TPO3_CANGA
ID TPO3_CANGA Reviewed; 630 AA.
AC Q6FQ03;
DT 28-FEB-2018, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2004, sequence version 1.
DT 25-MAY-2022, entry version 88.
DE RecName: Full=Multidrug transporter TPO3 {ECO:0000303|PubMed:24576949};
DE AltName: Full=Drug:H(+) antiporter TPO3 {ECO:0000303|PubMed:27148215};
DE Short=DHA TPO3 {ECO:0000303|PubMed:27148215};
DE AltName: Full=Polyamine transporter 3 {ECO:0000303|PubMed:24576949};
GN Name=TPO3 {ECO:0000303|PubMed:24576949}; OrderedLocusNames=CAGL0I10384g;
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, SUBCELLULAR LOCATION, FUNCTION, AND INDUCTION.
RX PubMed=24576949; DOI=10.1093/jac/dku044;
RA Costa C., Nunes J., Henriques A., Mira N.P., Nakayama H., Chibana H.,
RA Teixeira M.C.;
RT "Candida glabrata drug:H+ antiporter CgTpo3 (ORF CAGL0I10384g): role in
RT azole drug resistance and polyamine homeostasis.";
RL J. Antimicrob. Chemother. 69:1767-1776(2014).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
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).
CC -!- FUNCTION: Cell membrane polyamine/proton antiporter, involved in the
CC detoxification of excess polyamines in the cytoplasm (PubMed:24576949,
CC PubMed:27148215). Involved in the resistance to the imidazole
CC antifungal drugs tioconazole, miconazole, clotrimazole and
CC ketoconazole; to the triazole fluconazole; but not to the antifungals
CC flucytosine or amphotericin B (PubMed:24576949). Plays a role in
CC spermine homeostasis, but spermine accumulation in response to
CC clotrimazole is independent of TPO3 (PubMed:24576949, PubMed:27148215).
CC {ECO:0000269|PubMed:24576949, ECO:0000269|PubMed:27148215}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:24576949};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- INDUCTION: Expression is up-regulated under spermine stress and depends
CC on the pleiotropic drug resistance transcription factor PDR1
CC (PubMed:24576949). {ECO:0000269|PubMed:24576949}.
CC -!- DISRUPTION PHENOTYPE: Increases the susceptibility to the imidazole
CC antifungal drugs tioconazole, miconazole, clotrimazole and
CC ketoconazole; to the triazole fluconazole; but not to the antifungals
CC flucytosine or amphotericin B (PubMed:24576949, PubMed:27148215).
CC {ECO:0000269|PubMed:24576949, ECO:0000269|PubMed:27148215}.
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; CR380955; CAG60636.1; -; Genomic_DNA.
DR RefSeq; XP_447691.1; XM_447691.1.
DR AlphaFoldDB; Q6FQ03; -.
DR STRING; 5478.XP_447691.1; -.
DR EnsemblFungi; CAG60636; CAG60636; CAGL0I10384g.
DR GeneID; 2889240; -.
DR KEGG; cgr:CAGL0I10384g; -.
DR CGD; CAL0130223; TPO3.
DR VEuPathDB; FungiDB:CAGL0I10384g; -.
DR eggNOG; KOG0255; Eukaryota.
DR HOGENOM; CLU_008455_11_5_1; -.
DR InParanoid; Q6FQ03; -.
DR OMA; FPCIALF; -.
DR Proteomes; UP000002428; Chromosome I.
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:0000296; P:spermine transport; 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..630
FT /note="Multidrug transporter TPO3"
FT /id="PRO_0000443416"
FT TRANSMEM 190..210
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 222..242
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 252..272
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 282..302
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 312..332
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 342..362
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 423..443
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 453..473
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 494..514
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 519..539
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 553..575
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 587..607
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..46
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 107..157
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..36
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 107..137
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 135
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 630 AA; 70068 MW; B336BAD1B3150B22 CRC64;
MVDQESLVSF SSETSQSINS DIDIESQQQP RQYIPSNEKD GNKERLHLTR TETVKSLQEM
GMTQDAPIPD VNAPQTTTKN AIFPEEYTME TPTGLVPVAT LQSLGRTSTA ISKSRTRQIE
RSVSRRSQNI AASSNSSNKE ELEDEEEVSS DMSNQQPELD PEIEFVTFVT GDPTNPHNWP
LWIRWAYTVI LSCLVICVAY GSACITGGLF TVQEQYHVGL EAAILSCSLM VIGFSLGPLI
WSPVSDLYGR RLAYFISMGL YTIFNIPCAL SPNLGGLLVC RFLCGVFSSS GLCLVGGSIA
DMFPSETRGR AIAFFAFAPY TGPIIGPLVN GFVSVCTRRM DLIFWINMAF AGVMWIIVAF
IPETYAPVIL KWRAAKLRKE TGNPKIMTEQ EAQGVSVNEM MKACLIRPLY FAVTEPVLDL
TCFYVCLIYS LLYAFFFAFP VVFGELYGYK DNLIGLMFIP ILIGATMALA TTFYCENEYL
KLVKKRKPTP EDRLFGAMIG APFAAAALWI LGATSYKHII WVGPASSGLA FGYGMVLIYY
SLNNYIIDCY VQYASSALAT KVFLRSAGGA AFPLFTNQMY HKLGLQWASW LLAFISTAMI
LLPFGFYYYG KTLRHKLSKK DYSIDTIEGY
