Alternative titles; symbolsPHOSPHOLIPASE A2, SECRETED, GROUP IIIGIII-SPLA2SPLA2-IIIHGNC Approved Gene Symbol: PLA2G3Cytogenetic location: 22q12.2 Genomic coo...
Alternative titles; symbols
HGNC Approved Gene Symbol: PLA2G3
Cytogenetic location: 22q12.2 Genomic coordinates (GRCh38): 22:31,134,806-31,140,507 (from NCBI)
PLA2G3 belongs to the family of secreted phospholipase A2 (sPLA2; EC 188.8.131.52) proteins. These Ca(2+)-dependent lipolytic enzymes have a conserved Ca(2+)-binding loop and a his-asp dyad in the catalytic site (Murakami et al., 2003).
▼ Cloning and Expression
By searching databases for homologs of venom sPLA2s, followed by RT-PCR and RACE, Valentin et al. (2000) obtained a fetal lung cDNA encoding PLA2G3. The predicted 509-amino acid protein contains a 19-amino acid signal peptide, 5 putative N-glycosylation sites, a central 141-amino acid sPLA2 domain, and basic N- and C-terminal regions. The sPLA2 domain contains 10 conserved cysteines and key residues of the Ca(2+) loop and catalytic site, and the N and C termini contain 4 and 8 cysteines, respectively. Northern blot analysis revealed abundant expression of a 4.4-kb transcript in kidney, heart, liver, and skeletal muscle, with lower levels in placenta and blood leukocytes. Little or no expression was present in brain, colon, thymus, spleen, small intestine, and lung.
Using immunoblot analysis, Murakami et al. (2003) detected a 56-kD PLA2G3 protein in transfected HEK293 cells. Confocal microscopy demonstrated cytoplasmic and spindle edge expression of PLA2G3.
▼ Gene Function
Valentin et al. (2000) expressed human PLA2G3 in monkey kidney cells and found that it was secreted. PLA2G3 exhibited Ca2(+)-dependent enzymatic activity, with a preference for phosphatidylglycerol over phosphatidylcholine.
Murakami et al. (2003) found that PLA2G3 promoted spontaneous arachidonate (AA) release and prostaglandin (PG) production that was augmented by IL1B (147720) in transfected HEK293 cells. PLA2G3 enzymatic activity was mediated by its central sPLA2 domain, but not by its N- or C-terminal regions, which were required for heparanoid-dependent action on cells to augment AA release, cyclooxygenase-2 (PTGS2; 600262) induction, and PG production.
Murakami et al. (2005) found that the N- and C-terminal domains of PLA2G3 were proteolytically removed in several human cell types that intrinsically expressed the enzyme. Immunohistochemical analysis showed that PLA2G3 was preferentially expressed in microvascular endothelium in human tissues with inflammation, ischemic injury, and cancer. Stimulation of microvascular endothelial cells with proinflammatory cytokines induced PLA2G3 expression. PLA2G3 expression in colorectal cancer cells led to enhanced PGE2 production and cell proliferation. Murakami et al. (2005) concluded that PLA2G3 undergoes unique cell type-specific processing and N-glycosylation and may play a role in cancer development.
In a functional genomic screen using RNA interference, Kim et al. (2010) identified PLA2G3 as a gene involved in ciliogenesis control. Depletion of PLA2G3 facilitated cilium extension and induced ciliogenesis independently of serum starvation, indicating that PLA2G3 is a negative ciliogenesis regulator.
▼ Gene Structure
Valentin et al. (2000) determined that the PLA2G3 gene contains 7 exons and spans 7 kb.
By database analysis, Valentin et al. (2000) mapped the PLA2G3 gene to chromosome 22q.