BioPAX pathway converted from "PE is hydrolyzed to 1-acyl LPE by PLA2[16]" in the Reactome database.
LEFT-TO-RIGHT
3.1.1.4
PE is hydrolyzed to 1-acyl LPE by PLA2[16]
At the plasma membrane, phosphatidylethanolamine (PE) is hydrolyzed, removing one of its acyl groups, to 1-acyl phosphatidylethanolamine (LPE) by secretory phospholipase A2 proteins (Singer et al. 2002, Ishizaki et al. 1999). These include: Group IB (PLA2G1B) (Grataroli et al. 1982); Group IIA (PLA2G2A) (Seilhamer et al. 1989); Group IID (PLA2G2D) (Ishizaki et al. 1999); Group IIE (PLA2G2E) (Suzuki et al. 2000); Group IIF (PLA2G2F) (Valentin et al. 2000); Group III (PLA2G3) (Murakami et al. 2003, Murakami et al. 2005); Calcium-dependent Group V (PLA2G5) (Chen et al. 1994); Group X (PLA2G10) (Cupillard et al. 1997, Pan et al. 2002); and Group XIIA (PLA2G12A) (Gelb et al. 2000, Murakami et al. 2003).
作者:威廉姆斯,MG, 2011-09-14
Edited: Williams, MG, 2011-08-12
PE
phosphatidylethanolamine
Reactome DB_ID: 1602375
plasma membrane
GENE ONTOLOGY
GO:0005886
phosphatidylethanolamine [ChEBI:16038]
phosphatidylethanolamine
1,2-diacyl-sn-glycero-3-phosphoethanolamine
(3-Phosphatidyl)-ethanolamine
phosphatidylethanolamines
1-Acyl-2-acyl-sn-glycero-3-phosphoethanolamine
O-(1-beta-Acyl-2-acyl-sn-glycero-3-phospho)ethanolamine
Cephalin
(3-Phosphatidyl)ethanolamine
ChEBI
CHEBI:16038
Reactome Database ID Release 77
1602375
数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=1602375
Reactome
R-ALL-1602375
4
Reactome稳定identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-1602375.4
Reactome
//www.joaskin.com
H2O
water
Reactome DB_ID: 109276
extracellular region
GENE ONTOLOGY
GO:0005576
water [ChEBI:15377]
water
ChEBI
CHEBI:15377
Reactome Database ID Release 77
109276
数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=109276
Reactome
R-ALL-109276
4
Reactome稳定identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-109276.4
COMPOUND
C00001
additional information
MI
MI:0361
LCFA(-)
long-chain fatty acid anion
Reactome DB_ID: 1602366
long-chain fatty acid anion [ChEBI:57560]
long-chain fatty acid anion
ChEBI
CHEBI:57560
Reactome Database ID Release 77
1602366
数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=1602366
Reactome
R-ALL-1602366
4
Reactome稳定identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-1602366.4
COMPOUND
C00060
1-acyl LPE
1-acyl lysophosphatidylethanolamine
1-acyl-sn-glycero-3-phosphoethanolamine
L-2-Lysophosphatidylethanolamine
Reactome DB_ID: 1602372
1-acyl-sn-glycero-3-phosphoethanolamine [ChEBI:29017]
1-acyl-sn-glycero-3-phosphoethanolamine
ChEBI
CHEBI:29017
Reactome Database ID Release 77
1602372
数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=1602372
Reactome
R-ALL-1602372
3
Reactome稳定identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-1602372.3
COMPOUND
C04438
ACTIVATION
Converted from EntitySet in Reactome
PLA2(16)
Reactome DB_ID: 1602354
PLA2G1B:Ca2+
Reactome DB_ID: 1602365
PLA2G1B
Reactome DB_ID: 1500655
UniProt:P04054 PLA2G1B
PLA2G1B
PLA2
PLA2A
PPLA2
功能分泌calcium-dependent磷脂酶A2 that primarily targets dietary phospholipids in the intestinal tract (PubMed:1420353, PubMed:10681567, PubMed:17603006). Hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity) with preference for phosphatidylethanolamines and phosphatidylglycerols over phosphatidylcholines (PubMed:1420353, PubMed:10681567, PubMed:17603006). May play a role in the biosynthesis of N-acyl ethanolamines that regulate energy metabolism and inflammation in the intestinal tract. Hydrolyzes N-acyl phosphatidylethanolamines to N-acyl lysophosphatidylethanolamines, which are further cleaved by a lysophospholipase D to release N-acyl ethanolamines (By similarity). May act in an autocrine and paracrine manner (PubMed:7721806, PubMed:25335547). Upon binding to the PLA2R1 receptor can regulate podocyte survival and glomerular homeostasis (PubMed:25335547). Has anti-helminth activity in a process regulated by gut microbiota. Upon helminth infection of intestinal epithelia, directly affects phosphatidylethanolamine contents in the membrane of helminth larvae, likely controlling an array of phospholipid-mediated cellular processes such as membrane fusion and cell division while providing for better immune recognition, ultimately reducing larvae integrity and infectivity (By similarity).ACTIVITY REGULATION Regulated by bile acid salts. Up-regulated by cholate and down-regulated by taurochenodeoxycholate. Cholate-activated rate of hydrolysis is lowered by hypolipidemic drug ezetimibe.SUBUNIT The inactive pro-form is a homotrimer (PubMed:19297324). When anchored into the cell membrane, the inactive homotrimer is likely cleaved either by trypsin or by itself, producing an active trimer. The resulting conformational changes are thought to open up a center hole forming a channel for substrate entry (PubMed:19297324). Interacts with PLA2R1; this interaction mediates intracellular signaling as well as clearance of extracellular PLA2G1B via endocytotic pathway (PubMed:7721806).TISSUE SPECIFICITY Selectively expressed in pancreas, lung, liver and kidney. Also detected at lower levels in ovary and testis.PTM Activated by trypsin cleavage in the duodenum. Can also be activated by thrombin or autocatalytically.SIMILARITY Belongs to the phospholipase A2 family.
Homo sapiens
NCBI Taxonomy
9606
UniProt
P04054
23
EQUAL
148
EQUAL
Reactome Database ID Release 77
1500655
数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=1500655
Reactome
R-HSA-1500655
1
Reactome稳定identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1500655.1
1
Ca2+
Calcium
calcium(2+)
Reactome DB_ID: 74112
calcium(2+) [ChEBI:29108]
calcium(2+)
ChEBI
CHEBI:29108
Reactome Database ID Release 77
74112
数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=74112
Reactome
R-ALL-74112
4
Reactome稳定identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-74112.4
COMPOUND
C00076
1
Reactome Database ID Release 77
1602365
数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=1602365
Reactome
R-HSA-1602365
1
Reactome稳定identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1602365.1
PLA2G2A:Ca2+
Reactome DB_ID: 1602363
PLA2G2A
Group IIA phospholipase A2
Non-pancreatic secretory phospholipase A2
Reactome DB_ID: 1602364
UniProt:P14555 PLA2G2A
PLA2G2A
PLA2B
PLA2L
RASF-A
功能分泌calcium-dependent磷脂酶A2 that primarily targets extracellular phospholipids with implications in host antimicrobial defense, inflammatory response and tissue regeneration (PubMed:10455175, PubMed:10681567, PubMed:2925633). Hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity) with preference for phosphatidylethanolamines and phosphatidylglycerols over phosphatidylcholines (PubMed:10455175, PubMed:10681567). Contributes to lipid remodeling of cellular membranes and generation of lipid mediators involved in pathogen clearance. Displays bactericidal activity against Gram-positive bacteria by directly hydrolyzing phospholipids of the bacterial membrane (PubMed:11694541, PubMed:10358193). Upon sterile inflammation, targets membrane phospholipids of extracellular mitochondria released from activated platelets, generating free unsaturated fatty acids such as arachidonate that is used by neighboring leukocytes to synthesize inflammatory eicosanoids such as leukotrienes. Simultaneously, by compromising mitochondrial membrane integrity, promotes the release in circulation of potent damage-associated molecular pattern molecules that activate the innate immune response (PubMed:25082876). Plays a stem cell regulator role in the intestinal crypt. Within intracellular compartment mediates Paneth cell differentiation and its stem cell supporting functions by inhibiting Wnt signaling pathway in intestinal stem cell (ICS). Secreted in the intestinal lumen upon inflammation, acts in an autocrine way and promotes prostaglandin E2 synthesis that stimulates Wnt signaling pathway in ICS cells and tissue regeneration (By similarity). May play a role in the biosynthesis of N-acyl ethanolamines that regulate energy metabolism and inflammation. Hydrolyzes N-acyl phosphatidylethanolamines to N-acyl lysophosphatidylethanolamines, which are further cleaved by a lysophospholipase D to release N-acyl ethanolamines (PubMed:14998370). Independent of its catalytic activity, acts as a ligand for integrins (PubMed:18635536, PubMed:25398877). Binds to and activates integrins ITGAV:ITGB3, ITGA4:ITGB1 and ITGA5:ITGB1 (PubMed:18635536, PubMed:25398877). Binds to a site (site 2) which is distinct from the classical ligand-binding site (site 1) and induces integrin conformational changes and enhanced ligand binding to site 1 (PubMed:25398877). Induces cell proliferation in an integrin-dependent manner (PubMed:18635536).TISSUE SPECIFICITY Expressed in various tissues including heart, kidney, liver, lung, pancreas, placenta, skeletal muscle, prostate, ovary, colon and small intestine. Not detected in lymphoid organs and brain (PubMed:10455175, PubMed:10681567). Expressed in platelets (at protein level) (PubMed:25082876).MISCELLANEOUS Group II phospholipase A2 is found in many cells and also extracellularly. The membrane-bound and secreted forms are identical and are encoded by a single gene.MISCELLANEOUS Interaction with integrin ITGA4:ITGB3 is inhibited by a number of synthetic peptides including R-Ala-Trp-Asp-Ile and R-Gly-Arg-Gly-Asp-Asp-Asp which bind to PLA2G2A and disrupt its integrin-binding activity.SIMILARITY Belongs to the phospholipase A2 family.
UniProt
P14555
21
EQUAL
144
EQUAL
Reactome Database ID Release 77
1602364
数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=1602364
Reactome
R-HSA-1602364
1
Reactome稳定identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1602364.1
1
1
Reactome Database ID Release 77
1602363
数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=1602363
Reactome
R-HSA-1602363
1
Reactome稳定identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1602363.1
PLA2G2D:Ca2+
Reactome DB_ID: 1602360
SPLASH
PLA2G2D
Group IID secretory phospholipase A2
sPLA2-IID
Reactome DB_ID: 1498804
UniProt:Q9UNK4 PLA2G2D
PLA2G2D
SPLASH
功能分泌calcium-dependent磷脂酶A2 that primarily targets extracellular lipids, exerting anti-inflammatory and immunosuppressive functions (PubMed:10455175, PubMed:10681567). Hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity) with preference for phosphatidylethanolamines and phosphatidylglycerols over phosphatidylcholines (PubMed:10455175). In draining lymph nodes, selectively hydrolyzes diacyl and alkenyl forms of phosphatidylethanolamines, releasing omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoate and docosahexaenoate that are precursors of the anti-inflammatory lipid mediators, resolvins (By similarity). During the resolution phase of acute inflammation drives docosahexaenoate-derived resolvin D1 synthesis, which suppresses dendritic cell activation and T-helper 1 immune response (By similarity). May act in an autocrine and paracrine manner (By similarity). Via a mechanism independent of its catalytic activity, promotes differentiation of regulatory T cells (Tregs) and participates in the maintenance of immune tolerance (By similarity). May contribute to lipid remodeling of cellular membranes and generation of lipid mediators involved in pathogen clearance. Displays bactericidal activity against Gram-positive bacteria by directly hydrolyzing phospholipids of the bacterial membrane (By similarity).TISSUE SPECIFICITY Highly expressed in pancreas and spleen and less abundantly in colon, thymus, placenta, small intestine, and prostate.SIMILARITY Belongs to the phospholipase A2 family.
UniProt
Q9UNK4
21
EQUAL
145
EQUAL
Reactome Database ID Release 77
1498804
数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=1498804
Reactome
R-HSA-1498804
1
Reactome稳定identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1498804.1
1
1
Reactome Database ID Release 77
1602360
数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=1602360
Reactome
R-HSA-1602360
1
Reactome稳定identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1602360.1
PLA2G2E:Ca2+
Reactome DB_ID: 1602386
1
PLA2G2E
Group IIE secretory phospholipase A2
sPLA2-IIE
Reactome DB_ID: 1498800
UniProt:Q9NZK7 PLA2G2E
PLA2G2E
功能分泌calcium-dependent磷脂酶A2 that primarily targets extracellular phospholipids (PubMed:10681567, PubMed:11922621, PubMed:28883454). Hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity), releasing various unsaturated fatty acids including oleoate, linoleoate, arachidonate, docosahexaenoate and lysophosphatidylethanolamines in preference to lysophosphatidylcholines (PubMed:10681567, PubMed:28883454). In response to high-fat diet, hydrolyzes minor lipoprotein phospholipids including phosphatidylserines, phosphatidylinositols and phosphatidylglycerols, altering lipoprotein composition and fat storage in adipose tissue and liver (By similarity). May act in an autocrine and paracrine manner (PubMed:11922621). 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 (PubMed:11922621). Acts as a hair follicle phospholipase A2. Selectively releases lysophosphatidylethanolamines (LPE) and various unsaturated fatty acids in skin to regulate hair follicle homeostasis (By similarity). May regulate the inflammatory response by releasing arachidonate, a precursor of prostaglandins and leukotrienes (PubMed:11922621). Upon allergen exposure, may participate in allergic inflammatory response by enhancing leukotriene C4 synthesis and degranulation in mast cells (By similarity).TISSUE SPECIFICITY Restricted to the brain, heart, lung, and placenta.INDUCTION Up-regulated by inflammatory cytokine IL1B.SIMILARITY Belongs to the phospholipase A2 family.
UniProt
Q9NZK7
20
EQUAL
142
EQUAL
Reactome Database ID Release 77
1498800
数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=1498800
Reactome
R-HSA-1498800
1
Reactome稳定identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1498800.1
1
Reactome Database ID Release 77
1602386
数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=1602386
Reactome
R-HSA-1602386
1
Reactome稳定identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1602386.1
PLA2G2F:Ca2+
Reactome DB_ID: 1602383
PLA2G2F
Group IIF secretory phospholipase A2
sPLA2-IIF
Reactome DB_ID: 1602357
UniProt:Q9BZM2 PLA2G2F
PLA2G2F
功能分泌calcium-dependent磷脂酶A2 that primarily targets extracellular phospholipids. Hydrolyzes the ester bond of the fatty acyl group attached at the sn-2 position of phospholipids (phospholipase A2 activity), the catalytic efficiency decreasing in the following order: phosphatidylglycerols > phosphatidylethanolamines > phosphatidylcholines > phosphatidylserines (PubMed:11112443). May play a role in lipid mediator production in inflammatory conditions, by providing arachidonic acid to downstream cyclooxygenases and lipoxygenases (By similarity).TISSUE SPECIFICITY Expressed at high levels in placenta, testis, thymus and at lower levels in heart, kidney, liver and prostate (PubMed:11112443). Highly expressed in rheumatoid arthritic tissues, including synovial lining cells in the intima, capillary endothelial cells and plasma cells (PubMed:11877435).SIMILARITY Belongs to the phospholipase A2 family.
UniProt
Q9BZM2
21
EQUAL
168
EQUAL
Reactome Database ID Release 77
1602357
数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=1602357
Reactome
R-HSA-1602357
1
Reactome稳定identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1602357.1
1
1
Reactome Database ID Release 77
1602383
数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=1602383
Reactome
R-HSA-1602383
1
Reactome稳定identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1602383.1
PLA2G3:Ca2+
Reactome DB_ID: 1602411
PLA2G3
Group 3 secretory phospholipase A2
sPLA2-III
Reactome DB_ID: 1498787
UniProt:Q9NZ20 PLA2G3
PLA2G3
功能分泌calcium-dependent磷脂酶A2 that primarily targets extracellular phospholipids. Hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids without apparent head group selectivity (PubMed:12522102, PubMed:18801741, PubMed:15863501, PubMed:28947740). Contributes to phospholipid remodeling of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles. Hydrolyzes LDL phospholipids releasing unsaturated fatty acids that regulate macrophage differentiation toward foam cells (PubMed:18801741). May act in an autocrine and paracrine manner (PubMed:23624557). Secreted by immature mast cells, acts on nearby fibroblasts upstream to PTDGS to synthesize prostaglandin D2 (PGD2), which in turn promotes mast cell maturation and degranulation via PTGDR (PubMed:23624557). Secreted by epididymal epithelium, acts on immature sperm cells within the duct, modulating the degree of unsaturation of the fatty acyl components of phosphatidylcholines required for acrosome assembly and sperm cell motility. Facilitates the replacement of fatty acyl chains in phosphatidylcholines in sperm membranes from omega-6 and omega-9 to omega-3 polyunsaturated fatty acids (PUFAs). Coupled to lipoxygenase pathway, may process omega-6 PUFAs to generate oxygenated lipid mediators in the male reproductive tract (By similarity). At pericentrosomal preciliary compartment, negatively regulates ciliogenesis likely by regulating endocytotic recycling of ciliary membrane protein (PubMed:20393563). Coupled to cyclooxygenase pathway provides arachidonate to generate prostaglandin E2 (PGE2), a potent immunomodulatory lipid in inflammation and tumorigenesis (PubMed:12522102, PubMed:15863501). At colonic epithelial barrier, preferentially hydrolyzes phospholipids having arachidonate and docosahexaenoate at sn-2 position, contributing to the generation of oxygenated metabolites involved in colonic stem cell homeostasis (PubMed:28947740). Releases C16:0 and C18:0 lysophosphatidylcholine subclasses from neuron plasma membranes and promotes neurite outgrowth and neuron survival (PubMed:17868035).ACTIVITY REGULATION Arachidonic acid release is markedly increased by glypican, a glycosylphosphatidylinositol-anchored heparan sulfate proteoglycan.TISSUE SPECIFICITY Expressed in kidney, heart, liver, and skeletal muscle. Also present in placenta and peripheral blood leukocytes. Not detected in colon, thymus, spleen and small intestine. In lung, expressed in bronchial epithelial cells and alveolar macrophages, but scarcely detected in alveolar epithelium, arterial walls and interstitial fibroblasts (at protein level). In joints of osteoarthritis and rheumatoid arthritis, expressed in endothelial cells (at protein level). In normal heart, detected in some vessels. In myocardial tissues with acute infarction, expressed in vascular endothelial cells adjacent to cardiomyocytes and those in lesions with granulation. Expression in cardiomyocytes is scarce (at protein level). In uterus, breast and colon cancers, detected in tumor cells and neighboring microvascular endothelium, but not in normal glandular tissues (at protein level) (PubMed:15863501). Expressed in dermal resting mast cells (at protein level) and pulmonary mast cells (PubMed:23624557). Expressed in neuronal fibers (at protein level) (PubMed:17868035). Highly expressed in dorsal root ganglia neurons (at protein level) (PubMed:17868035). Expressed in Purkinje cells in cerebellum (at protein level) (PubMed:17868035). In stomach is preferentially expressed in neuronal fibers and in microvascular endothelium (PubMed:17868035). Sparsely expressed in normal aorta (at protein level). Highly expressed in macrophages and smooth muscle cells in aorta with atheroma (PubMed:18801741).INDUCTION By IL1B/interleukin-1 beta and TNF in microvascular endothelial cells (at protein level).DOMAIN The phospholipase A2-like domain represents the fully processed form after N- and C-termini are cleaved off. It is the secreted mature form found in biological fluids.PTM N-glycosylation does not affect the catalytic activity, but is required for proper secretion. A nonglycosylated form is observed in several cell types.PTM In several cell types, the N- and C-termini are cleaved off.SIMILARITY Belongs to the phospholipase A2 family.
UniProt
Q9NZ20
20
EQUAL
509
EQUAL
Reactome Database ID Release 77
1498787
数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=1498787
Reactome
R-HSA-1498787
1
Reactome稳定identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1498787.1
1
1
Reactome Database ID Release 77
1602411
数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=1602411
Reactome
R-HSA-1602411
1
Reactome稳定identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1602411.1
PLA2G5:Ca2+
Reactome DB_ID: 1500668
1
PLA2G5
Calcium-dependent phospholipase A2 precursor
Phosphatidylcholine 2-acylhydrolase
PLA2-10
Group V phospholipase A2
Reactome DB_ID: 61213
UniProt:P39877 PLA2G5
PLA2G5
功能分泌calcium-dependent磷脂酶A2 that primarily targets extracellular phospholipids (PubMed:8300559). Hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity), preferentially releasing fatty acyl groups with a low degree of unsaturation such as oleoyl (C18:1) and linoleoyl (C18:2) groups (PubMed:8300559, PubMed:14998370, PubMed:23533611). Hydrolyzes low-density lipoprotein (LDL) phospholipids releasing unsaturated fatty acids that drive macrophage polarization toward an M2 phenotype (By similarity). May act in an autocrine and paracrine manner. Contributes to lipid remodeling of cellular membranes at different subcellular locations and generation of lipid mediators involved in pathogen clearance. Cleaves sn-2 fatty acyl chains of cardiolipin, a major component of the inner membrane of mitochondria and bacterial membranes (PubMed:23533611). Promotes phagocytosis of bacteria in macrophages through production of lysophosphatidylethanolamines (PubMed:25725101). Displays bactericidal activity against Gram-positive bacteria by directly hydrolyzing phospholipids of the bacterial membrane (PubMed:11694541). Promotes phagocytosis and killing of ingested fungi likely through controlling phagosome-lysosome fusion and phagosome maturation (By similarity). Plays a role in biosynthesis of cysteinyl leukotrienes (CysLTs) in myeloid cells (PubMed:12124392, PubMed:12796497). In eosinophils, triggers perinuclear arachidonate release and LTC4 synthesis in a PLA2G4A-independent way (PubMed:12796497). In neutrophils, amplifies CysLTs biosynthesis initiated by PLA2G4A (PubMed:12124392). Promotes immune complex clearance in macrophages via stimulating synthesis of CysLTs, which act through CYSLTR1 to trigger phagocytosis (By similarity). May regulate antigen processing in antigen-presenting cells (By similarity). In pulmonary macrophages regulates IL33 production required for activation of group 2 innate lymphoid cells (By similarity). May play a role in the biosynthesis of N-acyl ethanolamines that regulate energy metabolism. Hydrolyzes N-acyl phosphatidylethanolamines to N-acyl lysophosphatidylethanolamines, which are further cleaved by a lysophospholipase D to release N-acyl ethanolamines (PubMed:14998370).ACTIVITY REGULATION Activated by cardiolipin.PATHWAY Lipid metabolism; phospholipid metabolism.PATHWAY Lipid metabolism; leukotriene B4 biosynthesis.PATHWAY Lipid metabolism; leukotriene C4 biosynthesis.TISSUE SPECIFICITY Heart, placenta and less abundantly, in lung. Detected in the outer and inner plexiform layers of the retina (at protein level) (PubMed:22137173). Expressed in monocytes and macrophages (PubMed:25725101).INDUCTION Up-regulated upon M2 macrophage polarization in response to IL4, CSF1 or IL10.PTM This enzyme lacks one of the seven disulfide bonds found in similar PLA2 proteins.SIMILARITY Belongs to the phospholipase A2 family.
UniProt
P39877
21
EQUAL
138
EQUAL
Reactome Database ID Release 77
61213
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Reactome
R-HSA-61213
1
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1
Reactome Database ID Release 77
1500668
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Reactome
R-HSA-1500668
1
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PLA2G10:Ca2+
Reactome DB_ID: 1602425
PLA2G10
Group 10 secretory phospholipase A2
sPLA2-X
Reactome DB_ID: 1498793
UniProt:O15496 PLA2G10
PLA2G10
功能分泌calcium-dependent磷脂酶A2 that primarily targets extracellular phospholipids (PubMed:9188469, PubMed:12021277). 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 (PubMed:12359733, PubMed:12021277). Contributes to phospholipid remodeling of very low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles (PubMed:12021277). Hydrolyzes LDL phospholipids releasing unsaturated fatty acids that regulate macrophage differentiation toward foam cells (PubMed:12021277). Efficiently hydrolyzes and inactivates platelet activating factor (PAF), a potent lipid mediator present in oxidized LDL (PubMed:16962371). 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 (PubMed:12359733). Displays bactericidal activity against Gram-positive bacteria by directly hydrolyzing phospholipids of the bacterial membrane (PubMed:11694541). 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 (PubMed:16146426). May play a role in maturation and activation of innate immune cells including macrophages, group 2 innate lymphoid cells and mast cells (By similarity).ACTIVITY REGULATION Inhibited by methyl indoxam.SUBUNIT Interacts with PLA2R1; this interaction mediates PLA2G10 clearance and inactivation.TISSUE SPECIFICITY Found in spleen, thymus, peripheral blood leukocytes, pancreas, lung, and colon (PubMed:9188469). Expressed in neuronal fibers in dorsal root ganglia and in peripheral tissues including stomach, white adipose tissue and prostate (at protein level) (PubMed:21266581).SIMILARITY Belongs to the phospholipase A2 family.
UniProt
O15496
43
EQUAL
165
EQUAL
Reactome Database ID Release 77
1498793
数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=1498793
Reactome
R-HSA-1498793
1
Reactome稳定identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-1498793.1
1
1
Reactome Database ID Release 77
1602425
数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=1602425
Reactome
R-HSA-1602425
1
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PLA2G12A:Ca2+
Reactome DB_ID: 1602352
1
PLA2G12
PLA2G12A
Group XIIA secretory phospholipase A2
sPLA2-XII
Reactome DB_ID: 1498790
UniProt: Q9BZM1 PLA2G12A
PLA2G12A
PLA2G12
FKSG38
UNQ2519/PRO6012
FUNCTION PA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides. Does not exhibit detectable activity toward sn-2-arachidonoyl- or linoleoyl-phosphatidylcholine or -phosphatidylethanolamine.TISSUE SPECIFICITY Abundantly expressed in heart, skeletal muscle, kidney, liver and pancreas.SIMILARITY Belongs to the phospholipase A2 family.
UniProt
Q9BZM1
23
EQUAL
189
EQUAL
Reactome Database ID Release 77
1498790
数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=1498790
Reactome
R-HSA-1498790
1
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1
Reactome Database ID Release 77
1602352
数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=1602352
Reactome
R-HSA-1602352
1
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Reactome Database ID Release 77
1602354
数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=1602354
Reactome
R-HSA-1602354
1
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GENE ONTOLOGY
GO:0004623
gene ontology term for cellular function
MI
MI:0355
Same Catalyst Activity
Reactome Database ID Release 77
1602353
数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=1602353
Reactome Database ID Release 77
1602398
数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=1602398
Reactome
R-HSA-1602398
3
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9188469
Pubmed
1997
Cloning, chromosomal mapping, and expression of a novel human secretory phospholipase A2
Cupillard, L
Koumanov, K
Matteï, MG
Lazdunski, M
Lambeau, G
J Biol Chem 272:15745-52
8300559
Pubmed
1994
Cloning and recombinant expression of a novel human low molecular weight Ca(2+)-dependent phospholipase A2
Chen, J
Engle, SJ
Seilhamer, JJ
Tischfield, JA
J Biol Chem 269:2365-8
12359733
Pubmed
2002
Interfacial kinetic and binding properties of the complete set of human and mouse groups I, II, V, X, and XII secreted phospholipases A2
Singer, AG
Ghomashchi, F
Le Calvez, C
Bollinger, J
Bezzine, S
Rouault, M
Sadilek, M
Nguyen, E
Lazdunski, M
Lambeau, G
Gelb, Michael H
J Biol Chem 277:48535-49
15863501
Pubmed
2005
Cellular distribution, post-translational modification, and tumorigenic potential of human group III secreted phospholipase A(2)
Murakami, M
Masuda, S
Shimbara, S
Ishikawa, Y
Ishii, T
Kudo, I
J Biol Chem 280:24987-98
10455175
Pubmed
1999
Cloning and characterization of novel mouse and human secretory phospholipase A(2)s
Ishizaki, J
Suzuki, N
Higashino, K
Yokota, Y
小野,T
Kawamoto, K
Fujii, N
Arita, H
Hanasaki, K
J Biol Chem 274:24973-9
7060561
Pubmed
1982
Studies on prophospholipase A2 and its enzyme from human pancreatic juice. Catalytic properties and sequence of the N-terminal region
Grataroli, R
Dijkman, R
Dutilh, CE
van der Ouderaa, F
De Haas, GH
Figarella, C
Eur J Biochem 122:111-7
10681567
Pubmed
2000
Structures, enzymatic properties, and expression of novel human and mouse secretory phospholipase A(2)s
Suzuki, N
Ishizaki, J
Yokota, Y
Higashino, K
小野,T
Ikeda, M
Fujii, N
Kawamoto, K
Hanasaki, K
J Biol Chem 275:5785-93
11830583
Pubmed
2002
Identification of a soluble form phospholipase A2 receptor as a circulating endogenous inhibitor for secretory phospholipase A2
Higashino Ki, Ken-ichi
Yokota, Yasunori
小野,Takashi
Kamitani, Shigeki
Arita, Hitoshi
Hanasaki, Kohji
J. Biol. Chem. 277:13583-8
12522102
Pubmed
2003
Cellular arachidonate-releasing function of novel classes of secretory phospholipase A2s (groups III and XII)
Murakami, M
Masuda, S
Shimbara, S
Bezzine, S
Lazdunski, M
Lambeau, G
Gelb, Michael H
Matsukura, S
Kokubu, F
Adachi, M
Kudo, I
J Biol Chem 278:10657-67
11031251
Pubmed
2000
Cloning and recombinant expression of a structurally novel human secreted phospholipase A2
Gelb, Michael H
Valentin, E
Ghomashchi, F
Lazdunski, M
Lambeau, G
J Biol Chem 275:39823-6
2925608
Pubmed
1989
Cloning and recombinant expression of phospholipase A2 present in rheumatoid arthritic synovial fluid
Seilhamer, JJ
Pruzanski, W
Vadas, P
Plant, S
米勒,是
Kloss, J
Johnson, LK
J Biol Chem 264:5335-8
12161451
Pubmed
2002
Crystal structure of human group X secreted phospholipase A2. Electrostatically neutral interfacial surface targets zwitterionic membranes
Pan, YH
Yu, BZ
Singer, AG
Ghomashchi, F
Lambeau, G
Gelb, Michael H
Jain, MK
Bahnson, BJ
J Biol Chem 277:29086-93
11112443
Pubmed
2000
Cloning and recombinant expression of human group IIF-secreted phospholipase A(2)
Valentin, E
Singer, AG
Ghomashchi, F
Lazdunski, M
Gelb, Michael H
Lambeau, G
Biochem Biophys Res Commun 279:223-8
INHIBITION
Reactome Database ID Release 77
8864276
数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=8864276
Reactome
R-HSA-8864276
2
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PLA2R_HUMAN
PLA2R1(21-?)
Secretory phospholipase A2 receptor
Reactome DB_ID: 8864270
UniProt:Q13018 PLA2R1
PLA2R1
CLEC13C
FUNCTION Receptor for secretory phospholipase A2 (sPLA2). Acts as a receptor for phospholipase sPLA2-IB/PLA2G1B but not sPLA2-IIA/PLA2G2A. Also able to bind to snake PA2-like toxins. Although its precise function remains unclear, binding of sPLA2 to its receptor participates in both positive and negative regulation of sPLA2 functions as well as clearance of sPLA2. Binding of sPLA2-IB/PLA2G1B induces various effects depending on the cell type, such as activation of the mitogen-activated protein kinase (MAPK) cascade to induce cell proliferation, the production of lipid mediators, selective release of arachidonic acid in bone marrow-derived mast cells. In neutrophils, binding of sPLA2-IB/PLA2G1B can activate p38 MAPK to stimulate elastase release and cell adhesion. May be involved in responses in proinflammatory cytokine productions during endotoxic shock. Also has endocytic properties and rapidly internalizes sPLA2 ligands, which is particularly important for the clearance of extracellular sPLA2s to protect their potent enzymatic activities. The soluble secretory phospholipase A2 receptor form is circulating and acts as a negative regulator of sPLA2 functions by blocking the biological functions of sPLA2-IB/PLA2G1B (PubMed:15611272, PubMed:7721806). In podocytes, binding of sPLA2-IB/PLA2G1B can regulate podocyte survival and glomerular homeostasis (PubMed:25335547).SUBUNIT Interacts with sPLA2-IB/PLA2G1B; this interaction mediates intracellular signaling as well as clearance of extracellular sPLA2-IB/PLA2G1B via endocytotic pathway (PubMed:7721806). Interacts with sPLA2-X/PLA2G10; this interaction mediates sPLA2-X/PLA2G10 clearance and inactivation (By similarity).TISSUE SPECIFICITY Expressed in podocytes (at protein level) (PubMed:25335547). Present in lung macrophage (at protein level). Highly expressed in kidney. Also expressed in pancreas, amnion, choriodecidua and placenta. Isoform 2 is expressed at much lower level.DOMAIN C-type lectin domains 3-5 mediate the interaction with phospholipase PLA2G1B.DOMAIN The endocytosis signal probably mediates endocytosis via clathrin-coated pits.PTM The secretory phospholipase A2 receptor form may be produced by the action of metalloproteinases. It contains all extracellular domains and only lacks transmembrane and cytosolic regions. It is however unclear whether this form is produced by proteolytic cleavage as suggested by some experiments, or by alternative splicing, as in the case of isoform 2 that shares all characteristics of secretory phospholipase A2 receptor form (By similarity).
UniProt
Q13018
21
EQUAL
-1
EQUAL
Reactome Database ID Release 77
8864270
数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=8864270
Reactome
R-HSA-8864270
2
Reactome稳定identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8864270.2