Identification of a human cDNA sequence which encodes a novel membrane-associated protein containing a zinc metalloprotease motif

We report the cloning and characterization of a human cDNA predicted to encode a novel hydrophobic protein containing four transmembrane domains and a zinc metalloprotease motif, HEXXH, between the. third and fourth transmembrane domains, and have named the molecule metalloprotease-related protein-1 (MPRP-1). The MPRP-1 gene was localized to chromosome 1-p32.3 by radiation hybrid mapping, and Northern blot analysis revealed expression in many organs, with strong expression in the heart, skeletal muscle, kidney and liver. Immunohistochemical analyisis showed that MPRP-1 was localized in the endoplasmic reticulum (ER), and not in the Golgi compartment. Fragments of DNA encoding a segment homologous to the HEXXH motif of MPRP-1 are widely found in bacteria, yeast, plants, and animals. These results suggest that the MPRP-1 may have highly conserved functions, such as in intracellular proteolytic processing in the ER.