The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

ADH2  -  alcohol dehydrogenase ADH2

Saccharomyces cerevisiae S288c

Synonyms: ADR2, Alcohol dehydrogenase 2, Alcohol dehydrogenase II, YADH-2, YM9952.05C, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of ADH2


High impact information on ADH2

  • This is consistent with the hypothesis that before the Adh1-Adh2 duplication, yeast did not accumulate ethanol for later consumption but rather used Adh(A) to recycle NADH generated in the glycolytic pathway [5].
  • Yeast later consumes the accumulated ethanol, exploiting Adh2, an Adh1 homolog differing by 24 (of 348) amino acids [5].
  • Our data suggest that glucose repression of ADH2 is in part mediated through a cAMP-dependent phosphorylation-inactivation of the ADR1 regulatory protein [6].
  • We report here the sequencing of the 5'-flanking regions of two such promoter-up, constitutive ADR2 mutants, in both of which the mutant phenotype is associated with an increase in length of a poly(A) X poly(T) tract 222 base pairs (bp) upstream of the gene [7].
  • If this region is deleted, ADR2 is no longer repressed by glucose [8].

Chemical compound and disease context of ADH2


Biological context of ADH2

  • In the context of the ADH2 upstream regulatory region, including UAS1, working in concert with the ADH2 basal promoter elements, UAS2-dependent gene activation was dependent on orientation, copy number, and helix phase [10].
  • Two cis-acting upstream activation sequences (UAS) that function synergistically in the derepression of ADH2 gene expression have been identified [10].
  • The nucleotide sequence of the presumed leader peptide has a high degree of identity with the untranslated leader regions of ADH1 and ADH2 mRNAs [11].
  • In contrast, UAS2-dependent expression of a reporter gene containing the ADH2 basal promoter and coding sequence was enhanced by multimerization of UAS2 and was independent of UAS2 orientation [10].
  • ADR1 has two zinc finger domains between amino acids 102 and 159, and it binds to an upstream activation sequence (UAS1) in the ADH2 promoter [12].

Anatomical context of ADH2

  • Mutations in the NOT genes affected many of the same genes and processes that are affected by defects in the CCR4 complex components, including reduction in ADH2 derepression, defective cell wall integrity and increased sensitivity to monoand divalent ions [13].
  • KIADH4, which encodes one of the two activities localized within mitochondria, is induced at the transcriptional level in the presence of ethanol as is the ADH2 gene in Saccharomyces cerevisiae [14].
  • The Saccharomyces cerevisiae transcriptional activator ADR1, which controls ADH2 gene expression, was shown to be involved in the regulation of peroxisome proliferation [15].

Associations of ADH2 with chemical compounds

  • In Saccharomyces cerevisiae, expression of the ADH2 gene is undetectable during growth on glucose [16].
  • These results suggest that SPT10 and SPT6, in negatively regulating transcription at ADH2, act through a factor that requires CCR4 function, but do not regulate CCR4 expression, control its activity, physically interact with it, or affect its binding to other factors [17].
  • The addition of ethanol causes in wild-type yeast strains a substantial increase in linking number both on the ADH2-containing plasmid and on the resident 2 microns DNA [18].
  • Here we show that after growth at 15 or 20 degrees C on glucose, 30% of the antimycin A resistance mutations are Ty insertions at ADH2 and another 65% of the mutations are Ty insertions at ADH4, a new locus identified and cloned as described in this paper [19].
  • Cyclic AMP-dependent protein kinase inhibits ADH2 expression in part by decreasing expression of the transcription factor gene ADR1 [20].

Physical interactions of ADH2


Regulatory relationships of ADH2

  • Multicopy MEU1 expression suppressed the constitutive ADH2 expression caused by cre2-1 [22].
  • In addition, yCAF1 (POP2) when fused to LexA was capable of activating transcription. mCAF1 could also activate transcription when fused to LexA and could functionally substitute for yCAF1 in allowing ADH2 expression in an spt10 mutant background [23].
  • In Saccharomyces cerevisiae, the unregulated cyclic AMP-dependent protein kinase (cAPK) activity of bcy1 mutant cells inhibits expression of the glucose-repressible ADH2 gene [20].
  • The ISWI and CHD1 chromatin remodelling activities influence ADH2 expression and chromatin organization [24].
  • The ability of ADR1 to increase the frequency of mitochondrial mutation is correlated with its ability to activate ADH II transcription but is independent of the level of ADH II being expressed [25].

Other interactions of ADH2

  • UAS2 has been shown to be important for ADH2 expression and confers glucose-regulated, ADR1-independent activity to a heterologous reporter gene [10].
  • In Saccharomyces cerevisiae, the protein phosphatase type 1 (PP1)-binding protein Reg1 is required to maintain complete repression of ADH2 expression during growth on glucose [26].
  • Surprisingly, however, mutant forms of the yeast PP1 homologue Glc7, which are unable to repress expression of another glucose-regulated gene, SUC2, fully repressed ADH2 [26].
  • Thus, the mutant search revealed previously unknown Snf1-dependent and -independent pathways of ADH2 expression [27].
  • Disruption of MEU1 reduced endogenous ADH2 expression about twofold but had no effect on cell viability or growth [22].

Analytical, diagnostic and therapeutic context of ADH2


  1. A series of yeast shuttle vectors for expression of cDNAs and other DNA sequences. Brunelli, J.P., Pall, M.L. Yeast (1993) [Pubmed]
  2. Similarity of Escherichia coli propanediol oxidoreductase (fucO product) and an unusual alcohol dehydrogenase from Zymomonas mobilis and Saccharomyces cerevisiae. Conway, T., Ingram, L.O. J. Bacteriol. (1989) [Pubmed]
  3. Over-expression of the Saccharomyces cerevisiae exo-beta-1,3-glucanase gene together with the Bacillus subtilis endo-beta-1,3-1,4-glucanase gene and the Butyrivibrio fibrisolvens endo-beta-1,4-glucanase gene in yeast. van Rensburg, P., van Zyl, W.H., Pretorius, I.S. J. Biotechnol. (1997) [Pubmed]
  4. Expression of bacterial hemoglobin in the yeast, Pichia pastoris, with a low O2-induced promoter. Chien, L.J., Lee, C.K. Biotechnol. Lett. (2005) [Pubmed]
  5. Resurrecting ancestral alcohol dehydrogenases from yeast. Thomson, J.M., Gaucher, E.A., Burgan, M.F., De Kee, D.W., Li, T., Aris, J.P., Benner, S.A. Nat. Genet. (2005) [Pubmed]
  6. Cyclic AMP-dependent protein kinase phosphorylates and inactivates the yeast transcriptional activator ADR1. Cherry, J.R., Johnson, T.R., Dollard, C., Shuster, J.R., Denis, C.L. Cell (1989) [Pubmed]
  7. DNA sequences of two yeast promoter-up mutants. Russell, D.W., Smith, M., Cox, D., Williamson, V.M., Young, E.T. Nature (1983) [Pubmed]
  8. Characterization of a regulatory region upstream of the ADR2 locus of S. cerevisiae. Beier, D.R., Young, E.T. Nature (1982) [Pubmed]
  9. Effect of acetic acid on xylose conversion to ethanol by genetically engineered E. coli. Lawford, H.G., Rousseau, J.D. Appl. Biochem. Biotechnol. (1992) [Pubmed]
  10. Synergistic activation of ADH2 expression is sensitive to upstream activation sequence 2 (UAS2) orientation, copy number and UAS1-UAS2 helical phasing. Donoviel, M.S., Kacherovsky, N., Young, E.T. Mol. Cell. Biol. (1995) [Pubmed]
  11. Isolation and DNA sequence of ADH3, a nuclear gene encoding the mitochondrial isozyme of alcohol dehydrogenase in Saccharomyces cerevisiae. Young, E.T., Pilgrim, D. Mol. Cell. Biol. (1985) [Pubmed]
  12. Localization of a minimal binding domain and activation regions in yeast regulatory protein ADR1. Thukral, S.K., Tavianini, M.A., Blumberg, H., Young, E.T. Mol. Cell. Biol. (1989) [Pubmed]
  13. The NOT proteins are part of the CCR4 transcriptional complex and affect gene expression both positively and negatively. Liu, H.Y., Badarinarayana, V., Audino, D.C., Rappsilber, J., Mann, M., Denis, C.L. EMBO J. (1998) [Pubmed]
  14. Ethanol-induced and glucose-insensitive alcohol dehydrogenase activity in the yeast Kluyveromyces lactis. Mazzoni, C., Saliola, M., Falcone, C. Mol. Microbiol. (1992) [Pubmed]
  15. A C-terminal region of the Saccharomyces cerevisiae transcription factor ADR1 plays an important role in the regulation of peroxisome proliferation by fatty acids. Simon, M.M., Pavlik, P., Hartig, A., Binder, M., Ruis, H., Cook, W.J., Denis, C.L., Schanz, B. Mol. Gen. Genet. (1995) [Pubmed]
  16. ADH2 expression is repressed by REG1 independently of mutations that alter the phosphorylation of the yeast transcription factor ADR1. Dombek, K.M., Camier, S., Young, E.T. Mol. Cell. Biol. (1993) [Pubmed]
  17. The yeast CCR4 protein is neither regulated by nor associated with the SPT6 and SPT10 proteins and forms a functionally distinct complex from that of the SNF/SWI transcription factors. Denis, C.L., Draper, M.P., Liu, H.Y., Malvar, T., Vallari, R.C., Cook, W.J. Genetics (1994) [Pubmed]
  18. DNA topoisomerase I controls the kinetics of promoter activation and DNA topology in Saccharomyces cerevisiae. Di Mauro, E., Camilloni, G., Verdone, L., Caserta, M. Mol. Cell. Biol. (1993) [Pubmed]
  19. Ty insertions at two loci account for most of the spontaneous antimycin A resistance mutations during growth at 15 degrees C of Saccharomyces cerevisiae strains lacking ADH1. Paquin, C.E., Williamson, V.M. Mol. Cell. Biol. (1986) [Pubmed]
  20. Cyclic AMP-dependent protein kinase inhibits ADH2 expression in part by decreasing expression of the transcription factor gene ADR1. Dombek, K.M., Young, E.T. Mol. Cell. Biol. (1997) [Pubmed]
  21. cAMP-dependent phosphorylation and inactivation of yeast transcription factor ADR1 does not affect DNA binding. Taylor, W.E., Young, E.T. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  22. Isolation and identification of genes activating UAS2-dependent ADH2 expression in Saccharomyces cerevisiae. Donoviel, M.S., Young, E.T. Genetics (1996) [Pubmed]
  23. Identification of a mouse protein whose homolog in Saccharomyces cerevisiae is a component of the CCR4 transcriptional regulatory complex. Draper, M.P., Salvadore, C., Denis, C.L. Mol. Cell. Biol. (1995) [Pubmed]
  24. The ISWI and CHD1 chromatin remodelling activities influence ADH2 expression and chromatin organization. Xella, B., Goding, C., Agricola, E., Di Mauro, E., Caserta, M. Mol. Microbiol. (2006) [Pubmed]
  25. Overexpression of the yeast transcriptional activator ADR1 induces mutation of the mitochondrial genome. Cherry, J.R., Denis, C.L. Curr. Genet. (1989) [Pubmed]
  26. Functional analysis of the yeast Glc7-binding protein Reg1 identifies a protein phosphatase type 1-binding motif as essential for repression of ADH2 expression. Dombek, K.M., Voronkova, V., Raney, A., Young, E.T. Mol. Cell. Biol. (1999) [Pubmed]
  27. Snf1-Dependent and Snf1-Independent Pathways of Constitutive ADH2 Expression in Saccharomyces cerevisiae. Voronkova, V., Kacherovsky, N., Tachibana, C., Yu, D., Young, E.T. Genetics (2006) [Pubmed]
  28. ADR1-mediated regulation of ADH2 requires an inverted repeat sequence. Shuster, J., Yu, J., Cox, D., Chan, R.V., Smith, M., Young, E. Mol. Cell. Biol. (1986) [Pubmed]
  29. Isoform-specific purification and substrate specificity of the 5'-AMP-activated protein kinase. Michell, B.J., Stapleton, D., Mitchelhill, K.I., House, C.M., Katsis, F., Witters, L.A., Kemp, B.E. J. Biol. Chem. (1996) [Pubmed]
  30. Oxygen and carbon source-regulated expression of PDC and ADH genes in the respiratory yeast Pichia anomala. Fredlund, E., Beerlage, C., Melin, P., Schn??rer, J., Passoth, V. Yeast (2006) [Pubmed]
  31. Transposable elements associated with constitutive expression of yeast alcohol dehydrogenase II. Williamson, V.M., Young, E.T., Ciriacy, M. Cell (1981) [Pubmed]
WikiGenes - Universities