PIP5K1C

This locus encodes a type I phosphatidylinositol 4-phosphate 5-kinase. The encoded protein catalyzes phosphorylation of phosphatidylinositol 4-phosphate, producing phosphatidylinositol 4,5-bisphosphate. This enzyme is found at synapses and has been found to play roles in endocytosis and cell migration. Mutations at this locus have been associated with lethal congenital contractural syndrome. Alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Sep 2010]

Phosphatidylinositol-4-Phosphate 5-Kinase Type 1 Gamma

Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns4P/PI4P) to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2/PIP2), a lipid second messenger that regulates several cellular processes such as signal transduction, vesicle trafficking, actin cytoskeleton dynamics, cell adhesion, and cell motility (PubMed:12422219, PubMed:22942276).
PtdIns(4,5)P2 can directly act as a second messenger or can be utilized as a precursor to generate other second messengers: inositol 1,4,5-trisphosphate (IP3), diacylglycerol (DAG) or phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3/PIP3) (Probable). PIP5K1A-mediated phosphorylation of PtdIns4P is the predominant pathway for PtdIns(4,5)P2 synthesis (By similarity).
Together with PIP5K1A, is required for phagocytosis, both enzymes regulating different types of actin remodeling at sequential steps (By similarity).
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 (By similarity).
Controls the plasma membrane pool of PtdIns(4,5)P2 implicated in synaptic vesicle endocytosis and exocytosis (PubMed:12847086).
Plays a role in endocytosis mediated by clathrin and AP-2 (adaptor protein complex 2) (PubMed:12847086).
Required for clathrin-coated pits assembly at the synapse (PubMed:17261850).
Participates in cell junction assembly (PubMed:17261850).
Modulates adherens junctions formation by facilitating CDH1/cadherin trafficking (PubMed:17261850).
Required for focal adhesion dynamics. Modulates the targeting of talins (TLN1 and TLN2) to the plasma membrane and their efficient assembly into focal adhesions (PubMed:12422219).
Regulates the interaction between talins (TLN1 and TLN2) and beta-integrins (PubMed:12422219).
Required for uropodium formation and retraction of the cell rear during directed migration (By similarity).
Has a role in growth factor-stimulated directional cell migration and adhesion (By similarity).
Required for talin assembly into nascent adhesions forming at the leading edge toward the direction of the growth factor (PubMed:17635937).
Negative regulator of T-cell activation and adhesion (By similarity).
Negatively regulates integrin alpha-L/beta-2 (LFA-1) polarization and adhesion induced by T-cell receptor (By similarity).
Together with PIP5K1A has a role during embryogenesis and together with PIP5K1B may have a role immediately after birth (By similarity).

Actin cytoskeleton organizationManual Assertion Based On ExperimentTAS:UniProtKB
Adherens junction assemblyManual Assertion Based On ExperimentTAS:UniProtKB
Cell-cell adhesionManual Assertion Based On ExperimentTAS:UniProtKB
Clathrin-dependent endocytosisManual Assertion Based On ExperimentTAS:UniProtKB
Membrane organizationTAS:Reactome
Neutrophil chemotaxisManual Assertion Based On ExperimentTAS:UniProtKB
PhagocytosisManual Assertion Based On ExperimentTAS:UniProtKB
Phosphatidylinositol biosynthetic processTAS:Reactome
Phosphatidylinositol phosphate biosynthetic processManual Assertion Based On ExperimentIBA:GO_Central
Regulation of phosphatidylinositol 3-kinase signalingTAS:Reactome
Synaptic vesicle endocytosisManual Assertion Based On ExperimentTAS:UniProtKB
Synaptic vesicle exocytosisManual Assertion Based On ExperimentTAS:UniProtKB

Cell membrane
Endomembrane system
Cytoplasm
Cell junction, focal adhesion
Cell junction, adherens junction
Cell projection, ruffle membrane
Cell projection, phagocytic cup
Cell projection, uropodium
Detected in plasma membrane invaginations. Isoform 3 is detected in intracellular vesicle-like structures.
Isoform 2
Cytoplasm
Nucleus

Lethal congenital contracture syndrome 3 (LCCS3):
A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy, and congenital non-progressive joint contractures (arthrogryposis). The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth. LCCS3 patients present at birth with severe multiple joint contractures and severe muscle wasting and atrophy, mainly in the legs. Death occurs minutes to hours after birth due to respiratory insufficiency. The phenotype can be distinguished from that of LCCS1 by the absence of hydrops, fractures and multiple pterygia, and from LCCS2 by the absence of neurogenic bladder defect.

Phosphorylation 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.
Acetylation at Lys-265 and Lys-268 seems to decrease lipid 1-phosphatidylinositol-4-phosphate 5-kinase activity. Deacetylation of these sites by SIRT1 positively regulates the exocytosis of TSH-containing granules from pituitary cells.