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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | PI4KB , NPIK, PI4K-BETA, PI4K92, PI4KBETA, PI4KIIIBETA, PIK4CB, phosphatidylinositol 4-kinase beta, PI4KIII | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 602758 MGI: 1334433 HomoloGene: 6741 GeneCards: PI4KB | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Phosphatidylinositol 4-kinase beta is an enzyme that in humans is encoded by the PI4KB gene. [5] [6] [7]
This gene encodes a phosphatidylinositol 4-kinase which catalyzes phosphorylation of phosphatidylinositol at the D-4 position, yielding phosphatidylinositol 4-phosphate (PI4P). Besides the fact, that PI4P serves as a precursor for other important phosphoinositides, such as phosphatidylinositol 4,5-bisphosphate, PI4P is an essential molecule in the cellular signaling and trafficking especially in the Golgi apparatus and the trans Golgi network.
Phosphatidylinositol 4-kinases are evolutionary conserved among eukaryotes and include four human isoforms
Phosphatidylinositol 4-kinase beta (PI4KB) is a soluble protein shuttling between the cytoplasm and the nucleus, [8] and can be recruited to the membranes of the Golgi system via protein-protein interactions, e.g. with small GTP binding proteins Arf1 [9] and Rab11, [10] or a Golgi adaptor protein ACBD3. [11] [12] PI4KB can be phosphorylated by the protein kinase D, [13] which promotes the interaction with 14-3-3 proteins and stabilization of the protein in its active conformation. [14] In cytoplasm PI4KB regulates the trafficking from the Golgi system to the plasma membrane, nevertheless, its nuclear function remains to be determined.
A wide range of positive-sense single-stranded RNA viruses (e.g. picornaviruses) including many important human pathogens hijack human PI4KB kinase to generate specific PI4P-enriched organelles called membranous webs. [15] These organelles are then used as specific platforms for the effective viral replication within the host cell.
Furthermore, PI4KB homologue from the protozoan parasite Plasmodium falciparum has been identified as a target of imidopyrazines, an antimalarial compound class. [16]
PI4KB is composed of a proline-rich N-terminal region, a central helical domain, and a kinase domain located C-terminally. The N-terminal region contains a physiologically important binding site for a Golgi adaptor protein ACBD3, but is likely disordered and dispensable for the kinase activity. The central helical domain is responsible for the interaction with a small guanosine triphosphatase Rab11. The kinase domain can be divided into N-terminal and C-terminal lobes with the ATP binding groove and putative phosphatidylinositol binding pocket in a cleft between the lobes. [17] In addition, an ALPS motif has been identified in the extreme C-terminal region of PI4KB, which favors its association with unsaturated or loosely packed membranes regions. [18]
Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membrane can follow this pathway all the way to lysosomes for degradation or can be recycled back to the cell membrane in the endocytic cycle. Molecules are also transported to endosomes from the trans Golgi network and either continue to lysosomes or recycle back to the Golgi apparatus.
Nerve growth factor (NGF) is a neurotrophic factor and neuropeptide primarily involved in the regulation of growth, maintenance, proliferation, and survival of certain target neurons. It is perhaps the prototypical growth factor, in that it was one of the first to be described. Since it was first isolated by Nobel Laureates Rita Levi-Montalcini and Stanley Cohen in 1956, numerous biological processes involving NGF have been identified, two of them being the survival of pancreatic beta cells and the regulation of the immune system.
Phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3), abbreviated PIP3, is the product of the class I phosphoinositide 3-kinases (PI 3-kinases) phosphorylation of phosphatidylinositol (4,5)-bisphosphate (PIP2). It is a phospholipid that resides on the plasma membrane.
Phosphoinositide 3-kinases (PI3Ks), also called phosphatidylinositol 3-kinases, are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer.
The phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha, also called p110α protein, is a class I PI 3-kinase catalytic subunit. The human p110α protein is encoded by the PIK3CA gene.
Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)P2, also known simply as PIP2 or PI(4,5)P2, is a minor phospholipid component of cell membranes. PtdIns(4,5)P2 is enriched at the plasma membrane where it is a substrate for a number of important signaling proteins. PIP2 also forms lipid clusters that sort proteins.
Pleckstrin homology domain or (PHIP) is a protein domain of approximately 120 amino acids that occurs in a wide range of proteins involved in intracellular signaling or as constituents of the cytoskeleton.
Phosphatidylinositol 3-kinase regulatory subunit alpha is an enzyme that in humans is encoded by the PIK3R1 gene.
Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform is an enzyme that in humans is encoded by the PIK3CG gene.
Cux1 is a homeodomain protein that in humans is encoded by the CUX1 gene.
Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta isoform is an enzyme that in humans is encoded by the PIK3CB gene.
Phosphatidylinositol-4-phosphate 3-kinase C2 domain-containing alpha polypeptide is an enzyme that in humans is encoded by the PIK3C2A gene.
Phosphatidylinositol-4-phosphate 3-kinase C2 domain-containing beta polypeptide is an enzyme that in humans is encoded by the PIK3C2B gene.
Phosphatidylinositol 4-kinase alpha is an enzyme that in humans is encoded by the PI4KA gene.
PIKfyve, a FYVE finger-containing phosphoinositide kinase, is an enzyme that in humans is encoded by the PIKFYVE gene.
Collagen type IV alpha-3-binding protein, also known as ceramide transfer protein (CERT) or StAR-related lipid transfer protein 11 (STARD11) is a protein that in humans is encoded by the COL4A3BP gene. The protein contains a pleckstrin homology domain at its amino terminus and a START domain towards the end of the molecule. It is a member of the StarD2 subfamily of START domain proteins.
Phosphatidylinositol 4-kinase 2-alpha is an enzyme that in humans is encoded by the PI4K2A gene.
In the field of biochemistry, PDPK1 refers to the protein 3-phosphoinositide-dependent protein kinase-1, an enzyme which is encoded by the PDPK1 gene in humans. It is implicated in the development and progression of melanomas.
Phosphoinositide 3-kinase regulatory subunit 4, also known as PI3-kinase regulatory subunit 4 or PI3-kinase p150 subunit or phosphoinositide 3-kinase adaptor protein, or VPS15 is an enzyme that in humans is encoded by the PIK3R4 gene.
Rubicon is a protein that in humans is encoded by the RUBCN gene. Rubicon is one of the few known negative regulators of autophagy, a cellular process that degrades unnecessary or damaged cellular components. Rubicon is recruited to its sites of action through interaction with the small GTPase Rab7, and impairs the autophagosome-lysosome fusion step of autophagy through inhibition of PI3KC3-C2.
