FRE6_YEAST
ID FRE6_YEAST Reviewed; 712 AA.
AC Q12473; D6VXV7;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Ferric reductase transmembrane component 6;
DE EC=1.16.1.9;
DE AltName: Full=Ferric-chelate reductase 6;
DE Flags: Precursor;
GN Name=FRE6; OrderedLocusNames=YLL051C; ORFNames=L0593;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169871;
RA Johnston M., Hillier L.W., Riles L., Albermann K., Andre B., Ansorge W.,
RA Benes V., Brueckner M., Delius H., Dubois E., Duesterhoeft A.,
RA Entian K.-D., Floeth M., Goffeau A., Hebling U., Heumann K.,
RA Heuss-Neitzel D., Hilbert H., Hilger F., Kleine K., Koetter P., Louis E.J.,
RA Messenguy F., Mewes H.-W., Miosga T., Moestl D., Mueller-Auer S.,
RA Nentwich U., Obermaier B., Piravandi E., Pohl T.M., Portetelle D.,
RA Purnelle B., Rechmann S., Rieger M., Rinke M., Rose M., Scharfe M.,
RA Scherens B., Scholler P., Schwager C., Schwarz S., Underwood A.P.,
RA Urrestarazu L.A., Vandenbol M., Verhasselt P., Vierendeels F., Voet M.,
RA Volckaert G., Voss H., Wambutt R., Wedler E., Wedler H., Zimmermann F.K.,
RA Zollner A., Hani J., Hoheisel J.D.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XII.";
RL Nature 387:87-90(1997).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [3]
RP INDUCTION.
RX PubMed=9726978; DOI=10.1074/jbc.273.37.23716;
RA Martins L.J., Jensen L.T., Simon J.R., Keller G.L., Winge D.R.;
RT "Metalloregulation of FRE1 and FRE2 homologs in Saccharomyces cerevisiae.";
RL J. Biol. Chem. 273:23716-23721(1998).
RN [4]
RP ERRATUM OF PUBMED:9726978.
RA Martins L.J., Jensen L.T., Simon J.R., Keller G.L., Winge D.R.;
RL J. Biol. Chem. 273:30056-30056(1998).
RN [5]
RP INDUCTION.
RX PubMed=10341420;
RX DOI=10.1002/(sici)1097-0061(199905)15:7<573::aid-yea404>3.0.co;2-7;
RA Georgatsou E., Alexandraki D.;
RT "Regulated expression of the Saccharomyces cerevisiae Fre1p/Fre2p Fe/Cu
RT reductase related genes.";
RL Yeast 15:573-584(1999).
RN [6]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [7]
RP INDUCTION BY AFT2.
RX PubMed=16024809; DOI=10.1128/mcb.25.15.6760-6771.2005;
RA Courel M., Lallet S., Camadro J.-M., Blaiseau P.-L.;
RT "Direct activation of genes involved in intracellular iron use by the yeast
RT iron-responsive transcription factor Aft2 without its paralog Aft1.";
RL Mol. Cell. Biol. 25:6760-6771(2005).
RN [8]
RP TOPOLOGY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 208353 / W303-1A;
RX PubMed=16847258; DOI=10.1073/pnas.0604075103;
RA Kim H., Melen K., Oesterberg M., von Heijne G.;
RT "A global topology map of the Saccharomyces cerevisiae membrane proteome.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:11142-11147(2006).
RN [9]
RP FUNCTION AS A REDUCTASE, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP 493-HIS--THR-496.
RX PubMed=17553781; DOI=10.1074/jbc.m703397200;
RA Rees E.M., Thiele D.J.;
RT "Identification of a vacuole-associated metalloreductase and its role in
RT Ctr2-mediated intracellular copper mobilization.";
RL J. Biol. Chem. 282:21629-21638(2007).
RN [10]
RP FUNCTION AS A REDUCTASE ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=17681937; DOI=10.1074/jbc.m703398200;
RA Singh A., Kaur N., Kosman D.J.;
RT "The metalloreductase Fre6p in Fe-efflux from the yeast vacuole.";
RL J. Biol. Chem. 282:28619-28626(2007).
CC -!- FUNCTION: Metalloreductase responsible for reducing vacuolar iron and
CC copper prior to transport into the cytosol. Catalyzes the reduction of
CC Fe(3+) to Fe(2+) and Cu(2+) to Cu(+), respectively, which can then be
CC transported by the respective vacuolar efflux systems to the cytosol.
CC {ECO:0000269|PubMed:17553781, ECO:0000269|PubMed:17681937}.
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 -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000305};
CC -!- SUBCELLULAR LOCATION: Vacuole membrane {ECO:0000269|PubMed:14562095,
CC ECO:0000269|PubMed:17553781, ECO:0000269|PubMed:17681937}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:14562095,
CC ECO:0000269|PubMed:17553781, ECO:0000269|PubMed:17681937}.
CC -!- INDUCTION: By transcription factor AFT2 upon iron deprivation.
CC {ECO:0000269|PubMed:10341420, ECO:0000269|PubMed:16024809,
CC ECO:0000269|PubMed:9726978}.
CC -!- SIMILARITY: Belongs to the ferric reductase (FRE) family.
CC {ECO:0000305}.
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DR EMBL; Z47973; CAA88006.1; -; Genomic_DNA.
DR EMBL; Z73156; CAA97503.1; -; Genomic_DNA.
DR EMBL; BK006945; DAA09273.1; -; Genomic_DNA.
DR PIR; S50969; S50969.
DR RefSeq; NP_013049.1; NM_001181871.1.
DR AlphaFoldDB; Q12473; -.
DR SMR; Q12473; -.
DR BioGRID; 31264; 31.
DR DIP; DIP-5019N; -.
DR IntAct; Q12473; 1.
DR STRING; 4932.YLL051C; -.
DR TCDB; 5.B.1.5.2; the phagocyte (gp91(phox)) nadph oxidase family.
DR iPTMnet; Q12473; -.
DR MaxQB; Q12473; -.
DR PaxDb; Q12473; -.
DR PRIDE; Q12473; -.
DR EnsemblFungi; YLL051C_mRNA; YLL051C; YLL051C.
DR GeneID; 850675; -.
DR KEGG; sce:YLL051C; -.
DR SGD; S000003974; FRE6.
DR VEuPathDB; FungiDB:YLL051C; -.
DR eggNOG; KOG0039; Eukaryota.
DR GeneTree; ENSGT00940000176303; -.
DR HOGENOM; CLU_010365_4_0_1; -.
DR InParanoid; Q12473; -.
DR OMA; HYFWNGE; -.
DR BioCyc; YEAST:G3O-32150-MON; -.
DR PRO; PR:Q12473; -.
DR Proteomes; UP000002311; Chromosome XII.
DR RNAct; Q12473; protein.
DR GO; GO:0000324; C:fungal-type vacuole; HDA:SGD.
DR GO; GO:0000329; C:fungal-type vacuole membrane; IDA:SGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0052851; F:ferric-chelate reductase (NADPH) activity; IEA:UniProtKB-EC.
DR GO; GO:0000293; F:ferric-chelate reductase activity; IDA:SGD.
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:SGD.
DR GO; GO:0006880; P:intracellular sequestering of iron ion; IMP:SGD.
DR GO; GO:0006826; P:iron ion transport; IBA:GO_Central.
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 1: Evidence at protein level;
KW Electron transport; FAD; Flavoprotein; Glycoprotein; Heme; Ion transport;
KW Iron; Iron transport; Membrane; Metal-binding; NADP; Oxidoreductase;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix; Transport;
KW Vacuole.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..712
FT /note="Ferric reductase transmembrane component 6"
FT /id="PRO_0000010142"
FT TOPO_DOM 18..167
FT /note="Vacuolar"
FT /evidence="ECO:0000255"
FT TRANSMEM 168..188
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 189..244
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 245..265
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 266..287
FT /note="Vacuolar"
FT /evidence="ECO:0000255"
FT TRANSMEM 288..308
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 309..328
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 329..349
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 350..360
FT /note="Vacuolar"
FT /evidence="ECO:0000255"
FT TRANSMEM 361..381
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 382..387
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 388..408
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 409..416
FT /note="Vacuolar"
FT /evidence="ECO:0000255"
FT TRANSMEM 417..437
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 438..712
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 287..411
FT /note="Ferric oxidoreductase"
FT DOMAIN 412..546
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT BINDING 323
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"
FT BINDING 337
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"
FT BINDING 393
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"
FT BINDING 407
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"
FT BINDING 493..499
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000255"
FT BINDING 538..541
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255"
FT BINDING 678..679
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255"
FT CARBOHYD 89
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 112
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 124
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 493..496
FT /note="HPFT->AAAA: Loss of function."
FT /evidence="ECO:0000269|PubMed:17553781"
SQ SEQUENCE 712 AA; 81989 MW; 5224F12B51544BAA CRC64;
MHRTLLFLTW LISLTKAFNI KLPHTEKKDH LESNAVLACA SYINTLKWSF DSSVVPGFYS
TICSYSPAFD TWSLCIFNSL TDQIIPMDNT SFEESLGNVR KTCSFVDKKF SNISLEQYYS
SLNNASSHAL EDYGSIESLS TSIRVDRETR SRWIRAFHAH AYNLDISSVY GAYLTYYFVI
VGIIAVFFHM SHYNGLNRAL FASRFVNYIR GHFVLPTFLV DKHANHFKFL NVEVFTGLMP
NSLEAWIIFG YTLANIIFLS ISYIIDPYNL IFNSHLSQFT RLLADRSGIL AFTQFPLIII
FTARNSFLEF LTGVKFNSFI SFHKWIGRIM VLNATIHSLS YSLFAIINHA FKISNKQLYW
KFGIASITVL CVLLVLSLGI VRKRHYEFFL YTHIILALLF FYCCWQHVKI FNGWKEWIVV
SLLIWGLEKL FRIWNILQFR FPKATLINLN TSNNPHDEMF KVIIPKYNRR WHSKPGQYCF
IYFLHPLVFW QCHPFTIIDE GEKCVLVIKP KSGLTRFIYN HILQSLNGKL QLRVAIEGPY
GPSNLHLDKF DHLLLLSGGT GLPGPLDHAI KLSRNPDKPK SIDLIMAIKN PSFLNGYKSE
ILELKNSRSH VNVQVYLTQK TAVTKAANAR DQLIHFDDIM TELTSFAHIG NARPNFSNVI
ENAIKSTPPG DSLAVVCCGP PVLVDDVRNT VSQKLLGYPE RIIEYFEEYQ CW
