STRIKING STRUCTURAL AND FUNCTIONAL SIMILARITIES SUGGEST THAT INTESTINAL SUCRASE-ISOMALTASE, HUMAN LYSOSOMAL ALPHA-GLUCOSIDASE AND SCHWANNIOMYCES-OCCIDENTALIS GLUCOAMYLASE ARE DERIVED FROM A COMMON ANCESTRAL GENE

Sequence comparison of the primary structure of the yeast Schwanniomyces occidentalis glucoamylase (GAM) with GAMs in different micro-organisms did not reveal significant similarities. By contrast, striking similarities were, surprisingly, found with 3 mammalian secretory and integral membrane proteins: the 2 subunits of intestinal brush border sucrase-isomaltase and human lysosomal alpha-glucosidase. The similarities among these proteins are found as clusters of up to 8 amino acids and distributed all over the protein sequences. The major sequence differences are found in the N-terminal regions accounting, probably, for the different cellular locations of these proteins. The high level of similarities between sucrase, isomaltase, Sch. occidentalis GAM and human lysosomal alpha-glucosidase suggest that these proteins are derived from the same ancestral gene. To our knowledge, this is the first report that describes similarities between a yeast secretory protein and mammalian secretory and integral membrane proteins.