ID   TPO11_CANGA             Reviewed;         567 AA.
AC   Q6FTB1;
DT   28-FEB-2018, integrated into UniProtKB/Swiss-Prot.
DT   19-JUL-2004, sequence version 1.
DT   03-AUG-2022, entry version 93.
DE   RecName: Full=Multidrug transporter TPO1_1 {ECO:0000303|PubMed:26512119};
DE   AltName: Full=Clotrimazole exporter TPO1_1 {ECO:0000303|PubMed:26512119};
DE   AltName: Full=Drug:H(+) antiporter TPO1_1 {ECO:0000303|PubMed:27148215};
DE            Short=DHA TPO1_1 {ECO:0000303|PubMed:27148215};
GN   Name=TPO1_1 {ECO:0000303|PubMed:26512119}; OrderedLocusNames=CAGL0G03927g;
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   DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION.
RX   PubMed=26512119; DOI=10.1074/mcp.m114.045344;
RA   Pais P., Costa C., Pires C., Shimizu K., Chibana H., Teixeira M.C.;
RT   "Membrane proteome-wide response to the antifungal drug clotrimazole in
RT   Candida glabrata: role of the transcription factor CgPdr1 and the drug:H+
RT   antiporters CgTpo1_1 and CgTpo1_2.";
RL   Mol. Cell. Proteomics 15:57-72(2016).
RN   [3]
RP   FUNCTION.
RX   PubMed=27148215; DOI=10.3389/fmicb.2016.00526;
RA   Costa C., Ribeiro J., Miranda I.M., Silva-Dias A., Cavalheiro M.,
RA   Costa-de-Oliveira S., Rodrigues A.G., Teixeira M.C.;
RT   "Clotrimazole drug resistance in Candida glabrata clinical isolates
RT   correlates with increased expression of the drug:H(+) antiporters CgAqr1,
RT   CgTpo1_1, CgTpo3, and CgQdr2.";
RL   Front. Microbiol. 7:526-526(2016).
RN   [4]
RP   DISRUPTION PHENOTYPE, AND FUNCTION.
RX   PubMed=27780306; DOI=10.1111/cmi.12686;
RA   Santos R., Costa C., Mil-Homens D., Romao D., de Carvalho C.C., Pais P.,
RA   Mira N.P., Fialho A.M., Teixeira M.C.;
RT   "The multidrug resistance transporters CgTpo1_1 and CgTpo1_2 play a role in
RT   virulence and biofilm formation in the human pathogen Candida glabrata.";
RL   Cell. Microbiol. 19:0-0(2017).
CC   -!- FUNCTION: Multidrug resistance transporter involved in resistance to
CC       azole antifungal drugs such as the imidazoles miconazole, ketoconazole,
CC       and tioconazole; as well as the triazoles itraconazole and fluconazole
CC       (PubMed:26512119). Also plays a role in the resistance to other
CC       antifungal drug families such as the polyene amphotericin B, the
CC       pyrimide analog flucytosine, the fungicide mancozeb, and the polyamine
CC       spermine (PubMed:26512119). Decreases the intracellular accumulation of
CC       clotrimazole by mediating its extrusion from cells (PubMed:26512119,
CC       PubMed:27148215). Involved in virulence by confering resistance to the
CC       human antimicrobial peptide histatin-5 (PubMed:27780306).
CC       {ECO:0000269|PubMed:26512119, ECO:0000269|PubMed:27148215,
CC       ECO:0000269|PubMed:27780306}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:26512119};
CC       Multi-pass membrane protein {ECO:0000255}.
CC   -!- INDUCTION: Expression is up-regulated by clotrimazole
CC       (PubMed:26512119). {ECO:0000269|PubMed:26512119}.
CC   -!- DISRUPTION PHENOTYPE: Leads to intracellular accumulation of
CC       clotrimazole and increases the susceptibility to clotrimazole but also
CC       to other imidazoles such as miconazole, ketoconazole, and tioconazole;
CC       as well as triazoles such as itraconazole and fluconazole
CC       (PubMed:26512119). Increases also susceptibility to other antifungal
CC       drug families such as the polyene amphotericin B, the pyrimide analog
CC       flucytosine, the fungicide mancozeb, and the polyamine spermine
CC       (PubMed:26512119). Decreases virulence in a Galleria mellonella model
CC       of infection (PubMed:27780306). {ECO:0000269|PubMed:26512119,
CC       ECO:0000269|PubMed:27780306}.
CC   -!- SIMILARITY: Belongs to the major facilitator superfamily. DHA1 family.
CC       Polyamines/proton antiporter (TC 2.A.1.2.16) subfamily. {ECO:0000305}.
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DR   EMBL; CR380953; CAG59460.1; -; Genomic_DNA.
DR   RefSeq; XP_446533.1; XM_446533.1.
DR   AlphaFoldDB; Q6FTB1; -.
DR   STRING; 5478.XP_446533.1; -.
DR   EnsemblFungi; CAG59460; CAG59460; CAGL0G03927g.
DR   GeneID; 2888403; -.
DR   KEGG; cgr:CAGL0G03927g; -.
DR   CGD; CAL0137711; TPO1_1.
DR   VEuPathDB; FungiDB:CAGL0G03927g; -.
DR   eggNOG; KOG0255; Eukaryota.
DR   HOGENOM; CLU_008455_11_4_1; -.
DR   InParanoid; Q6FTB1; -.
DR   PHI-base; PHI:6625; -.
DR   Proteomes; UP000002428; Chromosome G.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005886; C:plasma membrane; IDA:CGD.
DR   GO; GO:0022857; F:transmembrane transporter activity; IEA:InterPro.
DR   Gene3D; 1.20.1250.20; -; 1.
DR   InterPro; IPR011701; MFS.
DR   InterPro; IPR020846; MFS_dom.
DR   InterPro; IPR036259; MFS_trans_sf.
DR   Pfam; PF07690; MFS_1; 1.
DR   SUPFAM; SSF103473; SSF103473; 1.
DR   PROSITE; PS50850; MFS; 1.
PE   2: Evidence at transcript level;
KW   Cell membrane; Glycoprotein; Membrane; Reference proteome; Transmembrane;
KW   Transmembrane helix; Transport; Virulence.
FT   CHAIN           1..567
FT                   /note="Multidrug transporter TPO1_1"
FT                   /id="PRO_0000443414"
FT   TRANSMEM        128..148
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        157..177
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        194..214
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        224..244
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        253..273
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        283..303
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        358..378
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        396..416
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        436..456
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        471..491
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        498..520
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        531..551
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REGION          1..71
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        10..32
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        44..69
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        120
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   567 AA;  62560 MW;  D2B173C5C7B0F47F CRC64;
     MVEEISPKYT NEQAEASSSS SSSVSGEPKD FSGSLENQED LGELIERTNT MTSGAESKVE
     TNRRMSRILT GTQDDPEKIA IDYSNCPPMG GDRPFPPALP EQSQFEVTFD GPNDPIHPFN
     WSMKTKTIIC IVLCLNCICI SMGSSIFASG VPQICKIYHV IPVVAILGVT LYVFGFAASP
     VIYAPLSEVY GRRGVLVISA FGFAVFQFAV ATSKDLQSIM ICRFFGGLIG AAPMAVVPAA
     FADMFDVRVR GKAICLFSLG VFVGPILSPV MGSYIAQRTT WRWLEYVTGC FASALFVAVA
     LTFKETHHPT ILVQKAKEMR KSTNNWGIHA AHEHVELSVS EIAKKTITRP IKMLFTEPLL
     LIITIYNSFV YGILYLMLEA YPIVFVEGYG FEANGELPYI ALIIGMLVCT AFLWYFENDY
     LKRIQKAGKL VPEARLIPMV YAGVIFPIGI LWFCWTGYYP HKIHWMCPTV AGSFIGFGLM
     GIFLPCLNYI IESYLPLAAS AVAANTFMRS AFGAVFPLFA GYMFHGMGTG WAGLLLGLFA
     AALIPVPLFF LKYGERIRKN SKDAYYA