PIP5K1C
Description
The PIP5K1C (phosphatidylinositol-4-phosphate 5-kinase type 1 gamma) is a protein-coding gene located on chromosome 19.
Phosphatidylinositol-4-phosphate 5-kinase type-1 gamma is an enzyme that in humans is encoded by the PIP5K1C gene. This gene encodes a member of the type I phosphatidylinositol-4-phosphate 5-kinase family of enzymes. A similar protein in mice is found in synapses and focal adhesion plaques, and binds the FERM domain of talin through its C-terminus.
PIP5K1C catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns(4)P/PI4P) to produce phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2/PIP2), a crucial lipid second messenger involved in regulating various cellular processes, including signal transduction, vesicle trafficking, actin cytoskeleton dynamics, cell adhesion, and cell motility. PIP2 can directly act as a second messenger or serve as a precursor for generating other second messengers like inositol 1,4,5-trisphosphate (IP3), diacylglycerol (DAG), or phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3/PIP3). The phosphorylation of PtdIns(4)P by PIP5K1A is the primary pathway for PIP2 synthesis. Working together with PIP5K1A, PIP5K1C is essential for phagocytosis, with each enzyme regulating different actin remodeling steps sequentially. It promotes particle attachment by creating a pool of PIP2 that triggers controlled actin depolymerization, facilitating Fc-gamma-R clustering. PIP5K1C mediates RAC1-dependent reorganization of actin filaments. Additionally, it is required for synaptic vesicle transport and regulates the plasma membrane pool of PIP2 involved in synaptic vesicle endocytosis and exocytosis. It participates in endocytosis mediated by clathrin and AP-2 (adaptor protein complex 2) and is crucial for clathrin-coated pits assembly at the synapse. PIP5K1C plays a role in cell junction assembly, modulating adherens junctions formation by facilitating CDH1/cadherin trafficking. It is essential for focal adhesion dynamics, regulating the targeting of talins (TLN1 and TLN2) to the plasma membrane and their assembly into focal adhesions. It also regulates the interaction between talins (TLN1 and TLN2) and beta-integrins. PIP5K1C is required for uropodium formation and retraction of the cell rear during directed migration, contributing to growth factor-stimulated directional cell migration and adhesion. It facilitates talin assembly into nascent adhesions at the leading edge toward the direction of the growth factor. PIP5K1C is a negative regulator of T-cell activation and adhesion, negatively regulating integrin alpha-L/beta-2 (LFA-1) polarization and adhesion induced by the T-cell receptor. Together with PIP5K1A, it has a role during embryogenesis, and with PIP5K1B, it might play a role immediately after birth. PIP5K1C interacts with TLN1, TLN2, ARF6, AP2B1, AP2M1, CDH1, CSK, and PLCG1. Its interaction with TLN2 stimulates 1-phosphatidylinositol-4-phosphate 5-kinase activity. It may compete with beta-integrins for the same binding site on TLN1 and TLN2. Its interaction with ARF6 also stimulates 1-phosphatidylinositol-4-phosphate 5-kinase activity. It interacts with AP2B1 and AP2M1, and phosphorylation of PIP5K1C by CSK disrupts the interaction, with clathrin competing with PIP5K1C. It also interacts with CDH1 and CSK, and its interaction with PLCG1 is abolished upon EGF stimulation. PIP5K1C interacts with LAPTM4B, promoting SNX5 association with LAPTM4B. Its kinase activity is required for this interaction, which is regulated by phosphatidylinositol 4,5-bisphosphate generated by PIP5K1C. {ECO:0000250|UniProtKB:O70161, ECO:0000250|UniProtKB:P70182, ECO:0000269|PubMed:12422219, ECO:0000269|PubMed:12847086, ECO:0000269|PubMed:17261850, ECO:0000269|PubMed:17635937, ECO:0000269|PubMed:22942276, ECO:0000305|PubMed:19889969}
PIP5K1C is also known as LCCS3, PIP5K-GAMMA, PIP5K1-gamma, PIP5Kgamma.
