PROSITE documentation PDOC51210PLA2c 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.
Last update:May 2006 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
1 | Authors | Nalefski E.A. Sultzman L.A. Martin D.M. Kriz R.W. Towler P.S. Knopf J.L. Clark J.D. |
Title | 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. | |
Source | J. Biol. Chem. 269:18239-18249(1994) | |
PubMed ID | 8027085 |
2 | Authors | Dessen A. Tang J. Schmidt H. Stahl M. Clark J.D. Seehra J. Somers W.S. |
Title | Crystal structure of human cytosolic phospholipase A2 reveals a novel topology and catalytic mechanism. | |
Source | Cell 97:349-360(1999). | |
PubMed ID | 10319815 |
3 | Authors | Song C. Chang X.J. Bean K.M. Proia M.S. Knopf J.L. Kriz R.W. |
Title | Molecular characterization of cytosolic phospholipase A2-beta. | |
Source | J. Biol. Chem. 274:17063-17067(1999). | |
PubMed ID | 10358058 |
4 | Authors | Ohto T. Uozumi N. Hirabayashi T. Shimizu T. |
Title | Identification of novel cytosolic phospholipase A(2)s, murine cPLA(2)delta, epsilon, and zeta, which form a gene cluster with cPLA(2)beta. | |
Source | J. Biol. Chem. 280:24576-24583(2005). | |
PubMed ID | 15866882 | |
DOI | 10.1074/jbc.M413711200 |
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