Information on EC 2.7.1.149 - 1-phosphatidylinositol-5-phosphate 4-kinase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.7.1.149
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RECOMMENDED NAME
GeneOntology No.
1-phosphatidylinositol-5-phosphate 4-kinase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + 1-phosphatidyl-1D-myo-inositol 5-phosphate = ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
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-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
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-
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-
Phosphorylation
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
D-myo-inositol (1,4,5)-trisphosphate biosynthesis
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D-myo-inositol-5-phosphate metabolism
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Inositol phosphate metabolism
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SYSTEMATIC NAME
IUBMB Comments
ATP:1-phosphatidyl-1D-myo-inositol-5-phosphate 4-phosphotransferase
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CAS REGISTRY NUMBER
COMMENTARY hide
104645-76-3
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247907-17-1
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
ecotype Columbia-0
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Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
Site-directed mutagenesis is performed on the human type IIbeta PIPkin cloned into pEGFP-C1 using QuikChange mutagenesis method, to introduce an Glu300Asp amino acid substitution into the human nuclear localisation sequence producing the equivalent chicken sequence 289-DRAEQEEMEVE(E300D)RAEDEE-306
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Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
malfunction
physiological function
SUBSTRATE
PRODUCT                       
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 3-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
show the reaction diagram
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poor substrate compared to 1-phosphatidyl-1D-myo-inositol 5-phosphate
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
ATP + 1-phosphatidyl-1D-myo-inositol 5-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
ATP + dipalmitoyl-phosphatidyl-1D-myo-inositol 5-phosphate
ADP + dipalmitoyl-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
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-
-
-
?
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
ATP + 1-phosphatidyl-1D-myo-inositol 5-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
additional information
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2E)-2-(3,4-dihydroxybenzoyl)-3-(3,4-dihydroxyphenyl)prop-2-enenitrile
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-
(2E)-2-(3,4-dihydroxybenzoyl)-3-(4-hydroxy-3-iodo-5-methoxyphenyl)prop-2-enenitrile
-
-
(3E)-5-amino-3-[(2Z)-1-cyano-2-(3H-indol-3-ylidene)ethylidene]-2,3-dihydro-1H-pyrazole-4-carbonitrile
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-
(3Z)-2-amino-4-(3,4,5-trihydroxyphenyl)buta-1,3-diene-1,1,3-tricarbonitrile
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-
2,4-diamino-N-[3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide
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-
3-(trifluoromethyl)phenyl 4-amino-2-(4,4-dimethyl-2-oxoimidazolidin-1-yl)pyrimidine-5-carboxylate
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4-amino-2-(4,4-dimethyl-2-oxoimidazolidin-1-yl)-N-(3-phenoxyphenyl)pyrimidine-5-carboxamide
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-
4-amino-2-(4,4-dimethyl-2-oxoimidazolidin-1-yl)-N-methyl-N-[3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide
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-
4-amino-2-(4,4-dimethyl-2-oxoimidazolidin-1-yl)-N-[3-(2,2,2-trifluoroethoxy)phenyl]pyrimidine-5-carboxamide
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-
4-amino-2-(4,4-dimethyl-2-oxoimidazolidin-1-yl)-N-[4-methyl-3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide
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-
4-amino-2-(benzylamino)-N-[3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide
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-
4-amino-2-(dimethylamino)-N-[3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide
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4-amino-2-(methylsulfanyl)-N-[3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide
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-
4-amino-2-(piperidin-1-yl)-N-[3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide
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4-amino-2-hydroxy-N-[3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide
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4-amino-2-methoxy-N-[3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide
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4-amino-2-[(2,2-dimethylpropyl)amino]-N-[3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide
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4-amino-2-[(tert-butylcarbamoyl)amino]-N-[3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide
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4-amino-2-[[(1-methyl-1H-pyrazol-5-yl)methyl]amino]-N-[3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide
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4-amino-N-(1,3-benzothiazol-5-yl)-2-(4,4-dimethyl-2-oxoimidazolidin-1-yl)pyrimidine-5-carboxamide
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4-amino-N-(1-benzothiophen-5-yl)-2-(4,4-dimethyl-2-oxoimidazolidin-1-yl)pyrimidine-5-carboxamide
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4-amino-N-[3-(trifluoromethyl)phenyl]-2-(3,4,4-trimethyl-2-oxoimidazolidin-1-yl)pyrimidine-5-carboxamide
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4-amino-N-[3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide
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NIH-12848
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full designation NCGC00012848-02, specific inhibitor of isoform PI5P4Kgamma, does not inhibit the alpha and beta PI5P4K isoforms at concentrations up to 0.1 mM; inhibitor of isoform PI5P4Kgamma only
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piperine
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complete inhibition at 0.1 mM
SAR088
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tyrphostin
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ATP-competitive inhibitors, i.e. tyrosine phosphorylation inhibitors, of isozyme PI5P4Kalpha
tyrphostin 23
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tyrphostin 47
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tyrphostin AG 1478
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tyrphostin AG 490
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tyrphostin AG 494
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tyrphostin AG 537
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tyrphostin AG 555
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tyrphostin AG 698
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tyrphostin AG 808
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additional information
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high-throughput inhibitor screening method, counterscreen assay and ATP competition assay, overview
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00394 - 0.09418
ATP
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00000572 - 0.0105
ATP
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.014
(2E)-2-(3,4-dihydroxybenzoyl)-3-(3,4-dihydroxyphenyl)prop-2-enenitrile
Homo sapiens
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pH 7.4, 22C, isozyme PI5P4Kalpha
0.002
(2E)-2-(3,4-dihydroxybenzoyl)-3-(4-hydroxy-3-iodo-5-methoxyphenyl)prop-2-enenitrile
Homo sapiens
-
pH 7.4, 22C, isozyme PI5P4Kalpha
0.013
(3E)-5-amino-3-[(2Z)-1-cyano-2-(3H-indol-3-ylidene)ethylidene]-2,3-dihydro-1H-pyrazole-4-carbonitrile
Homo sapiens
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pH 7.4, 22C, isozyme PI5P4Kalpha
0.005
(3Z)-2-amino-4-(3,4,5-trihydroxyphenyl)buta-1,3-diene-1,1,3-tricarbonitrile
Homo sapiens
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pH 7.4, 22C, isozyme PI5P4Kalpha
0.03
2,4-diamino-N-[3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide
Homo sapiens
-
IC50 above 0.03 mM, at pH 7.4 and 26C
0.03
3-(trifluoromethyl)phenyl 4-amino-2-(4,4-dimethyl-2-oxoimidazolidin-1-yl)pyrimidine-5-carboxylate
Homo sapiens
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IC50 above 0.03 mM, at pH 7.4 and 26C
0.0054
4-amino-2-(4,4-dimethyl-2-oxoimidazolidin-1-yl)-N-(3-phenoxyphenyl)pyrimidine-5-carboxamide
Homo sapiens
-
at pH 7.4 and 26C
0.03
4-amino-2-(4,4-dimethyl-2-oxoimidazolidin-1-yl)-N-methyl-N-[3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide
Homo sapiens
-
IC50 above 0.03 mM, at pH 7.4 and 26C
0.0081
4-amino-2-(4,4-dimethyl-2-oxoimidazolidin-1-yl)-N-[3-(2,2,2-trifluoroethoxy)phenyl]pyrimidine-5-carboxamide
Homo sapiens
-
at pH 7.4 and 26C
0.013
4-amino-2-(4,4-dimethyl-2-oxoimidazolidin-1-yl)-N-[4-methyl-3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide
Homo sapiens
-
at pH 7.4 and 26C
0.025
4-amino-2-(benzylamino)-N-[3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide
Homo sapiens
-
at pH 7.4 and 26C
0.03
4-amino-2-(dimethylamino)-N-[3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide
Homo sapiens
-
IC50 above 0.03 mM, at pH 7.4 and 26C
0.03
4-amino-2-(methylsulfanyl)-N-[3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide
Homo sapiens
-
IC50 above 0.03 mM, at pH 7.4 and 26C
0.03
4-amino-2-(piperidin-1-yl)-N-[3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide
Homo sapiens
-
IC50 above 0.03 mM, at pH 7.4 and 26C
0.03
4-amino-2-hydroxy-N-[3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide
Homo sapiens
-
IC50 above 0.03 mM, at pH 7.4 and 26C
0.03
4-amino-2-methoxy-N-[3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide
Homo sapiens
-
IC50 above 0.03 mM, at pH 7.4 and 26C
0.008
4-amino-2-[(2,2-dimethylpropyl)amino]-N-[3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide
Homo sapiens
-
at pH 7.4 and 26C
0.03
4-amino-2-[(tert-butylcarbamoyl)amino]-N-[3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide
Homo sapiens
-
IC50 above 0.03 mM, at pH 7.4 and 26C
0.0041
4-amino-2-[[(1-methyl-1H-pyrazol-5-yl)methyl]amino]-N-[3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide
Homo sapiens
-
at pH 7.4 and 26C
0.025
4-amino-N-(1,3-benzothiazol-5-yl)-2-(4,4-dimethyl-2-oxoimidazolidin-1-yl)pyrimidine-5-carboxamide
Homo sapiens
-
at pH 7.4 and 26C
0.013
4-amino-N-(1-benzothiophen-5-yl)-2-(4,4-dimethyl-2-oxoimidazolidin-1-yl)pyrimidine-5-carboxamide
Homo sapiens
-
at pH 7.4 and 26C
0.03
4-amino-N-[3-(trifluoromethyl)phenyl]-2-(3,4,4-trimethyl-2-oxoimidazolidin-1-yl)pyrimidine-5-carboxamide
Homo sapiens
-
IC50 above 0.03 mM, at pH 7.4 and 26C
0.03
4-amino-N-[3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide
Homo sapiens
-
IC50 above 0.03 mM, at pH 7.4 and 26C
0.001
NIH-12848
Mus musculus
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at 22C, pH not specified in the publication; at pH 7.5 and 30C
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0.0038
SAR088
Homo sapiens
-
at pH 7.4 and 26C
-
0.001
tyrphostin
Homo sapiens
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pH 7.4, 22C, isozyme PI5P4Kalpha
0.045
tyrphostin 23
Homo sapiens
-
pH 7.4, 22C, isozyme PI5P4Kalpha
0.02
tyrphostin 47
Homo sapiens
-
pH 7.4, 22C, isozyme PI5P4Kalpha
0.1
tyrphostin AG 1478
Homo sapiens
-
pH 7.4, 22C, isozyme PI5P4Kalpha
0.089
tyrphostin AG 490
Homo sapiens
-
pH 7.4, 22C, isozyme PI5P4Kalpha
0.089
tyrphostin AG 494
Homo sapiens
-
pH 7.4, 22C, isozyme PI5P4Kalpha
0.032
tyrphostin AG 537
Homo sapiens
-
pH 7.4, 22C, isozyme PI5P4Kalpha
0.055
tyrphostin AG 555
Homo sapiens
-
pH 7.4, 22C, isozyme PI5P4Kalpha
0.05
tyrphostin AG 698
Homo sapiens
-
pH 7.4, 22C, isozyme PI5P4Kalpha
0.018
tyrphostin AG 808
Homo sapiens
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pH 7.4, 22C, isozyme PI5P4Kalpha
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22
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assay at room temperature
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
restricted expression in the thick ascending limb of the loop of Henle and in the intercalated cells of the collecting duct
Manually annotated by BRENDA team
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-
Manually annotated by BRENDA team
high mRNA expression; PIP4Kgamma in heart run predominantly as a 40 kDa band, suggesting that processing of this isoform occurs.
Manually annotated by BRENDA team
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highest expression
Manually annotated by BRENDA team
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quantitative real-time PCR enzyme expression analysis
Manually annotated by BRENDA team
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inner segment
Manually annotated by BRENDA team
high mRNA expression
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
partial Golgi localization, primarily the matrix of the cis-Golgi
Manually annotated by BRENDA team
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PI5P4Kalpha is membrane-bound in DT40 cells with a significant amount of endogenous PI5P4Kalpha in the nucleus
Manually annotated by BRENDA team
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isoform PI5P4Kgamma
Manually annotated by BRENDA team
additional information
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analysis of subcellular localization of native and recombinant isozyme PI5P4Kalpha, overview
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Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
49000
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2 * 49000, recombinant isozyme PIP4Kbeta, SDS-PAGE, and crystal structure of isozyme PIP4Kbeta
97000
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recombinant isozyme PIP4Kbeta
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homodimer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
affinity purification of FLAG-His6 tagged proteins using TALON beads
By using TALON metal affinity resin.
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glutathione Sepharose column chromatography; glutathione Sepharose column chromatography, and gel filtration
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heparin agarose column chromatography
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Ni-NTA column chromatography, and gel filtration
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Ni-NTA His binding resin column chromatography, and gel filtration
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recombinant GST-tagged isozymes by glutathione affinity chromatography, recombinant HA-tagged isozymes by affinity chromatography from HEK-293 cells
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recombinant Myc-tagged isozymes by affinity chromatography
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21 cells
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expressed in Escherichia coli BL21(DE3) cells
expressed in Escherichia coli BL21(DE3/pLysS) cells
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expression of EGFP-tagged isozymes PIPKIIbeta and PIPKIIalpha in SW480-ADH cells cytosol and nucleus or cytosol, respectively
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isozyme PIP4K IIbeta, functional expression in enzyme-deficient CHO-IR cells
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overexpression in COS-7 cells
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PI5P4Kalpha is predominantly in the cytoplasm, principally cytosolic, when recombinantly expressed
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PIP5K2 genes are amplified from a whole human brain marathon-ready cDNA library using gene-specific primers. Recombinant protein is expressed from Escherichia coli harbouring PIP5K2s in pET-32a. PCR products are cloned, via incorporated HindIII and BamHI restriction sites, into appropriate plasmid vectors. HeLa, HEK 293, COS-7 and NRK cells are transiently transfected with plasmid constructs.
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quantitative real-time PCR expression analysis, expression of isozyme PIPKIIalpha in Xenopus laevis oocytes
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recombinant expression of GST-tagged isozymes and of HA-tagged isozymes in HEK-293 cells
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recombinant expression of Myc-tagged isozymes, co-expression of the wild-type PIP4Kalpha isozyme suppresses ubiquitination of isozyme PIP4Kbeta
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The last 2.6 kbp of the human PIPkin IIbeta gene and the following 3.6 kbp are cloned and inserted into a plasmid which placed a FLAG-(His6)2 double-tag, followed by a puromycin selection cassette between them. Transfection of this into DT40 cells followed by puromycin selection produces cells which have the tag attached to the C-terminus of the protein when expressed by one of the two alleles. Experiments are conducted on one clonal line derived from this procedure calling JPR3. Successful integration of the tag at the correct genomic location was confirmed by PCR analysis.
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
at later embryonic stages, high PIP4Kalpha expression is detected in the head and the pectoral fins
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the expression of isoform PI5P4Kgamma increases when the cells grow to confluence and polarize
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D271K
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inactive
E300D
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Site-directed mutagenesis is performed on the human Type IIbeta PIPkin cloned into pEGFP-C1 using the QuikChange mutagenesis method, to introduce an Glu300Asp amino acid substitution into the human nuclear localisation sequence producing the equivalent chicken sequence.
D280K
inactive
E300D
Site-directed mutagenesis is performed on the human Type IIbeta PIPkin cloned into pEGFP-C1 using the QuikChange mutagenesis method, to introduce an Glu300Asp amino acid substitution into the human nuclear localisation sequence producing the equivalent chicken sequence.
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
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phosphatidylinositol-5-phosphate 4-kinase type II beta might be an effective therapeutic target for preventing of colon cancer progression