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Protein

Ferric/cupric reductase transmembrane component 2

Gene

FRE2

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.2 Publications

Catalytic activityi

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

Cofactori

Protein has several cofactor binding sites:

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi316 – 3161Iron (heme 1 axial ligand)By similarity
Metal bindingi330 – 3301Iron (heme 2 axial ligand)By similarity
Metal bindingi386 – 3861Iron (heme 1 axial ligand)By similarity
Metal bindingi400 – 4001Iron (heme 2 axial ligand)By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi479 – 4857FADSequence analysis
Nucleotide bindingi526 – 5294NADPSequence analysis
Nucleotide bindingi677 – 6782NADPSequence 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:YKL220C-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Ferric/cupric reductase transmembrane component 2 (EC:1.16.1.9)
Alternative name(s):
Ferric-chelate reductase 2
Gene namesi
Name:FRE2
Ordered Locus Names:YKL220C
OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Taxonomic identifieri559292 [NCBI]
Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
Proteomesi
  • UP000002311 Componenti: Chromosome XI

Organism-specific databases

EuPathDBiFungiDB:YKL220C.
SGDiS000001703. FRE2.

Subcellular locationi

  • Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini24 – 164141ExtracellularSequence analysisAdd
BLAST
Transmembranei165 – 18521Helical; Name=1Sequence analysisAdd
BLAST
Topological domaini186 – 23550CytoplasmicSequence analysisAdd
BLAST
Transmembranei236 – 25621Helical; Name=2Sequence analysisAdd
BLAST
Topological domaini257 – 28024ExtracellularSequence analysisAdd
BLAST
Transmembranei281 – 30121Helical; Name=3Sequence analysisAdd
BLAST
Topological domaini302 – 31716CytoplasmicSequence analysisAdd
BLAST
Transmembranei318 – 34023Helical; Name=4Sequence analysisAdd
BLAST
Topological domaini341 – 35313ExtracellularSequence analysisAdd
BLAST
Transmembranei354 – 37421Helical; Name=5Sequence analysisAdd
BLAST
Topological domaini375 – 3773CytoplasmicSequence analysis
Transmembranei378 – 39821Helical; Name=6Sequence analysisAdd
BLAST
Topological domaini399 – 4002ExtracellularSequence analysis
Transmembranei401 – 42323Helical; Name=7Sequence analysisAdd
BLAST
Topological domaini424 – 711288CytoplasmicSequence 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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2323Sequence analysisAdd
BLAST
Chaini24 – 711688Ferric/cupric reductase transmembrane component 2PRO_0000010138Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi85 – 851N-linked (GlcNAc...)Sequence analysis
Glycosylationi108 – 1081N-linked (GlcNAc...)Sequence analysis
Glycosylationi120 – 1201N-linked (GlcNAc...)Sequence analysis
Glycosylationi134 – 1341N-linked (GlcNAc...)Sequence analysis
Glycosylationi341 – 3411N-linked (GlcNAc...)Sequence analysis

Keywords - PTMi

Glycoprotein

Expressioni

Inductioni

By transcription factors AFT1 and AFT2 upon iron deprivation.6 Publications

Interactioni

Protein-protein interaction databases

BioGridi33945. 6 interactions.
DIPiDIP-7473N.
IntActiP36033. 1 interaction.
MINTiMINT-1363650.

Structurei

3D structure databases

ProteinModelPortaliP36033.
SMRiP36033. Positions 441-558.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini280 – 414135Ferric oxidoreductaseAdd
BLAST
Domaini415 – 534120FAD-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.
HOGENOMiHOG000000805.
InParanoidiP36033.
OMAiPPNERCV.
OrthoDBiEOG7PGF10.

Family and domain databases

InterProiIPR013112. FAD-bd_8.
IPR017927. Fd_Rdtase_FAD-bd.
IPR013130. Fe3_Rdtase_TM_dom.
IPR013121. Fe_red_NAD-bd_6.
IPR017938. Riboflavin_synthase-like_b-brl.
[Graphical view]
PfamiPF08022. FAD_binding_8. 1 hit.
PF01794. Ferric_reduct. 1 hit.
PF08030. NAD_binding_6. 1 hit.
[Graphical view]
SUPFAMiSSF63380. SSF63380. 1 hit.
PROSITEiPS51384. FAD_FR. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P36033-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MHWTSILSAI LLFCLSGARA SPAKTVIRNK VPLLVTNACT RIFQKVTWEY
60 70 80 90 100
TSKSKRSSPV CSYEPAFQSM LYCIYETLDE KGYSNKTLEK TFSTIKKNCA
110 120 130 140 150
SYSDALQNMT NSEFYDVLNN GTRHMTPYVK GSANLTYPVE MDTQLRKAYY
160 170 180 190 200
HALHGFYANL DVGNIYGGII CAYFVAIMAF AGVLHCMNYT PFKTVLLKQK
210 220 230 240 250
LVGYVRGYLT LPTIGSKHAS DFSYFRIFTG YLPTRLEGII ILGYLVLHTV
260 270 280 290 300
FLAYGYEYDP ENIIFKSRRV QVARYVADRS GVLAFAHFPL IVLFAGRNNF
310 320 330 340 350
LEYISGVKYT SFIMFHKWLG RMMFLDAMIH GSAYTSYTVA NKTWATSKNR
360 370 380 390 400
LYWQFGVAAL CLAGTMVFFS FAVFRKYFYE AFLFLHIVLG AMFFYACWEH
410 420 430 440 450
VVSLSGIEWI YTAIAIWIVD RIIRIIKASY FGFPKASLQL IGDDLIRLTV
460 470 480 490 500
KKPARPWRAK PGQYVFVSFL HPLYFWQSHP FTVLDSVSKN GELVIILKEK
510 520 530 540 550
KGVTRLVKKY VCRNGGKTSM RLAIEGPYGS SSPVNNYNNV LLLTGGTGLP
560 570 580 590 600
GPIAHAIKLG KTSAAAGKQS VKLVIAVRGF DVLEAYKPEL MCLENLNVQL
610 620 630 640 650
HIYNTMEVPS LTPSDSLDIS QQDEKADEKG TVVATTLEKS ANPLGFDGVV
660 670 680 690 700
FHCGRPNVKE LLHEAAELSG SLSVVCCGPP IFVDKVRNET AKIVLDKSAK
710
AIEYFEEYQC W
Length:711
Mass (Da):80,072
Last modified:June 1, 1994 - v1
Checksum:i3C60346577C80E53
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X75950 Genomic DNA. Translation: CAA53553.1.
Z28220 Genomic DNA. Translation: CAA82065.1.
BK006944 Genomic DNA. Translation: DAA08949.1.
PIRiS38063.
RefSeqiNP_012702.1. NM_001179785.1.

Genome annotation databases

EnsemblFungiiYKL220C; YKL220C; YKL220C.
GeneIDi853660.
KEGGisce:YKL220C.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X75950 Genomic DNA. Translation: CAA53553.1.
Z28220 Genomic DNA. Translation: CAA82065.1.
BK006944 Genomic DNA. Translation: DAA08949.1.
PIRiS38063.
RefSeqiNP_012702.1. NM_001179785.1.

3D structure databases

ProteinModelPortaliP36033.
SMRiP36033. Positions 441-558.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi33945. 6 interactions.
DIPiDIP-7473N.
IntActiP36033. 1 interaction.
MINTiMINT-1363650.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblFungiiYKL220C; YKL220C; YKL220C.
GeneIDi853660.
KEGGisce:YKL220C.

Organism-specific databases

EuPathDBiFungiDB:YKL220C.
SGDiS000001703. FRE2.

Phylogenomic databases

GeneTreeiENSGT00390000007891.
HOGENOMiHOG000000805.
InParanoidiP36033.
OMAiPPNERCV.
OrthoDBiEOG7PGF10.

Enzyme and pathway databases

BioCyciYEAST:YKL220C-MONOMER.

Miscellaneous databases

NextBioi974584.
PROiP36033.

Family and domain databases

InterProiIPR013112. FAD-bd_8.
IPR017927. Fd_Rdtase_FAD-bd.
IPR013130. Fe3_Rdtase_TM_dom.
IPR013121. Fe_red_NAD-bd_6.
IPR017938. Riboflavin_synthase-like_b-brl.
[Graphical view]
PfamiPF08022. FAD_binding_8. 1 hit.
PF01794. Ferric_reduct. 1 hit.
PF08030. NAD_binding_6. 1 hit.
[Graphical view]
SUPFAMiSSF63380. SSF63380. 1 hit.
PROSITEiPS51384. FAD_FR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Sequencing of a 13.2 kb segment next to the left telomere of yeast chromosome XI revealed five open reading frames and recent recombination events with the right arms of chromosomes III and V."
    Alexandraki D., Tzermia M.
    Yeast 10:S81-S91(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: ATCC 204508 / S288c.
  2. "Complete DNA sequence of yeast chromosome XI."
    Dujon B., Alexandraki D., Andre B., Ansorge W., Baladron V., Ballesta J.P.G., Banrevi A., Bolle P.-A., Bolotin-Fukuhara M., Bossier P., Bou G., Boyer J., Buitrago M.J., Cheret G., Colleaux L., Daignan-Fornier B., del Rey F., Dion C.
    , Domdey H., Duesterhoeft A., Duesterhus S., Entian K.-D., Erfle H., Esteban P.F., Feldmann H., Fernandes L., Fobo G.M., Fritz C., Fukuhara H., Gabel C., Gaillon L., Garcia-Cantalejo J.M., Garcia-Ramirez J.J., Gent M.E., Ghazvini M., Goffeau A., Gonzalez A., Grothues D., Guerreiro P., Hegemann J.H., Hewitt N., Hilger F., Hollenberg C.P., Horaitis O., Indge K.J., Jacquier A., James C.M., Jauniaux J.-C., Jimenez A., Keuchel H., Kirchrath L., Kleine K., Koetter P., Legrain P., Liebl S., Louis E.J., Maia e Silva A., Marck C., Monnier A.-L., Moestl D., Mueller S., Obermaier B., Oliver S.G., Pallier C., Pascolo S., Pfeiffer F., Philippsen P., Planta R.J., Pohl F.M., Pohl T.M., Poehlmann R., Portetelle D., Purnelle B., Puzos V., Ramezani Rad M., Rasmussen S.W., Remacha M.A., Revuelta J.L., Richard G.-F., Rieger M., Rodrigues-Pousada C., Rose M., Rupp T., Santos M.A., Schwager C., Sensen C., Skala J., Soares H., Sor F., Stegemann J., Tettelin H., Thierry A., Tzermia M., Urrestarazu L.A., van Dyck L., van Vliet-Reedijk J.C., Valens M., Vandenbol M., Vilela C., Vissers S., von Wettstein D., Voss H., Wiemann S., Xu G., Zimmermann J., Haasemann M., Becker I., Mewes H.-W.
    Nature 369:371-378(1994) [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. "Two distinctly regulated genes are required for ferric reduction, the first step of iron uptake in Saccharomyces cerevisiae."
    Georgatsou E., Alexandraki D.
    Mol. Cell. Biol. 14:3065-3073(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION, SUBCELLULAR LOCATION.
    Strain: ATCC 204508 / S288c.
  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. "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.
  7. "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.
  8. "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.
  9. Erratum
    Martins L.J., Jensen L.T., Simon J.R., Keller G.L., Winge D.R.
    J. Biol. Chem. 273:30056-30056(1998)
  10. "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.
  11. "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.
  12. "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 AND AFT2.
  13. "A global topology map of the Saccharomyces cerevisiae membrane proteome."
    Kim H., Melen K., Oesterberg M., von Heijne G.
    Proc. Natl. Acad. Sci. U.S.A. 103:11142-11147(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: TOPOLOGY [LARGE SCALE ANALYSIS].
    Strain: ATCC 208353 / W303-1A.

Entry informationi

Entry nameiFRE2_YEAST
AccessioniPrimary (citable) accession number: P36033
Secondary accession number(s): D6VWY3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: May 11, 2016
This is version 122 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Miscellaneousi

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 XI
    Yeast (Saccharomyces cerevisiae) chromosome XI: 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.