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Gene Review

GEF1  -  Gef1p

Saccharomyces cerevisiae S288c

Synonyms: Anion/proton exchange transporter GEF1, CLC protein GEF1, CLCY1, ClC-A, ClC-Y1, ...
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Disease relevance of GEF1

  • This process, which requires both Gef1 and the Menkes disease Cu2+-ATPase yeast homolog Ccc2, occurs in late- or post-Golgi vesicles, where Gef1 and Ccc2 are localized [1].
  • The functions of Gef1 in cation homeostasis provide clues to the understanding of diseases caused by chloride channel mutations in humans and cation toxicity in plants [1].

High impact information on GEF1

  • A defect in the yeast GEF1 gene, a CLC chloride channel homolog leads to an iron requirement and cation sensitivity [1].
  • The defects of gef1 mutants can be suppressed by the introduction of Torpedo marmorata CLC-0 or Arabidopsis thaliana CLC-c and -d chloride channel genes [1].
  • Mutations gef1, stp22, STP26, and STP27 in Saccharomyces cerevisiae were identified as suppressors of the temperature-sensitive alpha-factor receptor (mutation ste2-3) and arginine permease (mutation can1(ts)) [2].
  • We show that binding of Arr4p to the C terminus of Gef1p requires the presence of yeast cytosol and is sensitive to a highly specific copper chelator in vitro and in vivo [3].
  • Kex2p and Gef1p, which are considered to reside in the post-Golgi vesicles, were suggested as required for the V-ATPase function; hence, their null mutant phenotype should have been similar to the V-ATPase null mutants [4].

Biological context of GEF1

  • We show that, in addition to the known differences between those yeast phenotypes, deletions of KEX2 or GEF1 in yeast do not affect the distribution of Pma1p as the V-ATPase null mutant does [4].
  • CLCN3 protein also shows a high similarity with GEF1, an integral membrane protein of the yeast Saccharomyces cerevisiae known to be involved in respiration and iron-limited cell growth, and with the predicted protein product of a DNA sequence from the mold Septoria nodorum [5].
  • Oxygen consumption by intact gef1- cells and by mitochondrial fractions isolated from gef1- mutants was reduced 25-50% relative to wild type, indicating that mitochondrial function is defective in these mutants [6].
  • A gef1- deletion mutation generated in vitro and introduced into wild-type haploid strains by gene transplacement was not lethal [6].

Anatomical context of GEF1

  • Injection of OmCLC-3 and OmCLC-5 cRNAs into Xenopus oocytes did not elicit chloride currents, but these clones did functionally complement the gef1 phenotype of YPH250(gef), a yeast strain in which a single CLC channel (GEF1) has been disrupted by homologous recombination [7].
  • Copper alone can substitute for cytosol to support the interaction of Arr4p with the C terminus of Gef1p [3].

Associations of GEF1 with chemical compounds

  • Gef1- mutants also fail to grow on a fermentable carbon source, glucose, when iron is reduced to low concentrations in the medium, suggesting that the GEF1 gene is required for efficient metabolism of iron during growth on fermentable as well as respired carbon sources [6].
  • Systematic alanine scanning of the amino and the carboxyl terminus revealed several regions essential for Gef1p localization and function [8].
  • However, no defect in vacuolar acidification is apparent from quinacrine staining, and Gef1p co-localizes with Mnt1p in the medial Golgi [8].

Other interactions of GEF1

  • Since disruption of GEF2, a subunit of the vacuolar H+-ATPase, leads to a similar phenotype, it was previously suggested that the chloride conductance provided by Gef1p is necessary for vacuolar acidification [8].
  • The single yeast CLC protein Gef1p is localized to the Golgi and endosomal system [9].
  • Functional substitution for Gef1p was, however, achieved in the presence of an increased level of intact or C-terminally truncated yeast Kha1 protein [10].


  1. The yeast CLC chloride channel functions in cation homeostasis. Gaxiola, R.A., Yuan, D.S., Klausner, R.D., Fink, G.R. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  2. Yeast mutants affecting possible quality control of plasma membrane proteins. Li, Y., Kane, T., Tipper, C., Spatrick, P., Jenness, D.D. Mol. Cell. Biol. (1999) [Pubmed]
  3. The yeast Arr4p ATPase binds the chloride transporter Gef1p when copper is available in the cytosol. Metz, J., Wächter, A., Schmidt, B., Bujnicki, J.M., Schwappach, B. J. Biol. Chem. (2006) [Pubmed]
  4. Altered distribution of the yeast plasma membrane H+-ATPase as a feature of vacuolar H+-ATPase null mutants. Perzov, N., Nelson, H., Nelson, N. J. Biol. Chem. (2000) [Pubmed]
  5. Characterization of a human and murine gene (CLCN3) sharing similarities to voltage-gated chloride channels and to a yeast integral membrane protein. Borsani, G., Rugarli, E.I., Taglialatela, M., Wong, C., Ballabio, A. Genomics (1995) [Pubmed]
  6. The GEF1 gene of Saccharomyces cerevisiae encodes an integral membrane protein; mutations in which have effects on respiration and iron-limited growth. Greene, J.R., Brown, N.H., DiDomenico, B.J., Kaplan, J., Eide, D.J. Mol. Gen. Genet. (1993) [Pubmed]
  7. Molecular cloning of CLC chloride channels in Oreochromis mossambicus and their functional complementation of yeast CLC gene mutant. Miyazaki, H., Uchida, S., Takei, Y., Hirano, T., Marumo, F., Sasaki, S. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  8. Golgi localization and functionally important domains in the NH2 and COOH terminus of the yeast CLC putative chloride channel Gef1p. Schwappach, B., Stobrawa, S., Hechenberger, M., Steinmeyer, K., Jentsch, T.J. J. Biol. Chem. (1998) [Pubmed]
  9. The yeast CLC chloride channel is proteolytically processed by the furin-like protease Kex2p in the first extracellular loop. Wächter, A., Schwappach, B. FEBS Lett. (2005) [Pubmed]
  10. The functioning of mammalian ClC-2 chloride channel in Saccharomyces cerevisiae cells requires an increased level of Kha1p. Flis, K., Hinzpeter, A., Edelman, A., Kurlandzka, A. Biochem. J. (2005) [Pubmed]
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