title: Saccharomyces cerevisiae Ybr004c and its human homologue are required for addition of the second mannose during glycosylphosphatidylinositol precursor assembly.
abstract: Addition of the second mannose is the only obvious step in glycosylphosphatidylinositol (GPI) precursor assembly for which a responsible gene has not been discovered. A bioinformatics-based strategy identified the essential Saccharomyces cerevisiae Ybr004c protein as a candidate for the second GPI alpha-mannosyltransferase (GPI-MT-II). S. cerevisiae cells depleted of Ybr004cp have weakened cell walls and abnormal morphology, are unable to incorporate [3H]inositol into proteins, and accumulate a GPI intermediate having a single mannose that is likely modified with ethanolamine phosphate. These data indicate that Ybr004cp-depleted yeast cells are defective in second mannose addition to GPIs, and suggest that Ybr004cp is GPI-MT-II or an essential subunit of that enzyme. Ybr004cp homologues are encoded in all sequenced eukaryotic genomes, and are predicted to have 8 transmembrane domains, but show no obvious resemblance to members of established glycosyltransferase families. The human Ybr004cp homologue can substitute for its S. cerevisiae counterpart in vivo.
authors.affiliation: New England Biolabs, Beverly, MA 01915, USA.
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Fabre
authors.forename: Peter
authors.initials: P
authors.lastname: Orlean
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Taron
mesh_terms: D002470:Cell Survival; D019992:Databases as Topic; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D006801:Humans; D008358:Mannose / Q000378:metabolism*; D008364:Mannosyltransferases / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010957:Plasmids; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D017261:Glycosylphosphatidylinositols; D029701:Saccharomyces cerevisiae Proteins; D008364:Mannosyltransferases; D008358:Mannose