LMPD Database


UniProt Annotations

Entry Information
Gene Namephosphatidylinositol-4-phosphate 5-kinase, type I, gamma
Protein EntryO60331_HUMAN
UniProt IDO60331
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=4; Name=1; Synonyms=PIPKIgamma-90, PIPKIgamma-668, PIPkinIgamma-a, PIPKIgamma_i2; IsoId=O60331-1; Sequence=Displayed; Name=2; Synonyms=variant 700, PIPKIgamma-700, PIPKIgamma_i4; IsoId=O60331-2; Sequence=VSP_042078; Name=3; Synonyms=variant 707, PIPKIgamma-707, PIPKIgamma_i5; IsoId=O60331-3; Sequence=VSP_042080; Name=4; Synonyms=PIPKIgamma-87, PIPKIgamma-640, PIPkinIgamma-b, PIPKIgamma_i1; IsoId=O60331-4; Sequence=VSP_042079;
Catalytic ActivityATP + 1-phosphatidyl-1D-myo-inositol 4- phosphate = ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate.
DiseaseLethal congenital contracture syndrome 3 (LCCS3) [MIM
Enzyme RegulationActivated by interaction with TLN2.
FunctionCatalyzes 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
InteractionP46940:IQGAP1; NbExp=6; IntAct=EBI-8838062, EBI-297509;
PtmAcetylation 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.
PtmPhosphorylation on Ser-650 negatively regulates binding to TLN2 and is strongly stimulated in mitosis. Phosphorylation on Tyr-649 is necessary for targeting to focal adhesions. Phosphorylation on Ser-650 and Tyr-649 are mutually exclusive. Phosphorylated by SYK and CSK (By similarity). Tyrosine phosphorylation is enhanced by PTK2 signaling. Phosphorylated at Tyr-639 upon EGF stimulation. Some studies suggest that phosphorylation on Tyr-649 enhances binding to tailins (TLN1 and TLN2). According to PubMed:15738269 phosphorylation at Tyr-649 does not directly enhance binding to tailins (TLN1 and TLN2) but may act indirectly by inhibiting phosphorylation at Ser-650.
Sequence CautionSequence=BAA25515.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence= ;
SimilarityContains 1 PIPK domain. {ECO
Subcellular LocationCell 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=Detected in plasma membrane invaginations. Isoform 3 is detected in intracellular vesicle-like structures.
Subcellular LocationIsoform 2: Cytoplasm. Nucleus.
SubunitInteracts with TLN1 (By similarity). 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. Interacts with AP2B1. Interacts with AP2M1; phosphorylation of PIP5K1C by CSK disrupts the interaction; clathrin competes with PIP5K1C (By similarity). Interacts with CDH1. Interacts with CSK (By similarity). Interacts with PLCG1; interaction is abolished upon EGF stimulation (By similarity).
Tissue SpecificityIsoform 1 is strongly expressed in brain and also detected in heart and lung. Isoform 2 is strongly expressed in pancreas and liver and in lesser quantities in brain, heart, lung and kidney. Isoform 3 is detected in large amounts in heart and large intestine, is also present in lung, pancreas and thyroid, and to a lesser extent in brain, stomach and kidney.