FRE1_CANAL
ID FRE1_CANAL Reviewed; 760 AA.
AC Q5A446; A0A1D8PME9;
DT 07-JAN-2015, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2017, sequence version 2.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=Ferric/cupric reductase transmembrane component 1 {ECO:0000250|UniProtKB:P32791};
DE EC=1.16.1.9 {ECO:0000250|UniProtKB:P32791};
DE AltName: Full=Ferric-chelate reductase 1 {ECO:0000250|UniProtKB:P32791};
DE Flags: Precursor;
GN Name=CFL1 {ECO:0000303|PubMed:10784045}; Synonyms=FRE1;
GN OrderedLocusNames=CAALFM_C405770CA; ORFNames=CaO19.1263, CaO19.8848;
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 [LARGE SCALE GENOMIC DNA].
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 [2]
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 [3]
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 [4]
RP FUNCTION, AND INDUCTION.
RX PubMed=10784045; DOI=10.1099/00221287-146-4-869;
RA Hammacott J.E., Williams P.H., Cashmore A.M.;
RT "Candida albicans CFL1 encodes a functional ferric reductase activity that
RT can rescue a Saccharomyces cerevisiae fre1 mutant.";
RL Microbiology 146:869-876(2000).
RN [5]
RP INDUCTION.
RX PubMed=12760852; DOI=10.1128/aac.47.6.1805-1817.2003;
RA Niewerth M., Kunze D., Seibold M., Schaller M., Korting H.C., Hube B.;
RT "Ciclopirox olamine treatment affects the expression pattern of Candida
RT albicans genes encoding virulence factors, iron metabolism proteins, and
RT drug resistance factors.";
RL Antimicrob. Agents Chemother. 47:1805-1817(2003).
RN [6]
RP INDUCTION.
RX PubMed=15917516; DOI=10.1128/aac.49.6.2226-2236.2005;
RA Liu T.T., Lee R.E., Barker K.S., Lee R.E., Wei L., Homayouni R.,
RA Rogers P.D.;
RT "Genome-wide expression profiling of the response to azole, polyene,
RT echinocandin, and pyrimidine antifungal agents in Candida albicans.";
RL Antimicrob. Agents Chemother. 49:2226-2236(2005).
RN [7]
RP INDUCTION.
RX PubMed=15790671; DOI=10.1093/jac/dki089;
RA Sigle H.C., Thewes S., Niewerth M., Korting H.C., Schafer-Korting M.,
RA Hube B.;
RT "Oxygen accessibility and iron levels are critical factors for the
RT antifungal action of ciclopirox against Candida albicans.";
RL J. Antimicrob. Chemother. 55:663-673(2005).
RN [8]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=25130162; DOI=10.1111/1567-1364.12194;
RA Yu Q., Dong Y., Xu N., Qian K., Chen Y., Zhang B., Xing L., Li M.;
RT "A novel role of the ferric reductase Cfl1 in cell wall integrity,
RT mitochondrial function, and invasion to host cells in Candida albicans.";
RL FEMS Yeast Res. 14:1037-1047(2014).
CC -!- FUNCTION: Ferric reductase responsible for reducing extracellular iron
CC and copper prior to import. Catalyzes the reductive uptake of Fe(3+)-
CC salts and Fe(3+) bound to catecholate or hydroxamate siderophores.
CC Fe(3+) is reduced to Fe(2+), which then dissociates from the
CC siderophore and can be imported by the high-affinity Fe(2+) transport
CC complex in the plasma membrane. Also participates in Cu(2+) reduction
CC and Cu(+) uptake (By similarity). Involved in maintenance of cell wall
CC integrity (CWI), mitochondrial function, and interaction between the
CC pathogen and the host. {ECO:0000250|UniProtKB:P32791,
CC ECO:0000269|PubMed:10784045, ECO:0000269|PubMed:25130162}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 a Fe(II)-siderophore + H(+) + NADP(+) = 2 a Fe(III)-
CC siderophore + NADPH; Xref=Rhea:RHEA:28795, Rhea:RHEA-COMP:11342,
CC Rhea:RHEA-COMP:11344, ChEBI:CHEBI:15378, ChEBI:CHEBI:29033,
CC ChEBI:CHEBI:29034, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.16.1.9;
CC Evidence={ECO:0000250|UniProtKB:P32791};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:P32791};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P32791};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P32791};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:P32791}.
CC -!- INDUCTION: Transcription is negatively regulated by SFU1, copper,
CC amphotericin B, and caspofungin; and induced by ciclopirox olamine.
CC {ECO:0000269|PubMed:10784045, ECO:0000269|PubMed:12760852,
CC ECO:0000269|PubMed:15790671, ECO:0000269|PubMed:15917516}.
CC -!- DISRUPTION PHENOTYPE: Leads to abnormal cell wall composition,
CC decreased ability of adhesion, and hypersensitivity to cell wall
CC stresses. Increases mitochondrial activity and shows abnormal
CC mitochondrial morphology. Results also in up-regulation of the
CC expression of the cell wall integrity (CWI) genes PGA13 and CRH11,
CC enhanded secretion, and decreased ability to invade HeLa cells.
CC {ECO:0000269|PubMed:25130162}.
CC -!- SIMILARITY: Belongs to the ferric reductase (FRE) family.
CC {ECO:0000305}.
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DR EMBL; CP017626; AOW29307.1; -; Genomic_DNA.
DR RefSeq; XP_716571.2; XM_711478.2.
DR AlphaFoldDB; Q5A446; -.
DR SMR; Q5A446; -.
DR STRING; 237561.Q5A446; -.
DR GeneID; 3641810; -.
DR KEGG; cal:CAALFM_C405770CA; -.
DR CGD; CAL0000193490; CFL1.
DR VEuPathDB; FungiDB:C4_05770C_A; -.
DR eggNOG; KOG0039; Eukaryota.
DR HOGENOM; CLU_010365_4_0_1; -.
DR InParanoid; Q5A446; -.
DR OrthoDB; 1506659at2759; -.
DR PRO; PR:Q5A446; -.
DR Proteomes; UP000000559; Chromosome 4.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IGI:CGD.
DR GO; GO:0052851; F:ferric-chelate reductase (NADPH) activity; IEA:UniProtKB-EC.
DR GO; GO:0000293; F:ferric-chelate reductase activity; IGI:CGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006879; P:cellular iron ion homeostasis; IBA:GO_Central.
DR GO; GO:0015677; P:copper ion import; IGI:CGD.
DR GO; GO:0006826; P:iron ion transport; IGI:CGD.
DR Gene3D; 3.40.50.80; -; 1.
DR InterPro; IPR013112; FAD-bd_8.
DR InterPro; IPR017927; FAD-bd_FR_type.
DR InterPro; IPR013130; Fe3_Rdtase_TM_dom.
DR InterPro; IPR013121; Fe_red_NAD-bd_6.
DR InterPro; IPR039261; FNR_nucleotide-bd.
DR Pfam; PF08022; FAD_binding_8; 1.
DR Pfam; PF01794; Ferric_reduct; 1.
DR Pfam; PF08030; NAD_binding_6; 1.
DR SUPFAM; SSF52343; SSF52343; 1.
DR PROSITE; PS51384; FAD_FR; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Copper; Copper transport; Electron transport; FAD;
KW Flavoprotein; Glycoprotein; Heme; Ion transport; Iron; Iron transport;
KW Membrane; Metal-binding; NADP; Oxidoreductase; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix; Transport; Virulence.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..760
FT /note="Ferric/cupric reductase transmembrane component 1"
FT /evidence="ECO:0000255"
FT /id="PRO_0000431507"
FT TOPO_DOM 19..212
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 213..233
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 234..288
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 289..309
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 310..324
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 325..345
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 346..371
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 372..392
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 393..403
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 404..424
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 425..430
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 431..451
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 452..760
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT DOMAIN 330..445
FT /note="Ferric oxidoreductase"
FT /evidence="ECO:0000255"
FT DOMAIN 465..583
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT REGION 119..177
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 366
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_label="1"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P32791"
FT BINDING 380
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_label="2"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P32791"
FT BINDING 436
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_label="1"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P32791"
FT BINDING 450
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_label="2"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P32791"
FT BINDING 575..578
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255"
FT BINDING 726..727
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255"
FT CARBOHYD 78
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 91
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 111
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 143
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 155
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 207
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 615
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 744
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 760 AA; 84888 MW; 330AF6BC42AD23F1 CRC64;
MKIQQLIVFL FAVVLIDART PKRYSELDIV MSTCTTFIGK YGTVCTSTGK RSTNWNCYCK
TDAGFGTISD CLVRGFNNNT NIISKFTESC NMTESKFHAK YDKIQAEFKT NGTEYAKMTT
KSSSGSKTSA SASKSSKSTG SSNASKSSTN AHGSNSSTSS TSSSSSKSGK GNSGTSTTET
ITTPLLIDYK KFTPYKDAYQ MSNNNFNLSI NYGSGLLGYW AGILAIAIFA NMIKKMFPSL
TNYLSGSISN LFRKHLFLPA TFRKKKAQEF SIGVYGFFDG LIPTRLETII VVIFVVLTGL
FSALHIHHVK DNPQYATKNA ELGHLIADRT GILGTFLIPL LILFGGRNNF LQWLTGWDFA
TFIMYHRWIS RVDVLLIIVH AITFSVSDKA TGKYNTRMKR DFMIWGTVST ICGGFILFQA
MLFFRRKCYE VFFLIHIVLV VFFVVGGYYH LESQGYGDFM WAAIAVWAFD RVVRLGRIFF
FGARKATVSI KGDDTLKIEV PKPKYWKSVA GGHAFIHFLK PTLFLQSHPF TFTTTESNDK
IVLYAKIKNG ITSNIAKYLS PLPGNTATIR VLVEGPYGEP SSAGRNCKNV VFVAGGNGIP
GIYSECVDLA KKSKNQSIKL IWIIRHWKSL SWFTEELEYL KKTNVQSTIY VTQPQDCSGL
ECFEHDVSFE KKSDEKDSVE SSQYSLISNI KQGLSHVEFI EGRPDISTQV EQEVKQADGA
IGFVTCGHPA MVDELRFAVT QNLNVSKHRV EYHEQLQTWA
