SPHK2 Protein, Human (Active, sf9, His)

SphK2 is an enzyme that catalyzes the phosphorylation of sphingosine to form sphingosine-1-phosphate (SPP), a lipid mediator with both intracellular and extracellular functions. It also acts on D-erythro-dihydrosphingosine, D-erythro-sphingosine, and L-threo-dihydrosphingosine, and binds phosphoinositides. Unlike the prosurvival SPHK1, SphK2 positively affects intracellular ceramide levels, inhibits cell growth, and enhances apoptosis. In mitochondria, SphK2 is essential for cytochrome-c oxidase assembly and mitochondrial respiration, and the SPP it produces binds PHB2, modulating PHB2's regulation of complex IV assembly and respiration. In the nucleus, SphK2 plays a role in epigenetic regulation of gene expression by interacting with HDAC1 and HDAC2 and inhibiting their enzymatic activity through SPP production, preventing histone deacetylation and upregulating acetylation of histone H3-K9, H4-K5, and H2B-K12. It may also inhibit DNA synthesis and the cell cycle. In mast cells, SphK2 is the primary regulator of SPP production, mediating calcium influx, NF-kappa-B activation, cytokine production (e.g., TNF and IL6), and mast cell degranulation (By similarity). In dopaminergic neurons, SphK2 promotes mitochondrial function by regulating ATP and ROS levels (By similarity). Additionally, it is involved in glucose and lipid metabolism regulation (By similarity).