PIG-C, one of the three human genes involved in the first step of glycosylphosphatidylinositol biosynthesis is a homologue of Saccharomyces cerevisiae GPI2

Abstract

Glycosylphosphatidylinositol (GPI) protein anchors are ubiquitous in eukaryotic cells. GPI anchors are synthesized in the endoplasmic reticulum by actions of ten or more gene products. The first step of the biosynthesis, the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol, is mediated by at least three genes in mammalian cells (PIG-A, PIG-H and PIG-C) and in yeast (GPI1, GPI2 and GPI3/SPT14/CWH6). PIG-A is homologous to GPI3/SPTI4/CWH6. However, PIG-H has no homology with GPI1 or GPI2. Here we cloned a human homologue of GPI2 and showed that it is PIG-C. PIG-C protein is a 297 amino-acid membrane protein in the endoplasmic reticulum that has 20% amino acid identity with GPI2. Since there are several human EST sequences that have homology to GPI1, our results suggest that four genes are involved in the first step of GPI anchor synthesis in mammalian cells.