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Information on EC 2.7.4.24 - diphosphoinositol-pentakisphosphate 1-kinase and Organism(s) Homo sapiens
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2.7.4.24 diphosphoinositol-pentakisphosphate 1-kinaseIUBMB Comments
This enzyme is activated by osmotic shock . Ins(1,3,4,5,6)P5, 1D-myo-inositol diphosphate tetrakisphosphate and 1D-myo-inositol bisdiphosphate triphosphate are not substrates . The enzyme specifically phosphorylates the 1-position of the substrates .
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Word Map
- 2.7.4.24
- pyrophosphate
- polyphosphate
-
pp-insps
- hexakisphosphate
-
5-insp7
- tetrakisphosphate
-
bisdiphosphoinositol
- spx
- medicine
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Archaea
Reaction Schemes
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Synonyms
ppip5k, diphosphoinositol pentakisphosphate kinase, ip7 kinase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ATP:5-diphospho-1D-myo-inositol-pentakisphosphate phosphotransferase
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-
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diphospho-myo-inositol pentakisphosphate 5-kinase
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diphosphoinositol pentakisphosphate kinase
kinase (phosphorylating), diphosphoinositol 1,2,3,4,5-pentakisphosphate 5-
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-
-
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PP-InsP5 kinase
PP-IP5 kinase
PPIP5K
PPIP5K1
PPIP5K2
VIP1
VIP2
additional information
diphosphoinositol pentakisphosphate kinase
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-
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PP-InsP5 kinase
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PP-IP5 kinase
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-
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PPIP5K
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PPIP5K1
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-
-
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PPIP5K2
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-
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VIP1
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-
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VIP2
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-
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additional information
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the enzyme belongs to the VIP/diphosphoinositol pentakisphosphate kinase, PPIP5K, family of inositol phosphate kinases
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
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-
-
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PATHWAY SOURCE
PATHWAYS
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-
SYSTEMATIC NAME
IUBMB Comments
ATP:1D-myo-inositol-5-diphosphate-pentakisphosphate 1-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]. The enzyme specifically phosphorylates the 1-position of the substrates [6].
CAS REGISTRY NUMBER
COMMENTARY
188929-01-3
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
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
-
-
-
-
?
3-diphospho-1D-myo-inositol 1,2,4,5,6-pentakisphosphate + ATP
3,5-bisdiphospho-1D-myo-inositol 1,2,4,6-tetrakisphosphate + ADP
-
-
-
-
?
5-diphospho-1D-myo-inositol 1,2,3,4,6-pentakisphosphate + ATP
3,5-bisdiphospho-1D-myo-inositol 1,2,4,6-tetrakisphosphate + ADP
-
-
-
-
?
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
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-
-
r
ADP + 1-diphospho-1D-myo-inositol 2,3,4,5,6-pentakisphosphate
ATP + 1D-myo-inositol hexakisphosphate
-
-
-
r
ADP + 1D-myo-inositol 1,5-bis(diphosphate) 2,3,4,6-tetrakisphosphate
ATP + 1D-myo-inositol 5-diphosphate 1,2,3,4,6-pentakisphosphate
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
ATP + 1D-myo-inositol 5-diphosphate pentakisphosphate
ADP + 1D-myo-inositol bisdiphosphate tetrakisphosphate
ATP + 1D-myo-inositol hexakisphosphate
ADP + 1D-myo-inositol 1-diphosphate 2,3,4,5,6-pentakisphosphate
-
-
-
?
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
-
-
-
r
ADP + 1D-myo-inositol 1,5-bis(diphosphate) 2,3,4,6-tetrakisphosphate
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
ATP + 1D-myo-inositol 5-diphosphate 1,2,3,4,6-pentakisphosphate
i.e. non-natural enantiomer of 1D-myo-inositol 1,5-bis(diphosphate) 2,3,4,6-tetrakisphosphate
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-
?
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
-
-
-
r
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
-
-
-
?
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
-
-
-
r
ATP + 1D-myo-inositol 5-diphosphate pentakisphosphate
ADP + 1D-myo-inositol bisdiphosphate tetrakisphosphate
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-
-
?
ATP + 1D-myo-inositol 5-diphosphate pentakisphosphate
ADP + 1D-myo-inositol bisdiphosphate tetrakisphosphate
-
-
-
?
ATP + 1D-myo-inositol 5-diphosphate pentakisphosphate
ADP + 1D-myo-inositol bisdiphosphate tetrakisphosphate
(PP)2-InsP4 synthesis pathway, overview
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-
?
additional information
?
-
VIP1 also performs the reaction of EC 2.7.4.21
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-
?
additional information
?
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VIP1 also performs the reaction of EC 2.7.4.21
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-
?
additional information
?
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VIP1 also performs the reaction of EC 2.7.4.21
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-
?
additional information
?
-
VIP2 also performs the reaction of EC 2.7.4.21
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-
?
additional information
?
-
VIP2 also performs the reaction of EC 2.7.4.21
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-
?
additional information
?
-
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VIP2 also performs the reaction of EC 2.7.4.21
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-
?
additional information
?
-
-
recombinant Vip1 kinase domain catalyzes 5-diphospho-1D-myo-inositol (1,2,3,4,6)pentakisphosphate formation from inositol hexakisphosphate. NMR substrate and product analysis, overview
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-
?
additional information
?
-
the bifunctional enzyme also catalyzes the reaction of EC 2.7.4.21, InsP6 kinase. The enzyme exhibits an unusual, nonproductive, substrate-stimulated ATPase activity, that is stimulated by the natural substrates and by 5-O-alpha-phosphonoacetyl-myo-inositol 1,2,3,4,6-pentakisphosphate and 2-O-benzyl-5-O-alpha-phosphonoacetyl-myo-inositol 1,3,4,6-tetrakisphosphate. It also shows 1,5-[PP]2-InsP4 dephosphorylation activity. The enzyme has two adjacent ligand-binding sites, the architecture of this second ligand-binding site is represented by a deep cleft, which is walled on one side by K53, K54, and K103. The opposite face is formed from R213, and a loop created from residues E192 to H194
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-
?
additional information
?
-
enzyme additionally catalyzes the reaction of EC 2.7.4.21, i.e. conversion of 1D-myo-inositol hexakisphosphate to 5-diphospho-1D-myo-inositol 1,2,3,4,6-pentakisphosphate. The kinase activities toward 1D-myo-inositol hexakisphosphate are 4fold lower than the kinase activites toward -diphospho-1D-myo-inositol 1,2,3,4,6-pentakisphosphate
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-
-
additional information
?
-
enzyme additionally catalyzes the reaction of EC 2.7.4.21, i.e. conversion of 1D-myo-inositol hexakisphosphate to 5-diphospho-1D-myo-inositol 1,2,3,4,6-pentakisphosphate. The kinase activities toward 1D-myo-inositol hexakisphosphate are 4fold lower than the kinase activites toward -diphospho-1D-myo-inositol 1,2,3,4,6-pentakisphosphate
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-
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
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
-
-
-
-
?
3-diphospho-1D-myo-inositol 1,2,4,5,6-pentakisphosphate + ATP
3,5-bisdiphospho-1D-myo-inositol 1,2,4,6-tetrakisphosphate + ADP
-
-
-
-
?
5-diphospho-1D-myo-inositol 1,2,3,4,6-pentakisphosphate + ATP
3,5-bisdiphospho-1D-myo-inositol 1,2,4,6-tetrakisphosphate + ADP
-
-
-
-
?
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
-
-
-
?
ATP + 1D-myo-inositol 5-diphosphate pentakisphosphate
ADP + 1D-myo-inositol bisdiphosphate tetrakisphosphate
ATP + 1D-myo-inositol hexakisphosphate
ADP + 1D-myo-inositol 1-diphosphate 2,3,4,5,6-pentakisphosphate
-
-
-
?
ATP + 1D-myo-inositol 5-diphosphate pentakisphosphate
ADP + 1D-myo-inositol bisdiphosphate tetrakisphosphate
-
-
-
?
ATP + 1D-myo-inositol 5-diphosphate pentakisphosphate
ADP + 1D-myo-inositol bisdiphosphate tetrakisphosphate
(PP)2-InsP4 synthesis pathway, overview
-
-
?
additional information
?
-
VIP1 also performs the reaction of EC 2.7.4.21
-
-
?
additional information
?
-
VIP1 also performs the reaction of EC 2.7.4.21
-
-
?
additional information
?
-
-
VIP1 also performs the reaction of EC 2.7.4.21
-
-
?
additional information
?
-
VIP2 also performs the reaction of EC 2.7.4.21
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-
?
additional information
?
-
VIP2 also performs the reaction of EC 2.7.4.21
-
-
?
additional information
?
-
-
VIP2 also performs the reaction of EC 2.7.4.21
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
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
-
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-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
C8-PtdIns(4,5)P2
0.05 mM, inhibits 1D-myo-inositol 1,5-bis(diphosphate) 2,3,4,6-tetrakisphosphate dephosphorylation by approximately 60%
-
phosphate
1D-myo-inositol 5-diphosphate 1,2,3,4,6-pentakisphosphate phosphatase activities of PPIP5Ks are 40-90% inhibited by phosphate within the 0-1 mM range; 1D-myo-inositol 5-diphosphate 1,2,3,4,6-pentakisphosphate phosphatase activities of PPIP5Ks are 40-90% inhibited by phosphate within the 0-1 mM range
UNC10112646
directly inhibits PPIP5K-catalyzed phosphorylation of 1D-myo-inositol 5-diphosphate 1,2,3,4,6-pentakisphosphate to 1D-myo-inositol 1,5-bis(diphosphate) 2,3,4,6-tetrakisphosphate
-
UNC10225498
directly inhibits PPIP5K-catalyzed phosphorylation of 1D-myo-inositol 5-diphosphate 1,2,3,4,6-pentakisphosphate to 1D-myo-inositol 1,5-bis(diphosphate) 2,3,4,6-tetrakisphosphate
-
additional information
isoform PPIP5K2 is insensitive to physiological changes in either [AMP] or [ATP]/[ADP] ratios
-
additional information
-
isoform PPIP5K2 is insensitive to physiological changes in either [AMP] or [ATP]/[ADP] ratios
-
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
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
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-benzyl-5-O-alpha-phosphonoacetyl-myo-inositol 1,3,4,6-tetrakisphosphate
stimulates ATP hydrolysis 9fold
5-O-alpha-phosphonoacetyl-myo-inositol 1,2,3,4,6-pentakisphosphate
stimulates ATP hydrolysis 5fold
PtdIns(4,5)P2
increases net 1D-myo-inositol 5-diphosphate 1,2,3,4,6-pentakisphosphate kinase activity 5fold
-
additional information
activation of recombinant PPIP5K1 by hyperosmotic stress in HEK-293 cells
-
additional information
-
activation of recombinant PPIP5K1 by hyperosmotic stress in HEK-293 cells
-
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
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
0.00006
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
0.022
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
0.0001
1D-myo-inositol 5-diphosphate pentakisphosphate
pH 6.2, 37°C, VIP1
0.00019
1D-myo-inositol 5-diphosphate pentakisphosphate
pH 6.2, 37°C, VIP2
0.0052
ADP
isoform PPIP5K2, using 1-diphospho-1D-myo-inositol 2,3,4,5,6-pentakisphosphate as cosubstrate, in 20 mM HEPES-NaOH pH 7.2, 50 mM KCl, at 37°C
0.9
ADP
isoform PPIP5K2, using 1,5-bis-diphospho-1D-myo-inositol 2,3,4,6-tetrakisphosphate as cosubstrate, in 20 mM HEPES-NaOH pH 7.2, 50 mM KCl, at 37°C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
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
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
4
1D-myo-inositol 5-diphosphate pentakisphosphate
pH 6.2, 37°C, VIP1
38
1D-myo-inositol 5-diphosphate pentakisphosphate
pH 6.2, 37°C, VIP2
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
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
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
0.037
ADP
isoform PPIP5K2, using 1-diphospho-1D-myo-inositol 2,3,4,5,6-pentakisphosphate as cosubstrate, in 20 mM HEPES-NaOH pH 7.2, 50 mM KCl, at 37°C
0.21
ADP
isoform PPIP5K2, using 1,5-bis-diphospho-1D-myo-inositol 2,3,4,6-tetrakisphosphate as cosubstrate, in 20 mM HEPES-NaOH pH 7.2, 50 mM KCl, at 37°C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00017
2,5-O-benzyl-myo-inositol 1,3,4,6-tetrakisphosphate
Homo sapiens
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
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
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
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
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
pH and temperature not specified in the publication
1.386
5-(phosphonoacetic acid ester)-1D-myo-inositol tetrakisphosphate
Homo sapiens
pH and temperature not specified in the publication
0.0024
5-O-alpha-diphosphate-myo-inositol 1,3,4,6-tetrakisphosphate
Homo sapiens
inhibition of the 1,5-[PP]2-InsP4 dephosphorylation, pH 7.0, 37°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.007
pH 7.2, 37°C, substrate 1D-myo-inositol 1,5-bis(diphosphate) 2,3,4,6-tetrakisphosphate
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.2
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
-
positional specificity of the mammalian and yeast VIP/diphosphoinositol pentakisphosphate kinase family of inositol phosphate kinases, overview. The mammalian and yeast VIP/PPIP5K family enzymes phosphorylate the 1/3-position of the inositol ring in vitro and in vivo, phylogenetic variability within the crown taxa in the structures of inositol pyrophosphates, overview
physiological function
additional information
a time-resolved, fluorescence resonance energy transfer ADP-assay is optimized. Inhibition is competitive with ATP
physiological function
1D-myo-inositol 5-diphosphate 1,2,3,4,6-pentakisphosphate kinase activity is dominant when PPIP5K1 is expressed in intact cells. 1D-myo-inositol 1,5-bis(diphosphate) 2,3,4,6-tetrakisphosphate phosphatase activity prevails when the enzyme is isolated from its cellular environment. Exogenous expression of PPIP5K1 in Drosophila melanogaster S3 cells elevates levels of 1D-myo-inositol 5-diphosphate 1,2,3,4,6-pentakisphosphate and 1D-myo-inositol 1,5-bis(diphosphate) 2,3,4,6-tetrakisphosphate
physiological function
levels of both 1D-myo-inositol 1,5-bis(diphosphate) 2,3,4,6-tetrakisphosphate and ATP decrease upon phosphate starvation and subsequently recover during phosphate replenishment
physiological function
the enzyme synthesizes high-energy inositol pyrophosphates, which regulate cell function at the interface between cellular energy metabolism and signal transduction. Inhibition is competitive with ATP
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). VIP1_HUMAN
1433
0
159521
Swiss-Prot
other Location (Reliability: 2)
VIP2_HUMAN
1243
0
140407
Swiss-Prot
other Location (Reliability: 1)
A0A087WZV0_HUMAN
1278
0
144362
TrEMBL
other Location (Reliability: 1)
F8W9A8_HUMAN
1409
0
156651
TrEMBL
other Location (Reliability: 2)
B7WPL9_HUMAN
1429
0
158985
TrEMBL
other Location (Reliability: 2)
H0Y9S9_HUMAN
398
0
45034
TrEMBL
other Location (Reliability: 1)
B4DGV1_HUMAN
1270
0
143478
TrEMBL
other Location (Reliability: 1)
D6RBU4_HUMAN
452
0
51209
TrEMBL
other Location (Reliability: 2)
A0A2R8YGT1_HUMAN
499
0
55170
TrEMBL
other Location (Reliability: 3)
H7C398_HUMAN
259
0
28626
TrEMBL
other Location (Reliability: 3)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
the enzyme contains a putative ATP-grasp kinase domain
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
the Lys248 side chain is rather centered on a position enabling an optimal pulling force applied to the leaving group along the reaction coordinate. The actions of Lys248 pulling forces are influenced by substrate binding. Residue Glu192 makes a specific contribution to the ability of PPIP5K2 to significantly reduce the entropy toll for the catch-and-pass reaction mechanism
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D332A
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
R213A
the mutant shows a reduction in 1D-myo-inositol hexakisphosphate-stimulated ATPase activity of isofom PPIP5K2
R388A
2.4-4fold larger net formation of 1D-myo-inositol 5-diphosphate 1,2,3,4,6-pentakisphosphate, but mutation nearly completely impaires its hydrolysis
R837H
variant R837H segregates with DFNB100-associated hearing loss. Mutation reduces the phosphatase activity of PPIP5K2 and elevates its kinase activity
additional information
D332A
2.4-4fold larger net formation of 1D-myo-inositol 5-diphosphate 1,2,3,4,6-pentakisphosphate, but mutation nearly completely impaires its hydrolysis
additional information
VIP1 expression in mutant yeast restores IP7 synthesis
additional information
VIP1 expression in mutant yeast restores IP7 synthesis
additional information
-
construction of full-length recombinant human GSTIP6K1, plus either Saccharomyces cerevisiae GST fusion constructs comprising residues 1-387 of the human VIP1/PPIP5K1 kinase domain or residues 1-535 of the ScVip1 kinase domain
additional information
construction of an N-terminally truncated mutant PPIP5K2KD comprising residues 41-366
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
transition variant R837H segregates with DFNB100-associated hearing loss
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Fridy, P.C.; Otto, J.C.; Dollins, D.E.; York, J.D.
Cloning and characterization of two human VIP1-like inositol hexakisphosphate and diphosphoinositol pentakisphosphate kinases
J. Biol. Chem.
282
30754-30762
2007
Homo sapiens (O43314), Homo sapiens (Q6PFW1), Homo sapiens
Choi, J.H.; Williams, J.; Cho, J.; Falck, J.R.; Shears, S.B.
Purification, sequencing, and molecular identification of a mammalian PP-InsP5 kinase that is activated when cells are exposed to hyperosmotic stress
J. Biol. Chem.
282
30763-30775
2007
Rattus norvegicus (P0C644), Homo sapiens (Q6PFW1), Homo sapiens
Lin, H.; Fridy, P.C.; Ribeiro, A.A.; Choi, J.H.; Barma, D.K.; Vogel, G.; Falck, J.R.; Shears, S.B.; York, J.D.; Mayr, G.W.
Structural analysis and detection of biological inositol pyrophosphates reveal that the family of VIP/diphosphoinositol pentakisphosphate kinases are 1/3-kinases
J. Biol. Chem.
284
1863-1872
2009
Saccharomyces cerevisiae, Homo sapiens
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 (O43314), Homo sapiens
Riley, A.M.; Wang, H.; Weaver, J.D.; Shears, S.B.; Potter, B.V.
First synthetic analogues of diphosphoinositol polyphosphates: interaction with PP-InsP5 kinase
Chem. Commun. (Camb. )
48
11292-11294
2012
Homo sapiens (O43314)
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)
Nair, V.; Gu, C.; Janoshazi, A.; Jessen, H.; Wang, H.; Shears, S.
Inositol pyrophosphate synthesis by diphosphoinositol pentakisphosphate kinase-1 is regulated by phosphatidylinositol(4,5)bisphosphate
Biosci. Rep.
38
BSR20171549
2018
Homo sapiens (Q6PFW1)
Gu, C.; Nguyen, H.N.; Hofer, A.; Jessen, H.J.; Dai, X.; Wang, H.; Shears, S.B.
The significance of the bifunctional kinase/phosphatase activities of diphosphoinositol pentakisphosphate kinases (PPIP5Ks) for coupling inositol pyrophosphate cell signaling to cellular phosphate homeostasis
J. Biol. Chem.
292
4544-4555
2017
Homo sapiens (O43314), Homo sapiens (Q6PFW1)
Yousaf, R.; Gu, C.; Ahmed, Z.M.; Khan, S.N.; Friedman, T.B.; Riazuddin, S.; Shears, S.B.; Riazuddin, S.
Mutations in diphosphoinositol-pentakisphosphate kinase PPIP5K2 are associated with hearing loss in human and mouse
PLoS Genet.
14
e1007297
2018
Homo sapiens (O43314), Homo sapiens, Mus musculus (Q6ZQB6), Mus musculus
Baughman, B.M.; Wang, H.; An, Y.; Kireev, D.; Stashko, M.A.; Jessen, H.J.; Pearce, K.H.; Frye, S.V.; Shears, S.B.
A High-throughput screening-compatible strategy for the identification of inositol pyrophosphate kinase inhibitors
PLoS ONE
11
e0164378
2016
Homo sapiens (O43314)
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