The initial enzyme for glycosylphosphatidylinositol biosynthesis requires PIG-Y, a seventh component

Mol Biol Cell. 2005 Nov;16(11):5236-46. doi: 10.1091/mbc.e05-08-0743. Epub 2005 Sep 14.


Biosynthesis of glycosylphosphatidylinositol (GPI) is initiated by an unusually complex GPI-N-acetylglucosaminyltransferase (GPI-GnT) consisting of at least six proteins. Here, we report that human GPI-GnT requires another component, termed PIG-Y, a 71 amino acid protein with two transmembrane domains. The Burkitt lymphoma cell line Daudi, severely defective in the surface expression of GPI-anchored proteins, was a null mutant of PIG-Y. A complex of six components was formed without PIG-Y. PIG-Y appeared to be directly associated with PIG-A, implying that PIG-Y is the key molecule that regulates GPI-GnT activity by binding directly to the catalytic subunit PIG-A. PIG-Y is probably homologous to yeast Eri1p, a component of GPI-GnT. We did not obtain evidence for a functional linkage between GPI-GnT and ras GTPases in mammalian cells as has been reported for yeast cells. A single transcript encoded PIG-Y and, to its 5' side, another protein PreY that has homologues in a wide range of organisms and is characterized by a conserved domain termed DUF343. These two proteins are translated from one mRNA by leaky scanning of the PreY initiation site.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CHO Cells
  • Cloning, Molecular
  • Cricetinae
  • Cricetulus
  • Glycosylphosphatidylinositols / biosynthesis*
  • HeLa Cells
  • Humans
  • Lymphoma, B-Cell
  • Membrane Proteins / metabolism*
  • Molecular Sequence Data
  • Mutation
  • N-Acetylglucosaminyltransferases
  • Sequence Homology
  • Tumor Cells, Cultured
  • ras Proteins / metabolism


  • Glycosylphosphatidylinositols
  • Membrane Proteins
  • PIGY protein, human
  • phosphatidylinositol glycan-class A protein
  • N-Acetylglucosaminyltransferases
  • N-acetyllactosaminide beta-1,6-N-acetylglucosaminyltransferase
  • ras Proteins