PI4KB

Phosphatidylinositol 4-kinase beta is an is_associated_with::enzyme that in humans is encoded by the PI4KB 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 beta (PI4KB) is a soluble is_associated_with::protein shuttling between the is_associated_with::cytoplasm and the nucleus, and can be recruited to the membranes of the Golgi system via is_associated_with::protein-protein interactions, e.g. with small GTP binding proteins Arf1 and Rab11, or a Golgi adaptor protein is_associated_with::ACBD3. PI4KB can be phosphorylated by the protein kinase D, which promotes the interaction with is_associated_with::14-3-3 proteins and stabilization of the protein in its active conformation. In is_associated_with::cytoplasm PI4KB regulates the trafficking from the Golgi system to the plasma membrane, nevertheless, its nuclear function remains to be determined.

Clinical significance
A wide range of positive-sense single-stranded is_associated_with::RNA viruses (e.g. is_associated_with::picornaviruses) including many important human is_associated_with::pathogens hijack human PI4KB is_associated_with::kinase to generate specific PI4P-enriched is_associated_with::organelles called membranous webs. These is_associated_with::organelles are then used as specific platforms for the effective is_associated_with::viral replication within the host cell.

Furthermore, PI4KB homologue from the is_associated_with::protozoan is_associated_with::parasite is_associated_with::Plasmodium falciparum has been identified as a target of imidopyrazines, an antimalarial compound class.

Structure
PI4KB is composed of a is_associated_with::proline-rich N-terminal region, a central helical domain, and a is_associated_with::kinase domain located C-terminally. The N-terminal region contains a physiologically important binding site for a Golgi adaptor protein is_associated_with::ACBD3, but is likely disordered and dispensable for the is_associated_with::kinase activity. The central helical domain is responsible for the interaction with a small guanosine triphosphatase Rab11. 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 a cleft between the lobes.