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Information on EC 2.7.1.67 - 1-phosphatidylinositol 4-kinase and Organism(s) Homo sapiens and UniProt Accession Q8TCG2
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2.7.1.67 1-phosphatidylinositol 4-kinaseIUBMB Comments
This reaction is catalysed by at least two different isoforms.
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Word Map
- 2.7.1.67
- 4-phosphate
- 4,5-bisphosphate
- phospholipid
- phospholipase
-
ptdins4p
- wortmannin
- phosphatidylinositol-4-phosphate
- pip2
- 5-kinase
- diacylglycerol
-
polyphosphoinositides
-
ptdins4,5p2
-
phosphatidic
-
trans-golgi
-
gamma-32patp
-
1,4,5-trisphosphate
- phosphatidylinositol-4,5-bisphosphate
-
polyoma
- coxsackievirus
-
wortmannin-sensitive
-
pleckstrin
-
antiphosphotyrosine
-
oxysterol-binding
-
positive-sense
- enteroviruses
-
3hinositol
-
ovcar-5
- sensor-1
- ns5a
- poliovirus
- medicine
- pharmacology
- drug development
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
Synonyms
phosphatidylinositol kinase, pi kinase, pi4kb, pi 4-kinase, ptdins 4-kinase, pi4kiialpha, pi4ka, pi4kbeta, phosphatidylinositol-4-kinase, pik1p, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
kinase, phosphatidylinositol (phosphorylating)
-
-
-
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phosphatidylinositol 4-kinase
phosphatidylinositol 4-kinase IIalpha
phosphatidylinositol 4-kinase IIIbeta
phosphatidylinositol 4-kinase type IIalpha
phosphatidylinositol kinase
-
-
-
-
PI 4-kinase
PI kinase
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-
-
-
PI4K
PI4K2A
PI4KA
PI4KB
PtdIns 4-kinase
type II phosphatidylinositol kinase
-
-
-
-
phosphatidylinositol 4-kinase
-
-
-
-
phosphatidylinositol 4-kinase
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-
PI 4-kinase
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-
-
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PI4K
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-
-
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PtdIns 4-kinase
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-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:1-phosphatidyl-1D-myo-inositol 4-phosphotransferase
This reaction is catalysed by at least two different isoforms.
CAS REGISTRY NUMBER
COMMENTARY
37205-54-2
-
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
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
enzyme is involved in the regulation of endosomal membrane traffic in mammalian cells
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
type II PtdIns 4-kinase plays a role in lymphocyte infiltration to the sites of inflammation
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
-
-
641768, 641776, 641778, 641779, 641780, 641793, 641794, 641797, 641801, 641806, 641809, 641819, 662814, 672995, 673232, 674704, 674715, 674878, 721555, 721713, 721967, 722121, 723072, 723136, 723609, 723790, 723791, 737789, 738845, 738939, 739030, 758569, 758912, 759586, 759590, 759597
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
-
PI4K92 is a key enzyme regulating Golgi disintegration/reorganization during mitosis probably via phosphorylation by cyclin-dependent kinases on well-defined sites. PI4K55 is involved in the production of second messengers, diacylglycerol and inositol 1,4,5-triphosphate at the plasma membrane, moreover, in the endocytotic pathway in the cytoplasm
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
-
regulation by Ca2+ may act as a negative feedback system
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
-
plasma membrane PI4KII is a target of amyloid beta proteins in the pathogenesis of Alzheimers disease
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
-
various PI4Ks regulate phosphatidylinositol 4-phosphate synthesis in distinct cellular compartments
-
-
?
additional information
?
-
-
E3 ubiquitin ligase Itch is a binding partner and regulator of PI4KIIalpha function. Itch directly associates with and ubiquitinates PI4KIIa
-
-
?
additional information
?
-
-
PI4KB does not interact with NS5A in hepatitis C virus-infected cells
-
-
?
additional information
?
-
-
the 3A protein from multiple picornaviruses, ncluding Aichi virus, bovine kobuvirus, CVB, HRV14, poliovirus, associates with isozyme PI4KIIIbeta and ACBD3
-
-
?
additional information
additional information
-
-
PI4KIIbeta is associated with Hsp90
-
-
?
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
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
enzyme is involved in the regulation of endosomal membrane traffic in mammalian cells
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
type II PtdIns 4-kinase plays a role in lymphocyte infiltration to the sites of inflammation
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
-
-
721555, 721713, 721967, 722121, 723072, 723136, 723609, 723790, 723791, 737789, 738845, 738939, 739030, 758569, 758912, 759586, 759590, 759597
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
-
PI4K92 is a key enzyme regulating Golgi disintegration/reorganization during mitosis probably via phosphorylation by cyclin-dependent kinases on well-defined sites. PI4K55 is involved in the production of second messengers, diacylglycerol and inositol 1,4,5-triphosphate at the plasma membrane, moreover, in the endocytotic pathway in the cytoplasm
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
-
regulation by Ca2+ may act as a negative feedback system
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
-
plasma membrane PI4KII is a target of amyloid beta proteins in the pathogenesis of Alzheimers disease
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
-
various PI4Ks regulate phosphatidylinositol 4-phosphate synthesis in distinct cellular compartments
-
-
?
additional information
?
-
-
E3 ubiquitin ligase Itch is a binding partner and regulator of PI4KIIalpha function. Itch directly associates with and ubiquitinates PI4KIIa
-
-
?
additional information
?
-
-
PI4KB does not interact with NS5A in hepatitis C virus-infected cells
-
-
?
additional information
?
-
-
the 3A protein from multiple picornaviruses, ncluding Aichi virus, bovine kobuvirus, CVB, HRV14, poliovirus, associates with isozyme PI4KIIIbeta and ACBD3
-
-
?
additional information
additional information
-
-
PI4KIIbeta is associated with Hsp90
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
Mg2+
-
required, optimal concentrations for mPIK-I and mPIK-III at 5-10 mM, optimal concentration for cPIK-I and cPIK-II is 20-40 mM
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
resveratrol
inhibition of PtdIns 4-kinase activity by resveratrol/phenylarsine oxide reduces Jurkat cell adhesion to matrigel/fibronectin coated surfaces
(1-((5-(6-chloro-8-(((2-ethylpyridin-4-yl)methyl)amino)-2-methylimidazo[1,2-b]pyridazin-3-yl)-2-methoxyphenyl)sulfonyl)-piperidin-4-yl)methanol
-
(2-bromo-4,5-dimethoxyphenyl)(6,7-dimethoxyisoquinolin-1-yl)methanone
-
about 80% residual activity at 0.01 mM
1,6-dimethyl-3-propylpyrimido[5,4-e][1,2,4]triazine-5,7(1H,6H)-dione
-
about 65% residual activity at 0.01 mM
1-[3-[9-(3,4-dimethoxyphenyl)-8-methyl-6-[[2-(morpholin-4-yl)ethyl]amino]-9H-purin-2-yl]phenyl]-2-methylpropan-1-one
-
16% residual activity at 0.01 mM
1-[5-(6-chloro-8-[[(2-ethylpyridin-4-yl)methyl]amino]-2-methylimidazo[1,2-b]pyridazin-3-yl)-2-methoxybenzene-1-sulfonyl]piperidin-4-ol
-
2-(3-chlorophenyl)-9-(3,4-dimethoxyphenyl)-8-methyl-N-[2-(morpholin-4-yl)ethyl]-9H-purin-6-amine
-
67% residual activity at 0.01 mM
2-amino-1-(isopropylsulfonyl)-6-benzimidazole phenylketone oxime
-
i.e. enviroxime, inhibitor of the in vitro replication of rhinoviruses and enteroviruses, inhibits hepatitis C virus subgenomic replicon replication
2-[5-(1,3-benzodioxol-5-yl)-1,2,4-oxadiazol-3-yl]pyridine
-
about 18% residual activity at 0.01 mM
3-(3,4-dimethoxyphenyl)-2,5-dimethyl-N-[2-(morpholin-4-yl)ethyl]pyrazolo[1,5-a]pyrimidin-7-amine
3-(3,4-dimethoxyphenyl)-5-methyl-N-[2-(morpholin-4-yl)ethyl]-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-amine
-
31% residual activity at 0.01 mM
3-(3,4-dimethoxyphenyl)-N-[2-(morpholin-4-yl)ethyl]-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-amine
-
41% residual activity at 0.01 mM
3-(4-methylphenyl)-5H-indeno[1,2-c]pyridazin-5-one
-
about 55% residual activity at 0.01 mM
3-(6-chloro-2-methyl-8-[[(2-methylpyridin-4-yl)methyl]amino]imidazo[1,2-b]pyridazin-3-yl)-N,N-dimethylbenzene-1-sulfonamide
-
3-(6-chloro-2-methyl-8-[[(pyridin-3-yl)methyl]amino]imidazo[1,2-b]pyridazin-3-yl)-N,N-dimethylbenzene-1-sulfonamide
-
3-(6-chloro-2-methyl-8-[[(pyridin-4-yl)methyl]amino]imidazo[1,2-b]pyridazin-3-yl)-N,N-dimethylbenzene-1-sulfonamide
-
3-(6-chloro-8-[[(2-ethylpyridin-4-yl)methyl]amino]-2-methylimidazo[1,2-b]pyridazin-3-yl)-N,N-dimethylbenzene-1-sulfonamide
-
4-(quinoxalin-2-yl)phenyl furan-2-carboxylate
-
about 75% residual activity at 0.01 mM
4-[9-(3,4-dimethoxyphenyl)-2-methyl-6-[[2-(morpholin-4-yl)ethyl]amino]-9H-purin-8-yl]benzonitrile
-
97% residual activity at 0.01 mM
4-[9-(3,4-dimethoxyphenyl)-8-methyl-6-[[2-(morpholin-4-yl)ethyl]amino]-9H-purin-2-yl]benzonitrile
-
97% residual activity at 0.01 mM
4-[9-(3,4-dimethoxyphenyl)-8-methyl-6-[[2-(morpholin-4-yl)ethyl]amino]-9H-purin-2-yl]phenol
-
18% residual activity at 0.01 mM
5-(6-chloro-8-[[(2-ethylpyridin-4-yl)methyl]amino]-2-methylimidazo[1,2-b]pyridazin-3-yl)-2-methoxy-N,N-dimethylbenzene-1-sulfonamide
-
5-(6-chloro-8-[[(2-ethylpyridin-4-yl)methyl]amino]-2-methylimidazo[1,2-b]pyridazin-3-yl)-2-methoxy-N-(2-methoxyethyl)benzene-1-sulfonamide
-
5-(6-chloro-8-[[(2-ethylpyridin-4-yl)methyl]amino]-2-methylimidazo[1,2-b]pyridazin-3-yl)-2-methoxy-N-(prop-2-en-1-yl)benzene-1-sulfonamide
-
5-(6-chloro-8-[[(2-ethylpyridin-4-yl)methyl]amino]-2-methylimidazo[1,2-b]pyridazin-3-yl)-2-methoxybenzene-1-sulfonyl chloride
-
5-(6-chloro-8-[[(2-ethylpyridin-4-yl)methyl]amino]-2-methylimidazo[1,2-b]pyridazin-3-yl)-N-(1-hydroxybutan-2-yl)-2-methoxybenzene-1-sulfonamide
-
5-(6-chloro-8-[[(2-ethylpyridin-4-yl)methyl]amino]-2-methylimidazo[1,2-b]pyridazin-3-yl)-N-(2-hydroxyethyl)-2-methoxybenzene-1-sulfonamide
-
5-(6-chloro-8-[[(2-ethylpyridin-4-yl)methyl]amino]-2-methylimidazo[1,2-b]pyridazin-3-yl)-N-cyclopropyl-2-methoxybenzene-1-sulfonamide
-
5-(6-chloro-8-[[(2-ethylpyridin-4-yl)methyl]amino]-2-methylimidazo[1,2-b]pyridazin-3-yl)-N-[2-(dimethylamino)ethyl]-2-methoxybenzene-1-sulfonamide
-
5-[8-[(2-acetamidoethyl)amino]-6-chloro-2-methylimidazo[1,2-b]pyridazin-3-yl]-2-methoxybenzene-1-sulfonyl chloride
-
6-chloro-3-iodo-2-methyl-N-((2-methylpyridin-4-yl)methyl)-imidazo[1,2-b]pyridazin-8-amine
-
6-chloro-3-iodo-2-methyl-N-(pyridin-2-ylmethyl)imidazo[1,2-b]-pyridazin-8-amine
-
6-chloro-3-iodo-2-methyl-N-(pyridin-3-ylmethyl)imidazo[1,2-b]-pyridazin-8-amine
-
6-chloro-3-iodo-2-methyl-N-(pyridin-4-ylmethyl)imidazo[1,2-b]-pyridazin-8-amine
-
6-chloro-N-((2-ethylpyr idin-4-yl)methyl)-3-iodo-2-methylimidazo[1,2-b]pyridazin-8-amine
-
6-chloro-N-[(2-ethylpyridin-4-yl)methyl]-3-(4-methoxyphenyl)-2-methylimidazo[1,2-b]pyridazin-8-amine
-
6-chloro-N-[(2-ethylpyridin-4-yl)methyl]-3-[4-methoxy-3-(1H-pyrazole-1-sulfonyl)phenyl]-2-methylimidazo[1,2-b]pyridazin-8-amine
-
6-chloro-N-[(2-ethylpyridin-4-yl)methyl]-3-[4-methoxy-3-(morpholine-4-sulfonyl)phenyl]-2-methylimidazo[1,2-b]pyridazin-8-amine
-
6-chloro-N-[(2-ethylpyridin-4-yl)methyl]-3-[4-methoxy-3-(piperidine-1-sulfonyl)phenyl]-2-methylimidazo[1,2-b]pyridazin-8-amine
-
7-(3,4-dimethoxyphenyl)-N-[2-(morpholin-4-yl)ethyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine
-
74% residual activity at 0.01 mM
8-(cyclohex-3-en-1-yl)-9-(3,4-dimethoxyphenyl)-2-methyl-N-[2-(morpholin-4-yl)ethyl]-9H-purin-6-amine
-
75% residual activity at 0.01 mM
8-bromo-9-(3,4-dimethoxyphenyl)-2-methyl-N-[2-(morpholin-4-yl)ethyl]-9H-purin-6-amine
-
17% residual activity at 0.01 mM
8-cyclohexyl-9-(3,4-dimethoxyphenyl)-2-methyl-N-[2-(morpholin-4-yl)ethyl]-9H-purin-6-amine
-
79% residual activity at 0.01 mM
9-(3,4-dimethoxyphenyl)-2,8-dimethyl-N-[2-(morpholin-4-yl)ethyl]-5,9-dihydro-4H-purin-6-amine
-
14% residual activity at 0.01 mM
9-(3,4-dimethoxyphenyl)-2-(4-fluorophenyl)-8-methyl-N-[2-(morpholin-4-yl)ethyl]-9H-purin-6-amine
-
66% residual activity at 0.01 mM
9-(3,4-dimethoxyphenyl)-2-ethynyl-8-methyl-N-[2-(morpholin-4-yl)ethyl]-9H-purin-6-amine
-
18% residual activity at 0.01 mM
9-(3,4-dimethoxyphenyl)-2-iodo-8-methyl-N-[2-(morpholin-4-yl)ethyl]-9H-purin-6-amine
-
33% residual activity at 0.01 mM
9-(3,4-dimethoxyphenyl)-2-methoxy-8-methyl-N-[2-(morpholin-4-yl)ethyl]-9H-purin-6-amine
-
15% residual activity at 0.01 mM
9-(3,4-dimethoxyphenyl)-2-methyl-N-[2-(morpholin-4-yl)ethyl]-8-(3-phenylprop-1-yn-1-yl)-9H-purin-6-amine
-
96% residual activity at 0.01 mM
9-(3,4-dimethoxyphenyl)-2-methyl-N-[2-(morpholin-4-yl)ethyl]-8-(propan-2-yl)-9H-purin-6-amine
-
65% residual activity at 0.01 mM
9-(3,4-dimethoxyphenyl)-2-methyl-N-[2-(morpholin-4-yl)ethyl]-8-(thiophen-3-yl)-9H-purin-6-amine
-
94% residual activity at 0.01 mM
9-(3,4-dimethoxyphenyl)-2-methyl-N-[2-(morpholin-4-yl)ethyl]-8-(trifluoromethyl)-9H-purin-6-amine
-
99% residual activity at 0.01 mM
9-(3,4-dimethoxyphenyl)-2-methyl-N-[2-(morpholin-4-yl)ethyl]-9H-purin-6-amine
-
26% residual activity at 0.01 mM
9-(3,4-dimethoxyphenyl)-8-(4-fluorophenyl)-2-methyl-N-[2-(morpholin-4-yl)ethyl]-9H-purin-6-amine
-
78% residual activity at 0.01 mM
9-(3,4-dimethoxyphenyl)-8-iodo-2-methyl-N-[2-(morpholin-4-yl)ethyl]-9H-purin-6-amine
-
38% residual activity at 0.01 mM
9-(3,4-dimethoxyphenyl)-8-methoxy-2-methyl-N-[2-(morpholin-4-yl)ethyl]-9H-purin-6-amine
-
86% residual activity at 0.01 mM
9-(3,4-dimethoxyphenyl)-8-methyl-6-[[2-(morpholin-4-yl)ethyl]amino]-9H-purine-2-carbonitrile
-
24% residual activity at 0.01 mM
9-(3,4-dimethoxyphenyl)-8-methyl-N-[2-(morpholin-4-yl)ethyl]-2-(3-phenylprop-1-yn-1-yl)-9H-purin-6-amine
-
58% residual activity at 0.01 mM
9-(3,4-dimethoxyphenyl)-8-methyl-N-[2-(morpholin-4-yl)ethyl]-2-(pyridin-3-yl)-9H-purin-6-amine
-
36% residual activity at 0.01 mM
9-(3,4-dimethoxyphenyl)-8-methyl-N-[2-(morpholin-4-yl)ethyl]-2-(thiophen-3-yl)-9H-purin-6-amine
-
46% residual activity at 0.01 mM
9-(3,4-dimethoxyphenyl)-8-methyl-N-[2-(morpholin-4-yl)ethyl]-9H-purin-6-amine
-
13% residual activity at 0.01 mM
9-(3,4-dimethoxyphenyl)-8-methyl-N6-[2-(morpholin-4-yl)ethyl]-9H-purine-2,6-diamine
-
25% residual activity at 0.01 mM
amyloid beta
-
amino acids 1-42, inhibits type II phosphatidylinositol 4-kinase and enhances glutamate toxicity
-
amyloid beta protein
-
pathophysiological concentrations of amyloid beta proteins directly inhibit. Abeta25-35 inhibits in a non-competitive manner. Inhibition by 10 nM Abeta25-35 is reversible
-
MDL-860
-
irreversible inhibition. MDL-860 only affects in vivo isoform PI4KB activity
methyl N-[[(4-butyl-2-oxo-2H-1-benzopyran-7-yl)oxy]acetyl]-5-hydroxy-L-tryptophanate
-
-
N'-(4-methoxybenzoyl)pyridine-2-carbohydrazide
-
about 20% residual activity at 0.01 mM
N'-[(4-methoxybenzoyl)oxy]pyridine-2-carboximidamide
-
about 30% residual activity at 0.01 mM
N-(1H-benzimidazol-2-yl)-2-methoxybenzamide
-
about 65% residual activity at 0.01 mM
N-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-[[5-(3,4,5-trimethoxyphenyl)-1,3,4-oxadiazol-2-yl]sulfanyl]acetamide
-
about 40% residual activity at 0.01 mM
N-(2-((3-(3-((1H-pyrazol-1-yl)sulfonyl)-4-methoxyphenyl)-6-chloro-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)ethyl)-acetamide
-
N-(2-((3-(3-(N-(4-aminocyclohexyl)sulfamoyl)-4-methoxyphenyl)-6-chloro-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)ethyl)-acetamide
-
N-(2-((3-(3-(N-allylsulfamoyl)-4-methoxyphenyl)-6-chloro-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)ethyl)acetamide
-
N-(2-((6-chloro-3-(3-((4-(hydroxymethyl)piperidin-1-yl)sulfonyl)-4-methoxyphenyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)-ethyl)acetamide
-
N-(2-((6-chloro-3-(3-(N,N-dimethylsulfamoyl)-4-methoxyphenyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)ethyl)acetamide
-
N-(2-((6-chloro-3-(3-(N-(1-hydroxybutan-2-yl)sulfamoyl)-4-methoxyphenyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)ethyl)-acetamide
-
N-(2-((6-chloro-3-(3-(N-(2-(dimethylamino)ethyl)sulfamoyl)-4-methoxyphenyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)-ethyl)acetamide
-
N-(2-((6-chloro-3-(3-(N-(2-hydroxyethyl)sulfamoyl)-4-methoxyphenyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)ethyl)-acetamide
-
N-(2-((6-chloro-3-(3-(N-cyclopropylsulfamoyl)-4-methoxyphenyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)ethyl)acetamide
-
N-(2-((6-chloro-3-(4-methoxy-3-(morpholinosulfonyl)phenyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)ethyl)acetamide
-
N-(2-((6-chloro-3-(4-methoxy-3-(N-(2-methoxyethyl)sulfamoyl)-phenyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)ethyl)-acetamide
-
N-(2-((6-chloro-3-(4-methoxy-3-(N-methyl-N-(2-(methylamino)-ethyl)sulfamoyl)phenyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)-amino)ethyl)acetamide
-
N-(2-((6-chloro-3-(4-methoxy-3-(piperidin-1-ylsulfonyl)phenyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)ethyl)acetamide
-
N-(2-((6-chloro-3-(4-methoxyphenyl)-2-methylimidazo[1,2-b]-pyridazin-8-yl)amino)ethyl)acetamide
-
N-(2-((6-chloro-3-iodo-2-methylimidazo[1,2-b]pyridazin-8-yl)-amino)ethyl)acetamide
-
N-(4-aminocyclohexyl)-5-(6-chloro-8-[[(2-ethylpyridin-4-yl)methyl]amino]-2-methylimidazo[1,2-b]pyridazin-3-yl)-2-methoxybenzene-1-sulfonamide
-
N-(5-[4-chloro-3-[(2-hydroxyethyl)sulfamoyl]phenyl]-4-methyl-1,3-thiazol-2-yl)acetamide
-
i.e. PIK93, a phenylthiazole
N-[2-([6-chloro-3-[3-(dimethylsulfamoyl)phenyl]-2-methylimidazo[1,2-b]pyridazin-8-yl]amino)ethyl]acetamide
-
N-[3-[9-(3,4-dimethoxyphenyl)-8-methyl-6-[[2-(morpholin-4-yl)ethyl]amino]-9H-purin-2-yl]phenyl]acetamide
-
14% residual activity at 0.01 mM
N-[5-[4-(dimethylamino)phenyl]-3-oxo-2,3-dihydro-1H-pyrazol-4-yl]pyridine-2-carboxamide
-
about 95% residual activity at 0.01 mM
N-[[(4-butyl-2-oxo-2H-1-benzopyran-7-yl)oxy]acetyl]-5-hydroxy-L-tryptophan
-
about 20% residual activity at 0.01 mM
phosphatidylinositol 4,5-bisphosphate
-
50% inhibition when added in equimolar amounts to phosphatidylinositol
propan-2-yl N-[[(4-butyl-2-oxo-2H-1-benzopyran-7-yl)oxy]acetyl]-5-hydroxy-L-tryptophanate
-
-
tert-butyl N-[[8-(2-chlorophenyl)-4,5-dihydro[1,3]thiazolo[4,5-h]quinazolin-2-yl]carbamoyl]-beta-alaninate
-
i.e. Inhibitor A
Triton X-100
-
inhibits activity of mPIK-I but rather weakly enhances mPIK-III activity
[9-(3,4-dimethoxyphenyl)-2-methyl-6-[[2-(morpholin-4-yl)ethyl]amino]-9H-purin-8-yl]methanol
-
62% residual activity at 0.01 mM
3-(3,4-dimethoxyphenyl)-2,5-dimethyl-N-[2-(morpholin-4-yl)ethyl]pyrazolo[1,5-a]pyrimidin-7-amine
-
-
3-(3,4-dimethoxyphenyl)-2,5-dimethyl-N-[2-(morpholin-4-yl)ethyl]pyrazolo[1,5-a]pyrimidin-7-amine
-
[5-(4-[[4-(morpholin-4-yl)phenyl]amino]quinazolin-6-yl)furan-2-yl]methanol
-
i.e. AL-9
[5-(4-[[4-(morpholin-4-yl)phenyl]amino]quinazolin-6-yl)furan-2-yl]methanol
-
i.e. AL-9, a 4-anilino quinazoline, inhibits purified PI4KIIIalpha and, to a lesser extent, PI4KIIIbeta, and inhibits PI4KIIIalpha in vivo
additional information
-
some anti-viral molecules are isoform selective phosphatidylinositol 4-kinase inhibitors. Isozymes PI4KIIalpha and PI4KIIbeta are wortmannin-insensitive
-
additional information
-
MDL-860 does not affect in vitro isoform PI4KB activity
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-[[(2-methoxyphenyl)methyl]amino]-2-oxoethyl 2-(furan-2-yl)quinoline-4-carboxylate
-
-
4-[9-(3,4-dimethoxyphenyl)-2-methyl-6-[[2-(morpholin-4-yl)ethyl]amino]-9H-purin-8-yl]benzaldehyde
-
138% residual activity at 0.01 mM
4-[9-(3,4-dimethoxyphenyl)-2-methyl-6-[[2-(morpholin-4-yl)ethyl]amino]-9H-purin-8-yl]phenol
-
125% residual activity at 0.01 mM
9-(3,4-dimethoxyphenyl)-2,8-dimethyl-N-[2-(morpholin-4-yl)ethyl]-9H-purin-6-amine
-
126% residual activity at 0.01 mM
9-(3,4-dimethoxyphenyl)-2-methyl-N-[2-(morpholin-4-yl)ethyl]-8-(4-phenoxyphenyl)-9H-purin-6-amine
-
112% activity at 0.01 mM
amyloid beta31-34
-
fragment of amyloid beta, blocks amyloid beta1-42-induced inhibition of type II phosphatidylinositol 4-kinase activity
amyloid beta32-34
-
fragment of amyloid beta, blocks amyloid beta1-42-induced inhibition of type II phosphatidylinositol 4-kinase activity. 50% protection at around 1 nM
amyloid beta32-35
-
fragment of amyloid beta, blocks amyloid beta1-42-induced inhibition of type II phosphatidylinositol 4-kinase activity
dichlorodiphenyltrichloroethane
-
i.e. DDT, 0.01 mM enhances activity but no changes are observed by lower concentration, membrane associated enzyme
eukaryotic protein translation elongation factor 1 alpha 2
-
up to a 2fold molar excess of recombinant eEF1A2 is required to maximally increase PI4KIIIbeta activity
-
heptachlor
-
0.0001 mM enhances activity by 88%, 0.01 mM enhances activity by 52%, membrane associated enzyme
neuronal calcium sensor 1
-
Golgi-localized isozyme PI4KIIIbeta can be activated by protein kinase D phosphorylation, and also through interactions with neuronal calcium sensor 1
-
NS5A
-
stimulates phosphatidylinositol 4-phosphate production in vivo and enhances PI4KA kinase activity in vitro, but not other viral proteins from hepatitis C virus, overview
-
[4-[9-(3,4-dimethoxyphenyl)-2-methyl-6-[[2-(morpholin-4-yl)ethyl]amino]-9H-purin-8-yl]phenyl]methanol
-
103% residual activity at 0.01 mM
Triton X-100
-
inhibits activity of mPIK-I but rather weakly enhances mPIK-III activity
additional information
-
amyloid34-32, fragment of amyxloid beta with reversed amino acid sequence, shows no protective effects on the inhibition of type II phosphatidylinositol 4-kinase activity
-
additional information
-
elevated phosphatidylinositol kinase activity in Rous sarcoma virus-transformed and in Eppstein Barr virus-infected cells
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.04
N6-dimethylamine-adenosine 5'-triphosphate
-
pH 7.4, 25°C, in presence of 3 mM spermidine
1.9
N6-dimethylamine-adenosine 5'-triphosphate
-
pH 7.4, 25°C, in absence of spermidine
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0000415
(1-((5-(6-chloro-8-(((2-ethylpyridin-4-yl)methyl)amino)-2-methylimidazo[1,2-b]pyridazin-3-yl)-2-methoxyphenyl)sulfonyl)-piperidin-4-yl)methanol
Homo sapiens
pH and temperature not specified in the publication
0.00109
1-[3-[9-(3,4-dimethoxyphenyl)-8-methyl-6-[[2-(morpholin-4-yl)ethyl]amino]-9H-purin-2-yl]phenyl]-2-methylpropan-1-one
Homo sapiens
-
isoform PI4K IIIbeta, pH and temperature not specified in the publication
0.0000062
1-[5-(6-chloro-8-[[(2-ethylpyridin-4-yl)methyl]amino]-2-methylimidazo[1,2-b]pyridazin-3-yl)-2-methoxybenzene-1-sulfonyl]piperidin-4-ol
Homo sapiens
pH and temperature not specified in the publication
0.0000337
3-(6-chloro-2-methyl-8-[[(2-methylpyridin-4-yl)methyl]amino]imidazo[1,2-b]pyridazin-3-yl)-N,N-dimethylbenzene-1-sulfonamide
Homo sapiens
pH and temperature not specified in the publication
0.0000746 - 0.0001454
3-(6-chloro-2-methyl-8-[[(pyridin-3-yl)methyl]amino]imidazo[1,2-b]pyridazin-3-yl)-N,N-dimethylbenzene-1-sulfonamide
0.0000264
3-(6-chloro-2-methyl-8-[[(pyridin-4-yl)methyl]amino]imidazo[1,2-b]pyridazin-3-yl)-N,N-dimethylbenzene-1-sulfonamide
Homo sapiens
pH and temperature not specified in the publication
0.0000125
3-(6-chloro-8-[[(2-ethylpyridin-4-yl)methyl]amino]-2-methylimidazo[1,2-b]pyridazin-3-yl)-N,N-dimethylbenzene-1-sulfonamide
Homo sapiens
pH and temperature not specified in the publication
0.00237
4-[9-(3,4-dimethoxyphenyl)-8-methyl-6-[[2-(morpholin-4-yl)ethyl]amino]-9H-purin-2-yl]phenol
Homo sapiens
-
isoform PI4K IIIbeta, pH and temperature not specified in the publication
0.0000273
5-(6-chloro-8-[[(2-ethylpyridin-4-yl)methyl]amino]-2-methylimidazo[1,2-b]pyridazin-3-yl)-2-methoxy-N,N-dimethylbenzene-1-sulfonamide
Homo sapiens
pH and temperature not specified in the publication
0.0000172
5-(6-chloro-8-[[(2-ethylpyridin-4-yl)methyl]amino]-2-methylimidazo[1,2-b]pyridazin-3-yl)-2-methoxy-N-(2-methoxyethyl)benzene-1-sulfonamide
Homo sapiens
pH and temperature not specified in the publication
0.0000086
5-(6-chloro-8-[[(2-ethylpyridin-4-yl)methyl]amino]-2-methylimidazo[1,2-b]pyridazin-3-yl)-2-methoxy-N-(prop-2-en-1-yl)benzene-1-sulfonamide
Homo sapiens
pH and temperature not specified in the publication
0.0000053
5-(6-chloro-8-[[(2-ethylpyridin-4-yl)methyl]amino]-2-methylimidazo[1,2-b]pyridazin-3-yl)-N-(1-hydroxybutan-2-yl)-2-methoxybenzene-1-sulfonamide
Homo sapiens
pH and temperature not specified in the publication
0.0000061 - 0.0134
5-(6-chloro-8-[[(2-ethylpyridin-4-yl)methyl]amino]-2-methylimidazo[1,2-b]pyridazin-3-yl)-N-(2-hydroxyethyl)-2-methoxybenzene-1-sulfonamide
0.000056
5-(6-chloro-8-[[(2-ethylpyridin-4-yl)methyl]amino]-2-methylimidazo[1,2-b]pyridazin-3-yl)-N-cyclopropyl-2-methoxybenzene-1-sulfonamide
Homo sapiens
pH and temperature not specified in the publication
0.000009 - 0.001128
5-(6-chloro-8-[[(2-ethylpyridin-4-yl)methyl]amino]-2-methylimidazo[1,2-b]pyridazin-3-yl)-N-[2-(dimethylamino)ethyl]-2-methoxybenzene-1-sulfonamide
0.000441
6-chloro-N-[(2-ethylpyridin-4-yl)methyl]-3-(4-methoxyphenyl)-2-methylimidazo[1,2-b]pyridazin-8-amine
Homo sapiens
pH and temperature not specified in the publication
0.0000191
6-chloro-N-[(2-ethylpyridin-4-yl)methyl]-3-[4-methoxy-3-(1H-pyrazole-1-sulfonyl)phenyl]-2-methylimidazo[1,2-b]pyridazin-8-amine
Homo sapiens
pH and temperature not specified in the publication
0.000176
6-chloro-N-[(2-ethylpyridin-4-yl)methyl]-3-[4-methoxy-3-(morpholine-4-sulfonyl)phenyl]-2-methylimidazo[1,2-b]pyridazin-8-amine
Homo sapiens
pH and temperature not specified in the publication
0.0000592
6-chloro-N-[(2-ethylpyridin-4-yl)methyl]-3-[4-methoxy-3-(piperidine-1-sulfonyl)phenyl]-2-methylimidazo[1,2-b]pyridazin-8-amine
Homo sapiens
pH and temperature not specified in the publication
0.0052
8-bromo-9-(3,4-dimethoxyphenyl)-2-methyl-N-[2-(morpholin-4-yl)ethyl]-9H-purin-6-amine
Homo sapiens
-
isoform PI4K IIIbeta, pH and temperature not specified in the publication
0.00091
9-(3,4-dimethoxyphenyl)-2,8-dimethyl-N-[2-(morpholin-4-yl)ethyl]-5,9-dihydro-4H-purin-6-amine
Homo sapiens
-
isoform PI4K IIIbeta, pH and temperature not specified in the publication
0.00191
9-(3,4-dimethoxyphenyl)-2-ethynyl-8-methyl-N-[2-(morpholin-4-yl)ethyl]-9H-purin-6-amine
Homo sapiens
-
isoform PI4K IIIbeta, pH and temperature not specified in the publication
0.00299
9-(3,4-dimethoxyphenyl)-2-methoxy-8-methyl-N-[2-(morpholin-4-yl)ethyl]-9H-purin-6-amine
Homo sapiens
-
isoform PI4K IIIbeta, pH and temperature not specified in the publication
0.00207
9-(3,4-dimethoxyphenyl)-8-methyl-6-[[2-(morpholin-4-yl)ethyl]amino]-9H-purine-2-carbonitrile
Homo sapiens
-
isoform PI4K IIIbeta, pH and temperature not specified in the publication
0.00161
9-(3,4-dimethoxyphenyl)-8-methyl-N-[2-(morpholin-4-yl)ethyl]-9H-purin-6-amine
Homo sapiens
-
isoform PI4K IIIbeta, pH and temperature not specified in the publication
0.00144
9-(3,4-dimethoxyphenyl)-8-methyl-N6-[2-(morpholin-4-yl)ethyl]-9H-purine-2,6-diamine
Homo sapiens
-
isoform PI4K IIIbeta, pH and temperature not specified in the publication
0.000024
Cpd 6
Homo sapiens
-
isozyme PI4KIIIbeta, pH and temperature not specified in the publication
-
0.0001633
N-(2-((3-(3-((1H-pyrazol-1-yl)sulfonyl)-4-methoxyphenyl)-6-chloro-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)ethyl)-acetamide
Homo sapiens
pH and temperature not specified in the publication
0.0000269 - 0.00066
N-(2-((3-(3-(N-(4-aminocyclohexyl)sulfamoyl)-4-methoxyphenyl)-6-chloro-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)ethyl)-acetamide
0.0000199
N-(2-((3-(3-(N-allylsulfamoyl)-4-methoxyphenyl)-6-chloro-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)ethyl)acetamide
Homo sapiens
pH and temperature not specified in the publication
0.0000149 - 0.00819
N-(2-((6-chloro-3-(3-((4-(hydroxymethyl)piperidin-1-yl)sulfonyl)-4-methoxyphenyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)-ethyl)acetamide
0.0000024
N-(2-((6-chloro-3-(3-(N,N-dimethylsulfamoyl)-4-methoxyphenyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)ethyl)acetamide
Homo sapiens
pH and temperature not specified in the publication
0.00000723 - 0.01228
N-(2-((6-chloro-3-(3-(N-(1-hydroxybutan-2-yl)sulfamoyl)-4-methoxyphenyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)ethyl)-acetamide
0.00486 - 0.0935
N-(2-((6-chloro-3-(3-(N-(2-(dimethylamino)ethyl)sulfamoyl)-4-methoxyphenyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)-ethyl)acetamide
0.000022
N-(2-((6-chloro-3-(3-(N-(2-hydroxyethyl)sulfamoyl)-4-methoxyphenyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)ethyl)-acetamide
Homo sapiens
pH and temperature not specified in the publication
0.0001058
N-(2-((6-chloro-3-(3-(N-cyclopropylsulfamoyl)-4-methoxyphenyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)ethyl)acetamide
Homo sapiens
pH and temperature not specified in the publication
0.00000098 - 0.048
N-(2-((6-chloro-3-(4-methoxy-3-(morpholinosulfonyl)phenyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)ethyl)acetamide
0.0001348
N-(2-((6-chloro-3-(4-methoxy-3-(N-(2-methoxyethyl)sulfamoyl)-phenyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)ethyl)-acetamide
Homo sapiens
pH and temperature not specified in the publication
0.0001469 - 0.01707
N-(2-((6-chloro-3-(4-methoxy-3-(N-methyl-N-(2-(methylamino)-ethyl)sulfamoyl)phenyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)-amino)ethyl)acetamide
0.0001894
N-(2-((6-chloro-3-(4-methoxy-3-(piperidin-1-ylsulfonyl)phenyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)ethyl)acetamide
Homo sapiens
pH and temperature not specified in the publication
0.0000157 - 0.000553
N-(4-aminocyclohexyl)-5-(6-chloro-8-[[(2-ethylpyridin-4-yl)methyl]amino]-2-methylimidazo[1,2-b]pyridazin-3-yl)-2-methoxybenzene-1-sulfonamide
0.000019 - 0.0011
N-(5-[4-chloro-3-[(2-hydroxyethyl)sulfamoyl]phenyl]-4-methyl-1,3-thiazol-2-yl)acetamide
0.000054 - 0.1
N-[2-([6-chloro-3-[3-(dimethylsulfamoyl)phenyl]-2-methylimidazo[1,2-b]pyridazin-8-yl]amino)ethyl]acetamide
0.00214
N-[3-[9-(3,4-dimethoxyphenyl)-8-methyl-6-[[2-(morpholin-4-yl)ethyl]amino]-9H-purin-2-yl]phenyl]acetamide
Homo sapiens
-
isoform PI4K IIIbeta, pH and temperature not specified in the publication
0.00045
tert-butyl N-[[8-(2-chlorophenyl)-4,5-dihydro[1,3]thiazolo[4,5-h]quinazolin-2-yl]carbamoyl]-beta-alaninate
Homo sapiens
-
isozyme PI4KIIIalpha, pH and temperature not specified in the publication
0.00057 - 0.0031
[5-(4-[[4-(morpholin-4-yl)phenyl]amino]quinazolin-6-yl)furan-2-yl]methanol
0.00012
2-amino-1-(isopropylsulfonyl)-6-benzimidazole phenylketone oxime
Homo sapiens
-
isozyme PI4KIIIbeta, pH and temperature not specified in the publication
0.0014
2-amino-1-(isopropylsulfonyl)-6-benzimidazole phenylketone oxime
Homo sapiens
-
isozyme PI4KIIIalpha, pH and temperature not specified in the publication
0.0000746
3-(6-chloro-2-methyl-8-[[(pyridin-3-yl)methyl]amino]imidazo[1,2-b]pyridazin-3-yl)-N,N-dimethylbenzene-1-sulfonamide
Homo sapiens
pH and temperature not specified in the publication
0.0001454
3-(6-chloro-2-methyl-8-[[(pyridin-3-yl)methyl]amino]imidazo[1,2-b]pyridazin-3-yl)-N,N-dimethylbenzene-1-sulfonamide
Homo sapiens
pH and temperature not specified in the publication
0.0000061
5-(6-chloro-8-[[(2-ethylpyridin-4-yl)methyl]amino]-2-methylimidazo[1,2-b]pyridazin-3-yl)-N-(2-hydroxyethyl)-2-methoxybenzene-1-sulfonamide
Homo sapiens
pH and temperature not specified in the publication
0.0134
5-(6-chloro-8-[[(2-ethylpyridin-4-yl)methyl]amino]-2-methylimidazo[1,2-b]pyridazin-3-yl)-N-(2-hydroxyethyl)-2-methoxybenzene-1-sulfonamide
Homo sapiens
pH and temperature not specified in the publication
0.000009
5-(6-chloro-8-[[(2-ethylpyridin-4-yl)methyl]amino]-2-methylimidazo[1,2-b]pyridazin-3-yl)-N-[2-(dimethylamino)ethyl]-2-methoxybenzene-1-sulfonamide
Homo sapiens
pH and temperature not specified in the publication
0.001128
5-(6-chloro-8-[[(2-ethylpyridin-4-yl)methyl]amino]-2-methylimidazo[1,2-b]pyridazin-3-yl)-N-[2-(dimethylamino)ethyl]-2-methoxybenzene-1-sulfonamide
Homo sapiens
pH and temperature not specified in the publication
0.0000269
N-(2-((3-(3-(N-(4-aminocyclohexyl)sulfamoyl)-4-methoxyphenyl)-6-chloro-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)ethyl)-acetamide
Homo sapiens
pH and temperature not specified in the publication
0.00066
N-(2-((3-(3-(N-(4-aminocyclohexyl)sulfamoyl)-4-methoxyphenyl)-6-chloro-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)ethyl)-acetamide
Homo sapiens
pH and temperature not specified in the publication
0.0000149
N-(2-((6-chloro-3-(3-((4-(hydroxymethyl)piperidin-1-yl)sulfonyl)-4-methoxyphenyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)-ethyl)acetamide
Homo sapiens
pH and temperature not specified in the publication
0.0000438
N-(2-((6-chloro-3-(3-((4-(hydroxymethyl)piperidin-1-yl)sulfonyl)-4-methoxyphenyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)-ethyl)acetamide
Homo sapiens
pH and temperature not specified in the publication
0.00819
N-(2-((6-chloro-3-(3-((4-(hydroxymethyl)piperidin-1-yl)sulfonyl)-4-methoxyphenyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)-ethyl)acetamide
Homo sapiens
pH and temperature not specified in the publication
0.00000723
N-(2-((6-chloro-3-(3-(N-(1-hydroxybutan-2-yl)sulfamoyl)-4-methoxyphenyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)ethyl)-acetamide
Homo sapiens
pH and temperature not specified in the publication
0.01228
N-(2-((6-chloro-3-(3-(N-(1-hydroxybutan-2-yl)sulfamoyl)-4-methoxyphenyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)ethyl)-acetamide
Homo sapiens
pH and temperature not specified in the publication
0.00486
N-(2-((6-chloro-3-(3-(N-(2-(dimethylamino)ethyl)sulfamoyl)-4-methoxyphenyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)-ethyl)acetamide
Homo sapiens
pH and temperature not specified in the publication
0.0935
N-(2-((6-chloro-3-(3-(N-(2-(dimethylamino)ethyl)sulfamoyl)-4-methoxyphenyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)-ethyl)acetamide
Homo sapiens
pH and temperature not specified in the publication
0.00000098
N-(2-((6-chloro-3-(4-methoxy-3-(morpholinosulfonyl)phenyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)ethyl)acetamide
Homo sapiens
pH and temperature not specified in the publication
0.048
N-(2-((6-chloro-3-(4-methoxy-3-(morpholinosulfonyl)phenyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)amino)ethyl)acetamide
Homo sapiens
pH and temperature not specified in the publication
0.0001469
N-(2-((6-chloro-3-(4-methoxy-3-(N-methyl-N-(2-(methylamino)-ethyl)sulfamoyl)phenyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)-amino)ethyl)acetamide
Homo sapiens
pH and temperature not specified in the publication
0.01707
N-(2-((6-chloro-3-(4-methoxy-3-(N-methyl-N-(2-(methylamino)-ethyl)sulfamoyl)phenyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)-amino)ethyl)acetamide
Homo sapiens
pH and temperature not specified in the publication
0.0000157
N-(4-aminocyclohexyl)-5-(6-chloro-8-[[(2-ethylpyridin-4-yl)methyl]amino]-2-methylimidazo[1,2-b]pyridazin-3-yl)-2-methoxybenzene-1-sulfonamide
Homo sapiens
pH and temperature not specified in the publication
0.000553
N-(4-aminocyclohexyl)-5-(6-chloro-8-[[(2-ethylpyridin-4-yl)methyl]amino]-2-methylimidazo[1,2-b]pyridazin-3-yl)-2-methoxybenzene-1-sulfonamide
Homo sapiens
pH and temperature not specified in the publication
0.000019
N-(5-[4-chloro-3-[(2-hydroxyethyl)sulfamoyl]phenyl]-4-methyl-1,3-thiazol-2-yl)acetamide
Homo sapiens
-
isozyme PI4KIIIbeta, pH and temperature not specified in the publication
0.0011
N-(5-[4-chloro-3-[(2-hydroxyethyl)sulfamoyl]phenyl]-4-methyl-1,3-thiazol-2-yl)acetamide
Homo sapiens
-
isozyme PI4KIIIalpha, pH and temperature not specified in the publication
0.000054
N-[2-([6-chloro-3-[3-(dimethylsulfamoyl)phenyl]-2-methylimidazo[1,2-b]pyridazin-8-yl]amino)ethyl]acetamide
Homo sapiens
pH and temperature not specified in the publication
0.1
N-[2-([6-chloro-3-[3-(dimethylsulfamoyl)phenyl]-2-methylimidazo[1,2-b]pyridazin-8-yl]amino)ethyl]acetamide
Homo sapiens
pH and temperature not specified in the publication
0.1
N-[2-([6-chloro-3-[3-(dimethylsulfamoyl)phenyl]-2-methylimidazo[1,2-b]pyridazin-8-yl]amino)ethyl]acetamide
Homo sapiens
IC50 above 0.1 mM, pH and temperature not specified in the publication
0.00057
[5-(4-[[4-(morpholin-4-yl)phenyl]amino]quinazolin-6-yl)furan-2-yl]methanol
Homo sapiens
-
isozyme PI4KIIIalpha, pH 7.5, 22°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.5 - 9
-
pH 5.5: 60% of maximal activity for mPIK-I and 45% of maximal activity of mPIK-III, pH 8.5-9.0: pH-optimum for enzyme form mPIK-I and mPIK-III
6 - 9
-
activity of cPIK-I and cPIK-III is almost undetectable at pH 6.0, pH 9.0: about 80% of maximal activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
non-specific infiltrating duct and infiltrating lobular carcinomas
-
isozyme PI4KIIalpha expression is upregulated in many human cancers but is especially highly expressed in malignant melanoma, fibrosarcoma, breast cancer (non-specific infiltrating duct and infiltrating lobular carcinomas) bladder transitional cell carcinoma and thyroid papillary carcinoma
-
cell lines with inducible expression of the HCV polyprotein or individual viral proteins
-
existence of differentially active pooly of PI4KIIalpha in unstimulated A431 cells
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
PI4KIIbeta is primarily cytosolic and it associates peripherally with plasma membranes, endoplasmic reticulum and the Golgi apparatus
PI4KIIalpha is primarily Golgi-associated. Platelet-derived growth factor promotes PI4KIIbeta recruitment to membrane ruffles
additional information
-
isozyme PI4KIIbeta is distributed almost evenly between membranes and cytosol
-
highly active pool of type II phosphatidylinositol 4-kinase is localized in a p97/valosin-containing-protein-rich fraction of the endoplasmic reticulum
-
isozyme PI4KIIIbeta is recruited to and principally localizes to the Golgi complex through GTP-bound Arf1 binding
-
principal PI4Ks of the Golgi apparatus are PI4KIIalpha and PI4KIIIbeta
-
PI4K230 is distributed evenly on membranes that are ultra structurally cisterns of the rough endoplasmic reticulum, outer membranes of mitochondria, multivesicular bodies and are in close vicinity of synaptic contacts
-
isozyme PI4KIIbeta is distributed almost evenly between membranes and cytosol
additional information
-
phosphatidylinositol 4-phosphate localization has a distinct pattern in cells infected with hepatitis C virus (extensive cytoplasmic distribution) compared to uninfected cells
-
additional information
-
whereas the palmitoylated membrane-bound pool is catalytically active, the cytosolic kinase is inactive
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
-
in vertebrates, PtdIns4P is synthesized by four distinct PI4K enzymes that belong to either the type-II or type-III family, each having alpha- and beta-forms. The type-III PI4Ks are relatives of the PI 3-kinase family, while the smaller type-II enzymes form a separate family
malfunction
metabolism
physiological function
additional information
malfunction
-
depletion of PI4KIIalpha by siRNA-mediated knockdown reduces Wnt5a-triggered uptake and/or sorting of Fz4-eGFP into EEA1-positive endosomes. This effect is fully rescued by re-expression of siRNA-resistant PI4KIIalpha
malfunction
-
hepatitis C virus, by recruiting PI4KIIIa in the RNA replication complex, hijacks phosphatidylinositol-4 phosphate metabolism, ultimately resulting in a markedly altered subcellular distribution of the PI4KIIIalpha product. Antiviral effect of 4-anilino quinazoline compounds is mediated by the inhibition of PI4KIIIalpha and the consequent depletion of 1-phosphatidyl-1D-myo-inositol 4-phosphate required for the HCV membranous web. Inhibition of PI4KIIIalpha by AL-9 induces the formation of large viral NS5A protein clusters
malfunction
-
PI4KIIalpha knockdown causes enlarged LAMP-1-positive endosomal structures in fixed cells. Acute depletion of phosphatidylinositol 4-phosphate in the Golgi causes accumulation of LIMP-2 in this compartment, and PI4KIIIbeta is responsible for controlling the exit of LIMP-2 from the Golgi. In contrast, depletion of PI4KIIalpha blocks trafficking at a post-Golgi compartment, leading to accumulation of LIMP-2 in enlarged endosomal vesicles. PI4KIIalpha depletion also causes secretion of missorted GBA into the medium, which is attenuated by limiting LIMP-2/GBA exit from the Golgi by PI4KIIIbeta inhibitors, overview
malfunction
-
silencing of isozyme PI4KIIIbeta, but not ofisozyme PI4KIIIa strongly inhibits SARS CoV spike-mediated entry
malfunction
-
silencing of the PI 4-kinase PI4KA leads to abberrant membranous web morphology, and PI4KB silencing inhibits HCV infection, overview. PI4KA silencing-induced membrane clustering depends on HCV polyprotein cleavage but does not require integrity of the endoplasmic reticulum-Golgi secretory pathway
malfunction
-
siRNAs that reduce PI4KA accumulation appear to perturb membranous web formation. Cell viral polyprotein expression results in enhanced cytoplasmic phosphatidylinositol 4-phosphate production. Increased phosphatidylinositol 4-phosphate accumulation following hepatitis C virus protein expression is precluded by silencing the expression of isozyme PI4KA, but not the related isozyme PI4KB. Silencing PI4KA also results in aberrant agglomeration of viral replicase proteins, including NS5A, NS5B, and NS3. NS5A alone, but not other viral proteins, stimulates phosphatidylinositol 4-phosphate production in vivo and enhanced PI4KA kinase activity in vitro
malfunction
-
loss of the PI4K2B allele and underexpression of isoform PI4KIIbeta mRNA are associated with human cancers. Depletion of isoform PI4KIIbeta is sufficient to confer an aggressive invasive phenotype on minimally invasive HeLa and MCF-7 cell lines. Loss of isoform PI4KIIbeta induces the formation of invadopodia and leads to increased exocytic trafficking of membrane type I matrix metalloproteinase
metabolism
-
alterations to phosphatidylinositol 4-kinase expression levels can modulate MAP kinase and Akt signalling, and are important for chemoresistance, tumour angiogenesis and the suppression of apoptosis and metastases
metabolism
-
regulation of the Golgi system and 1-phosphatidyl-1D-myo-inositol 4-phosphate levels involving the enzyme, overview
metabolism
-
the enzyme interacts with hepatitis C virus nonstructural protein 5A
metabolism
-
the enzyme interacts with peroxiredoxin-1, Nedd4-1, and vesicle-mediated transport proteins such as clathrin heavy chain and the pallidin subunit of BLOC-1
physiological function
-
distinct phosphatidylinositol 4-kinases play important roles at multiple steps in the trafficking pathway of the LIMP-2/GBA complex. The phosphatidylinositol 4-kinases control lysosomal delivery of the Gaucher disease enzyme, beta-glucocerebrosidase, overview. Catalytic activity of PI4KIIIbeta in Golgi exit of the LIMP-2/GBA complex, which is followed by PI4KIIalpha-mediated trafficking to lysosomes. PI4KIalpha is involved in post-Golgi trafficking of LIMP-2 along the degradative pathway
physiological function
-
isozyme phosphatidylinositol 4-kinase IIIbeta is required for severe acute respiratory syndrome coronavirus spike-mediated cell entry. PI4P plays an essential role in SARS-CoV spike-mediated entry, which is regulated by the PI4P lipid microenvironment, overview
physiological function
-
isozyme PI4KA plays an essential role in hepatitis C virus membranous webs formation and colocalizes with the hepatitis C virus membranous webs, which show phosphatidylinositol 4-phosphate enrichment, while isozyme PI4KB supports the HCV life cycle but does not localize to or generate phosphatidylinositol 4-phosphate at membranous webs
physiological function
-
key role of isozyme PI4KIIalpha in TGN/endosomal membrane traffic, isozyme PI4KIIalpha regulates Wnt signalling, endosomal sorting of signalling receptors, and promotes adaptor protein recruitment to endosomes and the trans-Golgi network. E3 ubiquitin ligase Itch is a binding partner and regulator of PI4KIIa function. Itch directly associates with and ubiquitinates PI4KIIalpha, and both proteins co-localize on endosomes containing Wnt-activated frizzled 4 receptor. Itch and PI4KIIalpha reciprocally regulate each other
physiological function
-
phosphatidylinositol 4-kinase IIalpha is required for oxysterol binding protein-dependent activation of sphingomyelin synthesis in the Golgi apparatus, overview
physiological function
-
phosphatidylinositol 4-kinases regulate vesicle mediate export from the Golgi apparatus via phosphatidylinositol 4-phosphate binding effector proteins that control vesicle budding reactions and regulate membrane dynamics. Function of phosphatidylinositol 4-phosphate at the Golgi Membrane biogenesis and lipid homeostasis
physiological function
-
PI4KIIalpha recruits clathrin adaptors AP1, AP3 and GGAs to the trans-Golgi network, and controls fate of endocytic vesicles, PI4KIIalpha promotes EGF receptor degradation, and supports Wnt signaling. PI4KIIIbeta regulates exit of certain cargos from the Golgi, and supports CERT-mediated ceramide transport to the trans-Golgi. PI4KIIIalpha supplies PtdIns(4,5)P2 for the plasma membrane and regulates the endoplasmic reticulum exit. Phosphatidylinositide 4-phosphate lipids are involved in viral replications. They can be used as replication platforms in the host membranes that are hijacked by RNA viruses including the endoplasmic reticulum, Golgi apparatus, trans-Golgi network, endosomes, plasma membrane and mitochondrial outer membrane. Viral replication machinery is assembled on these platforms as a supramolecular complex and PtdIns4P lipids regulate viral RNA synthesis, detailed overview. Throughout infection, the viral replication membrane platforms contain high levels of the host enzyme phosphatidylinositol 4-kinase IIIbeta, PI4KIIIbeta, that generates PtdIns4P at these membranes. PI4KIIIbeta or PI4KIIIalpha, independently from making PtdIns4P lipids, can also serve as scaffolds to recruit other host proteins to the replication platform
physiological function
-
PI4KIIIalpha is a host factor for hepatitis C virus. Isozyme PI4KIIIbet is involved in the entry of SARS coronavirus. PI4KIIIbeta is not required for virus binding and internalization, but plays a role at, or before, virus fusion with the late endosomes. Modes of recruitment of PI4KIIIs to the replication complexes of hepattis C virus, enteroviruses, and the Aichi virus, overview
physiological function
-
PI4KIIIalpha is responsible for the phosphatidylinositol-4 phosphate pool present in the plasma membrane. Antiviral effect of 4-anilino quinazoline compounds is mediated by the inhibition of PI4KIIIalpha and the consequent depletion of 1-phosphatidyl-1D-myo-inositol 4-phosphate required for the HCV membranous web
physiological function
-
PI4KIIIbeta localised to the Golgi complex through GTP-bound Arf1 binding, can be activated by protein kinase D phosphorylation, and also through interactions with neuronal calcium sensor 1. 1-Phosphatidyl-1D-myo-inositol 4-phosphate PI4P is an essential phospholipid substrate for two phosphoinositide-dependent signalling pathways that control cell migration and proliferation. It induces expression of Girdin in several cancers, and its translocation to the plasma membrane where it activates heterotrimeric Gai proteins to stimulate PI(3,4,5)P3 synthesis by PI 3-kinase, overview. The enzyme shows a potential role for a plasma membrane pool of PI4P in regulating Girdin targeting and EGFR signalling. PI4KIIIa may have an underappreciated function in the constitutive chemoresistance of cancers which are recalcitrant to apoptotic induction. PI4KIIbeta isoform migh exhibit an anti-metastatic role in hepatocellular carcinoma
physiological function
-
whereas the palmitoylated membrane-bound pool is catalytically active, the cytosolic kinase is inactive
physiological function
-
the enzyme is associated with actin cytoskeleton and cell adhesion, required for CD3 receptor induced calcium release, and a key component in early T cell activation signaling cascades
physiological function
-
isoform PI4KIIbeta synthesizes a pool of 1-phosphatidyl-1D-myo-inositol 4-phosphate that maintains membrane type I matrix metalloproteinase traffic in the degradative pathway and suppresses the formation of invadopodia
additional information
-
hepatitis C virus stimulates the phosphatidylinositol 4-kinase III alpha-dependent phosphatidylinositol 4-phosphate production that is essential for its replication, overview. PI4KA is also implicated in HCV replication complex formation
additional information
-
molecular chaperone Hsp90 is a binding partner of isozyme PI4KIIbeta, PI4KIIbeta contains an Hsp90 interaction site, which most likely resides in the N-terminal lobe of the catalytic domain. PI4KIIbeta must bind to Hsp90 and is highly sensitive to its release, perhaps because a substantial portion of this isoform is cytosolic. Hsp90 selectively stabilizes the cytosolic pool of PI4KIIbeta.. Hsp90 protects PI4KIIbeta from degradation by the proteasome. Geldanamycin, a specific Hsp90 inhibitor, disrupts the Hsp90-PI4KIIbeta interaction and destabilizes PI4KIIbeta, reducing its half-life by 40% and increasing its susceptibility to ubiquitylation and proteasomal degradation. Cytosolic PI4KIIbeta is much more sensitive to geldanamycin treatment than is the integrally membrane-associated species. Stimuli such as PDGF receptor activation that also induce recruitment of the kinase to membranes disrupt the Hsp90-PI4KIIbeta interaction to a similar extent as inhibitor treatment. Dissociation of PI4KIIbeta from Hsp90 by exposure to geldanamycin results in transient translocation to membranes and increased kinase activity
additional information
-
PI4KA interacts with viral protein NS5A in hepatitis C virus-infected cells
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). P4K2B_HUMAN
481
0
54744
Swiss-Prot
other Location (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
55000
additional information
-
the enzyme binds substantial amounts of Triton X-100 and is actually present in detergent-containing solutions as a complex with a molecular weight of 120000 Da. It seems likely that the active species of the enzyme is a single 55000 Da polypeptide chain bound to essentially one Triton X-100 micelle
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
homodimer
additional information
additional information
-
two enzyme species a 45000 Da enzyme and a 50000 Da enzyme
additional information
-
domain organization of PI4Ks: PI4KIIalpha and PI4KIIbeta with a Pro-rich and acidic region, respectively, and two catalytic domains, one of which including a Cys-rich region, and PI4KIIIalpha Pro-rich domain, NS5A binding domain, lipid kinase unique domain, pleckstrin homology domain, and catalytic domain, and PI4KIIIbeta with LKU domain, Fq, hom2, and catalytic domain and two Pro-rich regions, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
additional information
-
PI4KIIalpha undergoes multi-ubiquitination via ubiquitin ligase Itch
phosphoprotein
phosphoprotein, additionally phosphate is incorporated by incubation with ATP/Mg or ATP/Mn. Phosphorylation sites are mapped by MALDI-MS and LC-MS/MS at the following positions: S258, T263, S266, S277, S294, T423, S496, T504
phosphoprotein
-
isozyme PI4KIIIbeta can be activated by protein kinase D phosphorylation
phosphoprotein
14-3-3 proteins bind isoform PI4KB upon its phosphorylation by protein kinase D. 14-3-3 proteins protect isoform PI4KB from proteolytic degradation in vitro
phosphoprotein
the enzyme is phosphorylated at S294 in order to interact with 14-3-3 protein
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
sitting drop vapor diffusion method, using 100 mM MES-imidazole pH 6.5, 10% (w/v) PEG 4000, 20% (v/v) glycerol, 20 mM 1,6-hexanediol, 20 mM 1-butanol, 20 mM 1,2-propanediol, 20 mM 2-propanol, 20 mM 1,4-butanediol, 20 mM 1,3-propanediol
isoform PI4KB in complex with 14-3-3 protein, sitting drop vapor diffusion method, using 0.1M MES pH6, 10% (w/v) PEG 8000, 20% (v/v) ethylene glycol
phosphatidylinositol 4-kinase type IIalpha in complex with ATP, vapor diffusion method
sitting drop vapor diffusion method, using 100 mM MES-imidazole pH 6.5, 10% (w/v) PEG 4000, 20% (v/v) glycerol, 20 mM 1,6-hexanediol, 20 mM 1-butanol, 20 mM 1,2-propanediol, 20 mM 2-propanol, 20 mM 1,4-butanediol, 20 mM 1,3-propanediol
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
K165-K172
when the entire membrane binding segment K165-K172 was mutated to alanines, the kinase is inactive
PI4K230 DELTA1-1189
-
deletion mutant with 97000 Da compared to wild-type enzyme of 230000 Da, the enzyme is stable but activity is not detectable
PI4K230 DELTA1-1427
-
deletion mutant with 68000 Da compared to wild-type enzyme of 230000 Da, the enzyme is stable but activity is not detectable
PI4K230 DELTA1-1531
-
deletion mutant with 56000 Da compared to wild-type enzyme of 230000 Da, the enzyme is stable but activity is not detectable
PI4K230 DELTA1-872
-
deletion mutant with 130000 Da compared to wild-type enzyme of 230000 Da, the enzyme is stable, 0.048 mM/mg*min compared to 0.058 mM/mg*min for the wild-type enzyme
R275W
-
the mutation is associated with inherited cutis laxa and leads to a large reduction in enzyme activity
additional information
additional information
-
Huh7.5.1 cells are transduced with a nontargeting lentiviral shRNA construct or shRNA constructs targeting PI4KA or PI4KB. Expression of shRNA-resistant wild-type PI4KA rescues HCV replication in OR6 cells silenced for endogenous PI4KA, while the kinase-dead PI4KA D1899A mutant cannot rescue viral replication in OR6 cells silenced for endogenous PI4KA
additional information
-
isozyme PI4KA depletion by siRNA expression in Huh-7.5 cells, transcomplementation, complementation with the siRNA-resistant PI4KA enhances infectious HCV production 110fold compared to the vector alone, overview. In cell lines expressing the HCV polyprotein, PI4KA siRNAs alter the localization of the HCV NS5A protein, while membranous webs are difficult to detect in HCV-infected cells pretreated with PI4KA siRNAs
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
molecular chaperone Hsp90 is a binding partner of isozyme PI4KIIbeta. Geldanamycin, a specific Hsp90 inhibitor, disrupts the Hsp90-PI4KIIbeta interaction and destabilizes PI4KIIbeta, reducing its half-life by 40% and increasing its susceptibility to ubiquitylation and proteasomal degradation. Cytosolic PI4KIIbeta is much more sensitive to geldanamycin treatment than is the integrally membrane-associated species. Stimuli such as PDGF receptor activation that also induce recruitment of the kinase to membranes disrupt the Hsp90-PI4KIIbeta interaction to a similar extent as inhibitor treatment
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, buffer containing 30% glycerol and 2 mM DTT, minimal loss of activity after 2 weeks
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Ni-NTA resin column chromatography, and Superdex 200 gel filtration
mPIK-I and mPIK-III from membrane fraction and cPIK-I and cPIK-II from cytoslic fraction
-
Ni-NTA resin column chromatography, and Superdex 200 gel filtration
Ni-NTA resin column chromatography, Mono Q column chromatography and Superdex S200 gel filtration
recombinant His-tagged catalytic domain of isozyme PI4KIIIalpha from Sf9 cells by nickel affinity chromatography
-
type III kinase, isoform PI4K92 is expressed as His6 tagged protein in Sf9 cells
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21 Star cells
expression of HA-tagged isozyme PI4KIIalpha in HEK-293 cells, co-expression of FLAG-tagged ubiquitin, PI4KIIalpha undergoes multi-ubiquitination
-
isoform PI4K92 is expressed as His6 tagged protein in Sf9 cells reaching a level of approximately 5% of cellular proteins
isolated catalytic domain of isozyme PI4KIIIalpha as His-tagged protein in Spodoptera frugiperda Sf9 cells via transfection by recombinant baculovirus
-
isozyme PI4KA, DNA and amino acid sequence determination and analysis, expression of GFP-tagged wild-type and mutant enzymes in HEK-293T cells and in U2OS cells
-
PI4KIIIalpha is one of the genes found in Chr22q11, region affected by chromosomal instability, no substantiation of the existence of a functionally relevant short form of PI4KIIIalpha, expression of a cDNA encoding isoform 1 yields a protein of about 97 kDa that shows no catalytic activity and fails to rescue hepatitis C virus replication. expression in COS-7 cells and HEK-293 cells
-
recombinant expression of N-terminal myc-tagged PI4KB and 3xFLAG-tagged PI4KA in Huh7.5.1 cells
-
transient expression of GFP-PI4KIIalpha in CHO cells, the tagged enzyme is present in perinuclear vesicles in control and 25-hydroxycholesterol-treated cells, overview
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
-
type II phosphatidylinositol 4-kinases are promising targets for therapeutic intervention against viral infections, detailed overview
pharmacology
-
type II phosphatidylinositol 4-kinases are promising targets for therapeutic intervention against viral infections, detailed overview
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Walker, D.H.; Dougherty, N.; Pike, L.J.
Purification and characterization of a phosphatidylinositol kinase from A431 cells
Biochemistry
27
6504-6511
1988
Homo sapiens
Vogel, S.; Hoppe, J.
Polyamines stimulate the phosphorylation of phosphatidylinositol in membranes from A431 cells
Eur. J. Biochem.
154
253-257
1986
Homo sapiens
Graziani, A.; Ling, L.E.; Endemann, G.; Carpenter, C.L.; Cantley, L.C.
Purification and characterization of human erythrocyte phosphatidylinositol 4-kinase. Phosphatidylinositol 4-kinase and phosphatidylinositol 3-monophosphate 4-kinase are distinct enzymes
Biochem. J.
284
39-45
1992
Homo sapiens
-
Nishioka, H.; Sawa, T.; Hamada, M.; Shimura, N.; Imoto, M.; Umezawa, K.
Inhibition of phosphatidylinositol kinase by toyocamycin
J. Antibiot.
43
1586-1589
1990
Homo sapiens
Suga, K.; Kambayashi, J.; Tsujinaka, T.; Sakon, M.; Mori, T.
Properties of phosphatidylinositol kinase of human platelets
Biochem. Int.
15
769-777
1987
Homo sapiens
Buckley, J.T.
Properties of human erythrocyte phosphatidylinositol kinase and inhibition by adenosine, ADP and related compounds
Biochim. Biophys. Acta
498
1-9
1977
Homo sapiens
Jenkins, G.H.; Subrahmanyam, G.; Anderson, R.A.
Purification and reconstitution of phosphatidylinositol 4-kinase from human erythrocytes
Biochim. Biophys. Acta
1080
11-18
1991
Homo sapiens
Wetzker, R.; Klinger, R.; Hsuan, J.; Fry, M.J.; Kauffmann-Zeh, A.; Mller, E.; Frunder, H.; Waterfield, M.
Purification and characterization of phosphatidylinositol 4-kinase from human erythrocyte membranes
Eur. J. Biochem.
200
179-185
1991
Homo sapiens
Kanoh, H.; Banno, Y.; Hirata, M.; Nozawa, Y.
Partial purification and characterization of phosphatidylinositol kinases from human platelets
Biochim. Biophys. Acta
1046
120-126
1990
Homo sapiens
Heilmeyer, L.Jr.; Vereb, G.Jr.; Vereb, G.; Kakuk, A.; Szivak, I.
Mammalian phosphatidylinositol 4-kinases
IUBMB Life
55
59-65
2003
Bos taurus, Homo sapiens, Mus musculus, Rattus norvegicus
Suer, S.; Sickmann, A.; Meyer, H.E.; Herberg, F.W.; Heilmeyer, L.M., Jr.
Human phosphatidylinositol 4-kinase isoform PI4K92. Expression of the recombinant enzyme and determination of multiple phosphorylation sites
Eur. J. Biochem.
268
2099-2106
2001
Homo sapiens (Q9UBF8), Homo sapiens
Waugh, M.G.; Minogue, S.; Anderson, J.S.; Balinger, A.; Blumenkrantz, D.; Calnan, D.P.; Cramer, R.; Hsuan, J.J.
Localization of a highly active pool of type II phosphatidylinositol 4-kinase in a p97/valosin-containing-protein-rich fraction of the endoplasmic reticulum
Biochem. J.
373
57-63
2003
Homo sapiens
Wei, Y.J.; Sun, H.Q.; Yamamoto, M.; Wlodarski, P.; Kunii, K.; Martinez, M.; Barylko, B.; Albanesi, J.P.; Yin, H.L.
Type II phosphatidylinositol 4-kinase beta is a cytosolic and peripheral membrane protein that is recruited to the plasma membrane and activated by Rac-GTP
J. Biol. Chem.
277
46586-46593
2002
Homo sapiens (Q8TCG2)
Balla, A.; Tuymetova, G.; Barshishat, M.; Geiszt, M.; Balla, T.
Characterization of type II phosphatidylinositol 4-kinase isoforms reveals association of the enzymes with endosomal vesicular compartments
J. Biol. Chem.
277
20041-20050
2002
Homo sapiens (Q8TCG2)
Prajda, N.; Singhal, R.L.; Yeh, Y.A.; Olah, E.; Look, K.Y.; Weber, G.
Linkage of reduction in 1-phosphatidylinositol 4-kinase activity and inositol 1,4,5-trisphosphate concentration in human ovarian carcinoma cells treated with quercetin
Life Sci.
56
1587-1593
1995
Homo sapiens
Waugh, M.G.; Minogue, S.; Blumenkrantz, D.; Anderson, J.S.; Hsuan, J.J.
Identification and characterization of differentially active pools of type IIalpha phosphatidylinositol 4-kinase activity in unstimulated A431 cells
Biochem. J.
376
497-503
2003
Homo sapiens
Srivastava, R.; Ratheesh, A.; Gude, R.K.; Rao, K.V.K.; Panda, D.; Subrahmanyam, G.
Resveratrol inhibits type II phosphatidylinositol 4-kinase: A key component in pathways of phosphoinositide turn over
Biochem. Pharmacol.
70
1048-1055
2005
Homo sapiens (Q8TCG2)
Souza, M.S.; Magnarelli de Potas, G.; Pechen de D'Angelo, A.M.
Organophosphorous and organochlorine pesticides affect human placental phosphoinositides metabolism and PI-4 kinase activity
J. Biochem. Mol. Toxicol.
18
30-36
2004
Homo sapiens
Wu, B.; Kitagawa, K.; Zhang, N.Y.; Liu, B.; Inagaki, C.
Pathophysiological concentrations of amyloid beta proteins directly inhibit rat brain and recombinant human type II phosphatidylinositol 4-kinase activity
J. Neurochem.
91
1164-1170
2004
Homo sapiens
Balla, A.; Tuymetova, G.; Tsiomenko, A.; Varnai, P.; Balla, T.
A plasma membrane pool of phosphatidylinositol 4-phosphate is generated by phosphatidylinositol 4-kinase type-III alpha: studies with the PH domains of the oxysterol binding protein and FAPP1
Mol. Biol. Cell
16
1282-1295
2005
Homo sapiens
Pizarro-Cerda, J.; Payrastre, B.; Wang, Y.J.; Veiga, E.; Yin, H.L.; Cossart, P.
Type II phosphatidylinositol 4-kinases promote Listeria monocytogenes entry into target cells
Cell. Microbiol.
9
2381-2390
2007
Homo sapiens
Kakuk, A.; Friedlaender, E.; Vereb, G.; Kasa, A.; Balla, A.; Balla, T.; Heilmeyer, L.M.; Gergely, P.; Vereb, G.
Nucleolar localization of phosphatidylinositol 4-kinase PI4K230 in various mammalian cells
Cytometry A
69
1174-1183
2006
Homo sapiens, Rattus norvegicus
Szivak, I.; Lamb, N.; Heilmeyer, L.M.
Subcellular localization and structural function of endogenous phosphorylated phosphatidylinositol 4-kinase (PI4K92)
J. Biol. Chem.
281
16740-16749
2006
Homo sapiens
Toth, B.; Balla, A.; Ma, H.; Knight, Z.A.; Shokat, K.M.; Balla, T.
Phosphatidylinositol 4-kinase IIIbeta regulates the transport of ceramide between the endoplasmic reticulum and Golgi
J. Biol. Chem.
281
36369-36377
2006
Homo sapiens
Waugh, M.G.; Minogue, S.; Chotai, D.; Berditchevski, F.; Hsuan, J.J.
Lipid and peptide control of phosphatidylinositol 4-kinase IIalpha activity on Golgi-endosomal rafts
J. Biol. Chem.
281
3757-3763
2006
Homo sapiens
Jeganathan, S.; Lee, J.M.
Binding of elongation factor eEF1A2 to phosphatidylinositol 4-kinase beta stimulates lipid kinase activity and phosphatidylinositol 4-phosphate generation
J. Biol. Chem.
282
372-380
2007
Homo sapiens
Minogue, S.; Waugh, M.G.; De Matteis, M.A.; Stephens, D.J.; Berditchevski, F.; Hsuan, J.J.
Phosphatidylinositol 4-kinase is required for endosomal trafficking and degradation of the EGF receptor
J. Cell Sci.
119
571-580
2006
Homo sapiens
Xiong, Z.M.; Kitagawa, K.; Nishiuchi, Y.; Kimura, T.; Inagaki, C.
Protective effects of Abeta-derived tripeptide, Abeta(32-34), on Abeta(1-42)-induced phosphatidylinositol 4-kinase inhibition and neurotoxicity
Neurosci. Lett.
419
247-252
2007
Homo sapiens
Delang, L.; Paeshuyse, J.; Neyts, J.
The role of phosphatidylinositol 4-kinases and phosphatidylinositol 4-phosphate during viral replication
Biochem. Pharmacol.
84
1400-1408
2012
Homo sapiens
Szentpetery, Z.; Szakacs, G.; Bojjireddy, N.; Tai, A.W.; Balla, T.
Genetic and functional studies of phosphatidyl-inositol 4-kinase type IIIalpha
Biochim. Biophys. Acta
1811
476-483
2011
Homo sapiens
Waugh, M.G.
Phosphatidylinositol 4-kinases, phosphatidylinositol 4-phosphate and cancer
Cancer Lett.
325
125-131
2012
Homo sapiens
Moessinger, J.; Wieffer, M.; Krause, E.; Freund, C.; Gerth, F.; Krauss, M.; Haucke, V.
Phosphatidylinositol 4-kinase IIalpha function at endosomes is regulated by the ubiquitin ligase Itch
EMBO Rep.
13
1087-1094
2012
Homo sapiens
Jung, G.; Barylko, B.; Lu, D.; Shu, H.; Yin, H.; Albanesi, J.P.
Stabilization of phosphatidylinositol 4-kinase type IIbeta by interaction with Hsp90
J. Biol. Chem.
286
12775-12784
2011
Homo sapiens, Rattus norvegicus
Yang, N.; Ma, P.; Lang, J.; Zhang, Y.; Deng, J.; Ju, X.; Zhang, G.; Jiang, C.
Phosphatidylinositol 4-kinase IIIbeta is required for severe acute respiratory syndrome coronavirus spike-mediated cell entry
J. Biol. Chem.
287
8457-8467
2012
Chlorocebus sabaeus, Homo sapiens
Berger, K.L.; Kelly, S.M.; Jordan, T.X.; Tartell, M.A.; Randall, G.
Hepatitis C virus stimulates the phosphatidylinositol 4-kinase III alpha-dependent phosphatidylinositol 4-phosphate production that is essential for its replication
J. Virol.
85
8870-8883
2011
Homo sapiens
Banerji, S.; Ngo, M.; Lane, C.F.; Robinson, C.A.; Minogue, S.; Ridgway, N.D.
Oxysterol binding protein-dependent activation of sphingomyelin synthesis in the Golgi apparatus requires phosphatidylinositol 4-kinase IIalpha
Mol. Biol. Cell
21
4141-4150
2010
Cricetulus griseus, Homo sapiens
Jovic, M.; Kean, M.J.; Szentpetery, Z.; Polevoy, G.; Gingras, A.C.; Brill, J.A.; Balla, T.
Two phosphatidylinositol 4-kinases control lysosomal delivery of the Gaucher disease enzyme, beta-glucocerebrosidase
Mol. Biol. Cell
23
1533-1545
2012
Homo sapiens
Tai, A.W.; Salloum, S.
The role of the phosphatidylinositol 4-kinase PI4KA in hepatitis C virus-induced host membrane rearrangement
PLoS ONE
6
e26300
2011
Homo sapiens
Bianco, A.; Reghellin, V.; Donnici, L.; Fenu, S.; Alvarez, R.; Baruffa, C.; Peri, F.; Pagani, M.; Abrignani, S.; Neddermann, P.; De Francesco, R.
Metabolism of phosphatidylinositol 4-kinase IIIalpha-dependent PI4P is subverted by HCV and is targeted by a 4-anilino quinazoline with antiviral activity
PLoS Pathog.
8
e1002576
2012
Homo sapiens
Altan-Bonnet, N.; Balla, T.
Phosphatidylinositol 4-kinases: hostages harnessed to build panviral replication platforms
Trends Biochem. Sci.
37
293-302
2012
Saccharomyces cerevisiae, Homo sapiens
Graham, T.R.; Burd, C.G.
Coordination of Golgi functions by phosphatidylinositol 4-kinases
Trends Cell Biol.
21
113-121
2011
Saccharomyces cerevisiae, Homo sapiens
Klima, M.; Baumlova, A.; Chalupska, D.; Hrebabecky, H.; Dejmek, M.; Nencka, R.; Boura, E.
The high-resolution crystal structure of phosphatidylinositol 4-kinase IIbeta and the crystal structure of phosphatidylinositol 4-kinase IIalpha containing a nucleoside analogue provide a structural basis for isoform-specific inhibitor design
Acta Crystallogr. Sect. D
71
1555-1563
2015
Homo sapiens (Q8TCG2), Homo sapiens (Q9BTU6)
Sinha, R.K.; Bojjireddy, N.; Kulkarni, D.; Ratheesh, A.; Chiplunkar, S.V.; Gude, R.; Subrahmanyam, G.
Type II phosphatidylinositol 4-kinase beta is an integral signaling component of early T cell activation mechanisms
Biochimie
95
1560-1566
2013
Homo sapiens
Baumlova, A.; Chalupska, D.; Rozycki, B.; Jovic, M.; Wisniewski, E.; Klima, M.; Dubankova, A.; Kloer, D.P.; Nencka, R.; Balla, T.; Boura, E.
The crystal structure of the phosphatidylinositol 4-kinase IIalpha
EMBO Rep.
15
1085-1092
2014
Homo sapiens (Q9BTU6)
Rutaganira, F.U.; Fowler, M.L.; McPhail, J.A.; Gelman, M.A.; Nguyen, K.; Xiong, A.; Dornan, G.L.; Tavshanjian, B.; Glenn, J.S.; Shokat, K.M.; Burke, J.E.
Design and structural characterization of potent and selective inhibitors of phosphatidylinositol 4 kinase IIIbeta
J. Med. Chem.
59
1830-1839
2016
Homo sapiens
Harak, C.; Radujkovic, D.; Taveneau, C.; Reiss, S.; Klein, R.; Bressanelli, S.; Lohmann, V.
Mapping of functional domains of the lipid kinase phosphatidylinositol 4-kinase type III alpha involved in enzymatic activity and hepatitis C virus replication
J. Virol.
88
9909-9926
2014
Homo sapiens
Ryder, P.V.; Vistein, R.; Gokhale, A.; Seaman, M.N.; Puthenveedu, M.A.; Faundez, V.
The WASH complex, an endosomal Arp2/3 activator, interacts with the Hermansky-Pudlak syndrome complex BLOC-1 and its cargo phosphatidylinositol-4-kinase type IIalpha
Mol. Biol. Cell
24
2269-2284
2013
Homo sapiens
Arita, M.; Dobrikov, G.; Puerstinger, G.; Galabov, A.S.
Allosteric Regulation of Phosphatidylinositol 4-Kinase III Beta by an Antipicornavirus Compound MDL-860
ACS Infect. Dis.
3
585-594
2017
Homo sapiens
Sala, M.; Koegler, M.; Plackova, P.; Mejdrova, I.; Hrebabecky, H.; Prochazkova, E.; Strunin, D.; Lee, G.; Birkus, G.; Weber, J.; Mertlikova-Kaiserova, H.; Nencka, R.
Purine analogs as phosphatidylinositol 4-kinase IIIbeta inhibitors
Bioorg. Med. Chem. Lett.
26
2706-2712
2016
Homo sapiens
Mohamed, M.; Gardeitchik, T.; Balasubramaniam, S.; Guerrero-Castillo, S.; Dalloyaux, D.; van Kraaij, S.; Venselaar, H.; Hoischen, A.; Urban, Z.; Brandt, U.; Al-Shawi, R.; Simons, J.P.; Frison, M.; Ngu, L.H.; Callewaert, B.; Spelbrink, H.; Kallemeijn, W.W.; Aerts, J.M.F.G.; Waugh, M.G.; Morava, E.; We, W.e.v.
Novel defect in phosphatidylinositol 4-kinase type 2-alpha (PI4K2A) at the membrane-enzyme interface is associated with metabolic cutis laxa
J. Inherit. Metab. Dis.
43
1382-1391
2020
Homo sapiens
Sengupta, N.; Jovic, M.; Barnaeva, E.; Kim, D.W.; Hu, X.; Southall, N.; Dejmek, M.; Mejdrova, I.; Nencka, R.; Baumlova, A.; Chalupska, D.; Boura, E.; Ferrer, M.; Marugan, J.; Balla, T.
A large scale high-throughput screen identifies chemical inhibitors of phosphatidylinositol 4-kinase type II alpha
J. Lipid Res.
60
683-693
2019
Homo sapiens
Mejdrova, I.; Chalupska, D.; Plackova, P.; Mueller, C.; Sala, M.; Klima, M.; Baumlova, A.; Hrebabecky, H.; Prochazkova, E.; Dejmek, M.; Strunin, D.; Weber, J.; Lee, G.; Matousova, M.; Mertlikova-Kaiserova, H.; Ziebuhr, J.; Birkus, G.; Boura, E.; Nencka, R.
Rational design of novel highly potent and selective phosphatidylinositol 4-kinase IIIbeta (PI4KB) inhibitors as broad-spectrum antiviral agents and tools for chemical biology
J. Med. Chem.
60
100-118
2017
Homo sapiens, Homo sapiens (Q9UBF8)
Chalupska, D.; Eisenreichova, A.; Rozycki, B.; Rezabkova, L.; Humpolickova, J.; Klima, M.; Boura, E.
Structural analysis of phosphatidylinositol 4-kinase IIIbeta (PI4KB) - 14-3-3 protein complex reveals internal flexibility and explains 14-3-3 mediated protection from degradation in vitro
J. Struct. Biol.
200
36-44
2017
Homo sapiens (Q9UBF8)
Alli-Balogun, G.O.; Gewinner, C.A.; Jacobs, R.; Kriston-Vizi, J.; Waugh, M.G.; Minogue, S.
Phosphatidylinositol 4-kinase IIbeta negatively regulates invadopodia formation and suppresses an invasive cellular phenotype
Mol. Biol. Cell
27
4033-4042
2016
Homo sapiens
Daboussi, L.; Costaguta, G.; Ghukasyan, R.; Payne, G.S.
Conserved role for Gga proteins in phosphatidylinositol 4-kinase localization to the trans-Golgi network
Proc. Natl. Acad. Sci. USA
114
3433-3438
2017
Saccharomyces cerevisiae, Homo sapiens
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