OMIM Result

*606467 Links

ALDEHYDE DEHYDROGENASE 8 FAMILY, MEMBER A1; ALDH8A1

Alternative titles; symbols
ALDH12

Gene map locus Chr.6

TEXT

Retinal dehydrogenase isozymes (e.g., RALDH1; 100640) are members of the ALDH family. Short-chain alcohol dehydrogenases convert all-trans- and 9-cis-retinol to all-trans- and 9-cis-retinal, while RALDH isozymes convert these into all-trans-retinoic acid and 9-cis-retinoic acid, respectively.

CLONING

By biochemical purification of rat kidney and liver Raldh isozymes, micropeptide sequencing, and genomic database analysis, followed by 5-prime and 3-prime RACE and PCR of a human kidney cDNA library, Lin and Napoli (2000) isolated a cDNA encoding ALDH8A1, which they termed ALDH12. Sequence analysis predicted that the 487-amino acid ALDH8A1 protein contains the 23 invariant residues and 4 conserved regions typical of the ALDH superfamily. It also has a cofactor-binding motif and a cys residue that serves as an active-site nucleophile. Northern blot analysis revealed expression of a 2.5-kb ALDH8A1 transcript only in liver and kidney. Dot-blot analysis detected low expression in brain and spinal cord and detectable expression in mammary gland, thymus, adrenal, testis, prostate, and parts of the gastrointestinal tract. Functional analysis showed increased RALDH activity of ALDH8A1, with greater efficiency for 9-cis-retinal, from pH7 to pH9 in vitro and in intact cells in the presence of type-1 cis-retinol androgen dehydrogenase (CRAD1). Lin and Napoli (2000) also identified an ALDH8A1 splice variant missing 1 exon and encoding a 433-amino acid protein that lacks 2 of the invariant residues, including the active-site nucleophile.

MAPPING

The International Radiation Hybrid Mapping Consortium mapped the ALDH8A1 gene to chromosome 6 (sts-N70701).

REFERENCES

1. Lin, M.; Napoli, J. L. :: cDNA cloning and expression of a human aldehyde dehydrogenase (ALDH) active with 9-cis-retinal and identification of a rat ortholog, ALDH12. J. Biol. Chem. 275: 40106-40112, 2000.
PubMed ID : 11007799

CREATION DATE

Paul J. Converse : 11/16/2001

EDIT HISTORY

mgross : 11/16/2001