ADH4/YGL256W Summary Help

Standard Name ADH4 1
Systematic Name YGL256W
Alias NRC465 2 , ZRG5 3
Feature Type ORF, Verified
Description Alcohol dehydrogenase isoenzyme type IV; dimeric enzyme demonstrated to be zinc-dependent despite sequence similarity to iron-activated alcohol dehydrogenases; transcription is induced in response to zinc deficiency (1, 3, 4, 5 and see Summary Paragraph)
Name Description Alcohol DeHydrogenase 1
Chromosomal Location
ChrVII:15159 to 16307 | ORF Map | GBrowse
Gbrowse
Genetic position: -169 cM
Gene Ontology Annotations All ADH4 GO evidence and references
  View Computational GO annotations for ADH4
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 5 genes
Resources
Pathways
Classical genetics
null
Large-scale survey
null
overexpression
Resources
60 total interaction(s) for 58 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 9
  • Affinity Capture-RNA: 2
  • Biochemical Activity: 4
  • PCA: 3

Genetic Interactions
  • Dosage Lethality: 2
  • Negative Genetic: 18
  • Phenotypic Enhancement: 5
  • Phenotypic Suppression: 1
  • Positive Genetic: 12
  • Synthetic Growth Defect: 1
  • Synthetic Lethality: 2
  • Synthetic Rescue: 1

Resources
Expression Summary
histogram
Resources
Length (a.a.) 382
Molecular Weight (Da) 41,142
Isoelectric Point (pI) 6.1
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrVII:15159 to 16307 | ORF Map | GBrowse
SGD ORF map
Genetic position: -169 cM
Last Update Coordinates: 2008-06-02 | Sequence: 2008-06-02
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1149 15159..16307 2008-06-02 2008-06-02
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 SGDIDS000003225
SUMMARY PARAGRAPH for ADH4

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 (6, 7, 8, 4, 9).

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 (10). 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 (11). They may also have physiological roles. For example, exposing cells to isoamyl alcohol, derived from catabolism of leucine, stimulates filamentous growth (12, 13). Similarly, other fusel alcohols also stimulate filamentous growth in S. cerevisiae and biofilm formation in the pathogens Candida albicans and Candida dubliniensis (14, 15, reviewed in 11).

Based on sequence, Adh4p is most closely related to a bacterial iron-activated alcohol dehydrogenase, but experimental evidence demonstrates that Adh4p activity is activated by zinc like the other S. cerevisiae ADH proteins (4, 16). However, unlike Adh1p, Adh2p, and Adh3p, which are thought to function as a tetramers (reviewed in 17), Adh4p is a dimeric protein (4). Adh4p requires zinc to function but depleting zinc from the media has been shown to induce ADH4 transcription (3). ADH4 expression is also upregulated by lithium, a compound that is toxic to yeast cells grown in galactose, and downregulated by DMSO (18, 19). Spontaneous chromosomal amplifications of ADH4 are able to rescue null mutations in the major isozyme ADH1 (20, 21, 22). While ADH4 is often expressed at only low levels in laboratory strains, it is often highly expressed in brewing strains (10).

Last updated: 2005-11-22 Contact SGD

References cited on this page View Complete Literature Guide for ADH4
1) Paquin CE and Williamson VM  (1986) 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. Mol Cell Biol 6(1):70-9
2) Coissac E, et al.  (1996) Sequence of a 39,411 bp DNA fragment covering the left end of chromosome VII of Saccharomyces cerevisiae. Yeast 12(15):1555-62
3) Yuan DS  (2000) Zinc-regulated genes in Saccharomyces cerevisiae revealed by transposon tagging. Genetics 156(1):45-58
4) Drewke C and Ciriacy M  (1988) Overexpression, purification and properties of alcohol dehydrogenase IV from Saccharomyces cerevisiae. Biochim Biophys Acta 950(1):54-60
5) Williamson VM and Paquin CE  (1987) Homology of Saccharomyces cerevisiae ADH4 to an iron-activated alcohol dehydrogenase from Zymomonas mobilis. Mol Gen Genet 209(2):374-81
6) Bennetzen JL and Hall BD  (1982) The primary structure of the Saccharomyces cerevisiae gene for alcohol dehydrogenase. J Biol Chem 257(6):3018-25
7) Russell DW, et al.  (1983) Nucleotide sequence of the yeast alcohol dehydrogenase II gene. J Biol Chem 258(4):2674-82
8) 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
9) Smith MG, et al.  (2004) Microbial synergy via an ethanol-triggered pathway. Mol Cell Biol 24(9):3874-84
10) 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
11) 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
12) 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
13) 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
14) Dickinson JR  (1996) 'Fusel' alcohols induce hyphal-like extensions and pseudohyphal formation in yeasts. Microbiology 142 ( Pt 6)():1391-7
15) Lorenz MC, et al.  (2000) Characterization of alcohol-induced filamentous growth in Saccharomyces cerevisiae. Mol Biol Cell 11(1):183-99
16) Larroy C, et al.  (2002) Characterization of a Saccharomyces cerevisiae NADP(H)-dependent alcohol dehydrogenase (ADHVII), a member of the cinnamyl alcohol dehydrogenase family. Eur J Biochem 269(22):5738-45
17) Leskovac V, et al.  (2002) The three zinc-containing alcohol dehydrogenases from baker's yeast, Saccharomyces cerevisiae. FEMS Yeast Res 2(4):481-94
18) Zhang W, et al.  (2003) Microarray analyses of the metabolic responses of Saccharomyces cerevisiae to organic solvent dimethyl sulfoxide. J Ind Microbiol Biotechnol 30(1):57-69
19) Bro C, et al.  (2003) Transcriptional, proteomic, and metabolic responses to lithium in galactose-grown yeast cells. J Biol Chem 278(34):32141-9
20) Walton JD, et al.  (1986) Resistance to antimycin A in yeast by amplification of ADH4 on a linear, 42 kb palindromic plasmid. Cell 46(6):857-63
21) Dorsey M, et al.  (1992) Spontaneous amplification of the ADH4 gene in Saccharomyces cerevisiae. Genetics 132(4):943-50
22) Dorsey MJ, et al.  (1993) Phenotypic identification of amplifications of the ADH4 and CUP1 genes of Saccharomyces cerevisiae. Curr Genet 23(5-6):392-6