Function
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:8955136, PubMed:21477596, 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) (PubMed:19158393, PubMed:20660631).
PIP5K1A-mediated phosphorylation of PtdIns4P is the predominant pathway for PtdIns(4,5)P2 synthesis (By similarity).
Can also use phosphatidylinositol (PtdIns) as substrate in vitro (PubMed:22942276).
Together with PIP5K1C, is required for phagocytosis, both enzymes regulating different types of actin remodeling at sequential steps (By similarity).
Promotes particle ingestion by activating the WAS GTPase-binding protein that induces Arp2/3 dependent actin polymerization at the nascent phagocytic cup (By similarity).
Together with PIP5K1B, is required, after stimulation by G-protein coupled receptors, for the synthesis of IP3 that will induce stable platelet adhesion (By similarity).
Recruited to the plasma membrane by the E-cadherin/beta-catenin complex where it provides the substrate PtdIns(4,5)P2 for the production of PtdIns(3,4,5)P3, IP3 and DAG, that will mobilize internal calcium and drive keratinocyte differentiation (PubMed:19158393).
Positively regulates insulin-induced translocation of SLC2A4 to the cell membrane in adipocytes (By similarity).
Together with PIP5K1C has a role during embryogenesis (By similarity).
Independently of its catalytic activity, is required for membrane ruffling formation, actin organization and focal adhesion formation during directional cell migration by controlling integrin-induced translocation of the small GTPase RAC1 to the plasma membrane (PubMed:20660631).
Also functions in the nucleus where it acts as an activator of TUT1 adenylyltransferase activity in nuclear speckles, thereby regulating mRNA polyadenylation of a select set of mRNAs (PubMed:18288197).
Biological Process
Actin cytoskeleton reorganizationManual Assertion Based On ExperimentIMP:UniProtKB
Activation of GTPase activityManual Assertion Based On ExperimentIMP:UniProtKB
Cell chemotaxisManual Assertion Based On ExperimentIMP:UniProtKB
Cell migration1 PublicationNAS:UniProtKB
Fibroblast migrationIEA:Ensembl
Focal adhesion assemblyManual Assertion Based On ExperimentIMP:UniProtKB
Glycerophospholipid metabolic processManual Assertion Based On ExperimentTAS:ProtInc
Keratinocyte differentiationManual 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
Phospholipid biosynthetic processManual Assertion Based On ExperimentIDA:UniProtKB
Protein localization to plasma membraneManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of phosphatidylinositol 3-kinase signalingTAS:Reactome
Ruffle assemblyManual Assertion Based On ExperimentIMP:UniProtKB
Signal transductionManual Assertion Based On ExperimentTAS:ProtInc
Cellular Location
Cell membrane
Cytoplasm
Nucleus
Nucleus speckle
Cell projection, ruffle
Cell projection, lamellipodium
Colocalizes with RAC1 at actin-rich membrane ruffles (PubMed:20660631).
Localizes to nuclear speckles and associates with TUT1 to regulate polyadenylation of selected mRNAs (PubMed:18288197).