LMP001317 UniProt Annotations
Gene Name phosphatidylinositol-4-phosphate 5-kinase, type 1 gamma
Protein Entry F8WHW6_MOUSE
UniProt ID O70161
Species Mouse
Comment type Description
Alternative Products Event=Alternative splicing; Named isoforms=3; Name=1; Synonyms=PIPKIgamma661; IsoId=O70161-1; Sequence=Displayed; Name=2; Synonyms=PIPKIgamma627; IsoId=O70161-2; Sequence=VSP_016013, VSP_016014; Note=No experimental confirmation available.; Name=3; Synonyms=PIPKIgamma635; IsoId=O70161-3; Sequence=VSP_016015;
Biophysicochemical Properties Kinetic parameters: KM=37 uM for PtdIns(4)P; KM=39 uM for ATP;
Catalytic Activity ATP + 1-phosphatidyl-1D-myo-inositol 4- phosphate = ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate.
Developmental Stage Expression increases during embryonic development and continued to steadily increase postnatally. {ECO:0000269|PubMed:20622009}.
Disruption Phenotype According to some authors, mutants die within hours after birth and are unable to feed after birth (PubMed:15386003). According to another report, mutants are embryonically lethal at organogenesis stage, and display cardiovascular and neuronal defects (PubMed:15386003). PIP5K1C and PIP5K1B double mutant mice die within minutes after birth. PIP5K1C and PIP5K1A double mutant mice are embryonic lethal. Bone marrow- derived macrophages are defective in phagocytosis, attachment to IgG-opsonized particles and Fc-gamma-R clustering, and display highly polymerized actin cytoskeleton. Neurons display defects in synaptic transmission due to defects in synaptic vesicle trafficking at different levels. T-cells mutant for isoform 1 display increase adhesion and polarization. {ECO:0000269|PubMed:15386003, ECO:0000269|PubMed:17609388, ECO:0000269|PubMed:19153220, ECO:0000269|PubMed:20622009, ECO:0000269|PubMed:20855869}.
Enzyme Regulation Activated by phosphatidic acid. {ECO:0000269|PubMed:9535851}.
Function Catalyzes the phosphorylation of phosphatidylinositol 4- phosphate (PtdIns4P) to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). PtdIns(4,5)P2 is involved in a variety of cellular processes and is the substrate to form phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3), another second messenger. The majority of PtdIns(4,5)P2 is thought to occur via type I phosphatidylinositol 4-phosphate 5-kinases given the abundance of PtdIns4P. Participates in a variety of cellular processes such as vesicle mediated transport, cell adhesion, cell polarization and cell migration. Together with PIP5K1A is required for phagocytosis, but they regulate different types of actin remodeling at sequential steps. Promotes particle attachment by generating the pool of PtdIns(4,5)P2 that induces controlled actin depolymerization to facilitate Fc-gamma-R clustering. Mediates RAC1-dependent reorganization of actin filaments. Required for synaptic vesicle transport. Controls the plasma membrane pool of PtdIns(4,5)P2 implicated in synaptic vesicle endocytosis and exocytosis. Plays a role in endocytosis mediated by clathrin and AP-2 (adaptor protein complex 2). Required for clathrin-coated pits assembly at the synapse. Participates in cell junction assembly. Modulates adherens junctions formation by facilitating CDH1 trafficking. Required for focal adhesion dynamics. Modulates the targeting of talins (TLN1 and TLN2) to the plasma membrane and their efficient assembly into focal adhesions. Regulates the interaction between talins (TLN1 and TLN2) and beta-integrins. Required for uropodium formation and retraction of the cell rear during directed migration. Has a role in growth factor- stimulated directional cell migration and adhesion. Required for talin assembly into nascent adhesions forming at the leading edge toward the direction of the growth factor. Negative regulator of T-cell activation and adhesion. Negatively regulates integrin alpha-L/beta-2 (LFA-1) polarization and adhesion induced by T-cell receptor. Together with PIP5K1A have a role during embryogenesis and together with PIP5K1B may have a role immediately after birth. {ECO:0000269|PubMed:12422220, ECO:0000269|PubMed:15386003, ECO:0000269|PubMed:16707488, ECO:0000269|PubMed:17609388, ECO:0000269|PubMed:17635937, ECO:0000269|PubMed:17928408, ECO:0000269|PubMed:19153220, ECO:0000269|PubMed:20622009, ECO:0000269|PubMed:20855869, ECO:0000269|PubMed:9535851}.
Interaction Q9DBG3-1:Ap2b1; NbExp=3; IntAct=EBI-773657, EBI-775239; Q9DBG3-2:Ap2b1; NbExp=8; IntAct=EBI-773657, EBI-7257021;
Ptm Acetylation at Lys-265 and Lys-268 seems to decrease lipid kinase activity. Deacetylation of these sites by SIRT1 positively regulates the exocytosis of TSH-containing granules from pituitary cells (By similarity). {ECO:0000250}.
Ptm Phosphorylation on Ser-645 negatively regulates binding to TLN2 and is strongly stimulated in mitosis. Phosphorylation on Tyr-644 is necessary for targeting to focal adhesions. Phosphorylation on Ser-645 and Tyr-644 are mutually exclusive. Phosphorylated by SYK and CSK. Tyrosine phosphorylation is enhanced by PTK2 signaling. Phosphorylated at Tyr-634 upon EGF stimulation. Some studies suggest that phosphorylation on Tyr-644 enhances binding to tailins (TLN1 and TLN2); others that phosphorylation at Tyr-644 does not directly enhance binding to tailins (TLN1 and TLN2) but may act indirectly by inhibiting phosphorylation at Ser-645. {ECO:0000269|PubMed:12422220, ECO:0000269|PubMed:14691141, ECO:0000269|PubMed:16707488, ECO:0000269|PubMed:17635937, ECO:0000269|PubMed:19153220}.
Sequence Caution Sequence=BAC65601.2; Type=Erroneous initiation; Evidence={ECO:0000305};
Similarity Contains 1 PIPK domain. {ECO:0000255|PROSITE- ProRule:PRU00781}.
Subcellular Location Cell membrane; Peripheral membrane protein; Cytoplasmic side. Endomembrane system. Cytoplasm. Cell junction, focal adhesion. Cell junction, adherens junction. Cell projection, ruffle membrane. Cell projection, phagocytic cup. Cell projection, uropodium. Note=During directional migration isoform 1 localized at the uropodium, and isoform 3 localized all along cell membrane including the uropodium and the leading edge.
Subunit Isoform 1 interacts with TLN1. Interacts with TLN2; interaction stimulates lipid kinase activity. May compete with beta-integrins for the same binding site on TLN1 and TLN2. Interacts with ARF6 (By similarity). Interacts with AP2B1. Isoform 1 interacts with AP2M1; phosphorylation of PIP5K1C by CSK disrupts the interaction; clathrin competes with PIP5K1C. Interacts with CDH1 (By similarity). Interacts with CSK. Interacts with PLCG1; interaction is abolished upon EGF stimulation. {ECO:0000250, ECO:0000269|PubMed:12422220, ECO:0000269|PubMed:14691141, ECO:0000269|PubMed:15623515, ECO:0000269|PubMed:16707488, ECO:0000269|PubMed:17635937, ECO:0000269|PubMed:19287005}.
Tissue Specificity High expression in brain. Also detected in lung, thymus, heart, testicle, kidney and embryo. Highly expressed in forebrain, in particular in cerebellum, hippocampus and cerebral cortex. {ECO:0000269|PubMed:14741049, ECO:0000269|PubMed:20622009, ECO:0000269|PubMed:9535851}.
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