Alternative titles; symbols
HGNC Approved Gene Symbol: AGPAT4
Cytogenetic location: 6q26 Genomic coordinates (GRCh38): 6:161,129,967-161,274,061 (from NCBI)
AGPAT4 is a member of a family of 1-acyl-sn-glycerol 3-phosphate acyltransferases (EC 2.3.1.51), also known as lysophosphatidic acid acyltransferases, that catalyze the acylation of lysophosphatidic acid to phosphatidic acid, the precursor of all glycerolipids (summary by Lu et al., 2005).
Dominguez et al. (1998) identified ED166-4A1, an AGPAT4 cDNA, among a collection of AU-rich element (ARE)-containing mRNAs. AREs are cis-acting sequences typically found in 3-prime untranslated regions of many labile mRNAs. AREs either mediate rapid degradation of mRNA or inhibit its translation.
Lu et al. (2005) cloned mouse Agpat4. The deduced 378-amino acid protein has a putative N-terminal signal sequence and 3 transmembrane domains. It contains catalytic and substrate-binding motifs and a third motif conserved among AGPAT family members. RT-PCR analysis revealed high Agpat4 expression in mouse brain and intermediate to low expression in skeletal muscle, gut, kidney, spleen, and lung. Little to no Agpat4 was detected in heart and liver.
Using real-time PCR, Prasad et al. (2011) found that AGPAT4 was variably expressed in all human tissues examined, with highest expression in skeletal muscle, followed by heart, liver, prostate, and thymus.
Hartz (2012) mapped the AGPAT4 gene to chromosome 6q26 based on an alignment of the AGPAT4 sequence (GenBank AF156776) with the genomic sequence (GRCh37).
Bradley et al. (2017) found that, compared with wildtype mice, Lpaat-delta -/- mice had significantly reduced brain content of total saturated fatty acids, largely due to significant reduction in palmitate. Lpaat-delta -/- brain mitochondria had reduced abundance of phosphatidylethanolamine, but not other phospholipid species, and mutant mitochondria appeared and functioned normally. Lpaat-delta -/- brain showed reduced content of the N-methyl-D-aspartate (NMDA) receptor subunits Nr1 (GRIN1; 138249), Nr2a (GRIN2A; 138253), and Nr2b (GRIN2B; 138252), as well as the alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit Glur1 (GRIA1; 138248). However, phosphatidylinositol-mediated signaling was unaffected in mutant mice. Deficiency in Lpaat-delta caused delay in spatial learning and memory in a water maze task.
Bradley, R. M., Mardian, E. B., Bloemberg, D., Henao, J. J. A., Mitchell, A. S., Marvyn, P. M., Moes, K. A., Stark, K. D., Quadrilatero, J., Duncan, R. E. Mice deficient in lysophosphatidic acid acyltransferase delta (Lpaat-delta)/acylglycerophosphate acyltransferase 4 (Agpat4) have impaired learning and memory. Molec. Cell. Biol. 37: e00245-17, 2017. Note: Electronic Article. [PubMed: 28807933] [Full Text: https://doi.org/10.1128/MCB.00245-17]
Dominguez, O., Ashhab, Y., Sabater, L., Belloso, E., Caro, P., Pujol-Borrell, R. Cloning of ARE-containing genes by AU-motif-directed display. Genomics 54: 278-286, 1998. [PubMed: 9828130] [Full Text: https://doi.org/10.1006/geno.1998.5548]
Hartz, P. A. Personal Communication. Baltimore, Md. 8/30/2012.
Lu, B., Jiang, Y. J., Zhou, Y., Xu, F. Y., Hatch, G. M., Choy, P. C. Cloning and characterization of murine 1-acyl-sn-glycerol 3-phosphate acyltransferases and their regulation by PPAR-alpha in murine heart. Biochem. J. 385: 469-477, 2005. [PubMed: 15367102] [Full Text: https://doi.org/10.1042/BJ20041348]
Prasad, S. S., Garg, A., Agarwal, A. K. Enzymatic activities of the human AGPAT isoform 3 and isoform 5: localization of AGPAT5 to mitochondria. J. Lipid Res. 52: 451-462, 2011. [PubMed: 21173190] [Full Text: https://doi.org/10.1194/jlr.M007575]