HYAL2, A HUMAN GENE EXPRESSED IN MANY CELLS, ENCODES A LYSOSOMAL HYALURONIDASE WITH A NOVEL TYPE OF SPECIFICITY

Using Expressed Sequence Tags (ESTs) deposited in the data banks, a cD NA has been assembled that encodes a protein related to the hyaluronid ases from bee venom and mammalian sperm. Expression of this cDNA yield ed a polypeptide termed HYAL2, which is located in lysosomes, The HYAL 2 protein was shown to have hyaluronidase activity below pH 4, However , it only hydrolyzed hyaluronan of high molecular mass from umbilical cord, rooster comb, and a Streptococcus strain. The reaction product w as a polysaccharide of about 20 kDa, which was further hydrolyzed to s mall oligosaccharides by the sperm hyaluronidase. Conversely, hyaluron an fragments from vitreous humor, which had a molecular mass of about 20 kDa, were not cleaved by the HYAL2 enzyme to any detectable extent. These results provide evidence for the existence of structural domain s in hyaluronan, which are resistant to the action of this enzyme, The structural and functional implications of these findings are discusse d.