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Protein

Ferric/cupric reductase transmembrane component 1

Gene

FRE1

Organism
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Metalloreductase responsible for reducing extracellular iron and copper prior to import. Catalyzes the reductive uptake of Fe3+-salts and Fe3+ bound to catecholate or hydroxamate siderophores. Fe3+ is reduced to Fe2+, which then dissociates from the siderophore and can be imported by the high-affinity Fe2+ transport complex in the plasma membrane. Also participates in Cu2+ reduction and Cu+ uptake.8 Publications

Catalytic activityi

2 Fe(II)-siderophore + NADP+ + H+ = 2 Fe(III)-siderophore + NADPH.5 Publications

Cofactori

Protein has several cofactor binding sites:

Enzyme regulationi

Inhibited by nitric oxide (NO).1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi294 – 2941Iron (heme 1 axial ligand)1 Publication
Metal bindingi308 – 3081Iron (heme 2 axial ligand)1 Publication
Metal bindingi364 – 3641Iron (heme 1 axial ligand)1 Publication
Metal bindingi378 – 3781Iron (heme 2 axial ligand)1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi462 – 4687FADSequence analysis
Nucleotide bindingi514 – 5174NADPSequence analysis
Nucleotide bindingi652 – 6532NADPSequence analysis

GO - Molecular functioni

GO - Biological processi

  • copper ion import Source: SGD
  • iron ion homeostasis Source: UniProtKB-KW
  • iron ion transport Source: SGD
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Copper transport, Electron transport, Ion transport, Iron transport, Transport

Keywords - Ligandi

Copper, FAD, Flavoprotein, Heme, Iron, Metal-binding, NADP

Enzyme and pathway databases

BioCyciYEAST:YLR214W-MONOMER.

Protein family/group databases

TCDBi5.B.1.5.1. the phagocyte (gp91(phox)) nadph oxidase family.

Names & Taxonomyi

Protein namesi
Recommended name:
Ferric/cupric reductase transmembrane component 1Curated (EC:1.16.1.95 Publications)
Alternative name(s):
Ferric-chelate reductase 1Curated
Gene namesi
Name:FRE1
Ordered Locus Names:YLR214W
ORF Names:L8167.2
OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Taxonomic identifieri559292 [NCBI]
Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
Proteomesi
  • UP000002311 Componenti: Chromosome XII

Organism-specific databases

EuPathDBiFungiDB:YLR214W.
SGDiS000004204. FRE1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini23 – 148126ExtracellularSequence analysisAdd
BLAST
Transmembranei149 – 16921Helical; Name=1Sequence analysisAdd
BLAST
Topological domaini170 – 21546CytoplasmicSequence analysisAdd
BLAST
Transmembranei216 – 23621Helical; Name=2Sequence analysisAdd
BLAST
Topological domaini237 – 25923ExtracellularSequence analysisAdd
BLAST
Transmembranei260 – 28021Helical; Name=3Sequence analysisAdd
BLAST
Topological domaini281 – 29616CytoplasmicSequence analysisAdd
BLAST
Transmembranei297 – 31721Helical; Name=4Sequence analysisAdd
BLAST
Topological domaini318 – 32811ExtracellularSequence analysisAdd
BLAST
Transmembranei329 – 34921Helical; Name=5Sequence analysisAdd
BLAST
Topological domaini350 – 3589CytoplasmicSequence analysis
Transmembranei359 – 37820Helical; Name=6Sequence analysisAdd
BLAST
Topological domaini379 – 3835ExtracellularSequence analysis
Transmembranei384 – 40118Helical; Name=7Sequence analysisAdd
BLAST
Topological domaini402 – 686285CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • integral component of membrane Source: UniProtKB-KW
  • plasma membrane Source: SGD
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Biotechnological usei

Responsible for the reduction of the azo bond of azo dyes, making yeasts efficient azo dye decolorizers.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi294 – 2941H → A: Impairs heme binding. 1 Publication
Mutagenesisi308 – 3081H → A: Impairs heme binding. 1 Publication
Mutagenesisi364 – 3641H → A: Impairs heme binding. 1 Publication
Mutagenesisi378 – 3781H → A: Impairs heme binding. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2222Sequence analysisAdd
BLAST
Chaini23 – 686664Ferric/cupric reductase transmembrane component 1PRO_0000010137Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi69 – 691N-linked (GlcNAc...)Sequence analysis
Glycosylationi100 – 1001N-linked (GlcNAc...)Sequence analysis
Glycosylationi124 – 1241N-linked (GlcNAc...)Sequence analysis

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiP32791.
PeptideAtlasiP32791.

Expressioni

Inductioni

Expression is repressed by the addition of iron (PubMed:1570306, PubMed:1431884). Induced by transription factor MAC1 upon copper deprivation (PubMed:7814363, PubMed:9153234, PubMed:9726978, PubMed:10341420). Induced by transcription factor AFT1 upon iron deprivation (PubMed:7720713, PubMed:9200812, PubMed:9726978, PubMed:10341420, PubMed:16024809).9 Publications

Interactioni

Protein-protein interaction databases

BioGridi31482. 34 interactions.
DIPiDIP-5349N.
IntActiP32791. 1 interaction.
MINTiMINT-492656.

Structurei

3D structure databases

ProteinModelPortaliP32791.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini258 – 398141Ferric oxidoreductaseSequence analysisAdd
BLAST
Domaini399 – 522124FAD-binding FR-typePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the ferric reductase (FRE) family.Curated
Contains 1 FAD-binding FR-type domain.PROSITE-ProRule annotation
Contains 1 ferric oxidoreductase domain.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

GeneTreeiENSGT00390000007891.
HOGENOMiHOG000001131.
InParanoidiP32791.
OMAiIMRITID.
OrthoDBiEOG7MPRPF.

Family and domain databases

InterProiIPR013112. FAD-bd_8.
IPR017927. Fd_Rdtase_FAD-bd.
IPR013130. Fe3_Rdtase_TM_dom.
IPR013121. Fe_red_NAD-bd_6.
[Graphical view]
PfamiPF08022. FAD_binding_8. 1 hit.
PF01794. Ferric_reduct. 1 hit.
PF08030. NAD_binding_6. 1 hit.
[Graphical view]
PROSITEiPS51384. FAD_FR. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P32791-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVRTRVLFCL FISFFATVQS SATLISTSCI SQAALYQFGC SSKSKSCYCK
60 70 80 90 100
NINWLGSVTA CAYENSKSNK TLDSALMKLA SQCSSIKVYT LEDMKNIYLN
110 120 130 140 150
ASNYLRAPEK SDKKTVVSQP LMANETAYHY YYEENYGIHL NLMRSQWCAW
160 170 180 190 200
GLVFFWVAVL TAATILNILK RVFGKNIMAN SVKKSLIYPS VYKDYNERTF
210 220 230 240 250
YLWKRLPFNF TTRGKGLVVL IFVILTILSL SFGHNIKLPH PYDRPRWRRS
260 270 280 290 300
MAFVSRRADL MAIALFPVVY LFGIRNNPFI PITGLSFSTF NFYHKWSAYV
310 320 330 340 350
CFMLAVVHSI VMTASGVKRG VFQSLVRKFY FRWGIVATIL MSIIIFQSEK
360 370 380 390 400
VFRNRGYEIF LLIHKAMNIM FIIAMYYHCH TLGWMGWIWS MAGILCFDRF
410 420 430 440 450
CRIVRIIMNG GLKTATLSTT DDSNVIKISV KKPKFFKYQV GAFAYMYFLS
460 470 480 490 500
PKSAWFYSFQ SHPFTVLSER HRDPNNPDQL TMYVKANKGI TRVLLSKVLS
510 520 530 540 550
APNHTVDCKI FLEGPYGVTV PHIAKLKRNL VGVAAGLGVA AIYPHFVECL
560 570 580 590 600
RLPSTDQLQH KFYWIVNDLS HLKWFENELQ WLKEKSCEVS VIYTGSSVED
610 620 630 640 650
TNSDESTKGF DDKEESEITV ECLNKRPDLK ELVRSEIKLS ELENNNITFY
660 670 680
SCGPATFNDD FRNAVVQGID SSLKIDVELE EESFTW
Length:686
Mass (Da):78,854
Last modified:October 1, 1993 - v1
Checksum:i7F6BB3B93A95D6A3
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M86908 Genomic DNA. Translation: AAA34608.1.
U14913 Genomic DNA. Translation: AAB67424.1.
BK006945 Genomic DNA. Translation: DAA09531.1.
PIRiS30075.
RefSeqiNP_013315.1. NM_001182101.1.

Genome annotation databases

EnsemblFungiiYLR214W; YLR214W; YLR214W.
GeneIDi850911.
KEGGisce:YLR214W.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M86908 Genomic DNA. Translation: AAA34608.1.
U14913 Genomic DNA. Translation: AAB67424.1.
BK006945 Genomic DNA. Translation: DAA09531.1.
PIRiS30075.
RefSeqiNP_013315.1. NM_001182101.1.

3D structure databases

ProteinModelPortaliP32791.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi31482. 34 interactions.
DIPiDIP-5349N.
IntActiP32791. 1 interaction.
MINTiMINT-492656.

Protein family/group databases

TCDBi5.B.1.5.1. the phagocyte (gp91(phox)) nadph oxidase family.

Proteomic databases

MaxQBiP32791.
PeptideAtlasiP32791.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblFungiiYLR214W; YLR214W; YLR214W.
GeneIDi850911.
KEGGisce:YLR214W.

Organism-specific databases

EuPathDBiFungiDB:YLR214W.
SGDiS000004204. FRE1.

Phylogenomic databases

GeneTreeiENSGT00390000007891.
HOGENOMiHOG000001131.
InParanoidiP32791.
OMAiIMRITID.
OrthoDBiEOG7MPRPF.

Enzyme and pathway databases

BioCyciYEAST:YLR214W-MONOMER.

Miscellaneous databases

PROiP32791.

Family and domain databases

InterProiIPR013112. FAD-bd_8.
IPR017927. Fd_Rdtase_FAD-bd.
IPR013130. Fe3_Rdtase_TM_dom.
IPR013121. Fe_red_NAD-bd_6.
[Graphical view]
PfamiPF08022. FAD_binding_8. 1 hit.
PF01794. Ferric_reduct. 1 hit.
PF08030. NAD_binding_6. 1 hit.
[Graphical view]
PROSITEiPS51384. FAD_FR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Ferric reductase of Saccharomyces cerevisiae: molecular characterization, role in iron uptake, and transcriptional control by iron."
    Dancis A., Roman D.G., Anderson G.J., Hinnebusch A.G., Klausner R.D.
    Proc. Natl. Acad. Sci. U.S.A. 89:3869-3873(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, INDUCTION.
    Strain: F113.
  2. "The nucleotide sequence of Saccharomyces cerevisiae chromosome XII."
    Johnston M., Hillier L.W., Riles L., Albermann K., Andre B., Ansorge W., Benes V., Brueckner M., Delius H., Dubois E., Duesterhoeft A., Entian K.-D., Floeth M., Goffeau A., Hebling U., Heumann K., Heuss-Neitzel D., Hilbert H.
    , Hilger F., Kleine K., Koetter P., Louis E.J., Messenguy F., Mewes H.-W., Miosga T., Moestl D., Mueller-Auer S., Nentwich U., Obermaier B., Piravandi E., Pohl T.M., Portetelle D., Purnelle B., Rechmann S., Rieger M., Rinke M., Rose M., Scharfe M., Scherens B., Scholler P., Schwager C., Schwarz S., Underwood A.P., Urrestarazu L.A., Vandenbol M., Verhasselt P., Vierendeels F., Voet M., Volckaert G., Voss H., Wambutt R., Wedler E., Wedler H., Zimmermann F.K., Zollner A., Hani J., Hoheisel J.D.
    Nature 387:87-90(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: ATCC 204508 / S288c.
  3. Cited for: GENOME REANNOTATION.
    Strain: ATCC 204508 / S288c.
  4. "Ferric iron reduction and iron assimilation in Saccharomyces cerevisiae."
    Anderson G.J., Lesuisse E., Dancis A., Roman D.G., Labbe P., Klausner R.D.
    J. Inorg. Biochem. 47:249-255(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, INDUCTION, SUBCELLULAR LOCATION.
  5. "AFT1: a mediator of iron regulated transcriptional control in Saccharomyces cerevisiae."
    Yamaguchi-Iwai Y., Dancis A., Klausner R.D.
    EMBO J. 14:1231-1239(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  6. "Evidence for Cu(II) reduction as a component of copper uptake by Saccharomyces cerevisiae."
    Hassett R., Kosman D.J.
    J. Biol. Chem. 270:128-134(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INDUCTION.
  7. "Evidence for the Saccharomyces cerevisiae ferrireductase system being a multicomponent electron transport chain."
    Lesuisse E., Casteras-Simon M., Labbe P.
    J. Biol. Chem. 271:13578-13583(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION.
  8. "The FRE1 ferric reductase of Saccharomyces cerevisiae is a cytochrome b similar to that of NADPH oxidase."
    Shatwell K.P., Dancis A., Cross A.R., Klausner R.D., Segal A.W.
    J. Biol. Chem. 271:14240-14244(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR.
  9. "Intramembrane bis-heme motif for transmembrane electron transport conserved in a yeast iron reductase and the human NADPH oxidase."
    Finegold A.A., Shatwell K.P., Segal A.W., Klausner R.D., Dancis A.
    J. Biol. Chem. 271:31021-31024(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: HEME BINDING, MUTAGENESIS OF HIS-294; HIS-308; HIS-364 AND HIS-378.
  10. "The yeast Fre1p/Fre2p cupric reductases facilitate copper uptake and are regulated by the copper-modulated Mac1p activator."
    Georgatsou E., Mavrogiannis L.A., Fragiadakis G.S., Alexandraki D.
    J. Biol. Chem. 272:13786-13792(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INDUCTION.
  11. "The AFT1 transcriptional factor is differentially required for expression of high-affinity iron uptake genes in Saccharomyces cerevisiae."
    Casas C., Aldea M., Espinet C., Gallego C., Gil R., Herrero E.
    Yeast 13:621-637(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  12. "Metalloregulation of FRE1 and FRE2 homologs in Saccharomyces cerevisiae."
    Martins L.J., Jensen L.T., Simon J.R., Keller G.L., Winge D.R.
    J. Biol. Chem. 273:23716-23721(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  13. Erratum
    Martins L.J., Jensen L.T., Simon J.R., Keller G.L., Winge D.R.
    J. Biol. Chem. 273:30056-30056(1998)
  14. "Regulated expression of the Saccharomyces cerevisiae Fre1p/Fre2p Fe/Cu reductase related genes."
    Georgatsou E., Alexandraki D.
    Yeast 15:573-584(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  15. "The role of the FRE family of plasma membrane reductases in the uptake of siderophore-iron in Saccharomyces cerevisiae."
    Yun C.-W., Bauler M., Moore R.E., Klebba P.E., Philpott C.C.
    J. Biol. Chem. 276:10218-10223(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY.
  16. "Fre1p Cu2+ reduction and Fet3p Cu1+ oxidation modulate copper toxicity in Saccharomyces cerevisiae."
    Shi X., Stoj C., Romeo A., Kosman D.J., Zhu Z.
    J. Biol. Chem. 278:50309-50315(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  17. Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
  18. "Inhibition of the yeast metal reductase heme protein fre1 by nitric oxide (NO): a model for inhibition of NADPH oxidase by NO."
    Shinyashiki M., Pan C.J., Lopez B.E., Fukuto J.M.
    Free Radic. Biol. Med. 37:713-723(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: CATALYTIC ACTIVITY, ENZYME REGULATION, SUBCELLULAR LOCATION.
  19. "Azo reductase activity of intact Saccharomyces cerevisiae cells is dependent on the Fre1p component of plasma membrane ferric reductase."
    Ramalho P.A., Paiva S., Cavaco-Paulo A., Casal M., Cardoso M.H., Ramalho M.T.
    Appl. Environ. Microbiol. 71:3882-3888(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: BIOTECHNOLOGY.
  20. "Direct activation of genes involved in intracellular iron use by the yeast iron-responsive transcription factor Aft2 without its paralog Aft1."
    Courel M., Lallet S., Camadro J.-M., Blaiseau P.-L.
    Mol. Cell. Biol. 25:6760-6771(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION BY AFT1.
  21. "Probing the membrane environment of the TOR kinases reveals functional interactions between TORC1, actin, and membrane trafficking in Saccharomyces cerevisiae."
    Aronova S., Wedaman K., Anderson S., Yates J.R. III, Powers T.
    Mol. Biol. Cell 18:2779-2794(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY.

Entry informationi

Entry nameiFRE1_YEAST
AccessioniPrimary (citable) accession number: P32791
Secondary accession number(s): D6VYL5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: October 1, 1993
Last modified: June 8, 2016
This is version 137 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Miscellaneousi

Miscellaneous

Present with 892 molecules/cell in log phase SD medium.1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Yeast
    Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD
  3. Yeast chromosome XII
    Yeast (Saccharomyces cerevisiae) chromosome XII: entries and gene names

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.