Information on EC 2.7.1.68 - 1-phosphatidylinositol-4-phosphate 5-kinase and Organism(s) Homo sapiens

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Homo sapiens


The taxonomic range for the selected organisms is: Homo sapiens

The enzyme appears in selected viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.7.1.68
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RECOMMENDED NAME
GeneOntology No.
1-phosphatidylinositol-4-phosphate 5-kinase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate = ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
an activation loop spanning the catalytic domain is responsible for determination of both substrate specificity and subcellular targeting
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
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-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
3-phosphoinositide biosynthesis
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D-myo-inositol (1,4,5)-trisphosphate biosynthesis
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Inositol phosphate metabolism
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Metabolic pathways
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SYSTEMATIC NAME
IUBMB Comments
ATP:1-phosphatidyl-1D-myo-inositol-4-phosphate 5-phosphotransferase
This enzyme can also phosphorylate PtdIns3P in the 4-position, and PtdIns, PtdIns3P and PtdIns(3,4)P2 in the 5-position in vitro, but to a lesser extent. The last of these reactions occurs in vivo and is physiologically relevant. Three different isoforms are known.
CAS REGISTRY NUMBER
COMMENTARY hide
104645-76-3
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9032-61-5
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
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phosphorylation of 1-phosphatidyl-1D-myo-inositol 4-phosphate by the type I PI 4-phosphate 5-kinase (PIP5K) family members including PIP5Kalpha, PIP5Kbeta, and PIP5Kgamma isoforms is the major pathway of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate synthesis in mammalian cells
physiological function
additional information
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upon activation by semaphorin 3E, plexin-D1 recruits phosphatidylinositol-4-phosphate 5-kinase, and its enzymatic lipid product, phosphatidylinositol 4,5-bisphosphate, binds to the pleckstrin homology domain of guanine nucleotide exchange protein 100, GEP100. Phosphatidylinositol 4,5-bisphosphate binding to GEP100 enhances its guanine nucleotide exchange factor activity toward Arf6, thus resulting in the disassembly of integrin-mediated focal adhesions and endothelial cell collapse
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 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
ATP + phosphatidylinositol 3-phosphate
ADP + phosphatidylinositol 3,4-bisphosphate
show the reaction diagram
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-
-
?
ATP + phosphatidylinsositol 3,4-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
show the reaction diagram
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-
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-
?
GTP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
GDP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
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0.05 mM GTP is 2fold more active than ATP with type II enzyme. 0.05 mM GTP is 5fold more active than ATP with the type I enzyme
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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
additional information
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mn2+
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Km: 0.2 mM, Mg2+ is three times more effective than Mn2+
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
H2O2
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the enzyme is inhibited after 20 min incubation with 0.6 mM H2O2
heparin
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type II kinase
Wortmannin
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additional information
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not inhibited by SP600125, SB203580, ZVAD-fmk, wortmannin or LY294002
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
advanced glycation end products
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may stimulate PIP5Kgamma to increase 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate production, which may enhance adaptor protein complex 2 localisation to clathrin pits, increase clathrin pit formation, enhance renal Na+/K+ ATPase cargo recognition by adaptor protein complex 2 and/or stimulate cytosolic phospholipase A2 alpha activity
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Ajuba
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dramatic activation of enzymatic activity
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CD28
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heparin
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type I enzyme is stimulated at low concentrations
lysophosphatidic acid
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mechanism overview
phosphatidic acid
small G proteins ARF
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ARF activation absolutely requires the presence of phosphatidic acid, which cannot be substituted by phosphatidylserine, phosphatidylethanolamine, or lysophosphatidic acid, but by competitive phosphatidylcholine
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small GTPase Arf
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involved in membrane receptor-mediated regulation, acts via effectors, mechanism overview
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small GTPase Rho
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involved in membrane receptor-mediated regulation, acts via effectors, mechanism overview
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spermine
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2 mM, 4fold increase in activity of type I enzyme, no effect on type II enzyme
Triton X-100
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the optimal activity obtained in Triton X-100 is 6fold higher than that obtained in the absence of Triton X-100
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.262
1-phosphatidyl-1D-inositol 4-phosphate
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pH 7.5, enzyme type Ibeta
0.005 - 0.065
1-phosphatidyl-1D-myo-inositol 3-phosphate
0.0012 - 4.1
1-phosphatidyl-1D-myo-inositol 4-phosphate
0.002 - 0.025
ATP
0.006 - 0.08
phosphatidylinositol 3,4-bisphosphate
0.12
phosphatidylinositol 3-phosphate
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pH 7.5, enzyme type IIalpha
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.015
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membrane bound type II enzyme
0.023
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cytosolic enzyme
0.117
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additional information
recombinant isozyme alpha
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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enzyme is enriched in the uropod during chemotaxis of primary neutrophils. Enrichment occurs early upon chemoattractant stimulation and is persistent during chemotaxis, concomitant with enrichment of phosphatidylinositol 4,5-bisphosphate
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
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Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
UNIPROT
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
53000
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x * 53000, SDS-PAGE
68000
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x * 68000, isozymes alpha or beta, x * 90000, isozyme gamma
87000
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SDS-PAGE
90000
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x * 68000, isozymes alpha or beta, x * 90000, isozyme gamma
150000
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gel filtration
237000
calculated from sequence
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homodimer or heterodimer
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isoforms PIP5KIbeta and PIP5KIgamma
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
sumoylation
SUMOylation at Lys-244 and Lys-490 directs the enzyme's nuclear entry and its interaction with H3K9me3/HP1-alpha, respectively
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-70°C, stable in concentrated form
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4°C, storage causes the 53000 Da enzyme to be slowly degraded to a 45000 Da peptide
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cytosolic enzyme type II enzyme and membrane-bound type I and type II enzyme
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recombinan GST-fusion isozyme alpha from Escherichia coli
Talon metal affinity column chromatography
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cloning of splice variant phosphatidylinositol 4-phosphate 5-kinase Igamma_v6, expression in COS-7 cells. In humans there is an alternative splice site 78 residues into exon 16c that splices out the rest of the Igamma_v5 insert, and then jumps either 1. to the start of exon 17 to generate human Igamma_v3 (the stop codon is then at the start of human exon 18), or 2. straight to that stop codon in exon 18 to generate human Igamma_v6, cloning of splice variants phosphatidylinositol 4-phosphate 5-kinase Igamma_v3, and Igamma_i2 and expression analysis
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expressed in CHO cells
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expressed in Escherichia coli BL21(DE3) cells
expressed in Sf9 cells and MEF cells
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expression in COS cells
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expression in HEK-203 cell
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expression of isozyme alpha as GST-fusion protein in Escherichia coli
functional expression in HeLa cells as GFP-fusion protein, translocation to the plasma membrane by coexpression of ARF6 upon stimulation by EGF, coexpression of ARF6 mutant N122I inhibits the membrane ruffling, overview
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isozyme PIP5K1beta expression in HEK-293T and COS-7 cells
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
the enzyme is overexpressed in triple-negative breast cancers
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D309N
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inactive mutant
D310K
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inactive
K138A
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inactive
K244A
the mutant protein localizes in the cytosol
R427Q
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inactive mutant
additional information