Alternative titles; symbols
HGNC Approved Gene Symbol: PLA2G12A
Cytogenetic location: 4q25 Genomic coordinates (GRCh38): 4:109,709,989-109,730,070 (from NCBI)
Secreted phospholipase A2 (sPLA2) enzymes liberate arachidonic acid from phospholipids for production of eicosanoids and exert a variety of physiologic and pathologic effects. Group XII sPLA2s, such as PLA2G12A, have relatively low specific activity and are structurally and functionally distinct from other sPLA2s (Gelb et al., 2000).
By searching EST databases for homologs of mammalian and venom sPLA2s, followed by RT-PCR of various human cDNA libraries, Gelb et al. (2000) cloned PLA2G12A, which they called GXII. The predicted 189-amino acid protein has a calculated molecular mass of 18.7 kD and contains a 22-residue signal sequence, 14 cysteines, a putative Ca(2+)-binding segment, and an 11-amino acid catalytic domain that includes 3 cys residues and an HD catalytic diad. It lacks consensus N-glycosylation sites. PLA2G12A is highly conserved among species, but its homology with other sPLA2s is limited to the active site region. Northern blot analysis detected a major 1.4-kb transcript that was abundant in heart, skeletal muscle, and kidney, with lower levels in brain, liver, small intestine, lung, and placenta. Little or no expression was present in colon, thymus, spleen, and blood leukocytes. RT-PCR showed a similar pattern and also revealed strong expression in pancreas and weak expression in ovary, testis, and prostate. Gelb et al. (2000) noted that the expression pattern of PLA2G12A was distinct from those of other human sPLA2s. SDS-PAGE of purified PLA2G12A showed an 18-kD protein.
Ho et al. (2001) cloned 2 splice variants of mouse Pla2g12a that they called GXII-1 and GXII-2. Human PLA2G12A is more than 90% homologous to the mouse GXII-1 protein. GXII-1 and, in particular, GXII-2 were selectively expressed in murine T-helper-2 (Th2) cells compared with Th1 cells.
Gelb et al. (2000) found that recombinant PLA2G12A had enzymatic activity that was strictly Ca(2+) dependent and lower than the activities of other sPLA2s. They concluded that PLA2G12A is not a housekeeping gene and likely has physiologic functions distinct from those of other human sPLA2s.
Murakami et al. (2003) found that PLA2G12A had weak enzymatic activity and minimally affected cellular arachidonate release and prostaglandin production compared with PLA2G3 (611651) in transfected HEK293 cells.
Munoz-Sanjuan and Brivanlou (2005) found that Xenopus Pla2g12a acted as a neural inducer in ectoderm by blocking bone morphogenetic protein (BMP; see 112264) signaling. Gain of function in Xenopus embryos led to ectopic neurogenesis and to specification of ectopic olfactory sensory structures, and this activity was conserved in Drosophila and mammalian orthologs. Because of its effect on olfactory neurogenesis, Munoz-Sanjuan and Brivanlou (2005) renamed the PLA2G12A gene Rossy, in homage to the Spanish actress Rossy de Palma, thought to have the 'most famous nose in Spain.' They found that Rossy caused specific inhibition of the BMP pathway in frog and mouse embryonic cells by interfering with the DNA-binding activity of Smad1 (601595)/Smad4 (600993) complexes.
Gelb et al. (2000) determined that the PLA2G12A gene contains at least 4 exons and spans 15 kb.
By sequence analysis, Gelb et al. (2000) mapped the PLA2G12A gene to chromosome 4q25.
Gelb, M. H., Valentin, E., Ghomashchi, F., Lazdunski, M., Lambeau, G. Cloning and recombinant expression of a structurally novel human secreted phospholipase A(2). J. Biol. Chem. 275: 39823-39826, 2000. [PubMed: 11031251] [Full Text: https://doi.org/10.1074/jbc.C000671200]
Ho, I.-C., Arm, J. P., Bingham, C. O., III, Choi, A., Austen, K. F., Glimcher, L. H. A novel group of phospholipase A(2)s preferentially expressed in type 2 helper T cells. J. Biol. Chem. 276: 18321-18326, 2001. [PubMed: 11278438] [Full Text: https://doi.org/10.1074/jbc.M008837200]
Munoz-Sanjuan, I., Brivanlou, A. H. Induction of ectopic olfactory structures and bone morphogenetic protein inhibition by Rossy, a group XII secreted phospholipase A(2). Molec. Cell. Biol. 25: 3608-3619, 2005. [PubMed: 15831466] [Full Text: https://doi.org/10.1128/MCB.25.9.3608-3619.2005]
Murakami, M., Masuda, S., Shimbara, S., Bezzine, S., Lazdunski, M., Lambeau, G., Gelb, M. H., Matsukura, S., Kokubu, F., Adachi, M., Kudo, I. Cellular arachidonate-releasing function of novel classes of secretory phospholipase A(2)s (groups III and XII). J. Biol. Chem. 278: 10657-10667, 2003. [PubMed: 12522102] [Full Text: https://doi.org/10.1074/jbc.M211325200]