{PDOC51210} {PS51210; PLA2C} {BEGIN} ************************ * PLA2c domain profile * ************************ The PLA2c domain is the catalytic lipase domain in cytosolic phospholipase A2 (cPLA2) (EC 3.1.1.4) and lysophospholipase or phospholipase B (PLB) (EC 3.1.1.5) of vertebrates and fungi. It catalyzes the carboxylic ester hydrolysis of glycerophospholipids or lysophospholipids. The mammalian cPLA2 group IVA enzymes cleave intracellular phospholipid membranes to produce lipid mediators, which also play a role in inflammatory diseases such as asthma and arthritis. This enzyme contains a N-terminal calcium-binding C2 domain (see ) that presents the catalytic domain to the membrane [1]. Fungal secreted lysophospholipase/PLB can possess three different enzymatic activities, the hydrolase activity of phospholipase, lysophospholipase and a lysophospholipase transacylase activity. The 3D structure of the PLA2c domain forms a central core of a 10-stranded mixed beta sheet surrounded by 9 alpha helices (see ). This central alpha/beta core resembles the alpha/beta hydrolase fold, but an additional 180-residue patch between strands 9 and 10 forms a catalytic domain 'cap' [2]. Ser 228 and Asp 549 of human cPLA2 alpha form the potential catalytic dyad. Parts of the cap-region are poorly conserved and are distinct among isoforms [3,4]. Some proteins known to contain a PLA2c domain: - Mammalian cytosolic phospholipase A2 (cPLA2) alpha/group IVA, which releases arachidonic acid from the sn-2 position of membrane glycerophospholipids and initiates the biosynthesis of prostaglandins, leukotrienes and platelet-activating factor. - Mammalian cytosolic phospholipase A2 (cPLA2) gamma/group IVC, which is implicated in the remodeling of membrane phospholipids. - Fungal lysophospholipases/PLB, which are considered to be important for virulence of pathogenic fungi. - Yeast sporulation-specific protein 1 (SPO1), which is required for meiosis. The profile we developed covers the entire PLA2c domain. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: May 2006 / First entry. [ 1] Nalefski E.A., Sultzman L.A., Martin D.M., Kriz R.W., Towler P.S., Knopf J.L., Clark J.D. "Delineation of two functionally distinct domains of cytosolic phospholipase A2, a regulatory Ca(2+)-dependent lipid-binding domain and a Ca(2+)-independent catalytic domain." J. Biol. Chem. 269:18239-18249(1994) PubMed=8027085 [ 2] Dessen A., Tang J., Schmidt H., Stahl M., Clark J.D., Seehra J., Somers W.S. "Crystal structure of human cytosolic phospholipase A2 reveals a novel topology and catalytic mechanism." Cell 97:349-360(1999). PubMed=10319815 [ 3] Song C., Chang X.J., Bean K.M., Proia M.S., Knopf J.L., Kriz R.W. "Molecular characterization of cytosolic phospholipase A2-beta." J. Biol. Chem. 274:17063-17067(1999). PubMed=10358058 [ 4] Ohto T., Uozumi N., Hirabayashi T., Shimizu T. "Identification of novel cytosolic phospholipase A(2)s, murine cPLA(2)delta, epsilon, and zeta, which form a gene cluster with cPLA(2)beta." J. Biol. Chem. 280:24576-24583(2005). PubMed=15866882; DOI=10.1074/jbc.M413711200 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}