Collagen‐binding domain of human plasma fibronectin contains a latent type‐IV collagenase

Cleavage of the 45‐kDa gelatin‐binding fragment of human plasma fibronectin with fibronectinase resulted in the activation of two forms of metalloproteinase with different substrate specificities. The 40‐kDa FN‐type‐IV collagenase A degrades heat‐denatured type‐I collagen, laminin and also native collagen type IV. The 27‐kDa FN‐type‐IV collagenase B degrades native collagen type IV, but it does not cleave laminin and only poorly degrades gelatin. Both enzymes begin with the same N‐terminal sequence VYQPQPH‐ (residues 262–268 of fibronectin) but, contrary to the FN‐type‐IV collagenase A, the FN‐type‐IV collagenase B has lost the C‐terminal region of type I repeats, where the major gelatin‐binding determinants of fibronectin are located. The FN‐type‐IV collagenases A and B are sequentially similar to the middle domain (domain II) of collagenase type IV, secreted by H‐ras‐transformed human bronchial epithelial cells. Substrate and inhibition specificity of FN‐type‐IV collagenase A and B are different from those of FN‐gelatinase and FN‐laminase, isolated previously from the central and C‐terminal fibronectin domains, respectively. The substrate specificity of both enzymes, characterized in this study, is also different from that of already known matrix‐degrading metalloproteinases.