Expression and enzymatic activity of human disintegrin and metalloproteinase ADAM19/meltrin beta

The adamalysins are involved in proteolysis, adhesion, fusion, and intracel lular signaling. Human ADAM19/adamalysin-19 (A disintegrin and metalloprote inase 19) was identified from primary dendritic cell cDNA libraries. It has a signal sequence, a prodomain with a "cysteine-switch" residue, a metallo proteinase domain with a zinc-binding site, a disintegrin, a cysteine-rich domain, an epidermal-growth-factor-like domain, a transmembrane domain, an d a cytoplasmic domain with putative SH3 ligand binding sites. Its mRNA was expressed in the placenta, heart, bladder, lymph nodes, and leukocytes, co lorectal ade nocarcinoma SW 480, and other organs/cells. The hADAM19 recomb inant protein was expressed in human cells. It formed a complex with and cl eaved alpha-a macroglobulin (alpha2-M). Its proteolytic activity was blocke d by 1,10-phenanthroline, EDTA, EGTA, and a synthetic matrix metalloprotein ase (MMP) inhibitor and not by the tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2. It did not cleave the MMP substrates tested, e.g., type I collagen and gelatin, casein, and four peptide substrates. Thus, hADAM19 is an active metalloproteinase and may have a specific substrate profile. ( C) 2001 Academic Press.