fmn reductase


Summary: An enzyme that utilizes NADH or NADPH to reduce FLAVINS. It is involved in a number of biological processes that require reduced flavin for their functions such as bacterial bioluminescence. Formerly listed as EC and EC

Top Publications

  1. Vargas J, Herpers B, McKie A, Gledhill S, McDonnell J, van den Heuvel M, et al. Stromal cell-derived receptor 2 and cytochrome b561 are functional ferric reductases. Biochim Biophys Acta. 2003;1651:116-23 pubmed
    ..Moreover, we demonstrate the presence of mouse sdr2 in the choroid plexus and in the ependymal cells lining the four ventricles, through in situ hybridization analysis. ..
  2. Schmidt W, Tittel J, Schikora A. Role of hormones in the induction of iron deficiency responses in Arabidopsis roots. Plant Physiol. 2000;122:1109-18 pubmed
    ..Our data indicate that the morphological and physiological components of the Fe stress syndrome are regulated separately. ..
  3. Ohgami R, Campagna D, Greer E, Antiochos B, McDonald A, Chen J, et al. Identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells. Nat Genet. 2005;37:1264-9 pubmed
    ..Taken together, these findings indicate that Steap3 is an endosomal ferrireductase required for efficient Tf-dependent iron uptake in erythroid cells. ..
  4. Vert G, Briat J, Curie C. Dual regulation of the Arabidopsis high-affinity root iron uptake system by local and long-distance signals. Plant Physiol. 2003;132:796-804 pubmed
    ..On the basis of the new molecular insights provided in this study and given the strict coregulation of IRT1 and FRO2 observed, we present a model of local and long-distance regulation of the root iron uptake system in Arabidopsis. ..
  5. Grissa I, Bidard F, Grognet P, Grossetete S, Silar P. The Nox/Ferric reductase/Ferric reductase-like families of Eumycetes. Fungal Biol. 2010;114:766-77 pubmed publisher
    ..Importantly, functional characterization of IMRs has been made on proteins belonging to only two families, while nothing or very little is known about the proteins of the other 22 families. ..
  6. Rogers E, Guerinot M. FRD3, a member of the multidrug and toxin efflux family, controls iron deficiency responses in Arabidopsis. Plant Cell. 2002;14:1787-99 pubmed
    ..The phenotypes of frd3 mutant plants, which are consistent with a defect in either iron deficiency signaling or iron distribution, indicate that FRD3 is an important component of iron homeostasis in Arabidopsis. ..
  7. Delhaize E. A metal-accumulator mutant of Arabidopsis thaliana. Plant Physiol. 1996;111:849-55 pubmed
    ..Taken together, these results suggest that the man1 mutation disrupts the regulation of metal-ion uptake or homeostasis in Arabidopsis. ..
  8. Yuan Y, Wu H, Wang N, Li J, Zhao W, Du J, et al. FIT interacts with AtbHLH38 and AtbHLH39 in regulating iron uptake gene expression for iron homeostasis in Arabidopsis. Cell Res. 2008;18:385-97 pubmed publisher
  9. Robinson N, Procter C, Connolly E, Guerinot M. A ferric-chelate reductase for iron uptake from soils. Nature. 1999;397:694-7 pubmed
    ..Introduction of functional FRO2 complements the frd1-1 phenotype in transgenic plants. The isolation of FRO2 has implications for the generation of crops with improved nutritional quality and increased growth in iron-deficient soils. ..

More Information


  1. Connolly E, Campbell N, Grotz N, Prichard C, Guerinot M. Overexpression of the FRO2 ferric chelate reductase confers tolerance to growth on low iron and uncovers posttranscriptional control. Plant Physiol. 2003;133:1102-10 pubmed
    ..Finally, the 35S-FRO2 plants grow better on low iron as compared with wild-type plants, supporting the idea that reduction of ferric iron to ferrous iron is the rate-limiting step in iron uptake. ..
  2. Wu H, Li L, Du J, Yuan Y, Cheng X, Ling H. Molecular and biochemical characterization of the Fe(III) chelate reductase gene family in Arabidopsis thaliana. Plant Cell Physiol. 2005;46:1505-14 pubmed
  3. Mukherjee I, Campbell N, Ash J, Connolly E. Expression profiling of the Arabidopsis ferric chelate reductase (FRO) gene family reveals differential regulation by iron and copper. Planta. 2006;223:1178-90 pubmed
    ..Together our results suggest that FRO family members function in metal ion homeostasis in a variety of locations in the plant. ..
  4. Colangelo E, Guerinot M. The essential basic helix-loop-helix protein FIT1 is required for the iron deficiency response. Plant Cell. 2004;16:3400-12 pubmed
    ..We demonstrate that FIT1 regulates FRO2 at the level of mRNA accumulation and IRT1 at the level of protein accumulation. We propose a new model for iron uptake in Arabidopsis where FRO2 and IRT1 are differentially regulated by FIT1. ..
  5. Fontecave M, Coves J, Pierre J. Ferric reductases or flavin reductases?. Biometals. 1994;7:3-8 pubmed
    ..This strongly suggests that, in general, the reduction of iron depends on reduced flavins provided by flavin reductases. ..
  6. Feng H, An F, Zhang S, Ji Z, Ling H, Zuo J. Light-regulated, tissue-specific, and cell differentiation-specific expression of the Arabidopsis Fe(III)-chelate reductase gene AtFRO6. Plant Physiol. 2006;140:1345-54 pubmed
    ..We propose that AtFRO6 expression is light regulated in a tissue- or cell differentiation-specific manner to facilitate the acquisition of iron in response to distinctive developmental cues. ..
  7. Wyman S, Simpson R, McKie A, Sharp P. Dcytb (Cybrd1) functions as both a ferric and a cupric reductase in vitro. FEBS Lett. 2008;582:1901-6 pubmed publisher
    ..In support of this hypothesis, we show that 59Fe uptake was significantly enhanced in Dcytb-EGFP expressing MDCK cells which endogenously express DMT1. ..
  8. Bernal M, Casero D, Singh V, Wilson G, Grande A, Yang H, et al. Transcriptome sequencing identifies SPL7-regulated copper acquisition genes FRO4/FRO5 and the copper dependence of iron homeostasis in Arabidopsis. Plant Cell. 2012;24:738-61 pubmed publisher
    ..These insights into root Cu uptake and the interaction between Cu and Fe homeostasis will advance plant nutrition, crop breeding, and biogeochemical research. ..
  9. Wilson M, Lewis T, Miller M, McCormick M, Britigan B. Leishmania chagasi: uptake of iron bound to lactoferrin or transferrin requires an iron reductase. Exp Parasitol. 2002;100:196-207 pubmed
  10. Zaharieva T, Abadía J. Iron deficiency enhances the levels of ascorbate, glutathione, and related enzymes in sugar beet roots. Protoplasma. 2003;221:269-75 pubmed
    ..This suggests that the ascorbate-glutathione cycle would play certain roles in the general Fe deficiency stress responses in strategy I plants. ..
  11. Singh A, Kaur N, Kosman D. The metalloreductase Fre6p in Fe-efflux from the yeast vacuole. J Biol Chem. 2007;282:28619-26 pubmed
    ..Demonstrating a role for a vacuolar metalloreductase in Fe-efflux supports the model that iron is stored in the vacuole in the ferric state. ..
  12. Vert G, Grotz N, Dedaldechamp F, Gaymard F, Guerinot M, Briat J, et al. IRT1, an Arabidopsis transporter essential for iron uptake from the soil and for plant growth. Plant Cell. 2002;14:1223-33 pubmed
    ..These results clearly demonstrate that IRT1 is the major transporter responsible for high-affinity metal uptake under iron deficiency. ..
  13. Rees E, Thiele D. Identification of a vacuole-associated metalloreductase and its role in Ctr2-mediated intracellular copper mobilization. J Biol Chem. 2007;282:21629-38 pubmed
    ..This work provides a model for communication between the extracellular Cu(I) uptake and the intracellular Cu(I) mobilization machinery. ..
  14. Stein R, Waters B. Use of natural variation reveals core genes in the transcriptome of iron-deficient Arabidopsis thaliana roots. J Exp Bot. 2012;63:1039-55 pubmed publisher
    ..This study demonstrates the use of natural variation to identify central Fe-deficiency-regulated genes in plants, and identified genes with potential new roles in signalling during Fe deficiency. ..
  15. Einset J, Winge P, Bones A, Connolly E. The FRO2 ferric reductase is required for glycine betaine's effect on chilling tolerance in Arabidopsis roots. Physiol Plant. 2008;134:334-41 pubmed publisher
    ..These experiments identify a new physiological function for FRO2, i.e. blocking ROS accumulation during chilling. They also suggest that GB has a major effect on FRO2 activity posttranscriptionally in the cold. ..
  16. Waters B, Blevins D, Eide D. Characterization of FRO1, a pea ferric-chelate reductase involved in root iron acquisition. Plant Physiol. 2002;129:85-94 pubmed
    ..These results indicate differential regulation of FRO1 in roots and shoots, and improper FRO1 regulation in response to a shoot-derived signal of iron status in the roots of the brz and dgl mutants. ..
  17. Jeong J, Cohu C, Kerkeb L, Pilon M, Connolly E, Guerinot M. Chloroplast Fe(III) chelate reductase activity is essential for seedling viability under iron limiting conditions. Proc Natl Acad Sci U S A. 2008;105:10619-24 pubmed publisher
    ..Overall, our results provide molecular evidence that FRO7 plays a role in chloroplast iron acquisition and is required for efficient photosynthesis in young seedlings and for survival under iron-limiting conditions. ..
  18. Yun C, Bauler M, Moore R, Klebba P, Philpott C. The role of the FRE family of plasma membrane reductases in the uptake of siderophore-iron in Saccharomyces cerevisiae. J Biol Chem. 2001;276:10218-23 pubmed
    ..We propose that Fre3p and Fre4p are siderophore-iron reductases and that the apparent redundancy of the FRE genes confers the capacity to utilize iron from a variety of siderophore sources. ..
  19. Leitsch D, Kolarich D, Duchene M. The flavin inhibitor diphenyleneiodonium renders Trichomonas vaginalis resistant to metronidazole, inhibits thioredoxin reductase and flavin reductase, and shuts off hydrogenosomal enzymatic pathways. Mol Biochem Parasitol. 2010;171:17-24 pubmed publisher
    ..Finally, we present direct evidence that the increased expression of antioxidant enzymes is dispensable for acquiring resistance to metronidazole. ..
  20. McKie A. A ferrireductase fills the gap in the transferrin cycle. Nat Genet. 2005;37:1159-60 pubmed
  21. Bérczi A, Su D, Asard H. An Arabidopsis cytochrome b561 with trans-membrane ferrireductase capability. FEBS Lett. 2007;581:1505-8 pubmed
    ..We provide evidence for the reduction of ferric-chelates by the reduced TCytb. It is also shown that TCytb is capable of trans-membrane electron transport from intracellular ascorbate to extracellular ferric-chelates in yeast cells. ..
  22. Roman D, Dancis A, Anderson G, Klausner R. The fission yeast ferric reductase gene frp1+ is required for ferric iron uptake and encodes a protein that is homologous to the gp91-phox subunit of the human NADPH phagocyte oxidoreductase. Mol Cell Biol. 1993;13:4342-50 pubmed
    ..It shows similarity to the Saccharomyces cerevisiae FRE1 gene product and the gp91-phox protein, a component of the human NADPH phagocyte oxidoreductase that is deficient in X-linked chronic granulomatous disease. ..
  23. Su D, Asard H. Three mammalian cytochromes b561 are ascorbate-dependent ferrireductases. FEBS J. 2006;273:3722-34 pubmed
    ..Possible roles of these residues in lysosomal cytochrome b are discussed. This study demonstrates the ascorbate-dependent transmembrane ferrireductase activities of members of the mammalian cytochrome b(561) family of proteins. ..
  24. Georgatsou E, Mavrogiannis L, Fragiadakis G, Alexandraki D. The yeast Fre1p/Fre2p cupric reductases facilitate copper uptake and are regulated by the copper-modulated Mac1p activator. J Biol Chem. 1997;272:13786-92 pubmed
    ..1993) EMBO J. 12, 5051-5056), accounts for both the copper-dependent induction of FRE1 and down-regulation of FRE2 gene. Finally, Mac1p transcriptional activation function is itself modulated by the availability of copper. ..
  25. Vorontsov I, Minasov G, Brunzelle J, Shuvalova L, Kiryukhina O, Collart F, et al. Crystal structure of an apo form of Shigella flexneri ArsH protein with an NADPH-dependent FMN reductase activity. Protein Sci. 2007;16:2483-90 pubmed
    ..function of the gene product is unknown, the ArsH protein was annotated as a member of the NADPH-dependent FMN reductase family based on a conserved (T/S)XRXXSX(T/S) fingerprint motif common for FMN binding proteins...
  26. Vasconcelos M, Eckert H, Arahana V, Graef G, Grusak M, Clemente T. Molecular and phenotypic characterization of transgenic soybean expressing the Arabidopsis ferric chelate reductase gene, FRO2. Planta. 2006;224:1116-28 pubmed
    ..These results suggest that heterologous expression of an iron chelate reductase in soybean can provide a route to alleviate iron deficiency chlorosis. ..
  27. Agarwal R, Bonanno J, Burley S, Swaminathan S. Structure determination of an FMN reductase from Pseudomonas aeruginosa PA01 using sulfur anomalous signal. Acta Crystallogr D Biol Crystallogr. 2006;62:383-91 pubmed publisher
    ..Here, the de novo automated crystal structure determination at 1.28 A resolution of an NAD(P)H-dependent FMN reductase flavoprotein from Pseudomonas aeruginosa PA01-derived protein Q9I4D4 using the anomalous signal from an ..
  28. Chen W, Yang J, Qin C, Jin C, Mo J, Ye T, et al. Nitric oxide acts downstream of auxin to trigger root ferric-chelate reductase activity in response to iron deficiency in Arabidopsis. Plant Physiol. 2010;154:810-9 pubmed publisher
    ..Therefore, we presented a novel signaling pathway where NO acts downstream of auxin to activate root FCR activity under Fe deficiency in Arabidopsis. ..
  29. Hassett R, Kosman D. Evidence for Cu(II) reduction as a component of copper uptake by Saccharomyces cerevisiae. J Biol Chem. 1995;270:128-34 pubmed
    ..This results in the reductive mobilization of the copper from periplasmic chelating agents, making the free ion available for translocation across the plasma membrane. ..
  30. Schröder I, Johnson E, de Vries S. Microbial ferric iron reductases. FEMS Microbiol Rev. 2003;27:427-47 pubmed
    ..Ferric reductases do not form a single family, but appear to be distinct enzymes suggesting that several independent strategies for iron reduction may have evolved. ..
  31. McKie A, Latunde Dada G, Miret S, McGregor J, Anderson G, Vulpe C, et al. Molecular evidence for the role of a ferric reductase in iron transport. Biochem Soc Trans. 2002;30:722-4 pubmed
    ..The protein is expressed in other tissues and may account for ferric reductase activity at other sites in the body. ..
  32. Kosman D. Redox cycling in iron uptake, efflux, and trafficking. J Biol Chem. 2010;285:26729-35 pubmed publisher
    ..As a transition metal ion, iron can be "metabolized" only by this redox cycling, which is catalyzed in aerobes by the coupled activities of ferric iron reductases (ferrireductases) and ferrous iron oxidases (ferroxidases). ..
  33. Santi S, Schmidt W. Laser microdissection-assisted analysis of the functional fate of iron deficiency-induced root hairs in cucumber. J Exp Bot. 2008;59:697-704 pubmed publisher
    ..The results also show that this includes the differential regulation of ATPase isoforms with similar function, but supposedly different characteristics, to counteract the imbalance in nutrient supply efficiently. ..
  34. Kosman D. Molecular mechanisms of iron uptake in fungi. Mol Microbiol. 2003;47:1185-97 pubmed
    ..The integration of these multiple uptake mechanisms and their regulation into over-all iron homeostasis in yeast concludes this brief review. ..
  35. Martins L, Jensen L, Simon J, Keller G, Winge D, Simons J. Metalloregulation of FRE1 and FRE2 homologs in Saccharomyces cerevisiae. J Biol Chem. 1998;273:23716-21 pubmed
    ..From the three Mac1-responsive elements in FRE7, a new consensus sequence for Mac1 binding can be established as TTTGC(T/G)C(A/G). ..
  36. Nyhus K, Jacobson E. Genetic and physiologic characterization of ferric/cupric reductase constitutive mutants of Cryptococcus neoformans. Infect Immun. 1999;67:2357-65 pubmed
    ..Sensitivity to oxidants may be related to iron acquisition by a variety of mechanisms and may model the interaction of the yeast with the immune system. ..
  37. Kwon D, el Zaatari F, Kato M, Osato M, Reddy R, Yamaoka Y, et al. Analysis of rdxA and involvement of additional genes encoding NAD(P)H flavin oxidoreductase (FrxA) and ferredoxin-like protein (FdxB) in metronidazole resistance of Helicobacter pylori. Antimicrob Agents Chemother. 2000;44:2133-42 pubmed
    ..These results are consistent with the hypothesis that null mutations in fdxB, frxA, or rdxA may be involved in Mtz resistance. ..
  38. Raza W, Shen Q. Growth, Fe3+ reductase activity, and siderophore production by Paenibacillus polymyxa SQR-21 under differential iron conditions. Curr Microbiol. 2010;61:390-5 pubmed publisher
    ..This article is the first to report the kinetic study of P. polymyxa under differential iron availability. The information provided here gives initial information about the iron uptake mechanism of P. polymyxa. ..
  39. Wang S, Wu Y, Outten F. Fur and the novel regulator YqjI control transcription of the ferric reductase gene yqjH in Escherichia coli. J Bacteriol. 2011;193:563-74 pubmed publisher
    ..Our results suggest that the YqjI protein controls expression of yqjH to help maintain iron homeostasis under conditions (such as elevated cellular nickel levels) that disrupt iron metabolism. ..
  40. Gao B, Ellis H. Altered mechanism of the alkanesulfonate FMN reductase with the monooxygenase enzyme. Biochem Biophys Res Commun. 2005;331:1137-45 pubmed
    The two-component alkanesulfonate monooxygenase system from Escherichia coli is comprised of an FMN reductase (SsuE) and a monooxygenase enzyme (SsuD) that together catalyze the oxidation of alkanesulfonate to the corresponding aldehyde ..
  41. Zhang X, Krause K, Xenarios I, Soldati T, Boeckmann B. Evolution of the ferric reductase domain (FRD) superfamily: modularity, functional diversification, and signature motifs. PLoS ONE. 2013;8:e58126 pubmed publisher
    ..The FRD superfamily most likely originated in bacteria. ..
  42. Singh A, Haldar S, Horback K, Tom C, Zhou L, Meyerson H, et al. Prion protein regulates iron transport by functioning as a ferrireductase. J Alzheimers Dis. 2013;35:541-52 pubmed publisher
    ..These observations explain the correlation between PrPC expression and cellular iron levels, and the cause of iron imbalance in sporadic-Creutzfeldt-Jakob-disease brains where PrPC accumulates as insoluble aggregates. ..
  43. Urzica E, Casero D, Yamasaki H, Hsieh S, Adler L, Karpowicz S, et al. Systems and trans-system level analysis identifies conserved iron deficiency responses in the plant lineage. Plant Cell. 2012;24:3921-48 pubmed publisher
    ..CGLD27/At5g67370 is a highly conserved, presumed chloroplast-localized pioneer protein and is important for growth of Arabidopsis thaliana in low iron. ..
  44. Louie T, Webster C, Xun L. Genetic and biochemical characterization of a 2,4,6-trichlorophenol degradation pathway in Ralstonia eutropha JMP134. J Bacteriol. 2002;184:3492-500 pubmed
    ..Sequence analysis suggests that tcpB may function as an FAD reductase, but experimental data did not support this hypothesis. The function of TcpB remains unknown. ..
  45. Bolychevtseva I, Mazhorova L, Terekhova I, Egorova E, Shugaev A, Rakhimberdieva M, et al. [A new type of adaptation of the cyanobacterium Spirulina platensis to illumination conditions]. Prikl Biokhim Mikrobiol. 2003;39:571-6 pubmed
  46. Vetrova E, Kudryasheva N, Kratasyuk V. Redox compounds influence on the NAD(P)H:FMN-oxidoreductase-luciferase bioluminescent system. Photochem Photobiol Sci. 2007;6:35-40 pubmed
    ..A comparative analysis of the effect of quinones, phenols and inorganic redox compounds on bioluminescent coupled enzyme systems has been carried out. ..
  47. Kozmin S, Wang J, Schaaper R. Role for CysJ flavin reductase in molybdenum cofactor-dependent resistance of Escherichia coli to 6-N-hydroxylaminopurine. J Bacteriol. 2010;192:2026-33 pubmed publisher
    ..In support of the proposed interaction of the CysJ and YcbX proteins, we show that an apparent CysJ-YcbX "hybrid" protein from two Vibrio species is capable of compensating for a double cysJ ycbX defect in E. coli. ..
  48. Gerasimova M, Sizykh A, Slyusareva E. The role of energy transfer in bioluminescence quenching by xanthene dyes. J Photochem Photobiol B. 2009;97:117-22 pubmed publisher
  49. Izumoto Y, Mori T, Yamamoto K. Cloning and nucleotide sequence of the gene for NADH:FMN oxidoreductase from Vibrio harveyi. Biochim Biophys Acta. 1994;1185:243-6 pubmed
    ..The deduced amino acid sequence, 237 amino acids long, shows 48% identity with E. coli NAD(P)H:flavin oxidoreductase and 40% identity with Vibrio harveyi luxG gene product. ..
  50. Moore C, Cook Johnson R, Rudhe C, Whelan J, Day D, Wiskich J, et al. Identification of AtNDI1, an internal non-phosphorylating NAD(P)H dehydrogenase in Arabidopsis mitochondria. Plant Physiol. 2003;133:1968-78 pubmed
    ..the in vitro translation product of AtNDI1 is imported into isolated mitochondria and located on the inside of the inner membrane. ..
  51. Rodríguez Celma J, Vázquez Reina S, Orduna J, Abadía A, Abadía J, Alvarez Fernández A, et al. Characterization of flavins in roots of Fe-deficient strategy I plants, with a focus on Medicago truncatula. Plant Cell Physiol. 2011;52:2173-89 pubmed publisher
    ..The possible roles of Rbfl and Rbfl derivatives in roots and nutrient solutions are discussed. Medicago truncatula is proposed as a model system for flavin studies. ..
  52. Yeom J, Jeon C, Madsen E, Park W. Ferredoxin-NADP+ reductase from Pseudomonas putida functions as a ferric reductase. J Bacteriol. 2009;191:1472-9 pubmed publisher
    ..putida as flavin and ferric reductases. Furthermore, our results indicated that FprB may perform a crucial role as a NADH-dependent ferric/flavin reductase under iron stress conditions. ..
  53. Durrett T, Connolly E, Rogers E. Arabidopsis cpFtsY mutants exhibit pleiotropic defects including an inability to increase iron deficiency-inducible root Fe(III) chelate reductase activity. Plant J. 2006;47:467-79 pubmed
    ..The presence of cpFtsY mRNA and protein in the roots of wild-type plants suggests additional roles for this protein, in addition to its known function in targeting proteins to the thylakoid membrane in chloroplasts. ..