title: A mutation in the 5' untranslated region of the human alpha-galactosidase A gene in high-activity variants inhibits specific protein binding.
abstract: Recently, normal individuals were identified who had high levels of plasma alpha-galactosidase A activity and a G to A transition in the 5' untranslated (5' UT) region of the alpha-galactosidase A gene. Electrophoretic mobility shift assays revealed that the wild-type sequence at the site of this mutation complexed with specific nuclear proteins. A standard NF-kappa B site competed with the 5' UT site for formation of these DNA-protein complexes. Complex formation was inhibited by the transition mutation. Therefore, the wild-type site might down-modulate expression of the alpha-galactosidase A gene from this 5' untranslated region, which includes a previously described protein-binding site for another family of sequence-specific DNA-binding proteins, methylated DNA-binding protein.
authors.affiliation: Molecular and Cellular Biology Program, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Saifudeen
authors.forename: R J
authors.initials: RJ
authors.lastname: Desnick
authors.forename: M
authors.initials: M
authors.lastname: Ehrlich
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D000519:alpha-Galactosidase / Q000235:genetics*
chemical_list: D016328:NF-kappa B; D009687:Nuclear Proteins; D004247:DNA; D000519:alpha-Galactosidase