CDR1_CANAL
ID CDR1_CANAL Reviewed; 1501 AA.
AC Q5ANA3; A0A1D8PK55;
DT 07-JAN-2015, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2017, sequence version 2.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Pleiotropic ABC efflux transporter of multiple drugs CDR1 {ECO:0000305};
DE AltName: Full=Pleiotropic drug resistance protein CDR1 {ECO:0000305};
GN Name=CDR1; OrderedLocusNames=CAALFM_C305220WA;
GN ORFNames=CaO19.13421, CaO19.6000;
OS Candida albicans (strain SC5314 / ATCC MYA-2876) (Yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Debaryomycetaceae; Candida/Lodderomyces clade; Candida.
OX NCBI_TaxID=237561;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=15123810; DOI=10.1073/pnas.0401648101;
RA Jones T., Federspiel N.A., Chibana H., Dungan J., Kalman S., Magee B.B.,
RA Newport G., Thorstenson Y.R., Agabian N., Magee P.T., Davis R.W.,
RA Scherer S.;
RT "The diploid genome sequence of Candida albicans.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:7329-7334(2004).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=17419877; DOI=10.1186/gb-2007-8-4-r52;
RA van het Hoog M., Rast T.J., Martchenko M., Grindle S., Dignard D.,
RA Hogues H., Cuomo C., Berriman M., Scherer S., Magee B.B., Whiteway M.,
RA Chibana H., Nantel A., Magee P.T.;
RT "Assembly of the Candida albicans genome into sixteen supercontigs aligned
RT on the eight chromosomes.";
RL Genome Biol. 8:RESEARCH52.1-RESEARCH52.12(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=24025428; DOI=10.1186/gb-2013-14-9-r97;
RA Muzzey D., Schwartz K., Weissman J.S., Sherlock G.;
RT "Assembly of a phased diploid Candida albicans genome facilitates allele-
RT specific measurements and provides a simple model for repeat and indel
RT structure.";
RL Genome Biol. 14:RESEARCH97.1-RESEARCH97.14(2013).
RN [4]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=8891134; DOI=10.1128/aac.40.10.2300;
RA Sanglard D., Ischer F., Monod M., Bille J.;
RT "Susceptibilities of Candida albicans multidrug transporter mutants to
RT various antifungal agents and other metabolic inhibitors.";
RL Antimicrob. Agents Chemother. 40:2300-2305(1996).
RN [5]
RP FUNCTION.
RX PubMed=9124851; DOI=10.1128/aac.40.12.2835;
RA Albertson G.D., Niimi M., Cannon R.D., Jenkinson H.F.;
RT "Multiple efflux mechanisms are involved in Candida albicans fluconazole
RT resistance.";
RL Antimicrob. Agents Chemother. 40:2835-2841(1996).
RN [6]
RP FUNCTION.
RX PubMed=9453158; DOI=10.1111/j.1574-6968.1998.tb12802.x;
RA Krishnamurthy S., Gupta V., Snehlata P., Prasad R.;
RT "Characterisation of human steroid hormone transport mediated by Cdr1p, a
RT multidrug transporter of Candida albicans, belonging to the ATP binding
RT cassette super family.";
RL FEMS Microbiol. Lett. 158:69-74(1998).
RN [7]
RP INDUCTION.
RX PubMed=9532737; DOI=10.1111/j.1574-6968.1998.tb12910.x;
RA Krishnamurthy S., Gupta V., Prasad R., Panwar S.L., Prasad R.;
RT "Expression of CDR1, a multidrug resistance gene of Candida albicans:
RT transcriptional activation by heat shock, drugs and human steroid
RT hormones.";
RL FEMS Microbiol. Lett. 160:191-197(1998).
RN [8]
RP INDUCTION.
RX PubMed=9605502;
RX DOI=10.1002/(sici)1097-0061(19980430)14:6<517::aid-yea250>3.0.co;2-d;
RA Hernaez M.L., Gil C., Pla J., Nombela C.;
RT "Induced expression of the Candida albicans multidrug resistance gene CDR1
RT in response to fluconazole and other antifungals.";
RL Yeast 14:517-526(1998).
RN [9]
RP FUNCTION.
RX PubMed=9605504;
RX DOI=10.1002/(sici)1097-0061(19980430)14:6<535::aid-yea254>3.0.co;2-5;
RA Krishnamurthy S., Chatterjee U., Gupta V., Prasad R., Das P., Snehlata P.,
RA Hasnain S.E., Prasad R.;
RT "Deletion of transmembrane domain 12 of CDR1, a multidrug transporter from
RT Candida albicans, leads to altered drug specificity: expression of a yeast
RT multidrug transporter in baculovirus expression system.";
RL Yeast 14:535-550(1998).
RN [10]
RP FUNCTION, AND INDUCTION.
RX PubMed=10428921; DOI=10.1128/aac.43.8.1968;
RA Henry K.W., Cruz M.C., Katiyar S.K., Edlind T.D.;
RT "Antagonism of azole activity against Candida albicans following induction
RT of multidrug resistance genes by selected antimicrobial agents.";
RL Antimicrob. Agents Chemother. 43:1968-1974(1999).
RN [11]
RP FUNCTION.
RX PubMed=10227177; DOI=10.1111/j.1574-6968.1999.tb13541.x;
RA Smriti X., Krishnamurthy S.S., Prasad R.;
RT "Membrane fluidity affects functions of Cdr1p, a multidrug ABC transporter
RT of Candida albicans.";
RL FEMS Microbiol. Lett. 173:475-481(1999).
RN [12]
RP INDUCTION.
RX PubMed=10556714; DOI=10.1111/j.1574-6968.1999.tb08798.x;
RA Puri N., Krishnamurthy S., Habib S., Hasnain S.E., Goswami S.K., Prasad R.;
RT "CDR1, a multidrug resistance gene from Candida albicans, contains multiple
RT regulatory domains in its promoter and the distal AP-1 element mediates its
RT induction by miconazole.";
RL FEMS Microbiol. Lett. 180:213-219(1999).
RN [13]
RP FUNCTION.
RX PubMed=10029989;
RX DOI=10.1002/(sici)1097-0061(19990130)15:2<111::aid-yea350>3.0.co;2-e;
RA Dogra S., Krishnamurthy S., Gupta V., Dixit B.L., Gupta C.M., Sanglard D.,
RA Prasad R.;
RT "Asymmetric distribution of phosphatidylethanolamine in C. albicans:
RT possible mediation by CDR1, a multidrug transporter belonging to ATP
RT binding cassette (ABC) superfamily.";
RL Yeast 15:111-121(1999).
RN [14]
RP INDUCTION.
RX PubMed=10952571; DOI=10.1128/aac.44.9.2296-2303.2000;
RA Lyons C.N., White T.C.;
RT "Transcriptional analyses of antifungal drug resistance in Candida
RT albicans.";
RL Antimicrob. Agents Chemother. 44:2296-2303(2000).
RN [15]
RP FUNCTION.
RX PubMed=11709310; DOI=10.1128/aac.45.12.3366-3374.2001;
RA Nakamura K., Niimi M., Niimi K., Holmes A.R., Yates J.E., Decottignies A.,
RA Monk B.C., Goffeau A., Cannon R.D.;
RT "Functional expression of Candida albicans drug efflux pump Cdr1p in a
RT Saccharomyces cerevisiae strain deficient in membrane transporters.";
RL Antimicrob. Agents Chemother. 45:3366-3374(2001).
RN [16]
RP INDUCTION.
RX PubMed=11918807; DOI=10.1046/j.1365-2958.2002.02814.x;
RA de Micheli M., Bille J., Schueller C., Sanglard D.;
RT "A common drug-responsive element mediates the upregulation of the Candida
RT albicans ABC transporters CDR1 and CDR2, two genes involved in antifungal
RT drug resistance.";
RL Mol. Microbiol. 43:1197-1214(2002).
RN [17]
RP FUNCTION.
RX PubMed=11870854; DOI=10.1002/yea.818;
RA Smriti X., Krishnamurthy S., Dixit B.L., Gupta C.M., Milewski S.,
RA Prasad R.;
RT "ABC transporters Cdr1p, Cdr2p and Cdr3p of a human pathogen Candida
RT albicans are general phospholipid translocators.";
RL Yeast 19:303-318(2002).
RN [18]
RP FUNCTION.
RX PubMed=12709320; DOI=10.1128/aac.47.5.1543-1554.2003;
RA Gauthier C., Weber S., Alarco A.M., Alqawi O., Daoud R., Georges E.,
RA Raymond M.;
RT "Functional similarities and differences between Candida albicans Cdr1p and
RT Cdr2p transporters.";
RL Antimicrob. Agents Chemother. 47:1543-1554(2003).
RN [19]
RP INDUCTION.
RX PubMed=15561818; DOI=10.1128/aac.48.12.4505-4512.2004;
RA Chen C.G., Yang Y.L., Shih H.I., Su C.L., Lo H.J.;
RT "CaNdt80 is involved in drug resistance in Candida albicans by regulating
RT CDR1.";
RL Antimicrob. Agents Chemother. 48:4505-4512(2004).
RN [20]
RP DOMAIN, AND MUTAGENESIS OF CYS-193.
RX PubMed=12962507; DOI=10.1021/bi0345900;
RA Jha S., Karnani N., Dhar S.K., Mukhopadhayay K., Shukla S., Saini P.,
RA Mukhopadhayay G., Prasad R.;
RT "Purification and characterization of the N-terminal nucleotide binding
RT domain of an ABC drug transporter of Candida albicans: uncommon cysteine
RT 193 of Walker A is critical for ATP hydrolysis.";
RL Biochemistry 42:10822-10832(2003).
RN [21]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ASP-232; GLY-296;
RP PHE-774; GLY-995; GLY-1000; THR-1351; CYS-1418; THR-1449 AND VAL-1456.
RX PubMed=14665469; DOI=10.1128/ec.2.6.1361-1375.2003;
RA Shukla S., Saini P., Smriti X., Jha S., Ambudkar S.V., Prasad R.;
RT "Functional characterization of Candida albicans ABC transporter Cdr1p.";
RL Eukaryot. Cell 2:1361-1375(2003).
RN [22]
RP INDUCTION, AND FUNCTION.
RX PubMed=15152937;
RA O'Keeffe J., Kavanagh K.;
RT "Adriamycin alters the expression of drug efflux pumps and confers
RT amphotericin B tolerance in Candida albicans.";
RL Anticancer Res. 24:405-408(2004).
RN [23]
RP INDUCTION.
RX PubMed=15273122; DOI=10.1128/aac.48.8.3064-3079.2004;
RA Karababa M., Coste A.T., Rognon B., Bille J., Sanglard D.;
RT "Comparison of gene expression profiles of Candida albicans azole-resistant
RT clinical isolates and laboratory strains exposed to drugs inducing
RT multidrug transporters.";
RL Antimicrob. Agents Chemother. 48:3064-3079(2004).
RN [24]
RP INDUCTION.
RX PubMed=15328097; DOI=10.1128/aac.48.9.3358-3366.2004;
RA Mateus C., Crow S.A. Jr., Ahearn D.G.;
RT "Adherence of Candida albicans to silicone induces immediate enhanced
RT tolerance to fluconazole.";
RL Antimicrob. Agents Chemother. 48:3358-3366(2004).
RN [25]
RP ACTIVITY REGULATION.
RX PubMed=15325261; DOI=10.1016/j.bbrc.2004.07.151;
RA Shukla S., Sauna Z.E., Prasad R., Ambudkar S.V.;
RT "Disulfiram is a potent modulator of multidrug transporter Cdr1p of Candida
RT albicans.";
RL Biochem. Biophys. Res. Commun. 322:520-525(2004).
RN [26]
RP INDUCTION.
RX PubMed=15590837; DOI=10.1128/ec.3.6.1639-1652.2004;
RA Coste A.T., Karababa M., Ischer F., Bille J., Sanglard D.;
RT "TAC1, transcriptional activator of CDR genes, is a new transcription
RT factor involved in the regulation of Candida albicans ABC transporters CDR1
RT and CDR2.";
RL Eukaryot. Cell 3:1639-1652(2004).
RN [27]
RP INDUCTION.
RX PubMed=14734019; DOI=10.1016/s1567-1356(03)00204-6;
RA Gaur N.A., Puri N., Karnani N., Mukhopadhyay G., Goswami S.K., Prasad R.;
RT "Identification of a negative regulatory element which regulates basal
RT transcription of a multidrug resistance gene CDR1 of Candida albicans.";
RL FEMS Yeast Res. 4:389-399(2004).
RN [28]
RP FUNCTION, MUTAGENESIS OF THR-1351, AND SUBCELLULAR LOCATION.
RX PubMed=15190023; DOI=10.1093/jac/dkh308;
RA Shukla S., Ambudkar S.V., Prasad R.;
RT "Substitution of threonine-1351 in the multidrug transporter Cdr1p of
RT Candida albicans results in hypersusceptibility to antifungal agents and
RT threonine-1351 is essential for synergic effects of calcineurin inhibitor
RT FK520.";
RL J. Antimicrob. Chemother. 54:38-45(2004).
RN [29]
RP FUNCTION.
RX PubMed=15486081; DOI=10.1093/jac/dkh456;
RA Niimi M., Niimi K., Takano Y., Holmes A.R., Fischer F.J., Uehara Y.,
RA Cannon R.D.;
RT "Regulated overexpression of CDR1 in Candida albicans confers multidrug
RT resistance.";
RL J. Antimicrob. Chemother. 54:999-1006(2004).
RN [30]
RP INDUCTION.
RX PubMed=14968428; DOI=10.1002/yea.1067;
RA Karnani N., Gaur N.A., Jha S., Puri N., Krishnamurthy S., Goswami S.K.,
RA Mukhopadhyay G., Prasad R.;
RT "SRE1 and SRE2 are two specific steroid-responsive modules of Candida drug
RT resistance gene 1 (CDR1) promoter.";
RL Yeast 21:219-239(2004).
RN [31]
RP INDUCTION.
RX PubMed=15896319; DOI=10.1016/j.bbrc.2005.04.113;
RA Gaur N.A., Manoharlal R., Saini P., Prasad T., Mukhopadhyay G., Hoefer M.,
RA Morschhaeuser J., Prasad R.;
RT "Expression of the CDR1 efflux pump in clinical Candida albicans isolates
RT is controlled by a negative regulatory element.";
RL Biochem. Biophys. Res. Commun. 332:206-214(2005).
RN [32]
RP DOMAIN, AND MUTAGENESIS OF TRP-326.
RX PubMed=15850398; DOI=10.1021/bi0474160;
RA Rai V., Shukla S., Jha S., Komath S.S., Prasad R.;
RT "Functional characterization of N-terminal nucleotide binding domain (NBD-
RT 1) of a major ABC drug transporter Cdr1p of Candida albicans: uncommon but
RT conserved Trp326 of Walker B is important for ATP binding.";
RL Biochemistry 44:6650-6661(2005).
RN [33]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ALA-1346; ALA-1347;
RP THR-1351; THR-1355 AND LEU-1358.
RX PubMed=15937063; DOI=10.1093/jac/dki183;
RA Saini P., Prasad T., Gaur N.A., Shukla S., Jha S., Komath S.S., Khan L.A.,
RA Haq Q.M., Prasad R.;
RT "Alanine scanning of transmembrane helix 11 of Cdr1p ABC antifungal efflux
RT pump of Candida albicans: identification of amino acid residues critical
RT for drug efflux.";
RL J. Antimicrob. Chemother. 56:77-86(2005).
RN [34]
RP INDUCTION.
RX PubMed=16569846; DOI=10.1128/aac.50.4.1311-1319.2006;
RA Lepak A., Nett J., Lincoln L., Marchillo K., Andes D.;
RT "Time course of microbiologic outcome and gene expression in Candida
RT albicans during and following in vitro and in vivo exposure to
RT fluconazole.";
RL Antimicrob. Agents Chemother. 50:1311-1319(2006).
RN [35]
RP FUNCTION.
RX PubMed=16475832; DOI=10.1021/bi0519147;
RA Shukla S., Rai V., Banerjee D., Prasad R.;
RT "Characterization of Cdr1p, a major multidrug efflux protein of Candida
RT albicans: purified protein is amenable to intrinsic fluorescence
RT analysis.";
RL Biochemistry 45:2425-2435(2006).
RN [36]
RP INDUCTION.
RX PubMed=16839415; DOI=10.1186/1471-2199-7-22;
RA Yang Y.L., Lin Y.H., Tsao M.Y., Chen C.G., Shih H.I., Fan J.C., Wang J.S.,
RA Lo H.J.;
RT "Serum repressing efflux pump CDR1 in Candida albicans.";
RL BMC Mol. Biol. 7:22-22(2006).
RN [37]
RP INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16400181; DOI=10.1128/ec.5.1.180-191.2006;
RA Cheng G., Yeater K.M., Hoyer L.L.;
RT "Cellular and molecular biology of Candida albicans estrogen response.";
RL Eukaryot. Cell 5:180-191(2006).
RN [38]
RP FUNCTION, AND MUTAGENESIS OF TRP-629.
RX PubMed=16782311; DOI=10.1016/j.ijantimicag.2006.02.016;
RA Gao P.H., Cao Y.B., Jia X.M., Cao Y.Y., Quan H., Wang Y., Jiang Y.Y.;
RT "Drug susceptibilities of yeast cells are affected when expressing mutant
RT Candida albicans drug resistance protein.";
RL Int. J. Antimicrob. Agents 28:69-74(2006).
RN [39]
RP INDUCTION, AND FUNCTION.
RX PubMed=16291868; DOI=10.1093/jac/dki402;
RA Tanida T., Okamoto T., Ueta E., Yamamoto T., Osaki T.;
RT "Antimicrobial peptides enhance the candidacidal activity of antifungal
RT drugs by promoting the efflux of ATP from Candida cells.";
RL J. Antimicrob. Chemother. 57:94-103(2006).
RN [40]
RP INDUCTION.
RX PubMed=17005790; DOI=10.1099/jmm.0.46650-0;
RA Wang J.S., Yang Y.L., Wu C.J., Ouyang K.J., Tseng K.Y., Chen C.G., Wang H.,
RA Lo H.J.;
RT "The DNA-binding domain of CaNdt80p is required to activate CDR1 involved
RT in drug resistance in Candida albicans.";
RL J. Med. Microbiol. 55:1403-1411(2006).
RN [41]
RP FUNCTION, DOMAIN, AND SUBCELLULAR LOCATION.
RX PubMed=16622073; DOI=10.1099/mic.0.28471-0;
RA Saini P., Gaur N.A., Prasad R.;
RT "Chimeras of the ABC drug transporter Cdr1p reveal functional
RT indispensability of transmembrane domains and nucleotide-binding domains,
RT but transmembrane segment 12 is replaceable with the corresponding
RT homologous region of the non-drug transporter Cdr3p.";
RL Microbiology 152:1559-1573(2006).
RN [42]
RP INDUCTION.
RX PubMed=16921553; DOI=10.1002/yea.1394;
RA Larsen B., Anderson S., Brockman A., Essmann M., Schmidt M.;
RT "Key physiological differences in Candida albicans CDR1 induction by
RT steroid hormones and antifungal drugs.";
RL Yeast 23:795-802(2006).
RN [43]
RP FUNCTION.
RX PubMed=17924650; DOI=10.1021/bi700453e;
RA Shukla S., Rai V., Saini P., Banerjee D., Menon A.K., Prasad R.;
RT "Candida drug resistance protein 1, a major multidrug ATP binding cassette
RT transporter of Candida albicans, translocates fluorescent phospholipids in
RT a reconstituted system.";
RL Biochemistry 46:12081-12090(2007).
RN [44]
RP INDUCTION, AND FUNCTION.
RX PubMed=17202662; DOI=10.1248/bpb.30.68;
RA Shen H., An M.M., Wang D.J., Xu Z., Zhang J.D., Gao P.H., Cao Y.Y.,
RA Cao Y.B., Jiang Y.Y.;
RT "Fcr1p inhibits development of fluconazole resistance in Candida albicans
RT by abolishing CDR1 induction.";
RL Biol. Pharm. Bull. 30:68-73(2007).
RN [45]
RP SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=18056285; DOI=10.1128/aac.00861-07;
RA Pasrija R., Panwar S.L., Prasad R.;
RT "Multidrug transporters CaCdr1p and CaMdr1p of Candida albicans display
RT different lipid specificities: both ergosterol and sphingolipids are
RT essential for targeting of CaCdr1p to membrane rafts.";
RL Antimicrob. Agents Chemother. 52:694-704(2008).
RN [46]
RP INDUCTION, AND FUNCTION.
RX PubMed=18268086; DOI=10.1128/aac.01106-07;
RA Manoharlal R., Gaur N.A., Panwar S.L., Morschhaeuser J., Prasad R.;
RT "Transcriptional activation and increased mRNA stability contribute to
RT overexpression of CDR1 in azole-resistant Candida albicans.";
RL Antimicrob. Agents Chemother. 52:1481-1492(2008).
RN [47]
RP FUNCTION.
RX PubMed=18710914; DOI=10.1128/aac.00463-08;
RA Holmes A.R., Lin Y.H., Niimi K., Lamping E., Keniya M., Niimi M.,
RA Tanabe K., Monk B.C., Cannon R.D.;
RT "ABC transporter Cdr1p contributes more than Cdr2p does to fluconazole
RT efflux in fluconazole-resistant Candida albicans clinical isolates.";
RL Antimicrob. Agents Chemother. 52:3851-3862(2008).
RN [48]
RP FUNCTION.
RX PubMed=19223631; DOI=10.1128/aac.00926-08;
RA Tsao S., Rahkhoodaee F., Raymond M.;
RT "Relative contributions of the Candida albicans ABC transporters Cdr1p and
RT Cdr2p to clinical azole resistance.";
RL Antimicrob. Agents Chemother. 53:1344-1352(2009).
RN [49]
RP FUNCTION, AND MUTAGENESIS OF THR-658; PRO-659; ALA-660; THR-661; VAL-662;
RP LEU-663; LEU-664; LEU-665; MET-667; VAL-668; ILE-669; TYR-670; THR-671;
RP GLY-672; PHE-673; VAL-674; ILE-675; PRO-676; THR-677 AND PRO-678.
RX PubMed=19393219; DOI=10.1016/j.bbamem.2009.04.009;
RA Puri N., Gaur M., Sharma M., Shukla S., Ambudkar S.V., Prasad R.;
RT "The amino acid residues of transmembrane helix 5 of multidrug resistance
RT protein CaCdr1p of Candida albicans are involved in substrate specificity
RT and drug transport.";
RL Biochim. Biophys. Acta 1788:1752-1761(2009).
RN [50]
RP INDUCTION.
RX PubMed=19420894; DOI=10.1248/yakushi.129.623;
RA Zhang H., Gao A., Li F., Zhang G., Ho H.I., Liao W.;
RT "Mechanism of action of tetrandrine, a natural inhibitor of Candida
RT albicans drug efflux pumps.";
RL Yakugaku Zasshi 129:623-630(2009).
RN [51]
RP DOMAIN.
RX PubMed=20546701; DOI=10.1016/j.bbamem.2010.05.017;
RA Kumar A., Shukla S., Mandal A., Shukla S., Ambudkar S.V., Prasad R.;
RT "Divergent signature motifs of nucleotide binding domains of ABC multidrug
RT transporter, CaCdr1p of pathogenic Candida albicans, are functionally
RT asymmetric and noninterchangeable.";
RL Biochim. Biophys. Acta 1798:1757-1766(2010).
RN [52]
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=20348384; DOI=10.1128/ec.00355-09;
RA Basso L.R. Jr., Gast C.E., Mao Y., Wong B.;
RT "Fluconazole transport into Candida albicans secretory vesicles by the
RT membrane proteins Cdr1p, Cdr2p, and Mdr1p.";
RL Eukaryot. Cell 9:960-970(2010).
RN [53]
RP FUNCTION.
RX PubMed=20876623; DOI=10.1093/jac/dkq354;
RA Siikala E., Rautemaa R., Richardson M., Saxen H., Bowyer P., Sanglard D.;
RT "Persistent Candida albicans colonization and molecular mechanisms of azole
RT resistance in autoimmune polyendocrinopathy-candidiasis-ectodermal
RT dystrophy (APECED) patients.";
RL J. Antimicrob. Chemother. 65:2505-2513(2010).
RN [54]
RP INDUCTION, AND FUNCTION.
RX PubMed=20002912; DOI=10.1111/j.1365-2672.2009.04429.x;
RA Sun L.M., Cheng A.X., Wu X.Z., Zhang H.J., Lou H.X.;
RT "Synergistic mechanisms of retigeric acid B and azoles against Candida
RT albicans.";
RL J. Appl. Microbiol. 108:341-348(2010).
RN [55]
RP INDUCTION.
RX PubMed=20377529; DOI=10.1042/bsr20100015;
RA Manoharlal R., Sharma M., Prasad R.;
RT "Molecular determinants of transient and reversible induced up-regulation
RT of CaCDR1 in azole susceptible clinical isolates of Candida albicans.";
RL Biosci. Rep. 31:31-43(2011).
RN [56]
RP INDUCTION.
RX PubMed=21856931; DOI=10.1128/ec.05041-11;
RA Shukla S., Yadav V., Mukhopadhyay G., Prasad R.;
RT "Ncb2 is involved in activated transcription of CDR1 in azole-resistant
RT clinical isolates of Candida albicans.";
RL Eukaryot. Cell 10:1357-1366(2011).
RN [57]
RP INDUCTION.
RX PubMed=21474609; DOI=10.1099/jmm.0.030692-0;
RA Watamoto T., Samaranayake L.P., Egusa H., Yatani H., Seneviratne C.J.;
RT "Transcriptional regulation of drug-resistance genes in Candida albicans
RT biofilms in response to antifungals.";
RL J. Med. Microbiol. 60:1241-1247(2011).
RN [58]
RP INDUCTION.
RX PubMed=20818920; DOI=10.3109/13693786.2010.512022;
RA Kofla G., Turner V., Schulz B., Storch U., Froelich D., Rognon B.,
RA Coste A.T., Sanglard D., Ruhnke M.;
RT "Doxorubicin induces drug efflux pumps in Candida albicans.";
RL Med. Mycol. 49:132-142(2011).
RN [59]
RP FUNCTION.
RX PubMed=22205973; DOI=10.1371/journal.pone.0028830;
RA Zhu J., Krom B.P., Sanglard D., Intapa C., Dawson C.C., Peters B.M.,
RA Shirtliff M.E., Jabra-Rizk M.A.;
RT "Farnesol-induced apoptosis in Candida albicans is mediated by Cdr1-p
RT extrusion and depletion of intracellular glutathione.";
RL PLoS ONE 6:E28830-E28830(2011).
RN [60]
RP FUNCTION, AND MUTAGENESIS OF CYS-1056; CYS-1091; CYS-1106; CYS-1294 AND
RP CYS-1336.
RX PubMed=22166216; DOI=10.1016/j.bbrc.2011.11.150;
RA Prasad R., Shah A.H., Sanwal H., Kapoor K.;
RT "Alanine scanning of all cysteines and construction of a functional
RT cysteine-less Cdr1p, a multidrug ABC transporter of Candida albicans.";
RL Biochem. Biophys. Res. Commun. 417:508-513(2012).
RN [61]
RP SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=23979757; DOI=10.1128/aac.00889-13;
RA Thomas E., Roman E., Claypool S., Manzoor N., Pla J., Panwar S.L.;
RT "Mitochondria influence CDR1 efflux pump activity, Hog1-mediated oxidative
RT stress pathway, iron homeostasis, and ergosterol levels in Candida
RT albicans.";
RL Antimicrob. Agents Chemother. 57:5580-5599(2013).
RN [62]
RP SUBCELLULAR LOCATION, FUNCTION, AND MUTAGENESIS OF PHE-551; PHE-552;
RP PHE-559; SER-561; GLU-564; MET-604; ASN-609; ARG-644; PHE-1230; THR-1331;
RP CYS-1336 AND PHE-1360.
RX PubMed=23824183; DOI=10.1074/jbc.m113.488353;
RA Rawal M.K., Khan M.F., Kapoor K., Goyal N., Sen S., Saxena A.K., Lynn A.M.,
RA Tyndall J.D., Monk B.C., Cannon R.D., Komath S.S., Prasad R.;
RT "Insight into pleiotropic drug resistance ATP-binding cassette pump drug
RT transport through mutagenesis of Cdr1p transmembrane domains.";
RL J. Biol. Chem. 288:24480-24493(2013).
CC -!- FUNCTION: Pleiotropic ABC efflux transporter that confers resistance to
CC numerous chemicals including anisomycin, cycloheximide, fluconazole,
CC miconazole, ketoconazole, itriconazole, nystatin, terbinafine,
CC amorolfine, brefeldin A, amphotericin B, fluphenazine, as well as
CC estrogen. Plays a role in farnesol-induced apoptotic process through
CC glutathione efflux activity. Mediates in-to-out translocation of
CC membrane phospholipids including aminophospholipids and thus regulates
CC asymmetric distribution of phosphatidylethanolamine. Exhibits
CC nucleoside triphosphatase activity. {ECO:0000269|PubMed:10029989,
CC ECO:0000269|PubMed:10227177, ECO:0000269|PubMed:10428921,
CC ECO:0000269|PubMed:11709310, ECO:0000269|PubMed:11870854,
CC ECO:0000269|PubMed:12709320, ECO:0000269|PubMed:14665469,
CC ECO:0000269|PubMed:15152937, ECO:0000269|PubMed:15190023,
CC ECO:0000269|PubMed:15486081, ECO:0000269|PubMed:15937063,
CC ECO:0000269|PubMed:16291868, ECO:0000269|PubMed:16475832,
CC ECO:0000269|PubMed:16622073, ECO:0000269|PubMed:16782311,
CC ECO:0000269|PubMed:17202662, ECO:0000269|PubMed:18056285,
CC ECO:0000269|PubMed:18268086, ECO:0000269|PubMed:18710914,
CC ECO:0000269|PubMed:19223631, ECO:0000269|PubMed:19393219,
CC ECO:0000269|PubMed:20002912, ECO:0000269|PubMed:20348384,
CC ECO:0000269|PubMed:20876623, ECO:0000269|PubMed:22166216,
CC ECO:0000269|PubMed:22205973, ECO:0000269|PubMed:23824183,
CC ECO:0000269|PubMed:23979757, ECO:0000269|PubMed:8891134,
CC ECO:0000269|PubMed:9124851, ECO:0000269|PubMed:9453158,
CC ECO:0000269|PubMed:9605504}.
CC -!- ACTIVITY REGULATION: Disulfiram reverses CDR1-mediated drug resistance
CC by interaction with both ATP and substrate-binding sites of the
CC transporter and may be useful for antifungal therapy.
CC {ECO:0000269|PubMed:15325261}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.8 uM for fluconazole {ECO:0000269|PubMed:20348384};
CC Vmax=0.91 pmol/min/mg enzyme for fluconazole transport
CC {ECO:0000269|PubMed:20348384};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14665469,
CC ECO:0000269|PubMed:15190023, ECO:0000269|PubMed:15937063,
CC ECO:0000269|PubMed:16622073, ECO:0000269|PubMed:18056285,
CC ECO:0000269|PubMed:23824183}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Accumulates at membrane rafts. Both ergosterol and
CC sphingolipids are essential for targeting to membrane rafts.
CC Mislocalizes to the vacuole in absence of FZO1.
CC {ECO:0000269|PubMed:18056285, ECO:0000269|PubMed:23979757}.
CC -!- INDUCTION: The distal promoter mediates the miconazole response whereas
CC the proximal promoter (-345/+1) contains all the regulatory domains
CC required for its induction by various other stresses. The promoter also
CC contains a steroid responsive region (SRR) conferring beta-oestradiol
CC and progesterone inducibility. Transcription is positively regulated by
CC NCB2, NTD80 and TAC1 and repressed by FCR1. Expression is up-regulated
CC during biofilm development, by heat-shock, and by benomyl, doxorubicin,
CC miconazole, vinblastine, adriamycin, fluphenazine, cycloheximide,
CC calcofluor, canavanine, 5'-fluorcytosine, cilofungin and caffeine.
CC Expression is repressed by serum and inhibited by tetrandrine.
CC Transcription is also reduced during in vitro fluconazole exposure but
CC in the postexposure period, the mRNA abundance increases.
CC {ECO:0000269|PubMed:10428921, ECO:0000269|PubMed:10556714,
CC ECO:0000269|PubMed:10952571, ECO:0000269|PubMed:11918807,
CC ECO:0000269|PubMed:14734019, ECO:0000269|PubMed:14968428,
CC ECO:0000269|PubMed:15273122, ECO:0000269|PubMed:15328097,
CC ECO:0000269|PubMed:15561818, ECO:0000269|PubMed:15590837,
CC ECO:0000269|PubMed:15896319, ECO:0000269|PubMed:16291868,
CC ECO:0000269|PubMed:16400181, ECO:0000269|PubMed:16569846,
CC ECO:0000269|PubMed:16839415, ECO:0000269|PubMed:16921553,
CC ECO:0000269|PubMed:17005790, ECO:0000269|PubMed:17202662,
CC ECO:0000269|PubMed:18268086, ECO:0000269|PubMed:19420894,
CC ECO:0000269|PubMed:20002912, ECO:0000269|PubMed:20377529,
CC ECO:0000269|PubMed:20818920, ECO:0000269|PubMed:21474609,
CC ECO:0000269|PubMed:21856931, ECO:0000269|PubMed:9532737,
CC ECO:0000269|PubMed:9605502}.
CC -!- DOMAIN: Contains 2 cytoplasmic nucleotide binding domains (NBDs). The
CC N-terminal NBD has ATPase activity. The 2 NBDs are asymmetric and non-
CC exchangeable and the drug efflux by CDR1 involves complex interactions
CC between the two halves of the protein. {ECO:0000269|PubMed:12962507,
CC ECO:0000269|PubMed:15850398, ECO:0000269|PubMed:16622073,
CC ECO:0000269|PubMed:20546701}.
CC -!- DISRUPTION PHENOTYPE: Leads to hypersusceptibility to the antifungal
CC agents terbinafine and amorolfine, and to the metabolic inhibitors
CC cycloheximide, brefeldin A, and fluphenazine. Shows a decreased number
CC of germ tube-forming cells in the presence of estradiol when CDR2 is
CC also deleted. {ECO:0000269|PubMed:16400181,
CC ECO:0000269|PubMed:8891134}.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU01700}.
CC ---------------------------------------------------------------------------
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DR EMBL; CP017625; AOW28537.1; -; Genomic_DNA.
DR RefSeq; XP_723209.2; XM_718116.2.
DR AlphaFoldDB; Q5ANA3; -.
DR SMR; Q5ANA3; -.
DR STRING; 237561.Q5ANA3; -.
DR PRIDE; Q5ANA3; -.
DR GeneID; 3635237; -.
DR KEGG; cal:CAALFM_C305220WA; -.
DR CGD; CAL0000186516; CDR1.
DR VEuPathDB; FungiDB:C3_05220W_A; -.
DR eggNOG; KOG0065; Eukaryota.
DR HOGENOM; CLU_000604_35_0_1; -.
DR InParanoid; Q5ANA3; -.
DR OrthoDB; 37708at2759; -.
DR PRO; PR:Q5ANA3; -.
DR Proteomes; UP000000559; Chromosome 3.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; IEA:InterPro.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR GO; GO:0046898; P:response to cycloheximide; IEA:UniProtKB-KW.
DR GO; GO:1990961; P:xenobiotic detoxification by transmembrane export across the plasma membrane; IEA:InterPro.
DR CDD; cd03233; ABCG_PDR_domain1; 1.
DR CDD; cd03232; ABCG_PDR_domain2; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR013525; ABC_2_trans.
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 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; SSF52540; 2.
DR TIGRFAMs; TIGR00956; 3a01205; 1.
DR PROSITE; PS00211; ABC_TRANSPORTER_1; 1.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 2.
PE 1: Evidence at protein level;
KW Antibiotic resistance; ATP-binding; Cell membrane; Coiled coil;
KW Cycloheximide resistance; Membrane; Nucleotide-binding; Reference proteome;
KW Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1501
FT /note="Pleiotropic ABC efflux transporter of multiple drugs
FT CDR1"
FT /id="PRO_0000431582"
FT TOPO_DOM 1..513
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 514..534
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 535..548
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 549..569
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 570..597
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 598..618
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 619..622
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 623..643
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 644..654
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 655..675
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 676..764
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 765..785
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 786..1195
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1196..1216
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1217..1229
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1230..1250
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1251..1280
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1281..1301
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1302..1314
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1315..1335
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1336..1355
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1356..1376
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1377..1466
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1467..1487
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1488..1501
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 150..404
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 859..1103
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2..512
FT /note="NBD1"
FT /evidence="ECO:0000303|PubMed:20546701"
FT REGION 786..1195
FT /note="NBD2"
FT /evidence="ECO:0000303|PubMed:20546701"
FT COILED 1137..1164
FT /evidence="ECO:0000255"
FT COMPBIAS 1..20
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 895..902
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT MUTAGEN 193
FT /note="C->A: Impairs NBD-mediated ATP hydrolysis."
FT /evidence="ECO:0000269|PubMed:12962507"
FT MUTAGEN 232
FT /note="D->K: Leads to general drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:14665469"
FT MUTAGEN 296
FT /note="G->D: Leads to selective drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:14665469"
FT MUTAGEN 326
FT /note="W->A: Impairs NBD ATP-binding."
FT /evidence="ECO:0000269|PubMed:15850398"
FT MUTAGEN 551
FT /note="F->A: Leads to selective drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:23824183"
FT MUTAGEN 552
FT /note="F->A: Leads to reduced drug efflux but shows normal
FT ATPase activity."
FT /evidence="ECO:0000269|PubMed:23824183"
FT MUTAGEN 559
FT /note="F->A: Leads to reduced drug efflux and ATPase
FT activity."
FT /evidence="ECO:0000269|PubMed:23824183"
FT MUTAGEN 561
FT /note="S->A: Leads to selective drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:23824183"
FT MUTAGEN 564
FT /note="E->A: Leads to selective drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:23824183"
FT MUTAGEN 604
FT /note="M->A: Leads to selective drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:23824183"
FT MUTAGEN 609
FT /note="N->A: Leads to selective drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:23824183"
FT MUTAGEN 629
FT /note="W->L: Leads to selective drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:16782311"
FT MUTAGEN 644
FT /note="R->A: Leads to reduced drug efflux but shows normal
FT ATPase activity."
FT /evidence="ECO:0000269|PubMed:23824183"
FT MUTAGEN 658
FT /note="T->A: Leads to general drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:19393219"
FT MUTAGEN 659
FT /note="P->A: Leads to selective drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:19393219"
FT MUTAGEN 660
FT /note="A->G: Leads to general drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:19393219"
FT MUTAGEN 661
FT /note="T->A: Leads to general drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:19393219"
FT MUTAGEN 662
FT /note="V->A: Leads to general drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:19393219"
FT MUTAGEN 663
FT /note="L->A: Leads to selective drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:19393219"
FT MUTAGEN 664
FT /note="L->A: Leads to selective drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:19393219"
FT MUTAGEN 665
FT /note="L->A: Leads to general drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:19393219"
FT MUTAGEN 667
FT /note="M->A: Leads to selective drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:19393219"
FT MUTAGEN 668
FT /note="V->A: Leads to selective drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:19393219"
FT MUTAGEN 669
FT /note="I->A: Leads to general drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:19393219"
FT MUTAGEN 670
FT /note="Y->A: Leads to general drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:19393219"
FT MUTAGEN 671
FT /note="T->A: Leads to selective drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:19393219"
FT MUTAGEN 672
FT /note="G->A: Leads to selective drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:19393219"
FT MUTAGEN 673
FT /note="F->A: Leads to selective drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:19393219"
FT MUTAGEN 674
FT /note="V->A: Leads to selective drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:19393219"
FT MUTAGEN 675
FT /note="I->A: Leads to selective drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:19393219"
FT MUTAGEN 676
FT /note="P->A: Leads to selective drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:19393219"
FT MUTAGEN 677
FT /note="T->A: Leads to selective drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:19393219"
FT MUTAGEN 678
FT /note="P->A: Leads to selective drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:19393219"
FT MUTAGEN 774
FT /note="F->A: Leads to selective drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:14665469"
FT MUTAGEN 774
FT /note="Missing: Leads to mislocalization and general drug-
FT sensitivity."
FT /evidence="ECO:0000269|PubMed:14665469"
FT MUTAGEN 995
FT /note="G->S: Leads to selective drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:14665469"
FT MUTAGEN 1000
FT /note="G->C: Leads to selective drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:14665469"
FT MUTAGEN 1056
FT /note="C->A: Leads to general drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:22166216"
FT MUTAGEN 1091
FT /note="C->A: Leads to general drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:22166216"
FT MUTAGEN 1106
FT /note="C->A: Leads to general drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:22166216"
FT MUTAGEN 1230
FT /note="F->A: Leads to selective drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:23824183"
FT MUTAGEN 1294
FT /note="C->A: Leads to general drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:22166216"
FT MUTAGEN 1331
FT /note="T->A: Leads to selective drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:23824183"
FT MUTAGEN 1336
FT /note="C->A: Leads to reduced drug efflux and ATPase
FT activity."
FT /evidence="ECO:0000269|PubMed:22166216,
FT ECO:0000269|PubMed:23824183"
FT MUTAGEN 1346
FT /note="A->G: Leads to selective drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:15937063"
FT MUTAGEN 1347
FT /note="A->G: Leads to selective drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:15937063"
FT MUTAGEN 1351
FT /note="T->A: Leads to selective drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:15937063"
FT MUTAGEN 1351
FT /note="T->F: Leads to general drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:14665469,
FT ECO:0000269|PubMed:15190023"
FT MUTAGEN 1355
FT /note="T->A: Leads to selective drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:15937063"
FT MUTAGEN 1358
FT /note="L->A: Leads to selective drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:15937063"
FT MUTAGEN 1360
FT /note="F->A: Leads to reduced drug efflux but shows normal
FT ATPase activity."
FT /evidence="ECO:0000269|PubMed:23824183"
FT MUTAGEN 1418
FT /note="C->Y: Leads to selective drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:14665469"
FT MUTAGEN 1449
FT /note="T->A: Leads to selective drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:14665469"
FT MUTAGEN 1456
FT /note="V->A: Leads to selective drug-sensitivity."
FT /evidence="ECO:0000269|PubMed:14665469"
SQ SEQUENCE 1501 AA; 169984 MW; 2403EBE361B3A332 CRC64;
MSDSKMSSQD ESKLEKAISQ DSSSENHSIN EYHGFDAHTS ENIQNLARTF THDSFKDDSS
AGLLKYLTHM SEVPGVNPYE HEEINNDQLN PDSENFNAKF WVKNLRKLFE SDPEYYKPSK
LGIGYRNLRA YGVANDSDYQ PTVTNALWKL ATEGFRHFQK DDDSRYFDIL KSMDAIMRPG
ELTVVLGRPG AGCSTLLKTI AVNTYGFHIG KESQITYDGL SPHDIERHYR GDVIYSAETD
VHFPHLSVGD TLEFAARLRT PQNRGEGIDR ETYAKHMASV YMATYGLSHT RNTNVGNDFV
RGVSGGERKR VSIAEASLSG ANIQCWDNAT RGLDSATALE FIRALKTSAV ILDTTPLIAI
YQCSQDAYDL FDKVVVLYEG YQIFFGKATK AKEYFEKMGW KCPQRQTTAD FLTSLTNPAE
REPLPGYEDK VPRTAQEFET YWKNSPEYAE LTKEIDEYFV ECERSNTRET YRESHVAKQS
NNTRPASPYT VSFFMQVRYG VARNFLRMKG DPSIPIFSVF GQLVMGLILS SVFYNLSQTT
GSFYYRGAAM FFAVLFNAFS SLLEIMSLFE ARPIVEKHKK YALYRPSADA LASIISELPV
KLAMSMSFNF VFYFMVNFRR NPGRFFFYWL MCIWCTFVMS HLFRSIGAVS TSISGAMTPA
TVLLLAMVIY TGFVIPTPSM LGWSRWINYI NPVGYVFESL MVNEFHGREF QCAQYVPSGP
GYENISRSNQ VCTAVGSVPG NEMVSGTNYL AGAYQYYNSH KWRNLGITIG FAVFFLAIYI
ALTEFNKGAM QKGEIVLFLK GSLKKHKRKT AASNKGDIEA GPVAGKLDYQ DEAEAVNNEK
FTEKGSTGSV DFPENREIFF WRDLTYQVKI KKEDRVILDH VDGWVKPGQI TALMGASGAG
KTTLLNCLSE RVTTGIITDG ERLVNGHALD SSFQRSIGYV QQQDVHLETT TVREALQFSA
YLRQSNKISK KEKDDYVDYV IDLLEMTDYA DALVGVAGEG LNVEQRKRLT IGVELVAKPK
LLLFLDEPTS GLDSQTAWSI CKLMRKLADH GQAILCTIHQ PSALIMAEFD RLLFLQKGGR
TAYFGELGEN CQTMINYFEK YGADPCPKEA NPAEWMLQVV GAAPGSHAKQ DYFEVWRNSS
EYQAVREEIN RMEAELSKLP RDNDPEALLK YAAPLWKQYL LVSWRTIVQD WRSPGYIYSK
IFLVVSAALF NGFSFFKAKN NMQGLQNQMF SVFMFFIPFN TLVQQMLPYF VKQRDVYEVR
EAPSRTFSWF AFIAGQITSE IPYQVAVGTI AFFCWYYPLG LYNNATPTDS VNPRGVLMWM
LVTAFYVYTA TMGQLCMSFS ELADNAANLA TLLFTMCLNF CGVLAGPDVL PGFWIFMYRC
NPFTYLVQAM LSTGLANTFV KCAEREYVSV KPPNGESCST YLDPYIKFAG GYFETRNDGS
CAFCQMSSTN TFLKSVNSLY SERWRNFGIF IAFIAINIIL TVIFYWLARV PKGNREKKNK
K
