• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of molcellbPermissionsJournals.ASM.orgJournalMCB ArticleJournal InfoAuthorsReviewers
Mol Cell Biol. Jul 1993; 13(7): 4342–4350.
PMCID: PMC359993

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.


We have identified a cell surface ferric reductase activity in the fission yeast Schizosaccharomyces pombe. A mutant strain deficient in this activity was also deficient in ferric iron uptake, while ferrous iron uptake was not impaired. Therefore, reduction is a required step in cellular ferric iron acquisition. We have cloned frp1+, the wild-type allele of the mutant gene. frp1+ mRNA levels were repressed by iron addition to the growth medium. Fusion of 138 nucleotides of frp1+ promoter sequences to a reporter gene, the bacterial chloramphenicol acetyltransferase gene, conferred iron-dependent regulation upon the latter when introduced into S. pombe. The predicted amino acid sequence of the frp1+ gene exhibits hydrophobic regions compatible with transmembrane domains. 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.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.8M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Chaney RL, Brown JC, Tiffin LO. Obligatory reduction of ferric chelates in iron uptake by soybeans. Plant Physiol. 1972 Aug;50(2):208–213. [PMC free article] [PubMed]
  • Crane FL, Roberts H, Linnane AW, Löw H. Transmembrane ferricyanide reduction by cells of the yeast Saccharomyces cerevisiae. J Bioenerg Biomembr. 1982 Jun;14(3):191–205. [PubMed]
  • Crichton RR, Charloteaux-Wauters M. Iron transport and storage. Eur J Biochem. 1987 May 4;164(3):485–506. [PubMed]
  • Dancis A, Klausner RD, Hinnebusch AG, Barriocanal JG. Genetic evidence that ferric reductase is required for iron uptake in Saccharomyces cerevisiae. Mol Cell Biol. 1990 May;10(5):2294–2301. [PMC free article] [PubMed]
  • Dancis A, Roman DG, Anderson GJ, Hinnebusch AG, Klausner RD. Ferric reductase of Saccharomyces cerevisiae: molecular characterization, role in iron uptake, and transcriptional control by iron. Proc Natl Acad Sci U S A. 1992 May 1;89(9):3869–3873. [PMC free article] [PubMed]
  • Devereux J, Haeberli P, Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. [PMC free article] [PubMed]
  • Eide D, Davis-Kaplan S, Jordan I, Sipe D, Kaplan J. Regulation of iron uptake in Saccharomyces cerevisiae. The ferrireductase and Fe(II) transporter are regulated independently. J Biol Chem. 1992 Oct 15;267(29):20774–20781. [PubMed]
  • Forsburg SL, Guarente L. Identification and characterization of HAP4: a third component of the CCAAT-bound HAP2/HAP3 heteromer. Genes Dev. 1989 Aug;3(8):1166–1178. [PubMed]
  • Ghosh D. TFD: the transcription factors database. Nucleic Acids Res. 1992 May 11;20 (Suppl):2091–2093. [PMC free article] [PubMed]
  • Grimm C, Kohli J, Murray J, Maundrell K. Genetic engineering of Schizosaccharomyces pombe: a system for gene disruption and replacement using the ura4 gene as a selectable marker. Mol Gen Genet. 1988 Dec;215(1):81–86. [PubMed]
  • Karplus PA, Daniels MJ, Herriott JR. Atomic structure of ferredoxin-NADP+ reductase: prototype for a structurally novel flavoenzyme family. Science. 1991 Jan 4;251(4989):60–66. [PubMed]
  • Kyte J, Doolittle RF. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. [PubMed]
  • Lesuisse E, Labbe P. Reductive and non-reductive mechanisms of iron assimilation by the yeast Saccharomyces cerevisiae. J Gen Microbiol. 1989 Feb;135(2):257–263. [PubMed]
  • Lesuisse E, Raguzzi F, Crichton RR. Iron uptake by the yeast Saccharomyces cerevisiae: involvement of a reduction step. J Gen Microbiol. 1987 Nov;133(11):3229–3236. [PubMed]
  • Marshall RD. Glycoproteins. Annu Rev Biochem. 1972;41:673–702. [PubMed]
  • Moreno S, Klar A, Nurse P. Molecular genetic analysis of fission yeast Schizosaccharomyces pombe. Methods Enzymol. 1991;194:795–823. [PubMed]
  • Núez MT, Gaete V, Watkins JA, Glass J. Mobilization of iron from endocytic vesicles. The effects of acidification and reduction. J Biol Chem. 1990 Apr 25;265(12):6688–6692. [PubMed]
  • Orita M, Suzuki Y, Sekiya T, Hayashi K. Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. Genomics. 1989 Nov;5(4):874–879. [PubMed]
  • Orkin SH. Molecular genetics of chronic granulomatous disease. Annu Rev Immunol. 1989;7:277–307. [PubMed]
  • Pearson WR, Lipman DJ. Improved tools for biological sequence comparison. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2444–2448. [PMC free article] [PubMed]
  • Quinn MT, Mullen ML, Jesaitis AJ. Human neutrophil cytochrome b contains multiple hemes. Evidence for heme associated with both subunits. J Biol Chem. 1992 Apr 15;267(11):7303–7309. [PubMed]
  • Raja KB, Simpson RJ, Peters TJ. Investigation of a role for reduction in ferric iron uptake by mouse duodenum. Biochim Biophys Acta. 1992 Jun 10;1135(2):141–146. [PubMed]
  • Rao KK, Shapiro D, Mattia E, Bridges K, Klausner R. Effects of alterations in cellular iron on biosynthesis of the transferrin receptor in K562 cells. Mol Cell Biol. 1985 Apr;5(4):595–600. [PMC free article] [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PMC free article] [PubMed]
  • Segal AW, West I, Wientjes F, Nugent JH, Chavan AJ, Haley B, Garcia RC, Rosen H, Scrace G. Cytochrome b-245 is a flavocytochrome containing FAD and the NADPH-binding site of the microbicidal oxidase of phagocytes. Biochem J. 1992 Jun 15;284(Pt 3):781–788. [PMC free article] [PubMed]
  • Toyama R, Okayama H. Human chorionic gonadotropin alpha and human cytomegalovirus promoters are extremely active in the fission yeast Schizosaccharomyces pombe. FEBS Lett. 1990 Jul 30;268(1):217–221. [PubMed]
  • Walters GO, Jacobs A, Worwood M, Trevett D, Thomson W. Iron absorption in normal subjects and patients with idiopathic haemochromatosis: relationship with serum ferritin concentration. Gut. 1975 Mar;16(3):188–192. [PMC free article] [PubMed]

Articles from Molecular and Cellular Biology are provided here courtesy of American Society for Microbiology (ASM)


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...