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.

Full Abstract

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 (hLPAATalpha) is 48% identical to the recently described hLPAAT (Eberhardt, C., Gray, P. W., and Tjoelker, L. W. (1997) 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 hLPAATalpha 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 hLPAATalpha 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 hLPAATalpha specifically converts LPA into PA, incorporating different acyl-CoAs with different affinities. The hLPAATalpha polypeptide expressed in the mammalian Chinese hamster ovary cell line was found, by confocal immunofluorescence, to be localized in the endoplasmic reticulum. Due to the known role of LPA and PA in intracellular signaling and inflammation, the hLPAATalpha gene represents a candidate gene for some MHC-associated diseases.

Author information

Author/s: Aguado, B (B); Campbell, R D (RD);

Affiliation: Medical Research Council Immunochemistry Unit, Department of Biochemistry, Oxford University, South Parks Road, Oxford OX1 3QU, United Kingdom.

Grants: (Agency:Wellcome Trust)

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: The Journal of biological chemistry (J Biol Chem), published in UNITED STATES. (Language: eng)

Reference: 1998-Feb; vol 273 (issue 7) : pp 4096-105

Dates: Created 1998/03/23; Completed 1998/03/23; Revised 2009/09/29;

PMID: 9461603, status: MEDLINE (last retrieval date: 9/29/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Acyltransferases - analysis; chemistry
Amino Acid Sequence
Base Sequence
Chromosomes, Human, Pair 6
Cloning, Molecular
Conserved Sequence - genetics
Gene Expression - genetics
Humans

Associated Chemicals: Lysophospholipids (0) ; Recombinant Proteins (0) ; lysophosphatidic acid (22002-87-5) ; Acyltransferases (EC 2.3.-) ; 2-acylglycerophosphate acyltransferase (EC 2.3.1.52)

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