PIP4K2A

Phosphatidylinositol-5,4-bisphosphate, the precursor to second messengers of the phosphoinositide signal transduction pathways, is thought to be involved in the regulation of secretion, cell proliferation, differentiation, and motility. The protein encoded by this gene is one of a family of enzymes capable of catalyzing the phosphorylation of phosphatidylinositol-5-phosphate on the fourth hydroxyl of the myo-inositol ring to form phosphatidylinositol-5,4-bisphosphate. The amino acid sequence of this enzyme does not show homology to other kinases, but the recombinant protein does exhibit kinase activity. This gene is a member of the phosphatidylinositol-5-phosphate 4-kinase family. [provided by RefSeq, Jul 2008]

Full Name

Phosphatidylinositol-5-Phosphate 4-Kinase Type 2 Alpha

Function

Catalyzes the phosphorylation of phosphatidylinositol 5-phosphate (PtdIns5P) on the fourth hydroxyl of the myo-inositol ring, to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) (PubMed:9367159, PubMed:23326584).
Has both ATP- and GTP-dependent kinase activities (PubMed:26774281).
May exert its function by regulating the levels of PtdIns5P, which functions in the cytosol by increasing AKT activity and in the nucleus signals through ING2 (PubMed:18364242).
May regulate the pool of cytosolic PtdIns5P in response to the activation of tyrosine phosphorylation (By similarity).
Required for lysosome-peroxisome membrane contacts and intracellular cholesterol transport through modulating peroxisomal PtdIns(4,5)P2 level (PubMed:29353240).
In collaboration with PIP4K2B, has a role in mediating autophagy in times of nutrient stress (By similarity).
Required for autophagosome-lysosome fusion and the regulation of cellular lipid metabolism (PubMed:31091439).
May be involved in thrombopoiesis, and the terminal maturation of megakaryocytes and regulation of their size (By similarity).
Negatively regulates insulin signaling through a catalytic-independent mechanism (PubMed:31091439).
PIP4Ks interact with PIP5Ks and suppress PIP5K-mediated PtdIns(4,5)P2 synthesis and insulin-dependent conversion to PtdIns(3,4,5)P3 (PubMed:31091439).

Biological Process

1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate biosynthetic processManual Assertion Based On ExperimentIDA:UniProtKB
Autophagosome-lysosome fusionISS:UniProtKB
Megakaryocyte developmentIEA:Ensembl
Negative regulation of 1-phosphatidylinositol-4-phosphate 5-kinase activityManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of insulin receptor signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Phosphatidylinositol phosphate biosynthetic processManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of autophagosome assemblyManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Regulation of autophagyManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Vesicle-mediated cholesterol transportManual Assertion Based On ExperimentIMP:UniProtKB

Cellular Location

Cell membrane
Nucleus
Lysosome
Cytoplasm
Photoreceptor inner segment
Cell projection, cilium, photoreceptor outer segment
May translocate from the cytosol to the cell membrane upon activation of tyrosine phosphorylation. May translocate from the inner to the outer segments of the rod photoreceptor cells in response to light (By similarity).
Localization to the nucleus is modulated by the interaction with PIP4K2B

PTM

Phosphorylated in tyrosines. Phosphorylation is induced by light and increases kinase activity.