FRE2_YEAST
ID FRE2_YEAST Reviewed; 711 AA.
AC P36033; D6VWY3;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Ferric/cupric reductase transmembrane component 2;
DE EC=1.16.1.9;
DE AltName: Full=Ferric-chelate reductase 2;
DE Flags: Precursor;
GN Name=FRE2; OrderedLocusNames=YKL220C;
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 [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8091865; DOI=10.1002/yea.320100011;
RA Alexandraki D., Tzermia M.;
RT "Sequencing of a 13.2 kb segment next to the left telomere of yeast
RT chromosome XI revealed five open reading frames and recent recombination
RT events with the right arms of chromosomes III and V.";
RL Yeast 10:S81-S91(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8196765; DOI=10.1038/369371a0;
RA Dujon B., Alexandraki D., Andre B., Ansorge W., Baladron V.,
RA Ballesta J.P.G., Banrevi A., Bolle P.-A., Bolotin-Fukuhara M., Bossier P.,
RA Bou G., Boyer J., Buitrago M.J., Cheret G., Colleaux L.,
RA Daignan-Fornier B., del Rey F., Dion C., Domdey H., Duesterhoeft A.,
RA Duesterhus S., Entian K.-D., Erfle H., Esteban P.F., Feldmann H.,
RA Fernandes L., Fobo G.M., Fritz C., Fukuhara H., Gabel C., Gaillon L.,
RA Garcia-Cantalejo J.M., Garcia-Ramirez J.J., Gent M.E., Ghazvini M.,
RA Goffeau A., Gonzalez A., Grothues D., Guerreiro P., Hegemann J.H.,
RA Hewitt N., Hilger F., Hollenberg C.P., Horaitis O., Indge K.J.,
RA Jacquier A., James C.M., Jauniaux J.-C., Jimenez A., Keuchel H.,
RA Kirchrath L., Kleine K., Koetter P., Legrain P., Liebl S., Louis E.J.,
RA Maia e Silva A., Marck C., Monnier A.-L., Moestl D., Mueller S.,
RA Obermaier B., Oliver S.G., Pallier C., Pascolo S., Pfeiffer F.,
RA Philippsen P., Planta R.J., Pohl F.M., Pohl T.M., Poehlmann R.,
RA Portetelle D., Purnelle B., Puzos V., Ramezani Rad M., Rasmussen S.W.,
RA Remacha M.A., Revuelta J.L., Richard G.-F., Rieger M.,
RA Rodrigues-Pousada C., Rose M., Rupp T., Santos M.A., Schwager C.,
RA Sensen C., Skala J., Soares H., Sor F., Stegemann J., Tettelin H.,
RA Thierry A., Tzermia M., Urrestarazu L.A., van Dyck L.,
RA van Vliet-Reedijk J.C., Valens M., Vandenbol M., Vilela C., Vissers S.,
RA von Wettstein D., Voss H., Wiemann S., Xu G., Zimmermann J., Haasemann M.,
RA Becker I., Mewes H.-W.;
RT "Complete DNA sequence of yeast chromosome XI.";
RL Nature 369:371-378(1994).
RN [3]
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 [4]
RP CHARACTERIZATION, AND SUBCELLULAR LOCATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8164662; DOI=10.1128/mcb.14.5.3065-3073.1994;
RA Georgatsou E., Alexandraki D.;
RT "Two distinctly regulated genes are required for ferric reduction, the
RT first step of iron uptake in Saccharomyces cerevisiae.";
RL Mol. Cell. Biol. 14:3065-3073(1994).
RN [5]
RP INDUCTION.
RX PubMed=7720713; DOI=10.1002/j.1460-2075.1995.tb07106.x;
RA Yamaguchi-Iwai Y., Dancis A., Klausner R.D.;
RT "AFT1: a mediator of iron regulated transcriptional control in
RT Saccharomyces cerevisiae.";
RL EMBO J. 14:1231-1239(1995).
RN [6]
RP FUNCTION, AND INDUCTION.
RX PubMed=9153234; DOI=10.1074/jbc.272.21.13786;
RA Georgatsou E., Mavrogiannis L.A., Fragiadakis G.S., Alexandraki D.;
RT "The yeast Fre1p/Fre2p cupric reductases facilitate copper uptake and are
RT regulated by the copper-modulated Mac1p activator.";
RL J. Biol. Chem. 272:13786-13792(1997).
RN [7]
RP INDUCTION.
RX PubMed=9200812;
RX DOI=10.1002/(sici)1097-0061(19970615)13:7<621::aid-yea121>3.0.co;2-u;
RA Casas C., Aldea M., Espinet C., Gallego C., Gil R., Herrero E.;
RT "The AFT1 transcriptional factor is differentially required for expression
RT of high-affinity iron uptake genes in Saccharomyces cerevisiae.";
RL Yeast 13:621-637(1997).
RN [8]
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 [9]
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 [10]
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 [11]
RP FUNCTION.
RX PubMed=11120744; DOI=10.1074/jbc.m010065200;
RA Yun C.-W., Bauler M., Moore R.E., Klebba P.E., Philpott C.C.;
RT "The role of the FRE family of plasma membrane reductases in the uptake of
RT siderophore-iron in Saccharomyces cerevisiae.";
RL J. Biol. Chem. 276:10218-10223(2001).
RN [12]
RP INDUCTION BY AFT1 AND 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 [13]
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).
CC -!- FUNCTION: Metalloreductase 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. {ECO:0000269|PubMed:11120744,
CC ECO:0000269|PubMed:9153234}.
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 -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:8164662};
CC Multi-pass membrane protein {ECO:0000269|PubMed:8164662}.
CC -!- INDUCTION: By transcription factors AFT1 and AFT2 upon iron
CC deprivation. {ECO:0000269|PubMed:10341420, ECO:0000269|PubMed:16024809,
CC ECO:0000269|PubMed:7720713, ECO:0000269|PubMed:9153234,
CC ECO:0000269|PubMed:9200812, ECO:0000269|PubMed:9726978}.
CC -!- SIMILARITY: Belongs to the ferric reductase (FRE) family.
CC {ECO:0000305}.
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DR EMBL; X75950; CAA53553.1; -; Genomic_DNA.
DR EMBL; Z28220; CAA82065.1; -; Genomic_DNA.
DR EMBL; BK006944; DAA08949.1; -; Genomic_DNA.
DR PIR; S38063; S38063.
DR RefSeq; NP_012702.1; NM_001179785.1.
DR AlphaFoldDB; P36033; -.
DR SMR; P36033; -.
DR BioGRID; 33945; 58.
DR DIP; DIP-7473N; -.
DR IntAct; P36033; 1.
DR MINT; P36033; -.
DR STRING; 4932.YKL220C; -.
DR TCDB; 5.B.1.5.3; the phagocyte (gp91(phox)) nadph oxidase family.
DR PaxDb; P36033; -.
DR PRIDE; P36033; -.
DR EnsemblFungi; YKL220C_mRNA; YKL220C; YKL220C.
DR GeneID; 853660; -.
DR KEGG; sce:YKL220C; -.
DR SGD; S000001703; FRE2.
DR VEuPathDB; FungiDB:YKL220C; -.
DR eggNOG; KOG0039; Eukaryota.
DR GeneTree; ENSGT00940000176303; -.
DR HOGENOM; CLU_010365_4_0_1; -.
DR InParanoid; P36033; -.
DR OMA; TFHRHIA; -.
DR BioCyc; MetaCyc:YKL220C-MON; -.
DR BioCyc; YEAST:YKL220C-MON; -.
DR PRO; PR:P36033; -.
DR Proteomes; UP000002311; Chromosome XI.
DR RNAct; P36033; protein.
DR GO; GO:0000324; C:fungal-type vacuole; HDA:SGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:SGD.
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; IDA:SGD.
DR GO; GO:0006826; P:iron ion transport; IDA:SGD.
DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; IDA:SGD.
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 InterPro; IPR017938; Riboflavin_synthase-like_b-brl.
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 SUPFAM; SSF63380; SSF63380; 1.
DR PROSITE; PS51384; FAD_FR; 1.
PE 1: Evidence at protein 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.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..711
FT /note="Ferric/cupric reductase transmembrane component 2"
FT /id="PRO_0000010138"
FT TOPO_DOM 24..164
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 165..185
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 186..235
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 236..256
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 257..280
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 281..301
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 302..317
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 318..340
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 341..353
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 354..374
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 375..377
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 378..398
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 399..400
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 401..423
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 424..711
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 280..414
FT /note="Ferric oxidoreductase"
FT DOMAIN 415..534
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT BINDING 316
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 330
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 386
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 400
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 479..485
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000255"
FT BINDING 526..529
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255"
FT BINDING 677..678
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255"
FT CARBOHYD 85
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 108
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 120
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 134
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 341
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 711 AA; 80072 MW; 3C60346577C80E53 CRC64;
MHWTSILSAI LLFCLSGARA SPAKTVIRNK VPLLVTNACT RIFQKVTWEY TSKSKRSSPV
CSYEPAFQSM LYCIYETLDE KGYSNKTLEK TFSTIKKNCA SYSDALQNMT NSEFYDVLNN
GTRHMTPYVK GSANLTYPVE MDTQLRKAYY HALHGFYANL DVGNIYGGII CAYFVAIMAF
AGVLHCMNYT PFKTVLLKQK LVGYVRGYLT LPTIGSKHAS DFSYFRIFTG YLPTRLEGII
ILGYLVLHTV FLAYGYEYDP ENIIFKSRRV QVARYVADRS GVLAFAHFPL IVLFAGRNNF
LEYISGVKYT SFIMFHKWLG RMMFLDAMIH GSAYTSYTVA NKTWATSKNR LYWQFGVAAL
CLAGTMVFFS FAVFRKYFYE AFLFLHIVLG AMFFYACWEH VVSLSGIEWI YTAIAIWIVD
RIIRIIKASY FGFPKASLQL IGDDLIRLTV KKPARPWRAK PGQYVFVSFL HPLYFWQSHP
FTVLDSVSKN GELVIILKEK KGVTRLVKKY VCRNGGKTSM RLAIEGPYGS SSPVNNYNNV
LLLTGGTGLP GPIAHAIKLG KTSAAAGKQS VKLVIAVRGF DVLEAYKPEL MCLENLNVQL
HIYNTMEVPS LTPSDSLDIS QQDEKADEKG TVVATTLEKS ANPLGFDGVV FHCGRPNVKE
LLHEAAELSG SLSVVCCGPP IFVDKVRNET AKIVLDKSAK AIEYFEEYQC W
