CLONING OF A HUMAN GENE POTENTIALLY ENCODING A NOVEL MATRIX METALLOPROTEINASE HAVING A C-TERMINAL TRANSMEMBRANE DOMAIN

Matrix metalloproteinases (MMPs) play key roles in tissue remodeling during physiological and pathological processes by degrading various extracellular matrix (ECM) components. Although nine distinct MMPs have been characterized by cDNA cloning, there are thought to be more corresponding to the complexity of the ECM. MMP genes expressed in human tissues and cell lines were analyzed by the polymerase chain reaction (PCR) using degenerate primers that corresponded to the conserved amino acid (aa) sequences of the MMPs. One isolated complementary DNA (cDNA) fragment had sequence homology to the reported MMPs, but was otherwise unique. A human placenta cDNA library (Clontech) was screened using the fragment as a probe and a 3.4-kb cDNA fragment containing a long open reading frame (potentially encoding 582 aa) was isolated. The putative gene product had a common domain structure and the conserved sequence of a MMP, but it had a unique transmembrane (TM)-like structure at the C terminus. It should, therefore, be an TM protein, whereas all the other reported MMPs are secretory proteins. Thus, the gene is thought to be the first of a new subclass of MMPs whose products are potentially expressed on the cell surface.