From UniProt: PLA2G4A mutations resulting in phospholipase A2 deficiency have been found in a patient affected by recurrent episodes of multiple complicated ulcers of the small intestine, not due to cyclooxygenase inhibitors use. Disease features also include platelet dysfunction, and globally decreased eicosanoid synthesis (PubMed:18451993).

     From NCBI Gene: This gene encodes a member of the cytosolic phospholipase A2 group IV family. The enzyme catalyzes the hydrolysis of membrane phospholipids to release arachidonic acid which is subsequently metabolized into eicosanoids. Eicosanoids, including prostaglandins and leukotrienes, are lipid-based cellular hormones that regulate hemodynamics, inflammatory responses, and other intracellular pathways. The hydrolysis reaction also produces lysophospholipids that are converted into platelet-activating factor. The enzyme is activated by increased intracellular Ca(2+) levels and phosphorylation, resulting in its translocation from the cytosol and nucleus to perinuclear membrane vesicles. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015] From UniProt: Selectively hydrolyzes arachidonyl phospholipids in the sn-2 position releasing arachidonic acid. Together with its lysophospholipid activity, it is implicated in the initiation of the inflammatory response.

The following transcription factors affect gene expression:

• NF-kappaB
• PPAR-gamma1
• PPAR-gamma2
• GR
• GR-alpha
• GR-beta
• AP-1
• c-Jun
• NF-kappaB1
• Sp1

Tissue specificity:

Expressed in various tissues such as macrophages, platelets, neutrophils, fibroblasts and lung endothelium.

Enzyme Regulation:

Stimulated by agonists such as ATP, EGF, thrombin and bradykinin as well as by cytosolic Ca(2+).

Molecular Function:

• Calcium-Dependent Phospholipase A2 Activity
• Calcium-Dependent Phospholipid Binding
• Calcium Ion Binding
• Lysophospholipase Activity
• Phosphatidylcholine 1-Acylhydrolase Activity
• Phospholipase A2 Activity

Biological Processes:

• Arachidonic Acid Metabolic Process
• Arachidonic Acid Secretion
• Cardiolipin Acyl-Chain Remodeling
• Cellular Response To Antibiotic
• Icosanoid Biosynthetic Process
• Icosanoid Metabolic Process
• Phosphatidic Acid Biosynthetic Process
• Phosphatidylcholine Acyl-Chain Remodeling
• Phosphatidylethanolamine Acyl-Chain Remodeling
• Phosphatidylglycerol Acyl-Chain Remodeling
• Phosphatidylinositol Acyl-Chain Remodeling
• Phosphatidylserine Acyl-Chain Remodeling
• Phospholipid Catabolic Process
• Phospholipid Metabolic Process
• Platelet Activating Factor Biosynthetic Process
• Regulation Of Cell Proliferation
• Aging
• Decidualization
• Luteolysis
• Ovulation From Ovarian Follicle
• Positive Regulation Of Apoptotic Process
• Positive Regulation Of Bone Mineralization
• Positive Regulation Of Cell Proliferation
• Positive Regulation Of Fever Generation
• Positive Regulation Of Prostaglandin Biosynthetic Process
• Positive Regulation Of Vesicle Fusion
• Response To Calcium Ion
• Response To Glucocorticoid
• Response To Heat
• Response To Hydrogen Peroxide
• Response To Lipopolysaccharide
• Response To Lithium Ion
• Response To Methylmercury
• Response To Organonitrogen Compound
• Response To Vitamin D
• Surfactant Homeostasis

Drug Bank:

• Fluticasone Propionate
• Carbachol
• Carbenicillin
• Epirubicin
• Niflumic Acid
• Orlistat
• Quinacrine
• Streptokinase
• Suramin
• Aldesleukin
• Fluocinolone Acetonide