Molecular cloning and structural characterization of the human histidase gene (HAL). Genomics 1995 Sep 01;29(1):98-104
Date
09/01/1995Pubmed ID
8530107DOI
10.1006/geno.1995.1219Scopus ID
2-s2.0-0029151627 (requires institutional sign-in at Scopus site) 42 CitationsAbstract
Histidase (EC 4.3.1.3) 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 lambda EMBL-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.
Author List
Suchi M, Sano H, Mizuno H, Wada YAuthor
Mariko Suchi MD, PhD Associate Professor in the Pathology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Alternative SplicingAmino Acid Metabolism, Inborn Errors
Animals
Base Sequence
Binding Sites
Cholesterol Side-Chain Cleavage Enzyme
Cloning, Molecular
DNA
DNA Primers
Exons
Genomic Library
Histidine
Histidine Ammonia-Lyase
Hominidae
Humans
Introns
Liver
Mice
Molecular Sequence Data
Polymerase Chain Reaction
Polymorphism, Genetic
RNA, Messenger
Restriction Mapping
Skin
TATA Box
Transcription Factors
