Information on EC 3.1.4.11 - phosphoinositide phospholipase C

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY hide
3.1.4.11
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RECOMMENDED NAME
GeneOntology No.
phosphoinositide phospholipase C
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O = 1D-myo-inositol 1,4,5-trisphosphate + diacylglycerol
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of phosphoric ester
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
D-myo-inositol (1,4,5)-trisphosphate biosynthesis
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D-myo-inositol-5-phosphate metabolism
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Inositol phosphate metabolism
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Metabolic pathways
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phosphatidate metabolism, as a signaling molecule
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phospholipases
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SYSTEMATIC NAME
IUBMB Comments
1-phosphatidyl-1D-myo-inositol-4,5-bisphosphate inositoltrisphosphohydrolase
These enzymes form some of the cyclic phosphate Ins(cyclic1,2)P(4,5)P2 as well as Ins(1,4,5)P3. They show activity towards phosphatidylinositol, i.e., the activity of EC 4.6.1.13, phosphatidylinositol diacylglycerol-lyase, in vitro at high [Ca2+]. Four beta-isoforms regulated by G-proteins, two gamma-forms regulated by tyrosine kinases, four delta-forms regulated at least in part by calcium and an epsilon-form, probably regulated by the oncogene ras, have been found.
CAS REGISTRY NUMBER
COMMENTARY hide
37213-51-7
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
cauliflower
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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UniProt
Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
serotype C; var. gattii serotype B; var. grubii serotype A
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Manually annotated by BRENDA team
serotype C; var. gattii serotype B; var. grubii serotype A
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Manually annotated by BRENDA team
DsPLC2, 6 weeks old
SwissProt
Manually annotated by BRENDA team
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Manually annotated by BRENDA team
adult
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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SwissProt
Manually annotated by BRENDA team
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SwissProt
Manually annotated by BRENDA team
C57BL strain
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Manually annotated by BRENDA team
Mus musculus C57BL/6
C57BL/6
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Manually annotated by BRENDA team
Lam
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Manually annotated by BRENDA team
daffodil
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-
Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
Rattus norvegicus PLC-delta1
PLC-delta1
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-
Manually annotated by BRENDA team
Rattus norvegicus PLCepsilon
PLCepsilon
SwissProt
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
Sprague-Dawley
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Manually annotated by BRENDA team
PLC1p
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Manually annotated by BRENDA team
several strains, 4 genes encoding 1 bacterial type PI-PLC and 3 eukaryotic type PI-PLCs
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Manually annotated by BRENDA team
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SwissProt
Manually annotated by BRENDA team
L. elite inbred line Ye 7922
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
1-acyl-2-arachidonoylphosphatidylinositol + H2O
?
show the reaction diagram
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?
1-acyl-2-linoleoylphosphatidylinositol + H2O
?
show the reaction diagram
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?
1-phosphatidyl-1D-myo-inositol
1D-myo-inositol 1-phosphate + diacylglycerol
show the reaction diagram
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in almost equal amounts with 1D-myo-inositol 1,2-cyclic phosphate
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?
1-phosphatidyl-1D-myo-inositol + H2O
1D-myo-inositol 1-phosphate
show the reaction diagram
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in almost equal amounts with 1D-myo-inositol 1,2-cyclic phosphate
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?
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O
1D-myo-inositol 1,4,5-trisphosphate + diacylglycerol
show the reaction diagram
arachidonoyl-phosphatidylinositol + H2O
1,2-diarachidonoyl-sn-glycerol + 1D-myo-inositol 1-phosphate
show the reaction diagram
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?
arachidonoylphosphatidylinositol + H2O
myo-inositol 1-phosphate + 1,2-diarachidonoylglycerol
show the reaction diagram
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?
diarachidonoylphosphatidylinositol + H2O
1,2-diacylglycerol + 1D-myo-inositol 1-phosphate
show the reaction diagram
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a mixture of 86% myoinositol 1-phosphate and 14% myoinositol 1,2-cyclic phosphate
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?
dibutyrylphosphatidylinositol + H2O
?
show the reaction diagram
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?
glycosylphosphatidylinositol + H2O
?
show the reaction diagram
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catalytic mechanism
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?
GPI-renal dipeptidase
?
show the reaction diagram
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?
phosphatidylinositol + H2O
1,2-diacylglycerol + 1D-myo-inositol 1-phosphate
show the reaction diagram
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1D-myo-inositol 1,2-cyclic phosphate is also formed
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?
phosphatidylinositol + H2O
1D-myo-inositol 1-phosphate
show the reaction diagram
phosphatidylinositol + H2O
1D-myo-inositol 1-phosphate + diacylglycerol
show the reaction diagram
phosphatidylinositol + H2O
1D-myo-inositol 1-phosphate + glycerophosphoinositol + phosphate
show the reaction diagram
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ratio between products decreased with increasing pH, 1D-myo-inositol 1,2-cyclic phosphate is also formed
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?
phosphatidylinositol + H2O
1D-myo-inositol-1-phosphate
show the reaction diagram
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in vitro 1D-myo-inositol-1,2-cyclic phosphate is also formed
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?
phosphatidylinositol + H2O
?
show the reaction diagram
phosphatidylinositol + H2O
diacylglycerol + 1D-myo-inositol 1-phosphate
show the reaction diagram
phosphatidylinositol + H2O
diacylglycerol + inositol 1,2-(cyclic)-phosphate
show the reaction diagram
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?
phosphatidylinositol + H2O
diacylglycerol + myo-inositol 1-phosphate
show the reaction diagram
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phosphatidylinositol-specific, catalytic mechanism
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?
phosphatidylinositol + H2O
myo-inositol 1-phosphate + diacylglycerol
show the reaction diagram
phosphatidylinositol 4,5-bisphosphate
inositol 1,4,5-trisphosphate
show the reaction diagram
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demonstration of the role of PLC in Ca2+-induced inactivation of TRPV6
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?
phosphatidylinositol 4,5-bisphosphate + H2O
?
show the reaction diagram
phosphatidylinositol 4,5-bisphosphate + H2O
D-myo-inositol 1,4,5-trisphosphate + diacylglycerol
show the reaction diagram
phosphatidylinositol 4,5-bisphosphate + H2O
diacylglycerol + 1D-myo-inositol 1,4,5-triphosphate
show the reaction diagram
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PLC4 and PLC6 encode catalytically active enzymes that convert phosphatidylinositol into diacylglycerol
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?
phosphatidylinositol 4-phosphate
?
show the reaction diagram
phosphatidylinositol 4-phosphate + H2O
1D-myo-inositol 4,5-bisphosphate + diacylglycerol
show the reaction diagram
phosphatidylinositol 4-phosphate + H2O
?
show the reaction diagram
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O
1D-myo-inositol 1,4,5-trisphosphate + diacylglycerol
show the reaction diagram
phosphatidylinositol 4,5-bisphosphate + H2O
D-myo-inositol 1,4,5-trisphosphate + diacylglycerol
show the reaction diagram
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the enzyme generates two second messengers: D-myo-inositol 1,4,5-trisphosphate and diacylglycerol
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?
additional information
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
(NH4)2SO4
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high salt concentration, (NH4)2SO4, 2 M, dissociates the high molecular weight form yielding the low molecular form and increasing the specific activity
CaCl2
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stimulates at pH 5.5, pH dependent
MgCl2
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stimulates at pH 5.5, but less active than CaCl2, pH dependent
Zn2+
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calcium, manganese, magnesium and zinc ions, in decreasing order of effectiveness, all partly restore the activity of the dialysed enzyme at a concentration of 2 mM. In each case 4 mM cation is less effective than 2 mM
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(1 -[6-[[17-beta-3-methoxyestra-1,3,5(10)-trien-17-yl]amino] hexyl]-1H-pyrrole-2,5-dione)
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1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid
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1-(6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine
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potent inhibitor
1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphorylcholine
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histamine-induced elevation of plasma noradrenaline and adrenaline is dose-dependently reduced by ET-18-OCH3
3beta,27-dihydroxyurs-12-en-28-oic acid
3beta,7'-diacetoxy-27- 4-(E)-coumaroyloxyurs-12-en-28-oic acid
3beta-4-(E)-coumaroyloxyurs-12-en-28-oic acid
3beta-hydroxy-27-(E)-feruloyloxyolea-12-en-28-oic acid
3beta-hydroxy-27-(E)-feruloyloxyurs-12-en-28-oic acid
3beta-hydroxy-27-(Z)-feruloyloxyolea-12-en-28-oic acid
3beta-hydroxy-27-(Z)-feruloyloxyurs-12-en-28-oic acid
3beta-hydroxy-27-4-(E)-2'-dihydrocoumaroyloxyurs-12-en-28-oic acid
3beta-hydroxy-27-4-(E)-coumaroyloxyolea-12-en-28-oic acid
3beta-hydroxy-27-4-(E)-coumaroyloxyurs-12-en-28-oic acid
3beta-hydroxy-27-4-(E)-coumaroyloxyurs-12-en-28-oic methyl ester
3beta-hydroxy-27-4-(Z)-coumaroyloxyolea-12-en-28-oic acid
3beta-hydroxy-27-4-(Z)-coumaroyloxyurs-12-en-28-oic acid
3beta-hydroxyurs-12-en-28-oic 4-(E)-coumaroyl ester
4-(E)-coumaric acid
48/80
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compound 48/80, oligomeric mixture of condensation products of N-methyl-p-methoxyphenethylamine and formaldehyde
adriamycin
aggregated amyloid beta protein
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full-length Abeta 1-40, aggregated form inhibits Ca2+-regulated phosphoinositide degradation by cytosolic and membrane-bound PLC by 30-40%, inhibitor may interact with the Ca2+-binding site of enzyme, no inhibition by nonaggregated soluble full-length amyloid beta protein
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amentoflavone
anionic amphipathic substances
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ATP
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1-5 mM
Ba2+
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at 0.05-5 mM, inhibition is completely reversed by Ca2+
Blood lipoprotein
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enzyme is strongly inhibited by blood plasma, serum and blood lipoproteins
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Blood plasma
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enzyme is strongly inhibited by blood plasma, serum and blood lipoproteins
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Blood serum
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enzyme is strongly inhibited by blood plasma, serum and blood lipoproteins
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CaCl2
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above 0.4 mM, pH 7.0
camphor
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inhibit the phospholipase C signaling
chlorpromazine
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at pH 7.0
cholic acid
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inhibits PLC-beta1 activity
choline plasmalogen
Cinchocaine
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at pH 7.0
cinnamaldehyde
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inhibit the phospholipase C signaling
CRM-51006
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i.e. 1-(3-ethyl-2,4-dihydroxyphenyl)-2-methylhexan-1-one
Cu2+
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is effective only after preincubation, suggesting that the effect of the metal may be derived from lipid peroxidation due to Cu2+-induced oxyradical production
CuCl2
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0.1 mM, 53% inhibition
deoxycholate
dibromo 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid
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Diethyl ether
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25% v/v, 22% inhibition
edelfosin
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edelfosine
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ET-18-OCH3, also inhibits Ca2+-induced inactivation of TRPV6
guanosine 5'-[gamma-thio]triphosphate
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activity is downregulated by 1-10 mM guanosine 5'-[gamma-thio]triphosphate
iodoacetamide
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1.0 mM, 16% inhibition
La3+
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at 0.05-5 mM, inhibition is completely reversed by Ca2+
lysocholine plasmalogen
lysophosphatidylcholine
menthol
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inhibit the phospholipase C signaling
Mn2+
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at 0.05-5 mM, inhibition is completely reversed by Ca2+
NaCl
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inhibits phosphatidylinositol hydrolysis of low molecular weight PLC. Conversely, PIP2 hydrolysis is stimulated by increasing concentrations of NaCl
NEM
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5 mM, 34% inhibition
neomycin
nod factor
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activity is decreased by up to 64% in the presence of increasing concentrations of Nod factors
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Octadecylamine
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decreases the film pressure of the phosphatidylinositol monolayer at an air/water interface at which cut-off occurs, as well as the rate of hydrolysis below this pressures
oleoyl sphingomyelin
Palmitoylcholine
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decreases the film pressure of the phosphatidylinositol monolayer at an air/water interface at which cut-off occurs, as well as the rate of hydrolysis below this pressures
Phenylmercuriacetate
phosphatidylcholine
phosphatidylethanolamine
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25% inhibition, in presence of 0.001 mM Ca2+
phosphatidylserine
reduced glutathione
Sodium deoxycholate
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activates from 0.05% to 0.08%, but severely inhibits activity above 0.08%, no activity at 0.3%
sphingomyelin
sphingosylphosphocholine
Sr2+
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at higher concentrations (greater than 0.25 mM) markedly inhibited, inhibition is completely reversed by Ca2+
stearoyl sphingomyelin
substance 48/80
inhibition is more pronounced with phosphatidylinositol as substrate than with 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
Triton X-100
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inhibits PLC-beta1 activity
U-73122
U-73343
U73122
additional information