FLR1_CANGA
ID FLR1_CANGA Reviewed; 557 AA.
AC Q6FRT6;
DT 28-FEB-2018, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2004, sequence version 1.
DT 25-MAY-2022, entry version 96.
DE RecName: Full=Multidrug transporter FLR1 {ECO:0000303|PubMed:17046176};
DE AltName: Full=Drug:H(+) antiporter FLR1 {ECO:0000303|PubMed:28066366};
DE Short=DHA FLR1 {ECO:0000303|PubMed:28066366};
DE AltName: Full=Flucytosine exporter FLR1 {ECO:0000303|PubMed:28066366};
GN Name=FLR1 {ECO:0000303|PubMed:17046176}; OrderedLocusNames=CAGL0H06017g;
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, AND INDUCTION.
RX PubMed=17046176; DOI=10.1016/j.gene.2006.08.010;
RA Chen K.H., Miyazaki T., Tsai H.F., Bennett J.E.;
RT "The bZip transcription factor Cgap1p is involved in multidrug resistance
RT and required for activation of multidrug transporter gene CgFLR1 in Candida
RT glabrata.";
RL Gene 386:63-72(2007).
RN [3]
RP DISRUPTION PHENOTYPE, FUNCTION, INDUCTION, AND SUBCELLULAR LOCATION.
RX PubMed=28066366; DOI=10.3389/fmicb.2016.02045;
RA Pais P., Pires C., Costa C., Okamoto M., Chibana H., Teixeira M.C.;
RT "Membrane Proteomics analysis of the Candida glabrata response to 5-
RT flucytosine: unveiling the role and regulation of the drug efflux
RT transporters CgFlr1 and CgFlr2.";
RL Front. Microbiol. 7:2045-2045(2016).
CC -!- FUNCTION: Multidrug transporter that confers resistance to 5-
CC flucytosine (5-FC) and clotrimazole (PubMed:28066366). Confers also
CC resistance to benomyl, but not 4-nitroquinoline-N-oxide, cycloheximide,
CC or fluconazole (PubMed:17046176). Plays direct roles in extrusion of 5-
CC flucytosine and clotrimazole (PubMed:28066366).
CC {ECO:0000269|PubMed:17046176, ECO:0000269|PubMed:28066366}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:28066366};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- INDUCTION: Expression is induced by benomyl via positive regulation by
CC the transcription factors AP1 and PDR1 (PubMed:17046176,
CC PubMed:28066366). The promoter contains the YAP1 response element (YRE)
CC 5'-TTAC/GTAA-3' which is recognized by AP1 (PubMed:17046176).
CC {ECO:0000269|PubMed:17046176, ECO:0000269|PubMed:28066366}.
CC -!- DISRUPTION PHENOTYPE: Leads to increased sensitivity to benomyl,
CC diamide, and menadione, but not 4-nitroquinoline-N-oxide,
CC cycloheximide, or fluconazole (PubMed:17046176). Increases the
CC intracellular accumulation of 5-flucytosine and clotrimazole
CC (PubMed:28066366). {ECO:0000269|PubMed:17046176,
CC ECO:0000269|PubMed:28066366}.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily.
CC {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; CR380954; CAG59991.1; -; Genomic_DNA.
DR RefSeq; XP_447058.1; XM_447058.1.
DR AlphaFoldDB; Q6FRT6; -.
DR STRING; 5478.XP_447058.1; -.
DR EnsemblFungi; CAG59991; CAG59991; CAGL0H06017g.
DR GeneID; 2888640; -.
DR KEGG; cgr:CAGL0H06017g; -.
DR CGD; CAL0131618; FLR1.
DR VEuPathDB; FungiDB:CAGL0H06017g; -.
DR eggNOG; KOG0255; Eukaryota.
DR HOGENOM; CLU_008455_11_1_1; -.
DR InParanoid; Q6FRT6; -.
DR OMA; ARPMFIN; -.
DR Proteomes; UP000002428; Chromosome H.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:CGD.
DR GO; GO:0042910; F:xenobiotic transmembrane transporter activity; ISA:CGD.
DR GO; GO:1990961; P:xenobiotic detoxification by transmembrane export across the plasma membrane; 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 InterPro; IPR004734; Multidrug-R.
DR Pfam; PF07690; MFS_1; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR TIGRFAMs; TIGR00880; 2_A_01_02; 1.
DR PROSITE; PS50850; MFS; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Glycoprotein; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..557
FT /note="Multidrug transporter FLR1"
FT /id="PRO_0000443411"
FT TRANSMEM 113..133
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 149..169
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 181..201
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 204..224
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 238..258
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 271..291
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 355..375
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 387..407
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 426..446
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 450..470
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 484..506
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 521..541
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 44..67
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 44..58
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 33
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 48
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 106
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 418
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 557 AA; 62260 MW; 4CC02C49B8428ED9 CRC64;
MNYLHNFKDT LFVDLLEVLN IVTIGEEHVN QLNLSGDASL SASSESSNMS FNSGSEENSQ
EKSVEDLEKQ NCEINIHKNS DKEADTKKDP FLVTFNGEDD PLMPYNWSTN KKALIIIQTM
LLTCVNYMGS SIYTPGQLEI QNEFHVGHVV GTLNLSLYVL GYGLGPIVFS PLTEISSIGR
LPVYMITFFL FTMLQIGCAL APNFAGLVIL RFITGVLCSP ALSTGGATLG DIVSQNYLAL
VLGLWSIGAV AAPVLAPLLG ASMVVAKDWR WIFWLLFFCC CATMLLLTFF FPETSSDTVL
HRKAARIRKL TGDNRYYTEK EREEAQLPKK QFLIETLYRP FSMMITEPIV LAFDLYIALC
YGAFYLFFEA FPIVFGGIYH FTLVEQGLAY FGFCVGCIFA YIILLVFSIK VAAKRFANNT
FTPETTLILA MCIGWCIPLA LFMFGWTAKV HWILPIISEV FFVLGCFNIF QASFSYLAIC
YPKYVASVFA GNGFARSSFA AAFPLFGQAM YNNLGTKNYP VAWGSSLVGF FTIGLWVIPF
VLYKYGPSLR SMSKYNR
