title: A Gln-281 to Arg substitution in alpha-L-fucosidase is responsible for a common polymorphism detected by isoelectric focusing.
abstract: A common polymorphism of human alpha-L-fucosidase consists of three phenotypes (Fu 1, Fu 2, and Fu 2-1) assigned by isoelectric focusing. The phenotypes are determined by two codominant alleles (Fu1 and Fu2). Isozymes with the Fu 2 phenotype have more basic pI than Fu 1, while Fu 2-1 is a mixture of Fu 2 and Fu 1. Recently, a missense mutation (A860-->G) in the alpha-L-fucosidase gene was described that did not affect alpha-L-fucosidase activity. The mutation causes the substitution of Arg (pKaGuan = 12.5) for Gln-281, which has no ionizable side chain. Isoelectric focusing profiles of extracts of COS-1 cells transfected with wild-type or mutant alpha-L-fucosidase cDNAs had phenotypes of Fu 1 and Fu 2, respectively. Next, 20 human lymphoid cell lines were examined for the occurrence of the A860-->G mutation and expression of the Fu 1, Fu 2, and Fu 2-1 phenotypes. Eight lines with Fu 2 were homozygous for the A860-->G mutation; six lines with Fu 1 were homozygous for the normal nucleotide (A860); and six lines with Fu 2-1 were heterozygous. Thus, the A860-->G mutation is the molecular basis for the protein phenotypes and the Fu1 and Fu2 alleles. The normal nucleotide (A860) is responsible for Fu1 and the A860-->G mutation for Fu2.
authors.affiliation: Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263.
authors.forename: M
authors.initials: M
authors.lastname: Yang
authors.forename: R A
authors.initials: RA
authors.lastname: DiCioccio
mesh_terms: D000818:Animals; D001120:Arginine; D001483:Base Sequence; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D005347:Fibroblasts; D005645:Fucosidosis / Q000235:genetics; D005973:Glutamine; D006801:Humans; D007525:Isoelectric Focusing; D007527:Isoenzymes / Q000235:genetics*; D008969:Molecular Sequence Data; D010641:Phenotype; D017354:Point Mutation; D011110:Polymorphism, Genetic; D014162:Transfection; D005644:alpha-L-Fucosidase / Q000235:genetics*
chemical_list: D017931:DNA Primers; D007527:Isoenzymes; D005973:Glutamine; D001120:Arginine; D005644:alpha-L-Fucosidase