Mannan-binding lectin-associated serine protease 3 cleaves synthetic peptides and insulin-like growth factor-binding protein 5.

Mannan-binding lectin-associated serine proteases (MASPs) are secreted as single-chain precursors and processed into two disulfide bond-linked chains. MASP-3 and MASP-1, derived from the same gene, contain identical A chains, but entirely different catalytic domain-containing B chains. In contrast to MASP-1 and MASP-2, the proteinase activity of MASP-3 has not been described previously. We show here the proteolytic activity of the purified recombinant human MASP-3 catalytic domain toward peptides and protein substrates. Among the fluorogenic peptides tested, it specifically cleaved peptides with Arg at the P1 position. Among seven insulin-like growth factor-binding proteins, it selectively cleaved IGFBP-5, which is the first protein substrate identified for MASP-3. All three cleavage sites identified contained Arg or Lys at the P1 position and Pro at the P2 position. As compared to MASP-1 and MASP-2, MASP-3 has distinct substrate specificity and inhibitor profile. These results should be useful for further studies of the structure and function of human MASP-3.