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Information on EC 2.7.1.68 - 1-phosphatidylinositol-4-phosphate 5-kinase and Organism(s) Homo sapiens and UniProt Accession Q9Y2I7
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2.7.1.68 1-phosphatidylinositol-4-phosphate 5-kinaseIUBMB Comments
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.
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Word Map
- 2.7.1.68
- 4,5-bisphosphate
- phosphoinositide
- fracture
- pip2
- actin
- femoral
- phospholipase
-
ptdins4,5p2
- phospholipid
- cytoskeleton
- dislocation
- phosphatidylinositol-4,5-bisphosphate
-
phosphatidic
-
posterior
- gtpases
- diacylglycerol
-
4-kinase
-
polyphosphoinositides
-
acetabular
-
accident
-
ossification
- talin
-
avascular
- rac1
-
fracture-dislocation
- bisphosphate
-
screw
- arf6
-
5-phosphatase
-
heterotopic
-
arthroplasty
- 3,4,5-trisphosphate
-
ptdins5p
-
trochanteric
-
ovcar-5
- osteonecrosis
-
inositide
-
osteotomy
-
kinase-dead
-
osteochondral
- tiazofurin
-
3hinositol
-
insps
-
merle
-
ptdins3,4,5p3
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
Synonyms
pipkin, pip5k, pip kinase, ptdinsp, phosphatidylinositol 4-phosphate 5-kinase, phosphatidylinositol-4-phosphate 5-kinase, pipk, pipkigamma, pip5k1a, pip5ks, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Diphosphoinositide kinase
-
-
-
-
MSS4p
-
-
-
-
phosphatidylinositol 4-phosphate kinase
-
-
-
-
phosphatidylinositol-4-phosphate 5-kinase
PI4P 5-kinase
-
-
-
-
PI4P5K
-
-
-
-
PIP kinase
-
-
-
-
PIP-5kin
-
-
-
-
PIP5K
PIP5Kalpha
PIP5Kbeta
PIP5Kgamma
PIP5KIbeta
PIP5KIgamma
PIP5Ks
-
-
-
-
PIPKIalpha
PIPKIgamma
PtdIns(4)P 5-kinase
-
-
-
-
phosphatidylinositol-4-phosphate 5-kinase
-
-
-
-
PIP5K
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate = ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
an activation loop spanning the catalytic domain is responsible for determination of both substrate specificity and subcellular targeting
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
-
-
-
-
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
104645-76-3
-
9032-61-5
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ATP + phosphatidylinositol 3-phosphate
ADP + phosphatidylinositol 3,4-bisphosphate
-
-
-
?
ATP + phosphatidylinsositol 3,4-bisphosphate
ADP + phosphatidylinositol 3,4,5-trisphosphate
-
-
-
-
?
GTP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
GDP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
-
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
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
-
-
641824, 641825, 641834, 641840, 660641, 661660, 672961, 673185, 675959, 721706, 722723, 738090, 738199, 738288, 738599, 738651, 738787, 738790, 738794, 738912, 759168, 759475, 760179
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
-
-
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
-
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
-
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
-
-
?
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
?
-
-
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
?
-
-
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
-
-
?
additional information
?
-
-
endosome-bound phosphatidylinositol 4-phosphate 5-kinase homolog PIP5K-like 1 recruits phosphatidylinositol 4-phosphate 5-kinases to intracellular compartments and interacts with them in cells
-
-
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
-
-
721706, 722723, 738090, 738199, 738288, 738599, 738651, 738787, 738790, 738794, 738912, 759168, 759475, 760179
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
-
-
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
-
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
-
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
-
-
?
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
?
-
-
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
?
-
-
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
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
not inhibited by SP600125, SB203580, ZVAD-fmk, wortmannin or LY294002
-
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
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
-
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
-
involved in membrane receptor-mediated regulation, acts via effectors, mechanism overview
-
small GTPase Rho
-
involved in membrane receptor-mediated regulation, acts via effectors, mechanism overview
-
spermine
-
2 mM, 4fold increase in activity of type I enzyme, no effect on type II enzyme
Triton X-100
-
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
LITERATURE
IMAGE
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
0.006
1-phosphatidyl-1D-myo-inositol 4-phosphate
-
in 1-phosphatidyl-1D-myo-inositol 4-phosphate micelles, type I enzyme
0.04
1-phosphatidyl-1D-myo-inositol 4-phosphate
-
in 1-phosphatidyl-1D-myo-inositol 4-phosphate liposomes, type II enzyme
0.06
1-phosphatidyl-1D-myo-inositol 4-phosphate
-
in 1-phosphatidyl-1D-myo-inositol 4-phosphate micelles, type II enzyme
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
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
-
phosphatidylinositol 4-phosphate 5-kinase Igamma_v6 is not a major brain variant
-
two form of PIP kinase: type I kinase is membrane bound and type II kinase is both membrane bound and cytosolic
-
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
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
localizes mainly to early endosomes. PIKfyve is distributed in microdomains
-
type I kinase is membrane bound and type II kinase is both membrane bound and cytosolic
-
type I kinase is membrane bound and type II kinase is both membrane bound and cytosolic
-
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
-
phosphatidylinositol 4-phosphate 5-kinase Igamma_v6 splice variant
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
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
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
-
enzyme knockdown impairs Akt activation in response to both FBS and ECM protein stimulation
malfunction
-
enzyme silencing impairs CD28-mediated IL-8 and IL-2 transcriptional activation
malfunction
downregulation of isoforms PIP5K1alpha and PIP5K1gamma strongly impairs the targeting of HIV-1 Gag polyprotein precursor Pr55Gag to the plasma membrane with a rerouting of the polyprotein within intracellular compartments
malfunction
-
knockdown of isoform PIPKIgammai5 leads to the loss of mitogen-inducible gene 6 expression, which dramatically enhances and prolongs epidermal growth factor receptor-mediated cell signaling
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
metabolism
enzyme isoform PIP5KIgamma regulates KCNQ2/3 currents and store-operated calcium entry in distinct ways in tsA201 cells
metabolism
enzyme isoforms PIP5KIbeta regulates KCNQ2/3 currents and store-operated calcium entry in distinct ways in tsA201 cells
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
-
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
-
CD28 induces the recruitment of the enzyme to the immunological synapse, where it regulates filamin A and lipid raft accumulation, as well as T cell activation, in a nonredundant manner
physiological function
-
enzyme overexpression promotes class I PI3K and the serine/threoninespecific protein kinase Akt signaling and oncogenic growth
physiological function
-
T lymphocyte triggering is finely tuned by phosphatidylinositol 4,5-biphosphate kinases activity
physiological function
-
the enzyme and sorting nexin 5 protein form a signaling nexus that controls epidermal growth factor receptor endosomal sorting, degradation, and signaling
physiological function
the enzyme functions as a member of the rDNA silencing complex
physiological function
the enzyme interacts with the cytoskeleton regulator IQGAP1 and modulates IQ motif containing GTPase activating protein 1 (IQGAP1) function in migration. The enzyme is required for IQGAP1 recruitment to the leading edge membrane in response to integrin or growth factor receptor activation
physiological function
-
the enzyme is a key modulator of CD28 costimulatory signals and required for CD28-mediated transcription of both interleukin-8 and interleukin-2 genes
physiological function
-
the enzyme is a key modulator of CD28 costimulatory signals leading to the efficient T cell activation. Enzyme recruitment and activation is essential for CD28-mediated cytoskeleton rearrangement necessary for organizing a complete signaling compartment leading to downstream signaling functions
physiological function
-
the enzyme prevents the decrease in the HRG (human ether-a-go-go-related gene) potassium current induced by Gq protein-coupled receptor stimulation
physiological function
-
the enzyme regulates Src activation downstream of growth factor receptors and integrins. The enzyme and Src synergistically control anchorage-independent tumor cell growth
physiological function
-
isoform PIPKIgammai5 controls Mig6 ubiquitination and degradation. Isoform PIPKIgammai5, the E3 ubiquitin ligase neuronal precursor cell-expressed developmentally down-regulated 4-1, and mitogen-inducible gene 6 form a molecular nexus that controls epidermal growth factor receptor activation and downstream signalling
physiological function
-
overexpression of isoform PIP5K1A results in significant enhancement of non-amyloidogenic amyloid precursor protein processing and a concomitant suppression of the amyloidogenic pathway, leading to a marked decrease in secreted amyloid-beta peptide
physiological function
the 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate pools produced by isoforms PIP5K1alpha and gamma are involved in HIV-1 Gag polyprotein precursor Pr55Gag plasma membrane targeting process
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
68000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
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
-
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
COMMENTARY
LITERATURE
phosphoprotein
sumoylation
SUMOylation at Lys-244 and Lys-490 directs the enzyme's nuclear entry and its interaction with H3K9me3/HP1-alpha, respectively
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
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D309N
additional information
additional information
-
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
additional information
-
knockdown of phosphatidylinositol 4-phosphate 5-kinase beta with siRNA inhibits cell polarization and impairs cell directionality during dHL60 chemotaxis
additional information
-
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
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4°C, storage causes the 53000 Da enzyme to be slowly degraded to a 45000 Da peptide
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
-
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
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Smith, P.M.; Wreggett, K.A.; Irvine, R.F.
The phosphatidylinositol 4-phosphate kinase of rat brain and human platelets
Biochem. Soc. Trans.
14
1145-1146
1986
Homo sapiens, Rattus norvegicus
-
Bazenet, C.E.; Anderson, R.A.
Phosphatidylinositol-4-phosphate 5-kinases from human erythrocytes
Methods Enzymol.
209
189-202
1992
Homo sapiens
Ling, L.E.; Schulz, J.T.; Cantley, L.C.
Characterization and purification of membrane-associated phosphatidylinositol-4-phosphate kinase from human red blood cells
J. Biol. Chem.
264
5080-5088
1989
Homo sapiens
Zhang, X.; Loijens, J.C.; Boronenkov, I.V.; Parker, G.J.; Norris, F.A.; Chen, J.; Thum, O.; Prestwich, G.D.; Majerus, P.W.; Anderson, R.A.
Phosphatidylinositol-4-phosphate 5-kinase isozymes catalyze the synthesis of 3-phosphate-containing phosphatidylinositol signaling molecules
J. Biol. Chem.
272
17756-17761
1997
Homo sapiens
Oude Weernink, P.A.; Schulte, P.; Guo, Y.; Wetzel, J.; Amano, M.; Kaibuchi, K.; Haverland, S.; Voss, M.; Schmidt, M.; Mayr, G.W.; Jakobs, K.H.
Stimulation of phosphatidylinositol-4-phosphate 5-kinase by Rho-kinase
J. Biol. Chem.
275
10168-10174
2000
Homo sapiens
Kanaho, Y.; Miyazaki, H.; Yamazaki, M.
Activation of PI(4)P 5-kinase by small G proteins
Adv. Enzyme Regul.
43
107-119
2003
Bos taurus, Homo sapiens, Mus musculus, Rattus norvegicus
Oude Weernink, P.A.; Schmidt, M.; Jakobs, K.H.
Regulation and cellular roles of phosphoinositide 5-kinases
Eur. J. Pharmacol.
500
87-99
2004
Saccharomyces cerevisiae, Candida albicans, Homo sapiens, Mus musculus, Schizosaccharomyces pombe
Perera, I.Y.; Davis, A.J.; Galanopoulou, D.; Im, Y.J.; Boss, W.F.
Characterization and comparative analysis of Arabidopsis phosphatidylinositol phosphate 5-kinase 10 reveals differences in Arabidopsis and human phosphatidylinositol phosphate kinases
FEBS Lett.
579
3427-3432
2005
Arabidopsis thaliana (Q56YP2), Arabidopsis thaliana (Q9LMN1), Homo sapiens (Q99755), Homo sapiens
Akiyama, C.; Shinozaki-Narikawa, N.; Kitazawa, T.; Hamakubo, T.; Kodama, T.; Shibasaki, Y.
Phosphatidylinositol-4-phosphate 5-kinase gamma is associated with cell-cell junction in A431 epithelial cells
Cell Biol. Int.
29
514-520
2005
Homo sapiens
Halstead, J.R.; van Rheenen, J.; Snel, M.H.; Meeuws, S.; Mohammed, S.; DSantos, C.S.; Heck, A.J.; Jalink, K.; Divecha, N.
A role for PtdIns(4,5)P2 and PIP5Kalpha in regulating stress-induced apoptosis
Curr. Biol.
16
1850-1856
2006
Homo sapiens, Mus musculus
Cabezas, A.; Pattni, K.; Stenmark, H.
Cloning and subcellular localization of a human phosphatidylinositol 3-phosphate 5-kinase, PIKfyve/Fab1
Gene
371
34-41
2006
Homo sapiens (Q9Y2I7)
Kisseleva, M.; Feng, Y.; Ward, M.; Song, C.; Anderson, R.A.; Longmore, G.D.
The LIM protein Ajuba regulates phosphatidylinositol 4,5-bisphosphate levels in migrating cells through an interaction with and activation of PIPKI alpha
Mol. Cell. Biol.
25
3956-3966
2005
Homo sapiens
Nelson, C.D.; Kovacs, J.J.; Nobles, K.N.; Whalen, E.J.; Lefkowitz, R.J.
Beta-arrestin scaffolding of phosphatidylinositol 4-phosphate 5-kinase Ialpha promotes agonist-stimulated sequestration of the beta2-adrenergic receptor
J. Biol. Chem.
283
21093-21101
2008
Homo sapiens
Lacalle, R.A.; Peregil, R.M.; Albar, J.P.; Merino, E.; Martinez-A, C.; Merida, I.; Manes, S.
Type I phosphatidylinositol 4-phosphate 5-kinase controls neutrophil polarity and directional movement
J. Cell Biol.
179
1539-1553
2007
Homo sapiens
Lokuta, M.A.; Senetar, M.A.; Bennin, D.A.; Nuzzi, P.A.; Chan, K.T.; Ott, V.L.; Huttenlocher, A.
Type Igamma PIP kinase is a novel uropod component that regulates rear retraction during neutrophil chemotaxis
Mol. Biol. Cell
18
5069-5080
2007
Homo sapiens, Mus musculus
Xia, Y.; Irvine, R.F.; Giudici, M.L.
Phosphatidylinositol 4-phosphate 5-kinase Igamma_v6, a new splice variant found in rodents and humans
Biochem. Biophys. Res. Commun.
411
416-420
2011
Homo sapiens, Mus musculus, Rattus norvegicus
Gallicchio, M.A.; Bach, L.A.
Advanced glycation end products inhibit Na+ K+ ATPase in proximal tubule epithelial cells: role of cytosolic phospholipase A2alpha and phosphatidylinositol 4-phosphate 5-kinase gamma
Biochim. Biophys. Acta
1803
919-930
2010
Homo sapiens, Sus scrofa
Sakurai, A.; Jian, X.; Lee, C.J.; Manavski, Y.; Chavakis, E.; Donaldson, J.; Randazzo, P.A.; Gutkind, J.S.
Phosphatidylinositol-4-phosphate 5-kinase and GEP100/Brag2 protein mediate antiangiogenic signaling by semaphorin 3E-plexin-D1 through Arf6 protein
J. Biol. Chem.
286
34335-34345
2011
Homo sapiens
Nguyen, T.T.; Kim, Y.M.; Kim, T.D.; Le, O.T.; Kim, J.J.; Kang, H.C.; Hasegawa, H.; Kanaho, Y.; Jou, I.; Lee, S.Y.
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 (TIRAP) location
J. Biol. Chem.
288
5645-5659
2013
Homo sapiens, Mus musculus (P70182)
Sun, Y.; Hedman, A.C.; Tan, X.; Schill, N.J.; Anderson, R.A.
Endosomal type Igamma PIP 5-kinase controls EGF receptor lysosomal sorting
Dev. Cell
25
144-155
2013
Homo sapiens
Choi, S.; Thapa, N.; Hedman, A.C.; Li, Z.; Sacks, D.B.; Anderson, R.A.
IQGAP1 is a novel phosphatidylinositol 4,5 bisphosphate effector in regulation of directional cell migration
EMBO J.
32
2617-2630
2013
Homo sapiens (O60331)
Lacalle, R.A.; de Karam, J.C.; Martinez-Munoz, L.; Artetxe, I.; Peregil, R.M.; Sot, J.; Rojas, A.M.; Goni, F.M.; Mellado, M.; Manes, S.
Type I phosphatidylinositol 4-phosphate 5-kinase homo- and heterodimerization determines its membrane localization and activity
FASEB J.
29
2371-2385
2015
Homo sapiens
Porciello, N.; Kunkl, M.; Viola, A.; Tuosto, L.
Phosphatidylinositol 4-phosphate 5-kinases in the regulation of T cell activation
Front. Immunol.
7
186
2016
Homo sapiens
Thapa, N.; Choi, S.; Hedman, A.; Tan, X.; Anderson, R.A.
Phosphatidylinositol phosphate 5-kinase Igammai2 in association with Src controls anchorage-independent growth of tumor cells
J. Biol. Chem.
288
34707-34718
2013
Homo sapiens
Thapa, N.; Choi, S.; Tan, X.; Wise, T.; Anderson, R.A.
Phosphatidylinositol phosphate 5-kinase Igamma and phosphoinositide 3-kinase/Akt signaling couple to promote oncogenic growth
J. Biol. Chem.
290
18843-18854
2015
Homo sapiens
Chakrabarti, R.; Sanyal, S.; Ghosh, A.; Bhar, K.; Das, C.; Siddhanta, A.
Phosphatidylinositol-4-phosphate 5-kinase 1alpha modulates ribosomal RNA gene silencing through its interaction with histone H3 lysine 9 trimethylation and heterochromatin protein HP1-alpha
J. Biol. Chem.
290
20893-20903
2015
Homo sapiens (Q99755)
Muscolini, M.; Camperio, C.; Capuano, C.; Caristi, S.; Piccolella, E.; Galandrini, R.; Tuosto, L.
Phosphatidylinositol 4-phosphate 5-kinase alpha activation critically contributes to CD28-dependent signaling responses
J. Immunol.
190
5279-5286
2013
Homo sapiens
Muscolini, M.; Camperio, C.; Porciello, N.; Caristi, S.; Capuano, C.; Viola, A.; Galandrini, R.; Tuosto, L.
Phosphatidylinositol 4-phosphate 5-kinase alpha and Vav1 mutual cooperation in CD28-mediated actin remodeling and signaling functions
J. Immunol.
194
1323-1333
2015
Homo sapiens
Kallikourdis, M.; Trovato, A.E.; Roselli, G.; Muscolini, M.; Porciello, N.; Tuosto, L.; Viola, A.
Phosphatidylinositol 4-phosphate 5-kinase beta controls recruitment of lipid rafts into the immunological synapse
J. Immunol.
196
1955-1963
2016
Homo sapiens
Kubo, T.; Ding, W.G.; Toyoda, F.; Fujii, Y.; Omatsu-Kanbe, M.; Matsuura, H.
Phosphatidylinositol4-phosphate 5-kinase prevents the decrease in the HERG potassium current induced by Gq protein-coupled receptor stimulation
J. Pharmacol. Sci.
127
127-134
2015
Homo sapiens
Wu, P.F.; Bhore, N.; Lee, Y.L.; Chou, J.Y.; Chen, Y.W.; Wu, P.Y.; Hsu, W.M.; Lee, H.; Huang, Y.S.; Lu, P.J.; Liao, Y.F.
Phosphatidylinositol-4-phosphate 5-kinase type 1alpha attenuates Abeta production by promoting non-amyloidogenic processing of amyloid precursor protein
FASEB J.
34
12127-12146
2020
Homo sapiens
Sun, M.; Cai, J.; Anderson, R.A.; Sun, Y.
Type I gamma phosphatidylinositol phosphate 5-kinase i5 controls the ubiquitination and degradation of the tumor suppressor mitogen-inducible gene 6
J. Biol. Chem.
291
21461-21473
2016
Homo sapiens
De La Cruz, L.; Traynor-Kaplan, A.; Vivas, O.; Hille, B.; Jensen, J.
Plasma membrane processes are differentially regulated by type I phosphatidylinositol phosphate 5-kinases and RASSF4
J. Cell Sci.
133
jcs233254
2020
Homo sapiens (O14986), Homo sapiens (O60331)
Gonzales, B.; de Rocquigny, H.; Beziau, A.; Durand, S.; Burlaud-Gaillard, J.; Lefebvre, A.; Krull, S.; Emond, P.; Brand, D.; Piver, E.
Type I phosphatidylinositol-4-phosphate 5-kinases alpha and gamma play a key role in targeting HIV-1 Pr55Gag to the plasma membrane
J. Virol.
94
e00189-20
2020
Homo sapiens (O60331), Homo sapiens (Q99755)
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