Molecular cloning and structural characterization of the human histidase gene (HAL)

Mariko Suchi, Hirofumi Sano, Haruo Mizuno, Yoshiro Wada

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40 Citations (Scopus)


Histidase (EC is a cytosolic enzyme that catalyzes the nonoxidative deamination of histidine to urocanic acid. Histidinemia, resulting from reduced histidase activity as reported in Cambridge stock his/his mice and in humans, is the most frequent inborn metabolic error in Japan. The histidase chromosomal gene (HAL) was isolated from a λEMBL-3 human genomic library using the human histidase cDNA as a probe. Restriction mapping and Southern blot analysis of the isolated clones reveal a single-copy gene spanning approximately 25 kb and consisting of 21 exons. Exon 1 encodes only 5′ untranslated sequence of liver histidase mRNA, with protein coding beginning in exon 2. A rarely observed 5′ GC, similar to that reported in the human P-450(SCC) gene, is present in intron 20. All other splicing junctions adhere to the canonical GT/AG rule. A TATA box sequence is located 25 bp upstream of the liver histidase transcription initiation site determined by S1 nuclease protection analysis. Several liver- and epidermis-specific transcription factor binding sites, including C/EBP, NFIL6, HNF5, AP2/KER1, MNF, and others, are also identified in the 5′ flanking region. Consistent with the hepatic and epidermal expression of histidase, this finding suggests that histidase transcription may be regulated by these factors. We further identify a polymorphism (A to G transition) in the histidase coding region of exon 16. The human histidase genomic structure presented here should facilitate the molecular investigation of symptomatic and asymptomatic forms of histidinemia.

Original languageEnglish
Pages (from-to)98-104
Number of pages7
Issue number1
Publication statusPublished - 01-09-1995
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics


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