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Information on EC 2.7.4.21 - inositol-hexakisphosphate kinase and Organism(s) Homo sapiens and UniProt Accession O43314

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IUBMB Comments
Three mammalian isoforms are known to exist.
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Select one or more organisms in this record:
This record set is specific for:
Homo sapiens
UNIPROT: O43314
Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Synonyms
AtIPK2alpha, AtIpk2beta, AtVip1, AtVip2, diphosphoinositol pentakisphosphate kinase 2, diphosphoinositol pentakisphosphate synthetase, EhIP6KA, IHPK2, inositol hexakisphosphate 5-kinase, inositol hexakisphosphate kinase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diphosphoinositol pentakisphosphate kinase 2
288412
-
diphosphoinositol pentakisphosphate synthetase
-
-
-
-
inositol hexakisphosphate 5-kinase
288412
-
inositol hexakisphosphate kinase
-
-
-
-
inositol hexakisphosphate kinase 1
inositol hexakisphosphate kinase 2
247
-
inositol hexakisphosphate kinase type 2
inositol hexakisphosphate kinase-2
247
-
InsP6 kinase
-
-
-
-
InsP6-kinase
247
-
InsP6K1
247
-
InsP6K2
InsP6K3
-
-
-
-
IP6 kinase
-
-
-
-
IP6K1
306239
-
IP6K2
kinase (phosphorylating), inositol hexakisphosphate
-
-
-
-
PPIP5K2
288412
isoform
RID-2
247
RID-2, regulator of interferon-induced death, is identical to inositol hexakisphosphate kinase 2, IP6K2
additional information
288412
cf. EC 2.7.4.24
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
-
-
phospho-group transfer
-
-
-
-
PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
ATP:1D-myo-inositol-hexakisphosphate 5-phosphotransferase
Three mammalian isoforms are known to exist.
CAS REGISTRY NUMBER
COMMENTARY hide
176898-37-6
-
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-diphosphate pentakisphosphate
ADP + 1D-myo-inositol 1,5-bis(diphosphate) 2,3,4,6-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
-
-
-
r
ATP + 1D-myo-inositol hexakisphosphate
ADP + 1D-myo-inositol 5-diphosphate 1,2,3,4,6-pentakisphosphate
show the reaction diagram
-
-
-
?
ATP + 1D-myo-inositol hexakisphosphate
ADP + 1D-myo-inositol 5-diphosphate 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
-
-
-
?
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-diphosphate pentakisphosphate
ADP + 1D-myo-inositol 1,5-bis(diphosphate) 2,3,4,6-tetrakisphosphate
show the reaction diagram
O43314
-
-
-
?
ATP + 1D-myo-inositol hexakisphosphate
ADP + 1D-myo-inositol 5-diphosphate 1,2,3,4,6-pentakisphosphate
show the reaction diagram
O43314
-
-
-
?
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
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mg2+
required
Mg2+
required
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2,5-O-benzyl-myo-inositol 1,3,4,6-tetrakisphosphate
activates the ATP hydrolysis activity and inhibits the PPIP5K2 activity and InsP6 kinase activity, and the 1,5-[PP]2-InsP4 dephosphorylation activity of the enzyme. The compound can inhibit inositol phosphate kinase activity without occupying the catalytic site
2-O-benzyl-5-O-alpha-phosphonoacetyl-myo-inositol 1,3,4,6-tetrakisphosphate
stimulates ATP hydrolysis 9fold, but inhibits 1,5-[PP]2-InsP4 dephosphorylation activity of the enzyme. The compound can inhibit inositol phosphate kinase activity without occupying the catalytic site
2-O-benzyl-5-O-diphosphate-myo-inositol 1,3,4,6-tetrakisphosphate
activates ATP hydrolysis activity but inhibits 1,5-[PP]2-InsP4 dephosphorylation activity of the enzyme
2-O-benzyl-myo-inositol 1,2,3,4,6-pentakisphosphate
activates ATP hydrolysis activity but inhibits 1,5-[PP]2-InsP4 dephosphorylation activity of the enzyme
5-O-alpha-diphosphate-myo-inositol 1,3,4,6-tetrakisphosphate
activates ATP hydrolysis activity but inhibits 1,5-[PP]2-InsP4 dephosphorylation activity of the enzyme
5-O-alpha-phosphonoacetyl-myo-inositol 1,2,3,4,6-pentakisphosphate
stimulates ATP hydrolysis 5fold, but inhibits 1,5-[PP]2-InsP4 dephosphorylation activity of the enzyme
N(2)-(m-(trifluoromethyl)benzyl) N(6)-(p-nitrobenzyl)purine
-
selective inhibitor in vitro
N2-(3-trifluorobenzyl)-N6-(4-nitrobenzyl)purine
-
TNP, a selective IP6K inhibitor, abolishes the production of enantiomer Ins(2,3,4,5,6)P5 in different typesof cells
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2,5-O-benzyl-myo-inositol 1,3,4,6-tetrakisphosphate
activates the ATP hydrolysis activity and inhibits the InsP6 kinase activity of the enzyme
2-O-aminoethyl-myo-inositol 1,2,3,4,6-pentakisphosphate
-
2-O-benzoyl-myo-inositol 1,2,3,4,6-pentakisphosphate
-
2-O-benzyl-5-O-alpha-phosphonoacetyl-myo-inositol 1,3,4,6-tetrakisphosphate
stimulates ATP hydrolysis 9fold
2-O-benzyl-5-O-diphosphate-myo-inositol 1,3,4,6-tetrakisphosphate
-
2-O-benzyl-myo-inositol 1,2,3,4,6-pentakisphosphate
-
2-O-butanoyl-myo-inositol 1,2,3,4,6-pentakisphosphate
-
5-O-alpha-diphosphate-myo-inositol 1,3,4,6-tetrakisphosphate
-
5-O-alpha-phoshonoacetyl-myo-inositol 1,3,4,6-tetrakisphosphate
-
5-O-alpha-phosphonoacetyl-myo-inositol 1,2,3,4,6-pentakisphosphate
stimulates ATP hydrolysis 5fold
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
synthesis and effects of inositol phosphates and analogues upon ATPase activity, overview. The compounds are also inhibitors of [PP]2-InsP4 dephosphorylation. Binding structures, overview
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00039
1D-myo-inositol hexakisphosphate
isoform PPIP5K2, in 20 mM HEPES-NaOH pH 7.2, 50 m MKCl, at 37C
0.037
ATP
isoform PPIP5K2, using 1D-myo-inositol hexakisphosphate as cosubstrate, in 20 mM HEPES-NaOH pH 7.2, 50 mM KCl, at 37C
0.0055
D-myo-inositol-1,3,4,5,6-pentakisphosphate
pH 7.0, 37C
0.0009
Inositol hexakisphosphate
pH 7.0, 37C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.03
1D-myo-inositol hexakisphosphate
isoform PPIP5K2, in 20 mM HEPES-NaOH pH 7.2, 50 mM KCl, at 37C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
76
1D-myo-inositol hexakisphosphate
isoform PPIP5K2, in 20 mM HEPES-NaOH pH 7.2, 50 mM KCl, at 37C
0.79
ATP
isoform PPIP5K2, using 1D-myo-inositol hexakisphosphate as cosubstrate, in 20 mM HEPES-NaOH pH 7.2, 50 mM KCl, at 37C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7 - 7.5
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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
low activity
Manually annotated by BRENDA team
co-localization with phosphorylated TDP-43 of InsP6K2 in the cytoplasm of anterior horn cells of the spinal cord
Manually annotated by BRENDA team
low activity
Manually annotated by BRENDA team
additional information
-
NIH-OVCAR-3 ovarian carcinoma cell
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
low level of activity
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
the absence of diphosphorylation in the IC(1-70)fragment suggests that the Ser-Pro cluster (residues 71-111) is required to facilitate pyrophosphorylation on Ser51. The site of diphosphorylation in mouse IC-2C is well conserved in human and rat, suggesting that the effect of IP7 on dynein is likely to be conserved in these species
malfunction
physiological function
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
Sequence
VIP2_HUMAN
1243
0
140407
Swiss-Prot
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
49200
-
calculated from amino acid sequence
50000
-
x * 50000, isoform InsP6K2, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
-
x * 50000, isoform InsP6K2, SDS-PAGE
CRYSTALLIZATION/commentary
ORGANISM
UNIPROT
LITERATURE
N-terminally truncated enzyme mutant, residues 41-366, hanging drop vapor diffusion against a well buffer of 12% w/v PEG 3350, 20 mM MgCl2, 0.1 M HEPES, pH 7.0, 0,1 mM AMP-PNP, and 2 mM CdCl2 at 4C, 3 days, 4C, X-ray diffraction structure determination and analysis
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
E192G
site-directed mutagenesis
E192Q
site-directed mutagenesis
K103A
site-directed mutagenesis
K213A
site-directed mutagenesis
K248A
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
K54A
site-directed mutagenesis
R213A
the mutant shows a reduction in 1D-myo-inositol hexakisphosphate-stimulated ATPase activity of isofom PPIP5K2
S347A/S359A
-
no IHPK2 activity
additional information
PURIFICATION/commentary
ORGANISM
UNIPROT
LITERATURE
GSTrap HP column chromatography
recombinant wild-type and truncated mutant enzymes
CLONED/commentary
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3) cells
recombinant expression of wild-type and mutant enzymes
expressed in NIH-OVCAR-3 cells
-
expression in Escherichia coli
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
recombinant co-overexpression of InsP6K2 and C-terminal residues 219-414 of TDP-43 from InsP6K2-pDsRed tag and TDP219-pEGFP tag plasmids in SHSY-5Y cells. Transfection of SHSY-5Y cells with a plasmid encoding a catalytically inactive, dominant-negative InsP6K2 (K2 K/A). HSP90 protein expression is reduced in the cytoplasmic fraction of TDP219- and InsP6K2-transfected cells. HSP90 expression is also significantly reduced in cells doubly transfected with TDP219M and InsP6K2 compared with control cells
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Saiardi, A.; Erdjument-Bromage, H.; Snowman, A.M.; Tempst, P.; Snyder, S.H.
Synthesis of diphosphoinositol pentakisphosphate by a newly identified family of higher inositol polyphosphate kinases
Curr. Biol.
9
1323-1326
1999
Homo sapiens (Q9UHH9), Mus musculus (Q6PD10)
Manually annotated by BRENDA team
Albert, C.; Safrany, S.T.; Bembenek, M.E.; Reddy, K.M.; Reddy, K.K.; Falck, J.R.; Brcker, M.; Shears, S.B.; Mayr, G.W.
Biological variability in the structures of diphosphoinositol polyphosphates in Dictyostelium discoideum and mammalian cells
Biochem. J.
327
553-560
1997
Cricetulus griseus, Homo sapiens, Mus musculus
-
Manually annotated by BRENDA team
Morrison, B.H.; Bauer, J.A.; Kalvakolanu, D.V.; Lindner, D.J.
Inositol hexakisphosphate kinase 2 mediates growth suppressive and apoptotic effects of interferon-beta in ovarian carcinoma cells
J. Biol. Chem.
276
24965-24970
2001
Homo sapiens, Homo sapiens (Q9UHH9)
Manually annotated by BRENDA team
Saiardi, A.; Nagata, E.; Luo, H.R.; Snowman, A.M.; Snyder, S.H.
Identification and characterization of a novel inositol hexakisphosphate kinase
J. Biol. Chem.
276
39179-39185
2001
Homo sapiens (Q96PC2), Mus musculus
Manually annotated by BRENDA team
Morrison, B.H.; Tang, Z.; Jacobs, B.S.; Bauer, J.A.; Lindner, D.J.
Apo2L/TRAIL induction and nuclear translocation of inositol hexakisphosphate kinase 2 during IFN-beta-induced apoptosis in ovarian carcinoma
Biochem. J.
385
595-603
2005
Homo sapiens
Manually annotated by BRENDA team
Nagata, E.; Luo, H.R.; Saiardi, A.; Bae, B.I.; Suzuki, N.; Snyder, S.H.
Inositol hexakisphosphate kinase-2, a physiologic mediator of cell death
J. Biol. Chem.
280
1634-1640
2005
Homo sapiens
Manually annotated by BRENDA team
Morrison, B.H.; Bauer, J.A.; Hu, J.; Grane, R.W.; Ozdemir, A.M.; Chawla-Sarkar, M.; Gong, B.; Almasan, A.; Kalvakolanu, D.V.; Lindner, D.J.
Inositol hexakisphosphate kinase 2 sensitizes ovarian carcinoma cells to multiple cancer therapeutics
Oncogene
21
1882-1889
2002
Homo sapiens
Manually annotated by BRENDA team
Morrison, B.H.; Bauer, J.A.; Lupica, J.A.; Tang, Z.; Schmidt, H.; DiDonato, J.A.; Lindner, D.J.
Effect of inositol hexakisphosphate kinase 2 on transforming growth factor beta-activated kinase 1 and NF-kappaB activation
J. Biol. Chem.
282
15349-15356
2007
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Weaver, J.D.; Wang, H.; Shears, S.B.
The kinetic properties of a human PPIP5K reveal that its kinase activities are protected against the consequences of a deteriorating cellular bioenergetic environment
Biosci. Rep.
33
e00022
2013
Homo sapiens, Homo sapiens (O43314)
Manually annotated by BRENDA team
Nagata, E.; Saiardi, A.; Tsukamoto, H.; Okada, Y.; Itoh, Y.; Satoh, T.; Itoh, J.; Margolis, R.L.; Takizawa, S.; Sawa, A.; Takagi, S.
Inositol hexakisphosphate kinases induce cell death in Huntington disease
J. Biol. Chem.
286
26680-26686
2011
Homo sapiens
Manually annotated by BRENDA team
Prasad, A.; Jia, Y.; Chakraborty, A.; Li, Y.; Jain, S.K.; Zhong, J.; Roy, S.G.; Loison, F.; Mondal, S.; Sakai, J.; Blanchard, C.; Snyder, S.H.; Luo, H.R.
Inositol hexakisphosphate kinase 1 regulates neutrophil function in innate immunity by inhibiting phosphatidylinositol-(3,4,5)-trisphosphate signaling
Nat. Immunol.
12
752-760
2011
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Koldobskiy, M.A.; Chakraborty, A.; Werner, J.K.; Snowman, A.M.; Juluri, K.R.; Vandiver, M.S.; Kim, S.; Heletz, S.; Snyder, S.H.
p53-mediated apoptosis requires inositol hexakisphosphate kinase-2
Proc. Natl. Acad. Sci. USA
107
20947-20951
2010
Homo sapiens
Manually annotated by BRENDA team
Wundenberg, T.; Grabinski, N.; Lin, H.; Mayr, G.W.
Discovery of InsP6-kinases as InsP6-dephosphorylating enzymes provides a new mechanism of cytosolic InsP6 degradation driven by the cellular ATP/ADP ratio
Biochem. J.
462
173-184
2014
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Chanduri, M.; Rai, A.; Malla, A.B.; Wu, M.; Fiedler, D.; Mallik, R.; Bhandari, R.
Inositol hexakisphosphate kinase 1 (IP6K1) activity is required for cytoplasmic dynein-driven transport
Biochem. J.
473
3031-3047
2016
Dictyostelium discoideum, Homo sapiens (Q92551), Mus musculus (Q6PD10), Mus musculus C57BL/6 (Q6PD10)
Manually annotated by BRENDA team
Wang, H.; Godage, H.Y.; Riley, A.M.; Weaver, J.D.; Shears, S.B.; Potter, B.V.
Synthetic inositol phosphate analogs reveal that PPIP5K2 has a surface-mounted substrate capture site that is a target for drug discovery
Chem. Biol.
21
689-699
2014
Homo sapiens (O43314)
Manually annotated by BRENDA team
Nagata, E.; Nonaka, T.; Moriya, Y.; Fujii, N.; Okada, Y.; Tsukamoto, H.; Itoh, J.; Okada, C.; Satoh, T.; Arai, T.; Hasegawa, M.; Takizawa, S.
Inositol hexakisphosphate kinase 2 promotes cell death in cells with cytoplasmic TDP-43 aggregation
Mol. Neurobiol.
53
5377-5383
2016
Homo sapiens, Homo sapiens (Q9UHH9)
Manually annotated by BRENDA team
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