Molecular cloning of a mammalian hyaluronidase reveals identity with hemopexin, a serum heme-binding protein.
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.
Zhu
L
L
Department of Pathology, University of California, San Francisco 94143-0506.
Hope
T J
TJ
Hall
J
J
Davies
A
A
Stern
M
M
Muller-Eberhard
U
U
Stern
R
R
Parslow
T G
TG
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D003001:Cloning, Molecular; D017124:Conserved Sequence; D018076:DNA, Complementary; D006420:Hemeproteins / Q000378:metabolism*; D006466:Hemopexin / Q000235:genetics*; D006821:Hyaluronoglucosaminidase / Q000235:genetics*; D008099:Liver / Q000201:enzymology; D008969:Molecular Sequence Data; D013552:Swine
D018076:DNA, Complementary; D006420:Hemeproteins; D006466:Hemopexin; D006821:Hyaluronoglucosaminidase