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FEBS J. 2005 Mar;272(5):1160-8.

Saccharomyces cerevisiae Ybr004c and its human homologue are required for addition of the second mannose during glycosylphosphatidylinositol precursor assembly.

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  • 1New England Biolabs, Beverly, MA 01915, USA.


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.

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