Dual specificity kinase implicated in myriad essential cellular processes such as maintenance of endomembrane homeostasis, and endocytic-vacuolar pathway, lysosomal trafficking, nuclear transport, stress- or hormone-induced signaling and cell cycle progression. The PI(3,5)P2 regulatory complex regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Sole enzyme to catalyze the phosphorylation of phosphatidylinositol 3-phosphate on the fifth hydroxyl of the myo-inositol ring, to form (PtdIns(3,5)P2). Also catalyzes the phosphorylation of phosphatidylinositol on the fifth hydroxyl of the myo-inositol ring, to form phosphatidylinositol 5-phosphate (PtdIns(5)P). Has serine-protein kinase activity and is able to autophosphorylate and transphosphorylate. Autophosphorylation inhibits its own phosphatidylinositol 3-phosphate 5-kinase activity, stimulates FIG4 lipid phosphatase activity and downregulates lipid product formation. Involved in key endosome operations such as fission and fusion in the course of endosomal cargo transport. Required for the maturation of early into late endosomes, phagosomes and lysosomes. Regulates vacuole maturation and nutrient recovery following engulfment of macromolecules, initiates the redistribution of accumulated lysosomal contents back into the endosome network. Critical regulator of the morphology, degradative activity, and protein turnover of the endolysosomal system in macrophages and platelets. In neutrophils, critical to perform chemotaxis, generate ROS, and undertake phagosome fusion with lysosomes. Plays a key role in the processing and presentation of antigens by major histocompatibility complex class II (MHC class II) mediated by CTSS. Regulates melanosome biogenesis by controlling the delivery of proteins from the endosomal compartment to the melanosome. Essential for systemic glucose homeostasis, mediates insulin-induced signals for endosome/actin remodeling in the course of GLUT4 translocation/glucose uptake activation. Supports microtubule-based endosome-to-trans-Golgi network cargo transport, through association with SPAG9 and RABEPK. Mediates EGFR trafficking to the nucleus.; (Microbial infection) Required for cell entry of coronaviruses SARS-CoV and SARS-CoV-2, as well as human coronavirus EMC (HCoV-EMC) by endocytosis.
