The yeast spt14 gene is homologous to the human PIG-A gene and is required for GPI anchor synthesis

The protein encoded by the yeast gene SPT14 shows high sequence similarity to the human protein, PIG-A, whose loss of activity is at the origin of the disease paroxysmal nocturnal hemoglobinuria. The symptoms of this disease are apparently due to a loss of cell surface, glycosylphosphatidylinositol (GPI)-anchored proteins. Like PIG-A mutant cells, spt14 mutant cells are defective in GPI anchoring due to a defect in the synthesis of GlcNAc-PI, the first step of GPI synthesis. The spt14 mutant causes several other abnormalities including transcriptional defects and a downregulation of inositolphosphoceramide synthesis. We suggest that these defects are indirect results of the loss of GPI anchoring.