PROSITE documentation PDOC51210 [for PROSITE entry PS51210]

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 <PDOC00380>) 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 β sheet surrounded by 9 α helices (see <PDB:1CJY>). This central α/β core resembles the α/β 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 α 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) α/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) γ/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.