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Gene Review

ERG2  -  C-8 sterol isomerase ERG2

Saccharomyces cerevisiae S288c

Synonyms: C-8 sterol isomerase, Delta-8--delta-7 sterol isomerase, YM8325.03, YMR202W
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High impact information on ERG2

  • Overexpression of the sterol isomerase-encoding gene, ERG2, confers enhanced SR resistance [1].
  • We found that the cdc50Delta mutation is synthetically lethal with mutations affecting the late steps of ergosterol synthesis (erg2 to erg6) [2].
  • We isolated a mutant defective in the internalization step of endocytosis in a gene (ERG2) encoding a C-8 sterol isomerase that acts in the late part of the ergosterol biosynthetic pathway [3].
  • In the absence of Erg2p, yeast cells accumulate sterols structurally different from ergosterol, which is the major sterol in wild-type yeast [3].
  • Interestingly, the deduced amino acid sequence was found to be related to fungal C8-C7 sterol isomerase, encoded by the ERG2 gene [4].

Biological context of ERG2

  • Importantly, the purified DNA binding domain of Upc2p bound in vitro to putative sterol response elements in the ERG2 promoter, suggesting that Upc2p increases the expression of the ERG genes by directly binding to their promoters [5].
  • In addition, a 2 mu plasmid overexpression of the ERG2 sequence did not produce FpR [6].
  • When grown under azole drug pressure, the parental, heterozygous deletion and reconstructed strains of CaUPC2 upregulate the ERG2 and ERG11 ergosterol biosynthesis genes, while the homozygous deletion strain shows no such upregulation [7].
  • We demonstrate that erg2 and erg24 mutants are viable in the deletion consortium background but are lethal when combined in the same haploid strain [8].
  • 9E10 c-myc antibodies specifically immunoprecipitated the c-myc tagged protein after [3H]haloperidol photolabeling, unequivocally proving that the drug binding site is localized on the ERG2 gene product [9].

Anatomical context of ERG2

  • Indeed the sigma ligands [3H]haloperidol (Kd = 0.3 nM) and [3H]ifenprodil (Kd = 1.4 nM) bound to a single population of sites in ERG2 wild type yeast microsomes (Bmax values of 77 and 61 pmol/mg of protein, respectively), whereas binding activity was absent in strains carrying ERG2 gene mutations or disruptions [9].

Associations of ERG2 with chemical compounds

  • These profiles were compared to the transcript profiles of strains containing deletions of one of the late-stage ergosterol genes: ERG2, ERG5, or ERG6 [10].
  • ERG2 and ERG24 are yeast sterol biosynthetic genes which are targets of morpholine antifungal compounds [8].
  • The ERG2 gene product has been identified recently as the molecular target of SR 31747A that mediates antiproliferative effects of the drug in yeast [4].
  • Exogenously-supplied zymosterol is entirely transformed into ergosterol, which represses ERG2 transcription [11].
  • Together with an absence of gene dosage effect for ERG2 on fenpropimorph sensitivity, this supports the hypothesis that sterol delta 8-->7-isomerase inhibition does not contribute to the fungicidal activity of fenpropimorph [12].

Other interactions of ERG2

  • A mutation in an otherwise nonessential ERG2 gene is synthetically lethal when combined with mutations in two transcription factors encoded by the UPC2 and ECM22 genes [13].
  • In order to determine whether the ERG2 gene was essential for yeast viability, a LEU2 gene was inserted into the NdeI site (made blunt) of this 1.0 kb fragment [14].
  • Erg2p and Erg3p, two enzymes catalyzing sequential reactions also appear to have different interaction partners [15].


  1. The immunosuppressant SR 31747 blocks cell proliferation by inhibiting a steroid isomerase in Saccharomyces cerevisiae. Silve, S., Leplatois, P., Josse, A., Dupuy, P.H., Lanau, C., Kaghad, M., Dhers, C., Picard, C., Rahier, A., Taton, M., Le Fur, G., Caput, D., Ferrara, P., Loison, G. Mol. Cell. Biol. (1996) [Pubmed]
  2. Defects in structural integrity of ergosterol and the Cdc50p-Drs2p putative phospholipid translocase cause accumulation of endocytic membranes, onto which actin patches are assembled in yeast. Kishimoto, T., Yamamoto, T., Tanaka, K. Mol. Biol. Cell (2005) [Pubmed]
  3. Specific sterols required for the internalization step of endocytosis in yeast. Munn, A.L., Heese-Peck, A., Stevenson, B.J., Pichler, H., Riezman, H. Mol. Biol. Cell (1999) [Pubmed]
  4. Purification and characterization of the human SR 31747A-binding protein. A nuclear membrane protein related to yeast sterol isomerase. Jbilo, O., Vidal, H., Paul, R., De Nys, N., Bensaid, M., Silve, S., Carayon, P., Davi, D., Galiègue, S., Bourrié, B., Guillemot, J.C., Ferrara, P., Loison, G., Maffrand, J.P., Le Fur, G., Casellas, P. J. Biol. Chem. (1997) [Pubmed]
  5. Candida albicans zinc cluster protein Upc2p confers resistance to antifungal drugs and is an activator of ergosterol biosynthetic genes. MacPherson, S., Akache, B., Weber, S., De Deken, X., Raymond, M., Turcotte, B. Antimicrob. Agents Chemother. (2005) [Pubmed]
  6. The identification of a gene family in the Saccharomyces cerevisiae ergosterol biosynthesis pathway. Lai, M.H., Bard, M., Pierson, C.A., Alexander, J.F., Goebl, M., Carter, G.T., Kirsch, D.R. Gene (1994) [Pubmed]
  7. Role of Candida albicans transcription factor Upc2p in drug resistance and sterol metabolism. Silver, P.M., Oliver, B.G., White, T.C. Eukaryotic Cell (2004) [Pubmed]
  8. Synthetically Lethal Interactions Involving Loss of the Yeast ERG24: The Sterol C-14 Reductase Gene. Shah Alam Bhuiyan, M., Eckstein, J., Barbuch, R., Bard, M. Lipids (2007) [Pubmed]
  9. Yeast sterol C8-C7 isomerase: identification and characterization of a high-affinity binding site for enzyme inhibitors. Moebius, F.F., Bermoser, K., Reiter, R.J., Hanner, M., Glossmann, H. Biochemistry (1996) [Pubmed]
  10. Genome-wide expression patterns in Saccharomyces cerevisiae: comparison of drug treatments and genetic alterations affecting biosynthesis of ergosterol. Bammert, G.F., Fostel, J.M. Antimicrob. Agents Chemother. (2000) [Pubmed]
  11. Sterol metabolism and ERG2 gene regulation in the yeast Saccharomyces cerevisiae. Soustre, I., Dupuy, P.H., Silve, S., Karst, F., Loison, G. FEBS Lett. (2000) [Pubmed]
  12. Investigation of the role of sterol delta 8-->7-isomerase in the sensitivity of Saccharomyces cerevisiae to fenpropimorph. Kelly, D.E., Rose, M.E., Kelly, S.L. FEMS Microbiol. Lett. (1994) [Pubmed]
  13. A mutation in sphingolipid synthesis suppresses defects in yeast ergosterol metabolism. Valachovic, M., Wilcox, L.I., Sturley, S.L., Bard, M. Lipids (2004) [Pubmed]
  14. Cloning and disruption of the yeast C-8 sterol isomerase gene. Ashman, W.H., Barbuch, R.J., Ulbright, C.E., Jarrett, H.W., Bard, M. Lipids (1991) [Pubmed]
  15. A systematic study of yeast sterol biosynthetic protein-protein interactions using the split-ubiquitin system. Mo, C., Bard, M. Biochim. Biophys. Acta (2005) [Pubmed]
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