Ynl038wp (Gpi15p) is the Saccharomyces cerevisiae homologue of human Pig-Hp and participates in the first step in glycosylphosphatidylinositol assembly.
Glycosylphosphatidylinositols (GPIs) are found in all eukaryotes and are synthesized in a pathway that starts with the transfer of N-acetylglucosamine (GlcNAc) from UDP-GlcNAc to phosphatidylinositol (PI). This reaction is carried out by a protein complex, three of whose subunits in humans, hGpi1p, Pig-Cp and Pig-Ap, have sequence and functional homologues in the Saccharomyces cerevisiae Gpi1, Gpi2 and Gpi3 proteins, respectively. Human GlcNAc-PI synthase contains two further subunits, Pig-Hp and PigPp. We report that the essential YNL038w gene encodes the S. cerevisiae homologue of Pig-Hp. Haploid YNL038w-deletion strains were created, in which Ynl038wp could be depleted by repressing YNL038w expression using the GAL10 promoter. Depletion of Ynl038wp from membranes virtually abolished in vitro GlcNAc-PI synthetic activity, indicating that Ynl038wp is necessary for GlcNAc-PI synthesis in vitro. Further, depletion of Ynl038wp in an smp3 mutant background prevented the formation of the trimannosylated GPI intermediates that normally accumulate in this late-stage GPI assembly mutant. Ynl038wp is therefore required for GPI synthesis in vivo. Because YNL038w encodes a protein involved in GPI biosynthesis, we designate the gene GPI15. Potential Pig-Hp/Gpi15p counterparts are also encoded in the genomes of Schizosacchomyces pombe and Candida albicans.
Yan
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Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Westfall
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BA
Orlean
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P
D000117:Acetylglucosamine / Q000031:analogs & derivatives* / Q000032:analysis / Q000096:biosynthesis; D000595:Amino Acid Sequence; D002855:Chromatography, Thin Layer; D017261:Glycosylphosphatidylinositols / Q000032:analysis / Q000096:biosynthesis*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010716:Phosphatidylinositols / Q000032:analysis / Q000096:biosynthesis; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D017261:Glycosylphosphatidylinositols; C448723:Gpi15 protein, S cerevisiae; D008565:Membrane Proteins; C081027:N-acetylglucosaminylphosphatidylinositol; C414442:PIGH protein, human; D010716:Phosphatidylinositols; D029701:Saccharomyces cerevisiae Proteins; D000117:Acetylglucosamine