Molecular cloning of a mammalian hyaluronidase reveals identity with hemopexin, a serum heme-binding protein

• Published in: The Journal of biological chemistry 1994-12, Vol.269 (51), p.32092-32097
• Main Authors: Zhu, L, Hope, T J, Hall, J, Davies, A, Stern, M, Muller-Eberhard, U, Stern, R, Parslow, T G
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Biological Evolution; Cloning, Molecular; Conserved Sequence; DNA, Complementary; Hemeproteins - metabolism; Hemopexin - genetics; Hyaluronoglucosaminidase - genetics; Liver - enzymology; Molecular Sequence Data; Swine
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)31605-3

Hyaluronan is the most abundant glycosaminoglycan of the extracellular matrix and is a critical substrate for cellular attachment and locomotion. Little is known about the class of enzymes, termed hyaluronidases, that are responsible for hyaluronan catabolism in mammals. We have determined a partial amino acid sequence from a purified preparation of porcine liver hyaluronidase and have used this information as the basis for cloning complementary DNA that encodes the corresponding protein. When expressed in a recombinant baculovirus system, the protein exhibited hyaluronidase activity in a substrate-gel assay. The deduced sequence of this mammalian hyaluronidase is that of a 459-amino-acid polypeptide bearing four potential N-glycosylation sites as well as a copy of a proposed hyaluronan binding motif. Remarkably, amino acid sequence comparisons and immunologic cross-reactivities strongly suggest that the cloned protein is identical to hemopexin, an abundant, heme-binding serum protein. Although hemopexin has not previously been reported to possess any enzymatic activity, it includes a conserved domain found in collagenases, stromelysins, and other enzymes that metabolize the extracellular matrix. We conclude that hemopexin is the predominant hyaluronidase expressed in mammalian liver.