Genomic organization of the human homologue of the rat pancreatic elastase I gene

Abstract

The homologue of the rat pancreatic elastase I gene was found in the human genome, but its transcription was completely suppressed in the adult human pancreas as we reported previously. In this study, we characterized the complete structure of the eight putative exons of the silent gene for human elastase I. A genotype analysis of the exon 1 DNA sequence revealed that at least two allelic elastase I genes are present in human genomes. A primate-specific repetitive DNA element (MER1) was identified in the 3'-flanking region of the human elastase I gene. The primary structure of human preproelastase I, deduced from the sequences of the eight exons, showed an 89% identity with that of porcine or rat pancreatic preproelastase I. The amino acid residues of the serine protease catalytic triad and the eight cysteine residues conserved in the elastase family were present at positions equivalent to those observed in porcine and rat elastase I, suggesting that the gene product may function as an elastolytic enzyme if this gene is expressed in any tissue.

Pancreatic Elastases

“…Rat PE I has a distinct elastinolytic activity [13] and is structurally related to pig PE I [2]. The human pancreas does not synthesize an elastase similar to pig PE I [52], because the human gene corresponding to the gene of rat pancreatic elastase I is silent in this tissue [53]. The enzyme, which is sometimes called 'human pancreatic elastase I' [54,55], is in fact protease E [52], now called pancreatic endopeptidase E. The other pancreatic 'elastases' either do not solubilize elastin or have not been sequenced.…”

Inactivity of Recombinant ELA2B Provides a New Example of Evolutionary Elastase Silencing in Humans

“…The common pancreatic elastase (ELA1) routinely purifi ed from pig or cow pancreas is not expressed in humans due to transcriptional silencing [1][2][3] . For unclear evolutionary reasons, the human ELA1 gene has accumulated mutations in the 5 upstream region which inactivated both its promoter and enhancer [3] .…”

Identification of activating enzymes of a novel FBPase inhibitor prodrug, CS‐917

“…In humans, six elastase genes (elastase 1 (ELA1), ELA2, ELA2A, ELA2B, ELA3A, and ELA3B) are known. ELA1 is expressed in skin keratinocytes (Kawashima et al 1992;Talas et al 2000). ELA2, also known as neutrophil elastase or leukocyte elastase, is expressed in bone marrow myelocytic precursor cells, mostly promyelocytes (Fouret et al 1989;Lee and Downey 2001).…”