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Volume 271, Number 38, Issue of September 20, 1996 pp. 22945-22948
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

COMMUNICATION:
Molecular Identification of a Putative Human Hyaluronan Synthase

(Received for publication, April 17, 1996, and in revised form, July 18, 1996)

Ken Watanabe and Yu Yamaguchi

From the Burnham Institute,  La Jolla, California 92037

To identify the putative mammalian hyaluronan synthase, we cloned a human cDNA that is related to the Streptococcus hyaluronan synthase (HasA) and the Xenopus developmental protein DG42 which has been shown to have chitin synthase activity. The cDNA, for which we propose the name Has2, encodes a novel protein with a predicted molecular mass of 63.6 kDa. Has2 shows 55% amino acid identity with Xenopus DG42 and 52% identity with the mouse HAS protein, another putative hyaluronan synthase recently reported by Itano and Kimata (Itano, N., and Kimata, K. (1996) J. Biol. Chem. 271, 9875-9878). The deduced primary structure revealed the presence of several hydrophobic stretches which can form multiple transmembrane domains. It also demonstrated the complete conservation of amino acid residues that are known to be critical for N-acetylglucosaminyltransferase activity of yeast chitin synthase. When the Has2 cDNA was transfected into human 293 and Chinese hamster ovary cells, the production of hyaluronan in the transfected cells increased up to 34- and 9-fold, respectively. Strong expression of Has2 mRNA was observed in exponentially proliferating human IMR-90 fibroblasts but not in growth-arrested IMR-90 cells. These results suggest that the Has2 protein is a crucial component of the human hyaluronan synthase system.


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