Information on EC 2.7.1.127 - inositol-trisphosphate 3-kinase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.7.1.127
-
RECOMMENDED NAME
GeneOntology No.
inositol-trisphosphate 3-kinase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + 1D-myo-inositol 1,4,5-trisphosphate = ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
-
-
-
-
phospho-group transfer
Phosphorylation
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
1D-myo-inositol hexakisphosphate biosynthesis I (from Ins(1,4,5)P3)
-
-
1D-myo-inositol hexakisphosphate biosynthesis II (mammalian)
-
-
D-myo-inositol (1,3,4)-trisphosphate biosynthesis
-
-
Inositol phosphate metabolism
-
-
Metabolic pathways
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:1D-myo-inositol-1,4,5-trisphosphate 3-phosphotransferase
Activated by Ca2+. Three isoforms have been shown to exist [3].
CAS REGISTRY NUMBER
COMMENTARY hide
106283-10-7
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
at least 3 isoforms: A, B and C
-
-
Manually annotated by BRENDA team
C75BL/6 mice
-
-
Manually annotated by BRENDA team
strain BY4741
-
-
Manually annotated by BRENDA team
strain BY4741
-
-
Manually annotated by BRENDA team
adult
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + 1D-myo-inositol 1,4,5-triphosphate
ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate
show the reaction diagram
-
-
-
r
ATP + 1D-myo-inositol 1,4,5-trisphosphate
ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate
show the reaction diagram
ATP + 1D-myo-inositol 2,4,5-trisphosphate
ADP + 1D-myo-inositol 2,4,5,6-tetrakisphosphate
show the reaction diagram
-
recombinant, catalytically active fragment of isoform C, in the presence of Ins(1,3,4,5)P4, authentic side activity of isoform C
-
?
ATP + D-2-deoxy-myo-inositol 1,4,5-trisphosphate
ADP + D-2-deoxy-myo-inositol 1,3,4,5-tetrakisphosphate
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
ATP + 1D-myo-inositol 1,4,5-triphosphate
ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate
show the reaction diagram
Q80ZG2
-
-
-
r
ATP + 1D-myo-inositol 1,4,5-trisphosphate
ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Calmodulin
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
assay in presence of Triton X-100 and ethylene glycol bis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2'S)-1D-1,2-O-[(2'-phosphoryloxy)propane-1',3'-diyl]-myo-inositol 4,5-bisphosphate
-
synthetic bicyclic inositol trisphosphate S epimer, IC50 is 0.156 mM
1D-myo-inositol 1,3,4,5-tetrakisphosphate
1D-myo-inositol 1,4,5-trisphosphate
2,3-diphosphoglycerate
-
-
3',4',7,8-tetrahydroxyflavone
aurintricarboxylic acid
chlorogenic acid
chlorpromazine
D-2-deoxyinositol 1,3,4,5-tetrakisphosphate
-
strong inhibition of isozyme A, IC50 is 0.0054 mM
D-2-deoxyinositol 1,4,5-trisphosphate
-
strong inhibition of isozyme A, IC50 is 0.0017 mM
D-3-deoxyinositol 1,4,6-trisphosphate
-
strong inhibition of isozyme A, IC50 is 0.0014 mM
D-6-deoxyinositol 1,3,4,5-tetrakisphosphate
-
strong inhibition of isozyme A, IC50 is 0.0051 mM
D-myo-inositol 1,4,5-trisphosphate
-
strong inhibition, purified recombinant enzyme, IC50 value is 0.003 mM in absence of Ca2+
D-myo-inositol 2,4,5-trisphosphate
-
IC50 is 0.117 mM
D-scyllo-inositol 1,2,3,4-tetrakisphosphate
-
purified recombinant enzyme, IC50 value is above 0.1 mM in absence of Ca2+
D-scyllo-inositol 1,2,4-trisphosphate
-
purified recombinant enzyme, IC50 value is 0.044 mM in absence of Ca2+
ellagic acid
epicatechin-3-gallate
epigallocatechin-3-gallate
F-actin
-
-
gossypol
heparin
-
mixed-type inhibition
hypericin
inositol phosphate
-
inhibitory effects of all possible 38 regioisomers of synthetic inositol phosphates, only inositol trisphosphates and tetrakisphosphates inhibit, not or very weak: inositol monophosphates, bisphosphates and pentakisphosphates, the recognition of myo-inositol phosphate regioisomers is highly structure-selective
KN-62
KN-93
L-scyllo-inositol 1,2,3,4-tetrakisphosphate
-
purified recombinant enzyme, IC50 value is above 0.1 mM in absence of Ca2+
L-scyllo-inositol 1,2,4-trisphosphate
-
purified recombinant enzyme, IC50 value is 0.006 mM in absence of Ca2+
myricetin
N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide
protein kinase A
-
isoforms A and B are differentially regulated via phosphorylation by the cAMP-dependent protein kinase, isoform A: stimulation in the presence or absence of Ca2+/calmodulin, isoform B: no effect on activity in the absence of Ca2+/calmodulin, 45% inhibition in the presence of Ca2+/calmodulin
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Protein kinase C
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quercetin
Rose bengal
RS-20
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calmodulin antagonist, prevents the Ca2+/calmodulin-mediated activation
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scyllo-inositol 1,2,3,5-tetrakisphosphate
-
weak inhibition, purified recombinant enzyme, IC50 value is 0.028 mM in absence of Ca2+
scyllo-inositol 1,2,3-trisphosphate
-
purified recombinant enzyme, IC50 value is 0.027 mM in absence of Ca2+
scyllo-inositol 1,2,4,5-tetrakisphosphate
-
weak inhibition, purified recombinant enzyme, IC50 value is 0.039 mM in absence of Ca2+
scyllo-inositol 1,3,5-trisphosphate
-
purified recombinant enzyme, IC50 value is 0.090 mM in absence of Ca2+
TSH
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thyroid-stimulating hormone, inhibits at a physiological concentration, inhibition is mimicked by dibuturyl cyclic AMP and forskolin, mechanism
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane
-
5-HT2 agonist DOI, 3fold activation
12-O-tetradecanoyl phorbol 13-acetate
12-O-tetradecanoylphorbol-13-acetate
1D-myo-inositol 1,3,4,5-tetrakisphosphate
-
recombinant, catalytically active fragment of isoform C, allosteric product activation in the absence of Ca2+/calmodulin, which per se activates enzyme and abolishes the allosteric effect
5-HT
-
2-3fold activation
Ca2+/calmodulin
for enzyme activation, Ca2+/calmodulin, 2.15 microg/ml calmodulin and 10-20 microM free CaCl2 is added to the assay mixture
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Ca2+/CaM-dependent kinase II
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Calmodulin
CaM kinase II
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cAMP-dependent protein kinase
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Carbachol
isoproterenol
-
activates
phorbol 12,13-dibutyrate
-
activates
protein kinase A
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Protein kinase C
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serotonin
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potentiates enzyme activity mediated through the activation of 5-HT2 receptors, enzyme up-regulation occurs through activation of PLC-coupled serotoninergic receptors and requires the phosphorylation of the enzyme by the ubiquitous multimeric protein kinase CaMKII
Triton X-100
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Antagonizing the effect of all inhibitors identified with GgIP3K-A. When 0.2% Triton X-100 is added to assays containing the respective inhibitors at IC50, the previous inhibition of GgIP3K-A is immediately reversed by an extent between 49 and 100%
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0002 - 0.011
1D-myo-inositol 1,4,5-trisphosphate
0.0015 - 0.005
1D-myo-inositol 2,4,5-trisphosphate
0.033 - 2.5
ATP
0.0002 - 0.0017
InsP3
additional information
additional information
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000096 - 0.0001
aurintricarboxylic acid
0.000043 - 0.00006
ellagic acid
0.00002 - 0.000043
epicatechin-3-gallate
0.000059
epigallocatechin-3-gallate
-
IP3K-A, mixed-type with respect to ATP; IP3K-A, non-competitive with respect to Ins(1,4,5)P3
0.000061 - 0.000077
gossypol
0.000074 - 0.000156
hypericin
0.12
N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide
-
-
0.000197 - 0.000312
quercetin
additional information
additional information
-
dose-response curve of antiproliferative synthetic and plant polyphenolics inhibition
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.156
(2'S)-1D-1,2-O-[(2'-phosphoryloxy)propane-1',3'-diyl]-myo-inositol 4,5-bisphosphate
Rattus norvegicus
-
synthetic bicyclic inositol trisphosphate S epimer, IC50 is 0.156 mM
0.013
1D-myo-inositol 1,3,4,5-tetrakisphosphate
Rattus norvegicus
-
product inhibition, IC50 is 0.013 mM
0.00018 - 0.0843
3',4',7,8-tetrahydroxyflavone
0.000062 - 0.00015
aurintricarboxylic acid
0.0054
D-2-deoxyinositol 1,3,4,5-tetrakisphosphate
Rattus norvegicus
-
strong inhibition of isozyme A, IC50 is 0.0054 mM
0.0017
D-2-deoxyinositol 1,4,5-trisphosphate
Rattus norvegicus
-
strong inhibition of isozyme A, IC50 is 0.0017 mM
0.0014
D-3-deoxyinositol 1,4,6-trisphosphate
Rattus norvegicus
-
strong inhibition of isozyme A, IC50 is 0.0014 mM
0.0051
D-6-deoxyinositol 1,3,4,5-tetrakisphosphate
Rattus norvegicus
-
strong inhibition of isozyme A, IC50 is 0.0051 mM
0.003
D-myo-inositol 1,4,5-trisphosphate
Rattus norvegicus
-
strong inhibition, purified recombinant enzyme, IC50 value is 0.003 mM in absence of Ca2+
0.117
D-myo-inositol 2,4,5-trisphosphate
Rattus norvegicus
-
IC50 is 0.117 mM
0.1
D-scyllo-inositol 1,2,3,4-tetrakisphosphate
Rattus norvegicus
-
purified recombinant enzyme, IC50 value is above 0.1 mM in absence of Ca2+
0.044
D-scyllo-inositol 1,2,4-trisphosphate
Rattus norvegicus
-
purified recombinant enzyme, IC50 value is 0.044 mM in absence of Ca2+
0.000036 - 0.00069
ellagic acid
0.000094 - 0.00056
epicatechin-3-gallate
0.00012 - 0.00278
epigallocatechin-3-gallate
0.000058 - 0.00034
gossypol
0.00017 - 0.00021
hypericin
0.1
L-scyllo-inositol 1,2,3,4-tetrakisphosphate
Rattus norvegicus
-
purified recombinant enzyme, IC50 value is above 0.1 mM in absence of Ca2+
0.006
L-scyllo-inositol 1,2,4-trisphosphate
Rattus norvegicus
-
purified recombinant enzyme, IC50 value is 0.006 mM in absence of Ca2+
0.00015 - 0.0042
myricetin
0.00018 - 0.00125
quercetin
0.00017 - 0.00312
Rose bengal
0.028
scyllo-inositol 1,2,3,5-tetrakisphosphate
Rattus norvegicus
-
weak inhibition, purified recombinant enzyme, IC50 value is 0.028 mM in absence of Ca2+
0.027
scyllo-inositol 1,2,3-trisphosphate
Rattus norvegicus
-
purified recombinant enzyme, IC50 value is 0.027 mM in absence of Ca2+
0.039
scyllo-inositol 1,2,4,5-tetrakisphosphate
Rattus norvegicus
-
weak inhibition, purified recombinant enzyme, IC50 value is 0.039 mM in absence of Ca2+
0.09
scyllo-inositol 1,3,5-trisphosphate
Rattus norvegicus
-
purified recombinant enzyme, IC50 value is 0.090 mM in absence of Ca2+
additional information
chlorogenic acid
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00029
-
-
0.00044
-
mouse brain second particulate fraction
0.00072
-
in absence of calmodulin
0.0008
-
liver
0.002
-
brain cortex
0.0026
-
recombinant enzyme in the first particulate fraction of transfected COS-7 cells
0.0048
-
37C, isoenzyme A, rat cortical slices
0.0244
-
pH 7.2, 37C
0.283
-
pH 7.4, 37C
0.75 - 1.45
-
pH 7.4, 37C, platelet, in presence of free Ca2+ and calmodulin
1.4
-
isoform B, in absence of the Ca2+/calmodulin complex
1.7
-
pH 7.4, 37C, purified recombinant isoenzyme A overexpressed in CHO cells
1.94
-
pH 7.2, 37C
3.5
-
30C, fully activated enzyme in presence of Ca2+/calmodulin
3.68
-
pH 7.5, 37C
10 - 20
-
pH 7.5, 37C
14
-
purified recombinant K268E catalytic/CaM binding domain
15.77
-
pH 7.5, 37C, recombinant isoform B
20
-
recombinant IP3K overexpressed in Escherichia coli, in absence of calmodulin
28.9
-
pH 7.5, 37C, in absence of calmodulin
36.32
-
pH 7.5, 37C, recombinant isoform A
60
-
pH 7.5, 37C, in presence of calmodulin
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7 - 7.5
-
-
7.6
-
in presence of EGTA
7.7
-
-
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5 - 8
-
below pH 5.5 and above pH 8 the activity is abolished
5.8 - 7.7
-
optimum pH range, increase from 75% of maximal activity at pH 5.8 to 100% at pH 7.7
6 - 8
-
steep increase in activity on raising pH from pH 6 to an optimum around pH 8
6.3 - 7.6
-
about half-maximal activity at pH 6.3 and 7.6
6.5 - 8
-
inactive at pH 6.5 and below, above pH 6.5 the activity rises steeply to a broad optimum at pH 8
7 - 9
-
about half-maximal activity at pH 7 and about 60% of maximal activity at pH 9
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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smooth muscle
Manually annotated by BRENDA team
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1321N1 cells, isoform B
Manually annotated by BRENDA team
-
isozyme IP33K-C
Manually annotated by BRENDA team
-
thyroid cells
Manually annotated by BRENDA team
-
human glioma cell line HTB-138, InsP3 3-kinase B mRNA
Manually annotated by BRENDA team
-
inositol trisphosphate 3-kinase B gene is expressed in all hematopoietic stem/progenitor cell populations
Manually annotated by BRENDA team
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endogenous isoenzyme A is localized to the dentritic spines of pyramidal neurons in primary hippocampal cultures from neonatal rats, highest expression of recombinant isoenzyme A in astrocytes
Manually annotated by BRENDA team
-
non-differentiated promyelocytic-leukaemia cell line, InsP3 3-kinase B mRNA
Manually annotated by BRENDA team
-
isoform C, low expression
Manually annotated by BRENDA team
-
human cell line SH-SY5Y, InsP3 3-kinase B mRNA
Manually annotated by BRENDA team
-
insulin-secreting
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
recombinant isoenzyme A has an N-terminal 66-amino acid F-actin-binding region that localizes the kinase to dentritic spines, endogenous isoenzyme A is localized to the dentritic spines of pyramidal neurons in primary hippocampal cultures
Manually annotated by BRENDA team
-
membrane-bound, intrinsic membrane protein, accounts for about 25% of total activity
Manually annotated by BRENDA team
isoform inositol 1,4,5-trisphosphate 3-kinase A is a microtubule-associated protein, and the N terminus of inositol 1,4,5-trisphosphate 3-kinase A is a critical region for direct binding to tubulin in dendritic shaft of hippocampal neurons. Protein kinase A phosphorylates residue Ser119 within inositol 1,4,5-trisphosphate 3-kinase A, leading to a significant reduction of microtubule binding affinity
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
36250
-
IP3K-A, determined with MALDI-TOF-MS. Calculated mass is 36228 Da
44000
-
gel filtration, in presence of Triton X-100
58000
-
minor peaks with MW of 39 kDa and 32 kDa, HPLC gel filtration
70000
-
gel filtration
84000
-
gel filtration
150000 - 160000
-
in the presence of Ca2+/calmodulin, gel filtration, the interaction of calmodulin with the monomeric catalytic subunit promotes dimerization of the enzyme
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
proteolytic modification
-
isozyme IP3-3KB is sensitive to proteolysis at the N-terminus generating active fragments of lower molecular mass
additional information
the enzyme is cleaved at the Asp-Pro clusters, residues 610, 617, and 765, at low pH and different temperatures producing 7 enzyme fragments of 17.4-82.3 kDa of the full-length enzyme of about 100 kDa, overview
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
purified recombinant unlabeled or selennomethionine-labeled wild-type and mutant catalytic domain residues 187-461 free or complexed to ATP, substrate, and product, automated sitting drop vapour diffusion method, 17C, 0.001 ml protein solution over reservoir solution containing 0.83-0.85 M tri-sodium citrate, 0.1 M Tris-HCl, pH 8.0, and 0.1 M NaCl, heavy atom derivative, substrates, or products complex formation by addition and removal of 0.001 ml of 2 M Li2SO4 and 100 mM Tris-HCl, pH 8.0, 4C, containing the relevant compound, i.e. 3 mM ATP, 3 mM MnCl2, or 5 mM 1D-myo-inositol 1,3,4,5-tetrakisphosphate, for 7times, and final soaking for 2.5 h, X-ray diffraction structure determination and analysis at 1.8-1.9 A resolution
-
purified recombinant unlabeled or selennomethionine-labeled mutant catalytic domain residues 185-459, 10 mg/ml protein in 25 mM Tris-HCl, pH 8.0, 150 mM NaCl, and 10 mM DTT, crystallization solution contains 2.2 M ammonium sulfate, 0.2 M sodium formate, 10 mM DTT, 10 mM ADP, 10 mM 1D-myo-inositol 1,3,4,5-tetrakisphosphate, and 10 mM MgCl2, cryoprotection of crystals by successive transfer into 5-15% glycerol in mother liquor, X-ray diffraction structure determination and analysis at 2.2 A resolution
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
enzyme activity remains stable in a wide neutral range of pH
640742
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
0.1% CHAPS or 0.1% Triton X-100 stabilizes, 0.5 mg/ml bovine serum albumin is less efficient in stabilizing
-
2-mercaptoethanol and Triton X-100 or CHAPS stabilize during purification
-
bovine serum albumin stabilizes dilute enzyme solutions
calpain inhibitors stabilize during purification
enzyme is more stable in Tris buffer than in potassium phosphate buffer
-
ethylene glycol, 10%, KCl or sucrose, 0.25 M, does not stabilize
-
isoform A is more susceptible to proteolysis during purification than isoform B
-
stable to dialysis against 0.15 M sucrose
-
Triton X-100 or bovine serum albumin enhances recovery during purification
-
ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Triton X-100
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-15C, partially purified brain enzyme, very stable
-
-20C or 4C, 0.1% CHAPS or Triton X-100, 4 days, less than 5% loss of activity
-
-20C, 4 days, 58% loss of activity
-
-70C, 50 mM Tris-HCl, pH 7.5, 1 mM EGTA, 3 mM MgCl2, 1 mM DTT, 10% v/v glycerol, several months, stable
-
-70C, buffer containing detergent and reducing agent, pH 7-8, at least 3 months, stable
-
4C, 20 mM Tris-HCl buffer, pH 7.2, 1 mM Mg(CH3COO)2, 1 mM DTT, 0.1 mM EGTA, 0.5 mg/ml bovine serum albumin, 3 months, less than 20% loss of activity
-
4C, 4 days, 20% loss of activity
-
4C, 48 h, 10-20% loss of activity