A novel human metalloprotease synthesized in the liver and secreted into the blood: Possibly, the von Willebrand factor-cleaving protease?

We identified a novel metalloprotease, which could be responsible for cleav ing the Tyr842-Met843 peptide bond of von Willebrand factor (vWF). This met alloprotease was purified from Cohn Fraction-I precipitate of human pooled plasma by the combination of get filtration, DEAE chromatography, and prepa rative polyacrylamide gel electrophoresis in the presence of SDS. The NH2-t erminal amino acid sequence of the isolated protein was: AAGGILHLELLVAVGPDV FQAHQEDTRRY. Based on this sequence, we searched human genomic and EST data bases, and identified compatible nucleotide sequences. These results sugges ted that this protein is a novel metalloprotease, a member of the family of a disintegrin and metalloprotease with thrombospondin type-1 motifs (ADAMT S), and its genomic DNA was mapped to human chromosome 9q34. Multiple human tissue northern blotting analysis indicated that the mRNA encoding this pr otease spanned approximately 5 kilobases and was uniquely expressed in the liver. Furthermore, we determined the cDNA sequence encoding this protease, and found that this protease was comprised of a signal peptide, a proregio n followed by the putative furin cleavage site, a reprolysin-type zinc-meta lloprotease domain, a disintegrin-like domain, a thrombospondin type-1 (TSP 1) motif, a cysteine-rich region, a spacer domain, and COOH-terminal TSP1 m otif repeats.