TPO12_CANGA
ID TPO12_CANGA Reviewed; 577 AA.
AC Q6FV98;
DT 28-FEB-2018, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 98.
DE RecName: Full=Multidrug transporter TPO1_2 {ECO:0000303|PubMed:26512119};
DE AltName: Full=Clotrimazole exporter TPO1_2 {ECO:0000303|PubMed:26512119};
DE AltName: Full=Drug:H(+) antiporter TPO1_2 {ECO:0000303|PubMed:26512119};
DE Short=DHA TPO1_2 {ECO:0000303|PubMed:26512119};
GN Name=TPO1_2 {ECO:0000303|PubMed:26512119}; OrderedLocusNames=CAGL0E03674g;
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 DISRUPTION PHENOTYPE, FUNCTION, AND INDUCTION.
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 Plays a role in biofilm formation (PubMed:27780306).
CC {ECO:0000269|PubMed:26512119, 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). Expression is also up-regulated during biofilm
CC formation (PubMed:27780306). {ECO:0000269|PubMed:26512119,
CC ECO:0000269|PubMed:27780306}.
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, limits the survival when exposed to phagocytosis and
CC impairs biofilm formation by decreasing the expression ofthe adhesin
CC encoding genes ALS1, EAP1, and EPA1 (PubMed:27780306).
CC {ECO:0000269|PubMed:26512119, 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; CR380951; CAG58765.1; -; Genomic_DNA.
DR RefSeq; XP_445846.1; XM_445846.1.
DR AlphaFoldDB; Q6FV98; -.
DR SMR; Q6FV98; -.
DR STRING; 5478.XP_445846.1; -.
DR EnsemblFungi; CAG58765; CAG58765; CAGL0E03674g.
DR GeneID; 2887382; -.
DR KEGG; cgr:CAGL0E03674g; -.
DR CGD; CAL0128758; TPO1_2.
DR VEuPathDB; FungiDB:CAGL0E03674g; -.
DR eggNOG; KOG0255; Eukaryota.
DR HOGENOM; CLU_008455_11_4_1; -.
DR InParanoid; Q6FV98; -.
DR OMA; WRWLEYV; -.
DR PHI-base; PHI:6626; -.
DR Proteomes; UP000002428; Chromosome E.
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 GO; GO:0044010; P:single-species biofilm formation; IMP:CGD.
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.
FT CHAIN 1..577
FT /note="Multidrug transporter TPO1_2"
FT /id="PRO_0000443415"
FT TRANSMEM 137..157
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 167..187
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 204..224
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 234..254
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 263..283
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 293..313
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 368..388
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 406..426
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 446..466
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 475..495
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 504..526
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 541..561
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..63
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 44
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 58
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 577 AA; 63342 MW; 7A864FFFAE95BD26 CRC64;
MSSTSSDRPY DPLAPENEGV ASSDVESTDS GEIRSYGPEE VLKNGSQIKD KGPALSKNST
QTSAVESAVA ANRRLSKILT NTVDEPDVLE VDYSKCPPMG GGRPFPPTLP EKTQFEVTFD
GPNDPLHPFN WPLRKKVMLC IILCLNCISI TMGSSIFATG IRQICEIYHV IPVVAILGIT
LYVLGFAASP VIYAPLSEIY GRRGVLVISS FGFALFNFAV ATAKDLQTIM ICRFFAGFIG
AAPLAVVPAA FADMFDTNIR GKAICLFSLG VFVGPILAPV IGSYITQHTT WRWLEYVIAC
FASAIFVAIL FFFEESHHPS ILVGKAKELR KLTGNWGIHA AHEDVELSVK EIAEKTITRP
IIMLFTEPLL LIVTIYNSFV YGILYLLLEA YPIVFEQGYG FHTNGELPYI SLIIGMAICG
AFIWWMDEDY LRRYRKKGGL VPEARLLPMV VAGIVFPIGI LWFCWTGNYP HKIHWIVPTI
AGAFTGFGLI GIFLPCLNYI IESYLLIAAS AVAANTFMRS GFGAAFPLFA GYMFNGMGVN
YAGLLLGLLA VAMIPVPLLF LKYGPGIRKR SKYAYSL
