Gene Symbol: FET3
Description: ferroxidase FET3
Alias: ferroxidase FET3
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Wu X, Kim H, Seravalli J, Barycki J, Hart P, Gohara D, et al. Potassium and the K+/H+ Exchanger Kha1p Promote Binding of Copper to ApoFet3p Multi-copper Ferroxidase. J Biol Chem. 2016;291:9796-806 pubmed publisher
    ..Our study reveals a novel functional role of K(+) in the binding of copper to apoFet3p and identifies a K(+)/H(+) exchanger at the secretory pathway as a new molecular factor associated with iron uptake in yeast. ..
  2. Castells Roca L, Muhlenhoff U, Lill R, Herrero E, Belli G. The oxidative stress response in yeast cells involves changes in the stability of Aft1 regulon mRNAs. Mol Microbiol. 2011;81:232-48 pubmed publisher
    Saccharomyces cerevisiae can import iron through a high-affinity system consisting of the Ftr1/Fet3-mediated reductive pathway and the siderophore-mediated non-reductive one...
  3. Askwith C, Eide D, Van Ho A, Bernard P, Li L, Davis Kaplan S, et al. The FET3 gene of S. cerevisiae encodes a multicopper oxidase required for ferrous iron uptake. Cell. 1994;76:403-10 pubmed
    ..We have isolated a mutant, fet3, defective for high affinity Fe(II) uptake...
  4. Bonaccorsi di Patti M, Felice M, De Domenico I, Lania A, Alaleona F, Musci G. Specific aspartate residues in FET3 control high-affinity iron transport in Saccharomyces cerevisiae. Yeast. 2005;22:677-87 pubmed
    Site-directed mutagenesis was performed on a set of six aspartate residues of Fet3, the multicopper ferroxidase involved in high-affinity iron transport in Saccharomyces cerevisiae, in order to comprehend the molecular determinants of the ..
  5. Sato M, Sato K, Nakano A. Endoplasmic reticulum quality control of unassembled iron transporter depends on Rer1p-mediated retrieval from the golgi. Mol Biol Cell. 2004;15:1417-24 pubmed
    ..These findings provide clear evidence that the ER quality control of unassembled membrane proteins can be achieved by retrieval from the Golgi and that Rer1p serves as a specific sorting receptor in this process. ..
  6. Protchenko O, Shakoury Elizeh M, Keane P, Storey J, Androphy R, Philpott C. Role of PUG1 in inducible porphyrin and heme transport in Saccharomyces cerevisiae. Eukaryot Cell. 2008;7:859-71 pubmed publisher
    ..The data from these experiments were consistent with a role for Pug1p in inducible protoporphyrin IX influx and heme efflux. ..
  7. Jensen L, Culotta V. Role of Saccharomyces cerevisiae ISA1 and ISA2 in iron homeostasis. Mol Cell Biol. 2000;20:3918-27 pubmed
    ..Both signals are needed for Isa2p function. A model for the nonredundant roles of Isa1p and Isa2p in delivering iron to sites of the Fe-S cluster assembly is discussed. ..
  8. Quintanar L, Stoj C, Wang T, Kosman D, Solomon E. Role of aspartate 94 in the decay of the peroxide intermediate in the multicopper oxidase Fet3p. Biochemistry. 2005;44:6081-91 pubmed
    ..These studies provide new insight into the role of D94 and proton involvement in the reductive cleavage of the O-O bond. ..
  9. Kwok E, Severance S, Kosman D. Evidence for iron channeling in the Fet3p-Ftr1p high-affinity iron uptake complex in the yeast plasma membrane. Biochemistry. 2006;45:6317-27 pubmed
    ..By analogy to the Fe(III) trafficking that leads to the mineralization of the ferritin core, we propose that ferric iron channeling is a conserved feature of iron homeostasis in aerobic organisms. ..

More Information


  1. Xue Y, Schmollinger S, Attar N, Campos O, Vogelauer M, Carey M, et al. Endoplasmic reticulum-mitochondria junction is required for iron homeostasis. J Biol Chem. 2017;292:13197-13204 pubmed publisher
    ..Our findings reveal that proper communication between the ER and mitochondria is required for appropriate maintenance of cellular iron levels. ..
  2. Xiong H, Kobayashi T, Kakei Y, Senoura T, Nakazono M, Takahashi H, et al. AhNRAMP1 iron transporter is involved in iron acquisition in peanut. J Exp Bot. 2012;63:4437-46 pubmed publisher
    ..Induced expression of AhNRAMP1 in tobacco conferred enhanced tolerance to iron deprivation. These results suggest that the AhNRAMP1 is possibly involved in iron acquisition in peanut plants. ..
  3. Shi X, Stoj C, Romeo A, Kosman D, Zhu Z. Fre1p Cu2+ reduction and Fet3p Cu1+ oxidation modulate copper toxicity in Saccharomyces cerevisiae. J Biol Chem. 2003;278:50309-15 pubmed
    ..Deletion of FET3 leads to iron deficiency; this deletion also causes a copper sensitivity not seen in wild type...
  4. Stearman R, Yuan D, Yamaguchi Iwai Y, Klausner R, Dancis A. A permease-oxidase complex involved in high-affinity iron uptake in yeast. Science. 1996;271:1552-7 pubmed
    ..Two proteins in the plasma membrane of yeast--a multicopper oxidase, encoded by the FET3 gene, and a permease, encoded by the FTR1 gene--were shown to mediate high-affinity iron uptake...
  5. De Freitas J, Liba A, Meneghini R, Valentine J, Gralla E. Yeast lacking Cu-Zn superoxide dismutase show altered iron homeostasis. Role of oxidative stress in iron metabolism. J Biol Chem. 2000;275:11645-9 pubmed
    ..Transcription of the high affinity iron transporter gene, FET3, was enhanced in the sod1 mutant, suggesting that iron transport systems were up-regulated...
  6. Li L, Vulpe C, Kaplan J. Functional studies of hephaestin in yeast: evidence for multicopper oxidase activity in the endocytic pathway. Biochem J. 2003;375:793-8 pubmed
    ..Yeast with a deletion in FET3, which encodes a cell-surface multicopper oxidase, cannot grow on low-iron media...
  7. de Silva D, Davis Kaplan S, Fergestad J, Kaplan J. Purification and characterization of Fet3 protein, a yeast homologue of ceruloplasmin. J Biol Chem. 1997;272:14208-13 pubmed
    The FET3 gene product of Saccharomyces cerevisiae is an essential component of the high affinity iron transport system...
  8. Yun C, Ferea T, Rashford J, Ardon O, Brown P, Botstein D, et al. Desferrioxamine-mediated iron uptake in Saccharomyces cerevisiae. Evidence for two pathways of iron uptake. J Biol Chem. 2000;275:10709-15 pubmed
    ..Deletion of ARN3 did not prevent yeast from using ferrioxamine B as an iron source; however, deletion of ARN3 and FET3, a component of the high affinity ferrous iron transport system, did prevent uptake of ferrioxamine-bound iron and ..
  9. Stoj C, Augustine A, Zeigler L, Solomon E, Kosman D. Structural basis of the ferrous iron specificity of the yeast ferroxidase, Fet3p. Biochemistry. 2006;45:12741-9 pubmed
    ..Indeed, this double mutant functions kinetically better as a laccase, albeit a relatively inefficient one. ..
  10. Protchenko O, Rodriguez Suarez R, Androphy R, Bussey H, Philpott C. A screen for genes of heme uptake identifies the FLC family required for import of FAD into the endoplasmic reticulum. J Biol Chem. 2006;281:21445-57 pubmed
    ..We propose that the FLC genes are required for import of FAD into the lumen of the endoplasmic reticulum, where it is required for disulfide bond formation. ..
  11. Sedlak E, Ziegler L, Kosman D, Wittung Stafshede P. In vitro unfolding of yeast multicopper oxidase Fet3p variants reveals unique role of each metal site. Proc Natl Acad Sci U S A. 2008;105:19258-63 pubmed publisher
    ..Our results suggest that there is a metal-induced tradeoff between overall protein stability and metal coordination in members of the MCO family. ..
  12. Strachotov√° D, Holoubek A, Kucerova H, Benda A, Humpolickova J, Vachova L, et al. Ato protein interactions in yeast plasma membrane revealed by fluorescence lifetime imaging (FLIM). Biochim Biophys Acta. 2012;1818:2126-34 pubmed publisher
    ..In addition, using specially prepared strains, we were able to detect an interaction between molecules of the same Ato protein, namely Ato1p-Ato1p and Ato3p-Ato3p, but not Ato2p-Ato2p. ..
  13. Batista Nascimento L, Toledano M, Thiele D, Rodrigues Pousada C. Yeast protective response to arsenate involves the repression of the high affinity iron uptake system. Biochim Biophys Acta. 2013;1833:997-1005 pubmed publisher
    ..iron responsive transcription factor, Aft1, as a consequence of a defective high-affinity iron uptake mediated by Fet3 and Ftr1, whose mRNAs are drastically decreased upon arsenic exposure...
  14. Kupchak B, Garitaonandia I, Villa N, Mullen M, Weaver M, Regalla L, et al. Probing the mechanism of FET3 repression by Izh2p overexpression. Biochim Biophys Acta. 2007;1773:1124-32 pubmed
    ..we show that the Nrg1p/Nrg2p and Msn2p/Msn4p pairs are epistatic to each other with respect to their effects on FET3 expression...
  15. Pozdnyakova I, Wittung Stafshede P. Non-linear effects of macromolecular crowding on enzymatic activity of multi-copper oxidase. Biochim Biophys Acta. 2010;1804:740-4 pubmed publisher
    ..The observations are compatible with ordering of a non-optimal substrate-binding site and restricted internal dynamics as a result of excluded volume effects making the protein less structurally 'strained'. ..
  16. Hassett R, Yuan D, Kosman D. Spectral and kinetic properties of the Fet3 protein from Saccharomyces cerevisiae, a multinuclear copper ferroxidase enzyme. J Biol Chem. 1998;273:23274-82 pubmed
    ..The Km values for Fe(II) and O2 were 4.8 and 1.3 microM, respectively, while kcat values for Fe(II) and O2 turnover were 9.5 and 2.3 min-1, consistent with an Fe(II):O2 reaction stoichiometry of 4:1. ..
  17. Spizzo T, Byersdorfer C, Duesterhoeft S, Eide D. The yeast FET5 gene encodes a FET3-related multicopper oxidase implicated in iron transport. Mol Gen Genet. 1997;256:547-56 pubmed
    The yeast FET3 gene encodes an integral membrane multicopper oxidase required for high-affinity iron uptake. The FET4 gene encodes an Fe(II) transporter required for low-affinity uptake...
  18. Sanvisens N, Romero A, An X, Zhang C, de Llanos R, Martínez Pastor M, et al. Yeast Dun1 kinase regulates ribonucleotide reductase inhibitor Sml1 in response to iron deficiency. Mol Cell Biol. 2014;34:3259-71 pubmed publisher
    ..by Dun1 under low-Fe conditions is highlighted by the synthetic growth defect observed between dun1? and fet3? fet4? mutants, which is rescued by SML1 deletion...
  19. Singh A, Severance S, Kaur N, Wiltsie W, Kosman D. Assembly, activation, and trafficking of the Fet3p.Ftr1p high affinity iron permease complex in Saccharomyces cerevisiae. J Biol Chem. 2006;281:13355-64 pubmed
    ..The results are consistent with a (minimal) heterodimer model of the Fet3p.Ftr1p complex that supports the trafficking of iron from Fet3p to Ftr1p for iron permeation across the yeast PM. ..
  20. Stoj C, Augustine A, Solomon E, Kosman D. Structure-function analysis of the cuprous oxidase activity in Fet3p from Saccharomyces cerevisiae. J Biol Chem. 2007;282:7862-8 pubmed
    The Fet3 protein from Saccharomyces cerevisiae is a multicopper oxidase with specificity toward Fe(II) and Cu(I)...