| Primary Identifier | IPR043548 | Type | Family |
| Short Name | PIKfyve |
| description | The PI(3,5)P2 regulatory complex regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). It catalyzes the phosphorylation of phosphatidylinositol 3-phosphate on the fifth hydroxyl of the myo-inositol ring, to form phosphatidylinositol 3,5-bisphosphate. The dynamic interconversion of PI3P and PI(3,5)P2 is regulated by a protein complex which is conserved from yeast to mammals. It includes at least five proteins in yeast, located in the vacuole membrane: the lipid kinase Fab1p, lipid phosphatase Fig4p, the Fab1p activator Vac7p, the Fab1p inhibitor Atg18p, and Vac14p. Homologues of Fab1p, Vac14p and Fig4p are found in all eukaryotes which in mammalian cells, are known as Fab1/PIKfyve/PIP5K3, Fig4/Sac3, and Vac14/ArPIKfyve, located on early and late endosomes. Fab1, Vac14, and Fig4 form a ternary complex where Fab1 lipid kinase and Fig4 lipid phosphatase bind to opposite ends of Vac14. A conformational change of Vac14 allows a quick effect on kinase and phosphatase activities. This complex is required for endocytic-vacuolar pathway and nuclear migration. It plays a role in the biogenesis of endosome carrier vesicles (ECV)/ multivesicular bodies (MVB) transport intermediates from early endosomes in mammals, being essential for nervous tissue function. It has been shown that alterations in this complex leads to reduced intracellular levels of PI(3,5)P2, cytoplasmic vacuolisation and neurodegeneration [, ].This entry represents the 1-phosphatidylinositol-3phosphate-5-kinase (PIKfyve) found in eukaryotes. |
