PI4K2A
Description
The PI4K2A (phosphatidylinositol 4-kinase type 2 alpha) is a protein-coding gene located on chromosome 10.
PI4K2A is an enzyme that in humans is encoded by the PI4K2A gene. This gene encodes a phosphatidylinositol 4-kinase, which catalyzes the phosphorylation of phosphatidylinositol at the D-4 position, yielding phosphatidylinositol 4-phosphate (PI4P). PI4P serves as a precursor for other phosphoinositides, such as phosphatidylinositol 4,5-bisphosphate, and is essential for cellular signaling and trafficking, especially within the Golgi apparatus and the trans Golgi network. Phosphatidylinositol 4-kinases are evolutionarily conserved among eukaryotes and include four human isoforms: phosphatidylinositol 4-kinase alpha (PI4KA), phosphatidylinositol 4-kinase beta (PI4KB), phosphatidylinositol 4-kinase 2-alpha (PI4K2A), and phosphatidylinositol 4-kinase 2-beta (PI4K2B). PI4K2A is the most abundant phosphatidylinositol 4-kinase in human cells, responsible for synthesizing approximately 50% of the total PI4P within the cell. It is primarily associated with the membranes of the trans Golgi network, early endosomes, and late endosomes, achieving membrane association through heavy palmitoylation within a specific cysteine-rich motif. Besides the synthesis of phosphatidylinositol 4,5-bisphosphate, PI4K2A plays a role in various cellular processes including membrane trafficking, regulation of endosomal sorting, promoting target protein recruitment to endosomes or the trans Golgi network, and signal transduction. It regulates the targeting of clathrin adaptor complexes to the Golgi apparatus, EGFR signaling, and the Wnt signaling pathway. PI4K2A is crucial for lysosomal quality control. It is the first essential enzyme of the phosphoinositide-initiated membrane tethering and lipid transport (PITT) pathway for rapid lysosomal repair.
PI4K2A is a membrane-bound enzyme that converts phosphatidylinositol (PI) to phosphatidylinositol 4-phosphate (PI4P), a crucial lipid involved in various cellular processes. PI4P plays a vital role in endocytosis, Golgi function, protein sorting, and membrane trafficking. It is essential for the prolonged survival of neurons. Furthermore, the conversion of PI to PI4P is the initial step in the production of phosphatidylinositol 4,5-bisphosphate (PIP2), a precursor of the second messenger inositol 1,4,5-trisphosphate (InsP3).
PI4K2A is also known as NEDMSB, PI4KII, PIK42A.
Associated Diseases
- Neurodevelopmental disorder with hyperkinetic movements, seizures and structural brain abnormalities
