Online Mendelian Inheritance in Man (OMIM) (original) (raw)

* 603099

1-ACYLGLYCEROL-3-PHOSPHATE O-ACYLTRANSFERASE 1; AGPAT1

Alternative titles; symbols

LYSOPHOSPHATIDIC ACID ACYLTRANSFERASE-ALPHA

LPAAT-ALPHA

HGNC Approved Gene Symbol: AGPAT1

Cytogenetic location: 6p21.32 Genomic coordinates (GRCh38) : 6:32,168,212-32,178,108 (from NCBI)

TEXT

Cloning and Expression

Lysophosphatidic acid (LPA) and phosphatidic acid (PA) are 2 phospholipids involved in signal transduction and in lipid biosynthesis in cells. LPA acyltransferase (LPAAT), or 1-acyl-sn-glycerol-3-phosphate acetyltransferase (EC 2.3.1.51), catalyzes the conversion of LPA to PA. By searching an EST database for human homologs of yeast LPAAT, West et al. (1997) identified cDNAs encoding 2 proteins that they designated LPAAT-alpha and LPAAT-beta (603100). The predicted LPAAT-alpha protein is 283 amino acids long. Northern blot analysis revealed LPAAT-alpha expression in all tissues tested, with highest expression in skeletal muscle. West et al. (1997) demonstrated that both human LPAATs complemented an E. coli LPAAT mutation. Overexpression of the human LPAATs in mammalian cell lines led to increased enzyme activity. This increase in activity correlated with enhanced transcription and synthesis of IL6 (147620) and TNF-alpha (191160), suggesting that LPAAT overexpression may amplify the cellular response to cytokine stimulation.

Independently, Stamps et al. (1997) and Aguado and Campbell (1998) isolated LPAAT-alpha cDNAs. Aguado and Campbell (1998) reported that the sequence of the LPAAT-alpha protein shares 48% and 31% identity with those of LPAAT-beta and yeast LPAAT, respectively. They proposed that, based on sequence analysis and immunofluorescence studies, LPAAT-alpha is an endoplasmic reticulum (ER) transmembrane protein with 4 transmembrane domains. The potential active center of the enzyme is located between the third and fourth domains, facing the cytosolic part of the ER. Analysis of expression in insect and Chinese hamster ovary (CHO) cells suggested that a 58-amino acid signal sequence is cleaved from LPAAT-alpha to form a mature protein that migrates at 26 kD by SDS-PAGE. The recombinant protein has affinity for fatty acids of acyl-chain lengths of 12 to 18 carbons, with a slight dependence on the degree of saturation.

Mapping

Aguado and Campbell (1998) determined that the LPAAT-alpha gene is located within a 220-kb segment separating the major histocompatibility complex class II region and the complement C4 genes of the class III region on chromosome 6p21.3. The authors noted that the LPAAT-alpha, NOTCH4 (164951), PBX2 (176311), and TNXA (see 600985) genes have respective family members LPAAT-beta, NOTCH1 (190198), PBX3 (176312), and TN-C (187380) located on 9q34, suggesting that these 2 regions arose from duplication of an ancestral chromosomal segment.

REFERENCES

  1. Aguado, B., Campbell, R. D.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. J. Biol. Chem. 273: 4096-4105, 1998. [PubMed: 9461603] [Full Text: https://doi.org/10.1074/jbc.273.7.4096\]
  2. Stamps, A. C., Elmore, M. A., Hill, M. E., Kelly, K., Makda, A. A., Finnen, M. J.A human cDNA sequence with homology to non-mammalian lysophosphatidic acid acyltransferases. Biochem. J. 326: 455-461, 1997. [PubMed: 9291118] [Full Text: https://doi.org/10.1042/bj3260455\]
  3. West, J., Tompkins, C. K., Balantac, N., Nudelman, E., Meengs, B., White, T., Bursten, S., Coleman, J., Kumar, A., Singer, J. W., Leung, D. W.Cloning and expression of two human lysophosphatidic acid acyltransferase cDNAs that enhance cytokine-induced signaling responses in cells. DNA Cell Biol. 16: 691-701, 1997. [PubMed: 9212163] [Full Text: https://doi.org/10.1089/dna.1997.16.691\]

Contributors:

Victor A. McKusick - updated : 4/30/2002

Creation Date:

Rebekah S. Rasooly : 10/7/1998

Edit History:

carol : 06/06/2005
alopez : 2/11/2004
alopez : 5/1/2002
terry : 4/30/2002
carol : 12/7/1999
alopez : 10/8/1998
alopez : 10/7/1998