title: Expression of cDNA encoding the human "protective protein" associated with lysosomal beta-galactosidase and neuraminidase: homology to yeast proteases.
abstract: The "protective protein" is a glycoprotein that associates with lysosomal beta-galactosidase and neuraminidase and is deficient in the autosomal recessive disorder galactosialidosis. We have isolated the cDNA encoding human "protective protein". The clone recognizes a 2 kb mRNA in normal cells that is not evident in fibroblasts of an early infantile galactosialidosis patient. The cDNA directs the synthesis of a 452 amino acid precursor molecule that is processed in vivo to yield mature "protective protein," a heterodimer of 32 kd and 20 kd polypeptides held together by disulfide bridges. This mature form is also biologically functional since it restores beta-galactosidase and neuraminidase activities in galactosialidosis cells. The predicted amino acid sequence of the "protective protein" bears homology to yeast carboxypeptidase Y and the KEX1 gene product. This suggests a protease activity for the "protective protein."
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002239:Carbohydrate Metabolism, Inborn Errors / Q000378:metabolism; D002268:Carboxypeptidases / Q000235:genetics*; D043402:Cathepsin A; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D005696:Galactosidases / Q000378:metabolism*; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008247:Lysosomes / Q000201:enzymology*; D008969:Molecular Sequence Data; D009439:Neuraminidase / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D010447:Peptide Hydrolases / Q000235:genetics; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D001616:beta-Galactosidase / Q000378:metabolism*
chemical_list: D006023:Glycoproteins; D012333:RNA, Messenger; D004247:DNA; D005696:Galactosidases; D009439:Neuraminidase; D001616:beta-Galactosidase; D002268:Carboxypeptidases; D010447:Peptide Hydrolases; C468629:CTSA protein, human; D043402:Cathepsin A; C022633:serine carboxypeptidase