Note The novel nucleotide sequences mentioned here have been submitted to the GenBank and are available under accession numbers U27275-27293.
Cloning and Characterization of the Human Leukotriene A4 Hydrolase Gene
Article first published online: 3 MAR 2005
European Journal of Biochemistry
Volume 231, Issue 1, pages 65–71, July 1995
How to Cite
Mancini, J. A. and Evans, J. F. (1995), Cloning and Characterization of the Human Leukotriene A4 Hydrolase Gene. European Journal of Biochemistry, 231: 65–71. doi: 10.1111/j.1432-1033.1995.0065f.x
- Issue published online: 3 MAR 2005
- Article first published online: 3 MAR 2005
- (Received 27 February/24 April 1995) – EJB 95 0313/2
- Leukotriene A4 hydrolase;
- leukotriene B4;
- epoxide hydrolase
The human gene encoding the bifunctional aminopeptidase and epoxide hydrolase enzyme, leukotriene A4 hydrolase (LTA4 hydrolase) has been cloned from a placental λ phage genomic library. The gene is greater than 35 kbp and contains 19 exons ranging in size over 24–312 bp. The introns range in size over 0.26–5.7 kbp. The essential zinc-binding histidine residues and glutamate residue, which delineate the zinc-binding domain required for both enzyme activities of LTA4 hydrolase, are divided between exons 10 and 11. The LTA4 hydrolase gene was localized to chromosome 12q22 utilizing fluorescence in situ hybridization. Based on the chromosome localization and genomic DNA analysis, LTA4 hydrolase was determined to be a single-copy gene. Primer-extension analysis demonstrated that the transcription initiation site of LTA4 hydrolase mRNA is 151 nucleotides upstream of the initiator ATG. Approximately 4 kbp of 5′-flanking region of the LTA4 hydrolase gene has been obtained and sequencing of 1.4 kb of this 5′-flanking region demonstrated several transcription-factor consensus sequences, including a phorbol-ester-response element (AP2) and two xenobiotic-response elements. The cloning and characterization of the human gene for LTA4 hydrolase provides a basis for further insight into transcriptional regulation of this bifunctional enzyme and its role in various inflammatory processes.