PIP4K2A
Description
The PIP4K2A (phosphatidylinositol-5-phosphate 4-kinase type 2 alpha) is a protein-coding gene located on chromosome 10.
Phosphatidylinositol-5-phosphate 4-kinase type-2 alpha is an enzyme that in humans is encoded by the PIP4K2A gene.
== Function == Phosphatidylinositol-4,5-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-4-phosphate on the fifth hydroxyl of the myo-inositol ring to form phosphatidylinositol-4,5-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-4-phosphate 5-kinase family.
== Clinical significance == Through genome wide association studies (GWAS), some of the single nucleotide polymorphisms (SNPs) located in this gene have been noticed to be significantly associated with susceptibility of childhood acute lymphoblastic leukaemia in ethnically diverse populations.
== PIP4K2A Inhibitors == THZ-P1-2 (covalent inhibitor) as well as BAY-091 and BAY-297 (reversible inhibitors) have been reported as potent and selective PIP4K2A inhibitors. BAY-091 fulfills the quality criteria for a 'Donated Chemical Probe' as defined by the Structural Genomics Consortium.
PIP4K2A catalyzes the phosphorylation of phosphatidylinositol 5-phosphate (PtdIns5P) to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). It has both ATP- and GTP-dependent kinase activities. PIP4K2A regulates the levels of PtdIns5P, which increases AKT activity in the cytosol and signals through ING2 in the nucleus. PIP4K2A may regulate the pool of cytosolic PtdIns5P in response to tyrosine phosphorylation activation. It is required for lysosome-peroxisome membrane contacts and intracellular cholesterol transport by modulating peroxisomal PtdIns(4,5)P2 levels. PIP4K2A collaborates with PIP4K2B in mediating autophagy during nutrient stress. It is essential for autophagosome-lysosome fusion and regulates cellular lipid metabolism. PIP4K2A might be involved in thrombopoiesis, megakaryocyte maturation, and size regulation. It negatively regulates insulin signaling through a catalytic-independent mechanism. PIP4Ks interact with PIP5Ks, suppressing PIP5K-mediated PtdIns(4,5)P2 synthesis and insulin-dependent conversion to PtdIns(3,4,5)P3.
PIP4K2A is also known as PI5P4KA, PIP5K2A, PIP5KII-alpha, PIP5KIIA, PIPK.
