InterPro domain: IPR039507

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 consisting of four subunits in humans, three of which, Gpi1p, Pig-C and Pig-A, have sequence and functional counterparts in theS. cerevisiae Gpi1, Gpi2 and Gpi3 proteins, respectively [ 1 ]. Pig-A/Gpi3 is the UDPGlcNAc-binding and catalytic subunit of the complex [ 2 , 3 ].

Pig-A is an X-linked gene in humans; mutations in this gene have been associated with the hematological disorder Paroxysmal Nocturnal Hemoglobinuria (PNH) [ 4 ].

1. Characterisation of the enzymatic complex for the first step in glycosylphosphatidylinositol biosynthesis. Int. J. Biochem. Cell Biol. 32, 339-50
2. Identification of SPT14/CWH6 as the yeast homologue of hPIG-A, a gene involved in the biosynthesis of GPI anchors. Biochim. Biophys. Acta 1243, 549-51
3. Photoaffinity labelling with P3-(4-azidoanilido)uridine 5'-triphosphate identifies gpi3p as the UDP-GlcNAc-binding subunit of the enzyme that catalyses formation of GlcNAc-phosphatidylinositol, the first glycolipid intermediate in glycosylphosphatidylinositol synthesis. Biochem. J. 350 Pt 3, 815-22
4. Paroxysmal nocturnal haemoglobinuria: nature's gene therapy? MP, Mol. Pathol. 55, 145-52