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Gene Review

ERG6  -  sterol 24-C-methyltransferase

Saccharomyces cerevisiae S288c

Synonyms: Delta(24)-sterol C-methyltransferase, ISE1, LIS1, SED6, Sterol 24-C-methyltransferase, ...
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Disease relevance of ERG6


High impact information on ERG6

  • NudEL targets dynein to microtubule ends through LIS1 [4].
  • However, in the erg6 mutant, Tat2p is missorted to the vacuole at low tryptophan [5].
  • It was known that the uptake of tryptophan is reduced in the yeast erg6 mutant, which is defective in a late step of ergosterol biosynthesis [5].
  • The erg6 mutation also caused missorting to the multivesicular body pathway in late endosomes [5].
  • The fact that NUDF and LIS1 interact with the same protein domain strengthens the notion that these two proteins are functionally related [6].

Biological context of ERG6


Anatomical context of ERG6

  • ERG6 overexpression rescues vrp1Delta vacuole fusion in a cytosol-dependent manner [11].
  • The 24-alkylated sterols have been shown previously to be absent in membranes of amphotericin B (AmB)-resistant Leishmania donovani promastigotes, suggesting that the S- adenosyl-l-methionine:C-24-Delta-sterol-methyltransferase (SCMT or ERG6) was not functional or not expressed in AmB-resistant (AmB-R) parasites [12].
  • Although erg6 delta cells are unable to methylate ergosterol precursors at C-24, they exhibit normal vegatative growth, suggesting that C-28 sterols are not essential in S. cerevisiae [2].
  • Slow diffusion requires neither the cell wall nor polymerized actin, but it is affected in the ergosterol synthesis mutant erg6 [13].
  • Subsequently, Erg28p was shown to function as an endoplasmic reticulum transmembrane protein, acting as a scaffold to tether the C-4 demethylation enzymatic complex and also to interact with a downstream enzyme, Erg6p [14].

Associations of ERG6 with chemical compounds

  • In the triple mutants, all but 1 (ERG6) of the 13 subsequent reactions of the ergosterol pathway are inactive [15].
  • We now report that under these conditions, an otherwise nonessential, but also fungal-specific, structural modification of the major sterol of yeast, ergosterol, becomes essential, because mutations in ELO3 are synthetically lethal with mutations in ERG6 [8].
  • C. lusitaniae amphotericin B-resistant isolates were found to have increased levels of ERG6 transcript as well as reduced ergosterol content [7].
  • This yeast strain, which is a double mutant of the ERG6 (sterol transmethylase) and ERG2 (C-8 sterol isomerase) genes, accumulates zymosterol as its major sterol component [16].
  • The ERG6 gene that encodes (S)-adenosyl-L-methionine: delta 24(25)-to delta 24(28)-sterol methyl transferase (SMT) enzyme from Saccharomyces cerevisiae was introduced into plasmid pET23a(+) and the resulting native protein was overexpressed in BL21 (DE3) host cells under control of a T7 promoter [17].

Physical interactions of ERG6

  • We conclude that Erg28p may not only anchor the C-4 demethylation enzyme complex to the ER but also acts as a protein bridge to the Erg6p enzyme required for the next ergosterol biosynthetic step [18].

Other interactions of ERG6

  • These profiles were compared to the transcript profiles of strains containing deletions of one of the late-stage ergosterol genes: ERG2, ERG5, or ERG6 [19].
  • ERG6 and PDR5 regulate small lipophilic drug accumulation in yeast cells via distinct mechanisms [20].
  • In erg28 strains, the Erg6p level in the ER fraction was decreased by about 50% relative to the wild-type strain, while ER protein levels of the four other ergosterol proteins showed no significant differences [18].
  • Vacuole-associated actin turnover is decreased in the vrp1Delta strain, but recovered by ERG6 overexpression linking sterol enrichment to actin remodeling [11].
  • Las17p (Vrp1p functional partner) antibodies, which inhibit wild-type vacuole fusion, do not inhibit the fusion of vacuoles from the vrp1Delta-ERG6 overexpression strain [11].

Analytical, diagnostic and therapeutic context of ERG6

  • Immunofluorescence double staining with Erg6p, a marker of lipid particles in yeast, indicates that Srt1p is mainly localized to lipid particles (lipid bodies) [21].


  1. Sterol specificity of the Saccharomyces cerevisiae ERG6 gene product expressed in Escherichia coli. Venkatramesh, M., Guo, D.A., Harman, J.G., Nes, W.D. Lipids (1996) [Pubmed]
  2. The yeast gene ERG6 is required for normal membrane function but is not essential for biosynthesis of the cell-cycle-sparking sterol. Gaber, R.F., Copple, D.M., Kennedy, B.K., Vidal, M., Bard, M. Mol. Cell. Biol. (1989) [Pubmed]
  3. Deletion of the Hsp70 chaperone gene SSB causes hypersensitivity to guanidine toxicity and curing of the [PSI+] prion by increasing guanidine uptake in yeast. Jones, G.W., Song, Y., Masison, D.C. Mol. Genet. Genomics (2003) [Pubmed]
  4. NudEL targets dynein to microtubule ends through LIS1. Li, J., Lee, W.L., Cooper, J.A. Nat. Cell Biol. (2005) [Pubmed]
  5. Ergosterol is required for targeting of tryptophan permease to the yeast plasma membrane. Umebayashi, K., Nakano, A. J. Cell Biol. (2003) [Pubmed]
  6. The LIS1-related NUDF protein of Aspergillus nidulans interacts with the coiled-coil domain of the NUDE/RO11 protein. Efimov, V.P., Morris, N.R. J. Cell Biol. (2000) [Pubmed]
  7. Disruption of ergosterol biosynthesis confers resistance to amphotericin B in Candida lusitaniae. Young, L.Y., Hull, C.M., Heitman, J. Antimicrob. Agents Chemother. (2003) [Pubmed]
  8. A specific structural requirement for ergosterol in long-chain fatty acid synthesis mutants important for maintaining raft domains in yeast. Eisenkolb, M., Zenzmaier, C., Leitner, E., Schneiter, R. Mol. Biol. Cell (2002) [Pubmed]
  9. Transcriptional response pathways in a yeast strain sensitive to saframycin a and a more potent analog: evidence for a common basis of activity. Plowright, A.T., Schaus, S.E., Myers, A.G. Chem. Biol. (2002) [Pubmed]
  10. A genetic analysis of glucocorticoid receptor signaling. Identification and characterization of ligand-effect modulators in Saccharomyces cerevisiae. Sitcheran, R., Emter, R., Kralli, A., Yamamoto, K.R. Genetics (2000) [Pubmed]
  11. Enhanced membrane fusion in sterol-enriched vacuoles bypasses the Vrp1p requirement. Tedrick, K., Trischuk, T., Lehner, R., Eitzen, G. Mol. Biol. Cell (2004) [Pubmed]
  12. Cloning of S-adenosyl-L-methionine:C-24-Delta-sterol-methyltransferase (ERG6) from Leishmania donovani and characterization of mRNAs in wild-type and amphotericin B-Resistant promastigotes. Pourshafie, M., Morand, S., Virion, A., Rakotomanga, M., Dupuy, C., Loiseau, P.M. Antimicrob. Agents Chemother. (2004) [Pubmed]
  13. Slow diffusion of proteins in the yeast plasma membrane allows polarity to be maintained by endocytic cycling. Valdez-Taubas, J., Pelham, H.R. Curr. Biol. (2003) [Pubmed]
  14. Erg28p is a key protein in the yeast sterol biosynthetic enzyme complex. Mo, C., Bard, M. J. Lipid Res. (2005) [Pubmed]
  15. A yeast sterol auxotroph (erg25) is rescued by addition of azole antifungals and reduced levels of heme. Gachotte, D., Pierson, C.A., Lees, N.D., Barbuch, R., Koegel, C., Bard, M. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  16. A simple method for the isolation of zymosterol from a sterol mutant of Saccharomyces cerevisiae. Heiderpriem, R.W., Livant, P.D., Parish, E.J., Barbuch, R.J., Broaddus, M.G., Bard, M. J. Steroid Biochem. Mol. Biol. (1992) [Pubmed]
  17. Overexpression, purification, and stereochemical studies of the recombinant (S)-adenosyl-L-methionine: delta 24(25)- to delta 24(28)-sterol methyl transferase enzyme from Saccharomyces cerevisiae. Nes, W.D., McCourt, B.S., Zhou, W.X., Ma, J., Marshall, J.A., Peek, L.A., Brennan, M. Arch. Biochem. Biophys. (1998) [Pubmed]
  18. The ERG28-encoded protein, Erg28p, interacts with both the sterol C-4 demethylation enzyme complex as well as the late biosynthetic protein, the C-24 sterol methyltransferase (Erg6p). Mo, C., Valachovic, M., Bard, M. Biochim. Biophys. Acta (2004) [Pubmed]
  19. 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]
  20. ERG6 and PDR5 regulate small lipophilic drug accumulation in yeast cells via distinct mechanisms. Emter, R., Heese-Peck, A., Kralli, A. FEBS Lett. (2002) [Pubmed]
  21. Yeast Saccharomyces cerevisiae has two cis-prenyltransferases with different properties and localizations. Implication for their distinct physiological roles in dolichol synthesis. Sato, M., Fujisaki, S., Sato, K., Nishimura, Y., Nakano, A. Genes Cells (2001) [Pubmed]
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