FLU1_CANAL
ID FLU1_CANAL Reviewed; 610 AA.
AC G1UB37; Q5AGW2; Q9HF77;
DT 10-OCT-2018, integrated into UniProtKB/Swiss-Prot.
DT 19-OCT-2011, sequence version 1.
DT 03-AUG-2022, entry version 67.
DE RecName: Full=Major facilitator superfamily multidrug transporter FLU1 {ECO:0000303|PubMed:11065353};
DE AltName: Full=Fluconazole resistance protein 1 {ECO:0000303|PubMed:11065353};
GN Name=FLU1 {ECO:0000303|PubMed:11065353};
GN OrderedLocusNames=CAALFM_C701520WA; ORFNames=orf19.6577;
OS Candida albicans (strain SC5314 / ATCC MYA-2876) (Yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Debaryomycetaceae; Candida/Lodderomyces clade; Candida.
OX NCBI_TaxID=237561;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=11065353; DOI=10.1099/00221287-146-11-2743;
RA Calabrese D., Bille J., Sanglard D.;
RT "A novel multidrug efflux transporter gene of the major facilitator
RT superfamily from Candida albicans (FLU1) conferring resistance to
RT fluconazole.";
RL Microbiology 146:2743-2754(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=15937140; DOI=10.1534/genetics.104.034652;
RA Chibana H., Oka N., Nakayama H., Aoyama T., Magee B.B., Magee P.T.,
RA Mikami Y.;
RT "Sequence finishing and gene mapping for Candida albicans chromosome 7 and
RT syntenic analysis against the Saccharomyces cerevisiae genome.";
RL Genetics 170:1525-1537(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=15123810; DOI=10.1073/pnas.0401648101;
RA Jones T., Federspiel N.A., Chibana H., Dungan J., Kalman S., Magee B.B.,
RA Newport G., Thorstenson Y.R., Agabian N., Magee P.T., Davis R.W.,
RA Scherer S.;
RT "The diploid genome sequence of Candida albicans.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:7329-7334(2004).
RN [4]
RP GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=17419877; DOI=10.1186/gb-2007-8-4-r52;
RA van het Hoog M., Rast T.J., Martchenko M., Grindle S., Dignard D.,
RA Hogues H., Cuomo C., Berriman M., Scherer S., Magee B.B., Whiteway M.,
RA Chibana H., Nantel A., Magee P.T.;
RT "Assembly of the Candida albicans genome into sixteen supercontigs aligned
RT on the eight chromosomes.";
RL Genome Biol. 8:RESEARCH52.1-RESEARCH52.12(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=24025428; DOI=10.1186/gb-2013-14-9-r97;
RA Muzzey D., Schwartz K., Weissman J.S., Sherlock G.;
RT "Assembly of a phased diploid Candida albicans genome facilitates allele-
RT specific measurements and provides a simple model for repeat and indel
RT structure.";
RL Genome Biol. 14:RESEARCH97.1-RESEARCH97.14(2013).
RN [6]
RP FUNCTION.
RX PubMed=11181345; DOI=10.1128/aac.45.3.696-700.2001;
RA Marchetti O., Majcherczyk P.A., Glauser M.P., Bille J., Moreillon P.,
RA Sanglard D.;
RT "Sensitive bioassay for determination of fluconazole concentrations in
RT plasma using a Candida albicans mutant hypersusceptible to azoles.";
RL Antimicrob. Agents Chemother. 45:696-700(2001).
RN [7]
RP INDUCTION.
RX PubMed=19395663; DOI=10.1128/ec.00002-09;
RA Znaidi S., Barker K.S., Weber S., Alarco A.M., Liu T.T., Boucher G.,
RA Rogers P.D., Raymond M.;
RT "Identification of the Candida albicans Cap1p regulon.";
RL Eukaryot. Cell 8:806-820(2009).
RN [8]
RP INDUCTION.
RX PubMed=19420894; DOI=10.1248/yakushi.129.623;
RA Zhang H., Gao A., Li F., Zhang G., Ho H.I., Liao W.;
RT "Mechanism of action of tetrandrine, a natural inhibitor of Candida
RT albicans drug efflux pumps.";
RL Yakugaku Zasshi 129:623-630(2009).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23380720; DOI=10.1128/aac.02295-12;
RA Li R., Kumar R., Tati S., Puri S., Edgerton M.;
RT "Candida albicans flu1-mediated efflux of salivary histatin 5 reduces its
RT cytosolic concentration and fungicidal activity.";
RL Antimicrob. Agents Chemother. 57:1832-1839(2013).
RN [10]
RP INDUCTION.
RX PubMed=23769565;
RA Guo H., Zhang X.L., Gao L.Q., Li S.X., Song Y.J., Zhang H.;
RT "Alcohol dehydrogenase I expression correlates with CDR1, CDR2 and FLU1
RT expression in Candida albicans from patients with vulvovaginal
RT candidiasis.";
RL Chin. Med. J. 126:2098-2102(2013).
RN [11]
RP INDUCTION.
RX PubMed=23527892; DOI=10.3109/13880209.2013.764537;
RA Zhang X., Guo H., Gao L., Song Y., Li S., Zhang H.;
RT "Molecular mechanisms underlying the tetrandrine-mediated reversal of the
RT fluconazole resistance of Candida albicans.";
RL Pharm. Biol. 51:749-752(2013).
RN [12]
RP INDUCTION.
RX PubMed=24962255; DOI=10.1111/myc.12204;
RA Zhang J.Y., Liu J.H., Liu F.D., Xia Y.H., Wang J., Liu X., Zhang Z.Q.,
RA Zhu N., Yan Y., Ying Y., Huang X.T.;
RT "Vulvovaginal candidiasis: species distribution, fluconazole resistance and
RT drug efflux pump gene overexpression.";
RL Mycoses 57:584-591(2014).
RN [13]
RP FUNCTION, AND INDUCTION.
RX PubMed=28953977; DOI=10.1371/journal.ppat.1006655;
RA Hampe I.A.I., Friedman J., Edgerton M., Morschhaeuser J.;
RT "An acquired mechanism of antifungal drug resistance simultaneously enables
RT Candida albicans to escape from intrinsic host defenses.";
RL PLoS Pathog. 13:E1006655-E1006655(2017).
CC -!- FUNCTION: Major facilitator superfamily transporter that mediates
CC resistance to structurally and functionally unrelated compounds
CC including cycloheximide but also azoles such as fuconazole,
CC ketoconazole and itraconazole (PubMed:11065353, PubMed:11181345).
CC Mediates also efflux of histatin 5, a salivary human antimicrobial
CC peptide, and is responsible for reduction of its toxicity in C.albicans
CC (PubMed:23380720, PubMed:28953977). {ECO:0000269|PubMed:11065353,
CC ECO:0000269|PubMed:11181345, ECO:0000269|PubMed:23380720,
CC ECO:0000269|PubMed:28953977}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- INDUCTION: Expression is positively regulated by the CAP1 transcription
CC activator (PubMed:19395663). Expression is also regulated by the MRR1
CC transcription factor (PubMed:28953977). Expression is inhibited by
CC tetrandrine (TET), a compound known to act in a synergistic manner with
CC fluconazole (PubMed:19420894, PubMed:23527892). Expression is increased
CC in clinical azole-resistant isolates (PubMed:23769565,
CC PubMed:24962255). {ECO:0000269|PubMed:19395663,
CC ECO:0000269|PubMed:19420894, ECO:0000269|PubMed:23527892,
CC ECO:0000269|PubMed:23769565, ECO:0000269|PubMed:24962255,
CC ECO:0000269|PubMed:28953977}.
CC -!- DISRUPTION PHENOTYPE: Increases the susceptibility to mycophenolic
CC acid, fuconazole, ketoconazole and itraconazole (PubMed:11065353).
CC Reduces the efflux of spermidine as well as of histatin 5, a salivary
CC human antimicrobial peptide that is toxic to the opportunistic yeast
CC C.albicans (PubMed:23380720). Leads also to reduced biofilm formation
CC (PubMed:23380720). {ECO:0000269|PubMed:11065353,
CC ECO:0000269|PubMed:23380720}.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily. DHA1 family.
CC Polyamines/proton antiporter (TC 2.A.1.2.16) subfamily. {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; AF188621; AAF99573.1; -; Genomic_DNA.
DR EMBL; AP006852; BAE44672.1; -; Genomic_DNA.
DR EMBL; CP017629; AOW30519.1; -; Genomic_DNA.
DR RefSeq; XP_721413.1; XM_716320.1.
DR AlphaFoldDB; G1UB37; -.
DR STRING; 237561.G1UB37; -.
DR PRIDE; G1UB37; -.
DR EnsemblFungi; KHC71836; KHC71836; W5Q_05195.
DR EnsemblFungi; KHC80960; KHC80960; I503_05154.
DR GeneID; 3637048; -.
DR KEGG; cal:CAALFM_C701520WA; -.
DR CGD; CAL0000199735; FLU1.
DR VEuPathDB; FungiDB:C7_01520W_A; -.
DR eggNOG; KOG0255; Eukaryota.
DR HOGENOM; CLU_008455_11_4_1; -.
DR InParanoid; G1UB37; -.
DR OMA; WRWLEYV; -.
DR OrthoDB; 901786at2759; -.
DR Proteomes; UP000000559; Chromosome 7.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:CGD.
DR GO; GO:0022857; F:transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0042910; F:xenobiotic transmembrane transporter activity; IMP:CGD.
DR GO; GO:0015903; P:fluconazole transport; IGI:CGD.
DR GO; GO:0015833; P:peptide transport; IMP:CGD.
DR GO; GO:0015848; P:spermidine transport; IMP:CGD.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
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 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..610
FT /note="Major facilitator superfamily multidrug transporter
FT FLU1"
FT /id="PRO_0000445105"
FT TRANSMEM 165..185
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 209..229
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 231..251
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 262..282
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 292..312
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 323..343
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 408..428
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 437..457
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 478..498
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 507..527
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 530..550
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 573..593
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 47..74
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 3
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 21
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 568
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 610 AA; 67607 MW; 865D5F028786CF91 CRC64;
MNNNTNSNHN DIAPEATITQ NTTTSVSNDE LQHITNNNNV NVQSYVGPTD SVESSSNTAD
EENEINSFNA QNVKDYEANV GGELPPDDEL SRIESNTELS RRATRSIMNT ESLLRTASQS
SKPLPPMGGG KEYPPMLGSR DPYVVAFDGP DDPDHPHNYP TWKKILYCAS VGLAALSVSM
GSAMFSQASA DIMQIYHIGW TPATLTTSLF VFGFASGPVI YGPLSELFGR KLVMVPSCLG
YVCFSFAVAT AKDIQTIMIC RFFAGFIGAA PLVVAPAVMA DMFNNRYRGT AIAIFSMLLF
GGPMLAPILG AFTVKNSALG WRWTSYFCGI IGSLALFMNT FLLQETHHPL ILTRRAEELR
RRTGNWGIYA PHEELKLSMK EIVENNIARP LKMLFTEPIL FLVSLYNAFI YGMLYLFLTA
IPLIFLGEYH FVQGVAELPY LAMLIGILIG GGMIMLFEKR YIKAMEDNGG KIIPEKRLEP
MMVGGFTFVI GIFWLGWTGN YPQHVHWIVP VIGAAFVGNG LMLIFLPCFN YIIDCYLLYA
ATALAGNTFI RSAFGAVFPL FARQMFTNLT IKWASTLLGC IGILLLPMPF VFYYYGKSLR
HKSKFAFVLE
