., Shen W.C.; RT "ELM1 is required for multidrug resistance in Saccharomyces cerevisiae."; RL Genetics 173:1919-1937(2006). RN [69] RP TOPOLOGY [LARGE SCALE ANALYSIS]. RC STRAIN=ATCC 208353 / W303-1A; RX PubMed=16847258; DOI=10.1073/pnas.0604075103; RA Kim H., Melen K., Oesterberg M., von Heijne G.; RT "A global topology map of the Saccharomyces cerevisiae membrane proteome."; RL Proc. Natl. Acad. Sci. U.S.A. 103:11142-11147(2006). RN [70] RP FUNCTION. RX PubMed=17316560; DOI=10.1016/j.bbrc.2007.02.011; RA Golin J., Ambudkar S.V., May L.; RT "The yeast Pdr5p multidrug transporter: how does it recognize so many RT substrates?"; RL Biochem. Biophys. Res. Commun. 356:1-5(2007). RN [71] RP TRANSCRIPTION REGULATION. RX PubMed=17158869; DOI=10.1074/jbc.m610197200; RA Fardeau V., Lelandais G., Oldfield A., Salin H., Lemoine S., Garcia M., RA Tanty V., Le Crom S., Jacq C., Devaux F.; RT "The central role of PDR1 in the foundation of yeast drug resistance."; RL J. Biol. Chem. 282:5063-5074(2007). RN [72] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-49; SER-54; SER-61; SER-837; RP SER-849; SER-850 AND SER-854, AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RC STRAIN=ADR376; RX PubMed=17330950; DOI=10.1021/pr060559j; RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J., RA Elias J.E., Gygi S.P.; RT "Large-scale phosphorylation analysis of alpha-factor-arrested RT Saccharomyces cerevisiae."; RL J. Proteome Res. 6:1190-1197(2007). RN [73] RP TRAFFICKING. RX PubMed=17302805; DOI=10.1111/j.1365-2958.2006.05562.x; RA de Thozee C.P., Cronin S., Goj A., Golin J., Ghislain M.; RT "Subcellular trafficking of the yeast plasma membrane ABC transporter, RT Pdr5, is impaired by a mutation in the N-terminal nucleotide-binding RT fold."; RL Mol. Microbiol. 63:811-825(2007). RN [74] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-837; SER-840 AND SER-841, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=17287358; DOI=10.1073/pnas.0607084104; RA Chi A., Huttenhower C., Geer L.Y., Coon J.J., Syka J.E.P., Bai D.L., RA Shabanowitz J., Burke D.J., Troyanskaya O.G., Hunt D.F.; RT "Analysis of phosphorylation sites on proteins from Saccharomyces RT cerevisiae by electron transfer dissociation (ETD) mass spectrometry."; RL Proc. Natl. Acad. Sci. U.S.A. 104:2193-2198(2007). RN [75] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-837; SER-849 AND SER-850, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200; RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.; RT "A multidimensional chromatography technology for in-depth phosphoproteome RT analysis."; RL Mol. Cell. Proteomics 7:1389-1396(2008). RN [76] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-22; THR-51; SER-54; SER-58; RP SER-849; SER-850 AND SER-854, AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19779198; DOI=10.1126/science.1172867; RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.; RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights RT into evolution."; RL Science 325:1682-1686(2009). CC -!- FUNCTION: Active efflux of weakly charged organic compounds of 90 cubic CC Angstroms to 300 cubic Angstroms surface volume. Confers resistance to CC numerous chemicals including cycloheximide, sulfomethuron methyl, CC steroids, antiseptics, antibiotics, anticancer, herbicides, mycotoxins, CC insecticides, ionophores, alkaloids, flavonoids, phenothiazines, CC organotin compounds, carbazoles, lysosomotropic aminoesters, CC detergents, rhodamines and other fluorophores, azoles and other CC antifungals. Exhibits nucleoside triphosphatase activity. CC {ECO:0000269|PubMed:10841772, ECO:0000269|PubMed:11321575, CC ECO:0000269|PubMed:12896805, ECO:0000269|PubMed:13678835, CC ECO:0000269|PubMed:14960317, ECO:0000269|PubMed:15836770, CC ECO:0000269|PubMed:16751665, ECO:0000269|PubMed:17316560, CC ECO:0000269|PubMed:7753868, ECO:0000269|PubMed:8810273, CC ECO:0000269|PubMed:8940170, ECO:0000269|PubMed:8985171, CC ECO:0000269|PubMed:9450972, ECO:0000269|PubMed:9818966}. CC -!- ACTIVITY REGULATION: FK506, isonitrile, enniatin, RU49953, CC kitasatospora E420, staurosporine CGP42700, prenyl-flavonoids, D- CC octapeptides were found to be inhibitors in vivo. Vanadate and CC oligomycin were found to be inhibitors in vitro. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.5 mM for MgATP {ECO:0000269|PubMed:8175692}; CC Vmax=2.5 umol/min/mg enzyme {ECO:0000269|PubMed:8175692}; CC Note=Activity measured in plasma membranes.; CC pH dependence: CC Optimum pH is 7.0. {ECO:0000269|PubMed:8175692}; CC -!- INTERACTION: CC P33302; P32465: HXT1; NbExp=3; IntAct=EBI-13038, EBI-8759; CC P33302; Q12200: NCR1; NbExp=2; IntAct=EBI-13038, EBI-32032; CC P33302; Q02785: PDR12; NbExp=3; IntAct=EBI-13038, EBI-13065; CC P33302; P33302: PDR5; NbExp=4; IntAct=EBI-13038, EBI-13038; CC P33302; P32568: SNQ2; NbExp=5; IntAct=EBI-13038, EBI-17590; CC P33302; P40062: YER097W; NbExp=2; IntAct=EBI-13038, EBI-20799372; CC P33302; Q08234: YOL075C; NbExp=3; IntAct=EBI-13038, EBI-29278; CC P33302; P32804: ZRT1; NbExp=2; IntAct=EBI-13038, EBI-29677; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12469340}; CC Multi-pass membrane protein {ECO:0000269|PubMed:12469340}. Note=The CC ERAD mutants 'Pro-183' and 'Tyr-1427' fail to reach the plasma CC membrane. The mutant 'Pro-183' accumulates into ER-associated CC compartments. CC -!- INDUCTION: Expressed during exponential growth. Transcription is CC transiently activated within 40 minutes after induction by benomyl and CC other toxic chemicals. Multidrug resistance and PDR5 mRNA level are CC activated by the transcription regulators PDR1, PDR3, YAP1, YAP2, STB5 CC and by the mitochondrial rho zero mutation. Mutations or deletion in CC the PDR1 or PDR3 transcription factors strongly activate PDR5 mRNA and CC PDR5 translation. The transcription regulator RDR1 represses PDR5 CC expression. {ECO:0000269|PubMed:15294907, ECO:0000269|PubMed:15713640, CC ECO:0000269|PubMed:16061415, ECO:0000269|PubMed:16487346, CC ECO:0000269|PubMed:17156010, ECO:0000269|PubMed:9393438}. CC -!- DOMAIN: The N-terminal ABC transporter domain (positions 161 to 410) CC contains degenerated Walker A and B ATP-binding motifs, suggesting that CC it may be less efficient in ATP binding or not functional at all. This CC is a distinctive feature of the PDR subfamily. CC {ECO:0000269|PubMed:8294477}. CC -!- DOMAIN: The unusual length of the two extracellular loops at positions CC 686 to 774 and 1408 to 1476 is another specific feature of the PDR CC subfamily which may have an important role for function. CC {ECO:0000269|PubMed:8294477}. CC -!- PTM: Ubiquitinylation mediates endocytosis and vacuolar degradation. CC Phosphorylation by casein kinase I stabilizes the protein half-life. CC {ECO:0000269|PubMed:10601275}. CC -!- BIOTECHNOLOGY: Strains lacking PDR5 are used for toxicity tests. CC Strains overexpressing PDR5 are used for screening antifungal CC sensitizers. {ECO:0000269|PubMed:11515543, ECO:0000269|PubMed:14599467, CC ECO:0000269|PubMed:15047528}. CC -!- MISCELLANEOUS: Present with 42000 molecules/cell in log phase SD medium CC in log phase SD medium. {ECO:0000269|PubMed:14562106}. CC -!- MISCELLANEOUS: Full-sized PDR5 orthologs are found only in fungi and CC plants. Their topology and substrate specificity are distinct from CC mammalian MDR transporters. CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCG family. CC PDR (TC 3.A.1.205) subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA05547.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; D26548; BAA05547.1; ALT_FRAME; Genomic_DNA. DR EMBL; X74113; CAA52212.1; -; Genomic_DNA. DR EMBL; L19922; AAB53769.1; -; Genomic_DNA. DR EMBL; U55020; AAC49639.1; -; Genomic_DNA. DR EMBL; Z75061; CAA99359.1; -; Genomic_DNA. DR EMBL; BK006948; DAA10926.1; -; Genomic_DNA. DR PIR; A53151; A53151. DR RefSeq; NP_014796.3; NM_001183572.3. DR PDB; 7P03; EM; 3.45 A; A=1-1511. DR PDB; 7P04; EM; 2.85 A; A=1-1511. DR PDB; 7P05; EM; 3.13 A; A=1-1511. DR PDB; 7P06; EM; 3.77 A; A=1-1511. DR AlphaFoldDB; P33302; -. DR EMDB; EMD-13142; -. DR EMDB; EMD-13143; -. DR EMDB; EMD-13144; -. DR EMDB; EMD-13145; -. DR SMR; P33302; -. DR BioGRID; 34549; 171. DR DIP; DIP-6776N; -. DR FunCoup; P33302; 495. DR IntAct; P33302; 74. DR MINT; P33302; -. DR STRING; 4932.YOR153W; -. DR BindingDB; P33302; -. DR ChEMBL; CHEMBL1697658; -. DR DrugCentral; P33302; -. DR SwissLipids; SLP:000000523; -. DR TCDB; 3.A.1.205.1; the atp-binding cassette (abc) superfamily. DR GlyCosmos; P33302; 2 sites, No reported glycans. DR GlyGen; P33302; 2 sites. DR iPTMnet; P33302; -. DR PaxDb; 4932-YOR153W; -. DR PeptideAtlas; P33302; -. DR EnsemblFungi; YOR153W_mRNA; YOR153W; YOR153W. DR GeneID; 854324; -. DR KEGG; sce:YOR153W; -. DR AGR; SGD:S000005679; -. DR SGD; S000005679; PDR5. DR VEuPathDB; FungiDB:YOR153W; -. DR eggNOG; KOG0065; Eukaryota. DR HOGENOM; CLU_000604_35_0_1; -. DR InParanoid; P33302; -. DR OMA; RTSMRHD; -. DR OrthoDB; 245989at2759; -. DR BioCyc; YEAST:G3O-33670-MONOMER; -. DR BioGRID-ORCS; 854324; 0 hits in 10 CRISPR screens. DR PRO; PR:P33302; -. DR Proteomes; UP000002311; Chromosome XV. DR RNAct; P33302; protein. DR GO; GO:0071944; C:cell periphery; HDA:SGD. DR GO; GO:0005739; C:mitochondrion; HDA:SGD. DR GO; GO:0005886; C:plasma membrane; IDA:SGD. DR GO; GO:0008559; F:ABC-type xenobiotic transporter activity; IDA:SGD. DR GO; GO:0005524; F:ATP binding; IEA:InterPro. DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0030003; P:intracellular monoatomic cation homeostasis; IMP:SGD. DR GO; GO:0009410; P:response to xenobiotic stimulus; IMP:SGD. DR GO; GO:1990961; P:xenobiotic detoxification by transmembrane export across the plasma membrane; IMP:SGD. DR CDD; cd03233; ABCG_PDR_domain1; 1. DR CDD; cd03232; ABCG_PDR_domain2; 1. DR FunFam; 3.40.50.300:FF:000054; ABC multidrug transporter atrF; 1. DR FunFam; 3.40.50.300:FF:001262; ABC transporter CDR4; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 2. DR InterPro; IPR003593; AAA+_ATPase. DR InterPro; IPR013525; ABC2_TM. DR InterPro; IPR029481; ABC_trans_N. DR InterPro; IPR003439; ABC_transporter-like_ATP-bd. DR InterPro; IPR017871; ABC_transporter-like_CS. DR InterPro; IPR034001; ABCG_PDR_1. DR InterPro; IPR034003; ABCG_PDR_2. DR InterPro; IPR005285; Drug-R_PDR/CDR. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR010929; PDR_CDR_ABC. DR NCBIfam; TIGR00956; 3a01205; 1. DR PANTHER; PTHR19241; ATP-BINDING CASSETTE TRANSPORTER; 1. DR Pfam; PF01061; ABC2_membrane; 2. DR Pfam; PF00005; ABC_tran; 2. DR Pfam; PF14510; ABC_trans_N; 1. DR Pfam; PF06422; PDR_CDR; 1. DR SMART; SM00382; AAA; 2. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 2. DR PROSITE; PS00211; ABC_TRANSPORTER_1; 1. DR PROSITE; PS50893; ABC_TRANSPORTER_2; 2. DR PDBsum; 7P03; -. DR PDBsum; 7P04; -. DR PDBsum; 7P05; -. DR PDBsum; 7P06; -. PE 1: Evidence at protein level; KW 3D-structure; Antibiotic resistance; ATP-binding; Cell membrane; KW Cycloheximide resistance; Direct protein sequencing; Glycoprotein; KW Isopeptide bond; Membrane; Nucleotide-binding; Phosphoprotein; KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport; KW Ubl conjugation. FT CHAIN 1..1511 FT /note="Pleiotropic ABC efflux transporter of multiple FT drugs" FT /id="PRO_0000093442" FT TOPO_DOM 1..517 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 518..542 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 543..558 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 559..579 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 580..611 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 612..628 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 629..631 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 632..650 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 651..665 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 666..685 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 686..774 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 775..793 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 794..1237 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 1238..1260 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1261..1291 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 1292..1313 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1314..1324 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 1325..1349 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1350..1354 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 1355..1379 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1380..1388 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 1389..1407 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1408..1476 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 1477..1499 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1500..1511 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 161..410 FT /note="ABC transporter 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434" FT DOMAIN 869..1112 FT /note="ABC transporter 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434" FT REGION 1..32 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 52..71 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 824..858 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1..14 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 833..846 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 905..912 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434" FT MOD_RES 22 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19779198" FT MOD_RES 49 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:17330950" FT MOD_RES 51 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:19779198" FT MOD_RES 54 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17330950, FT ECO:0007744|PubMed:19779198" FT MOD_RES 58 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19779198" FT MOD_RES 61 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17330950" FT MOD_RES 837 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17287358, FT ECO:0007744|PubMed:17330950, ECO:0007744|PubMed:18407956" FT MOD_RES 840 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17287358" FT MOD_RES 841 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17287358" FT MOD_RES 849 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17330950, FT ECO:0007744|PubMed:18407956, ECO:0007744|PubMed:19779198" FT MOD_RES 850 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17330950, FT ECO:0007744|PubMed:18407956, ECO:0007744|PubMed:19779198" FT MOD_RES 854 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17330950, FT ECO:0007744|PubMed:19779198" FT CARBOHYD 734 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1447 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CROSSLNK 825 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:12872131, FT ECO:0000269|PubMed:14557538" FT MUTAGEN 183 FT /note="L->P: Activates ER-associated degradation." FT MUTAGEN 257 FT /note="T->I: Alters drug specificity." FT MUTAGEN 302 FT /note="G->D: Confers generalized drug resistance." FT MUTAGEN 648 FT /note="S->F: Alters drug specificity." FT MUTAGEN 905 FT /note="G->S: Inactivates drug transport." FT MUTAGEN 908 FT /note="G->S: Inactivates drug transport." FT MUTAGEN 1009 FT /note="G->C: Confers generalized drug resistance." FT MUTAGEN 1040 FT /note="G->D: Alters drug specificity." FT MUTAGEN 1048 FT /note="S->V: Alters drug specificity." FT MUTAGEN 1289 FT /note="E->K: Alters drug specificity." FT MUTAGEN 1311 FT /note="Y->S: Alters drug specificity." FT MUTAGEN 1360 FT /note="S->F: Alters drug specificity." FT MUTAGEN 1393 FT /note="T->I: Alters drug specificity." FT MUTAGEN 1427 FT /note="C->Y: Activates ER-associated degradation." FT CONFLICT 171 FT /note="N -> L (in Ref. 1; BAA05547)" FT /evidence="ECO:0000305" FT CONFLICT 190 FT /note="V -> I (in Ref. 1; BAA05547)" FT /evidence="ECO:0000305" FT CONFLICT 214 FT /note="D -> T (in Ref. 1; BAA05547)" FT /evidence="ECO:0000305" FT CONFLICT 308 FT /note="G -> V (in Ref. 1; BAA05547)" FT /evidence="ECO:0000305" FT CONFLICT 340..345 FT /note="Missing (in Ref. 1; BAA05547)" FT /evidence="ECO:0000305" FT CONFLICT 476 FT /note="R -> H (in Ref. 1; BAA05547)" FT /evidence="ECO:0000305" FT CONFLICT 648 FT /note="Missing (in Ref. 1; BAA05547)" FT /evidence="ECO:0000305" FT CONFLICT 770 FT /note="D -> H (in Ref. 1; BAA05547)" FT /evidence="ECO:0000305" FT HELIX 37..55 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 93..95 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 97..101 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 104..116 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 129..133 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 136..139 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 145..147 FT /evidence="ECO:0007829|PDB:7P04" FT TURN 149..151 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 152..164 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 172..176 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 180..183 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 188..192 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 199..206 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 212..215 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 220..223 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 228..231 FT /evidence="ECO:0007829|PDB:7P04" FT TURN 232..234 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 238..243 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 254..264 FT /evidence="ECO:0007829|PDB:7P04" FT TURN 268..270 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 276..290 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 294..296 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 304..306 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 311..325 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 328..332 FT /evidence="ECO:0007829|PDB:7P04" FT TURN 333..338 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 341..358 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 361..365 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 371..375 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 378..384 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 387..393 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 394..404 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 407..409 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 414..420 FT /evidence="ECO:0007829|PDB:7P04" FT TURN 424..426 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 431..435 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 444..453 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 455..469 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 501..518 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 520..540 FT /evidence="ECO:0007829|PDB:7P04" FT TURN 541..544 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 545..547 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 550..552 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 553..570 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 571..574 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 575..590 FT /evidence="ECO:0007829|PDB:7P04" FT TURN 591..593 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 596..606 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 608..626 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 632..659 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 660..662 FT /evidence="ECO:0007829|PDB:7P05" FT HELIX 663..679 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 681..685 FT /evidence="ECO:0007829|PDB:7P04" FT TURN 687..689 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 692..694 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 695..700 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 702..715 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 719..721 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 725..727 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 730..732 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 737..739 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 742..744 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 752..755 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 756..763 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 768..770 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 773..795 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 810..815 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 863..865 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 869..882 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 885..895 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 900..904 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 906..908 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 911..918 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 924..933 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 942..944 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 946..949 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 961..972 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 975..977 FT /evidence="ECO:0007829|PDB:7P03" FT HELIX 979..992 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 996..998 FT /evidence="ECO:0007829|PDB:7P05" FT STRAND 1006..1010 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 1012..1024 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 1029..1038 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 1043..1059 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 1063..1066 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 1072..1076 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 1079..1085 FT /evidence="ECO:0007829|PDB:7P04" FT TURN 1086..1088 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 1089..1095 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 1098..1100 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 1101..1108 FT /evidence="ECO:0007829|PDB:7P04" FT TURN 1109..1111 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 1112..1114 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 1121..1128 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 1129..1134 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 1141..1146 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 1149..1163 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 1180..1182 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 1184..1199 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 1203..1223 FT /evidence="ECO:0007829|PDB:7P04" FT TURN 1224..1226 FT /evidence="ECO:0007829|PDB:7P05" FT HELIX 1231..1245 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 1248..1265 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 1266..1270 FT /evidence="ECO:0007829|PDB:7P04" FT TURN 1271..1274 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 1278..1308 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 1310..1316 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 1320..1348 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 1352..1368 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 1370..1374 FT /evidence="ECO:0007829|PDB:7P04" FT TURN 1376..1378 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 1381..1383 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 1384..1389 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 1391..1404 FT /evidence="ECO:0007829|PDB:7P04" FT TURN 1413..1415 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 1416..1419 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 1420..1422 FT /evidence="ECO:0007829|PDB:7P03" FT HELIX 1427..1437 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 1442..1444 FT /evidence="ECO:0007829|PDB:7P04" FT STRAND 1452..1456 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 1460..1467 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 1471..1473 FT /evidence="ECO:0007829|PDB:7P04" FT HELIX 1474..1499 FT /evidence="ECO:0007829|PDB:7P04" SQ SEQUENCE 1511 AA; 170438 MW; 4540DC0BF04744BA CRC64; MPEAKLNNNV NDVTSYSSAS SSTENAADLH NYNGFDEHTE ARIQKLARTL TAQSMQNSTQ SAPNKSDAQS IFSSGVEGVN PIFSDPEAPG YDPKLDPNSE NFSSAAWVKN MAHLSAADPD FYKPYSLGCA WKNLSASGAS ADVAYQSTVV NIPYKILKSG LRKFQRSKET NTFQILKPMD GCLNPGELLV VLGRPGSGCT TLLKSISSNT HGFDLGADTK ISYSGYSGDD IKKHFRGEVV YNAEADVHLP HLTVFETLVT VARLKTPQNR IKGVDRESYA NHLAEVAMAT YGLSHTRNTK VGNDIVRGVS GGERKRVSIA EVSICGSKFQ CWDNATRGLD SATALEFIRA LKTQADISNT SATVAIYQCS QDAYDLFNKV CVLDDGYQIY YGPADKAKKY FEDMGYVCPS RQTTADFLTS VTSPSERTLN KDMLKKGIHI PQTPKEMNDY WVKSPNYKEL MKEVDQRLLN DDEASREAIK EAHIAKQSKR ARPSSPYTVS YMMQVKYLLI RNMWRLRNNI GFTLFMILGN CSMALILGSM FFKIMKKGDT STFYFRGSAM FFAILFNAFS SLLEIFSLYE ARPITEKHRT YSLYHPSADA FASVLSEIPS KLIIAVCFNI IFYFLVDFRR NGGVFFFYLL INIVAVFSMS HLFRCVGSLT KTLSEAMVPA SMLLLALSMY TGFAIPKKKI LRWSKWIWYI NPLAYLFESL LINEFHGIKF PCAEYVPRGP AYANISSTES VCTVVGAVPG QDYVLGDDFI RGTYQYYHKD KWRGFGIGMA YVVFFFFVYL FLCEYNEGAK QKGEILVFPR SIVKRMKKRG VLTEKNANDP ENVGERSDLS SDRKMLQESS EEESDTYGEI GLSKSEAIFH WRNLCYEVQI KAETRRILNN VDGWVKPGTL TALMGASGAG KTTLLDCLAE RVTMGVITGD ILVNGIPRDK SFPRSIGYCQ QQDLHLKTAT VRESLRFSAY LRQPAEVSIE EKNRYVEEVI KILEMEKYAD AVVGVAGEGL NVEQRKRLTI GVELTAKPKL LVFLDEPTSG LDSQTAWSIC QLMKKLANHG QAILCTIHQP SAILMQEFDR LLFMQRGGKT VYFGDLGEGC KTMIDYFESH GAHKCPADAN PAEWMLEVVG AAPGSHANQD YYEVWRNSEE YRAVQSELDW MERELPKKGS ITAAEDKHEF SQSIIYQTKL VSIRLFQQYW RSPDYLWSKF ILTIFNQLFI GFTFFKAGTS LQGLQNQMLA VFMFTVIFNP ILQQYLPSFV QQRDLYEARE RPSRTFSWIS FIFAQIFVEV PWNILAGTIA YFIYYYPIGF YSNASAAGQL HERGALFWLF SCAFYVYVGS MGLLVISFNQ VAESAANLAS LLFTMSLSFC GVMTTPSAMP RFWIFMYRVS PLTYFIQALL AVGVANVDVK CADYELLEFT PPSGMTCGQY MEPYLQLAKT GYLTDENATD TCSFCQISTT NDYLANVNSF YSERWRNYGI FICYIAFNYI AGVFFYWLAR VPKKNGKLSK K //