IDENTIFICATION OF A SIALIDASE ENCODED IN THE HUMAN MAJOR HISTOCOMPATIBILITY COMPLEX

Mammalian sialidases are important in modulating the sialic acid conte nt of cell-surface and intracellular glycoproteins. However, the full extent of this enzyme family and the physical and biochemical properti es of its individual members are unclear. We have identified a novel g ene, G9, in the human major histocompatibility complex (MHC), that enc odes a 415-amino acid protein sharing 21-28% sequence identity with th e bacterial sialidases and containing three copies of the Asp-block mo tif characteristic of these enzymes. The level of sequence identity be tween human G9 and a cytosolic sialidase identified in rat and hamster (28-29%) is much less than would be expected for analogous proteins i n these species, suggesting that G9 is distinct from the cytosolic enz yme. Expression of G9 in insect cells has confirmed that it encodes a sialidase, which shows optimal activity at pH 4.6, but appears to have limited substrate specificity. The G9 protein carries an N-terminal s ignal sequence and immunofluorescence staining of COS7 cells expressin g recombinant G9 shows localization of this sialidase exclusively to t he endoplasmic reticulum. The location of the G9 gene, within the huma n MHC, corresponds to that of the murine Neu-1 locus, suggesting that these are analogous genes. One of the functions attributed to Neu-1 is the up-regulation of sialidase activity during T cell activation.