Phospholipase

Phospholipase A2 (PLA2) enzymes are a family of proteins and to date at least 20 members have been identified in mammals. The family can be classified into four classes on the basis of their nucleotide and amino acid sequence homology. First, there are at present ten secreted phospholipase A2 enzymes (sPLA2-IB, -IIA, -IIC, -IID, -IIE, -IIF, -III, -V, -X, and -XII), which are of low molecular weight (13-18 kDa) with a catalytic histidine in their active site and a requirement for calcium for enzyme activity. Second, there are three characterized human cytosolic PLA2 enzymes (cPLA2-α, -β, and -γ, also known as Group IVA, IVB, and IVC PLA2) that use a catalytic serine in their active site. cPLA2-α and -β contain a C2 calcium binding domain and enzyme activity is calcium-dependent while cPLA2-γ lacks this domain and is thus a calcium-independent PLA2. Recently, a comprehensive homology search against the murine genome and EST databases using conserved sequences of cPLA2 as the query, led to the identification of cPLA2-δ, cPLA2-ε, and cPLA2-ξ (also known as Group IVD, IVE, and IVF PLA2), all of which are calcium-dependent enzymes. Third, three calcium-independent cytosolic PLA2 enzymes (iPLA2-α, -β, and -γ also known as Group VIA-1, VIA-2, and VIB) with an active-site serine, and fourth, four platelet-activating factor acetylhydrolase (PAF-AH) enzymes (Group VIIA, VIIB, VIIIA, and VIIIB) also involve a catalytic serine. Many of the different forms of PLA2 are differentially expressed in a tissue-, species-, and/or genotype-specific manner.