A gene for rabbit synovial cell collagenase: member of a family of metalloproteinases that degrades the connective tissue matrix

Abstract

We have determined the nucelotide sequence of a collagenase mRNA from rabbit synovial cells from which the primary structure of the encoded protein was deduced. This proteinase is 51% homologous to the enzyme that activates it from the zymogen form, rabbits synovial cell activator/stromelysin. Rabbit collagenase and activator/stromelysin thus share comembership in a gene family that includes human skin collagenase; the human and rabbit metalloproteinase, activator/stomelysin; and an oncogene-induced proteinase from rat named transin. The mRNA sequence of collagenase enabled us to completely map the structure of its gene, which is 9.1 kilobases and is composed of 10 exons and 9 introns. This is the first report of the structure of a collagenase gene. We show that it has striking similarity to additional members of this metalloproteinase gene family, transin genes I and II of rat. We have further sequenced genomic DNA flanking the collagenase gene and have identified nucleic acid elements of possible importance in gene regulation.