Information on EC 2.7.4.21 - inositol-hexakisphosphate kinase

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The expected taxonomic range for this enzyme is: Euteleostomi

EC NUMBER
COMMENTARY
2.7.4.21
-
RECOMMENDED NAME
GeneOntology No.
inositol-hexakisphosphate kinase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
ATP + 1D-myo-inositol 1-diphosphate 2,3,4,5,6-pentakisphosphate = ADP + 1D-myo-inositol 1,5-bis(diphosphate) 2,3,4,6-tetrakisphosphate
show the reaction diagram
(2)
-
-
-
ATP + 1D-myo-inositol hexakisphosphate = ADP + 1D-myo-inositol 5-diphosphate 1,2,3,4,6-pentakisphosphate
show the reaction diagram
(1)
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
phospho group transfer
-
-
phospho group transfer
-
-
phospho-group transfer
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
inositol pyrophosphates biosynthesis
-
SYSTEMATIC NAME
IUBMB Comments
ATP:1D-myo-inositol-hexakisphosphate 5-phosphotransferase
Three mammalian isoforms are known to exist.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
diphosphoinositol pentakisphosphate kinase 2
O43314
-
diphosphoinositol pentakisphosphate synthetase
-
-
-
-
IHPK2
-
-
inositol hexakisphosphate kinase
-
-
-
-
inositol hexakisphosphate kinase
-
-
inositol hexakisphosphate kinase
-
-
inositol hexakisphosphate kinase 1
-
-
inositol hexakisphosphate kinase 1
-
-
inositol hexakisphosphate kinase 1
-
isoform
inositol hexakisphosphate kinase 2
-
-
inositol hexakisphosphate kinase 2
-
-
inositol hexakisphosphate kinase type 2
-
-
inositol hexakisphosphate kinase-1
-
-
inositol hexakisphosphate kinase-2
-
-
inositol hexakisphosphate kinase-2
-
-
inositol hexakisphosphate kinase-2
-
-
InsP6 kinase
-
-
-
-
InsP6K3
-
-
-
-
IP6 kinase
-
-
-
-
IP6K1
-
isoform
IP6K1
-
isoform
IP6K2
-
-
IP6K2
-
-
IP6K2
-
isoform
IP6K3
-
isoform
Pi uptake stimulator
-
-
PiUS
-
-
PPIP5K2
O43314
isoform
RID-2
-
RID-2, regulator of interferon-induced death, is identical to inositol hexakisphosphate kinase 2, IP6K2
kinase (phosphorylating), inositol hexakisphosphate
-
-
-
-
additional information
-
IP6K1 belongs to the family of inositol hexakisphosphate kinases
CAS REGISTRY NUMBER
COMMENTARY
176898-37-6
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
inositol hexakisphosphate kinase 2
SwissProt
Manually annotated by BRENDA team
insP6 kinase 2
SwissProt
Manually annotated by BRENDA team
gene Ihpk1
-
-
Manually annotated by BRENDA team
InsP6 kinase 1
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
deletion of isoform IP6K2 prevents the apoptotic actions of interferon beta and gamma-irradiation and cisplatin in different cancer cell lines
malfunction
-
cells lacking isoform IP6K1 arrest after genotoxic stress, and markers associated with DNA repair are recruited to DNAdamage sites indicating that homologous recombination repair is initiated in these cells. However, repair does not proceed to completion. Enzyme loss increases chromosomal damage susceptibility
malfunction
-
glycogen synthase kinase 3 activity is inhibited in the brains of IP6K1-deleted mice. Enzyme deletion disrupts social behavior
malfunction
-
isoform InsP6K1 disruption augments phosphatidylinositol-(3,4,5)-trisphosphate signaling and enhances superoxide production in neutrophils
malfunction
-
isoform IP6K2 depletion inhibits Hh target gene expression. Inhibiting enzyme activity results in altered Hedgehog signal transduction. Isoform IP6K2 knockdown alters craniofacial and somite structures and inhibits the development and migration of neural crest cells
malfunction
-
gene disruption of isoform IP6K2 in colorectal cancer cells selectively impairs p53-mediated apoptosis, instead favoring cell-cycle arrest
metabolism
-
isoform inositol hexakisphosphate kinase-2 acts as an effector of the vertebrate Hedgehog pathway. IP6K2 activity is required at the level or downstream of Smoothened but upstream of the transcription activator Gli1
physiological function
-
isoform IP6K2 plays a specific role in regulating cell death. Isoform IP6K2 overexpression, that causes 10 to 20fold increase in IP7 level, enhances cell death
physiological function
-
inositol hexakisphosphate kinase induces cell death in Huntington disease. The enzyme mediates apoptotic cell death via its translocation from the nucleus to the cytoplasm. Overexpression of the enzyme leads to the depletion of Akt phosphorylation and the induction of cell death
physiological function
-
loss of inositol pyrophosphate synthesis by inositol hexakisphosphate kinase 1 impairs homologous recombination in mammalian cells, leading to increased cell death
physiological function
-
IP6K1 binds and stimulates (4fold) glycogen synthase kinase 3 alpha and beta isoforms enzymatic activity in vitro in a catalytically independent mechanism (physiological activator)
physiological function
-
inositol hexakisphosphate kinase 1 regulates neutrophil function in innate immunity by inhibiting phosphatidylinositol-(3,4,5)-trisphosphate signaling. The enzyme does not regulate neutrophil trafficking and survival
physiological function
-
isoform P6K2 activity is required for normal development of craniofacial structures, somites, and neural crest cells
physiological function
-
isoform IP6K2 is required for p53-mediated apoptosis and modulates the outcome of the p53 response. IP6K2 acts by binding directly to p53 and decreasing expression of proarrest gene targets such as the cyclin-dependent kinase inhibitor p21
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + 1D-myo-inositol hexakisphosphate
ADP + 5-diphospho-1D-myo-inositol 1,2,3,4,6-pentakisphosphate
show the reaction diagram
-
-
-
?
ATP + 1D-myo-inositol hexakisphosphate
ADP + 5-diphospho-1D-myo-inositol 1,2,3,4,6-pentakisphosphate
show the reaction diagram
-
-
-
-
?
ATP + 1D-myo-inositol hexakisphosphate
ADP + 5-diphospho-1D-myo-inositol 1,2,3,4,6-pentakisphosphate
show the reaction diagram
-
-
-
?
ATP + 1D-myo-inositol hexakisphosphate
ADP + 5-diphospho-1D-myo-inositol 1,2,3,4,6-pentakisphosphate
show the reaction diagram
Q96PC2
-
-
-
?
ATP + 1D-myo-inositol hexakisphosphate
ADP + 5-diphospho-1D-myo-inositol 1,2,3,4,6-pentakisphosphate
show the reaction diagram
-
-
-
-
?
ATP + 1D-myo-inositol hexakisphosphate
ADP + 5-diphospho-1D-myo-inositol 1,2,3,4,6-pentakisphosphate
show the reaction diagram
Q9UHH9
-
-
-
?
ATP + 1D-myo-inositol hexakisphosphate
ADP + 5-diphospho-1D-myo-inositol 1,2,3,4,6-pentakisphosphate
show the reaction diagram
Q6PD10
-
-
-
?
ATP + 1D-myo-inositol hexakisphosphate
ADP + 5-diphospho-1D-myo-inositol 1,2,3,4,6-pentakisphosphate
show the reaction diagram
-
forward and reverse reaction are random bireactant systems
-
-
?, r
ATP + 1D-myo-inositol hexakisphosphate
ADP + 5-diphospho-1D-myo-inositol 1,2,3,4,6-pentakisphosphate
show the reaction diagram
-
enzyme is responsible for the biosynthesis of diphospho-myo-inositol pentakisphosphate. The enzyme also has a ATP synthase activity, implying that 5-diphospho-1D-myo-inositol pentakisphosphate functions as high-energy phosphate donor
-
r
ATP + 1D-myo-inositol hexakisphosphate
ADP + 5-diphospho-1D-myo-inositol 1,2,3,4,6-pentakisphosphate
show the reaction diagram
-
apoptosis regulation
-
-
?
ATP + 1D-myo-inositol hexakisphosphate
ADP + diphosphoinositol pentakisphosphate + bisdiphosphoinositol tetrakisphosphate
show the reaction diagram
-
-
-
-
?
ATP + 1D-myo-inositol hexakisphosphate
ADP + 1-diphospho-1D-myo-inositol 2,3,4,5,6-pentakisphosphate
show the reaction diagram
O43314
-
-
-
r
ATP + 1D-myo-inositol hexakisphosphate
ADP + 5-diphospho-1D-myo-inositol (1,2,3,4,6)-pentakisphosphate
show the reaction diagram
-
-
-
-
?
ATP + 1D-myo-inositol hexakisphosphate
ADP + 5-diphospho-1D-myo-inositol (1,2,3,4,6)-pentakisphosphate
show the reaction diagram
-
-
-
-
?
ATP + 1D-myo-inositol hexakisphosphate
ADP + 5-diphospho-1D-myo-inositol (1,2,3,4,6)-pentakisphosphate
show the reaction diagram
-
-
-
-
?
ATP + 1D-myo-inositol hexakisphosphate
ADP + 5-diphospho-1D-myo-inositol (1,2,3,4,6)-pentakisphosphate
show the reaction diagram
-
-
-
-
?
ATP + 1D-myo-inositol-1,3,4,5,6-pentakisphosphate
ADP + diphospho-1D-myo-inositol tetrakisphosphate
show the reaction diagram
Q96PC2
-
-
-
?
additional information
?
-
-, Q9UHH9
role of the enzyme as a mediator of growth inhibition and apoptosis in response to interferon-beta treatment. The cellular level of the enzyme is posttranscriptionally enhanced by interferon-beta, in ovarian carcinoma cells
-
-
-
additional information
?
-
-
IHPK2 binds to tumor necrosis factor receptor-associated factor 2 and interferes with phosphorylation of transforming growth factor beta-activated kinase 1, TAK1, thereby inhibiting NF-kappaB signaling. IHPK2 contains two sites required for TRAF2 binding, Ser347 and Ser359. IHPK2-TRAF2 binding leads to attenuation of TAK1- and NF-kappa B-mediated signaling and is partially responsible for the apoptotic activity of IHPK2. A portion of the death-promoting function of IHPK2 is independent of its kinase activity
-
-
-
additional information
?
-
-
IP6K2 belongs to a family of enzymes generating the inositol pyrophosphate IP7 [diphosphoinositol pentakisphosphate (5-PP-IP5)], it mediates apoptosis, increased IP6K2 activity sensitizes cancer cells to stressors, whereas its depletion blocks cell death
-
-
-
additional information
?
-
-
isoforms IP6K1 and IP6K2 bind to AP3B1protein
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + 1D-myo-inositol hexakisphosphate
ADP + 5-diphospho-1D-myo-inositol 1,2,3,4,6-pentakisphosphate
show the reaction diagram
-
enzyme is responsible for the biosynthesis of diphospho-myo-inositol pentakisphosphate. The enzyme also has a ATP synthase activity, implying that 5-diphospho-1D-myo-inositol pentakisphosphate functions as high-energy phosphate donor
-
r
ATP + 1D-myo-inositol hexakisphosphate
ADP + 5-diphospho-1D-myo-inositol 1,2,3,4,6-pentakisphosphate
show the reaction diagram
-
apoptosis regulation
-
-
?
additional information
?
-
-, Q9UHH9
role of the enzyme as a mediator of growth inhibition and apoptosis in response to interferon-beta treatment. The cellular level of the enzyme is posttranscriptionally enhanced by interferon-beta, in ovarian carcinoma cells
-
-
-
additional information
?
-
-
IHPK2 binds to tumor necrosis factor receptor-associated factor 2 and interferes with phosphorylation of transforming growth factor beta-activated kinase 1, TAK1, thereby inhibiting NF-kappaB signaling. IHPK2 contains two sites required for TRAF2 binding, Ser347 and Ser359. IHPK2-TRAF2 binding leads to attenuation of TAK1- and NF-kappa B-mediated signaling and is partially responsible for the apoptotic activity of IHPK2. A portion of the death-promoting function of IHPK2 is independent of its kinase activity
-
-
-
additional information
?
-
-
IP6K2 belongs to a family of enzymes generating the inositol pyrophosphate IP7 [diphosphoinositol pentakisphosphate (5-PP-IP5)], it mediates apoptosis, increased IP6K2 activity sensitizes cancer cells to stressors, whereas its depletion blocks cell death
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Mg2+
-
-
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1,3,4,5,6-inositol pentakisphosphate
-
IC50 for inositol hexakisphosphate kinase activity is 0.022 mM, IC50 for ATP synthase activity is 0.0128 mM
diphosphoinositol pentakisphosphate
-
IC50 for inositol hexakisphosphate kinase activity is 0.0066 mM, IC50 for ATP synthase activity is 0.0018 mM
H2O2
-
H2O2 as low as 0.1 mM dramatically reduces enzymatic activity
heat shock protein Hsp90
-
binding of HSP90 inhibits IP6K2 catalytic activity, IP6K2 binds to HSP90's C terminus. Depletion of HSP90 by RNAi in HEK-293 cells increases IP6K catalytic activity about 2.5fold, specificity of IP6K2-HSP90 interaction, overview. Drugs and selective mutations that abolish HSP90IP6K2 binding elicit activation of IP6K2, leading to cell death. Overexpression of HSP90 markedly and specifically reduces IP6K catalytic activity in HEK-293 cells, overexpression of HSP90 does not influence catalytic activity of IP6K1
-
inositol 1,2,4,5,6-pentakisphosphate
-
IC50 for inositol hexakisphosphate kinase activity is 0.022 mM
Inositol 1,3,4,5-tetrakisphosphate
-
IC50 for inositol hexakisphosphate kinase activity is 0.061 mM, IC50 for ATP synthase activity is 0.0325 mM
Inositol 1,4,5-trisphosphate
-
IC50 for ATP synthase activity is 0.253 mM
N(2)-(3-(trifluoromethy)lbenzyl) N(6)-(4-nitrobenzyl)purine
-
-
-
N(2)-(m-(trifluoromethy)lbenzyl) N(6)-(p-nitrobenzyl)purine
-
selective inhibitor in vitro
-
Inositol hexakisphosphate
-
IC50 for inositol hexakisphosphate kinase activity is 0.0008 mM, IC50 for ATP synthase activity is 0.0018 mM
additional information
O43314
isoform PPIP5K2 is insensitive to physiological changes in either [AMP] or [ATP]/[ADP] ratios
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
interferon beta
-
treatment with interferon beta enhances binding of IHPK2 to TNF receptor-associated factor 2
-
interferon-beta
-
induces IHPK2 activity after 4 h exposure
-
additional information
-
drugs and selective mutations that abolish HSP90IP6K2 binding elicit activation of IP6K2, leading to cell death
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.00039
-
1D-myo-inositol hexakisphosphate
O43314
isoform PPIP5K2, in 20 mM HEPES-NaOH pH 7.2, 50 m MKCl, at 37C
0.00197
-
5-diphospho-1D-myo-inositol (1,2,3,4,6)pentakisphosphate
-
pH 6.8, 37C
1.57
-
ADP
-
pH 6.8, 37C
0.037
-
ATP
O43314
isoform PPIP5K2, using 1D-myo-inositol hexakisphosphate as cosubstrate, in 20 mM HEPES-NaOH pH 7.2, 50 mM KCl, at 37C
1.35
-
ATP
-
pH 6.8, 37C
1.4
-
ATP
-
pH and temperature not specified in the publication
0.0055
-
D-myo-inositol-1,3,4,5,6-pentakisphosphate
Q96PC2
pH 7.0, 37C
0.0007
-
Inositol hexakisphosphate
-
pH 6.8, 37C
0.0009
-
Inositol hexakisphosphate
Q96PC2
pH 7.0, 37C
0.0061
-
Inositol hexakisphosphate
-
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.03
-
1D-myo-inositol hexakisphosphate
O43314
isoform PPIP5K2, in 20 mM HEPES-NaOH pH 7.2, 50 mM KCl, at 37C
kcat/KM VALUE [1/mMs-1]
kcat/KM VALUE [1/mMs-1] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
76
-
1D-myo-inositol hexakisphosphate
O43314
isoform PPIP5K2, in 20 mM HEPES-NaOH pH 7.2, 50 mM KCl, at 37C
143097
0.79
-
ATP
O43314
isoform PPIP5K2, using 1D-myo-inositol hexakisphosphate as cosubstrate, in 20 mM HEPES-NaOH pH 7.2, 50 mM KCl, at 37C
22040
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0128
-
1,3,4,5,6-inositol pentakisphosphate
-
IC50 for inositol hexakisphosphate kinase activity is 0.022 mM, IC50 for ATP synthase activity is 0.0128 mM
0.0018
-
diphosphoinositol pentakisphosphate
-
IC50 for inositol hexakisphosphate kinase activity is 0.0066 mM, IC50 for ATP synthase activity is 0.0018 mM
0.022
-
inositol 1,2,4,5,6-pentakisphosphate
-
IC50 for inositol hexakisphosphate kinase activity is 0.022 mM
0.0018
-
Inositol hexakisphosphate
-
IC50 for inositol hexakisphosphate kinase activity is 0.0008 mM, IC50 for ATP synthase activity is 0.0018 mM
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.4
-
-
assay at
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
37
-
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
coexpression with Hsp90
Manually annotated by BRENDA team
-
high expression
Manually annotated by BRENDA team
Q96PC2
highest activity occurs in Purkinje cells with somewhat lower levels in granule cells. In hippocampus substantial densities occur in CA1-CA4 layers of the hippocampus as well as the dentate gyrus
Manually annotated by BRENDA team
Q6PD10
faintly expressed
Manually annotated by BRENDA team
-
weak activity
Manually annotated by BRENDA team
Q9UHH9
low activity
Manually annotated by BRENDA team
Q6PD10
faintly expressed
Manually annotated by BRENDA team
Q96PC2
moderate activity
Manually annotated by BRENDA team
-
coexpression with Hsp90
Manually annotated by BRENDA team
Q9UHH9
low activity
Manually annotated by BRENDA team
-
weak activity
Manually annotated by BRENDA team
Q6PD10
faintly expressed
Manually annotated by BRENDA team
Q6PD10
faintly expressed
Manually annotated by BRENDA team
Q9UHH9
low activity
Manually annotated by BRENDA team
additional information
-
NIH-OVCAR-3 ovarian carcinoma cell
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Q96PC2
predominate in cytoplasm with only modest nuclear levels
Manually annotated by BRENDA team
-
comparable amounts of activity in the nucleus and cytoplasm
Manually annotated by BRENDA team
-
isoform InsP6K2 is localized mainly in the cytoplasm of lymphoblast cells from patients with Huntington disease
Manually annotated by BRENDA team
Q96PC2
low level of activity
Manually annotated by BRENDA team
Q96PC2
predominate in cytoplasm with only modest nuclear levels
Manually annotated by BRENDA team
-
comparable amounts of activity in the nucleus and cytoplasm
Manually annotated by BRENDA team
-
after treatment of transfected cells (fusion protein consisting of IKPK2 and enhanced green fluorescent protein) with interferon-beta the protein translocated to the nucleus, additionally treatment of HEK-293T cells with tamoxifen (30 microM, 24 h) causes translocation of IHPK2 into the condensing nucleus, transfection with NLS-eGFP results in restricted expression of the fusion protein in the cytoplasm in untreated and in apoptotic cells
Manually annotated by BRENDA team
-
cytotoxicity is associated with a translocation of InsP6K2 from nuclei to mitochondria
Manually annotated by BRENDA team
-
isoform InsP6K2 is localized mainly in the nucleus of normal lymphoblast cells
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
49200
-
-
calculated from amino acid sequence
57000
-
-
SDS-PAGE
60000
-
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 50000, isoform InsP6K2, SDS-PAGE
?
-
x * 50000, isoform IP6K1, SDS-PAGE
monomer
-
1 * 54000, SDS-PAGE
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-
O43314
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-70C, 20% glycerol, optimal stability
-
4C, 7 days, 50% loss of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-
Q9UHH9
GSTrap HP column chromatography
O43314
-
Q6PD10
glutathione Sepharose column chromatography, and gel filtration
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expressed in Escherichia coli BL21(DE3) cells
O43314
expressed in NIH-OVCAR-3 cells
-
expression in Escherichia coli
Q96PC2
expression in Escherichia coli and HEK-293T cells, additionally wild-type IHPK2 and the NLS mutant is cloned into the pCXN2 mammalian expression vector and electroporated into NIH-OVCAR-3 cells
-
expression in Escherichia coli, NIH-OVCAR-3 and Hey ovarian carcinoma cells, IP6K2 mRNA is not induced in NIH-OVCAR-3 cells following treatment with interferon-beta or gamma-irradiation, both gamma-irradiation and interferon-beta induce IP6K2 protein via a post-translational mechanism
-
expression in HeLa cells, PC12 cells, Jurkat T cells, OVCAR-3 cells, HL-60 cells and HEK-293 cells
-
GST fusion protein is transfected into HEK293T cells
Q9UHH9
expressed in Escherichia coli BL21 cells
-
expression of the wild-type enzyme in Saccharomyces cerevisiae mutant strains, overexpression of the GST-tagged or Myc-tagged enzyme in HEK-293, HeLa, and HCT116 cells, expression of wild-type and mutant enzymes in HEK-293 cells
-
gene Ihpk1, located on chromosome 9, has 6 exons, of which exon 1 is exclusively noncoding, the start codon is located in exon 2, and the stop codon is located in exon 6, DNA and amino acid sequence determination and analysis. Expressionin MEF cell lines
-
GST fusion protein is transfected into HEK293T cells
Q6PD10
overexpression of wild-type and inactive mutant IHPK2 in ovarian carcinoma cell lines
-
expression in Escherichia coli
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
R213A
O43314
the mutant shows a reduction in 1D-myo-inositol hexakisphosphate-stimulated ATPase activity of isofom PPIP5K2
S347A/S359A
-
no IHPK2 activity
R133A
-
mutation of IP6K2 in its putative HSP90-binding motif, mutation of Arg133 abolishes IP6K2-HSP90 binding
R136A
-
mutation of IP6K2 in its putative HSP90-binding motif, mutation of Arg136 abolishes IP6K2-HSP90 binding
S347A/S359A
-
site-directed mutagenesis, the mutant displays 3.5fold greater TAK1 activation following TNF-alpha, the mutant demonstrates a 6-10fold increase in NF-kappaB DNA binding following TNF-alpha compared with wild type IHPK2-expressing cells in which NF-kappa B DNA binding is inhibited
W131A
-
mutation of IP6K2 in its putative HSP90-binding motif, mutation of Trp131 modestly diminishes IP6K2-HSP90 binding, the catalytically impaired IP6K2-W131A does not induce cell death
K248A
O43314
the mutant shows a reduction in 1D-myo-inositol hexakisphosphate-stimulated ATPase activity of isofom PPIP5K2. The mutant shows a significant reduction in the rate of 1D-myo-inositol phosphate-independent ATPase activity of isofom PPIP5K2
additional information
-
NLS (nuclear localization sequence) mutant of IHPK2 (4 point mutations in the NLS) remains in the cytoplasm, even after interferon-beta treatment
K226A/S334A
-
catalytically inactive
additional information
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construction of an inactive enzyme mutant, overexpression of wild-type IHPK2 sensitizes ovarian carcinoma cell lines to the growth-suppressive and apoptotic effects of interferon beta, IFN-alpha2, and gamma-irradiation. Expression of a kinase-dead mutant abrogates 50% of the apoptosis induced by IFN-beta
additional information
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depletion of IP6K2 in HEK-293 cells by RNAi leads to 40-50% reduced cell death, overview. Deletion mapping of IP6K2 to identify HSP90-binding motif, overview. The yeast Saccharomyces cerevisiae possesses constitutive and inducible homologues of HSP90, designated HSC82 and HSP82, respectively. In HSC82 KO yeast, IP6K activity is 2.5fold higher than murine wild-type, in yeast HSP82 null mutant, IP6K catalytic activity is increased but to a lesser extent. Overexpression of HSP90 markedly reduces IP6K catalytic activity in HEK-293 cells
additional information
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gene deletion of IP6K1 in mice leads to markedly diminished production of inositol diphosphates. Male mutant mice are sterile with defects in spermiogenesis. Mutant mice are smaller than wild-type despite normal food intake. The mutants display markedly lower circulating insulin, phenotype, overview
Renatured/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
dialysis against renaturing buffer (25% sucrose, 0.1% Tween 40, 84 mM HEPES pH 7.5) after elution with denaturing buffer containing 150 mM imidazole
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APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
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selectively blocking HSP90-IP6K2 binding could provide effective and safer modes of chemotherapy to block apoptosis