PROSITE documentation PDOC00068
Aldehyde dehydrogenases active sites


Aldehyde dehydrogenases (EC and EC are enzymes which oxidize a wide variety of aliphatic and aromatic aldehydes. In mammals at least four different forms of the enzyme are known [1]: class-1 (or Ald C) a tetrameric cytosolic enzyme, class-2 (or Ald M) a tetrameric mitochondrial enzyme, class-3 (or Ald D) a dimeric cytosolic enzyme, and class IV a microsomal enzyme. Aldehyde dehydrogenases have also been sequenced from fungal and bacterial species. A number of enzymes are known to be evolutionary related to aldehyde dehydrogenases; these enzymes are listed below.

  • Plants and bacterial βine-aldehyde dehydrogenase (EC [2], an enzyme that catalyzes the last step in the biosynthesis of βine.
  • Plants and bacterial NADP-dependent glyceraldehyde-3-phosphate dehydrogenase (EC
  • Escherichia coli succinate-semialdehyde dehydrogenase (NADP+) (EC (gene gabD) [3], which reduces succinate semialdehyde into succinate.
  • Escherichia coli lactaldehyde dehydrogenase (EC (gene ald) [4].
  • Mammalian succinate semialdehyde dehydrogenase (NAD+) (EC
  • Escherichia coli phenylacetaldehyde dehydrogenase (EC
  • Escherichia coli 5-carboxymethyl-2-hydroxymuconate semialdehyde dehydrogenase (gene hpcC).
  • Pseudomonas putida 2-hydroxymuconic semialdehyde dehydrogenase [5] (genes dmpC and xylG), an enzyme in the meta-cleavage pathway for the degradation of phenols, cresols and catechol.
  • Bacterial and mammalian methylmalonate-semialdehyde dehydrogenase (MMSDH) (EC [6], an enzyme involved in the distal pathway of valine catabolism.
  • Yeast delta-1-pyrroline-5-carboxylate dehydrogenase (EC [7] (gene PUT2), which converts proline to glutamate.
  • Bacterial multifunctional putA protein, which contains a delta-1-pyrroline- 5-carboxylate dehydrogenase domain.
  • 26G, a garden pea protein of unknown function which is induced by dehydration of shoots [8].
  • Mammalian formyltetrahydrofolate dehydrogenase (EC [9]. This is a cytosolic enzyme responsible for the NADP-dependent decarboxylative reduction of 10-formyltetrahydrofolate into tetrahydrofolate. It is an protein of about 900 amino acids which consist of three domains; the C- terminal domain (480 residues) is structurally and functionally related to aldehyde dehydrogenases.
  • Yeast hypothetical protein YBR006w.
  • Yeast hypothetical protein YER073w.
  • Yeast hypothetical protein YHR039c.
  • Caenorhabditis elegans hypothetical protein F01F1.6.

A glutamic acid and a cysteine residue have been implicated in the catalytic activity of mammalian aldehyde dehydrogenase. These residues are conserved in all the enzymes of this family. We have derived two patterns for this family, one for each of the active site residues.


Omega-crystallins are minor structural components of squids and octopi eye lens. They are evolutionary related to aldehyde dehydrogenases but have lost their catalytic activity. These patterns will not detect them.

Expert(s) to contact by email:

Joernvall H.
Persson B.

Last update:

April 2006 / Pattern revised.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

ALDEHYDE_DEHYDR_CYS, PS00070; Aldehyde dehydrogenases cysteine active site  (PATTERN)

ALDEHYDE_DEHYDR_GLU, PS00687; Aldehyde dehydrogenases glutamic acid active site  (PATTERN)


1AuthorsHempel J. Harper K. Lindahl R.
TitleInducible (class 3) aldehyde dehydrogenase from rat hepatocellular carcinoma and 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated liver: distant relationship to the class 1 and 2 enzymes from mammalian liver cytosol/mitochondria.
SourceBiochemistry 28:1160-1167(1989).
PubMed ID2713359

2AuthorsWeretilnyk E.A. Hanson A.D.
TitleMolecular cloning of a plant betaine-aldehyde dehydrogenase, an enzyme implicated in adaptation to salinity and drought.
SourceProc. Natl. Acad. Sci. U.S.A. 87:2745-2749(1990).
PubMed ID2320587

3AuthorsNiegemann E. Schulz A. Bartsch K.
TitleMolecular organization of the Escherichia coli gab cluster: nucleotide sequence of the structural genes gabD and gabP and expression of the GABA permease gene.
SourceArch. Microbiol. 160:454-460(1993).
PubMed ID8297211

4AuthorsHidalgo E. Chen Y.-M. Lin E.C.C. Aguilar J.
TitleMolecular cloning and DNA sequencing of the Escherichia coli K-12 ald gene encoding aldehyde dehydrogenase.
SourceJ. Bacteriol. 173:6118-6123(1991).
PubMed ID1917845

5AuthorsNordlund I. Shingler V.
TitleNucleotide sequences of the meta-cleavage pathway enzymes 2-hydroxymuconic semialdehyde dehydrogenase and 2-hydroxymuconic semialdehyde hydrolase from Pseudomonas CF600.
SourceBiochim. Biophys. Acta 1049:227-230(1990).
PubMed ID2194577

6AuthorsSteele M.I. Lorenz D. Hatter K. Park A. Sokatch J.R.
TitleCharacterization of the mmsAB operon of Pseudomonas aeruginosa PAO encoding methylmalonate-semialdehyde dehydrogenase and 3-hydroxyisobutyrate dehydrogenase.
SourceJ. Biol. Chem. 267:13585-13592(1992).
PubMed ID1339433

7AuthorsKrzywicki K.A. Brandriss M.C.
TitlePrimary structure of the nuclear PUT2 gene involved in the mitochondrial pathway for proline utilization in Saccharomyces cerevisiae.
SourceMol. Cell. Biol. 4:2837-2842(1984).
PubMed ID6098824

8AuthorsGuerrero F.D. Jones J.T. Mullet J.E.
TitleTurgor-responsive gene transcription and RNA levels increase rapidly when pea shoots are wilted. Sequence and expression of three inducible genes.
SourcePlant Mol. Biol. 15:11-26(1990).
PubMed ID1715781

9AuthorsCook R.J. Lloyd R.S. Wagner C.
TitleIsolation and characterization of cDNA clones for rat liver 10-formyltetrahydrofolate dehydrogenase.
SourceJ. Biol. Chem. 266:4965-4973(1991).
PubMed ID1848231

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