Information on EC 3.1.4.11 - phosphoinositide phospholipase C and Organism(s) Homo sapiens

for references in articles please use BRENDA:EC3.1.4.11
Word Map on EC 3.1.4.11
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Select one or more organisms in this record:
This record set is specific for:
Homo sapiens
Show additional data
Do not include text mining results
Include (text mining) results
Include results (AMENDA + additional results, but less precise)


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


The taxonomic range for the selected organisms is: Homo sapiens

EC NUMBER
COMMENTARY hide
3.1.4.11
-
RECOMMENDED NAME
GeneOntology No.
phosphoinositide phospholipase C
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of phosphoric ester
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
D-myo-inositol (1,4,5)-trisphosphate biosynthesis
-
-
D-myo-inositol-5-phosphate metabolism
-
-
phosphatidate metabolism, as a signaling molecule
-
-
phospholipases
-
-
Inositol phosphate metabolism
-
-
Metabolic pathways
-
-
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
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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
-
-
-
-
?
1-acyl-2-linoleoylphosphatidylinositol + H2O
?
show the reaction diagram
-
-
-
-
?
1-phosphatidyl-1D-myo-inositol + H2O
1D-myo-inositol 1-phosphate
show the reaction diagram
-
-
in almost equal amounts with 1D-myo-inositol 1,2-cyclic phosphate
-
?
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
-
-
-
-
?
phosphatidylinositol + H2O
1D-myo-inositol 1-phosphate
show the reaction diagram
-
-
in vitro myo-inositol 1,2-cyclic phosphate also formed
-
?
phosphatidylinositol + H2O
1D-myo-inositol-1-phosphate
show the reaction diagram
-
-
in vitro 1D-myo-inositol-1,2-cyclic phosphate is also formed
-
?
phosphatidylinositol + H2O
?
show the reaction diagram
phosphatidylinositol + H2O
diacylglycerol + 1D-myo-inositol 1-phosphate
show the reaction diagram
-
Pi-PLC (membrane) and Pi-PLC (cytosol) are specific for this substrate
-
-
?
phosphatidylinositol 4,5-bisphosphate
inositol 1,4,5-trisphosphate
show the reaction diagram
-
demonstration of the role of PLC in Ca2+-induced inactivation of TRPV6
-
-
?
phosphatidylinositol 4,5-bisphosphate + H2O
D-myo-inositol 1,4,5-trisphosphate + diacylglycerol
show the reaction diagram
phosphatidylinositol 4-phosphate
?
show the reaction diagram
additional information
?
-
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
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
(NH4)2SO4
-
high salt concentration, (NH4)2SO4, 2 M, dissociates the high molecular weight form yielding the low molecular form and increasing the specific activity
Mg2+
-
no requirement for the membrane enzyme solubilized with sodium cholate, activates the membrane enzyme after solubilization in octyl glucoside with maximal activity at 0.1 mM
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1-(6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
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
-
compound 48/80, oligomeric mixture of condensation products of N-methyl-p-methoxyphenethylamine and formaldehyde
adriamycin
-
-
amentoflavone
-
-
camphor
-
inhibit the phospholipase C signaling
choline plasmalogen
-
18.5% of choline plasmalogen is needed for 50% inhibition
cinnamaldehyde
-
inhibit the phospholipase C signaling
deoxycholate
-
weak inhibition. Concentration of 2 mM inhibits the phospholipase C activity in all fractions by 20-30%
edelfosine
-
ET-18-OCH3, also inhibits Ca2+-induced inactivation of TRPV6
lysocholine plasmalogen
-
8.5% of choline plasmalogen is needed for 50% inhibition
-
lysophosphatidylcholine
-
50% inhibition is produced by 7% molar
menthol
-
inhibit the phospholipase C signaling
neomycin
-
-
oleoyl sphingomyelin
-
-
phosphatidylcholine
-
low effect, 50% inhibition is produced by 18% molar egg phosphatidylcholine
phosphatidylethanolamine
-
25% inhibition, in presence of 0.001 mM Ca2+
phosphatidylserine
-
50% inhibition, in presence of 0.001 mM Ca2+
sphingomyelin
-
50% inhibition at 6.5% molar, and 97% at 20% molar
sphingosylphosphocholine
-
-
stearoyl sphingomyelin
-
-
U-73122
U-73343
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-nonenal
-
at 1-100 nM: activates PL-C in DMSO-differentiated HL-60 cells, at 1-10 nM: activates PL-C in undifferentiated HL-60 cells
4-hydroxynonenal
-
at 10-1000 nM, activates PL-C in both undifferentiated and DMSO-differentiated HL-60 cells
ARGHAP6
a GTPase-activating protein for RhoA. Activates PLC-gamma1 and increases the Vmax of PLC-beta1 and enhances its response to Ca2+ stimulation. ARHGAP6 protein binds to and up-regulates PLC-beta1 both under in vitro and in vivo conditions
-
beta-estradiol
-
-
Ca2+
-
requirement of all PLCs, the delta isoenzymes are most sensitive to Ca2+
diacylglycerol
-
the addition of choline phospholipids containing two long hydrophobic chains or choline lysophospholipids containing one long hydrophobic chain produced a total inhibition of the activation which had been produced by diacylglycerol
Epidermal growth factor
epidermal growth factor stimulates PI-PLC activity of both splice variants
G protein alpha12
-
activates PLC-epsilon
-
Gbetagamma
-
G protein betagamma subunits, the reconstituted enzymes, like wild-type PLC-beta2, are activated by Gbetagamma
-
phosphatidylethanolamine
phosphatidylserine
-
stimulation in presence of 1 mM Ca2+
PTEN
-
ubiquitously expressed tumor suppressor. PTEN overexpression results in changes in cellular phospholipid levels. Increased PTEN expression in unstimulated MCF-7 breast cancer cells results in a 51% increase in phosphatidic acid, with a decrease in phosphatidylcholine, PTEN activates also phospholipase D (PLD). PTEN induces translocation of PLC-gamma from the cytosol to the membrane
-
Ras
-
activator of PLC-epsilon
-
spermine
-
sphingosine 1-phosphate
sphingosine-1-phosphate stimulates PI-PLC activity of both splice variants
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.1 - 0.15
1-phosphatidyl-1D-myo-inositol
-
-
0.0123 - 0.0391
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
0.143
phosphatidylinositol
-
-
0.031
phosphatidylinositol 4,5-bisphosphate
-
-
0.031
phosphatidylinositol 4-phosphate
-
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.001
phosphatidylserine
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.006
1-(6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
Homo sapiens;
-
significant inhibition of PLC-beta with IC50: 0.006 mM, little effect on PLC-beta1, PLC-beta3, or PLC-beta4
0.001 - 0.0666
3beta-hydroxy-27-(E)-feruloyloxyolea-12-en-28-oic acid
0.0028 - 0.0355
3beta-hydroxy-27-(E)-feruloyloxyurs-12-en-28-oic acid
0.0021 - 0.0503
3beta-hydroxy-27-(Z)-feruloyloxyolea-12-en-28-oic acid
0.0009 - 0.0441
3beta-hydroxy-27-(Z)-feruloyloxyurs-12-en-28-oic acid
0.0836
3beta-hydroxy-27-4-(E)-2'-dihydrocoumaroyloxyurs-12-en-28-oic acid
Homo sapiens;
-
pH 7.0, 37°C
0.0008 - 0.0524
3beta-hydroxy-27-4-(E)-coumaroyloxyolea-12-en-28-oic acid
0.0009 - 0.0737
3beta-hydroxy-27-4-(E)-coumaroyloxyurs-12-en-28-oic acid
0.1213
3beta-hydroxy-27-4-(E)-coumaroyloxyurs-12-en-28-oic methyl ester
Homo sapiens;
-
pH 7.0, 37°C
0.0017 - 0.059
3beta-hydroxy-27-4-(Z)-coumaroyloxyolea-12-en-28-oic acid
0.0014 - 0.0733
3beta-hydroxy-27-4-(Z)-coumaroyloxyurs-12-en-28-oic acid
0.0001 - 0.0246
adriamycin
0.029
amentoflavone
Homo sapiens;
-
pH 7.0, 37°C
additional information
additional information
Homo sapiens;
-
IC50 value is less than 0.1 microM for adriamycin in MCF7 cells, pH 7.0, 37°C; the IC50 values for 3beta,7'-diacetoxy-27-4-(E)-coumaroyloxyurs-12-en-28-oic acid, 3beta-hydroxyurs-12-en-28-oic 4-(E)-coumaroyl ester, 3beta,27-dihydroxyurs-12-en-28-oic acid, 3beta-4-(E)-coumaroyloxyurs-12-en-28-oic acid, and 4-(E)-coumaric acidare above 0.250 mM, pH 7.0, 37°C
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.5784
-
-
136
-
HeLa S3 cells; hydrolysis of phosphatidylinositol 4,5-bisphosphate
additional information
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5
-
hydrolysis of phosphatidylinositol 4,5-bisphosphate, in presence of sodium deoxycholate, enzyme from plasma membrane
6.7
assay at
6.8
-
hydrolysis of phosphatidylinositol 4,5-diphosphate
7
-
Pi-PLC (cytosol); Pi-PLC (membrane) solubilized with sodium cholate
7 - 7.5
-
pH 7.0: about 30% of maximal activity, pH 7.5: about 75% of maximal activity, hydrolysis of phosphatidylinositol 4,5-diphosphate
7.3
-
hydrolysis of phosphatidylinositol 4,5-bisphosphate, in presence of sodium deoxycholate, enzyme from cytoplasm
7.4
-
platelet enzyme
7.8
-
assay at
8
-
Pi-PLC (membrane) solubilized with octyl glucoside
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.7 - 8
-
pH 5.7: about 70% of maximal activity, pH 8.0: about 50% of maximal activity
6 - 7
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
assay at
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.2
-
purified Pi-PLC (cytosol)
9 - 9.2
-
purified Pi-PLC (membrane)
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
highest expression level of PLCbeta1 in brain, especially in the amygdala, caudate nucleus and hippocampus
Manually annotated by BRENDA team
-
anaplastic, PLC-eta2; PLC-eta2
Manually annotated by BRENDA team
highest expression level of PLCbeta1 in brain, especially in the amygdala, caudate nucleus and hippocampus
Manually annotated by BRENDA team
-
isoenzyme PI-PLC-ß1
Manually annotated by BRENDA team
-
W-138 fibroblasts, expression of PLC delta isoenzymes
Manually annotated by BRENDA team
-
TRPV6-expressing cell
Manually annotated by BRENDA team
PLC epsilon1b is enriched in
Manually annotated by BRENDA team
-
PLC-eta1; PLC-eta2
Manually annotated by BRENDA team
-
metastases
Manually annotated by BRENDA team
-
PLC-beta2 may be responsible, by modifying the phosphoinositide pools, for the changes of cytoskeleton architecture that take place during the acquisition of migration capability of differentiating promyelocytes
Manually annotated by BRENDA team
-
PLC-eta1; PLC-eta2
Manually annotated by BRENDA team
-
PLC-eta1; PLC-eta2
Manually annotated by BRENDA team
-
PLC-eta1; PLC-eta2
Manually annotated by BRENDA team
-
PLC-eta1; PLC-eta2
Manually annotated by BRENDA team
PLC epsilon1b is enriched in
Manually annotated by BRENDA team
-
PLC-eta1; PLC-eta2
Manually annotated by BRENDA team
only PLC epsilon1a, splice variant PLC epsilon1b can not be detected
Manually annotated by BRENDA team
only PLC epsilon1a, splice variant PLC epsilon1b can not be detected
Manually annotated by BRENDA team
only PLC epsilon1a, splice variant PLC epsilon1b can not be detected
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
inner side, PLCbeta1
-
Manually annotated by BRENDA team
additional information
PDB
SCOP
CATH
UNIPROT
ORGANISM
Homo sapiens;
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
18000
-
purified Pi-PLC (membrane) has a molecular weight of about 18000, SDS-PAGE or gel filtration
57000
-
purified Pi-PLC (cytosol), SDS-PAGE or gel filtration
110000
-
gel filtration
115000
x * 115000, calculated from sequence
158500
-
gel filtration
230000
-
x * 230000, x * 260000, two alternatively spliced PLC-epsilon forms
260000
-
x * 230000, x * 260000, two alternatively spliced PLC-epsilon forms
additional information
-
PI-PLC, can be resolved into two peaks of activity of high M (60000-70000) and low M (16000-18000)
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
-
-
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
both PI-PLC (membrane) and PI-PLC (cytosol) are fairly stable proteins when incubated for short periods of time (30 min) to a wide range of pH. PI-PLC (membrane) shows a fall of about 20-30% activity below pH 5.0 and is stable to alkaline pH up to 11
285237
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
confirmed by Coomassie blue staining after SDS-PAGE
-
enzyme from platelet membrane
-
preparation of nuclei, method development
recombinant PLCgamma2, expressed in Sf9 cells
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed cDNA constructs encoding PLC-beta2 fragments of different lengths in COS-7 cell. Separate expression of amino- and C-terminal fragments of enzyme, requirements for reconstitution of enzyme activity and activation by Gbetagamma
-
expression in baculovirus-infected insect cells
-
expression in COS or HEK293 cells
expression in COS-7 cells
expression in Escherichia coli
-
two distinct PLCbeta1 cDNAs, PLCbeta1a and b, generated through alternative splicing at their 3’ end, sequencing, overexpression in CHO and PC12 cells, gene structure, located on chromosome 20
wild-type and mutant PLCgamma2, expression in DT40 B-cells
-
wild-type and mutant PLCgamma2, expression in DT40 cells, A431 cells and in Sf9 cells
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
R257H
-
increased expression of mutant PLC delta1 in patients with coronary spastic angina
R564A/R672A
-
PLCgamma2 SH2 domain double mutant
T753F
PLCgamma2 mutant
T753F/T759F
T759F
PLCgamma2 mutant
Y1217F
phosphorylation site mutant
Y753F
phosphorylation site mutant
Y759F
phosphorylation site mutant
Y783F
-
PLC construct
additional information
-
constructs of PLCgamma2 containing either PLCdelta1 PH domain or the N-terminal tag of Lyn are targeted to the plasma membrane, recombinant wild-type PLCgamma2 not
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
-
PLCgamma1 inhibitors may have potential therapeutic applications for the clinical treatment of tumor metastasis
medicine
pharmacology
-
showing that pharmacological inhibition of PLC enhances intestinal Ca2+ transport. This raises the possibility that pharmacological tools targeting PLC can be used to enhance intestinal Ca2+ absorption. Given the prevalence of osteoporosis, which generally comes with negative Ca2+ balance, PLC can be a clinically relevant pharmacological target in the future