Review The expanding superfamily of phospholipase A2 enzymes: classi¢cation and characterization

The phospholipase A2 (PLA2) superfamily consists of a broad range of enzymes defined by their ability to catalyze the hydrolysis of the middle (sn-2) ester bond of substrate phospholipids. The hydrolysis products of this reaction, free fatty acid and lysophospholipid, have many important downstream roles, and are derived from the activity of a diverse and growing superfamily of PLA2 enzymes. This review updates the classification of the various PLA2’s now described in the literature. Four criteria have been employed to classify these proteins into one of the 11 Groups (I^XI) of PLA2’s. First, the enzyme must catalyze the hydrolysis of the sn-2 ester bond of a natural phospholipid substrate, such as long fatty acid chain phospholipids, platelet activating factor, or short fatty acid chain oxidized phospholipids. Second, the complete amino acid sequence of the mature protein must be known. Third, each PLA2 Group should include all of those enzymes that have readily identifiable sequence homology. If more than one homologous PLA2 gene exists within a species, then each paralog should be assigned a Subgroup letter, as in the case of Groups IVA, IVB, and IVC PLA2. Homologs from different species should be classified within the same Subgroup wherever such assignments are possible as is the case with zebra fish and human Group IVA PLA2 orthologs. The current classification scheme does allow for historical exceptions of the highly homologous Groups I, II, V, and X PLA2’s. Fourth, catalytically active splice variants of the same gene are classified as the same Group and Subgroup, but distinguished using Arabic numbers, such as for Group VIA-1 PLA2 and VIA-2 PLA2’s. These four criteria have led to the expansion or realignment of Groups VI, VII and VIII, as well as the addition of Group X