ORGANIZATION OF THE GENE ENCODING THE HUMAN ENDOTHELIN-CONVERTING ENZYME (ECE-1)

The two human endothelin-converting enzyme (ECE-1) isoforms, which dif fer by their N-terminal region, are encoded by a single gene. The gene is composed of 19 exons that span more than 68 kilobases and has been mapped 60 the 1p36 band of the human genome, The two isoform mRNAs di splay different tissue distributions, Their precursors are transcribed from two distinct start sites, upstream from exon 1 and exon 3, respe ctively. Sequence analysis of the two putative promoters revealed the presence of motifs characteristic for several transcription factors. C omparison of the ECE-1 gene structure with those of other zinc metallo proteases, as well as a phylogenetic study, confirm the existence of a metalloprotease subfamily composed of ECE-I, ECE-2, neutral endopepti dase, Kell blood group protein, and two bacterial enzymes.