ALD4/YOR374W Summary Help

Standard Name ALD4
Systematic Name YOR374W
Alias ALD7
Feature Type ORF, Verified
Description Mitochondrial aldehyde dehydrogenase; required for growth on ethanol and conversion of acetaldehyde to acetate; phosphorylated; activity is K+ dependent; utilizes NADP+ or NAD+ equally as coenzymes; expression is glucose repressed; can substitute for cytosolic NADP-dependent aldehyde dehydrogenase when directed to the cytosol (1, 2, 3, 4 and see Summary Paragraph)
Also known as: ALDH2 5
Name Description ALdehyde Dehydrogenase
Chromosomal Location
ChrXV:1039840 to 1041399 | ORF Map | GBrowse
Gene Ontology Annotations All ALD4 GO evidence and references
  View Computational GO annotations for ALD4
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 15 genes
Classical genetics
Large-scale survey
26 total interaction(s) for 25 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 9
  • Affinity Capture-RNA: 2
  • Affinity Capture-Western: 1

Genetic Interactions
  • Negative Genetic: 6
  • Phenotypic Enhancement: 1
  • Phenotypic Suppression: 2
  • Positive Genetic: 3
  • Synthetic Growth Defect: 2

Expression Summary
Length (a.a.) 519
Molecular Weight (Da) 56,723
Isoelectric Point (pI) 6.72
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrXV:1039840 to 1041399 | ORF Map | GBrowse
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..1560 1039840..1041399 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000005901

Aldehyde dehydrogenases play a critical role in the conversion of acetaldehyde to acetyl-CoA during growth on non-fermentable carbon sources and in the breakdown of toxic aldehydes accumulated under stress conditions (6). Acetaldehyde arises during the metabolism of pyruvate to acetate by the cytoplasmic pyruvate dehydrogenase bypass (PDH) pathway, which involves the enzymatic activities pyruvate decarboxylase (PDC6, PDC5, PDC1), acetaldehyde dehydrogenase (ALD6), and acetyl-CoA synthetase (ACS1, ACS2) (7). In an alternate mitochondrial pyruvate dehydrogenase bypass pathway, pyruvate is first decarboxylated to acetaldehyde in the cytosol by pyruvate decarboxylase and is then converted to acetate by the mitochondrial acetaldehyde dehydrogenases (ALD4 and ALD5) (8).

In the yeast genome, there are five genes known to encode aldehyde dehydrogenases, as well as an additional gene with sequence similarity. Ald2p and Ald3p are cytosolic enzymes which use only NAD+ as cofactor. Both genes are induced in response to ethanol or stress and repressed by glucose. Ald4p and Ald5p are mitochondrial, use NAD and NADP as cofactors, and are K+ dependent. Ald4p, the major isoform, is glucose repressed and ald4 mutants do not grow on ethanol, while Ald5p, the minor isoform, is constitutively expressed (5, 2). ALD6 encodes the Mg2+ activated cytosolic enzyme, which uses NADP+ as cofactor and is constitutively expressed. HFD1 has been predicted to encode a fatty aldehyde dehydrogenase (1, 9, 8, 10).

Expression of ALD4 is regulated by several different proteins. The transcription factor Stb5p induces transcription of ALD4 (11), while the transcription repressors Nrg1p and Nrg2p decrease it (12).

Aldehyde dehydrogenases are conserved across many species and are key enzymes in metabolic pathways, some of which function to detoxify harmful chemical intermediates. In humans, mutations in aldehyde dehydrogenase genes (ALDH1, ALDH2, ALDH4 and ALDH10) are associated with alcoholism and carcinogenesis. In plants, these enzymes play important roles in fertility and in fruit ripening (1 and references therein).

Last updated: 2009-08-14 Contact SGD

References cited on this page View Complete Literature Guide for ALD4
1) Navarro-Avino JP, et al.  (1999) A proposal for nomenclature of aldehyde dehydrogenases in Saccharomyces cerevisiae and characterization of the stress-inducible ALD2 and ALD3 genes. Yeast 15(10A):829-42
2) Tessier WD, et al.  (1998) Identification and disruption of the gene encoding the K(+)-activated acetaldehyde dehydrogenase of Saccharomyces cerevisiae. FEMS Microbiol Lett 164(1):29-34
3) Reinders J, et al.  (2007) Profiling phosphoproteins of yeast mitochondria reveals a role of phosphorylation in assembly of the ATP synthase. Mol Cell Proteomics 6(11):1896-906
4) Mukhopadhyay A, et al.  (2013) Mitochondrial NAD dependent aldehyde dehydrogenase either from yeast or human replaces yeast cytoplasmic NADP dependent aldehyde dehydrogenase for the aerobic growth of yeast on ethanol. Biochim Biophys Acta 1830(6):3391-8
5) Wang X, et al.  (1998) Molecular cloning, characterization, and potential roles of cytosolic and mitochondrial aldehyde dehydrogenases in ethanol metabolism in Saccharomyces cerevisiae. J Bacteriol 180(4):822-30
6) Aranda A and del Olmo Ml M  (2003) Response to acetaldehyde stress in the yeast Saccharomyces cerevisiae involves a strain-dependent regulation of several ALD genes and is mediated by the general stress response pathway. Yeast 20(8):747-59
7) Boubekeur S, et al.  (1999) A mitochondrial pyruvate dehydrogenase bypass in the yeast Saccharomyces cerevisiae. J Biol Chem 274(30):21044-8
8) Boubekeur S, et al.  (2001) Participation of acetaldehyde dehydrogenases in ethanol and pyruvate metabolism of the yeast Saccharomyces cerevisiae. Eur J Biochem 268(19):5057-65
9) Kurita O and Nishida Y  (1999) Involvement of mitochondrial aldehyde dehydrogenase ALD5 in maintenance of the mitochondrial electron transport chain in Saccharomyces cerevisiae. FEMS Microbiol Lett 181(2):281-7
10) Zahedi RP, et al.  (2006) Proteomic analysis of the yeast mitochondrial outer membrane reveals accumulation of a subclass of preproteins. Mol Biol Cell 17(3):1436-50
11) Larochelle M, et al.  (2006) Oxidative stress-activated zinc cluster protein Stb5 has dual activator/repressor functions required for pentose phosphate pathway regulation and NADPH production. Mol Cell Biol 26(17):6690-701
12) Vyas VK, et al.  (2005) Repressors Nrg1 and Nrg2 regulate a set of stress-responsive genes in Saccharomyces cerevisiae. Eukaryot Cell 4(11):1882-91