MetaCyc Enzyme: retinal dehydrogenase 2

Gene: ALDH1A2 Accession Number: HS05232 (MetaCyc)

Synonyms: RALDH2, aldehyde dehydrogenase family 1 member A2, RALDH 2, RALDH(II), retinaldehyde-specific dehydrogenase type 2

Species: Homo sapiens

Retinal dehydrogenase 2 can bind both free retinal and RBP1-bound retinal and oxidize it into retinoate.

ALDH1A2 was first cloned from rat testis, and later a human cDNA encoding the gene was isolated from P19 teratocarcinoma cells. Expression of the gene in COS cells showed that the enzyme was highly effective in oxidation of retinal, with no detectable activity on any other aldehyde tested [Zhao96a]. In an independent study a homologous cDNA was isolated from rat testis library and expressed in Escherichia coli. The recombinant enzyme had a Km of approximately 0.7 μM for the free retinal, and a Km of approximately 0.2 μM for cellular retinol-binding protein-bound retinal [Wang96a]

The enzyme is known to be active in embryos, where retinoic acid play a crucial role in early development [Zhao96a, Niederreither99]. ALDH1A2-null mice do not live beyond e10.5. The embryos are malformed and do not undergo the axial rotation that normally occurs on or about e8.5 [Niederreither99].

ALDH1A2 enjoys widespread tissue expression, often overlapping with ALDH1A1, but is regulated differently than ALDH1A1 by vitamin A status, and is not inhibited by apo-CRBP1, even though it does recognize CRBP1-bound retinal as substrate with a Km value of 0.2 μM [Zhai01].

Map Position: [51,292,689 <- 51,404,953]

Molecular Weight of Polypeptide: 56.724 kD (from nucleotide sequence)

Unification Links: ArrayExpress:O94788 , Entrez-gene:8854 , PhosphoSite:O94788 , PhylomeDB:O94788 , Pride:O94788 , Protein Model Portal:O94788 , SMR:O94788 , String:9606.ENSP00000249750 , UniProt:O94788

Relationship Links: InterPro:IN-FAMILY:IPR015590 , InterPro:IN-FAMILY:IPR016160 , InterPro:IN-FAMILY:IPR016161 , InterPro:IN-FAMILY:IPR016162 , InterPro:IN-FAMILY:IPR016163 , InterPro:IN-FAMILY:IPR029510 , Pfam:IN-FAMILY:PF00171 , Prosite:IN-FAMILY:PS00070 , Prosite:IN-FAMILY:PS00687

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Instance reaction of [an aldehyde + NAD+ + H2O → a carboxylate + NADH + 2 H+] (
i1: all-trans-retinal + NAD+ + H2O = all-trans-retinoate + NADH + 2 H+ (

GO Terms:

Biological Process: GO:0006776 - vitamin A metabolic process
GO:0008152 - metabolic process
Molecular Function: GO:0003824 - catalytic activity
GO:0004028 - 3-chloroallyl aldehyde dehydrogenase activity
GO:0004029 - aldehyde dehydrogenase (NAD) activity
GO:0016491 - oxidoreductase activity

Created 10-Aug-2011 by Caspi R , SRI International

Enzymatic reaction of: all-trans-retinal dehydrogenase (retinal dehydrogenase 2)

EC Number:

an all-trans retinal-[cellular-retinol-binding-protein] + NAD+ + H2O <=> all-trans-retinoate + a cellular-retinol-binding protein + NADH + 2 H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: retinoate biosynthesis I

Enzymatic reaction of: all-trans-retinal dehydrogenase (retinal dehydrogenase 2)

EC Number:

all-trans-retinal + NAD+ + H2O <=> all-trans-retinoate + NADH + 2 H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

Reversibility of this reaction is unspecified.

Alternative Substrates for all-trans-retinal: octanal [Wang96a ] , decanal [Wang96a ]


Schematic showing introns, exons and/or isoforms of ALDH1A2


Niederreither99: Niederreither K, Subbarayan V, Dolle P, Chambon P (1999). "Embryonic retinoic acid synthesis is essential for early mouse post-implantation development." Nat Genet 21(4);444-8. PMID: 10192400

Wang96a: Wang X, Penzes P, Napoli JL (1996). "Cloning of a cDNA encoding an aldehyde dehydrogenase and its expression in Escherichia coli. Recognition of retinal as substrate." J Biol Chem 271(27);16288-93. PMID: 8663198

Zhai01: Zhai Y, Sperkova Z, Napoli JL (2001). "Cellular expression of retinal dehydrogenase types 1 and 2: effects of vitamin A status on testis mRNA." J Cell Physiol 186(2);220-32. PMID: 11169459

Zhao96a: Zhao D, McCaffery P, Ivins KJ, Neve RL, Hogan P, Chin WW, Drager UC (1996). "Molecular identification of a major retinoic-acid-synthesizing enzyme, a retinaldehyde-specific dehydrogenase." Eur J Biochem 240(1);15-22. PMID: 8797830

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 19.0 on Tue Oct 13, 2015, biocyc13.