ADH3/YMR083W Summary Help

Standard Name ADH3 1
Systematic Name YMR083W
Feature Type ORF, Verified
Description Mitochondrial alcohol dehydrogenase isozyme III; involved in the shuttling of mitochondrial NADH to the cytosol under anaerobic conditions and ethanol production (2, 3 and see Summary Paragraph)
Name Description Alcohol DeHydrogenase
Chromosomal Location
ChrXIII:434788 to 435915 | ORF Map | GBrowse
Gbrowse
Genetic position: 45 cM
Gene Ontology Annotations All ADH3 GO evidence and references
  View Computational GO annotations for ADH3
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 16 genes
Resources
Pathways
Classical genetics
null
Large-scale survey
null
overexpression
Resources
154 total interaction(s) for 147 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 22
  • Affinity Capture-RNA: 3

Genetic Interactions
  • Negative Genetic: 62
  • Phenotypic Enhancement: 6
  • Positive Genetic: 58
  • Synthetic Growth Defect: 2
  • Synthetic Lethality: 1

Resources
Expression Summary
histogram
Resources
Length (a.a.) 375
Molecular Weight (Da) 40,369
Isoelectric Point (pI) 8.52
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXIII:434788 to 435915 | ORF Map | GBrowse
SGD ORF map
Genetic position: 45 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1128 434788..435915 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000004688
SUMMARY PARAGRAPH for ADH3

In S. cerevisiae, there are five genes that encode alcohol dehydrogenases involved in ethanol metabolism, ADH1 to ADH5. Four of these enzymes, Adh1p, Adh3p, Adh4p, and Adh5p, reduce acetaldehyde to ethanol during glucose fermentation, while Adh2p catalyzes the reverse reaction of oxidizing ethanol to acetaldehyde (4, 5, 6, 7, 8).

The five ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, and Adh5p) as well as the bifunctional enzyme Sfa1p are also involved in the production of fusel alcohols during fermentation (9). Fusel alcohols are end products of amino acid catabolism (of valine, leucine, isoleucine, methionine, phenylalanine, tryptophan, and tyrosine) via the Ehrlich pathway and contribute to the flavor and aroma of yeast-fermented foods and beverages (10). They may also have physiological roles. For example, exposing cells to isoamyl alcohol, derived from catabolism of leucine, stimulates filamentous growth (11, 12). Similarly, other fusel alcohols also stimulate filamentous growth in S. cerevisiae and biofilm formation in the pathogens Candida albicans and Candida dubliniensis (13, 14, reviewed in 10).

ADH3 is a nuclear gene that encodes the alcohol dehydrogenase isozyme of the mitochondrial matrix. Adh3p shares roughly 80% amino acid identity with Adh1p and Adh2p (6). The presence of glucose in the media represses ADH3 expression, although ADH3 glucose-repression is not as severe as that of ADH2 (6, 15). Null mutations in ADH3 do not confer a phenotype under aerobic conditions (6), but under anaerobic conditions mutant cells grow noticeably slower than wild type cells (2). This may be due to the suggested involvement of Adh3p in an ethanol-acetaldehyde redox shuttle that is involved in maintaining the mitochondrial redox balance during anaerobic growth (2).

About the medium-chain dehydrogenase/reductase (MDR) family

Medium-chain dehydrogenase/reductases (MDRs), sometimes referred to as long-chain dehydrogenases (16), constitute an ancient and widespread enzyme superfamily with members found in Bacteria, Archaea, and Eukaryota (17, 18). Many MDR members are basic metabolic enzymes acting on alcohols or aldehydes, and thus these enzymes may have roles in detoxifying alcohols and related compounds, protecting against environmental stresses such as osmotic shock, reduced or elevated temperatures, or oxidative stress (17). The family also includes the mammalian zeta-crystallin lens protein, which may protect the lens against oxidative damage and enzymes which produce lignocellulose in plants (17).

MDR enzymes typically have subunits of about 350 aa residues and are two-domain proteins, with a catalytic domain and a second domain for binding to the nicotinamide cofactor, either NAD(H) or NADP(H) (17, 18). They contain 0, 1, or 2 zinc atoms (19). When zinc is present, it is involved in catalysis at the active site.

Based on phylogenetic and sequence analysis, the members of the MDR superfamily can be further divided into more closely related subgroups (17, 18). In families which are widespread from prokaryotes to eukaryotes, some members appear conserved across all species, while others appear to be due to lineage specific duplications. Some subgroups are only found in certain taxa. S. cerevisiae contains fifteen (17) or twenty-one (18) members of the MDR superfamily, listed below. The difference in number is due to six sequences that were included as members of the quinone oxidoreductase family by Riveros-Rosas et al. (18) but not by Nordling et al. (17).

Zinc-containing enzyme groups:
- PDH; "polyol" dehydrogenase family - BDH1, BDH2, SOR1, SOR2, XYL2
- ADH; class III alcohol dehydrogenase family - SFA1
- Y-ADH; "yeast" alcohol dehydrogenase family - ADH1, ADH2, ADH3, ADH5
- CADH; cinnamyl alcohol dehydrogenase family - ADH6, ADH7

Non-zinc-containing enzyme groups:
- NRBP; nuclear receptor binding protein (18) or MRF; mitochondrial respiratory function (17) family - ETR1
- QOR; quinone oxidoreductase family - ZTA1 (17, 18), AST1, AST2, YCR102C, YLR460C, YMR152W, YNL134C (18)
- LTD; leukotriene B4 dehydrogenases - YML131W
- ER; enoyl reductases (18) or ACR; acyl-CoA reductase (17) family - no members in S. cerevisiae

Last updated: 2005-11-22 Contact SGD

References cited on this page View Complete Literature Guide for ADH3
1) Ciriacy, M.  (1985) Personal Communication, Mortimer Map Edition 9
2) Bakker BM, et al.  (2000) The mitochondrial alcohol dehydrogenase Adh3p is involved in a redox shuttle in Saccharomyces cerevisiae. J Bacteriol 182(17):4730-7
3) Bakker BM, et al.  (2001) Stoichiometry and compartmentation of NADH metabolism in Saccharomyces cerevisiae. FEMS Microbiol Rev 25(1):15-37
4) Bennetzen JL and Hall BD  (1982) The primary structure of the Saccharomyces cerevisiae gene for alcohol dehydrogenase. J Biol Chem 257(6):3018-25
5) Russell DW, et al.  (1983) Nucleotide sequence of the yeast alcohol dehydrogenase II gene. J Biol Chem 258(4):2674-82
6) Young ET and Pilgrim D  (1985) Isolation and DNA sequence of ADH3, a nuclear gene encoding the mitochondrial isozyme of alcohol dehydrogenase in Saccharomyces cerevisiae. Mol Cell Biol 5(11):3024-34
7) Drewke C and Ciriacy M  (1988) Overexpression, purification and properties of alcohol dehydrogenase IV from Saccharomyces cerevisiae. Biochim Biophys Acta 950(1):54-60
8) Smith MG, et al.  (2004) Microbial synergy via an ethanol-triggered pathway. Mol Cell Biol 24(9):3874-84
9) Dickinson JR, et al.  (2003) The catabolism of amino acids to long chain and complex alcohols in Saccharomyces cerevisiae. J Biol Chem 278(10):8028-34
10) Hazelwood LA, et al.  (2008) The Ehrlich pathway for fusel alcohol production: a century of research on Saccharomyces cerevisiae metabolism. Appl Environ Microbiol 74(8):2259-66
11) Kern K, et al.  (2004) Isoamyl alcohol-induced morphological change in Saccharomyces cerevisiae involves increases in mitochondria and cell wall chitin content. FEMS Yeast Res 5(1):43-9
12) Hauser M, et al.  (2007) A transcriptome analysis of isoamyl alcohol-induced filamentation in yeast reveals a novel role for Gre2p as isovaleraldehyde reductase. FEMS Yeast Res 7(1):84-92
13) Dickinson JR  (1996) 'Fusel' alcohols induce hyphal-like extensions and pseudohyphal formation in yeasts. Microbiology 142 ( Pt 6)():1391-7
14) Lorenz MC, et al.  (2000) Characterization of alcohol-induced filamentous growth in Saccharomyces cerevisiae. Mol Biol Cell 11(1):183-99
15) Ciriacy M  (1975) Genetics of alcohol dehydrogenase in Saccharomyces cerevisiae. II. Two loci controlling synthesis of the glucose-repressible ADH II. Mol Gen Genet 138(2):157-64
16) Jornvall H, et al.  (1981) Alcohol and polyol dehydrogenases are both divided into two protein types, and structural properties cross-relate the different enzyme activities within each type. Proc Natl Acad Sci U S A 78(7):4226-30
17) Nordling E, et al.  (2002) Medium-chain dehydrogenases/reductases (MDR). Family characterizations including genome comparisons and active site modeling. Eur J Biochem 269(17):4267-76
18) Riveros-Rosas H, et al.  (2003) Diversity, taxonomy and evolution of medium-chain dehydrogenase/reductase superfamily. Eur J Biochem 270(16):3309-34
19) Persson B, et al.  (1999) Bioinformatics in studies of SDR and MDR enzymes. Adv Exp Med Biol 463():373-7