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Information on EC 2.7.1.127 - inositol-trisphosphate 3-kinase and Organism(s) Rattus norvegicus and UniProt Accession P17105

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EC Tree
IUBMB Comments
Activated by Ca2+. Three isoforms have been shown to exist .
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This record set is specific for:
Rattus norvegicus
UNIPROT: P17105
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Word Map
The taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
itpka, itpkb, itpkc, insp3 3-kinase, ip3k, ip3k-a, ip3kb, ins(1,4,5)p3 kinase, insp3kinase, inositol 1,4,5-trisphosphate 3-kinase c, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
inositol 1,4,5-trisphosphate 3-kinase A
-
inositol(1,4,5)P3 3-kinase
-
inositol(1,4,5)trisphosphate 3-kinases
-
Ins(1,4,5)P3 kinase
-
1D-myo-inositol-trisphosphate 3-kinase
-
-
-
-
D-myo-inositol 1,4,5-trisphosphate 3-kinase
-
-
-
-
inositol (1,4,5) trisphosphate 3-kinase
-
-
inositol 1,4,5-trisphosphate 3-kinase
inositol 1,4,5-trisphosphate 3-kinase A
-
-
inositol 1,4,5-trisphosphate 3-kinase C
-
-
inositol 1,4,5-trisphosphate 3-kinases
-
-
inositol 1,4,5-trisphosphate kinase
-
-
-
-
inositol polyphosphate multikinase
inositol(1,4,5)P3 3-kinase
-
inositol(1,4,5)trisphosphate 3-kinases
-
inositol-1,4,5-trisphosphate 3-kinase
inositol-1,4,5-trisphosphate-3-kinase
-
-
-
-
Ins(1,4,5)P3 3-kinase
-
-
-
-
Ins(1,4,5)P3 3-kinase isoform B
-
Ins(1,4,5)P3 kinase
-
InsP3 3-kinase
-
-
-
-
InsP3 3-kinase A
-
-
InsP3 3-kinase B
-
-
InsP3 3-kinase C
-
-
IP3 3-kinase
-
-
IP3kin
-
-
-
-
kinase (phosphorylating), inositol 1,4,5-trisphosphate 3-
-
-
-
-
additional information
-
the enzyme is a member of the protein kinase superfamily
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
Phosphorylation
-
phospho group transfer
-
-
-
-
phospho-group transfer
-
PATHWAY SOURCE
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
-
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-trisphosphate
ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate
show the reaction diagram
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 SUBSTRATE
NATURAL 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-trisphosphate
ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate
show the reaction diagram
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
additional information
?
-
-
the enzyme might be involved in brain development, memory, and learning
-
-
?
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
INHIBITOR
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
-
recombinant, catalytically active fragment of isoform C, substrate inhibition by high concentrations
3',4',7,8-tetrahydroxyflavone
aurintricarboxylic acid
chlorogenic acid
-
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+
EGTA
-
Ca2+/calmodulin-activated enzyme
epicatechin-3-gallate
epigallocatechin-3-gallate
gossypol
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
-
i.e. W-7, calmodulin-antagonist
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
-
Protein kinase C
-
quercetin
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
-
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
Calmodulin
the enzyme is activated by Ca2+/calmodulin. The isozyme contains a CaM binding domain
Carbachol
activates the enzyme up to 7fold in rat brain cortical slices
1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane
-
5-HT2 agonist DOI, 3fold activation
12-O-tetradecanoyl phorbol 13-acetate
-
stimulating in presence of cAMP
12-O-tetradecanoylphorbol-13-acetate
-
2fold activation, isoform B
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+/CaM-dependent kinase II
-
i.e. CaMKII, activates the enzyme by phosphorylation of threonine residue
-
Calmodulin
CaM kinase II
-
cAMP-dependent protein kinase
-
i.e. PKA, activates the enzyme by phosphorylation at Ser109, simultaneous phosphorylation at SEr109 and Ser175 inactivates the enzyme
-
Carbachol
protein kinase A
-
isoforms A and B are differentially regulated via phosphorylation by the cAMP-dependent protein kinase, isoform A: phosphorylated to the extent of 0.9 mol/mol, 2.5fold stimulation in the absence of Ca2+/calmodulin, 1.5fold stimulation in the presence of Ca2+/calmodulin, isoform B: phosphorylated to the extent of 1 mol/mol, no effect on activity in the absence of Ca2+/calmodulin, 45% inhibition in the presence of Ca2+/calmodulin
-
Protein kinase C
-
phosphorylation of isoenzyme B by calmodulin kinase II and protein kinase C added together results in a maximal 60-70fold activation, but protein kinase C alone inhibits in the presence of Ca2+ and calmodulin, no effect on the sensitivity to the Ca2+/calmodulin complex
-
serotonin
-
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
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 - 0.0876
ATP
0.0002 - 0.0017
InsP3
additional information
additional information
All potent inhibitors increases the KM-value for ATP
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.12
N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide
-
-
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
0.00019 - 0.00061
3',4',7,8-tetrahydroxyflavone
0.000062
aurintricarboxylic acid
Rattus norvegicus
IP3K-C, maximal inhibition 100%
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+
0.00069
ellagic acid
Rattus norvegicus
IP3K-C, maximal inhibition 85%
0.000385
epicatechin-3-gallate
Rattus norvegicus
IP3K-C, maximal inhibition 100%
0.00021
epigallocatechin-3-gallate
Rattus norvegicus
IP3K-C, maximal inhibition 100%
0.000175
gossypol
Rattus norvegicus
IP3K-C, maximal inhibition 100%
0.00017
hypericin
Rattus norvegicus
IP3K-C, maximal inhibition 100%
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+
0.00029
myricetin
Rattus norvegicus
IP3K-C, maximal inhibition 62%
0.00039
quercetin
Rattus norvegicus
IP3K-C, maximal inhibition 71%
0.00017
Rose bengal
Rattus norvegicus
IP3K-C, maximal inhibition 100%
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
0.00072
-
in absence of calmodulin
0.0008
-
liver
0.002
-
brain cortex
1.4
-
isoform B, in absence of the Ca2+/calmodulin complex
1.7
-
pH 7.4, 37°C, purified recombinant isoenzyme A overexpressed in CHO cells
15.77
-
pH 7.5, 37°C, recombinant isoform B
20
-
recombinant IP3K overexpressed in Escherichia coli, in absence of calmodulin
28.9
-
pH 7.5, 37°C, in absence of calmodulin
3.5
-
30°C, fully activated enzyme in presence of Ca2+/calmodulin
3.68
-
pH 7.5, 37°C
36.32
-
pH 7.5, 37°C, recombinant isoform A
60
-
pH 7.5, 37°C, in presence of calmodulin
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
Itpka is particularly active in neurons of the hippocampus and cerebellum
Manually annotated by BRENDA team
high expression level
Manually annotated by BRENDA team
-
isozyme IP33K-C
Manually annotated by BRENDA team
-
thyroid cells
Manually annotated by BRENDA team
-
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
-
isoform C, low expression
Manually annotated by BRENDA team
-
insulin-secreting
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
cytoskeletal localization for isozyme Itpka
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
-
recombinant isoenzyme A has an N-terminal 66-amino acid F-actin-binding region, isoform A co-localizes with F-actin
Manually annotated by BRENDA team
-
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
-
not activated isoenzyme B: 65% soluble, 35% particulate fraction, carbachol-activated isoenzyme B shows a redistribution of enzyme from soluble to particulate fraction, only 10% remain soluble
-
Manually annotated by BRENDA team
-
recombinant isoenzyme A associates with
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
inositol(1,4,5)trisphosphate 3-kinases (Itpks) occur in three isoenzyme forms, Itpka/b and c, in human, rat and mouse. They share a catalytic domain relatively well conserved at the C-terminal end and a quite isoenzyme specific regulatory domain at the N-terminal end of the protein
malfunction
neurite length is significantly decreased in cells overexpressing isozymes Itpka and Itpkb but not Itpkc or IPMK. This result does not depend on the overexpression level of any of the kinases. PC12 cells overexpressing GFP-tagged kinase-dead mutants Itpka/b have shorter neurites than GFP control cells
metabolism
1D-myo-inositol 1,3,4,5-tetrakisphosphate, Ins(1,3,4,5)P4 can interact with a relatively specific Ins(1,3,4,5)P4 binding protein Rasa3, alternatively, Ins(1,3,4,5)P4 can also compete with phosphoinositides to the binding of PH domain containing proteins such as Akt, protein kinase B. In neutrophils and hematopoietic progenitors, elevated levels of Ins(1,3,4,5)P4 inhibit the recruitment of Akt at the plasma membrane, and its activation, acting as a competitor of PtdIns(3,4,5)P3 binding to its PH domain
physiological function
evolution
inositol(1,4,5)trisphosphate 3-kinases (Itpks) occur in three isoenzyme forms, Itpka/b and c, in human, rat and mouse. They share a catalytic domain relatively well conserved at the C-terminal end and a quite isoenzyme specific regulatory domain at the N-terminal end of the protein
malfunction
neurite length is significantly decreased in cells overexpressing isozymes Itpka and Itpkb but not Itpkc or IPMK. This result does not depend on the overexpression level of any of the kinases. PC-12 cells overexpressing GFP-tagged kinase-dead mutants Itpka/b have shorter neurites than GFP control cells
metabolism
1D-myo-inositol 1,3,4,5-tetrakisphosphate, Ins(1,3,4,5)P4 can interact with a relatively specific Ins(1,3,4,5)P4 binding protein Rasa3, alternatively, Ins(1,3,4,5)P4 can also compete with phosphoinositides to the binding of PH domain containing proteins such as Akt, protein kinase B. In neutrophils and hematopoietic progenitors, elevated levels of Ins(1,3,4,5)P4 inhibit the recruitment of Akt at the plasma membrane, and its activation, acting as a competitor of PtdIns(3,4,5)P3 binding to its PH domain
physiological function
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
IP3KA_RAT
459
0
50871
Swiss-Prot
Mitochondrion (Reliability: 3)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
100000
-
x * 100000, SDS-PAGE
150000 - 160000
-
in the presence of Ca2+/calmodulin, gel filtration, the interaction of calmodulin with the monomeric catalytic subunit promotes dimerization of the enzyme
44000
-
x * 44000, SDS-PAGE
50000
50900
-
x * 50900, isozyme IP33K-A, x * 74000, isozyme IP33K-B, x * 74500, isozyme IP33K-C
53000
59000
-
x * 59000, recombinant isoform A, x * 92000, recombinant isoform B, SDS-PAGE
70000
-
gel filtration
74000
-
x * 50900, isozyme IP33K-A, x * 74000, isozyme IP33K-B, x * 74500, isozyme IP33K-C
74500
88000
-
x * 88000, isoform B, SDS-PAGE, Western blot analysis
92000
-
x * 59000, recombinant isoform A, x * 92000, recombinant isoform B, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 50000, isozyme Itpka from rat brain, SDS-PAGE
dimer
monomer
-
1 * 53000, SDS-PAGE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
proteolytic modification
Itpka undergoes proteolysis in intact cells, leading to the accumulation of a stable C-terminal domain of 83 kDa to the endoplasmic reticulum, incubation of Itpka at 37°C for 30 min totally destroys Ins(1,4,5)P3 3-kinase activity unless the enzyme is mixed with 0.1% SDS
phosphoprotein
proteolytic modification
Itpkb is very sensitive to proteolysis
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 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
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
K262A
the green fluorescent protein-inositol 1,4,5-trisphosphate 3-kinase A point mutant is generated by site-directed mutagenesis, point mutant lacks kinase activity
D423N
-
crystal structure determination and analysis
L217M
-
crystal structure determination and analysis
additional information
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
-
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
-
ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Triton X-100
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-15°C, partially purified brain enzyme, very stable
-
-20°C or 4°C, 0.1% CHAPS or Triton X-100, 4 days, less than 5% loss of activity
-
-20°C, 4 days, 58% loss of activity
-
-70°C, buffer containing detergent and reducing agent, pH 7-8, at least 3 months, stable
-
4°C, 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
-
4°C, 4 days, 20% loss of activity
-
4°C, 48 h, 10-20% loss of activity
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
elution of recombinant Itpka isozyme with 0.5% SDS and 0.1 mM EGTA from calmodulin affinity column
By phosphocellulose.
isoenzyme B
-
native enzyme partially by nuclear fraction preparation
-
purified in the presence of SDS as a doublet of a MW of approximately 50000
-
recombinant GST-fusion isoform B comprising residues 108-170 by glutathione affinity chromatography, recombinant truncated Strep-tagged isozyme B by affinity chromatography
recombinant IP3K overexpressed in Escherichia coli
-
recombinant isoforms A and B, overexpressed in B31 rat fibroblast, isoform A: 11005fold, isoform B: 43806fold
-
recombinant N-terminally His-tagged and S-tagged C-terminal catalytic domain 3KA-cat30, comprising residues Ser185-Arg459, from Escherichia coli strain BL21(DE3) by nickel and S-protein affinity chromatography, and gel filtration
-
unlabeled or selenomethionine-labeled recombinant residues 185-459 of the catalytic domain of isozyme A fused to GST from Escherichia coli by glutathione affinity chromatography, removal of the GST-tag by recombinant TEV protease, further purification by a second step of glutathione affinity chromatography, adsorption chromatography, and gel filtration
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
generation of knock-out rats and point mutant, IP3K-A is overexpressed in DIV 22 hippocampal neurons by infection with adenovirus containing full-length IP3K-A
a cDNA encoding InsP3 3-kinase B is cloned from a thymus cDNA library and expressed in Escherichia coli, sequence of the 673 amino acids protein
-
cDNAs encoding enzyme isoforms A from brain and B are cloned and overexpressed in B31 cells, a rat-1 fibroblast cell line expressing pp60v-src
-
cloning of a full-length cDNA encoding IP3K isoform C from tongue epithelium, cloning of an enzymatically active and Ca2+/calmodulin-regulated fragment of isoform C and expression in Escherichia coli BL21(DE3)pRIL
-
Cloning, Expression, and Purification of RnIP3K-C isoform and of two different recombinant fragments IP3K-C, one comprising the catalytic domain and the calmodulin binding domain, the other comprising only the catalytic domain, are expressed in Escherichi coli BL21(DE3) cells.
entire gene encoding IP3K is cloned and 130fold overexpressed in Escherichia coli BL21(DE3), when induced by isopropyl-beta-D-thiogalactoside
-
expression of HA-tagged enzyme in human HEK293 and in COS-7 cells
-
expression of mutant cDNA fragment encoding for residues 185-459 of the catalytic domain of isozyme A as unlabeled or selenomethionine-labeled GST fusion proteins in Escherichia coli
-
full-length and truncated isoenzyme A is cloned and expressed in HeLa cells, COS-7 cells and primary neuronal cultures
-
fusion protein of HsIP3K-C with an N-terminal EGFP tag (EGFP/HsIP3KC) is transiently expressed in NRK52E cells
-
IP3K is overexpressed in Escherichia coli
-
isoform B is cloned and expressed in pTet-Off-transfected HeLa cells
-
stable expression of the C-terminal catalytic domain 3KA-cat30, comprising residues Ser185-Arg459, as N-terminally His-tagged and S-tagged protein in Escherichia coli strain BL21(DE3)
-
transient expression of isozyme B in NRK 52E and PC12 cells, DNA and amino acid sequence determination and analysis, expression of isoform B comprising residues 555-934 as Strep-Tactin-tagged enzyme in Escherichia coli strain XL1-Blue, expression of isoform B comprising residues 108-170 as GST-fusion protein in Escherichia coli strain BL21(DE3)
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
overexpression of IP3K-A in DIV 22 hippocampal neurons by infection with adenovirus containing full-length inositol 1,4,5-trisphosphate 3-kinase A leads to a markedly increased number of dendritic structure 18 h after infection, overexpressed GFP-IP3K-A signals are highly localized in the heads of dendritic protrusions
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Hansen, C.A.; Mah, S.; Williamson, J.R.
Formation and metabolism of inositol 1,3,4,5-tetrakisphosphate in liver
J. Biol. Chem.
261
8100-8103
1986
Rattus norvegicus
Manually annotated by BRENDA team
Irvine, R.F.; Letcher, A.J.; Heslop, J.P.; Berridge, M.J.
The inositol tris/tetrakisphosphate pathway--demonstration of Ins(1,4,5)P3 3-kinase activity in animal tissues
Nature
320
631-634
1986
Rattus norvegicus, Xenopus sp.
Manually annotated by BRENDA team
Johanson, R.A.; Hansen, C.A.; Williamson, J.R.
Purification of D-myo-inositol 1,4,5-trisphosphate 3-kinase from rat brain
J. Biol. Chem.
263
7465-7471
1988
Rattus norvegicus
Manually annotated by BRENDA team
Lee, S.Y.; Sim, S.S.; Kim, J.W.; Moon, K.H.; Kim, J.H.; Rhee, S.G.
Purification and properties of D-myo-inositol 1,4,5-trisphosphate 3-kinase from rat brain. Susceptibility to calpain
J. Biol. Chem.
265
9434-9440
1990
Rattus norvegicus
Manually annotated by BRENDA team
Takazawa, K.; Lemos, M.; Delvaux, A.; Lejeune, C.; Dumont, J.E.; Erneux, C.
Rat brain inositol 1,4,5-trisphosphate 3-kinase. Ca2(+)-sensitivity, purification and antibody production
Biochem. J.
268
213-217
1990
Rattus norvegicus
Manually annotated by BRENDA team
Takazawa, K.; Passareiro, H.; Dumont, J.E.; Erneux, C.
Ca2+/calmodulin-sensitive inositol 1,4,5-trisphosphate 3-kinase in rat and bovine brain tissues
Biochem. Biophys. Res. Commun.
153
632-641
1988
Bos taurus, Rattus norvegicus
Manually annotated by BRENDA team
Biden, T.J.; Comte, M.; Cox, J.A.; Wollheim, C.B.
Calcium-calmodulin stimulates inositol 1,4,5-trisphosphate kinase activity from insulin-secreting RINm5F cells
J. Biol. Chem.
262
9437-9440
1987
Rattus norvegicus
Manually annotated by BRENDA team
Collin, T.
Serotonin induces an increase in D-myo-inositol (1,4,5)-trisphosphate 3-kinase activity in rat brainstem slices
Neurosci. Lett.
255
67-70
1998
Rattus norvegicus
Manually annotated by BRENDA team
Choi, G.; Chang, Y.T.; Chung, S.K.; Choi, K.Y.
Molecular interactions of all possible regioisomers of synthetic myo-inositol phosphates with inositol 1,4,5-trisphosphate 3-kinase
Bioorg. Med. Chem. Lett.
7
2709-2714
1997
Rattus norvegicus
-
Manually annotated by BRENDA team
Shin, Y.S.; Choi, G.; Choi, K.Y.
Overexpression, purification and characterization of inositol 1,4,5-triphosphate 3-kinase from rat brain
Mol. Cells
5
348-353
1995
Rattus norvegicus
-
Manually annotated by BRENDA team
Vanweyenberg, V.; Communi, D.; D'Santos, C.S.; Erneux, C.
Tissue- and cell-specific expression of Ins(1,4,5)P3 3-kinase isoenzymes
Biochem. J.
306
429-435
1995
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Takazawa, K.; Go, M.; Endo, T.; Erneux, C.; Onaya, T.
Inositol 1,4,5-trisphosphate 3-kinase activity in FRTL-5 cells: regulation of the enzyme activity by TSH
J. Endocrinol.
144
527-532
1995
Rattus norvegicus
Manually annotated by BRENDA team
Communi, D.; Vanweyenberg, V.; Erneux, C.
D-myo-inositol 1,4,5-trisphosphate 3-kinase A is activated by receptor activation through a calcium:calmodulin-dependent protein kinase II phosphorylation mechanism
EMBO J.
16
1943-1952
1997
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Millard, T.H.; Cullen, P.J.; Banting, G.
Effects of elevated expression of inositol 1,4,5-trisphosphate 3-kinase B on Ca2+ homoeostasis in HeLa cells
Biochem. J.
352
709-715
2000
Rattus norvegicus
Manually annotated by BRENDA team
Communi, D.; Dewaste, V.; Erneux, C.
Calcium-calmodulin-dependent protein kinase II and protein kinase C-mediated phosphorylation and activation of D-myo-inositol 1,4, 5-trisphosphate 3-kinase B in astrocytes
J. Biol. Chem.
274
14734-14742
1999
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Woodring, P.J.; Garrison, J.C.
Expression, purification, and regulation of two isoforms of the inositol 1,4,5-trisphosphate 3-kinase
J. Biol. Chem.
272
30447-30454
1997
Rattus norvegicus
Manually annotated by BRENDA team
Schell, M.J.; Erneux, C.; Irvine, R.F.
Inositol 1,4,5-trisphosphate 3-kinase A associates with F-actin and dendritic spines via its N terminus
J. Biol. Chem.
276
37537-37546
2001
Rattus norvegicus
Manually annotated by BRENDA team
Nalaskowski, M.M.; Bertsch, U.; Fanick, W.; Stockebrand, M.C.; Schmale, H.; Mayr, G.W.
Rat inositol 1,4,5-trisphosphate 3-kinase C is enzymatically specialized for basal cellular inositol trisphosphate phosphorylation and shuttles actively between nucleus and cytoplasm
J. Biol. Chem.
278
19765-19776
2003
Rattus norvegicus
Manually annotated by BRENDA team
Brehm, M.A.; Schreiber, I.; Bertsch, U.; Wegner, A.; Mayr, G.W.
Identification of the actin-binding domain of Ins(1,4,5)P3 3-kinase isoform B (IP3K-B)
Biochem. J.
382
353-362
2004
Homo sapiens, Rattus norvegicus (P42335)
Manually annotated by BRENDA team
Kwon, Y.U.; Im, J.; Choi, G.; Kim, Y.S.; Choi, K.Y.; Chung, S.K.
Synthesis of three enantiomeric pairs of scyllo-inositol phosphate and molecular interactions between all possible regioisomers of scyllo-inositol phosphate and inositol 1,4,5-trisphosphate 3-kinase
Bioorg. Med. Chem. Lett.
13
2981-2984
2003
Rattus norvegicus
Manually annotated by BRENDA team
Xia, H.J.; Yang, G.
Inositol 1,4,5-trisphosphate 3-kinases: functions and regulations
Cell Res.
15
83-91
2005
Drosophila melanogaster, Homo sapiens, Rattus norvegicus, Sus scrofa
Manually annotated by BRENDA team
Poinas, A.; Backers, K.; Riley, A.M.; Mills, S.J.; Moreau, C.; Potter, B.V.; Erneux, C.
Interaction of the catalytic domain of inositol 1,4,5-trisphosphate 3-kinase A with inositol phosphate analogues
Chembiochem
6
1449-1457
2005
Rattus norvegicus
Manually annotated by BRENDA team
Mayr, G.W.; Windhorst, S.; Hillemeier, K.
Antiproliferative plant and synthetic polyphenolics are specific inhibitors of vertebrate inositol-1,4,5-trisphosphate 3-kinases and inositol polyphosphate multikinase
J. Biol. Chem.
280
13229-13240
2005
Gallus gallus, Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Miller, G.J.; Hurley, J.H.
Crystal structure of the catalytic core of inositol 1,4,5-trisphosphate 3-kinase
Mol. Cell
15
703-711
2004
Rattus norvegicus
Manually annotated by BRENDA team
Resnick, A.C.; Snowman, A.M.; Kang, B.N.; Hurt, K.J.; Snyder, S.H.; Saiardi, A.
Inositol polyphosphate multikinase is a nuclear PI3-kinase with transcriptional regulatory activity
Proc. Natl. Acad. Sci. USA
102
12783-12788
2005
Rattus norvegicus, Saccharomyces cerevisiae, Saccharomyces cerevisiae BY4741
Manually annotated by BRENDA team
Nalaskowski, M.M.; Windhorst, S.; Stockebrand, M.C.; Mayr, G.W.
Subcellular localisation of human inositol 1,4,5-trisphosphate 3-kinase C: species-specific use of alternative export sites for nucleo-cytoplasmic shuttling indicates divergent roles of the catalytic and N-terminal domains
Biol. Chem.
387
583-593
2006
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Stokes, A.J.; Shimoda, L.M.; Lee, J.W.; Rillero, C.; Chang, Y.; Turner, H.
FceRI control of Ras via inositol (1,4,5) trisphosphate 3-kinase and inositol tetrakisphosphate
Cell. Signal.
18
640-651
2006
Rattus norvegicus
Manually annotated by BRENDA team
Lloyd-Burton, S.M.; Yu, J.C.; Irvine, R.F.; Schell, M.J.
Regulation of inositol 1,4,5-trisphosphate 3-kinases by calcium and localization in cells
J. Biol. Chem.
282
9526-9535
2007
Rattus norvegicus
Manually annotated by BRENDA team
Sun, W.; Kang, Y.; Kim, I.H.; Kim, E.H.; Rhyu, I.J.; Kim, H.; Kim, H.
Inhibition of rat brain inositol 1,4,5-trisphosphate 3-kinase A expression by kainic acid
Neurosci. Lett.
392
181-186
2006
Rattus norvegicus
Manually annotated by BRENDA team
Mayr, G.W.; Windhorst, S.; Hillemeier, K.
Antiproliferative plant and synthetic polyphenolics are specific inhibitors of vertebrate inositol-1,4,5-trisphosphate 3-kinases and inositol polyphosphate multikinase. [Erratum to document cited in CA143:003106]
J. Biol. Chem.
282
35424
2007
Gallus gallus, Homo sapiens (P23677), Homo sapiens (P27987), Rattus norvegicus (Q80ZG2)
-
Manually annotated by BRENDA team
Kim, I.H.; Park, S.K.; Hong, S.T.; Jo, Y.S.; Kim, E.J.; Park, E.H.; Han, S.B.; Shin, H.S.; Sun, W.; Kim, H.T.; Soderling, S.H.; Kim, H.
Inositol 1,4,5-trisphosphate 3-kinase a functions as a scaffold for synaptic Rac signaling
J. Neurosci.
29
14039-14049
2009
Mus musculus, Rattus norvegicus (P17105)
Manually annotated by BRENDA team
Lee, D.; Lee, H.W.; Hong, S.; Choi, B.I.; Kim, H.W.; Han, S.B.; Kim, I.H.; Bae, J.Y.; Bae, Y.C.; Rhyu, I.J.; Sun, W.; Kim, H.
Inositol 1,4,5-trisphosphate 3-kinase A is a novel microtubule-associated protein: PKA-dependent phosphoregulation of microtubule binding affinity
J. Biol. Chem.
287
15981-15995
2012
Rattus norvegicus (P17105)
Manually annotated by BRENDA team
Erneux, C.; Ghosh, S.; Koenig, S.
Inositol(1,4,5)P3 3-kinase isoenzymes: catalytic properties and importance of targeting to F-actin to understand function
Adv. Biol. Regul.
60
135-143
2016
Homo sapiens (P23677), Homo sapiens (P27987), Homo sapiens (Q96DU7), Homo sapiens, Mus musculus (B2RXC2), Mus musculus (Q7TS72), Mus musculus (Q8R071), Mus musculus, Rattus norvegicus (P17105), Rattus norvegicus (P42335), Rattus norvegicus (Q80ZG2)
Manually annotated by BRENDA team
Koenig, S.; Moreau, C.; Dupont, G.; Scoumanne, A.; Erneux, C.
Regulation of NGF-driven neurite outgrowth by Ins(1,4,5)P3 kinase is specifically associated with the two isoenzymes Itpka and Itpkb in a model of PC12 cells
FEBS J.
282
2553-2569
2015
Rattus norvegicus (P17105), Rattus norvegicus (P42335), Rattus norvegicus (Q80ZG2)
Manually annotated by BRENDA team