Characterization of a human lysophosphatidic acid acyltransferase that is encoded by a gene located in the class III region of the human major histocompatibility complex

Sequence analysis of cDNA clones corresponding to a number of genes located in the class III region of the human major histocompatibility complex (MHC), in the chromosome band 6p21.3, has shown that the G15 gene encodes a 283-amino acid polypeptide with significant homology over the entire polypeptide with the enzyme lysophosphatidic acid acyltransferase (LPAAT) from different yeast, plant, and bacterial species, The amino acid sequence of the MHC-encoded human LPAAT (hLPAAT alpha) is 48% identical to the recently described hLPAAT (Eberhardt, C., Gray, P. W., and Tjoelker, L. W. (1991) J, Biol. Chem. 272, 20299 - 20305), which is encoded by a gene located on chromosome 9p34.3, LPAAT is the enzyme that in lipid metabolism converts lysophosphatidic acid (LPA) into phosphatidic acid (PA), The expression of the hEPAAT alpha polypeptide in the baculovirus system and in mammalian cells has shown that it is an intracellular protein that contains LPAAT activity. Cell extracts from insect cells overexpressing hLPAAT alpha were analyzed in different LPAAT enzymatic assays using as substrates, different acyl acceptors and acyl donors, These cell extracts were found to contain up to 5-fold more LPAAT activity compared with control cell extracts, indicating that the hLPAAT alpha specifically converts LPA into PA, incorporating different acyl-CoAs with different affinities, The hLPAAT alpha polypeptide expressed in the mammalian Chinese hamster ovary cell Pine was found, by confocal immunofluorescence, to be localized in the endoplasmic reticulum, Due to the known role of EPA anti PA in intracellular signaling and inflammation, the hLPAAT alpha gene represents a candidate gene for some MHC-associated diseases.