CDR1_CANGA
ID CDR1_CANGA Reviewed; 1499 AA.
AC Q6FK23;
DT 12-SEP-2018, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Pleiotropic ABC efflux transporter of multiple drugs CDR1 {ECO:0000303|PubMed:10543759};
DE AltName: Full=Pleiotropic drug resistance protein CDR1 {ECO:0000303|PubMed:10543759};
GN Name=CDR1 {ECO:0000303|PubMed:10543759}; OrderedLocusNames=CAGL0M01760g;
OS Candida glabrata (strain ATCC 2001 / CBS 138 / JCM 3761 / NBRC 0622 / NRRL
OS Y-65) (Yeast) (Torulopsis glabrata).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Nakaseomyces;
OC Nakaseomyces/Candida clade.
OX NCBI_TaxID=284593;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 2001 / CBS 138 / JCM 3761 / NBRC 0622 / NRRL Y-65;
RX PubMed=15229592; DOI=10.1038/nature02579;
RA Dujon B., Sherman D., Fischer G., Durrens P., Casaregola S., Lafontaine I.,
RA de Montigny J., Marck C., Neuveglise C., Talla E., Goffard N., Frangeul L.,
RA Aigle M., Anthouard V., Babour A., Barbe V., Barnay S., Blanchin S.,
RA Beckerich J.-M., Beyne E., Bleykasten C., Boisrame A., Boyer J.,
RA Cattolico L., Confanioleri F., de Daruvar A., Despons L., Fabre E.,
RA Fairhead C., Ferry-Dumazet H., Groppi A., Hantraye F., Hennequin C.,
RA Jauniaux N., Joyet P., Kachouri R., Kerrest A., Koszul R., Lemaire M.,
RA Lesur I., Ma L., Muller H., Nicaud J.-M., Nikolski M., Oztas S.,
RA Ozier-Kalogeropoulos O., Pellenz S., Potier S., Richard G.-F.,
RA Straub M.-L., Suleau A., Swennen D., Tekaia F., Wesolowski-Louvel M.,
RA Westhof E., Wirth B., Zeniou-Meyer M., Zivanovic Y., Bolotin-Fukuhara M.,
RA Thierry A., Bouchier C., Caudron B., Scarpelli C., Gaillardin C.,
RA Weissenbach J., Wincker P., Souciet J.-L.;
RT "Genome evolution in yeasts.";
RL Nature 430:35-44(2004).
RN [2]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INDUCTION.
RX PubMed=10543759; DOI=10.1128/aac.43.11.2753;
RA Sanglard D., Ischer F., Calabrese D., Majcherczyk P.A., Bille J.;
RT "The ATP binding cassette transporter gene CgCDR1 from Candida glabrata is
RT involved in the resistance of clinical isolates to azole antifungal
RT agents.";
RL Antimicrob. Agents Chemother. 43:2753-2765(1999).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=11257032; DOI=10.1128/aac.45.4.1174-1183.2001;
RA Sanglard D., Ischer F., Bille J.;
RT "Role of ATP-binding-cassette transporter genes in high-frequency
RT acquisition of resistance to azole antifungals in Candida glabrata.";
RL Antimicrob. Agents Chemother. 45:1174-1183(2001).
RN [4]
RP FUNCTION, PHOSPHORYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=12244114; DOI=10.1074/jbc.m207817200;
RA Wada S., Niimi M., Niimi K., Holmes A.R., Monk B.C., Cannon R.D.,
RA Uehara Y.;
RT "Candida glabrata ATP-binding cassette transporters Cdr1p and Pdh1p
RT expressed in a Saccharomyces cerevisiae strain deficient in membrane
RT transporters show phosphorylation-dependent pumping properties.";
RL J. Biol. Chem. 277:46809-46821(2002).
RN [5]
RP INDUCTION.
RX PubMed=12458010; DOI=10.1016/s1570-0232(02)00668-2;
RA Niimi M., Nagai Y., Niimi K., Wada S.I., Cannon R.D., Uehara Y., Monk B.C.;
RT "Identification of two proteins induced by exposure of the pathogenic
RT fungus Candida glabrata to fluconazole.";
RL J. Chromatogr. B 782:245-252(2002).
RN [6]
RP FUNCTION.
RX PubMed=15105111; DOI=10.1128/aac.48.5.1600-1613.2004;
RA Kaur R., Castano I., Cormack B.P.;
RT "Functional genomic analysis of fluconazole susceptibility in the
RT pathogenic yeast Candida glabrata: roles of calcium signaling and
RT mitochondria.";
RL Antimicrob. Agents Chemother. 48:1600-1613(2004).
RN [7]
RP FUNCTION.
RX PubMed=15105136; DOI=10.1128/aac.48.5.1788-1796.2004;
RA Brun S., Berges T., Poupard P., Vauzelle-Moreau C., Renier G., Chabasse D.,
RA Bouchara J.P.;
RT "Mechanisms of azole resistance in petite mutants of Candida glabrata.";
RL Antimicrob. Agents Chemother. 48:1788-1796(2004).
RN [8]
RP FUNCTION, AND INDUCTION.
RX PubMed=15388433; DOI=10.1128/aac.48.10.3773-3781.2004;
RA Vermitsky J.P., Edlind T.D.;
RT "Azole resistance in Candida glabrata: coordinate upregulation of multidrug
RT transporters and evidence for a Pdr1-like transcription factor.";
RL Antimicrob. Agents Chemother. 48:3773-3781(2004).
RN [9]
RP FUNCTION, PHOSPHORYLATION AT SER-307 AND SER-484, AND MUTAGENESIS OF
RP SER-307 AND SER-484.
RX PubMed=15498768; DOI=10.1074/jbc.m408252200;
RA Wada S., Tanabe K., Yamazaki A., Niimi M., Uehara Y., Niimi K., Lamping E.,
RA Cannon R.D., Monk B.C.;
RT "Phosphorylation of candida glabrata ATP-binding cassette transporter Cdr1p
RT regulates drug efflux activity and ATPase stability.";
RL J. Biol. Chem. 280:94-103(2005).
RN [10]
RP INDUCTION.
RX PubMed=16735426; DOI=10.1093/jac/dkl221;
RA Rogers P.D., Vermitsky J.P., Edlind T.D., Hilliard G.M.;
RT "Proteomic analysis of experimentally induced azole resistance in Candida
RT glabrata.";
RL J. Antimicrob. Chemother. 58:434-438(2006).
RN [11]
RP INDUCTION.
RX PubMed=16891541; DOI=10.1128/jcm.00526-06;
RA Posteraro B., Tumbarello M., La Sorda M., Spanu T., Trecarichi E.M.,
RA De Bernardis F., Scoppettuolo G., Sanguinetti M., Fadda G.;
RT "Azole resistance of Candida glabrata in a case of recurrent fungemia.";
RL J. Clin. Microbiol. 44:3046-3047(2006).
RN [12]
RP FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16803598; DOI=10.1111/j.1365-2958.2006.05235.x;
RA Vermitsky J.P., Earhart K.D., Smith W.L., Homayouni R., Edlind T.D.,
RA Rogers P.D.;
RT "Pdr1 regulates multidrug resistance in Candida glabrata: gene disruption
RT and genome-wide expression studies.";
RL Mol. Microbiol. 61:704-722(2006).
RN [13]
RP INDUCTION.
RX PubMed=17158937; DOI=10.1128/aac.01510-06;
RA Vandeputte P., Tronchin G., Berges T., Hennequin C., Chabasse D.,
RA Bouchara J.P.;
RT "Reduced susceptibility to polyenes associated with a missense mutation in
RT the ERG6 gene in a clinical isolate of Candida glabrata with pseudohyphal
RT growth.";
RL Antimicrob. Agents Chemother. 51:982-990(2007).
RN [14]
RP FUNCTION, AND INDUCTION.
RX PubMed=17581937; DOI=10.1128/jcm.00381-07;
RA Shin J.H., Chae M.J., Song J.W., Jung S.I., Cho D., Kee S.J., Kim S.H.,
RA Shin M.G., Suh S.P., Ryang D.W.;
RT "Changes in karyotype and azole susceptibility of sequential bloodstream
RT isolates from patients with Candida glabrata candidemia.";
RL J. Clin. Microbiol. 45:2385-2391(2007).
RN [15]
RP FUNCTION, AND INDUCTION.
RX PubMed=18591262; DOI=10.1128/aac.00462-08;
RA Gygax S.E., Vermitsky J.P., Chadwick S.G., Self M.J., Zimmerman J.A.,
RA Mordechai E., Adelson M.E., Trama J.P.;
RT "Antifungal resistance of Candida glabrata vaginal isolates and development
RT of a quantitative reverse transcription-PCR-based azole susceptibility
RT assay.";
RL Antimicrob. Agents Chemother. 52:3424-3426(2008).
RN [16]
RP INDUCTION.
RX PubMed=18782778; DOI=10.1093/jac/dkn381;
RA Tumbarello M., Sanguinetti M., Trecarichi E.M., La Sorda M., Rossi M.,
RA de Carolis E., de Gaetano Donati K., Fadda G., Cauda R., Posteraro B.;
RT "Fungaemia caused by Candida glabrata with reduced susceptibility to
RT fluconazole due to altered gene expression: risk factors, antifungal
RT treatment and outcome.";
RL J. Antimicrob. Chemother. 62:1379-1385(2008).
RN [17]
RP INDUCTION.
RX PubMed=19380598; DOI=10.1128/aac.01384-08;
RA Vandeputte P., Tronchin G., Rocher F., Renier G., Berges T., Chabasse D.,
RA Bouchara J.P.;
RT "Hypersusceptibility to azole antifungals in a clinical isolate of Candida
RT glabrata with reduced aerobic growth.";
RL Antimicrob. Agents Chemother. 53:3034-3041(2009).
RN [18]
RP INDUCTION.
RX PubMed=19196495; DOI=10.1016/j.ijantimicag.2008.11.011;
RA Berila N., Borecka S., Dzugasova V., Bojnansky J., Subik J.;
RT "Mutations in the CgPDR1 and CgERG11 genes in azole-resistant Candida
RT glabrata clinical isolates from Slovakia.";
RL Int. J. Antimicrob. Agents 33:574-578(2009).
RN [19]
RP INDUCTION, AND FUNCTION.
RX PubMed=18651314; DOI=10.1080/13693780802210726;
RA Song J.W., Shin J.H., Kee S.J., Kim S.H., Shin M.G., Suh S.P., Ryang D.W.;
RT "Expression of CgCDR1, CgCDR2, and CgERG11 in Candida glabrata biofilms
RT formed by bloodstream isolates.";
RL Med. Mycol. 47:545-548(2009).
RN [20]
RP INDUCTION.
RX PubMed=19148266; DOI=10.1371/journal.ppat.1000268;
RA Ferrari S., Ischer F., Calabrese D., Posteraro B., Sanguinetti M.,
RA Fadda G., Rohde B., Bauser C., Bader O., Sanglard D.;
RT "Gain of function mutations in CgPDR1 of Candida glabrata not only mediate
RT antifungal resistance but also enhance virulence.";
RL PLoS Pathog. 5:E1000268-E1000268(2009).
RN [21]
RP FUNCTION, AND INDUCTION.
RX PubMed=20038613; DOI=10.1128/aac.01138-09;
RA Chapeland-Leclerc F., Hennequin C., Papon N., Noel T., Girard A., Socie G.,
RA Ribaud P., Lacroix C.;
RT "Acquisition of flucytosine, azole, and caspofungin resistance in Candida
RT glabrata bloodstream isolates serially obtained from a hematopoietic stem
RT cell transplant recipient.";
RL Antimicrob. Agents Chemother. 54:1360-1362(2010).
RN [22]
RP FUNCTION, AND INDUCTION.
RX PubMed=20450660;
RA Shen Y.Z., Lu H.Z., Zhang Y.X.;
RT "Molecular mechanisms of fluconazole resistance in clinical isolates of
RT Candida glabrata.";
RL Zhonghua Nei Ke Za Zhi 49:245-249(2010).
RN [23]
RP INDUCTION.
RX PubMed=21282443; DOI=10.1128/aac.00791-10;
RA Lignell A., Loewdin E., Cars O., Sanglard D., Sjoelin J.;
RT "Voriconazole-induced inhibition of the fungicidal activity of amphotericin
RT B in Candida strains with reduced susceptibility to voriconazole: an effect
RT not predicted by the MIC value alone.";
RL Antimicrob. Agents Chemother. 55:1629-1637(2011).
RN [24]
RP INDUCTION.
RX PubMed=21321146; DOI=10.1128/aac.01271-10;
RA Ferrari S., Sanguinetti M., De Bernardis F., Torelli R., Posteraro B.,
RA Vandeputte P., Sanglard D.;
RT "Loss of mitochondrial functions associated with azole resistance in
RT Candida glabrata results in enhanced virulence in mice.";
RL Antimicrob. Agents Chemother. 55:1852-1860(2011).
RN [25]
RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION, AND MUTAGENESIS OF CYS-188;
RP SER-660 AND PHE-773.
RX PubMed=21134356; DOI=10.1016/j.bbrc.2010.11.123;
RA Puri N., Manoharlal R., Sharma M., Sanglard D., Prasad R.;
RT "Overcoming the heterologous bias: an in vivo functional analysis of
RT multidrug efflux transporter, CgCdr1p in matched pair clinical isolates of
RT Candida glabrata.";
RL Biochem. Biophys. Res. Commun. 404:357-363(2011).
RN [26]
RP INDUCTION.
RX PubMed=21131438; DOI=10.1128/ec.00277-10;
RA Paul S., Schmidt J.A., Moye-Rowley W.S.;
RT "Regulation of the CgPdr1 transcription factor from the pathogen Candida
RT glabrata.";
RL Eukaryot. Cell 10:187-197(2011).
RN [27]
RP INDUCTION.
RX PubMed=21193550; DOI=10.1128/ec.00073-10;
RA Caudle K.E., Barker K.S., Wiederhold N.P., Xu L., Homayouni R.,
RA Rogers P.D.;
RT "Genomewide expression profile analysis of the Candida glabrata Pdr1
RT regulon.";
RL Eukaryot. Cell 10:373-383(2011).
RN [28]
RP FUNCTION, AND INDUCTION.
RX PubMed=21408004; DOI=10.1371/journal.pone.0017589;
RA Ferrari S., Sanguinetti M., Torelli R., Posteraro B., Sanglard D.;
RT "Contribution of CgPDR1-regulated genes in enhanced virulence of azole-
RT resistant Candida glabrata.";
RL PLoS ONE 6:E17589-E17589(2011).
RN [29]
RP ACTIVITY REGULATION.
RX PubMed=22203607; DOI=10.1128/aac.05706-11;
RA Holmes A.R., Keniya M.V., Ivnitski-Steele I., Monk B.C., Lamping E.,
RA Sklar L.A., Cannon R.D.;
RT "The monoamine oxidase A inhibitor clorgyline is a broad-spectrum inhibitor
RT of fungal ABC and MFS transporter efflux pump activities which reverses the
RT azole resistance of Candida albicans and Candida glabrata clinical
RT isolates.";
RL Antimicrob. Agents Chemother. 56:1508-1515(2012).
RN [30]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=22788839; DOI=10.1111/j.1365-2958.2012.08140.x;
RA Niimi K., Harding D.R., Holmes A.R., Lamping E., Niimi M., Tyndall J.D.,
RA Cannon R.D., Monk B.C.;
RT "Specific interactions between the Candida albicans ABC transporter Cdr1p
RT ectodomain and a D-octapeptide derivative inhibitor.";
RL Mol. Microbiol. 85:747-767(2012).
RN [31]
RP ACTIVITY REGULATION.
RX PubMed=23208712; DOI=10.1128/aac.02040-12;
RA Silva L.V., Sanguinetti M., Vandeputte P., Torelli R., Rochat B.,
RA Sanglard D.;
RT "Milbemycins: more than efflux inhibitors for fungal pathogens.";
RL Antimicrob. Agents Chemother. 57:873-886(2013).
RN [32]
RP INDUCTION.
RX PubMed=23229483; DOI=10.1128/aac.01278-12;
RA Noble J.A., Tsai H.F., Suffis S.D., Su Q., Myers T.G., Bennett J.E.;
RT "STB5 is a negative regulator of azole resistance in Candida glabrata.";
RL Antimicrob. Agents Chemother. 57:959-967(2013).
RN [33]
RP INDUCTION.
RX PubMed=23979762; DOI=10.1128/aac.02394-12;
RA Steier Z., Vermitsky J.P., Toner G., Gygax S.E., Edlind T., Katiyar S.;
RT "Flucytosine antagonism of azole activity versus Candida glabrata: role of
RT transcription factor Pdr1 and multidrug transporter Cdr1.";
RL Antimicrob. Agents Chemother. 57:5543-5547(2013).
RN [34]
RP INDUCTION.
RX PubMed=24645630; DOI=10.1080/08927014.2014.886108;
RA Fonseca E., Silva S., Rodrigues C.F., Alves C.T., Azeredo J., Henriques M.;
RT "Effects of fluconazole on Candida glabrata biofilms and its relationship
RT with ABC transporter gene expression.";
RL Biofouling 30:447-457(2014).
RN [35]
RP ACTIVITY REGULATION.
RX PubMed=24838041; DOI=10.1111/1567-1364.12164;
RA Walker B., Izumikawa K., Tsai H.F., Bennett J.E.;
RT "Milbemycin A4 oxime as a probe of azole transport in Candida glabrata.";
RL FEMS Yeast Res. 14:755-761(2014).
RN [36]
RP INDUCTION.
RX PubMed=25818698; DOI=10.1099/jmm.0.000062;
RA Szweda P., Gucwa K., Romanowska E., Dzierzanowska-Fangrat K., Naumiuk L.,
RA Brillowska-Dabrowska A., Wojciechowska-Koszko I., Milewski S.;
RT "Mechanisms of azole resistance among clinical isolates of Candida glabrata
RT in Poland.";
RL J. Med. Microbiol. 64:610-619(2015).
RN [37]
RP FUNCTION.
RX PubMed=26482310; DOI=10.1128/aac.02157-15;
RA Sanglard D., Coste A.T.;
RT "Activity of isavuconazole and other azoles against Candida clinical
RT isolates and yeast model systems with known azole resistance mechanisms.";
RL Antimicrob. Agents Chemother. 60:229-238(2016).
RN [38]
RP FUNCTION, AND INDUCTION.
RX PubMed=27486188; DOI=10.1128/mbio.00655-16;
RA Ben-Ami R., Zimmerman O., Finn T., Amit S., Novikov A., Wertheimer N.,
RA Lurie-Weinberger M., Berman J.;
RT "Heteroresistance to Fluconazole Is a Continuously Distributed Phenotype
RT among Candida glabrata Clinical Strains Associated with In Vivo
RT Persistence.";
RL MBio 7:0-0(2016).
RN [39]
RP INDUCTION.
RX PubMed=28894714;
RA Shahrokhi S., Noorbakhsh F., Rezaie S.;
RT "Quantification of CDR1 gene expression in fluconazole resistant Candida
RT glabrata strains using real-time PCR.";
RL Iran. J. Public Health 46:1118-1122(2017).
RN [40]
RP FUNCTION, AND INDUCTION.
RX PubMed=29371812; DOI=10.5941/myco.2017.45.4.426;
RA Kim M., Lee H., Hwang S.Y., Lee I., Jung W.H.;
RT "Isolated from the urinary tract of a dog with diabetes mellitus.";
RL Mycobiology 45:426-429(2017).
RN [41]
RP INDUCTION.
RX PubMed=29507891; DOI=10.1128/msphere.00466-17;
RA Whaley S.G., Caudle K.E., Simonicova L., Zhang Q., Moye-Rowley W.S.,
RA Rogers P.D.;
RT "Jjj1 is a negative regulator of Pdr1-mediated fluconazole resistance in
RT Candida glabrata.";
RL MSphere 3:0-0(2018).
RN [42]
RP INDUCTION.
RX PubMed=29464833; DOI=10.1111/myc.12756;
RA Ni Q., Wang C., Tian Y., Dong D., Jiang C., Mao E., Peng Y.;
RT "CgPDR1 gain-of-function mutations lead to azole-resistance and increased
RT adhesion in clinical Candida glabrata strains.";
RL Mycoses 61:430-440(2018).
RN [43]
RP FUNCTION, AND INDUCTION.
RX PubMed=29784839; DOI=10.1128/aac.00591-18;
RA Goemaere B., Lagrou K., Spriet I., Hendrickx M., Becker P.;
RT "bloodstream isolates and fluconazole resistance affected by prolonged
RT exposure: a 12-year single-center study in Belgium.";
RL Antimicrob. Agents Chemother. 0:0-0(2018).
CC -!- FUNCTION: Pleiotropic ABC efflux transporter that transports and
CC confers resistance to structurally and functionally unrelated compounds
CC including rhodamine 6G, Nile red, caspofungin, cycloheximide, or azoles
CC such as fluconazole, itraconazole, ketoconazole, posaconazole,
CC voriconazole, and isavuconazole (PubMed:10543759, PubMed:12244114,
CC PubMed:15105111, PubMed:15105136, PubMed:15388433, PubMed:15498768,
CC PubMed:16803598, PubMed:17581937, PubMed:18591262, PubMed:20038613,
CC PubMed:20450660, PubMed:21134356, PubMed:21408004, PubMed:22788839,
CC PubMed:26482310, PubMed:27486188, PubMed:29371812, PubMed:29784839).
CC Chlorbromuron, itraconazole, yohimbine, ketoconazole, miconazole,
CC clotrimazole, DE-11, tamoxifen, quinidine, verapamil can compete for
CC rhodamine 6G's binding site(s) while compounds such as propanil,
CC chloramphenicol, benomyl, voriconazole, tritylimidazole, ketoconazole,
CC miconazole, tamoxifen, gefitinib shared binding site(s) with
CC fluconazole. Nile red mediated efflux appears to be relatively more
CC specific since only five compounds such as ZW3-12, rhodamine 123,
CC miconazole, clotrimazole, and itraconazole can inhibit its accumulation
CC (PubMed:21134356). Does not use as substrates 4-nitroquinoline 1-oxide
CC (4-NQO) and disulfiram (PubMed:21134356). Does not play a role in the
CC azole resistance in mature biofilms (PubMed:18651314).
CC {ECO:0000269|PubMed:10543759, ECO:0000269|PubMed:12244114,
CC ECO:0000269|PubMed:15105111, ECO:0000269|PubMed:15105136,
CC ECO:0000269|PubMed:15388433, ECO:0000269|PubMed:15498768,
CC ECO:0000269|PubMed:16803598, ECO:0000269|PubMed:17581937,
CC ECO:0000269|PubMed:18591262, ECO:0000269|PubMed:18651314,
CC ECO:0000269|PubMed:20038613, ECO:0000269|PubMed:20450660,
CC ECO:0000269|PubMed:21134356, ECO:0000269|PubMed:21408004,
CC ECO:0000269|PubMed:22788839, ECO:0000269|PubMed:26482310,
CC ECO:0000269|PubMed:27486188, ECO:0000269|PubMed:29371812,
CC ECO:0000269|PubMed:29784839}.
CC -!- ACTIVITY REGULATION: Inhibited by clorgyline (PubMed:22203607).
CC Inhibited by RC21v3, a 4-methoxy-2,3,6-trimethylbenzenesulphonyl
CC derivative of the D-octapeptide D-FFKWQRRR, via the interaction with
CC the ectodomain (PubMed:22788839). FK506, enniatin, milbemycin alpha-11,
CC and milbemycin beta-9 also inhibit CDR1 activity (PubMed:22788839).
CC Inhibited by milbemycin A3/A4 oxim derivatives (PubMed:23208712,
CC PubMed:24838041). {ECO:0000269|PubMed:22203607,
CC ECO:0000269|PubMed:22788839, ECO:0000269|PubMed:23208712,
CC ECO:0000269|PubMed:24838041}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12244114,
CC ECO:0000269|PubMed:21134356}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- INDUCTION: Azole exposure induced expression 4- to 12-fold via
CC regulation by the transcription factor PDR1 that stimulates gene
CC expression via binding to elements called pleiotropic drug response
CC elements (PDREs) (PubMed:12458010, PubMed:10543759, PubMed:16803598,
CC PubMed:21193550, PubMed:21408004, PubMed:23979762, PubMed:24645630,
CC PubMed:19148266, PubMed:21131438, PubMed:29464833). Expression is
CC highly up-regulated in azole-resistant isolates (PubMed:10543759,
CC PubMed:16735426, PubMed:16891541, PubMed:17158937, PubMed:17581937,
CC PubMed:18591262, PubMed:18782778, PubMed:19380598, PubMed:19196495,
CC PubMed:20038613, PubMed:20450660, PubMed:21134356, PubMed:25818698,
CC PubMed:27486188, PubMed:28894714, PubMed:29371812, PubMed:29784839).
CC Loss of mitochondrial functions leads to increased expression
CC (PubMed:21321146). Expression is temporary increased during the
CC intermediate phase of biofilm development (PubMed:18651314). Expression
CC is down-regulated by the transcription factor STB5 (PubMed:23229483).
CC Expression is negatively regulated by the transcription factor JJJ1 via
CC inactivation of the PDR1 transcriptional pathway (PubMed:29507891).
CC Expression is also decreased by amphotericin B in voriconazole-
CC resistant strains (PubMed:21282443). {ECO:0000269|PubMed:10543759,
CC ECO:0000269|PubMed:12458010, ECO:0000269|PubMed:16735426,
CC ECO:0000269|PubMed:16803598, ECO:0000269|PubMed:16891541,
CC ECO:0000269|PubMed:17158937, ECO:0000269|PubMed:17581937,
CC ECO:0000269|PubMed:18591262, ECO:0000269|PubMed:18651314,
CC ECO:0000269|PubMed:18782778, ECO:0000269|PubMed:19148266,
CC ECO:0000269|PubMed:19196495, ECO:0000269|PubMed:19380598,
CC ECO:0000269|PubMed:20038613, ECO:0000269|PubMed:20450660,
CC ECO:0000269|PubMed:21131438, ECO:0000269|PubMed:21134356,
CC ECO:0000269|PubMed:21193550, ECO:0000269|PubMed:21282443,
CC ECO:0000269|PubMed:21321146, ECO:0000269|PubMed:21408004,
CC ECO:0000269|PubMed:23229483, ECO:0000269|PubMed:23979762,
CC ECO:0000269|PubMed:24645630, ECO:0000269|PubMed:25818698,
CC ECO:0000269|PubMed:27486188, ECO:0000269|PubMed:28894714,
CC ECO:0000269|PubMed:29371812, ECO:0000269|PubMed:29464833,
CC ECO:0000269|PubMed:29507891, ECO:0000269|PubMed:29784839}.
CC -!- PTM: Phosphorylated at Ser-307 and Ser-484. Ser-307 and Ser-484 are
CC dephosphorylated on glucose depletion and independently
CC rephosphorylated during glucose exposure or under stress.
CC {ECO:0000269|PubMed:12244114, ECO:0000269|PubMed:15498768}.
CC -!- DISRUPTION PHENOTYPE: Leads to susceptibility to the antifungal azole
CC derivatives in azole-resistant clinical isolates (PubMed:10543759,
CC PubMed:16803598). Suppresses the development of high-frequency azole
CC resistance (HFAR) in a medium containing fluconazole (PubMed:11257032).
CC {ECO:0000269|PubMed:10543759, ECO:0000269|PubMed:11257032,
CC ECO:0000269|PubMed:16803598}.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. {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; CR380959; CAG62397.1; -; Genomic_DNA.
DR RefSeq; XP_449421.1; XM_449421.1.
DR AlphaFoldDB; Q6FK23; -.
DR SMR; Q6FK23; -.
DR STRING; 5478.XP_449421.1; -.
DR iPTMnet; Q6FK23; -.
DR EnsemblFungi; CAG62397; CAG62397; CAGL0M01760g.
DR GeneID; 2891191; -.
DR KEGG; cgr:CAGL0M01760g; -.
DR CGD; CAL0136775; CDR1.
DR VEuPathDB; FungiDB:CAGL0M01760g; -.
DR eggNOG; KOG0065; Eukaryota.
DR HOGENOM; CLU_000604_35_0_1; -.
DR InParanoid; Q6FK23; -.
DR OMA; IAEATLC; -.
DR Proteomes; UP000002428; Chromosome M.
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:0008559; F:ABC-type xenobiotic transporter activity; IDA:CGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IEA:EnsemblFungi.
DR GO; GO:0045117; P:azole transmembrane transport; IMP:CGD.
DR GO; GO:0030003; P:cellular cation homeostasis; IEA:EnsemblFungi.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:EnsemblFungi.
DR GO; GO:1990961; P:xenobiotic detoxification by transmembrane export across the plasma membrane; ISA:CGD.
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; IPR043926; ABCG_dom.
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; PF19055; ABC2_membrane_7; 1.
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 ATP-binding; Cell membrane; Glycoprotein; Membrane; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Repeat; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..1499
FT /note="Pleiotropic ABC efflux transporter of multiple drugs
FT CDR1"
FT /id="PRO_0000445080"
FT TRANSMEM 510..530
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 548..568
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 597..617
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 622..642
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 654..674
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 763..783
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1193..1213
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1228..1248
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1278..1298
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1314..1334
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1342..1362
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1466..1486
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 146..399
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 857..1099
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 1..29
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 9..25
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 893..900
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT MOD_RES 307
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:15498768"
FT MOD_RES 484
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:15498768"
FT CARBOHYD 24
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 96
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 99
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 323
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 537
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 813
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1159
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1301
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1412
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT MUTAGEN 188
FT /note="C->A: Leads to loss of resistance to cycloheximide,
FT DE-11, fluconazole, voriconazole, and ketoconazole."
FT /evidence="ECO:0000269|PubMed:21134356"
FT MUTAGEN 307
FT /note="S->A: Fails to efflux the substrate rhodamine 6G,
FT and increases fluconazole susceptibility; when associated
FT with A-484."
FT /evidence="ECO:0000269|PubMed:15498768"
FT MUTAGEN 484
FT /note="S->A: Fails to efflux the substrate rhodamine 6G,
FT and increases fluconazole susceptibility; when associated
FT with A-307."
FT /evidence="ECO:0000269|PubMed:15498768"
FT MUTAGEN 660
FT /note="S->A: Leads to loss of resistance to cycloheximide,
FT DE-11, fluconazole, voriconazole, and ketoconazole."
FT /evidence="ECO:0000269|PubMed:21134356"
FT MUTAGEN 773
FT /note="Missing: Leads to loss of resistance to
FT cycloheximide, DE-11, fluconazole, voriconazole, and
FT ketoconazole."
FT /evidence="ECO:0000269|PubMed:21134356"
SQ SEQUENCE 1499 AA; 169312 MW; 5F395297D29AAE84 CRC64;
MSLASDKKDA DVASTTTTAQ DDDNLSTYHG FDHHVQDQVR QLARTLTQQS SLHQKKEHTL
PEEGINPIFT NTEADDYNPR LDPTSDEFSS AEWVQNMSNI SNSDPDYYKP YSLGCYWKDL
VATGESADIE YQANFLNGPY KGLKTVYNTV VPSTASSKDK NFKILKSMEG AVNPGELLVV
LGRPGSGCTT LLKSISSNTH GFNIAKESTI SYSGMTPNDI RKHFRGEVVY NAEADIHLPH
LTVYQTLLTV ARLKTPQNRL KGIDRETYAR HLTEVAMATF GLSHTRNTKV GNDLVRGVSG
GERKRVSIAE VSICGSKFQC WDNATRGLDS ATALEFIRAL KVQASISNAA ATVAIYQCSQ
DAYDLFDKVC VLYDGYQIYF GPAGKAKEYF QKMGYVSPER QTTADFLTAV TSPSERIINQ
DYINRGIFVP QTPKEMWEYW RASEDHADLI KEIDSKLSDN YDANLAEIKD AHVARQSKRA
RPSSPYTVSY GMQIKYLLIR NFWRIKQSSG VTLFMVIGNS SMAFILGSMF YKVMKHNTTS
TFYFRGAAMF FAVLFNAFSS LLEIFSLFEA RPITEKHRTY SLYHPSADAF ASILSEVPAK
LITAVCFNII YYFLVNFRRN GGVFFFYFLI NIVAVFAMSH LFRCVGSVSK TLSAAMVPAS
MLLLGLSMYS GFAIPRTKIL GWSKWIWYIN PLAYLFESLM INEFHDRKFP CSQYIPSGSV
YNNVPADSRI CSSVGAIRGN DYVLGDDFLR ESYSYLHKHK WRGFGIGLAY VIFFLVLYLI
LCEYNEGAKQ KGEILVFPQN IVRRMKKERK LKNVSSDNDV EIGDVSDISD KKILADSSDE
SEESGANIGL SQSEAIFHWR NLCYDVQIKK ETRRILNNVD GWVKPGTLTA LMGASGAGKT
TLLDCLAERV TMGVITGEVS VDGKQRDDSF ARSIGYCQQQ DLHLKTSTVR ESLRFSAYLR
QPADVSIEEK NQYVEDVIKI LEMEQYADAV VGVPGEGLNV EQRKRLTIGV ELAAKPKLLV
FLDEPTSGLD SQTAWSICQL MKKLANHGQA ILCTIHQPSA ILMQEFDRLL FLQRGGKTVY
FGDLGDGCKT MIDYFESHGS HKCPPDANPA EWMLEVVGAA PGSHANQDYH EVWRNSDEYQ
KVQEELEWMS NELPKKNTNN SETVHKEFAT GVLYQCKLVS LRLFQQYWRS PDYLWSKFFL
TIFNNIFIGF TFFKADRSLQ GLQNQMLAVF MFTVIFNPLL QQYLPSFVQQ RDLYEARERP
SRTFSWKAFI VSQILVEIPW NILAGTVAFV IYYYAIGFYS NASVAHQLHE RGALFWLFSC
AFYVYIGSLA LFCISFNQVA EAAANMASLM FTLSLSFCGV LVTPNGMPRF WIFMYRVSPL
TYLIDGMLST GVANVAIKCS NYELLRFSPA ANLTCGEYLG PYLQTVKTGY IVDPSATDTC
ELCPYSHTND FLSSVSSKYS RRWRNWGIFI CYIAFNYIAG IFLYWLARVP KKSGKLAKK
