Alternative titles; symbols
HGNC Approved Gene Symbol: PLA2G2D
Cytogenetic location: 1p36.12 Genomic coordinates (GRCh38) : 1:20,111,939-20,119,536 (from NCBI)
Phospholipase A2 (PLA2) family members (e.g., PLA2G2A; 172411) are lipolytic enzymes that hydrolyze the sn-2 fatty acid ester bond of glycerophospholipids to produce free fatty acid and lysophospholipids. PLA2s are involved in phospholipid digestion, remodeling of cell membranes, and host defense, as well as pathophysiologic processes involving the production prostaglandins, leukotrienes, thromboxanes, and platelet-activating factor.
By searching an EST database using the catalytically essential residues of secretory PLA2s as the probe, followed by PCR of mouse and human spleen cDNA, Ishizaki et al. (1999) obtained cDNAs encoding mouse and human PLA2G2D. Sequence analysis predicted that the 145-amino acid human secretory protein, 48% identical PLA2G2A, contains a 20-residue signal peptide, a potential N-linked glycosylation site, 14 cys residues, and conserved his48 and asp49 sites. Analysis of enzymatic activity detected most activity in culture supernatant and determined that PLA2G2D preferentially hydrolyzes phosphatidylglycerol and phosphatidylethanolamine, followed by phosphatidylcholine, but does not hydrolyze phosphatidylserine or phosphatidic acid. Northern blot analysis revealed variable expression of 2.0- and 1.0-kb transcripts, with highest expression in pancreas and spleen. In a rat model, expression in thymus increased dramatically after lipopolysaccharide injection.
By subtractive cDNA cloning using spleens from wildtype and tumor necrosis factor (Tnf; 191160)/lymphotoxin-alpha (Lta; 153440) double-knockout mice, followed by probing a spleen cDNA library, Shakhov et al. (2000) isolated a cDNA encoding mouse Pla2g2d, which they designated Splash (secretory-type PLA, stroma-associated homolog). Splash was expressed 6-fold less in mutant than wildtype mice. By screening a human cDNA library, they isolated cDNAs encoding human PLA2G2D. Shakhov et al. (2000) noted that the human and mouse protein sequences are 73% identical and 81% homologous. Northern blot analysis detected mouse Pla2g2d expression in adult but not embryonic spleen.
By radiation hybrid mapping, Ishizaki et al. (1999) mapped the PLA2G2D gene to 1p36.12. Also using radiation hybrid analysis, Shakhov et al. (2000) mapped the PLA2G2D gene to 1p36.1-p35, near the PLA2G2A gene and a region known for frequent loss of heterozygosity in human tumors. Shakhov et al. (2000) mapped the mouse gene to chromosome 4.
Ishizaki, J., Suzuki, N., Higashino, K., Yokota, Y., Ono, T., Kawamoto, K., Fujii, N., Arita, H., Hanasaki, K. Cloning and characterization of novel mouse and human secretory phospholipase A(2)s. J. Biol. Chem. 274: 24973-24979, 1999. [PubMed: 10455175] [Full Text: https://doi.org/10.1074/jbc.274.35.24973]
Shakhov, A. N., Rubtsov, A. V., Lyakhov, I. G., Tumanov, A. V., Nedospasov, S. A. SPLASH (PLA(2)IID), a novel member of phospholipase A2 family, is associated with lymphotoxin-deficiency. Genes Immun. 1: 191-199, 2000. [PubMed: 11196711] [Full Text: https://doi.org/10.1038/sj.gene.6363659]