Group 10 secretory phospholipase A2
Also known as: PLA2G10
Function
Secretory calcium-dependent phospholipase A2 that primarily targets extracellular phospholipids. Hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids with preference for phosphatidylcholines and phosphatidylglycerols over phosphatidylethanolamines. Preferentially releases sn-2 omega-6 and omega-3 polyunsaturated fatty acyl (PUFA) chains over saturated fatty acyls. Contributes to phospholipid remodeling of very low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles. Hydrolyzes LDL phospholipids releasing unsaturated fatty acids that regulate macrophage differentiation toward foam cells. Efficiently hydrolyzes and inactivates platelet activating factor (PAF), a potent lipid mediator present in oxidized LDL. May act in an autocrine and paracrine manner. Secreted by lung epithelium, targets membrane phospholipids of infiltrating eosinophils, releasing arachidonate and boosting eicosanoid and cysteinyl leukotriene synthesis involved in airway inflammatory response (By similarity). Secreted by gut epithelium, hydrolyzes dietary and biliary phosphatidylcholines in the gastrointestinal lumen (By similarity). Plays a stem cell regulator role in colon epithelium. Within intracellular compartment, mediates Paneth-like cell differentiation and its stem cell supporting functions by inhibiting the Wnt signaling pathway in intestinal stem cell (ISC). Secreted in the intestinal lumen upon inflammation, acts in an autocrine way and promotes prostaglandin E2 synthesis that stimulates Wnt signaling pathway in ISCs and tissue regeneration (By similarity). May participate in hair follicle morphogenesis by regulating phosphatidylethanolamines metabolism at the outermost epithelial layer and facilitating melanin synthesis (By similarity). By releasing lysophosphatidylcholines (LPCs) at sperm acrosome, controls sperm cell capacitation, acrosome reaction and overall fertility (By similarity). May promote neurite outgrowth in neuron fibers involved in nociception (By similarity). Contributes to lipid remodeling of cellular membranes and generation of lipid mediators involved in pathogen clearance. Cleaves sn-2 fatty acyl chains of phosphatidylglycerols and phosphatidylethanolamines, which are major components of membrane phospholipids in bacteria. Displays bactericidal activity against Gram-positive bacteria by directly hydrolyzing phospholipids of the bacterial membrane. In pulmonary epithelium, may contribute to host defense response against adenoviral infection. Prevents adenovirus entry into host cells by hydrolyzing host cell plasma membrane, releasing C16:0 LPCs that inhibit virus-mediated membrane fusion and viral infection. Likely prevents adenoviral entry into the endosomes of host cells. May play a role in maturation and activation of innate immune cells including macrophages, group 2 innate lymphoid cells and mast cells (By similarity).
Classification
- Family (Pfam)
- PF00068 Phospholip_A2_1
- InterPro
- PLA2, PLA2-like_dom, PLA2_Asp_AS, PLA2_histidine, PLipase_A2_dom_sf
- Functional cluster
- Secreted Growth Factors & Cytokines
Experimental structures · PDB · 7
- 1LE6 X-ray 1.97A
- 1LE7 X-ray 2.09A
- 4UY1 X-ray 2.20A
- 5G3M X-ray 1.85A
- 5OW8 X-ray 1.90A
- 5OWC X-ray 1.75A
- 6G5J X-ray 1.85A
A predicted model is available from AlphaFold.
Gene Ontology · 37
- GO:0001669 acrosomal vesicle
- GO:0005576 extracellular region
- GO:0005615 extracellular space
- GO:0005764 lysosome
- GO:0003847 1-alkyl-2-acetylglycerophosphocholine esterase activity
- GO:0004623 A2-type glycerophospholipase activity
- GO:0005509 calcium ion binding
- GO:0004620 glycerophospholipase activity
- GO:0005543 phospholipid binding
- GO:0019369 arachidonate metabolic process
- GO:0050482 arachidonate secretion
- GO:0007411 axon guidance
- GO:0042632 cholesterol homeostasis
- GO:0051607 defense response to virus
- GO:0031069 hair follicle morphogenesis
- GO:0036335 intestinal stem cell homeostasis
- GO:0034374 low-density lipoprotein particle remodeling
- GO:0051977 lysophospholipid transport
- GO:0090370 negative regulation of cholesterol efflux
- GO:0000122 negative regulation of transcription by RNA polymerase II
- GO:0141193 nuclear receptor-mediated signaling pathway
- GO:0046473 phosphatidic acid metabolic process
- GO:0034638 phosphatidylcholine catabolic process
- GO:0046470 phosphatidylcholine metabolic process
- GO:0046337 phosphatidylethanolamine metabolic process
- GO:0046471 phosphatidylglycerol metabolic process
- GO:0006658 phosphatidylserine metabolic process
- GO:0062234 platelet activating factor catabolic process
- GO:2000344 positive regulation of acrosome reaction
- GO:0090238 positive regulation of arachidonate secretion
- GO:0010884 positive regulation of lipid storage
- GO:0010744 positive regulation of macrophage derived foam cell differentiation
- GO:0032308 positive regulation of prostaglandin secretion
- GO:0051247 positive regulation of protein metabolic process
- GO:0001516 prostaglandin biosynthetic process
- GO:0043030 regulation of macrophage activation
- GO:0023019 signal transduction involved in regulation of gene expression
Drugs targeting this protein · 1
- VARESPLADIB METHYL inhibitor
Related proteins · sequence + function similarity
- Group 10 secretory phospholipase A2 0.96
- Group 10 secretory phospholipase A2 0.94
- Group IID secretory phospholipase A2 0.86
- Group IID secretory phospholipase A2 0.84
- Group IIE secretory phospholipase A2 0.84
- Acidic phospholipase A2 0.83
- Group IIE secretory phospholipase A2 0.82
- Phospholipase A2 group V 0.82
- Acidic phospholipase A2 Cvv-E6a 0.82
- Acidic phospholipase A2 Cvv-E6h 0.82
- Basic phospholipase A2 DAV-N6 0.82
- Acidic phospholipase A2 beta 0.81
Co-cited proteins · studied together in the literature
- Group 10 secretory phospholipase A2 3 shared papers
- Phospholipase A2 group V 1 shared papers
- Phospholipase A2 group V 1 shared papers
- Phospholipase A2, membrane associated 1 shared papers
- Group IID secretory phospholipase A2 1 shared papers
- Phospholipase A2, membrane associated 1 shared papers
Literature · 10 cited papers
- Physiological roles of group X-secreted phospholipase A2 in reproduction, gastrointestinal phospholipid digestion, and neuronal function. J. Biol. Chem. · 2011
- The proinflammatory mediator Platelet Activating Factor is an effective substrate for human group X secreted phospholipase A2. Biochim. Biophys. Acta · 2006
- Group V and X secretory phospholipase A2 prevents adenoviral infection in mammalian cells. Biochem. J. · 2006
- The sequence and analysis of duplication-rich human chromosome 16. Nature · 2004
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- Interfacial kinetic and binding properties of the complete set of human and mouse groups I, II, V, X, and XII secreted phospholipases A2. J. Biol. Chem. · 2002
- Crystal structure of human group X secreted phospholipase A2. Electrostatically neutral interfacial surface targets zwitterionic membranes. J. Biol. Chem. · 2002
- Potent modification of low density lipoprotein by group X secretory phospholipase A2 is linked to macrophage foam cell formation. J. Biol. Chem. · 2002
- Bactericidal properties of human and murine groups I, II, V, X, and XII secreted phospholipases A(2). J. Biol. Chem. · 2002
- Cloning, chromosomal mapping, and expression of a novel human secretory phospholipase A2. J. Biol. Chem. · 1997