Cloning and characterization of the ADH5 gene encoding human alcohol dehydrogenase 5, formaldehyde dehydrogenase

Man Wook Hur, Howard J. Edenberg

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Abstract

Human χ-alcohol dehydrogenase (χ-ADH) is a zinc-containing dimeric enzyme responsible for the oxidation of longchain alcohols and (ω-hydroxyfatty acids. Class-III ADHs, of which χ-ADH is the prototype, are widely produced and well conserved during evolution. This suggests that they fulfill important housekeeping roles in cellular metabolism. Recent evidence suggests that class-III ADH and formaldehyde dehydrogenase (FDH) are the same enzyme. We have isolated and characterized two overlapping genomic clones that cover the entire ADH5 (FDH) gene. ADH5 is composed of nine exons and eight introns. Two major transcription start points were identified by primer extension. The 5′ nontranslated region is unusual in that it contains two additional upstream ATG codons, which would encode peptides of 20 and 10 amino acids. Neither of the upstream ATGs is in a good context for translation initiation, whereas the ATG initiating &khgr;-ADH is in a favorable context. The 5′ region of ADH5 is a CpG island; it is extremely G+C rich and has many CpG doublets. It does not contain either a TATA box or a CAAT box. This is consistent with ubiquitous expression, and contrasts with the promoters of all previously cloned ADH genes, which are expressed in a tissue-specific manner. The 5′ region of ADH5 contains consensus binding sites for the transcriptional regulatory proteins, Sp1, AP2, LF-A1, NF-1, NF-A2, and NF-E1. A 1.5-kb upstream fragment from ADH5 was able to drive the transcription of a cat reporter gene at high levels in monkey kidney cells (CV-1). Several processed pseudogenes were also isolated.

Original languageEnglish (US)
Pages (from-to)305-311
Number of pages7
JournalGene
Volume121
Issue number2
DOIs
StatePublished - Nov 16 1992

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Keywords

  • alcoholism
  • CpG island
  • housekeeping gene
  • promoter
  • pseudogene
  • Recombinant DNA
  • transcriptional factors

ASJC Scopus subject areas

  • Genetics

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