Information on EC 2.7.1.67 - 1-phosphatidylinositol 4-kinase

Word Map on EC 2.7.1.67
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)


The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY hide
2.7.1.67
-
RECOMMENDED NAME
GeneOntology No.
1-phosphatidylinositol 4-kinase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + 1-phosphatidyl-1D-myo-inositol = ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
3-phosphoinositide biosynthesis
-
-
D-myo-inositol (1,4,5)-trisphosphate biosynthesis
-
-
Inositol phosphate metabolism
-
-
Metabolic pathways
-
-
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 hide
37205-54-2
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
PI4KIIalpha; PI4KIIIbeta
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
fragment; Oryza sativa subspecies indica
SwissProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
strain ade5 MATa
-
-
Manually annotated by BRENDA team
three PtdIns 4-kinases: Pik1, Stt4, and Lsb6
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
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
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2'-dATP + 1-phosphatidyl-1D-myo-inositol
2'-dADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
show the reaction diagram
-
-
-
-
?
ADP + 1-phosphatidyl-1D-myo-inositol
AMP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
show the reaction diagram
-
12% of the activity with ATP
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
show the reaction diagram
CTP + 1-phosphatidyl-1D-myo-inositol
CDP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
show the reaction diagram
-
10% of the activity with ATP
-
-
?
dATP + 1-phosphatidyl-1D-myo-inositol
dADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
show the reaction diagram
-
104% of the activity with ATP
-
-
?
GTP + 1-phosphatidyl-1D-myo-inositol
GDP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
show the reaction diagram
ITP + 1-phosphatidyl-1D-myo-inositol
IDP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
show the reaction diagram
-
11% of the activity with ATP
-
-
?
TTP + 1-phosphatidyl-1D-myo-inositol
TDP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
show the reaction diagram
-
3% of the activity with ATP
-
-
?
UTP + 1-phosphatidyl-1D-myo-inositol
UDP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
show the reaction diagram
-
18% of the activity with ATP
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
show the reaction diagram
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Co2+
-
divalent metal ions stimulate in decreasing order of efficiency: Mg2+, Fe2+, Mn2+, Fe3+, Co2+
Fe2+
-
divalent metal ions stimulate in decreasing order of efficiency: Mg2+, Fe2+, Mn2+, Fe3+, Co2+
Fe3+
-
divalent metal ions stimulate in decreasing order of efficiency: Mg2+, Fe2+, Mn2+, Fe3+, Co2+
NaCl
-
enhances activity up to about 1.3fold at 1 M
additional information
-
no direct effect by Ca2+
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2'(3')-O-(2,4,6-Trinitrophenyl)ATP
-
-
2'-dATP
-
-
2,3-Dihydroxybenzaldehyde
-
-
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
3'-dATP
-
-
5'-AMP
-
0.5 mM, 10% inhibition
5,5'-dithiobis(2-nitrobenzoate)
-
0.03 mM, 10 min, 95% inhibition
8-bromo-ATP
adenosine
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
-
amyloid beta protein 2-42
-
10 nM
-
amyloid beta protein 25-35
-
10 nM, 78% residual activity
-
arachidonic acid
-
0.5 mg/ml, 91.3% inhibition of mPIK-III
ATPgammaS
Caffeine
-
6.5 mM, 18% inhibition
Cetyltrimethylammonium bromide
-
-
cholesterol
-
cholesterol sensitivity of PI4KIIalpha
Co2+
-
-
Cpd 6
-
-
-
Cu2+
-
0.25 mM CuCl2, complete inhibition
Cutsum
-
above 2% v/v
-
deoxycholate
Fe2+
-
-
Formycin A
-
-
GMP
-
1 mM, 20% inhibition
guanosine
-
1 mM, 50% inhibition
HgCl2
-
5 mM, complete inhibition
inosithin
-
a commercial preparation of ethanol-insoluble phospholipids from soybean; at high concentration
-
iodoacetate
-
0.1 mM, complete loss of activity
KCl
-
slight inhibition
La3+
-
0.2 mM, 78% inhibition
Lubrol Px
-
1%, 72% inhibition
Ly-294002
-
IC50: 0.05-0.1 mM; IC50: 0.1 mM
LY294002
MES
-
IC50: 4 mM
Mg2+
-
above 20 mM PI kinase I and II are inhibited. PI kinase III is only slightly inhibited at 50 mM
MgADP-
-
IC50: 0.5 mM
N-(5-[4-chloro-3-[(2-hydroxyethyl)sulfamoyl]phenyl]-4-methyl-1,3-thiazol-2-yl)acetamide
-
i.e. PIK93, a phenylthiazole
N6-dimethylamine-adenosine 5'-triphosphate
Ni2+
-
-
orobol
-
-
PAO
-
inhibitor of type III PI4Ks, with greater specificity for PI4KIIIalpha than for PI4KIIIbeta
Phenylarsine oxide
phosphate
-
20 mM, 50% inhibition
phosphatidic acid
-
slight
phosphatidylcholine
phosphatidylethanolamine
phosphatidylglycerol
phosphatidylinositol 4,5-bisphosphate
phosphatidylinositol 4-phosphate
phosphatidylserine
PIK93
quercetin
resveratrol
-
inhibition of PtdIns 4-kinase activity by resveratrol/phenylarsine oxide reduces Jurkat cell adhesion to matrigel/fibronectin coated surfaces
SDS
-
0.05%, complete
sodium cholate
-
inhibits activity of both mPIK-I and mPIK-III
Sodium deoxycholate
-
-
Sodium mersalyl
-
0.1 mM, 78% inhibition
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
theophylline
-
2 mM, 21% inhibition
Toyocamycin
-
IC50 is 0.0033 mg/ml
Triton X-100
Wortmannin
[5-(4-[[4-(morpholin-4-yl)phenyl]amino]quinazolin-6-yl)furan-2-yl]methanol
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-mercaptoethanol
-
enhances activity
25-hydroxycholesterol
-
activates Golgi/endosome-associated PI4K activity, PI4K activation by 25-hydroxycholesterol is dependent on oxysterol binding protein, overview
3-Mercaptopropionic acid
-
enhances activity
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
cetyltrimethyl ammonium bromide
-
weak stimulation
Cutsum
-
stimulates
-
dichlorodiphenyltrichloroethane
-
i.e. DDT, 0.01 mM enhances activity but no changes are observed by lower concentration, membrane associated enzyme
Dimethylsulfoxide
-
1.0%, activation to 160% of the original activity
EDTA
-
2 mM, marked stimulation, even in presence of 30 mM Mg2+
eukaryotic protein translation elongation factor 1 alpha 2
-
up to a 2fold molar excess of recombinant eEF1A2 is required to maximally increase PI4KIIIbeta activity
-
FcepsilonRI
-
ross-linking activates type II phosphatidylinositol 4-kinase
-
GSH
-
enhances activity
heparin
-
0.01 mM, activation to 116% of the orginal activity
heptachlor
-
0.0001 mM enhances activity by 88%, 0.01 mM enhances activity by 52%, membrane associated enzyme
histone
-
stimulates
inosithin
-
at low concentrations
-
M7 analogue of mastoparan
-
0.02 mM
Mastoparan
-
0.01 mM, 3-4fold increase of activity
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
-
octyl beta-D-glucoside
-
10-20 mM, stimulates
oxysterol binding protein
-
activates Golgi/endosome-associated PI4K activity, required for PI4K activation by 25-hydroxycholesterol, overview
-
phosvitin
-
stimulates
-
PIK-A49
-
purification of the phosphatidylinositol 4-kinase activator from carrot cells
-
poly(L-lysine)
Polyarginine
-
stimulates
RAB1
-
activates PI4KIIIalpha and stimulates the production of phosphatidylinositol 4-phosphate at the Golgi
-
salicylic acid
-
0.25 mM
sodium cholate
-
stimulates 3.8fold at 14 mM
Sodium deoxycholate
-
stimulates
sodium taurocholate
-
weak stimulation
spermidine
-
half-maximal stimulation at 1.5 mM
spermine
Trifluoperazine
-
stimulates activity of the purified enzyme less efficiently than that of the membrane-bound enzyme
Triton X-100
Tween-20
-
weak stimulation
yeast frequenin
-
2fold increase of activity at 0.05 mM
-
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.016 - 0.1
1-phosphatidyl-1D-myo-inositol
0.01 - 1.7
ATP
0.62
GTP
-
pH 7.1, 25C
0.044 - 0.36
MgATP2-
0.017 - 1
phosphatidylinositol
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2.77
1-phosphatidyl-1D-myo-inositol
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.032
2'(3')-O-(2,4,6-Trinitrophenyl)ATP
-
pH 7.4, 30C
0.014
2'-dATP
-
pH 7.4, 25C, in presence of 3 mM spermidine
0.012
3'-dATP
-
pH 7.4, 25C, in absence of spermidine
0.11
8-bromo-ATP
-
pH 7.4, 25C, in presence of 3 mM spermidine
0.01 - 1.52
adenosine
0.01 - 0.57
ADP
0.027 - 2.82
AMP
0.088
ATP
-
type II enzyme
0.18
ATPgammaS
-
pH 7.4, 30C
0.0019 - 12
Ca2+
0.5 - 1.68
cAMP
2.9
CDP
-
pH 7.8, 28C
1.68
CTP
-
pH 7.8, 28C
0.013 - 1.75
GTP
0.04 - 1.9
N6-dimethylamine-adenosine 5'-triphosphate
0.235 - 0.774
phosphatidylinositol 4-phosphate
3.6
UTP
-
pH 7.8, 28C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00012 - 0.0014
2-amino-1-(isopropylsulfonyl)-6-benzimidazole phenylketone oxime
0.07 - 0.15
adenosine
0.12
ADP
Sus scrofa
-
IC50: 0.12 mM. 1 mM, 92% inhibition
0.4 - 5.6
Ca2+
0.000024
Cpd 6
Homo sapiens
-
isozyme PI4KIIIbeta, pH and temperature not specified in the publication
-
0.05 - 0.1
Ly-294002
4
MES
Bos taurus
-
IC50: 4 mM
0.5
MgADP-
Saccharomyces cerevisiae
-
IC50: 0.5 mM
0.000019 - 0.0011
N-(5-[4-chloro-3-[(2-hydroxyethyl)sulfamoyl]phenyl]-4-methyl-1,3-thiazol-2-yl)acetamide
0.001 - 0.1
Phenylarsine oxide
0.004 - 0.1
quercetin
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
0.00005 - 0.3
Wortmannin
0.00057 - 0.0031
[5-(4-[[4-(morpholin-4-yl)phenyl]amino]quinazolin-6-yl)furan-2-yl]methanol
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0051
-
-
0.0075
-
-
0.027
-
-
0.044
-
-
1.05
-
-
1.149
-
-
1.18
-
-
2.7
-
-
8.824
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6 - 7
-
-
6 - 8
-
-
6.5 - 7.5
-
in presence of endogenous substrate
6.5
-
when the substrate is added in form of phosphatidylinositol/phosphatidylserine mixed micelles, 1 mM phosphatidylinositol in 0.025% v/v final concentration of Triton X-100
6.5 - 7.5
-
PI kinase III
6.5 - 8
-
activity in presence of 0.25% Triton X-100
6.5 - 7
-
phosphorylation of endogenous 1-phosphatidyl-1D-myo-inositol without Triton X-100
6.5 - 8.6
-
phosphorylation of endogenous 1-phosphatidyl-1D-myo-inositol without 0.01% Triton X-100
7 - 8
-
-
7.5 - 9
-
PI kinase I
8 - 8.5
-
-
8.5 - 9
-
mPIK-I and mPIK-III
9
-
PI kinase II
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5 - 8
-
pH 5.0: about 40% of maximal activity, pH 8.0: about 50% of maximal activity
5.3 - 9
-
pH 5.3: about 80% of maximal activity, pH 8.6: about 60% of maximal activity
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
5.5 - 8
-
rapid decrease of activity above pH 8.0 and below pH 5.5
6 - 9
-
activity of cPIK-I and cPIK-III is almost undetectable at pH 6.0, pH 9.0: about 80% of maximal activity
6 - 8.5
-
pH 7.5: about 75% of maximal activity, pH 10.5: about 40% of maximal activity, PI kinase III
6 - 9
-
active from pH 6.0 to pH 9.0 with Tris maleate buffer
6 - 9.5
-
pH 6.0: about 75% of maximal activity, pH 9.5: about 60% of maximal activity
6.3 - 8.7
-
pH 6.3: about 50% of maximal activity, pH 8.7: about 80% of maximal activity
6.5 - 8.5
-
pH 6.5: about 40% of maximal activity, pH 8.0-8.5: optimium
7 - 8
-
pH 7.0: about 70% of maximal activity, pH 8.0: about 45% of maximal activity
7 - 8.5
-
pH 7.0: about 50% of maximal activity, pH 8.5: about 40% of maximal activity, enzyme form QII
7.3 - 9
-
pH 7.3: about 75% of maximal activity, pH 9.0: about 95% of maximal activity
7.5 - 10.5
-
pH 7.5: about 50% of maximal activity, pH 10.5: about 65% of maximal activity, PI kinase I
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22
-
assay at room temperature
28
-
at 30 mM MgCl2
42
-
at 2 mM MgCl2 and 10 mM MnCl2
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
20 - 40
-
20C: about 65% of maximal activity, 40C: about 65% of maximal activity
20 - 50
-
20C: about 20% of maximal activity, 50C: about 15% of maximal activity
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5
-
chromatofocusing
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
non-specific infiltrating duct and infiltrating lobular carcinomas
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
PI4KIIalpha normally present both in perinuclear and peripheral organelles is substantially decreased in the peripheral membranes of AP-3-deficient mocha fibroblasts
Manually annotated by BRENDA team
-
PI4KIIalpha is strongly reduced in the nerve terminals of mocha hippocampal mossy fibers
Manually annotated by BRENDA team
-
Madin-darby canine kidney cell
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
dark grown
Manually annotated by BRENDA team
-
dark grown
Manually annotated by BRENDA team
-
localized in the principal piece, midpiece and the postacrosomal region
Manually annotated by BRENDA team
-
cell lines with inducible expression of the HCV polyprotein or individual viral proteins
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
phosphatidylinositol-4-kinase type II alpha is a component of
Manually annotated by BRENDA team
-
PI4KIIalpha normally present both in perinuclear and peripheral organelles is substantially decreased in the peripheral membranes of AP-3-deficient mocha fibroblasts
-
Manually annotated by BRENDA team
-
glucose-transporter
Manually annotated by BRENDA team
additional information
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
44000
SDS-PAGE
46730
calculated from amino acid sequence
54000
-
calculated from amino acid sequence
60000
-
gel filtration
66000
-
calculated from amino acid sequence
76000
-
mPIK-I, gel filtration
83000
-
gel filtration
91000
-
isozyme PI4KIIIbeta
100000
-
SDS-PAGE
110000
-
SDS-PAGE
126000
-
calculated from amino acid sequence
150000
-
gel filtration
200000
-
enzyme type I, gel filtration
230000
550000
-
cPIK-I and cPIK-II, gel filtration
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
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
additional information