Information on EC 2.7.1.68 - 1-phosphatidylinositol-4-phosphate 5-kinase

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The expected taxonomic range for this enzyme is: Eukaryota

EC NUMBER
COMMENTARY
2.7.1.68
-
RECOMMENDED NAME
GeneOntology No.
1-phosphatidylinositol-4-phosphate 5-kinase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
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 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
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
phospho group transfer
-
-
-
-
Phosphorylation
O48709
-
PATHWAY
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-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.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
MSS4p
-
-
-
-
phosphatidylinositol 4-phosphate 5-kinase
O48709
-
phosphatidylinositol 4-phosphate 5-kinase
-
-
phosphatidylinositol 4-phosphate 5-kinase
C8BX38
-
phosphatidylinositol 4-phosphate 5-kinase
Eimeria maxima Weybridge strain
C8BX38
-
-
phosphatidylinositol 4-phosphate 5-kinase
A1YQB1
-
phosphatidylinositol 4-phosphate 5-kinase
-
-
phosphatidylinositol 4-phosphate 5-kinase
-
-
phosphatidylinositol 4-phosphate 5-kinase
-
-
phosphatidylinositol 4-phosphate 5-kinase
-
-
phosphatidylinositol 4-phosphate 5-kinase alpha
-
-
phosphatidylinositol 4-phosphate 5-kinase alpha
-
-
phosphatidylinositol 4-phosphate 5-kinase alpha
P70182
-
phosphatidylinositol 4-phosphate 5-kinase gamma
-
-
phosphatidylinositol 4-phosphate 5-kinase gamma661
-
-
phosphatidylinositol 4-phosphate 5-kinase Igamma b
-
-
phosphatidylinositol 4-phosphate 5-kinase Igamma_i2
-
-
phosphatidylinositol 4-phosphate 5-kinase Igamma_v3
-
-
phosphatidylinositol 4-phosphate 5-kinase Igamma_v6
-
-
phosphatidylinositol 4-phosphate 5-kinase-Ibeta
-
-
phosphatidylinositol 4-phosphate kinase
-
-
-
-
phosphatidylinositol 5-kinase gamma
-
-
phosphatidylinositol kinase type I
-
-
phosphatidylinositol monophosphate 5-kinase
Q8L850
-
phosphatidylinositol phosphate 5-kinase
O48709
-
phosphatidylinositol phosphate 5-kinase 1
Q56YP2
-
phosphatidylinositol phosphate 5-kinase 10
Q9LMN1
-
phosphatidylinositol phosphate 5-kinase Ibeta
-
-
phosphatidylinositol phosphate kinase type I gamma
-
-
phosphatidylinositol-4-phosphate 5' kinase
-
-
phosphatidylinositol-4-phosphate 5-kinase
-
-
-
-
phosphatidylinositol-4-phosphate 5-kinase
-
-
phosphatidylinositol-4-phosphate 5-kinase
-
-
phosphatidylinositol-4-phosphate 5-kinase
-
-
phosphatidylinositol-4-phosphate 5-kinase gamma 635
-
-
phosphoinositol-4-phosphate-5-kinase
-
-
PI 4-phosphate 5-kinase
-
-
PI 4-phosphate 5-kinase
P70182
-
PI(4)P 5-kinase
-
-
PI(4)P 5-kinase
-
-
PI(4)P 5-kinase
-
-
PI4P 5-kinase
-
-
-
-
PI4P5K
-
-
-
-
PIP kinase
-
-
-
-
PIP-5kin
-
-
-
-
PIP5K
-
-
-
-
PIP5K
O48709
Arabidopsis genome contains 11 genes encoding proteins with significant sequence similarity to animal PIP5Ks. These are classified into two subfamilies: subfamily A proteins (PIP5K10 and PIP5K11) consist of dimerization and catalytic domains similar to those in the animal enzymes, while subfamily B proteins (PIP5K1 to PIP5K9) have an additional domain containing a repeat of the membrane occupation and recognition nexus motif at the N-terminus.
PIP5K
C8BX38
-
PIP5K
Eimeria maxima Weybridge strain
C8BX38
-
-
PIP5K
A1YQB1
-
PIP5K
-
-
PIP5K
P70182
-
PIP5K-Ib
-
-
PIP5K3
O48709
PIP5K3 encodes the enzyme activity producing PtdIns(4,5)P2.
PIP5K9
Q8L850
-
PIP5Kalpha
-
-
PIP5Kalpha
-
-
PIP5Kalpha
P70182
-
PIP5Kbeta
-
-
PIP5Kgamma
-
-
PIP5Kgamma
-
-
PIP5Kgamma
-
-
PIP5Kgamma635
-
-
PIP5Kgamma661
-
-
PIP5KIgamma_i2
-
-
PIP5KIgamma_v3
-
-
PIP5Ks
-
-
-
-
PIPK1
Q56YP2
-
PIPK10
Q9LMN1
-
PIPK1gamma-87
-
-
PIPKalpha
-
-
PIPKIalpha
-
-
PIPKIalpha
Q99755
-
PIPkin Igammab
-
-
PIPkinIgamma93
-
-
PtdIns(4)P 5-kinase
-
-
-
-
PtdIns4P5K
-
-
PtdInsP
Q56YP2, Q9LMN1
-
type I phosphatidylinositol-4-phosphate 5-kinase
-
-
type I PI 4-phosphate 5-kinase
-
-
type I PI 4-phosphate 5-kinase
P70182
-
type I PtdInsP kinase
O48709
-
type Igamma phosphatidylinositol 4-phosphate 5-kinase
-
-
Diphosphoinositide kinase
-
-
-
-
additional information
Q56YP2
phosphatidylinositol phosphate 5-kinase 1 belongs to the subfamily B
additional information
Q9LMN1
phosphatidylinositol phosphate 5-kinase 10 belongs to the subfamily A
CAS REGISTRY NUMBER
COMMENTARY
104645-76-3
-
9032-61-5
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
enzyme form 10; enzyme form 10
SwissProt
Manually annotated by BRENDA team
enzyme form 1; enzyme form 1
SwissProt
Manually annotated by BRENDA team
type B enzyme, isoform PIP5K3
-
-
Manually annotated by BRENDA team
Used Arabidopsis thaliana lines are in the Columbia background, and Columbia is used as the wild type.
UniProt
Manually annotated by BRENDA team
isoform Ppk-1, type I enzyme
UniProt
Manually annotated by BRENDA team
Eimeria maxima Weybridge strain
-
UniProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
3 isozymes alpha, beta, and gamma
-
-
Manually annotated by BRENDA team
enzyme form type I, 3 isozymes alpha, beta, gamma in several splicing variants
-
-
Manually annotated by BRENDA team
isoform phosphatidylinositol 4-phosphate 5-kinase beta, type I enzyme
-
-
Manually annotated by BRENDA team
isoform phosphatidylinositol 4-phosphate 5-kinase type Igamma
-
-
Manually annotated by BRENDA team
isozyme alpha type I; type I isozyme alpha
SwissProt
Manually annotated by BRENDA team
isozymes PIP5Kalpha, PIP5Kbeta, and PIP5Kgamma
-
-
Manually annotated by BRENDA team
three splice variants phosphatidylinositol 4-phosphate 5-kinase Igamma_v6, Igamma_v3, and Igamma_i2
-
-
Manually annotated by BRENDA team
3 isozymes alpha, beta, and gamma
-
-
Manually annotated by BRENDA team
enzyme form type I, 3 isozymes alpha, beta, gamma in several splicing variants
-
-
Manually annotated by BRENDA team
isoform phosphatidylinositol 4-phosphate 5-kinase alpha
-
-
Manually annotated by BRENDA team
isoform phosphatidylinositol 4-phosphate 5-kinase type Igamma
-
-
Manually annotated by BRENDA team
isozymes PIP5K1A, PIP5K1B, and PIP5K1C
-
-
Manually annotated by BRENDA team
isozymes PIP5Kalpha, PIP5Kbeta, and PIP5Kgamma
UniProt
Manually annotated by BRENDA team
type I enzymes, isozyme gamma
-
-
Manually annotated by BRENDA team
3 isozymes alpha, beta, and gamma
-
-
Manually annotated by BRENDA team
type I phosphatidylinositol 4-phosphate 5-kinase isozyme gamma, 3 splicing forms a-c
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
evolution
C8BX38, -
PIP5K sequences and inferred apicomplexan PIP5K gene tree, overview
evolution
Eimeria maxima Weybridge strain
-
PIP5K sequences and inferred apicomplexan PIP5K gene tree, overview
-
malfunction
-
enzyme knockoout mutants are infertile, phenotypes, overview. Flagella of sperm from isozyme Pip5k1a knockout mutant and even more of Pip5k1a/Pip5k1b double-knockout mutant mice remarkably undergo morphological changes and impairment, whereas Pip5k1b-knockout mutant sperm is morphologically normal. F-actin organization in the seminiferous epithelium is disrupted by the loss of PIP5K1A and PIP5K1B
malfunction
-
isozyme PIP5Kalpha knockdown reduces 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate levels and disrupts Toll/IL-1 receptor domain-containing adaptor protein membrane targeting by lipopolysaccharide
malfunction
P70182
isozyme PIP5Kalpha knockdown reduces 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate levels and disrupts Toll/IL-1 receptor domain-containing adaptor protein membrane targeting by lipopolysaccharide. Isozyme PIP5Kalpha shRNA-15 knockdown cells are less effective inducing iNOS protein expression and nitric oxide production after lipopolysaccharide stimulation overnight and for 24 h, respectively, compared with control cells
malfunction
-
overexpression of PIPKalpha inhibits axon elongation via KIF2A in N1E-115 neuroblastoma cells
metabolism
-
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
-
phosphatidylinositol 4,5 bisphosphate is a major membrane phospholipid that affects cellular processes such as actin cytoskeleton modulation, membrane trafficking and ion channel activity. Isozyme PIP5Kgamma is essential for advanced glycation end products induced inhibition of renal Na+/K+ ATPase activity
physiological function
-
the lipid kinase phosphatidylinositol 4-phosphate 5-kinase produces a versatile signaling phospholipid, phosphatidylinositol 4,5-bisphosphate, isozymes PIP5K1A and PIP5K1B may coordinately and/or redundantly function in the maintenance of sperm number and morphology during spermatogenesis
physiological function
-
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate regulates many critical cellular events and mediates plasma membrane localization of the Toll/IL-1 receptor domain-containing adaptor protein (TIRAP), required for the MyD88-dependent Toll-like receptor 4 signaling pathway. Phosphatidylinositol 4-phosphate 5-kinase alpha facilitates toll-like receptor 4-mediated microglial inflammation through regulation of the toll/interleukin-1 receptor domain-containing adaptor protein location
physiological function
P70182
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate regulates many critical cellular events and mediates plasma membrane localization of the Toll/IL-1 receptor domain-containing adaptor protein (TIRAP), required for the MyD88-dependent Toll-like receptor 4 signaling pathway. Phosphatidylinositol 4-phosphate 5-kinase alpha facilitates toll-like receptor 4-mediated microglial inflammation through regulation of the toll/interleukin-1 receptor domain-containing adaptor protein location
physiological function
C8BX38, -
phosphatidylinositol 4-phosphate 5-kinase play an important role in host-cell invasion by the Eimeria species. The protozoan parasites can cause severe intestinal disease in livestock
physiological function
-
isozyme phosphatidylinositol 4-phosphate 5-kinase alpha, PIPKalpha, regulates neuronal microtubule depolymerase kinesin, KIF2A and suppresses elongation of axon branches, unique PIPK-mediated KIF2A-dependent mechanism controlling microtubule dynamics in neuronal development, overview. Murine PIPKalpha as a negative regulator of neurite formation in N1E-115 neuroblastoma cells and early-stage hippocampal neurons
physiological function
Eimeria maxima Weybridge strain
-
phosphatidylinositol 4-phosphate 5-kinase play an important role in host-cell invasion by the Eimeria species. The protozoan parasites can cause severe intestinal disease in livestock
-
metabolism
P70182
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
additional information
-
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
additional information
-
identification of the binding domain for His6-tagged KIF2A and GST-tagged PIPKalpha interaction, overview
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + 1,2-dipalmitoyl phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1,2-dipalmitoyl phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
-
-
-
?
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 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
-
-
-
?
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 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
-
-
-
?
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 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
-
-
-
?
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 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
-
-
-
?
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 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
-
-
-
?
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 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
Q56YP2, Q9LMN1
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
Q99755
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
Q8L850
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-, O01759
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
-
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate has several important physiologic functions, overview
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
-
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate has several important physiological functions, overview
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
enzyme activity is regulated by cAMP levels. This regulation may be critical in the initiation of cell growth for which 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate seems to be necessary
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
the activity of the enzyme is regulated by the reversible balance between cAMP-dependent protein kinase-dependent phosphorylation and protein phosphatase 1-dependent dephosphorylation
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
the enzyme catalyzes the last step in the synthesis of phosphatidylinositol 4,5-bisphosphate, which is a precursor of diacylglycerol and inositol 1,4,5-triphosphate and is also involved in regulation of actin cytoskeleton remodeling and membrane traffic. The enzyme is regulated by casein kinase Cki1
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
enzyme type 1beta is essential for epidermal growth factor receptor-mediated endocytosis
-
-
-
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
the MSS4 gene product functions in regulation of actin-binding proteins through generation of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate from 1-phosphatidyl-1D-myo-inositol 4-phosphate in or near the plasma membrane
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
in addition to regulating early steps in endocytosis, the enzyme acts through 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to regulate endosomal trafficking and/or fusion
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
the product 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate is a key precursor in phosphoinositide signaling that also regulates some proteins and cellular processes directly
-
-
-
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
PIP-5kina-alpha functions as a downstream effector for RhoA/ROCK to couple lysophosphatidic acid signaling to neurite retraction presumably through its product phosphatidylinositol 4,5-bisphosphate
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
Rho-kinase is involved in the Rho-controlled synthesis of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate by phosphatidylinositol-4-phosphate 5-kinase
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
the enzyme from liver membrane is possible regulated by a G-protein
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
the enzyme may be under control of phosphatidic acid level in membranes
-
-
-
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
the enzyme is stimulated during temperature-induced morphogenesis, i.e. switch to the hyphal growth form
-
-
-
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
the enzyme form PIPKIgamma may cooperate with synaptojanin in the regulation of actin and synaptic vesicle traffic
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
PIPKIalpha activity is involved in the actin remodeling that is a prerequisite for efficient phagocytosis. PIPKIalpha appears to contribute to the transient changes in 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate levels that are associated with, and likely required for, the recruitment and regulation of actin-modulating proteins
-
-
-
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
enzyme is induced by water stress and abscisic acid. The enzyme is involved in water-stress signal transduction
-
-
-
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
PIP 5-kinase alpha is a critical mediator of thrombin- and Rac-dependent actin assembly
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
the enzyme plays an essential role during neurite retraction in response to a number of diverse stimuli
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
type I phosphatidylinositol 4-phosphate 5-kinase directly interacts with ADP-ribosylation factor 1 and is responsible for phosphatidylinositol 4,5-bisphosphate synthesis in the Golgi compartment
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate is an important lipid in several cellular processes e.g. in actin cytoskeleton regulation and membrane trafficking
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate is an important membrane lipid in several cellular processes e.g. in actin cytoskeleton regulation and membrane trafficking, in signaling of membrane receptors, for ion channel activity, and in gene expression and cell survival, overview
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate is an important membrane lipid in several cellular processes e.g. in actin cytoskeleton regulation and membrane trafficking, in signaling of membrane receptors, for ion channel activity, in gene expression and cell survival, and in establishment of cell morphology and during temperature-induced hyphal growth, respectively, overview
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate, especially produced by isozyme beta, is required for constitutive endocytosis of transferrin receptors via clathrin-coated pits, and probably also for the regulation thereof
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
the enzyme activity is regulated by Arf6 activation
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol-4,5-bisphosphate
show the reaction diagram
O48709
-
PIP5K3 is involved in localizing 1-phosphatidyl-1D-myo-inositol-4,5-bisphosphate to the elongating root hair apex and is a key regulator of the machinery that initiates and promotes root hair tip growth.
-
r
ATP + 1-stearoyl-2-arachidonoyl phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-stearoyl-2-arachidonoyl phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
-
-
-
?
ATP + 1-stearoyl-2-oleoyl phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-stearoyl-2-oleoyl phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
-
-
-
?
ATP + dipalmitoyl phosphatidylinositol 4-phosphate
ADP + dipalmitoylphosphatidylinositol 4,5-bisphosphate
show the reaction diagram
-
-
-
-
?
ATP + phosphatidylinositol 3-phosphate
ADP + phosphatidylinositol 3,4-bisphosphate
show the reaction diagram
-
-
-
?
ATP + phosphatidylinsositol 3,4-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
show the reaction diagram
-
-
-
-
?
GTP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
GDP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
no activity
-
-
-
GTP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
GDP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
50% of the activity with ATP
-
-
?
GTP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
GDP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
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
-
-
?
additional information
?
-
-
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate production by the enzyme, presence of Arf6, and binding of the bacterial invasin protein to beta1 integrin receptors are required for the small GTPase Rac1-dependent pathway, which is activated for efficient entry of the bacterium Yersinia pseudotuberculosis, into mammalian cells, overview
-
-
-
additional information
?
-
-
activities of isozymes are regulated by membrane receptors, by phosphorylation, and by small GTPases of the Rho and Arf families, detailed phosphoinositide metabolism, overview
-
-
-
additional information
?
-
-
ARF6-dependent enzyme activation plays an important role in signal transduction of membrane ruffling formation through 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
-
-
-
additional information
?
-
-
enzyme is important in cell signaling and cell shaping, overview, the enzyme is essential for regulation of neurite modeling, ARF6-dependent enzyme activation plays an important role in signal transduction of membrane ruffling formation through 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
-
-
-
additional information
?
-
-
splicing form a of the isozyme gamma is inactive, splicing form c is involved in maintenance of some neuronal cellular processes
-
-
-
additional information
?
-
-
subcellular localization and activity of isozymes are regulated by membrane receptors, by phosphorylation, and by small GTPases of the Rho and Arf families, detailed phosphoinositide metabolism, overview
-
-
-
additional information
?
-
O48709
GST-PIP5K3 produces 1-phosphatidyl-1D-myo-inositol 4,5 by phosphorylating 1-phosphatidyl-1D-myo-inositol 4-phosphate, both the natural and synthetic forms. Its also phosphorylates 1-phosphatidyl-1D-myo-inositol 5-phosphate, but less efficiently. PIP5K3 catalyzes the synthesis of 1-phosphatidyl-1D-myo-inositol 4,5 preferentially from 1-phosphatidyl-1D-myo-inositol 4-phosphate in vitro., PIP5K3 may function as a downstream effector of rho-related GTPases of plants (ROPs) in regulatory mechanisms, not only for the planar polarity of bulge initiation but also for the promotion of root hair tip growth., Reduced expression of functional PIP5K3 is responsible for the short-root hair phenotype. Inducible overexpression of PIP5K3 enhanced root hair elongation and increased the rate of 1-phosphatidyl-1D-myo-inositol-4,5-bisphosphate
-
-
-
additional information
?
-
-
beta-arrestins direct the localization of phosphatidylinositol 4-phosphate 5-kinase 1alpha and phosphatidylinositol 4,5-bisphosphate production to agonist-activated 7-transmembrane receptors, thereby regulating receptor internalization
-
-
-
additional information
?
-
-
phosphatidylinositol 4-phosphate 5-kinase beta is involved in polarization at the uropod of neutrophil-differentiated HL60 cells. Phosphatidylinositol 4-phosphate 5-kinase beta localization is independent of its lipid kinase activity, but requires the 83 C-terminal amino acids. The C-terminus interacts with 4.1-ezrin-radixin-moesin-binding phosphoprotein 50, which enables further interactions with ezrin-radixin-moesin proteins and the Rho-GDP dissociation inhibitor
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
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 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
-
-
-
?
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 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
Q56YP2, Q9LMN1
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
Q99755
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
-
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate has several important physiologic functions, overview
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
-
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate has several important physiological functions, overview
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
enzyme activity is regulated by cAMP levels. This regulation may be critical in the initiation of cell growth for which 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate seems to be necessary
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
the activity of the enzyme is regulated by the reversible balance between cAMP-dependent protein kinase-dependent phosphorylation and protein phosphatase 1-dependent dephosphorylation
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
the enzyme catalyzes the last step in the synthesis of phosphatidylinositol 4,5-bisphosphate, which is a precursor of diacylglycerol and inositol 1,4,5-triphosphate and is also involved in regulation of actin cytoskeleton remodeling and membrane traffic. The enzyme is regulated by casein kinase Cki1
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
enzyme type 1beta is essential for epidermal growth factor receptor-mediated endocytosis
-
-
-
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
the MSS4 gene product functions in regulation of actin-binding proteins through generation of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate from 1-phosphatidyl-1D-myo-inositol 4-phosphate in or near the plasma membrane
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
in addition to regulating early steps in endocytosis, the enzyme acts through 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to regulate endosomal trafficking and/or fusion
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
the product 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate is a key precursor in phosphoinositide signaling that also regulates some proteins and cellular processes directly
-
-
-
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
PIP-5kina-alpha functions as a downstream effector for RhoA/ROCK to couple lysophosphatidic acid signaling to neurite retraction presumably through its product phosphatidylinositol 4,5-bisphosphate
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
Rho-kinase is involved in the Rho-controlled synthesis of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate by phosphatidylinositol-4-phosphate 5-kinase
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
the enzyme from liver membrane is possible regulated by a G-protein
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
the enzyme may be under control of phosphatidic acid level in membranes
-
-
-
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
the enzyme is stimulated during temperature-induced morphogenesis, i.e. switch to the hyphal growth form
-
-
-
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
the enzyme form PIPKIgamma may cooperate with synaptojanin in the regulation of actin and synaptic vesicle traffic
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
PIPKIalpha activity is involved in the actin remodeling that is a prerequisite for efficient phagocytosis. PIPKIalpha appears to contribute to the transient changes in 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate levels that are associated with, and likely required for, the recruitment and regulation of actin-modulating proteins
-
-
-
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
enzyme is induced by water stress and abscisic acid. The enzyme is involved in water-stress signal transduction
-
-
-
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
PIP 5-kinase alpha is a critical mediator of thrombin- and Rac-dependent actin assembly
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
the enzyme plays an essential role during neurite retraction in response to a number of diverse stimuli
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
type I phosphatidylinositol 4-phosphate 5-kinase directly interacts with ADP-ribosylation factor 1 and is responsible for phosphatidylinositol 4,5-bisphosphate synthesis in the Golgi compartment
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate is an important lipid in several cellular processes e.g. in actin cytoskeleton regulation and membrane trafficking
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate is an important membrane lipid in several cellular processes e.g. in actin cytoskeleton regulation and membrane trafficking, in signaling of membrane receptors, for ion channel activity, and in gene expression and cell survival, overview
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate is an important membrane lipid in several cellular processes e.g. in actin cytoskeleton regulation and membrane trafficking, in signaling of membrane receptors, for ion channel activity, in gene expression and cell survival, and in establishment of cell morphology and during temperature-induced hyphal growth, respectively, overview
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate, especially produced by isozyme beta, is required for constitutive endocytosis of transferrin receptors via clathrin-coated pits, and probably also for the regulation thereof
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
show the reaction diagram
-
the enzyme activity is regulated by Arf6 activation
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol-4,5-bisphosphate
show the reaction diagram
O48709
-
PIP5K3 is involved in localizing 1-phosphatidyl-1D-myo-inositol-4,5-bisphosphate to the elongating root hair apex and is a key regulator of the machinery that initiates and promotes root hair tip growth.
-
r
additional information
?
-
-
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate production by the enzyme, presence of Arf6, and binding of the bacterial invasin protein to beta1 integrin receptors are required for the small GTPase Rac1-dependent pathway, which is activated for efficient entry of the bacterium Yersinia pseudotuberculosis, into mammalian cells, overview
-
-
-
additional information
?
-
-
activities of isozymes are regulated by membrane receptors, by phosphorylation, and by small GTPases of the Rho and Arf families, detailed phosphoinositide metabolism, overview
-
-
-
additional information
?
-
-
ARF6-dependent enzyme activation plays an important role in signal transduction of membrane ruffling formation through 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
-
-
-
additional information
?
-
-
enzyme is important in cell signaling and cell shaping, overview, the enzyme is essential for regulation of neurite modeling, ARF6-dependent enzyme activation plays an important role in signal transduction of membrane ruffling formation through 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
-
-
-
additional information
?
-
-
splicing form a of the isozyme gamma is inactive, splicing form c is involved in maintenance of some neuronal cellular processes
-
-
-
additional information
?
-
-
subcellular localization and activity of isozymes are regulated by membrane receptors, by phosphorylation, and by small GTPases of the Rho and Arf families, detailed phosphoinositide metabolism, overview
-
-
-
additional information
?
-
O48709
GST-PIP5K3 produces 1-phosphatidyl-1D-myo-inositol 4,5 by phosphorylating 1-phosphatidyl-1D-myo-inositol 4-phosphate, both the natural and synthetic forms. Its also phosphorylates 1-phosphatidyl-1D-myo-inositol 5-phosphate, but less efficiently. PIP5K3 catalyzes the synthesis of 1-phosphatidyl-1D-myo-inositol 4,5 preferentially from 1-phosphatidyl-1D-myo-inositol 4-phosphate in vitro., PIP5K3 may function as a downstream effector of rho-related GTPases of plants (ROPs) in regulatory mechanisms, not only for the planar polarity of bulge initiation but also for the promotion of root hair tip growth., Reduced expression of functional PIP5K3 is responsible for the short-root hair phenotype. Inducible overexpression of PIP5K3 enhanced root hair elongation and increased the rate of 1-phosphatidyl-1D-myo-inositol-4,5-bisphosphate
-
-
-
additional information
?
-
-
beta-arrestins direct the localization of phosphatidylinositol 4-phosphate 5-kinase 1alpha and phosphatidylinositol 4,5-bisphosphate production to agonist-activated 7-transmembrane receptors, thereby regulating receptor internalization
-
-
-
additional information
?
-
-
phosphatidylinositol 4-phosphate 5-kinase beta is involved in polarization at the uropod of neutrophil-differentiated HL60 cells. Phosphatidylinositol 4-phosphate 5-kinase beta localization is independent of its lipid kinase activity, but requires the 83 C-terminal amino acids. The C-terminus interacts with 4.1-ezrin-radixin-moesin-binding phosphoprotein 50, which enables further interactions with ezrin-radixin-moesin proteins and the Rho-GDP dissociation inhibitor
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Ca2+
-
activates to a smaller extent than Mg2+
Co2+
-
2 mM, activates
Co2+
-
activates to a smaller extent than Mg2+
Co2+
-
stimulates
Fe2+
-
2 mM, slight inhibition
K+
O48709
70 mM in the activity assay
KCl
-
at 80 mM
Mg2+
-
with exogenous substrate maximal activity is obtained at 5 mM Mg2+. Maximal phosphorylation of endogenous substrate is in shoot plasma membranes at around 12.5 mM Mg2+. In root membranes 5-40 mM Mg2+ stimulate the phosphorylation of the endogenous substrate
Mg2+
-
2 mM, dependent on; activates
Mg2+
-
activates
Mg2+
-
required, optimal concentration is 20-30 mM
Mg2+
-
maximal activity at 10 mM MgCl2
Mg2+
-
required, Km: 10 mM
Mg2+
-
stimulates
Mg2+
-
required, optimal stimulation between 10-30 mM
Mg2+
-
Km: 2 mM, Mg2+ is three times more effective than Mn2+
Mg2+
Q56YP2, Q9LMN1
;
Mg2+
O48709
10 mM in the activity assay
Mg2+
-
required
Mg2+
-
required
Mg2+
-
required
MgCl2
-
at 10 mM
Mn2+
-
stimulatory effect of Mg2+ can only be partly substituted by Mn2+
Mn2+
-
2 mM, activates
Mn2+
-
activates to a smaller extent than Mg2+
Mn2+
-
Km: 0.2 mM, Mg2+ is three times more effective than Mn2+
Zn2+
-
2 mM, slight inhibition
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
-
product inhibition
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
-
20 nM, maximal inhibition
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
-
50% inhibition at equimolar concentrations of product and substrate
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
-
-
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
-
half-maximal inhibition at a ratio of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to 1-phosphatidyl-1D-myo-inositol 4-phosphate of 1.5:1
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
-
0.1 mM, 55% inhibition
2'(3')-O-(2,4,6-Trinitrophenyl)ATP
-
competitive
ATP
-
above 4 mM
Ca2+
-
inhibits in presence of optimal Mg2+ concentrations
Ca2+
-
free Ca2+, IC50: about 0.0001 mM
Cetyltrimethylammonium bromide
-
-
Cutsum
-
-
-
cysteine
-
1 mM, 49% inhibition
EDTA
-
slight inhibition between 0.5-5 mM
GSSG
-
0.1 mM, 17% inhibition
H2O2
-
the enzyme is inhibited after 20 min incubation with 0.6 mM H2O2
heparin
-
type II kinase
heparin
-
IC50: 0.002 mg/ml, competitive towards 1-phosphatidyl-1D-myo-inositol 4-phosphate
NEM
-
1 mM, 26% inhibition
PCMB
-
0.1 mM, complete inhibition
phosphatidic acid
-
0.1 mM, 125% stimulation
phosphatidic acid
-
2-3fold activation of the brain cytosol enzyme, 30fold enhancement of the activation by GTPgammaS, even higher activation by addition of recombinant mouse isozyme alpha
phosphatidylinositol
-
0.1 mM, 125% stimulation
phosphatidylserine
-
0.1 mM, 125% stimulation
quercetin
-
IC50: 0.0002 mM, competitive towards ATP or GTP
small G proteins ARF
-
ARF activation absolutely requires the presence of phosphatidic acid, which cannot be substituted by phosphatidylserine, phosphatidylethanolamine, or lysophophatidic acid, but by competitive phosphatidylcholine, proteins ARF1 and ARF3, from brain cytosol, purification and identification, the 21 kDa G-proteins are activated by GTPgammaS, not by GDP, and activate themselves the PI(4)P 5-kinase
-
Sodium deoxycholate
-
-
spermine
-
0.03 mg/ml, 50% inhibition
Trifluoperazine
-
IC50: about 0.015 mM
Triton X-100
-
above 0.015%, phosphorylation of endogenous substrate is inhibited
Triton X-100
-
-
Triton X-100
-
0.5-3.0% w/v, 40% inhibition
Wortmannin
-
phosphatidylinositol 4-kinase activity of STT4, but not of PIK1 is potently inhibited
ZnSO4
-
sensitive to 9 mM ZnSO4
ISP-1/myriocin
-
potent inhibitor, 750ng/ml
additional information
-
GTPgammaS shows poor or no activation of the brain cytosol enzyme but acts synergistically with phosphatidic acid
-
additional information
-
not inhibited by SP600125, SB203580, ZVAD-fmk, wortmannin or LY294002
-
additional information
-
not inhibited by micafungin
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1,2-diarachidonoyl phosphatidic acid
-
-
1,2-dilinoleoyl phosphatidic acid
-
-
-
1,2-dioleoyl phosphatidic acid
-
-
1-arachidoyl-2-arachidonoyl phosphatidic acid
-
-
1-stearoyl-2-arachidonoyl phosphatidic acid
-
-
1-stearoyl-2-oleoyl phosphatidic acid
-
-
Acetylcholine
-
0.01 mM or 0.1 mM, each in presence of 0.1 mM eserine, stimulates the enzyme in homogenates by 30-40%
ADP-ribosylation factor 1
-
0.001 mM
-
ADP-ribosylation factor 6
-
0.001 mM
-
advanced glycation end products
-
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
-
Ajuba
-
dramatic activation of enzymatic activity
-
AP-2mu-endocytic cargo complex
-
clathrin adaptor complex, leads to a potent stimulation of PIPK activity
-
Arf6
-
activates the enzyme via binding of small GTPase Rac1, regulatory function, mutant Arf6 N121I is defective for nucleotide binding, mutant Q67L is similarly active as the wild-type Arf6
-
beta2 adaptin
-
the beta2 subunit of beta2 adaptin binds to the C-terminal tail of PIP5Kgamma661 and causes activation of the enzyme
-
heparin
-
type I enzyme is stimulated at low concentrations
lipid phosphatidate
-
0.1 mM
-
lysophosphatidic acid
-
-
lysophosphatidic acid
-
mechanism overview
myelin basic protein
-
enhances activity when phosphatidylinositol 4-phosphate/phosphatidylethanolamine vesicles are used as substrate
-
phosphatidic acid
-
stimulates in a concentration-dependent manner up to 20fold when an equal molar ratio of phosphatidic acid to phosphatidylinositol 4-phosphate is attained
phosphatidic acid
-
stimulates
phosphatidic acid
-
activation
phosphatidic acid
Q56YP2, Q9LMN1
activates enzyme form 1 by 2.1fold
phosphatidic acid
Q99755
activates isozyme alpha by 2.0fold
phosphatidic acid
-
0.14 mM, potent activator, the enzyme is unable to produce 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate unless phosphatidic acid is bound
phosphatidic acid
-
-
small G protein ARF
-
ARF activation absolutely requires the presence of phosphatidic acid, which cannot be substituted by phosphatidylserine, phosphatidylethanolamine, or lysophosphatidic acid, but by competitive phosphatidylcholine, reconstitution of the recombinant either isozyme alpha, beta, or gamma with recombinant class II and III ARFs, ARF5 and ARF6, respectively, as well as myristoylated class I ARF in presence of GTPgammaS or GDP, and phosphatidic acid activates the isozymes
-
small G protein RHO
-
activates the enzyme in neurits, crucial in cell shapig together with the enzyme, overview
-
small G proteins
-
-
-
small G proteins ARF
-
ARF activation absolutely requires the presence of phosphatidic acid, which cannot be substituted by phosphatidylserine, phosphatidylethanolamine, or lysophosphatidic acid, but by competitive phosphatidylcholine
-
small GTPase Arf
-
-
-
small GTPase Arf
-
involved in membrane receptor-mediated regulation, acts via effectors, mechanism overview
-
small GTPase ARF/phosphatidic acid
-
regulation of isozyme gamma
-
small GTPase Rho
-
-
-
small GTPase Rho
-
involved in membrane receptor-mediated regulation, acts via effectors, mechanism overview
-
spermidine
-
enhances activity
spermine
-
2 mM, 4fold increase in activity of type I enzyme, no effect on type II enzyme
spermine
-
1 mM, 3fold stimulation. Stimulation decreases to half at physiological ionic strength and is not affected appreciably by variations in the concentration of ATP and MgCl2
spermine
-
strong activation in presence of micromolar concentrations, at 2 mM Mg2+ optimal spermine concentration is 0.1-0.2 mM spermine
spermine
-
enhances activity severalfold. Causes a shift in the MgCl2 saturation curve from sigmoidal to hyperbolic, lowering the Mg2+ concentration required for optimum kinase activity to the physiological range. 0.6 mM, 4fold increase of phosphorylation activity in phosphatidylinositol/phosphatidylethanolamine vesicles
spermine
-
0.5 mM, 300% increase in activity
Triton X-100
-
0.3% stimulates phosphorylation of exogenous substrate 2-3fold
Triton X-100
-
the optimal activity obtained in Triton X-100 is 6fold higher than that obtained in the absence of Triton X-100
Triton X-100
-
optimal phosphatidic acid-stimulation of type I PIP5K activity occurs in the presence of Triton X-100
additional information
Q56YP2, Q9LMN1
enzyme form 10 is insensitive to phosphatidic acid
-
additional information
-
not affected by 1-butanol
-
additional information
-
PIP5K activation depends on the acyl chain composition of both substrate and activator
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.262
-
1-phosphatidyl-1D-inositol 4-phosphate
-
pH 7.5, enzyme type Ibeta
0.005
-
1-phosphatidyl-1D-myo-inositol 3-phosphate
-
pH 7.5, enzyme type Ibeta
0.065
-
1-phosphatidyl-1D-myo-inositol 3-phosphate
-
pH 7.5, enzyme type Ialpha
0.0012
-
1-phosphatidyl-1D-myo-inositol 4-phosphate
-
in 1-phosphatidyl-1D-myo-inositol 4-phosphate in membranes, type I enzyme
0.0014
-
1-phosphatidyl-1D-myo-inositol 4-phosphate
-
in 1-phosphatidyl-1D-myo-inositol 4-phosphate liposomes, type I enzyme
0.005
-
1-phosphatidyl-1D-myo-inositol 4-phosphate
-
-
0.006
-
1-phosphatidyl-1D-myo-inositol 4-phosphate
-
in 1-phosphatidyl-1D-myo-inositol 4-phosphate micelles, type I enzyme
0.01
-
1-phosphatidyl-1D-myo-inositol 4-phosphate
-
pH 7.5, 25C
0.04
-
1-phosphatidyl-1D-myo-inositol 4-phosphate
-
in 1-phosphatidyl-1D-myo-inositol 4-phosphate liposomes, type II enzyme
0.047
-
1-phosphatidyl-1D-myo-inositol 4-phosphate
-
pH 7.5, enzyme type Ialpha
0.05
-
1-phosphatidyl-1D-myo-inositol 4-phosphate
-
pH 7.5, enzyme type IIalpha
0.06
-
1-phosphatidyl-1D-myo-inositol 4-phosphate
-
in 1-phosphatidyl-1D-myo-inositol 4-phosphate micelles, type II enzyme
0.065
-
1-phosphatidyl-1D-myo-inositol 4-phosphate
Q56YP2, Q9LMN1
recombinant enzyme form 10
0.25
-
1-phosphatidyl-1D-myo-inositol 4-phosphate
-
pH 7.4, 37C
0.6
-
1-phosphatidyl-1D-myo-inositol 4-phosphate
Q56YP2, Q9LMN1
recombinant enzyme form 1
4.1
-
1-phosphatidyl-1D-myo-inositol 4-phosphate
Q99755
recombinant isozyme alpha
4.9
-
1-stearoyl-2-arachidonoyl phosphatidyl-1D-myo-inositol 4-phosphate
-
isozyme PIP5Kbeta, pH 7.5, temperature not specified in the publication
-
15
-
1-stearoyl-2-arachidonoyl phosphatidyl-1D-myo-inositol 4-phosphate
-
isozyme PIP5Kgamma, pH 7.5, temperature not specified in the publication
-
16
-
1-stearoyl-2-arachidonoyl phosphatidyl-1D-myo-inositol 4-phosphate
-
isozyme PIP5Kalpha, pH 7.5, temperature not specified in the publication
-
1.6
-
1-stearoyl-2-oleoyl phosphatidyl-1D-myo-inositol 4-phosphate
-
isozyme PIP5Kgamma, pH 7.5, temperature not specified in the publication
-
2.8
-
1-stearoyl-2-oleoyl phosphatidyl-1D-myo-inositol 4-phosphate
-
isozyme PIP5Kalpha, pH 7.5, temperature not specified in the publication
-
3.7
-
1-stearoyl-2-oleoyl phosphatidyl-1D-myo-inositol 4-phosphate
-
isozyme PIP5Kbeta, pH 7.5, temperature not specified in the publication
-
0.002
-
ATP
-
pH 7.4, 23-25C
0.005
-
ATP
-
type II enzyme
0.019
-
ATP
-
-
0.025
-
ATP
-
type I enzyme
0.025
-
ATP
-
pH 7.5, 22C
0.043
-
ATP
-
pH 7.4, 30C
0.065
-
ATP
-
pH 7.5, 25C
0.133
-
GTP
-
pH 7.5, 22C
0.129
-
MgATP2-
-
pH 7.0, 25C
0.006
-
phosphatidylinositol 3,4-bisphosphate
-
pH 7.5, enzyme type Ibeta
0.08
-
phosphatidylinositol 3,4-bisphosphate
-
pH 7.5, enzyme type IIalpha
0.12
-
phosphatidylinositol 3-phosphate
-
pH 7.5, enzyme type IIalpha
0.13
-
MgATP2-
-
pH 7, 25C, at 5 mM Mg2+
additional information
-
additional information
-
Km-value for 1-phosphatidyl-1D-myo-inositol 4-phosphate is 0.0033 mg/ml
-
additional information
-
additional information
-
Km for 1-phosphatidyl-1D-myo-inositol 4-phosphate is 1.0 mol%
-
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.055
-
2'(3')-O-(2,4,6-Trinitrophenyl)ATP
-
pH 7.4, 30C
0.035
-
quercetin
-
pH 7.5, 25C
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0001
-
Ca2+
-
free Ca2+, IC50: about 0.0001 mM
0.015
-
Trifluoperazine
-
IC50: about 0.015 mM
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.0057
-
-
-
0.015
-
-
membrane bound type II enzyme
0.023
-
-
cytosolic enzyme
0.085
-
-
-
0.117
-
-
-
0.171
-
-
-
1.75
-
-
-
additional information
-
Q56YP2, Q9LMN1
enzyme form 10 shows 10fold lower activity than enzyme form 1 in recombinant Sf9 cells, overview
additional information
-
Q99755
recombinant isozyme alpha
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.5
7
-
shoot and root plasma membrane, endogenous substrate
7.2
-
-
-
7.4
-
-
assay at
7.5
8.2
-
shoot plasma membrane, exogenous substrate
7.5
-
O48709
asay at
7.5
-
-
assay at
7.8
8.2
-
root plasma membrane, exogenous substrate
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5
8
-
pH 5.0: about 65% of maximal activity, pH 8.0: about 75% of maximal activity
5.5
8.5
-
pH 5.5: about 35% of maximal activity, pH 8.5: about 60% of maximal activity
6.1
7.9
-
pH 6.1: about 85% of maximal activity, pH 7.9: about 85% of maximal activity
6.5
8.5
-
pH 6.5: about 35% of maximal activity, pH 8.5: about 60% of maximal activity
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
30
-
-
assay at
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.8
-
-
isoelectric focusing
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
moderate expression of PIP5KIbeta, low expression of PIP5KIalpha
Manually annotated by BRENDA team
-
phosphatidylinositol 4-phosphate 5-kinase Igamma_v6 is not a major brain variant
Manually annotated by BRENDA team
-
in situ hybridisation of phosphatidylinositol 4-phosphate 5-kinase Igamma_v6 splice variant, which is not a major brain variant
Manually annotated by BRENDA team
-
phosphatidylinositol 4-phosphate 5-kinase Igamma_v6 is not a major brain variant
Manually annotated by BRENDA team
P70182
isozymes type I PIP5Kalpha, PIP5Kbeta, and PIP5Kgamma are all expressed in BV-2 microglial cells
Manually annotated by BRENDA team
O48709
Escherichia coli BL21 cell is used for cloning and expression
Manually annotated by BRENDA team
-
two form of PIP kinase: type I kinase is membrane bound and type II kinase is both membrane bound and cytosolic
Manually annotated by BRENDA team
Q56YP2, Q9LMN1
enzyme form 10, most abundant in
Manually annotated by BRENDA team
-
high expression of PIP5KIbeta and PIP5KIalpha
Manually annotated by BRENDA team
-
dentate gyrus, pyramidal cells
Manually annotated by BRENDA team
-
enzyme is enriched in the uropod during chemotaxis of differentiated HL-60 cells. Enrichment occurs early upon chemoattractant stimulation and is persistent during chemotaxis, concomitant with enrichment of phosphatidylinositol 4,5-bisphosphate
Manually annotated by BRENDA team
Q56YP2, Q9LMN1
enzyme form 10, most abundant in
Manually annotated by BRENDA team
-
high expression of PIP5KIbeta
Manually annotated by BRENDA team
-
low expression of PIP5KIalpha
Manually annotated by BRENDA team
-
low expression of PIP5KIalpha
Manually annotated by BRENDA team
-
neuroblastoma
Manually annotated by BRENDA team
-
neuroblastoma cell
Manually annotated by BRENDA team
-, O01759
strong expression
Manually annotated by BRENDA team
-
in the pyramidal cells of the hippocampus and of the cerebral cortex, splicing form c of isozyme gamma is neuronal-specific
Manually annotated by BRENDA team
-
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
-
moderate expression of PIP5KIbeta, high expression of PIP5KIalpha
Manually annotated by BRENDA team
-
phosphatidylinositol 4-phosphate 5-kinase Igamma_v6 splice variant
Manually annotated by BRENDA team
-
high expression of PIP5KIbeta
Manually annotated by BRENDA team
O48709
t-DNA insertion mutations that reduces the expression of PIP5K3 cause shorter root hairs than in the wild type. Overexpression causes longer root hairs and multiple protruding sites on a single trichoblast.
Manually annotated by BRENDA team
-
enzyme localizes to the periphery of the apical region of root hair cells
Manually annotated by BRENDA team
P70182
isozymes type I PIP5Kalpha, PIP5Kbeta, and PIP5Kgamma are all expressed in BV-2 microglial cells
Manually annotated by BRENDA team
additional information
Q56YP2, Q9LMN1
tissue distribution; tissue distribution, enzyme form 1 is present in all tissues
Manually annotated by BRENDA team
additional information
-
PIP5KIgamma_v6 tissue expression pattern, overview
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
type I kinase is membrane bound and type II kinase is both membrane bound and cytosolic
Manually annotated by BRENDA team
Q9Y2I7
localizes mainly to early endosomes. PIKfyve is distributed in microdomains
Manually annotated by BRENDA team
-
ARF recruits brain cytosol enzyme from the cytosol to the Golgi complex in an in vitro system
Manually annotated by BRENDA team
-
type I kinase is membrane bound and type II kinase is both membrane bound and cytosolic
Manually annotated by BRENDA team
-
associated with, peripheral membrane protein
Manually annotated by BRENDA team
-
co-localization of KIF2A and PIPKalpha at the tips of neurites
-
Manually annotated by BRENDA team
-
isozyme PIP5Kalpha
Manually annotated by BRENDA team
-
synaptosomal plasma membrane
Manually annotated by BRENDA team
-
translocation to the plasma membrane of isozyme beta is dependent on ARF6 and EGF, and is completely inhibited by the recombinant GTP-binding-deficient ARF6 mutant N122I
Manually annotated by BRENDA team
-
translocation to the plasma membrane of isozyme alpha is dependent on ARF6 and EGF
Manually annotated by BRENDA team
-
type I isozyme gamma, the highly conserved central kinase domain KHD is necessary and sufficient for plasma membrane localization, with the C-termnal Arg-Lys dibasic sequence being responsible for plasma membrane targeting
Manually annotated by BRENDA team
-
only during cell-cell contact
Manually annotated by BRENDA team
-, O01759
enzyme can localize to the plasma membrane
Manually annotated by BRENDA team
-
upon overexpression in CCD cells, enzyme localizes exclusively in apical plasma membrane
Manually annotated by BRENDA team
-
phosphatidylinositol 4-phosphate 5-kinase Igamma_v6 splice variant
Manually annotated by BRENDA team
-
KIF2A and PIPKalpha bind near the plasma membrane
Manually annotated by BRENDA team
-
isozyme PIP5Kalpha
Manually annotated by BRENDA team
additional information
-
subcellular localization of isozymes is regulated by membrane receptors, by phosphorylation, and by small GTPases of the Rho and Arf families, overview
-
Manually annotated by BRENDA team
additional information
O48709
cytoplasmic space of elongating root hair apices
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
87000
-
-
SDS-PAGE
130000
-
-
gel filtration
150000
-
-
gel filtration
237000
-
Q9Y2I7
calculated from sequence
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 110000, SDS-PAGE
?
-
x * 45000, SDS-PAGE
?
-
x * 53000, SDS-PAGE
?
-
x * 63000, SDS-PAGE
?
-
x * 75600, isozyme splicing form c, SDS-PAGE
?
-
x * 68000, isozymes alpha or beta, x * 90000, isozyme gamma
?
A1YQB1, -
x * 28170, calculated
dimer
-
x * 60000, SDS-PAGE
additional information
-
the enzyme possesses a central socalled kinase core domain containing the activation loop which is responsible for substrate specificity and subcellular targeting of the enzyme
additional information
-
the enzyme possesses a central so-called kinase core domain containing the activation loop which is responsible for substrate specificity and subcellular targeting of the enzyme
additional information
-
the enzyme possesses a central socalled kinase core domain containing the activation loop which is responsible for substrate specificity and subcellular targeting of the enzyme
additional information
-
2 dimerization domains may be involved in subcellular targeting in isozyme beta
additional information
-
following stimulation of the beta2-adrenergic receptor, beta-arrestins bind phosphatidylinositol 4-phosphate 5-kinase 1alpha. A beta-arrestin mutant deficient in phosphatidylinositol 4,5-bisphosphate binding fails to interact with phosphatidylinositol 4-phosphate 5-kinase 1alpha and is not associated with phosphatidylinositol kinase activity in vitro, and no longer internalizes beta2-adrenergic receptor
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
phosphoprotein
-
the enzyme is negatively regulated by, besides other mechanisms, phosphorylation, autophosphorylation is enhanced by phosphatidylinositol
phosphoprotein
-
the enzyme is negatively regulated by, besides other mechanisms, phosphorylation, autophosphorylation is enhanced by phosphatidylinositol, Ca2+ induces dephosphorylation of isozyme gamma at serine 264, phosphorylation by 9,11-dideoxy-9alpha,11alpha-methanoepoxyprostaglandin U46619 is inhibited by genistein in platelets, tyrosine phosphorylation by focal adhesion kinase of isozyme gamma brain splice variant associated to the FERM domain of talin in brain
phosphoprotein
-
the enzyme is negatively regulated by, besides other mechanisms, phosphorylation, autophosphorylation is enhanced by phosphatidylinositol, isozyme alpha is phosphorylated by cAMP-dependent protein kinase at serine 214, Ca2+ induces dephosphorylation of isozyme gamma at serine 264, phosphorylation by 9,11-dideoxy-9alpha,11alpha-methanoepoxyprostaglandin U46619 is inhibited by genistein in platelets, tyrosine phosphorylation by focal adhesion kinase of isozyme gamma brain splice variant associated to the FERM domain of talin in brain
phosphoprotein
-
the enzyme is negatively regulated by, besides other mechanisms, phosphorylation, autophosphorylation is enhanced by phosphatidylinositol
phosphoprotein
-
phosphorylation by Cki1 in vitro decreases the activity of the enzyme
phosphoprotein
-
the enzyme is negatively regulated by, besides other mechanisms, phosphorylation by casein kinase I
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
sucrose and PEG 20000 in the assay medium are required to stabilize the enzyme during phosphorylation reaction
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-20C, 50 MM Tris-HCl, pH 8.0, 1 mM EDTA, 0.25 M sucrose, 0.3% v/v 2-mercaptoethanol, 0.1% Triton X-100, 0.1% PEG 20000, 0.05 mM ATP, 0.1 mM PMSF, stable for several months
-
-70C, stable in concentrated form
-
4C, storage causes the 53000 Da enzyme to be slowly degraded to a 45000 Da peptide
-
4C, about 10% loss of activity after overnight storage
-
-80C, stable for at least 3 months
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
Partial purification from Escherichia coli culture cells. The cells are suspended in PBS buffer, sonicated on ice, and centrifuged. Supernatant is mixed with glutathione-Sepharose 4B and incubated at 48C for 2 h. The Sepharose beads are collected and washed with an excess volume of PBS.
O48709
recombinant GST-fusion protein from Escherichia coli in presence of Triton X-100 and PtdOH; recombinant GST-fusion protein from Escherichia coli in presence of Triton X-100 and PtdOH
Q56YP2, Q9LMN1
cytosolic enzyme type II enzyme and membrane-bound type I and type II enzyme
-
recombinan GST-fusion isozyme alpha from Escherichia coli
Q99755
Talon metal affinity column chromatography
-
glutathione-Sepharose chromatography
-
wild-type and mutant isozyme gamma, partially by immunoprecipitation and protein G affinity chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
a yellow fluorescent (YFP) und GUS fusion PIP5K3 protein is expressed in Escherichia coli cells and transformed in Arabidopsis thaliana to produce trangenic plants. Overexpression and mutant is investigated.
O48709
expressed in Nicotiana tabacum
Q8L850
expression in Escherichia coli
-
expression of enzyme form 10 as GST-fusion protein in Escherichia coli, expression of His-tagged enzyme form 10 in Spodoptera frugiperda Sf9 cells via baculovirus infection system; expression of enzyme form 1 as GST-fusion protein in Escherichia coli, expression of His-tagged enzyme form 1 in Spodoptera frugiperda Sf9 cells via baculovirus infection system
Q56YP2, Q9LMN1
enzyme form PIP5KIalpha
-
expressed in Escherichia coli strain HT115 (DE3)
-
EmPIP5K gene, DNA and amino acid sequence determination and analysis, located at position 710-8036 nt on the complimentary strand, structural organization of the PIP5K gene, and phylogenetic analysis and tree
C8BX38, -
-
Q9Y2I7
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
-
expressed in Sf9 cells and MEF cells
-
expression in COS cells
-
expression in HEK-203 cell
-
expression of isozyme alpha as GST-fusion protein in Escherichia coli
Q99755
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
-
isozyme PIP5K1beta expression in HEK-293T and COS-7 cells
-
cloning of splice variant phosphatidylinositol 4-phosphate 5-kinase Igamma_v6, expression in COS-7 cells
-
coexpression of wild-type HA-tagged isozyme alpha or HA-tagged isozyme alpha mutant D227A with HA-tagged Arf6 or HA-tagged Arf6 mutant N121I in COS-1 cells
-
expressed in Escherichia coli
-
expressed in Escherichia coli; expressed in HEK-293T cells
-
expressed in HEK-293T cells; expression in COS-7 cells
-
expressed in HeLa cells
-
expression in Xenopus laevis oocyte
-
expression of HA-tagged PIP5K isozymes in COS-7 cells, expression of isozyme PIP5Kalpha mutant D322A
-
expression of isozyme PIP5Kalpha tagged with monomeric red fluorescent protein, haemagglutinin, or FLAG in HEK-293T cells
P70182
expression of mutant enzymes K181A, D309N, D309N/R429Q and R427Q in Escherichia coli, expression of mutant enzymes in human MG-63 osteosarcoma cells
-
functional complementation of a yeast Mss4-1 mutant strain YOC808 by the wild-type isozyme gamma and the deletion mutants localizing to the plasma membrane, while the deletion mutants localized to the cytosol cannot support yeast cell growth, expression of wild-type and mutant type I HA-tagged or EGFP-tagged isozymes gamma in Neuro 2A cells and in COS-1 cells
-
overexpression of isozymes alpha, beta, and gamma in HeLa cells, overexpression of isozymes alpha, beta, and gamma in CV-1 cells: isozymes alpha and beta are active, the latter shows the highest activity, isozyme gamma is not active, small interference RNA inhibition of isozyme beta expression also reduces expression of isozyme alpha, but increased expression of isozyme gamma, with a 50% loss in activity, reduction of isozyme alpha expression increases expression of isozymes beta and gamma and leaves the 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate synthesis level unaltered, inhibition of isozyme gamma increases expression of isozymes alpha and beta, overview, expression of isozyme beta increases the internalization of influenza virus hemagglutinin Y543, enzyme expression prevents the cells of disruption of their actine cytoskeleton by drugs, e.g. cytochalasin D or latrunculin, and increases the number of clathrin-coated pits
-
overexpression of mutant D266A in N1E-115 cells, expression of isozyme alpha in COS-7 cells, expression of isozyme alpha in Escherichia coli
-
overexpression of PIPKalpha in N1E-115 neuroblastoma cells, co-expression of His6-tagged KIF2A and GST-tagged PIPKalpha in Escherichia coli, binding analysis
-
cloning of splice variant phosphatidylinositol 4-phosphate 5-kinase Igamma_v6 from hippocampus, expression in COS-7 cells
-
identification of splicing form c of type I phosphatidylinositol 4-phosphate 5-kinase isoform gamma possessing additional 26 amino acids at the C-terminus from a hippocampus library, DNA and amino acid sequence determination and analysis, overvexpression of the catalytically inactive mutants D316K and K188A of isozyme gamma splicing form c in rat cerebellar granule cells, expression of isozyme gamma splicing form a, expression of wild-type and FLAG-tagged isozyme gamma splicing form c in COS-7 cells
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
R427Q
-
inactive mutant
D203A
-
catalytically inactive. Expression in Xenopus laevis oocyte has no effect on epithelial sodium channel activity
D227A
-
site-directed muatgenesis, inactive mutant
D227A
-
catalytically inactive. Expression in Xenopus laevis oocyte has no effect on epithelial sodium channel activity
D253A
-
mutant lacking kinase activity. Overexpression compromises uropod formation and rear retraction during chemotaxis
D266A
-
site-directed mtagenesis, mutation of the putative ATP and 1-phosphatidyl-1D-myo-inositol 4-phosphate binding site, cells form extremely extended bipolar neurits even in presence of serum, failed to interfere with cell flattening and neurite extension
D309N
-
greatly reduced kinase activity towards 1-phosphatidyl-1D-myo-inositol 4-phosphate
D309N/R427Q
-
greatly reduced kinase activity towards 1-phosphatidyl-1D-myo-inositol 4-phosphate
D316K
-
no activity
D322A
-
isozyme PIP5Kalpha mutant that shows reduced activity compared to the wild-type enzyme
K138A
-
no activity
K181A
-
greatly reduced kinase activity towards 1-phosphatidyl-1D-myo-inositol 4-phosphate
L202I
-
the mutations of PIP5Kalpha decreases the substrate affinity and the enzyme efficiency for 1-stearoyl-2-arachidonoyl phosphatidylinositol-4-phosphate compared to the wild-type enzyme
R332H
P70182
YFP-tagged tubby mutant
R427Q
-
greatly reduced kinase activity towards 1-phosphatidyl-1D-myo-inositol 4-phosphate
D316K
-
site-directed mutagenesis, overexpression of the catalytically inactive construct of isozyme gamma splicing form c in rat cerebellar granule cells causes progressive loss of their neuronal processes, not observed with expression of isozyme gamma splicing form a
K188A
-
site-directed mutagenesis, overexpression of the catalytically inactive construct of isozyme gamma splicing form c in rat cerebellar granule cells causes progressive loss of their neuronal processes, not observed with expression of isozyme gamma splicing form a
D598A
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no activity
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Q8L850
T-DNA insertion mutant pip5k9-d shows enhanced PIP5K9 transcript levels
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mutant plants homozygous for T-DNA-disrupted PIP5K3 alleles are compromised in root hair formation. Root hair-specific PIP5K3 overexpression results in root hair deformation and loss of cell polarity with increasing accumulation of PIP5K3 transcript. An N-terminal domain containing membrane occupation and recognition nexus repeats, which is not required for catalytic activity, is essential for the establishment of root hair growth. Transient heterologous expression of full-length PIP5K3 in Nicotiana tabacum pollen tubes increases plasma membrane association of a phosphatidylinositol 4,5-bisphoshate-specific reporter
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-, O01759
overexpression of isoform PPK-1 in Caenorhabditis elegans causes an increase in 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate levels in vivo. In developing neurons, PPK-1 overexpression leads to growth cones that become stalled, produce ectopic membrane projections, and branched axons. Once neurons are established, PPK-1 overexpression results in progressive membrane overgrowth and degeneration during adulthood
D309N
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inactive mutant
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chimeric protein in which the core kinase domain of phosphatidylinositol 4-phosphate 5-kinase 1alpha has been fused to a beta-arrestin mutant deficient in phosphatidylinositol 4,5-bisphosphate binding rescues internalization of beta2-adrenergic receptor
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knockdown of phosphatidylinositol 4-phosphate 5-kinase beta with siRNA inhibits cell polarization and impairs cell directionality during dHL60 chemotaxis
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PIP5Kgamma isozyme knockout by siRNA. Transfection of HK2 cells with PIP5Kgamma siRNA prevents advanced glycation end products-bovine serum albumin inhibition of renal Na+/K+ ATPase activity
L210I
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the mutations of PIP5Kalpha decreases the substrate affinity and the enzyme efficiency for 1-stearoyl-2-arachidonoyl phosphatidylinositol-4-phosphate compared to the wild-type enzyme
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construction of N-terminal deletion mutants DELTA68, DELTA 72, and DELTA74 are still localized to the plasma membrane, while the N-terminal deletion mutants DELTA82, DELTA 97 are mislocated to the cytosol, construction of C-terminal deletion mutant DELTA446 is still localized to the plasma membrane, while the N-terminal deletion mutant DELTA444 is mislocated to the cytosol, mutant fusion protein DELTA68-DELTA444 localizes to the plasma membrane
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expression of phosphatidylinositol 4-phosphate 5-kinase alpha in Xenopus laevis oocytes decreases epithelial sodium channel currents by 80%, entirely due to a decrease in cell surface epithelial sodium channel levels. Expression of catalytically inactive mutants has no effect on epithelial sodium channel activity. Knock-down of phosphatidylinositol 4-phosphate 5-kinase alpha with isoform-specific siRNA results in a 4fold enhancement of epithelial sodium channel activity
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construction of single knockout mutants of isozymes Pip5k1a and Pip5k1b, and double knockout mutants
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P70182
construction of PIP5Kalpha knockdown BV-2 cells by shRNA
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knockdown of isozyme PIPKalpha in neurites
D636A
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no activity
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mutant its3-1 shows defective PIP5K activity and sensitivity to micafungin, aculeacin A, and BE49385A
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PIP5Kgamma isozyme knockout by siRNA. Transfection of HK2 cells with PIP5Kgamma siRNA prevents advanced glycation end products-bovine serum albumin inhibition of renal Na+/K+ ATPase activity