Information on EC 2.7.4.24 - diphosphoinositol-pentakisphosphate kinase

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The enzyme appears in viruses and cellular organisms

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EC NUMBER
COMMENTARY hide
2.7.4.24
-
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RECOMMENDED NAME
GeneOntology No.
diphosphoinositol-pentakisphosphate kinase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + 1D-myo-inositol 5-diphosphate 1,2,3,4,6-pentakisphosphate = ADP + 1D-myo-inositol 1,5-bis(diphosphate) 2,3,4,6-tetrakisphosphate
show the reaction diagram
; (1)
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-
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ATP + 1D-myo-inositol hexakisphosphate = ADP + 1D-myo-inositol 1-diphosphate 2,3,4,5,6-pentakisphosphate
show the reaction diagram
(2)
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
-
-
-
-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
inositol pyrophosphates biosynthesis
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-
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SYSTEMATIC NAME
IUBMB Comments
ATP:1D-myo-inositol-5-diphosphate-pentakisphosphate phosphotransferase
This enzyme is activated by osmotic shock [4]. Ins(1,3,4,5,6)P5, 1D-myo-inositol diphosphate tetrakisphosphate and 1D-myo-inositol bisdiphosphate triphosphate are not substrates [4].
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CAS REGISTRY NUMBER
COMMENTARY hide
188929-01-3
-
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
physiological function
-
the yeast VIP/PPIP5K family enzymes phosphorylate the 1/3-position of the inositol ring in vitro and in vivo, and convert inositol hexakisphosphate to 1/3-diphosphoinositol pentakisphosphate with determination of unequivocally 1/3,5-(PP)2-IP4 is the isomeric structure of the bis-diphosphoinositol tetrakisphosphate
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
1-diphospho-1D-myo-inositol 2,3,4,5,6-pentakisphosphate + ATP
1,5-bisdiphospho-1D-myo-inositol 2,3,4,6-tetrakisphosphate + ADP
show the reaction diagram
3-diphospho-1D-myo-inositol 1,2,4,5,6-pentakisphosphate + ATP
3,5-bisdiphospho-1D-myo-inositol 1,2,4,6-tetrakisphosphate + ADP
show the reaction diagram
5-diphospho-1D-myo-inositol 1,2,3,4,6-pentakisphosphate + ATP
3,5-bisdiphospho-1D-myo-inositol 1,2,4,6-tetrakisphosphate + ADP
show the reaction diagram
ADP + 1,5-bis-diphospho-1D-myo-inositol 2,3,4,6-tetrakisphosphate
ATP + 5-diphospho-1D-myo-inositol 1,2,3,4,6-pentakisphosphate
show the reaction diagram
-
-
-
r
ADP + 1-diphospho-1D-myo-inositol 2,3,4,5,6-pentakisphosphate
ATP + 1D-myo-inositol hexakisphosphate
show the reaction diagram
-
-
-
r
ADP + diphosphoinositol pentakisphosphate
ATP + ?
show the reaction diagram
-
enzyme has ATP synthase activity
-
-
?
ATP + 1D-myo-inositol 5-diphosphate 1,2,3,4,6-pentakisphosphate
ADP + 1D-myo-inositol 1,5-bis(diphosphate) 2,3,4,6-tetrakisphosphate
show the reaction diagram
-
-
-
?
ATP + 1D-myo-inositol 5-diphosphate pentakisphosphate
ADP + 1D-myo-inositol bisdiphosphate tetrakisphosphate
show the reaction diagram
ATP + 1D-myo-inositol hexakisphosphate
ADP + 1D-myo-inositol 1-diphosphate 2,3,4,5,6-pentakisphosphate
show the reaction diagram
-
-
-
?
ATP + 5-diphospho-1D-myo-inositol 1,2,3,4,6-pentakisphosphate
ADP + 1,5-bis-diphospho-1D-myo-inositol 2,3,4,6-tetrakisphosphate
show the reaction diagram
-
-
-
r
ATP + 5-diphospho-1D-myo-inositol pentakisphosphate
ADP + bis(diphospho)-1D-myo-inositol tetrakisphosphate
show the reaction diagram
ATP + 5-diphospho-1D-myo-inositol-pentakisphosphate
ADP + bis(diphospho)-1D-myo-inositol tetrakisphosphate
show the reaction diagram
additional information
?
-
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
1-diphospho-1D-myo-inositol 2,3,4,5,6-pentakisphosphate + ATP
1,5-bisdiphospho-1D-myo-inositol 2,3,4,6-tetrakisphosphate + ADP
show the reaction diagram
3-diphospho-1D-myo-inositol 1,2,4,5,6-pentakisphosphate + ATP
3,5-bisdiphospho-1D-myo-inositol 1,2,4,6-tetrakisphosphate + ADP
show the reaction diagram
5-diphospho-1D-myo-inositol 1,2,3,4,6-pentakisphosphate + ATP
3,5-bisdiphospho-1D-myo-inositol 1,2,4,6-tetrakisphosphate + ADP
show the reaction diagram
ATP + 1D-myo-inositol 5-diphosphate 1,2,3,4,6-pentakisphosphate
ADP + 1D-myo-inositol 1,5-bis(diphosphate) 2,3,4,6-tetrakisphosphate
show the reaction diagram
O43314
-
-
-
?
ATP + 1D-myo-inositol 5-diphosphate pentakisphosphate
ADP + 1D-myo-inositol bisdiphosphate tetrakisphosphate
show the reaction diagram
ATP + 1D-myo-inositol hexakisphosphate
ADP + 1D-myo-inositol 1-diphosphate 2,3,4,5,6-pentakisphosphate
show the reaction diagram
O43314
-
-
-
?
ATP + 5-diphospho-1D-myo-inositol pentakisphosphate
ADP + bis(diphospho)-1D-myo-inositol tetrakisphosphate
show the reaction diagram
-
bis(diphospho)-1D-myo-inositol tetrakisphosphate specifically impedes protein trafficking, no regulation by extracellular signal-regulated kinase or phopholipase D
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-
?
ATP + 5-diphospho-1D-myo-inositol-pentakisphosphate
ADP + bis(diphospho)-1D-myo-inositol tetrakisphosphate
show the reaction diagram
-
-
-
-
?
additional information
?
-
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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INHIBITORS
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-(phosphonoacetic acid ester)-1D-myo-inositol tetrakisphosphate
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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-(phosphonoacetic acid ester)-1D-myo-inositol pentakisphosphate
most potent inhibitor
5-(phosphonoacetic acid ester)-1D-myo-inositol tetrakisphosphate
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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
chlorpromazine
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inhibition in vivo
F-
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50% inhibition at 0.03 mM
genistein
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rapid inhibition in vivo
N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide
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i.e. W-7, rapid inhibition in vivo
additional information
-
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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
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2-O-benzoyl-myo-inositol 1,2,3,4,6-pentakisphosphate
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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
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2-O-benzyl-myo-inositol 1,2,3,4,6-pentakisphosphate
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2-O-butanoyl-myo-inositol 1,2,3,4,6-pentakisphosphate
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5-O-alpha-diphosphate-myo-inositol 1,3,4,6-tetrakisphosphate
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5-O-alpha-phoshonoacetyl-myo-inositol 1,3,4,6-tetrakisphosphate
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5-O-alpha-phosphonoacetyl-myo-inositol 1,2,3,4,6-pentakisphosphate
stimulates ATP hydrolysis 5fold
monoperoxo(picolinato)oxovanadate(V)
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15fold activation
sorbitol
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rapid activation in vivo
Sucrose
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rapid activation in vivo
additional information
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000022
1,5-bis-diphospho-1D-myo-inositol 2,3,4,6-tetrakisphosphate
isoform PPIP5K2, in 20 mM HEPES-NaOH pH 7.2, 50 mM KCl, at 37°C
0.00011
1-diphospho-1D-myo-inositol 2,3,4,5,6-pentakisphosphate
isoform PPIP5K2, in 20 mM HEPES-NaOH pH 7.2, 50 m MKCl, at 37°C
0.0001 - 0.00019
1D-myo-inositol 5-diphosphate pentakisphosphate
0.00006
5-diphospho-1D-myo-inositol 1,2,3,4,6-pentakisphosphate
isoform PPIP5K2, in 20 mM HEPES-NaOH pH 7.2, 50 mM KCl, at 37°C
0.0052 - 1.39
ADP
0.022 - 1.89
ATP
0.7
diphosphoinositol pentakisphosphate
-
pH 6.8, 37°C
1.94
diphosphoinositol tetrakisphosphate
-
pH 6.8, 37°C
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.19
1,5-bis-diphospho-1D-myo-inositol 2,3,4,6-tetrakisphosphate
isoform PPIP5K2, in 20 mM HEPES-NaOH pH 7.2, 50 mM KCl, at 37°C
0.002
1-diphospho-1D-myo-inositol 2,3,4,5,6-pentakisphosphate
isoform PPIP5K2, in 20 mM HEPES-NaOH pH 7.2, 50 m MKCl, at 37°C
4 - 38
1D-myo-inositol 5-diphosphate pentakisphosphate
0.13
5-diphospho-1D-myo-inositol 1,2,3,4,6-pentakisphosphate
isoform PPIP5K2, in 20 mM HEPES-NaOH pH 7.2, 50 mM KCl, at 37°C
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
8500
1,5-bis-diphospho-1D-myo-inositol 2,3,4,6-tetrakisphosphate
isoform PPIP5K2, in 20 mM HEPES-NaOH pH 7.2, 50 mM KCl, at 37°C
17
1-diphospho-1D-myo-inositol 2,3,4,5,6-pentakisphosphate
isoform PPIP5K2, in 20 mM HEPES-NaOH pH 7.2, 50 m MKCl, at 37°C
2200
5-diphospho-1D-myo-inositol 1,2,3,4,6-pentakisphosphate
isoform PPIP5K2, in 20 mM HEPES-NaOH pH 7.2, 50 mM KCl, at 37°C
0.037 - 0.21
ADP
5.9
ATP
isoform PPIP5K2, using 5-diphospho-1D-myo-inositol 1,2,3,4,6-pentakisphosphate as cosubstrate, in 20 mM HEPES-NaOH pH 7.2, 50 mM KCl, at 37°C
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00017
2,5-O-benzyl-myo-inositol 1,3,4,6-tetrakisphosphate
Homo sapiens
O43314
inhibition of the 1,5-[PP]2-InsP4 dephosphorylation, pH 7.0, 37°C
0.391
2-O-benzyl-5-(phosphonoacetic acid ester)-1D-myo-inositol tetrakisphosphate
Homo sapiens
O43314
pH and temperature not specified in the publication
0.00042
2-O-benzyl-5-O-alpha-phosphonoacetyl-myo-inositol 1,3,4,6-tetrakisphosphate
Homo sapiens
O43314
inhibition of the 1,5-[PP]2-InsP4 dephosphorylation, pH 7.0, 37°C
0.0005
2-O-benzyl-5-O-diphosphate-myo-inositol 1,3,4,6-tetrakisphosphate
Homo sapiens
O43314
inhibition of the 1,5-[PP]2-InsP4 dephosphorylation, pH 7.0, 37°C
0.00044
2-O-benzyl-myo-inositol 1,2,3,4,6-pentakisphosphate
Homo sapiens
O43314
inhibition of the 1,5-[PP]2-InsP4 dephosphorylation, pH 7.0, 37°C
0.129
5-(phosphonoacetic acid ester)-1D-myo-inositol pentakisphosphate
Homo sapiens
O43314
pH and temperature not specified in the publication
1.386
5-(phosphonoacetic acid ester)-1D-myo-inositol tetrakisphosphate
Homo sapiens
O43314
pH and temperature not specified in the publication
0.0024
5-O-alpha-diphosphate-myo-inositol 1,3,4,6-tetrakisphosphate
Homo sapiens
O43314
inhibition of the 1,5-[PP]2-InsP4 dephosphorylation, pH 7.0, 37°C
0.00014
5-O-alpha-phosphonoacetyl-myo-inositol 1,2,3,4,6-pentakisphosphate
Homo sapiens
O43314
inhibition of the 1,5-[PP]2-InsP4 dephosphorylation, pH 7.0, 37°C
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7 - 7.5
assay at
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5 - 8.5
-
half maximal acitvity at pH 5.5 and pH 8.5
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25 - 40
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70% activity at 25°C and 40°C
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
smooth muscle cell line
Manually annotated by BRENDA team
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
primarily; primarily
Manually annotated by BRENDA team
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
56000
-
SDS-PAGE
60000
-
gel filtration
138000
about, isozyme PPIP5K2, mass spectrometry
160000
200000
sucrose density gradient centrifugation
400000
gel filtration
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SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
the enzyme contains a putative ATP-grasp kinase domain
monomer
-
1 * 56000, SDS-PAGE
additional information
the enzyme contains a putative ATP-grasp kinase domain
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Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
N-terminally truncated PPIP5K2 kinase 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 4°C, 3 days, 4°C, X-ray diffraction structure determination and analysis
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4
-
complete loss of activity within 18 h
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 50% loss of activity in 20% glycerol after 1 week
-
-70°C, no loss of activity in 20% glycerol for 3 months
-
4°C, complete loss of activity within 18 h
-
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
GSTrap HP column chromatography
native PPIP5K1 from rat brain by anion exchange and heparin affinity chromatography, followed by nickel affinity chromatography and sucrose gradient centrifugation
recombinant FLAG-tagged or untagged isozymes PPIP5K1 and PPIP5K2 from HEK-293 cells and isozyme PPIP5K1 from Escherichia coli, respectively
recombinant GST-tagged wild-type Saccharomyces cerevisiae Vip1 kinase domain and mutant Vip1 fused to human GSTIP6K1 from bacteria
recombinant wild-type and truncated mutant enzymes
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
DNA and amino acid sequence determination and analysis
expressed in Escherichia coli BL21(DE3) cells
expression of wild-type Saccharomyces cerevisiae Vip1 kinase domain and of mutant Vip1 fused to human GSTIP6K1 as GST-tagged proteins in bacteria
functional overexpression of isozymes PPIP5K1 and PPIP5K2 in HEK-293 cells, expression of isozyme PPIP5K1 in Escherichia coli
gene VIP1, DNA and amino acid sequence determination and analysis, VIP1 expression in mutant yeast, functional expression of CFP- or GST-tagged VIP1 in HEK-293T cells; gene VIP2, DNA and amino acid sequence determination and analysis, functional expression of CFP- or GST-tagged VIP2 in HEK-293T cells
recombinant expression of wild-type and mutant enzymes
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D332A
catalytically inactive mutant of isozyme PPIP5K1
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
additional information
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LINKS TO OTHER DATABASES (specific for EC-Number 2.7.4.24)
ExplorEnz
ExPASy
KEGG
MetaCyc
SABIO-RK
NCBI: PubMed, Protein, Nucleotide, Structure, Genome, OMIM
IUBMB Enzyme Nomenclature
PROSITE Database of protein families and domains
InterPro (database of protein families, domains and functional sites)