FRE4_YEAST
ID FRE4_YEAST Reviewed; 719 AA.
AC P53746; D6W1N5;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Ferric reductase transmembrane component 4;
DE EC=1.16.1.9;
DE AltName: Full=Ferric-chelate reductase 4;
DE Flags: Precursor;
GN Name=FRE4; OrderedLocusNames=YNR060W; ORFNames=N3518;
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=9169873;
RA Philippsen P., Kleine K., Poehlmann R., Duesterhoeft A., Hamberg K.,
RA Hegemann J.H., Obermaier B., Urrestarazu L.A., Aert R., Albermann K.,
RA Altmann R., Andre B., Baladron V., Ballesta J.P.G., Becam A.-M.,
RA Beinhauer J.D., Boskovic J., Buitrago M.J., Bussereau F., Coster F.,
RA Crouzet M., D'Angelo M., Dal Pero F., De Antoni A., del Rey F., Doignon F.,
RA Domdey H., Dubois E., Fiedler T.A., Fleig U., Floeth M., Fritz C.,
RA Gaillardin C., Garcia-Cantalejo J.M., Glansdorff N., Goffeau A.,
RA Gueldener U., Herbert C.J., Heumann K., Heuss-Neitzel D., Hilbert H.,
RA Hinni K., Iraqui Houssaini I., Jacquet M., Jimenez A., Jonniaux J.-L.,
RA Karpfinger-Hartl L., Lanfranchi G., Lepingle A., Levesque H., Lyck R.,
RA Maftahi M., Mallet L., Maurer C.T.C., Messenguy F., Mewes H.-W., Moestl D.,
RA Nasr F., Nicaud J.-M., Niedenthal R.K., Pandolfo D., Pierard A.,
RA Piravandi E., Planta R.J., Pohl T.M., Purnelle B., Rebischung C.,
RA Remacha M.A., Revuelta J.L., Rinke M., Saiz J.E., Sartorello F.,
RA Scherens B., Sen-Gupta M., Soler-Mira A., Urbanus J.H.M., Valle G.,
RA Van Dyck L., Verhasselt P., Vierendeels F., Vissers S., Voet M.,
RA Volckaert G., Wach A., Wambutt R., Wedler H., Zollner A., Hani J.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIV and its
RT evolutionary implications.";
RL Nature 387:93-98(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 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).
CC -!- FUNCTION: Siderophore-iron reductase responsible for reducing
CC extracellular iron prior to import. Catalyzes the reductive uptake of
CC Fe(3+) bound to dihydroxamate rhodotorulic acid. Fe(3+) is reduced to
CC Fe(2+), which then dissociates from the siderophore and can be imported
CC by the high-affinity Fe(2+) transport complex in the plasma membrane.
CC {ECO:0000269|PubMed:11120744}.
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: Cell membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- INDUCTION: By iron deprivation. {ECO:0000269|PubMed:10341420,
CC ECO:0000269|PubMed:9726978}.
CC -!- SIMILARITY: Belongs to the ferric reductase (FRE) family.
CC {ECO:0000305}.
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DR EMBL; Z71675; CAA96342.1; -; Genomic_DNA.
DR EMBL; BK006947; DAA10601.1; -; Genomic_DNA.
DR PIR; S63392; S63392.
DR RefSeq; NP_014458.1; NM_001183237.1.
DR AlphaFoldDB; P53746; -.
DR SMR; P53746; -.
DR BioGRID; 35886; 26.
DR DIP; DIP-7626N; -.
DR IntAct; P53746; 1.
DR MINT; P53746; -.
DR STRING; 4932.YNR060W; -.
DR iPTMnet; P53746; -.
DR PaxDb; P53746; -.
DR PRIDE; P53746; -.
DR EnsemblFungi; YNR060W_mRNA; YNR060W; YNR060W.
DR GeneID; 855797; -.
DR KEGG; sce:YNR060W; -.
DR SGD; S000005343; FRE4.
DR VEuPathDB; FungiDB:YNR060W; -.
DR eggNOG; KOG0039; Eukaryota.
DR GeneTree; ENSGT00940000176303; -.
DR HOGENOM; CLU_010365_4_0_1; -.
DR InParanoid; P53746; -.
DR OMA; VTHAINM; -.
DR BioCyc; YEAST:G3O-33364-MON; -.
DR PRO; PR:P53746; -.
DR Proteomes; UP000002311; Chromosome XIV.
DR RNAct; P53746; protein.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IMP:SGD.
DR GO; GO:0052851; F:ferric-chelate reductase (NADPH) activity; IEA:UniProtKB-EC.
DR GO; GO:0000293; F:ferric-chelate reductase activity; IGI: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; IBA:GO_Central.
DR GO; GO:0006826; P:iron ion transport; IBA:GO_Central.
DR GO; GO:0015891; P:siderophore transport; IMP: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 2: Evidence at transcript level;
KW Cell membrane; Electron transport; FAD; Flavoprotein; Glycoprotein; Heme;
KW Ion transport; Iron; Iron transport; Membrane; Metal-binding; NADP;
KW Oxidoreductase; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix; Transport.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..719
FT /note="Ferric reductase transmembrane component 4"
FT /id="PRO_0000010140"
FT TOPO_DOM 19..156
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 157..177
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 178..228
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 229..249
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 250..267
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 268..288
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 289..304
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 305..325
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 326..346
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 347..367
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 368..373
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 374..394
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 395
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 396..416
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 417..719
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT DOMAIN 273..407
FT /note="Ferric oxidoreductase"
FT DOMAIN 408..527
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT REGION 606..643
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 309
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 323
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 379
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 393
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 472..478
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000255"
FT BINDING 519..522
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255"
FT BINDING 685..686
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255"
FT CARBOHYD 51
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 80
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 101
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 113
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 127
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 135
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 719 AA; 82015 MW; 9CA91F1F890AF1F9 CRC64;
MLLVHIISFL LFFQLSAAKA PPSKTSLINT HERRSIYSCY VGLRKETWGF NGSAICRYEP
AIQSMLYCLY EDTHEKGYSN KTLEKGFEEM RQFCYTPKFL NMTDAEFYTS LDNGTYYIQD
QPKAGINITY PIRLNTTLRK AYYDAYYGYY YNHDIPYYFG GIICAYFVGV MLLAGLIRFL
NYTPIKKIMF QQKLVNYVRG YTTLPTLYEK HAEPFSYLKV ITGYLPTRFE TLVILGYLIL
HTIFMAYKYQ YDPYHIIFAA HRAEVAHFVA YRSGILSFAH LPLIVLFAGR NNFLQLISGL
KHTSFIVFHK WLGRMMFLDA IIHAAGFTNY YLYYKKWNTV RLRVYWKFGI ATTCLAGMLI
FFSIAAFRRH YYETFMALHI VFAALFLYTC WEHVTNFSGI EWIYAAIAIW GVDRIVRITR
IALLGFPKAD LQLVGSDLVR VTVKKPKKFW KAKPGQYVFV SFLRPLCFWQ SHPFTVMDSC
VNDRELVIVL KAKKGVTKLV RNFVERKGGK ASMRLAIEGP YGSKSTAHRF DNVLLLAGGS
GLPGPISHAL ELGKTTAASG KNFVQLVIAV RGLDMLNACK KELMALKGLN VQVHIYNSKQ
ELASAEKISS NEVKNGETTA EKAPSSLSNS EKAPSESENT ELPLSLNDTS ISDLEFATFH
VGRPNVEEIL NESVNHSGSL AVVCCGPPIF VDTARNQTAK AVIRNPSRMI EYLEEYQAW
