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Information on EC 3.1.1.4 - phospholipase A2 and Organism(s) Mus musculus and UniProt Accession P47713
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3.1.1.4 phospholipase A2IUBMB Comments
Also acts on phosphatidylethanolamine, choline plasmalogen and phosphatides, removing the fatty acid attached to the 2-position. Requires Ca2+.
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Word Map
- 3.1.1.4
-
arachidonic
- phospholipid
- prostaglandin
-
cyclooxygenase
-
eicosanoids
-
leukotriene
- necrosis
- indomethacin
- agonist
- lysophosphatidylcholine
- endothelial
- neutrophil
- bromide
- phosphatidylethanolamine
- crotalus
- lipoxygenase
- cox-2
-
phorbol
-
ionophore
- pkc
- inositol
- artery
-
neurotoxic
- quinacrine
-
thromboxane
- peroxiredoxins
-
platelet-activating
- diacylglycerols
- nephropathy
- lysophospholipids
-
bilayer
- phosphatidylinositol
-
prelabeled
- edema
-
prostanoids
- phosphatidylserine
- pertussis
-
interfacial
-
phosphatidic
-
envenom
- glycerophospholipids
-
nordihydroguaiaretic
-
presynaptic
- synovial
- prostacyclin
- viper
-
micelle
- pharmacology
- analysis
- food industry
- biotechnology
-
lipoprotein-associated
- ndga
- industry
- drug development
- zymosan
- medicine
- synthesis
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
phospholipase a2, cpla2, spla2, spla(2), prdx6, cytosolic phospholipase a2, crotoxin, pla2s, ipla2, spla2-iia, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
14 kDa phospholipase A2
-
-
-
-
Agkistrotoxin
-
-
-
-
amdI1
-
-
-
-
Ammodytin I2
-
-
-
-
APLA
-
-
-
-
APP-D-49
-
-
-
-
ASPLA1
-
-
-
-
ASPLA10
-
-
-
-
ASPLA11
-
-
-
-
ASPLA12
-
-
-
-
ASPLA13
-
-
-
-
ASPLA14
-
-
-
-
ASPLA15
-
-
-
-
ASPLA16
-
-
-
-
ASPLA17
-
-
-
-
ASPLA2
-
-
-
-
ASPLA3
-
-
-
-
ASPLA4
-
-
-
-
ASPLA5
-
-
-
-
ASPLA6
-
-
-
-
ASPLA7
-
-
-
-
ASPLA8
-
-
-
-
ASPLA9
-
-
-
-
ATX
-
-
-
-
Basic protein I/II
-
-
-
-
BJ-PLA2
-
-
-
-
BJUPLA2
-
-
-
-
BPI/BPII
-
-
-
-
CaI-PLA2
-
-
-
-
Caudoxin
-
-
-
-
cPm09
-
-
-
-
Enhancing factor
-
-
-
-
GIIC sPLA2
-
-
-
-
GIID sPLA2
-
-
-
-
GIIE sPLA2
-
-
-
-
GIIF sPLA2
-
-
-
-
GIII sPLA2
-
-
-
-
Group IB phospholipase A2
-
-
-
-
Group IIA phospholipase A2
-
-
-
-
Group V phospholipase A2
-
-
-
-
Group VI phospholipase A2
-
-
-
-
GVI PLA2
-
-
-
-
GX sPLA2
GXII sPLA2
-
-
-
-
GXIII sPLA2
-
-
-
-
iPLA2
lecithinase A
-
-
-
-
MP-III 4R
-
-
-
-
Muscarinic inhibitor
-
-
-
-
Myotoxin
-
-
-
-
NAJPLA-2A
-
-
-
-
NAJPLA-2B
-
-
-
-
NAJPLA-2C
-
-
-
-
Nigexine
-
-
-
-
Non-pancreatic secretory phospholipase A2
-
-
-
-
Notechis 11'2
-
-
-
-
Notexin
-
-
-
-
NPLA
-
-
-
-
NPS-PLA2
-
-
-
-
OHV A-PLA2
-
-
-
-
OHV-APLA2
-
-
-
-
pgPLA 1a/pgPLA 2a
-
-
-
-
phosphatidase
-
-
-
-
phosphatide 2-acylhydrolase
-
-
-
-
phosphatidolipase
-
-
-
-
Phosphatidylcholine 2-acylhydrolase
-
-
-
-
Phosphatidylcholine 2-acylhydrolase GIIC
-
-
-
-
Phosphatidylcholine 2-acylhydrolase GIID
-
-
-
-
Phosphatidylcholine 2-acylhydrolase GIIE
-
-
-
-
Phosphatidylcholine 2-acylhydrolase GIIF
-
-
-
-
Phosphatidylcholine 2-acylhydrolase GIII
-
-
-
-
Phosphatidylcholine 2-acylhydrolase GX
-
-
-
-
Phosphatidylcholine 2-acylhydrolase GXII
-
-
-
-
Phosphatidylcholine 2-acylhydrolase GXIII
-
-
-
-
phospholipase A
-
-
-
-
Phospholipase A2 inhibitor
-
-
-
-
pkP5
-
-
-
-
PLA2-10
-
-
-
-
PLA2-VI
-
-
-
-
PLA2-VII
-
-
-
-
PLA2IID
-
-
-
-
platelet activating factor acetyl hydrolase
-
-
-
-
Pt-PLA1
-
-
-
-
Pt-PLA2
-
-
-
-
secreted phospholipase A2
Secretory-type PLA, stroma-associated homolog
-
-
-
-
sPLA(2)-IID
-
-
-
-
sPLA(2)-IIE
-
-
-
-
sPLA(2)-IIF
-
-
-
-
sPLA2
sPLA2-X
TMV-K49
-
-
-
-
Toxin VI
-
-
-
-
Toxin VI:5
-
-
-
-
additional information
GX sPLA2
-
-
-
-
iPLA2
-
-
-
-
additional information
-
secreted phospholipase A2 isozymes from groups A, B, D, E, F, V, and X
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of carboxylic ester
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
KEGG
-
-, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
phosphatidylcholine 2-acylhydrolase
Also acts on phosphatidylethanolamine, choline plasmalogen and phosphatides, removing the fatty acid attached to the 2-position. Requires Ca2+.
CAS REGISTRY NUMBER
COMMENTARY
9001-84-7
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
1,2-bis-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-undecanoyl)-sn-glycero-3-phosphocholine + H2O
?
-
-
-
-
?
1,2-dipalmitoyl-sn-glycero-3-phosphocholine + H2O
1-palmitoyl-sn-glycero-3-phosphocholine + palmitate
-
-
-
-
?
1,2-dipalmitoyl-sn-glycero-3-phosphorylcholine + H2O
1-palmitoyl-sn-glycero-3-phosphorylcholine + palmitic acid
-
in mixed micelles with Triton X-100
-
?
1,2-dipalmitoyl-sn-phosphatidylcholine + H2O
1-palmitoyl-sn-phosphatidylcholine + palmitate
the catalytic site for aiPLA2 activity is an S32-H26-D140 triad
-
-
?
1-acyl-2-arachidonoyl-sn-glycerophosphocholine + H2O
1-acyl-sn-glycerophosphocholine + arachidonic acid
-
-
-
?
1-acyl-2-arachidonoyl-sn-glycerophosphoethanolamine + H2O
1-acyl-sn-glycerophosphoethanolamine + arachidonic acid
-
-
-
?
1-acyl-2-linoleoyl-sn-glycerophosphocholine + H2O
1-acyl-sn-glycerophosphocholine + linoleic acid
-
-
-
?
1-acyl-2-oleoyl-sn-glycerophosphocholine + H2O
1-acyl-sn-glycerophosphocholine + oleic acid
-
-
-
?
1-acyl-2-palmitoyl-sn-glycerophosphocholine + H2O
1-acyl-sn-glycerophosphocholine + palmitic acid
-
-
-
?
1-oleoyl-2-palmitoyl-sn-glycero-3-phosphocholine + H2O
1-oleoyl-sn-glycero-3-phosphocholine + palmitate
-
-
-
-
?
1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine + H2O
1-palmitoyl-sn-glycero-3-phosphorylcholine + arachidonic acid
-
in mixed micelles with Triton X-100
-
?
1-palmitoyl-2-arachidonoylphosphatidylcholine + H2O
1-palmitoyl-glycerophosphorylcholine + arachidonic acid
-
-
-
-
?
1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine + H2O
1-palmitoyl-sn-glycero-3-phosphocholine + oleate
-
-
-
-
?
1-stearoyl-2-arachidonoylphosphatidylcholine + H2O
1-stearoyl-glycerophosphorylcholine + arachidonic acid
-
-
-
?
arachidonyl thio-PC + H2O
arachidonic acid + (7R)-4-hydroxy-N,N,N-trimethyl-7-sulfanyl-3,5,9-trioxa-4-phosphapentacosan-1-aminium 4-oxide
-
-
-
-
?
oxidized phosphatidylcholine + H2O
lysophosphatidylcholine + fatty acid
-
great amount of oxidized phosphatidylcholine of oxidized LDL is hydrolyzed at the sn-2 position
-
-
?
phosphatidylinositol + arachidonic acid
arachidonoyl phosphatidylinositol + fatty acid
-
-
-
?
phospholipid + H2O
lysophospholipid + fatty acid
the enzyme is essential for production of two classes of lipid mediators, fatty acid metabolites, and lysophospholipid-related lipids, and is involved in the remodeling of membrane phospholipids, physiologic functions, overview
-
-
?
additional information
?
-
-
enzyme exhibits lyspohospholipase activity, lysophospholipid transacylase acitivty and phospholipase A2 activity
-
?
additional information
?
-
-
during apoptosis, changes occur in lymphocyte membranes that render them susceptible to hydrolysis by secretory phospholipase A2, mechanism, the membranes of apoptotic cells become susceptible to sPLA2 through a reduction in lipid-neighbor interactions that facilitates migration of phospholipids into the enzyme active site, overview
-
-
?
additional information
?
-
-
substrate specificity, overview, Lpla2 also shows transacylase activity transferring fatty acids from phosphatidylcholine or phosphatidylethanolamine liposomes onto N-acetylsphingosine incorporated into phospholipid liposomes, positional specificity, overview
-
-
?
additional information
?
-
-
prion infection greatly increased both the phosphorylation of cPLA2 and prostaglandin E2 production, the alternatively folded prion protein PrPSc causes a dose-dependent increase in the free cholesterol concentration of cortical neurons, overview
-
-
?
additional information
?
-
-
the phospholipase A2 superfamily consists of many different groups of enzymes that catalyze the hydrolysis of the sn-2 ester bond in a variety of different phospholipids, products of the hydrolysis of the sn-2 ester bond of phospholipid are a free fatty acid and lysophospholipid
-
-
?
additional information
?
-
-
cPLA2 may release fatty acid hydroperoxides from membranes following denervation
-
-
?
additional information
?
-
-
isoform cPLA2beta shows no activity with 1-palmitoyl-2-oleoyl-phosphatidylcholine
-
-
?
additional information
?
-
-
sPLA2-IIE preferentially hydrolyzes the minor lipoprotein phospholipids, phosphatidylethanolamine and phosphatidylserine, with no fatty acid selectivity
-
-
?
additional information
?
-
sPLA2-IIE preferentially hydrolyzes the minor lipoprotein phospholipids, phosphatidylethanolamine and phosphatidylserine, with no fatty acid selectivity
-
-
?
additional information
?
-
-
sPLA2-X secreted from sperm acrosomes selectively hydrolyzes docosahexaenoic acid- or docosapentaenoic acid-containing phosphatidylcholine in the sperm membrane to release docosahexaenoic acid, docosapentaenoic acid, and lysophosphatidylcholine
-
-
?
additional information
?
-
sPLA2-X secreted from sperm acrosomes selectively hydrolyzes docosahexaenoic acid- or docosapentaenoic acid-containing phosphatidylcholine in the sperm membrane to release docosahexaenoic acid, docosapentaenoic acid, and lysophosphatidylcholine
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
phospholipid + H2O
lysophospholipid + fatty acid
the enzyme is essential for production of two classes of lipid mediators, fatty acid metabolites, and lysophospholipid-related lipids, and is involved in the remodeling of membrane phospholipids, physiologic functions, overview
-
-
?
additional information
?
-
-
during apoptosis, changes occur in lymphocyte membranes that render them susceptible to hydrolysis by secretory phospholipase A2, mechanism, the membranes of apoptotic cells become susceptible to sPLA2 through a reduction in lipid-neighbor interactions that facilitates migration of phospholipids into the enzyme active site, overview
-
-
?
additional information
?
-
-
prion infection greatly increased both the phosphorylation of cPLA2 and prostaglandin E2 production, the alternatively folded prion protein PrPSc causes a dose-dependent increase in the free cholesterol concentration of cortical neurons, overview
-
-
?
additional information
?
-
-
the phospholipase A2 superfamily consists of many different groups of enzymes that catalyze the hydrolysis of the sn-2 ester bond in a variety of different phospholipids, products of the hydrolysis of the sn-2 ester bond of phospholipid are a free fatty acid and lysophospholipid
-
-
?
additional information
?
-
-
sPLA2-IIE preferentially hydrolyzes the minor lipoprotein phospholipids, phosphatidylethanolamine and phosphatidylserine, with no fatty acid selectivity
-
-
?
additional information
?
-
sPLA2-IIE preferentially hydrolyzes the minor lipoprotein phospholipids, phosphatidylethanolamine and phosphatidylserine, with no fatty acid selectivity
-
-
?
additional information
?
-
-
sPLA2-X secreted from sperm acrosomes selectively hydrolyzes docosahexaenoic acid- or docosapentaenoic acid-containing phosphatidylcholine in the sperm membrane to release docosahexaenoic acid, docosapentaenoic acid, and lysophosphatidylcholine
-
-
?
additional information
?
-
sPLA2-X secreted from sperm acrosomes selectively hydrolyzes docosahexaenoic acid- or docosapentaenoic acid-containing phosphatidylcholine in the sperm membrane to release docosahexaenoic acid, docosapentaenoic acid, and lysophosphatidylcholine
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
additional information
Ca2+
-
is required for catalytic activity. With increase in the concentration of calcium, increase of recombinant sPLA2 activity
Ca2+
-
cytosolic isoform PLA2beta action on phosphatidylcholine vesicles displays a requirement for Ca2+ only in the presence of cardiolipin
additional information
-
Ca2+ independent PLA2, iPLA2s, includes three different types GVIA, GVIB, and GVIC PLA2
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
([1-[amino(oxo)acetyl]-3-(biphenyl-2-ylmethyl)-2-(2-methylpropyl)indolizin-8-yl]oxy)acetic acid
-
-
([3-[amino(oxo)acetyl]-1-benzyl-2-(2-methylpropyl)-1H-benzo[g]indol-4-yl]oxy)acetic acid
-
-
1-palmitylthio-2-palmitoylamido-1,2-dideoxy-sn-glycero-3-phosphorylcholine
-
competitive inhibitor toward recombinant sPLA2, dose-dependent inhibition
2-(3-(2-amino-2-oxoacetyl)-1-benzyl-2-ethyl-1H-6,7-benzoindol-4-yloxy)acetic acid
-
-
2-([3-[amino(oxo)acetyl]-1-benzyl-2-(2-methylpropyl)-1H-benzo[g]indol-4-yl]oxy)-N-(phenylsulfonyl)acetamide
-
-
2-([3-[amino(oxo)acetyl]-1-benzyl-2-(2-methylpropyl)-1H-indol-4-yl]oxy)-N-(phenylsulfonyl)acetamide
-
-
2-([3-[amino(oxo)acetyl]-1-benzyl-2-ethyl-1H-benzo[g]indol-4-yl]oxy)-N-(phenylsulfonyl)acetamide
-
-
2-([3-[amino(oxo)acetyl]-1-benzyl-2-ethyl-1H-indol-4-yl]oxy)-N-(phenylsulfonyl)acetamide
-
-
2-[1-benzyl-2-(2-methylpropyl)-4-(2-oxopropoxy)-1H-indol-3-yl]-2-oxoacetamide
-
-
2-[3-(biphenyl-2-ylmethyl)-2-ethyl-8-(2-oxopropoxy)indolizin-1-yl]-2-oxoacetamide
-
-
4-[2-aminoethyl]benzensulfonyl fluoride
-
pefabloc, inhibition of activity at 1 mM
AACOCF3
-
PLA2 inhibitor, does not affect basal Mn2+ entry, but strongly reduces the enhanced Mn2+ entry of thapsigargin-treated fibers
LY315920
-
i.e. [[3-(aminooxoacetyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetate
pyrrophenone
-
pretreatment of cells with pyrrophenone reduces Kdo2-lipid A stimulated arachidonic acid release to background levels
pyrroxyphene
-
significantly inhibits both the increase in levels of cPLA2 alpha and eicosanoids as well as the mRNA expression of matrix metalloproteinase-3, -8, -9, -13, and cyclooxygenase-2. Strongly inhibits the incidence of arthritis and bone destruction
tert-butyl ([3-[amino(oxo)acetyl]-1-benzyl-2-(2-methylpropyl)-1H-indol-4-yl]oxy)acetate
-
-
arachidonyl trifluoromethyl ketone
-
AACOCF3, both de novo lysophosphatidic acid production and neuropathic pain-like behaviors are substantially abolished by intrathecal injection of arachidonyl trifluoromethyl ketone, a mixed inhibitor of cPLA2 and iPLA2, at 1 h after injury
arachidonyl trifluoromethyl ketone
-
AACOCF3, highly selective cPLA2 inhibitor, inhibits the Amplex Red signal in mitochondria from denervated muscle and from Sod1-/- mice
bromoenol lactone
-
both de novo lysophosphatidic acid production and neuropathic pain-like behaviors are substantially abolished by intrathecal injection of bromoenol lactone, an iPLA2 inhibitor, at 1 h after injury
bromoenol lactone
-
specific suicide substrate of PLA2, does not affect basal Mn2+ entry, but strongly reduces the enhanced Mn2+ entry of thapsigargin-treated fibers
additional information
-
substituted indole and 6,7-benzoindole inhibitor binding, molecular modeling, overview
-
additional information
-
during low density lipoprotein oxidation with 0.005 mM CuSO4, the remaining Lp-PLA2 activity after 6h is approximately 40-50% while after 24h only 10-15% of the initial activity is preserved
-
additional information
-
neither PAP-1 nor PKC inhibition reduces GIVA PLA2 synergistic activation by stimulation with Kdo2-Lipid A and ATP. Neither EDTA nor EGTA reduce the arachidonic acid release
-
additional information
-
recombinant sPLA2 is not inhibited by bromoenol lactone or AACOCF3 (arachidonyl trifluoromethyl ketone)
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ATP
-
cellular GIVA PLA2 activity is induced by the treatment of cells with Ca+2 mobilizing agonists, such as the purinergic P2X7 receptor agonist ATP
cardiolipin
-
cytosolic isoform PLA2beta action on phosphatidylcholine vesicles is activated by anionic phosphoinositides and cardiolipin
diacylglycerol
-
exogenous diacylglycerol stimulates GIVA PLA2-mediated arachidonic acid release
additional information
-
in apoptosis the initial rate of hydrolysis is elevated at all enzyme concentrations, the total amount of reaction product is increased fourfold, and adsorption of the enzyme to the membrane surface is unaltered
-
additional information
-
cPLA2 is activated by phosphorylation involving the cellular prion protein, overview
-
additional information
-
involvement of phosphatidic acid phosphohydrolase 1 (PAP-1) and protein kinase C (PKC) in the Toll-like receptor-4 (TLR-4) activation of GIVA PLA2. Ca+2 influx is not required for TLR-4 mediated activation of the GIVA PLA2
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
kinetics of interaction between sPLA2 and lymphocyte cell membranes, overview
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0011
([1-[amino(oxo)acetyl]-3-(biphenyl-2-ylmethyl)-2-(2-methylpropyl)indolizin-8-yl]oxy)acetic acid
Mus musculus
-
isozyme sPLA2 group IIF
0.00013
([3-[amino(oxo)acetyl]-1-benzyl-2-(2-methylpropyl)-1H-benzo[g]indol-4-yl]oxy)acetic acid
Mus musculus
-
isozyme sPLA2 group IIF
0.000034
2-(1-benzyl-2-ethyl-4-methoxy-1H-benzo[g]indol-3-yl)-2-oxoacetamide
Mus musculus
-
isozyme sPLA2 group IIA
0.000006
2-(3-(2-amino-2-oxoacetyl)-1-benzyl-2-ethyl-1H-6,7-benzoindol-4-yloxy)acetic acid
Mus musculus
-
isozyme sPLA2 group IIX
0.00045
2-([3-[amino(oxo)acetyl]-1-benzyl-2-(2-methylpropyl)-1H-benzo[g]indol-4-yl]oxy)-N-(phenylsulfonyl)acetamide
Mus musculus
-
isozyme sPLA2 group IIF
0.0016
2-([3-[amino(oxo)acetyl]-1-benzyl-2-(2-methylpropyl)-1H-indol-4-yl]oxy)-N-(phenylsulfonyl)acetamide
Mus musculus
-
above, isozyme sPLA2 group IIA-IIX
0.000035
2-([3-[amino(oxo)acetyl]-1-benzyl-2-ethyl-1H-benzo[g]indol-4-yl]oxy)-N-(phenylsulfonyl)acetamide
Mus musculus
-
isozyme sPLA2 group IIX
0.000012
2-([3-[amino(oxo)acetyl]-1-benzyl-2-ethyl-1H-indol-4-yl]oxy)-N-(phenylsulfonyl)acetamide
Mus musculus
-
isozyme sPLA2 group IIE
0.00058
2-[1-benzyl-2-(2-methylpropyl)-4-(2-oxopropoxy)-1H-indol-3-yl]-2-oxoacetamide
Mus musculus
-
isozyme sPLA2 group IIB
0.00002
2-[1-benzyl-4-(2-oxopropoxy)-2-propyl-1H-indol-3-yl]-2-oxoacetamide
Mus musculus
-
isozyme sPLA2 group IIX
0.00041
2-[3-(biphenyl-2-ylmethyl)-2-ethyl-8-(2-oxopropoxy)indolizin-1-yl]-2-oxoacetamide
Mus musculus
-
isozyme sPLA2 group IIE
0.00023
2-[3-(biphenyl-2-ylmethyl)-2-ethyl-8-methoxyindolizin-1-yl]-2-oxoacetamide
Mus musculus
-
isozyme sPLA2 group IIE
additional information
additional information
Mus musculus
-
IC50 values of diverse isozymes, overview
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.000245
-
isoform cPLA2beta, using 1-palmitoyl-2-arachidonyl-sn-glycerol-3-phosphocholine as substrate, in 10 mM MOPS, pH 7.2, 0.5 mM EGTA, 100 mM KCl, 0.5 mg/ml bovine serum albumin, in the absence of Ca2+, at 37°C
0.000295
-
isoform cPLA2beta, using 1-palmitoyl-2-arachidonyl-sn-glycerol-3-phosphocholine as substrate, in 10 mM MOPS, pH 7.2, 0.5 mM EGTA, 100 mM KCl, 0.5 mg/ml bovine serum albumin, 0.02 mM Ca2+, at 37°C
0.00245
-
isoform cPLA2zeta, using 1-palmitoyl-2-arachidonyl-sn-glycerol-3-phosphocholine as substrate, in 10 mM MOPS, pH 7.2, 0.5 mM EGTA, 100 mM KCl, 0.5 mg/ml bovine serum albumin, in the absence of Ca2+, at 37°C
0.06
-
isoform cPLA2zeta, using 1-palmitoyl-2-arachidonyl-sn-glycerol-3-phosphocholine as substrate, in 10 mM MOPS, pH 7.2, 0.5 mM EGTA, 100 mM KCl, 0.5 mg/ml bovine serum albumin, 0.02 mM Ca2+, at 37°C
0.365
-
isoform cPLA2beta, using 1-palmitoyl-sn-glycero-3-phosphocholine as substrate, in 10 mM MOPS, pH 7.2, 0.5 mM EGTA, 100 mM KCl, 0.5 mg/ml bovine serum albumin, 0.02 mM Ca2+, at 37°C
0.3695
-
isoform cPLA2zeta, using 1-palmitoyl-sn-glycero-3-phosphocholine as substrate, in 10 mM MOPS, pH 7.2, 0.5 mM EGTA, 100 mM KCl, 0.5 mg/ml bovine serum albumin, 0.02 mM Ca2+, at 37°C
0.372
-
isoform cPLA2zeta, using 1-palmitoyl-sn-glycero-3-phosphocholine as substrate, in 10 mM MOPS, pH 7.2, 0.5 mM EGTA, 100 mM KCl, 0.5 mg/ml bovine serum albumin, in the absence of Ca2+, at 37°C
0.381
-
isoform cPLA2beta, using 1-palmitoyl-sn-glycero-3-phosphocholine as substrate, in 10 mM MOPS, pH 7.2, 0.5 mM EGTA, 100 mM KCl, 0.5 mg/ml bovine serum albumin, in the absence of Ca2+, at 37°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
secreted phospholipase A2-IID is preferentially and abundantly expressed in dendritic cells in lymphoid organs
sPLA2-IIF is expressed in terminally differentiated keratinocytes in the suprabasal epidermis and markedly increased in psoriatic skin
additional information
-
the enzyme co-precipitates with the alternatively folded cellular prion protein isoform PrPSc
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
iPLA2 is primarily located in the vicinity of the sarcolemma
-
-
sPLA2 isozymes of groups IIC, IIE, IIF, IID, IIi, V, X, and XII
-
-
binding of the GIVA PLA2 to the membrane is mediated through three mechanisms: Ca2+ mediated translocation, binding of secondary lipid messengers, and phosphorylation
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
malfunction
physiological function
malfunction
lack of cPLA2alpha prolongs the G1 phase and reduces the proliferating capacity in response to mitogen stimulation without a significant change in the duration of the other phases of the cell cycle
malfunction
primary microglial cells isolated from cPLA2alpha-deficient mice generate significantly less nitric oxide and reactive oxygen species as compared with the wild-type mice. Microglia isolated from iPLA2beta-deficient mice do not show a decrease in LPS-induced nitric oxide and reactive oxygen species production
physiological function
isoform PLA2IValpha is selectively activated upon Fc receptor-mediated phagocytosis in macrophages and rapidly translocates to the site of the nascent phagosome. Pharmacological inhibition of PLA2IValpha by pyrrophenone reduces particle internalization by up to 50%. Fibroblasts from PLA2IValpha knock-out mice overexpressing FcRIIA and able to internalize IgG-opsonized beads show 50% lower phagocytosis, compared with wild-type cells. Transfection of the catalytically inactive deleted PLA2IValpha mutant PLA2IValpha(1-525) and point mutant PLA2IValpha-S228C promotes recovery of this impaired function. Transfection of the PLA2IValpha C2 domain, but not of PLA2IValpha-D43N, which cannot bind to membranes, rescues FcR-mediated phagocytosis
physiological function
the enzyme plays a crucial role in reactive oxygen species/nitric oxide signaling during microglial activation through the lipoxygenase pathway
physiological function
the enzyme plays an important role in induction of cell cycle progression at the G1 phase in mesangial cells through inhibition of FOXO1 activity
malfunction
-
absence of the GIVA PLA2 gene significantly reduces the effects of many inflammatory disease
malfunction
-
progressive inactivation of Lp-PLA2 during low density lipoprotein oxidation leads to an increased uptake of oxidized low density lipoprotein by macrophages, which can be primarily attributed to the increased uptake of the oxidized phospholipids enriched lipid moiety of oxidized low density lipoprotein. Inhibition of Lp-PLA2 activity has no effect on the uptake of ApoB-liposomes conjugates with ApoB isolated from moderately oxidized low density lipoprotein, moderately oxidized low density lipoprotein with inhibited LpPLA2 activity, heavily oxidized low density lipoprotein and heavily oxidized low density lipoprotein with inhibited LpPLA2 activity
malfunction
mice deficient in secreted phospholipase A2 IIF are protected from epidermal hyperplasia in psoriasis, contact dermatitis, and skin cancer, where ethanolamine lysoplasmalogen is selectively reduced in the KO skin relative to wild-type skin
malfunction
primary microglial cells isolated from cPLA2alpha-deficient mice generate significantly less nitric oxide and reactive oxygen species as compared with the wild-type mice. Microglia isolated from iPLA2beta-deficient mice do not show a decrease in LPS-induced nitric oxide and reactive oxygen species production
malfunction
when fed a high-fat diet, sPLA2-IIE-deficient mice display lower weight gain, adiposity, and fatty liver, accompanied by alterations in plasma lipoprotein profiles
physiological function
-
cPLA2 alpha plays an important role in the pathogenesis of collagen-induced arthritis. cPLA2 alpha activity increases in hind paws of collagen-induced arthritic mice
physiological function
-
cPLA2 may be a potential source of fatty acid hydroperoxides. cPLA2 is a key mediator of the high state 1 Amplex Red signal (thought to be highly specific for hydrogen peroxide) that occurs in response to denervation, most likely by preventing the release of fatty acid hydroperoxides from lipid hydroperoxides in the bilayer. Elevation of cPLA2 is potentially a common phenomenon in mice that exhibit muscle atrophy associated with a loss of innervation
physiological function
-
GVIA PLA2 plays an important role in bone formation, apoptosis, insulin secretion, and sperm development. GVIA PLA2 in combination with the GIVA PLA2 play an important role in Wallerian degeneration and axon regeneration in nerve injury. GIVA PLA2 is generally considered to be a central enzyme mediating generation of eicosanoids and hence many inflammatory processes
physiological function
-
iPLA2 is responsible for the enhanced Mn2+ entry occurring upon Ca2+ store depletion, iPLA2 hydrolysis products are involved in the gating of store-operated channels
physiological function
-
Lp-PLA2 activity reduces the uptake of oxidized low density lipoprotein by peritoneal macrophages. Lp-PLA2 does not affect the uptake of oxidized low density lipoprotein via the ApoB moiety. Lp-PLA2 reduces the uptake of oxidized low density lipoprotein via the lipid moiety
physiological function
-
PLA2- and autotaxin-mediated de novo lysophosphatidic acid production in the early phase is involved in nerve injury-induced neuropathic pain
physiological function
-
group X secreted phospholipase A2 (sPLA2) acts as a potent inhibitor of sperm motility that decreases track speed and lateral displacement of the head of both noncapacitated and capacitated sperm. sPLA2 selects a sperm subpopulation for fertilization based on its effect on sperm motility
physiological function
adipocyte inducible sPLA2-IIE targets phospholipids in lipoproteins
physiological function
role in adaptive immunity. secreted phospholipase A2-IID preferentially hydrolyzes arachidonic acid- or docosahexaenoic acid-containing phosphatidylethanolamine in lymph nodes, thereby mobilizing arachidonic acid- and particularly docosahexaenoic acid-derived antiinflammatory lipid mediators that attenuate the Th1-mediated immunity
physiological function
secreted phospholipase A2 IIF referentially hydrolyzes plasmalogen secreted from keratinocytes to produce lysoplasmalogen, which in turn promotes the hyperproliferation and activation of keratinocytes, leading to aggravation of epidermal-hyperplasic disorders. sPLA2-IIF transgenic mice spontaneously developed psoriasis-like epidermal hyperplasia and alopecia, with preferential hydrolysis of DHA-containing phosphatidylethanolamine to give rise to acyl and plasmalogen (P-) forms of lysophosphatidylethanolamine molecular species in addition to (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoate (DHA)
physiological function
the enzyme has important physiological roles in the turnover (synthesis and degradation) of lung surfactant phospholipids, in the repair of peroxidized cell membranes, and in the activation of NADPH oxidase type 2
physiological function
the enzyme plays a crucial role in reactive oxygen species/nitric oxide signaling during microglial activation through the lipoxygenase pathway
physiological function
the enzyme plays a role as an omega3 PUFA mobilizer. sPLA2-X secreted from sperm acrosomes selectively hydrolyzes docosahexaenoic acid- or docosapentaenoic acid-containing phosphatidylcholine in the sperm membrane to release docosahexaenoic acid, docosapentaenoic acid, and lysophosphatidylcholine, and the defective fertilization ability of sPLA2-X KO sperm was corrected by these lipids (docosapentaenoic acid in particular), suggesting the importance of the sPLA2-X-driven docosapentaenoic acid for successful fertilization
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PA24A_MOUSE
748
0
85222
Swiss-Prot
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
the enzyme contains a catalytic lipase domain and a C2 CaLB domain, domain structure, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
phosphoprotein
phosphoprotein
the enzyme contains phosphorylation sites at Ser505, Ser515, and Ser727
phosphoprotein
on both primary and BV-2 microglial cells, stimulation with lipopolysaccharide or interferon gamma results in a time-dependent increase in phosphorylation of cPLA2
phosphoprotein
-
prion infection greatly increased the phosphorylation of cPLA2 leading to increased activation of the PLA2 pathway
phosphoprotein
on both primary and BV-2 microglial cells, stimulation with lipopolysaccharide or interferon gamma results in a time-dependent increase in phosphorylation of cPLA2
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
construction of cytosolic PLA2 null mutant mice, phenotype, e.g. with loss of renal concentration function, overview
additional information
-
construction and phenoytpe of Lpla2-deficient mice, overview
additional information
-
knockout mice deficient in GIVA PLA2 show significant decreases in allergic response, damage from acute lung injury, and postischaemic brain injury
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of sPLA2s from groups IIE, III, V, and X in HEK-293T and CHO-K1 cells and secretion of the recombinant protein. Enhancement of expression and secretion of the isozymes by co-expression of several different engineered His6-tagged human small ubiquitin-like modifier, i.e. SUMO, proteins, overview
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
cPLA2 protein levels are increased ca. 2fold in muscle homogenates 7 days post-denervation. The cPLA2 protein levels are also elevated in Sod1-/- and G93A mice
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pharmacology
pharmacological targeting of the enzyme may have important therapeutic benefits in disease mechanisms that involve excessive cell proliferation, in particular, cancer and proliferative glomerulopathies
drug development
drug development
-
inhibition of iPLA2 and lysophospholipid production may be of interest to reduce Ca2+ entry and subsequent degeneration of dystrophic muscle
drug development
-
potential therapeutic role for cPLA2 alpha inhibitors in the treatment of human rheumatoid arthritis. Oral administration of pyrroxyphene achieves anti-arthritic activity through inhibition of cPLA2 alpha activity, which leads to a reduction in eicosanoid levels and suppression of matrix metalloproteinases and cyclooxygenase-2 mRNA expression
drug development
-
targeted inhibition of PLA2- and autotaxin-mediated lysophosphatidic acid synthesis may be a potential strategy for the prevention of nerve injury-induced neuropathic pain
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Chen, D.; Dennis, E.A.
Expression and characterization of human group V phospholipase A2
Biochim. Biophys. Acta
1394
57-64
1998
Homo sapiens, Mus musculus, Rattus norvegicus
Steiner, M.
Localization and characterization of phospholipase A2 in mouse mammary gland-derived cells
Arch. Biochem. Biophys.
286
293-299
1991
Mus musculus
Winstead, M.V.; Balsinde, J.; Dennis, E.A.
Calcium-independent phospholipase A2: structure and function
Biochim. Biophys. Acta
1488
28-39
2000
Homo sapiens, Mammalia, Mus musculus, Rattus norvegicus
Kita, Y.; Ohto, T.; Uozumi, N.; Shimizu, T.
Biochemical properties and pathophysiological roles of cytosolic phospholipase A2s
Biochim. Biophys. Acta
1761
1317-1322
2006
Mus musculus (P47713)
Bailey, R.W.; Olson, E.D.; Vu, M.P.; Brueseke, T.J.; Robertson, L.; Christensen, R.E.; Parker, K.H.; Judd, A.M.; Bell, J.D.
Relationship between membrane physical properties and secretory phospholipase A2 hydrolysis kinetics in S49 cells during ionophore-induced apoptosis
Biophys. J.
93
2350-2362
2007
Mus musculus
Abe, A.; Hiraoka, M.; Shayman, J.A.
Positional specificity of lysosomal phospholipase A2
J. Lipid Res.
47
2268-2279
2006
Mus musculus
Grkovich, A.; Armando, A.; Quehenberger, O.; Dennis, E.A.
TLR-4 mediated group IVA phospholipase A2 activation is phosphatidic acid phosphohydrolase 1 and protein kinase C dependent
Biochim. Biophys. Acta
1791
975-982
2009
Mus musculus
Bate, C.; Tayebi, M.; Williams, A.
Sequestration of free cholesterol in cell membranes by prions correlates with cytoplasmic phospholipase A2 activation
BMC Biol.
6
8
2008
Mus musculus
Burke, J.E.; Dennis, E.A.
Phospholipase A2 biochemistry
Cardiovasc. Drugs Ther.
23
49-59
2009
Apis mellifera, Bitis gabonica, Bos taurus, Crotalus sp., Homo sapiens, Mus musculus, Naja naja, Oryza sativa, Rattus norvegicus, Sus scrofa, Protoparvovirus
Oslund, R.C.; Cermak, N.; Gelb, M.H.
Highly specific and broadly potent inhibitors of mammalian secreted phospholipases A2
J. Med. Chem.
51
4708-4714
2008
Homo sapiens, Mus musculus
Peroutka, R.J.; Elshourbagy, N.; Piech, T.; Butt, T.R.
Enhanced protein expression in mammalian cells using engineered SUMO fusions: secreted phospholipase A2
Protein Sci.
17
1586-1595
2008
Mus musculus (Q9QUL3), Mus musculus
Ma, L.; Uchida, H.; Nagai, J.; Inoue, M.; Aoki, J.; Ueda, H.
Evidence for de novo synthesis of lysophosphatidic acid in the spinal cord through phospholipase A2 and autotaxin in nerve injury-induced neuropathic pain
J. Pharmacol. Exp. Ther.
333
540-546
2010
Mus musculus
Boittin, F.X.; Shapovalov, G.; Hirn, C.; Ruegg, U.T.
Phospholipase A2-derived lysophosphatidylcholine triggers Ca2+ entry in dystrophic skeletal muscle fibers
Biochem. Biophys. Res. Commun.
391
401-406
2010
Mus musculus
Chalbot, S.; Zetterberg, H.; Blennow, K.; Fladby, T.; Grundke-Iqbal, I.; Iqbal, K.
Cerebrospinal fluid secretory Ca2+-dependent phospholipase A2 activity is increased in Alzheimer disease
Clin. Chem.
55
2171-2179
2009
Homo sapiens, Mus musculus
Tai, N.; Kuwabara, K.; Kobayashi, M.; Yamada, K.; Ono, T.; Seno, K.; Gahara, Y.; Ishizaki, J.; Hori, Y.
Cytosolic phospholipase A2 alpha inhibitor, pyrroxyphene, displays anti-arthritic and anti-bone destructive action in a murine arthritis model
Inflamm. Res.
59
53-62
2010
Mus musculus
Bhattacharya, A.; Muller, F.L.; Liu, Y.; Sabia, M.; Liang, H.; Song, W.; Jang, Y.C.; Ran, Q.; Van Remmen, H.
Denervation induces cytosolic phospholipase A2-mediated fatty acid hydroperoxide generation by muscle mitochondria
J. Biol. Chem.
284
46-55
2009
Mus musculus
Burke, J.; Dennis, E.
Phospholipase A2 structure/function, mechanism, and signaling
J. Lipid Res.
50 Suppl
S237-S242
2009
Apis mellifera, Homo sapiens, Mus musculus, Naja naja
Markakis, K.P.; Koropouli, M.K.; Grammenou-Savvoglou, S.; van Winden, E.C.; Dimitriou, A.A.; Demopoulos, C.A.; Tselepis, A.D.; Kotsifaki, E.E.
Implication of lipoprotein associated phospholipase A2 activity on oxidized low density lipoprotein uptake by macrophages
J. Lipid Res.
51
2191-2201
2010
Mus musculus
Ghomashchi, F.; Naika, G.S.; Bollinger, J.G.; Aloulou, A.; Lehr, M.; Leslie, C.C.; Gelb, M.H.
Interfacial kinetic and binding properties of mammalian group IVB phospholipase A2 (cPLA2beta) and comparison with the other cPLA2 isoforms
J. Biol. Chem.
285
36100-36111
2010
Homo sapiens, Mus musculus
Escoffier, J.; Pierre, V.; Jemel, I.; Munch, L.; Boudhraa, Z.; Ray, P.; De Waard, M.; Lambeau, G.; Arnoult, C.
Group X secreted phospholipase A2 specifically decreases sperm motility in mice
J. Cell. Physiol.
226
2601-2609
2011
Mus musculus
Zizza, P.; Iurisci, C.; Bonazzi, M.; Cossart, P.; Leslie, C.C.; Corda, D.; Mariggio, S.
Phospholipase A2IValpha regulates phagocytosis independent of its enzymatic activity
J. Biol. Chem.
287
16849-16859
2012
Mus musculus (P47713)
Naini, S.M.; Choukroun, G.J.; Ryan, J.R.; Hentschel, D.M.; Shah, J.V.; Bonventre, J.V.
Cytosolic phospholipase A2alpha regulates G1 progression through modulating FOXO1 activity
FASEB J.
30
1155-1170
2016
Mus musculus (P47713), Mus musculus, Danio rerio (P50392), Danio rerio
Fisher, A.B.
The phospholipase A2 activity of peroxiredoxin 6
J. Lipid Res.
59
1132-1147
2018
Trematomus bernacchii, Xenopus tropicalis (B1WAZ6), Mus musculus (O08709), Rattus norvegicus (O35244), Bos taurus (O77834), Homo sapiens (P30041), Gallus gallus (Q5ZJF4), Arabidopsis thaliana (Q8S8N6)
Chuang, D.Y.; Simonyi, A.; Kotzbauer, P.T.; Gu, Z.; Sun, G.Y.
Cytosolic phospholipase A2 plays a crucial role in ROS/NO signaling during microglial activation through the lipoxygenase pathway
J. Neuroinflammation
12
199
2015
Mus musculus (P0C871), Mus musculus (P47713), Mus musculus
EXTERNAL LINKS (specific for EC-Number 3.1.1.4)
Transporter Classification Database (TCDB): 1.N.2.1.6, 1.B.84.1.6, 1.B.84.1.5, 1.B.84.1.3, 1.B.84.1.1, 1.B.84.1.4, 1.B.84.1.2
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