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Information on EC 2.7.1.151 - inositol-polyphosphate multikinase and Organism(s) Homo sapiens and UniProt Accession Q8NFU5

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EC Tree
IUBMB Comments
This enzyme also phosphorylates Ins(1,4,5)P3 to Ins(1,3,4,5)P4, Ins(1,3,4,5)P4 to Ins(1,3,4,5,6)P5, and Ins(1,3,4,5,6)P4 to Ins(PP)P4, isomer unknown. The enzyme from the plant Arabidopsis thaliana can also phosphorylate Ins(1,3,4,6)P4 and Ins(1,2,3,4,6)P5 at the D-5-position to produce 1,3,4,5,6-pentakisphosphate and inositol hexakisphosphate (InsP6), respectively . Yeast produce InsP6 from Ins(1,4,5)P3 by the actions of this enzyme and EC 2.7.1.158, inositol-pentakisphosphate 2-kinase .
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Homo sapiens
UNIPROT: Q8NFU5
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Synonyms
5-kinase, arg82, ins(1,4,5)p3 3-kinase, inositol polyphosphate multikinase, itpk1, inositol 1,4,5-trisphosphate 3-kinase, argriii, inositol polyphosphate kinase, ip3 3-kinase, atipk2beta, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
inositol phosphate multikinase
-
inositol polyphosphate multikinase
-
1,3,4,6-tetrakisphosphate 5-kinase
-
-
5-kinase
-
-
Impk
-
-
inositol phosphate multikinase
-
-
inositol polyphosphate kinase
-
-
-
-
inositol polyphosphate multikinase
-
-
Ins(1,4,5)P3 3-kinase
-
-
InsP4 5-kinase
ITPK1
-
-
phosphoinositol kinase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + 1D-myo-inositol 1,4,5-trisphosphate = ADP + 1D-myo-inositol 1,4,5,6-tetrakisphosphate
show the reaction diagram
the catalytic site contains an important Ser-Ser-Leu-Leu motif
ATP + 1D-myo-inositol 1,4,5,6-tetrakisphosphate = ADP + 1D-myo-inositol 1,3,4,5,6-pentakisphosphate
show the reaction diagram
the catalytic site contains an important Ser-Ser-Leu-Leu motif
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho-group transfer
PATHWAY SOURCE
PATHWAYS
-
-, -, -
SYSTEMATIC NAME
IUBMB Comments
ATP:1D-myo-inositol-1,4,5-trisphosphate 6-phosphotransferase
This enzyme also phosphorylates Ins(1,4,5)P3 to Ins(1,3,4,5)P4, Ins(1,3,4,5)P4 to Ins(1,3,4,5,6)P5, and Ins(1,3,4,5,6)P4 to Ins(PP)P4, isomer unknown. The enzyme from the plant Arabidopsis thaliana can also phosphorylate Ins(1,3,4,6)P4 and Ins(1,2,3,4,6)P5 at the D-5-position to produce 1,3,4,5,6-pentakisphosphate and inositol hexakisphosphate (InsP6), respectively [3]. Yeast produce InsP6 from Ins(1,4,5)P3 by the actions of this enzyme and EC 2.7.1.158, inositol-pentakisphosphate 2-kinase [4].
CAS REGISTRY NUMBER
COMMENTARY hide
9077-69-4
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2 ATP + 1D-myo-inositol 1,4,5-trisphosphate
2 ADP + 1D-myo-inositol 1,3,4,5,6-pentakisphosphate
show the reaction diagram
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
show the reaction diagram
-
-
-
?
ATP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate
ADP + 1D-myo-inositol 1,3,4,5,6-pentakisphosphate
show the reaction diagram
-
-
-
?
ATP + 1D-myo-inositol 1,4,5,6-tetrakisphosphate
ADP + 1D-myo-inositol 1,3,4,5,6-pentakisphosphate
show the reaction diagram
-
-
-
?
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-trisphosphate
ADP + 1D-myo-inositol 1,4,5,6-tetrakisphosphate
show the reaction diagram
ATP + 1D-myo-inositol 4,5-bisphosphate
ADP + 1D-myo-inositol 3,4,5-trisphosphate
show the reaction diagram
-
-
-
?
2 ATP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate + 1D-myo-inositol 1,4,5,6-tetrakisphosphate
2 ADP + 2 1D-myo-inositol 1,3,4,5,6-pentakisphosphate
show the reaction diagram
-
in rats and humans
-
-
?
2 ATP + 1D-myo-inositol 1,4,5-trisphosphate
2 ADP + 1D-myo-inositol 1,3,4,5,6-pentakisphosphate
show the reaction diagram
-
-
-
-
r
3 ATP + 2 1D-myo-inositol 1,4,5-trisphosphate
3 ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate + 1D-myo-inositol 1,3,4,5,6-pentakisphosphate
show the reaction diagram
-
in rats and humans
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
show the reaction diagram
-
-
-
-
?
ATP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate
ADP + 1D-myo-inositol 1,3,4,5,6-pentakisphosphate
show the reaction diagram
ATP + 1D-myo-inositol 1,3,4,6-tetrakisphosphate
ADP + 1D-myo-inositol 1,3,4,5,6-pentakisphosphate
show the reaction diagram
ATP + 1D-myo-inositol 1,4,5,6-tetrakisphosphate
ADP + 1D-myo-inositol 1,3,4,5,6-pentakisphosphate
show the reaction diagram
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-trisphosphate
ADP + 1D-myo-inositol 1,3,4,6-tetrakisphosphate
show the reaction diagram
-
2fold less active compared to 1D-myo-inositol 1,3,4,6-tetrakisphosphate
-
-
?
ATP + 1D-myo-inositol 1,4,5-trisphosphate
ADP + 1D-myo-inositol 1,4,5,6-tetrakisphosphate
show the reaction diagram
ATP + inositol 1,3,4,5-tetrakisphosphate
ADP + inositol (1,3,4,5,6)-pentakisphosphate
show the reaction diagram
-
substrate preference for inositol 1,3,4,6-tetrakisphosphate over inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate
-
-
?
ATP + inositol 1,4,5,6-tetrakisphosphate
ADP + inositol (1,3,4,5,6)-pentakisphosphate
show the reaction diagram
ATP + inositol 1,4,5-trisphosphate
ADP + inositol (1,3,4,5)-tetrakisphosphate
show the reaction diagram
-
substrate preference for inositol 1,3,4,6-tetrakisphosphate over inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate
-
-
?
inositol (1,3,4,6)-tetrakisphosphate + ATP
ADP + inositol (1,3,4,5,6)-pentakisphosphate
show the reaction diagram
-
substrate preference for inositol 1,3,4,6-tetrakisphosphate over inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate
-
-
?
inositol (1,4,5,6)-tetrakisphosphate + ATP
inositol (1,3,4,5,6)-pentakisphosphate + ADP
show the reaction diagram
-
hITPK1 has more than 13000fold preference for inositol (3,4,5,6)-tetrakisphosphate over its enantiomer inositol (1,4,5,6)-tetrakisphosphate
-
-
?
inositol (3,4,5,6)-tetrakisphosphate + ATP
inositol (1,3,4,5,6)-pentakisphosphate + ADP
show the reaction diagram
-
hITPK1 has more than 13000fold preference for inositol (3,4,5,6)-tetrakisphosphate over its enantiomer inositol (1,4,5,6)-tetrakisphosphate
-
-
?
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 + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
show the reaction diagram
-
-
-
?
ATP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate
ADP + 1D-myo-inositol 1,3,4,5,6-pentakisphosphate
show the reaction diagram
-
-
-
?
ATP + 1D-myo-inositol 1,4,5,6-tetrakisphosphate
ADP + 1D-myo-inositol 1,3,4,5,6-pentakisphosphate
show the reaction diagram
-
-
-
?
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-trisphosphate
ADP + 1D-myo-inositol 1,4,5,6-tetrakisphosphate
show the reaction diagram
-
-
-
?
ATP + 1D-myo-inositol 4,5-bisphosphate
ADP + 1D-myo-inositol 3,4,5-trisphosphate
show the reaction diagram
-
-
-
?
2 ATP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate + 1D-myo-inositol 1,4,5,6-tetrakisphosphate
2 ADP + 2 1D-myo-inositol 1,3,4,5,6-pentakisphosphate
show the reaction diagram
-
in rats and humans
-
-
?
2 ATP + 1D-myo-inositol 1,4,5-trisphosphate
2 ADP + 1D-myo-inositol 1,3,4,5,6-pentakisphosphate
show the reaction diagram
-
-
-
-
r
3 ATP + 2 1D-myo-inositol 1,4,5-trisphosphate
3 ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate + 1D-myo-inositol 1,3,4,5,6-pentakisphosphate
show the reaction diagram
-
in rats and humans
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
show the reaction diagram
-
-
-
-
?
ATP + 1D-myo-inositol 1,3,4,6-tetrakisphosphate
ADP + 1D-myo-inositol 1,3,4,5,6-pentakisphosphate
show the reaction diagram
-
-
-
-
?
ATP + 1D-myo-inositol 1,4,5,6-tetrakisphosphate
ADP + 1D-myo-inositol 1,3,4,5,6-pentakisphosphate
show the reaction diagram
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-trisphosphate
ADP + 1D-myo-inositol 1,4,5,6-tetrakisphosphate
show the reaction diagram
ATP + inositol 1,4,5,6-tetrakisphosphate
ADP + inositol (1,3,4,5,6)-pentakisphosphate
show the reaction diagram
-
stable over-expression of the human protein in HEK-293 cells abrogates the in vivo elevation of inositol 1,4,5,6-tetrakisphosphate from the Salmonella dublin SopB protein. The enzyme may play a role in regulation of the level of inositol 1,4,5,6-tetrakisphosphate in human cells
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
free enzyme and inhibited enzyme are not affected by Ca2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
aurintricarboxylic acid
-
mixed-type versus ATP, noncompetitive versus 1D-myo-inositol 1,4,5-trisphosphate, strong inhibition, IC50 is 44 nM
chlorogenic acid
-
mixed-type versus ATP, noncompetitive versus 1D-myo-inositol 1,4,5-trisphosphate, slight inhibition, IC50 is 0.0012 mM
ellagic acid
-
mixed-type versus ATP, noncompetitive versus 1D-myo-inositol 1,4,5-trisphosphate, slight inhibition, IC50 is 0.0014 mM
gossypol
-
mixed-type versus ATP, noncompetitive versus 1D-myo-inositol 1,4,5-trisphosphate, slight inhibition, IC50 is 0.0034 mM
inositol(1,3,4)-trisphosphate
-
potently inhibits hITPK1 activity towards insositol (3,4,5,6)-tetrakisphosphate, IC50: 0.0076 mM
inositol(3,5,6)-trisphosphate
-
IC50: 0.1 mM
Rose bengal
-
mixed-type versus ATP, noncompetitive versus 1D-myo-inositol 1,4,5-trisphosphate, slight inhibition, IC50 is 620 nM
additional information
-
inhibitory effects are not due to inactivating aggregation of the enzyme, no inhibition by quercetin, 3',4',7,8-tetrahydroxyflavone, myricetin, hypericin, epigallocatechin-3-gallate, and epicatechin-3-gallate, the enzyme contains a unique basic segment of 105 amino acids, which is inserted between the SSLL motif and the DFG motif, being probably involved in inhibition by acidic polyphenols
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00028
1D-myo-inositol 1,4,5-trisphosphate
pH 7.8, 30°C, 0.5 mM ATP, recombinant enzyme
0.00013
1D-myo-inositol 1,3,4,5-tetrakisphosphate
-
recombinant enzyme, pH 7.2, 37°C
0.0003
1D-myo-inositol 1,3,4,6-tetrakisphosphate
-
recombinant enzyme, pH 7.2, 37°C
0.00022
1D-myo-inositol 1,4,5,6-tetrakisphosphate
-
recombinant enzyme, pH 7.2, 37°C
0.00011 - 0.0004
1D-myo-inositol 1,4,5-trisphosphate
0.000222
1D-myo-inositol-1,4,5,6-tetrakisphosphate
-
37°C, pH 7.2
0.017 - 0.039
ATP
0.000129
inositol (1,3,4,5)-tetrakisphosphate
-
37°C, pH 7.2
0.000295
inositol (1,3,4,6)-tetrakisphosphate
-
37°C, pH 7.2
0.000112
inositol (1,4,5)-trisphosphate
-
37°C, pH 7.2
0.00018
inositol (1,4,5,6)-tetrakisphosphate
-
-
additional information
additional information
-
kinetics
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00015
inositol (1,3,4)-trisphosphate
-
-
0.002
inositol (3,5,6)-trisphosphate
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000044
aurintricarboxylic acid
Homo sapiens
-
mixed-type versus ATP, noncompetitive versus 1D-myo-inositol 1,4,5-trisphosphate, strong inhibition, IC50 is 44 nM
0.0012
chlorogenic acid
Homo sapiens
-
mixed-type versus ATP, noncompetitive versus 1D-myo-inositol 1,4,5-trisphosphate, slight inhibition, IC50 is 0.0012 mM
0.0014
ellagic acid
Homo sapiens
-
mixed-type versus ATP, noncompetitive versus 1D-myo-inositol 1,4,5-trisphosphate, slight inhibition, IC50 is 0.0014 mM
0.0034
gossypol
Homo sapiens
-
mixed-type versus ATP, noncompetitive versus 1D-myo-inositol 1,4,5-trisphosphate, slight inhibition, IC50 is 0.0034 mM
0.0076
inositol(1,3,4)-trisphosphate
Homo sapiens
-
potently inhibits hITPK1 activity towards insositol (3,4,5,6)-tetrakisphosphate, IC50: 0.0076 mM
0.1
inositol(3,5,6)-trisphosphate
Homo sapiens
-
IC50: 0.1 mM
0.00062
Rose bengal
Homo sapiens
-
mixed-type versus ATP, noncompetitive versus 1D-myo-inositol 1,4,5-trisphosphate, slight inhibition, IC50 is 620 nM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.45
purified recombinant enzyme, 1D-myo-inositol 1,3,4,5,6-pentakisphosphate formation from 1D-myo-inositol 1,4,5-trisphosphate, 0.5 mM ATP
2.5
-
recombinant wild-type enzyme, substrate 1D-myo-inositol 1,4,5-trisphosphate
5.5
-
recombinant deletion mutant enzyme, substrate 1D-myo-inositol 1,4,5-trisphosphate
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.2
assay at
7.8
assay at
7.2
-
assay at
7.5
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
assay at
37
assay at
30
-
assay at
37
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
from Huntington's disease patients and healthy persons
Manually annotated by BRENDA team
from Huntington's disease patients and healthy persons, severe loss of IPMK in the striatum of Huntington's disease patients
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
IPMK is a member of the so-called IP-kinase family that includes IP3Ks and IP6Ks, evolutionary relationships and structure comparisons, overview. There has been co-evolution of Ins(1,4,5)P3 and PtdIns(4,5)P2 3-kinase activities
malfunction
metabolism
physiological function
physiological function
-
IPMK is a pleiotropic enzyme. Gene transcription by p53 requires inositol polyphosphate multikinase as a co-activator. IPMK subsequently phosphorylates IP4 into IP5, and is the rate-limiting enzyme for this metabolite. IPMK serves as the gate-keeping enzyme for the synthesis of all higher inositol polyphosphate species, including inositol diphosphates, which are implicated in diverse physiologic processes. Independent of catalytic activity, IPMK binds to p53 and enhances its association with p300. The enhancement of p300s histone acetyltransferase activity by IPMK leads to increased acetylation of p53 and histone H3, as well as p53 association to target promoters. This augmentation of p53-dependent gene transcription enhances cell death. IPMK is also a major PI3 kinase, which acts together with the wortmannin-sensitive p110/p85 PI3 kinase, EC 2.7.1.153, to generatephosphatidylinositol-3,4,5-trisphosphate that activates Akt and protein synthesis. Both wild-type and catalytically inactive IPMK stabilize the mTOR-1 complex to facilitate protein translation
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
IPMK_HUMAN
416
0
47222
Swiss-Prot
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
47219
x * 47219, amino acid sequence calculation
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 47219, amino acid sequence calculation
additional information
-
domain structure analysis, the enzyme contains an IP3-binding domain, a nucleus localization signal sequence, and an ATP/Mg2+ binding domain, but no F-actin-binding or CaM-binding domain
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
-
-
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinant core catalytic domain of HsIMPK, that contains residues 50 to 416, from which an internal domain comprising residues 263 to 377 is deleted and replaced with a simple Gly-Gly-Ser-Gly-Gly linker, apostructure and catalytic core domain with bound ADP-Ins (1,4,5)P3-Mg and ADP-DiC4-PtdInsP2-Mg, hanging drop vapor diffusion, mixing of 0.002 ml of 38 mg/ml protein solution with 0.002 ml of well solution containing 35% w/v PEG 400, 0.1 M Li2SO4, 100 mM MES-imidazole, pH 6.0, and 50 mM 2-mercaptoethanol, 25°C, to obtain complex structures, apoenzyme crystals are further soaked for 1 day in 35% w/v PEG 400, 100 mM Li2SO4, 100 mM HEPES, pH 7.5, at 25°C, in the presence of 20 mM Ins(1,4,5)P3 or a soluble diC4-analogue of PtdIns(4,5)P2, 10 mM MgCl2, and 5 mM of either Na2ATP or Li2AMP-PNP, X-ray diffraction structure determination and analysis at 1.63-1.93 A resolution. The structure of the IPMK apoenzyme is determined by a molecular replacement approach using a model constructed from the template of yeast ScIPMK (PDB ID 2IF8)
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D144N
site-directed mutagenesis
D144N/K146A
site-directed mutagenesis
H388A
site-directed mutagenesis, the mutant shows no Ins(1,4,5)P3 3-kinase activity and reduced Ins(1,3,4,5)P4 6-kinase activity compared to wild-type
K129A/S235A
catalytically inactive mutant
K146A
site-directed mutagenesis
K160A
site-directed mutagenesis, the mutant shows no Ins(1,4,5)P3 3-kinase activity and reduced Ins(1,3,4,5)P4 6-kinase activity compared to wild-type
K167A
site-directed mutagenesis, the mutant shows reduced Ins(1,4,5)P3 3-kinase activity and Ins(1,3,4,5)P4 6-kinase activity compared to wild-type
K327Q/K328Q
site-directed mutagenesis, generation of an IPMK mutant with inactivated nuclear localization signal, NLS, whose intracellular distribution is unaffected by inhibition of conventional protein import
Q163A
site-directed mutagenesis, the mutant shows no Ins(1,4,5)P3 3-kinase activity and reduced Ins(1,3,4,5)P4 6-kinase activity compared to wild-type
Q163K
site-directed mutagenesis, the mutant shows reduced Ins(1,4,5)P3 3-kinase activity and increased Ins(1,3,4,5)P4 6-kinase activity compared to wild-type
Q163R
site-directed mutagenesis, the mutant shows reduced Ins(1,4,5)P3 3-kinase activity and increased Ins(1,3,4,5)P4 6-kinase activity compared to wild-type
Q164A
site-directed mutagenesis, the mutant shows reduced Ins(1,4,5)P3 3-kinase activity and Ins(1,3,4,5)P4 6-kinase activity compared to wild-type
Q164K
site-directed mutagenesis, the mutant shows reduced Ins(1,4,5)P3 3-kinase activity and increased Ins(1,3,4,5)P4 6-kinase activity compared to wild-type
Q164R
site-directed mutagenesis, the mutant shows reduced Ins(1,4,5)P3 3-kinase activity and increased Ins(1,3,4,5)P4 6-kinase activity compared to wild-type
Q196A
site-directed mutagenesis, the mutant shows reduced Ins(1,4,5)P3 3-kinase activity and Ins(1,3,4,5)P4 6-kinase activity compared to wild-type
Q196K
site-directed mutagenesis, the mutant shows reduced Ins(1,4,5)P3 3-kinase activity and increased Ins(1,3,4,5)P4 6-kinase activity compared to wild-type
Q196R
site-directed mutagenesis, the mutant shows reduced Ins(1,4,5)P3 3-kinase activity and increased Ins(1,3,4,5)P4 6-kinase activity compared to wild-type
Q78A
site-directed mutagenesis, the mutant shows no Ins(1,4,5)P3 3-kinase activity and reduced Ins(1,3,4,5)P4 6-kinase activity compared to wild-type
R82A
site-directed mutagenesis, the mutant shows no Ins(1,4,5)P3 3-kinase activity and reduced Ins(1,3,4,5)P4 6-kinase activity compared to wild-type
additional information
ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
enzyme is not affected by 3% v/v DMSO
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme from Escherichia coli strain BL21(DE3) to near homogeneity by ion exchange and phosphocellulose resin chromatography
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli by nickel affinity and heparin affinity chromatography, followed by tag cleavage through TEV protease, another step of heparin affinity chromatography, and gel filtration
recombinant N-terminally His-tagged enzyme from Escherichia coli strain BL21(DE3) by cobalt affinity chromatography
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recombinant wild-type enzyme and deletion mutant from Escherichia coli by ion exchange and phosphocellulose resin chromatography
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
DNA and amino acid sequence determination and analysis, overexpression as C-terminally GFP-tagged fusion protein in Escherichia coli strain BL21(DE3), transient expression in NRK 52E cells as C- or N-terminally GFP-tagged fusion protein
gene impk, adeno-associated virus serotype 2-mediated delivery of IPMK into mouse brain, in the striatum of R6/2 Huntington's disease mice
gene impk, recombinant GST-tagged IMPK overexpression in human colon cancer cell line HCT-116 and the human osteosarcoma cell line U2-OS. Overexpression of kinase-deficient IPMK inhibits cell proliferation in etoposide-treated U2OS cells to a similar extent as does wild-type IPMK
gene ipmk, recombinant expression of His-tagged wild-type and mutant enzymes in Escherichia coli
DNA and amino acid sequence determination and analysis, no functional complementation of yeast mutant strains, expression of the N-terminally His-tagged enzyme in Escherichia coli strain BL21(DE3)
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expression in enzyme-deficient yeast cells, stable overexpression in HEK-293 cells, abrogates the in vivo elevation of 1D-myo-inositol 1,4,5,6-tetrakisphosphate from the Salmonella dublin SopB protein
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expression of wild-type enzyme and deletion mutant in Escherichia coli
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IPMK knockout mice demonstrates the critical roles of IPMK in embryogenesis and central nevous system development. Deletion of IPMK in mice results in early lethality.
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
delivery of IPMK in a transgenic Huntington's disease model improves pathological changes and motor performance. The Ctip2-IPMK-Akt signaling pathway provides a previously unidentified therapeutic target for Huntington's disease
medicine
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putative treatment of cancer
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Chang, S.C.; Miller, A.L.; Feng, Y.; Wente, S.R.; Majerus, P.W.
The human homolog of the rat inositol phosphate multikinase is an inositol 1,3,4,6-tetrakisphosphate 5-kinase
J. Biol. Chem.
277
43836-43843
2002
Homo sapiens
Manually annotated by BRENDA team
Chang, S.C.; Majerus, P.W.
Inositol polyphosphate multikinase regulates inositol 1,4,5,6-tetrakisphosphate
Biochem. Biophys. Res. Commun.
339
209-216
2006
Homo sapiens
Manually annotated by BRENDA team
Nalaskowski, M.M.; Deschermeier, C.; Fanick, W.; Mayr, G.W.
The human homologue of yeast ArgRIII protein is an inositol phosphate multikinase with predominantly nuclear localization
Biochem. J.
366
549-556
2002
Homo sapiens (Q8NFU5), Homo sapiens
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
Arabidopsis thaliana, Homo sapiens, Saccharomyces cerevisiae
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
Homo sapiens
Manually annotated by BRENDA team
Riley, A.M.; Deleu, S.; Qian, X.; Mitchell, J.; Chung, S.; Adelt, S.; Vogel, G.; Potter, B.V.; Shears, S.B.
On the contribution of stereochemistry to human ITPK1 specificity: Ins(1,4,5,6)P4 is not a physiologic substrate
FEBS Lett.
580
324-330
2006
Homo sapiens
Manually annotated by BRENDA team
Resnick, A.C.; Saiardi, A.
Inositol polyphosphate multikinase: metabolic architect of nuclear inositides
Front. Biosci.
13
856-866
2008
Arabidopsis thaliana, Saccharomyces cerevisiae, Drosophila melanogaster, Homo sapiens, Rattus norvegicus, Solanum tuberosum
Manually annotated by BRENDA team
Xu, R.; Snyder, S.
Gene transcription by p53 requires inositol polyphosphate multikinase as a co-activator
Cell Cycle
12
1819-1820
2013
Homo sapiens
Manually annotated by BRENDA team
Wickramasinghe, V.O.; Savill, J.M.; Chavali, S.; Jonsdottir, A.B.; Rajendra, E.; Gruener, T.; Laskey, R.A.; Babu, M.M.; Venkitaraman, A.R.
Human inositol polyphosphate multikinase regulates transcript-selective nuclear mRNA export to preserve genome integrity
Mol. Cell
51
737-750
2013
Homo sapiens (Q8NFU5), Homo sapiens
Manually annotated by BRENDA team
Ahmed, I.; Sbodio, J.I.; Harraz, M.M.; Tyagi, R.; Grima, J.C.; Albacarys, L.K.; Hubbi, M.E.; Xu, R.; Kim, S.; Paul, B.D.; Snyder, S.H.
Huntingtons disease: neural dysfunction linked to inositol polyphosphate multikinase
Proc. Natl. Acad. Sci. USA
112
9751-9756
2015
Homo sapiens (Q8NFU5), Homo sapiens
Manually annotated by BRENDA team
Xu, R.; Sen, N.; Paul, B.D.; Snowman, A.M.; Rao, F.; Vandiver, M.S.; Xu, J.; Snyder, S.H.
Inositol polyphosphate multikinase is a coactivator of p53-mediated transcription and cell death
Sci. Signal.
6
ra22
2013
Homo sapiens (Q8NFU5)
Manually annotated by BRENDA team
Wang, H.; Shears, S.B.
Structural features of human inositol phosphate multikinase rationalize its inositol phosphate kinase and phosphoinositide 3-kinase activities
J. Biol. Chem.
292
18192-18202
2017
Homo sapiens (Q8NFU5), Homo sapiens
Manually annotated by BRENDA team