PI4K2A

Phosphatidylinositol 4-kinase 2-alpha is an is_associated_with::enzyme that in humans is encoded by the PI4K2A is_associated_with::gene.

Classification
This is_associated_with::gene encodes a phosphatidylinositol 4-kinase which catalyzes is_associated_with::phosphorylation of is_associated_with::phosphatidylinositol at the D-4 position, yielding is_associated_with::phosphatidylinositol 4-phosphate (PI4P). Besides the fact, that PI4P serves as a precursor for other important phosphoinositides, such as is_associated_with::phosphatidylinositol 4,5-bisphosphate, PI4P is an essential molecule in the cellular signaling and trafficking especially in the is_associated_with::Golgi apparatus and the trans Golgi network.

Phosphatidylinositol 4-kinases are evolutionary conserved among is_associated_with::eukaryotes and include four human isoforms
 * phosphatidylinositol 4-kinase alpha (PI4KA)
 * phosphatidylinositol 4-kinase beta (PI4KB)
 * phosphatidylinositol 4-kinase 2-alpha (PI4K2A)
 * phosphatidylinositol 4-kinase 2-beta (PI4K2B)

Function
Phosphatidylinositol 4-kinase 2-alpha (PI4K2A) is the most abundant phosphatidylinositol 4-kinase in human cells and is responsible for the synthesis of approximately 50% of the total PI4P within the cell. PI4K2A is associated mainly with the membranes of the trans Golgi network and early and late is_associated_with::endosomes; its membrane association is achieved by a heavy is_associated_with::palmitoylation within a specific is_associated_with::cysteine-rich motif. Besides the synthesis of is_associated_with::phosphatidylinositol 4,5-bisphosphate, PI4K2A is involved in various cell processes including membrane trafficking, regulation of endosomal sorting promoting target protein recruitment to is_associated_with::endosomes or trans Golgi network, or is_associated_with::signal transduction. Particularly, it regulates e.g. targeting of is_associated_with::clathrin adaptor complexes to the is_associated_with::Golgi apparatus, EGFR signaling, or the is_associated_with::Wnt signaling pathway.

Clinical significance
Dysfunction of PI4K2A may contribute to tumour growth, is_associated_with::spastic paraplegia, is_associated_with::Gaucher's disease, or is_associated_with::Alzheimer's disease.

Structure
PI4K2A is composed of a is_associated_with::proline-rich N-terminal region and a is_associated_with::kinase domain located C-terminally. The is_associated_with::proline-rich N-terminal region contains physiologically important binding sites for a is_associated_with::ubiquitin ligase Itch and is_associated_with::clathrin adaptor complex 3, but is likely disordered and dispensable for the kinase activity. The is_associated_with::kinase domain can be divided into N-terminal and C-terminal lobes with the ATP binding groove and putative is_associated_with::phosphatidylinositol binding pocket in between. The C-lobe of the is_associated_with::kinase domain contains an additional lateral hydrophobic pocket with no distinct function assigned yet.