Catalyzes the phosphorylation of sphingosine to form sphingosine 1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions. Also acts on D-erythro-sphingosine and to a lesser extent sphinganine, but not other lipids, such as D,L-threo-dihydrosphingosine, N,N-dimethylsphingosine, diacylglycerol, ceramide, or phosphatidylinositol (  ). In contrast to proapoptotic SPHK2, has a negative effect on intracellular ceramide levels, enhances cell growth and inhibits apoptosis . Involved in the regulation of inflammatory response and neuroinflammation. Via the product sphingosine 1-phosphate, stimulates TRAF2 E3 ubiquitin ligase activity, and promotes activation of NF-kappa-B in response to TNF signaling leading to IL17 secretion . In response to TNF and in parallel to NF-kappa-B activation, negatively regulates RANTES induction through p38 MAPK signaling pathway . Involved in endocytic membrane trafficking induced by sphingosine, recruited to dilate endosomes, also plays a role on later stages of endosomal maturation and membrane fusion independently of its kinase activity (, ). In Purkinje cells, seems to be also involved in the regulation of autophagosome-lysosome fusion upon VEGFA .
Has serine acetyltransferase activity on PTGS2/COX2 in an acetyl-CoA dependent manner. The acetyltransferase activity increases in presence of the kinase substrate, sphingosine. During neuroinflammation, through PTGS2 acetylation, promotes neuronal secretion of specialized preresolving mediators (SPMs), especially 15-R-lipoxin A4, which results in an increase of phagocytic microglia.
Subcellular locations: Cytoplasm, Nucleus, Cell membrane, Endosome membrane, Membrane, Clathrin-coated pit, Synapse
Translocated from the cytoplasm to the plasma membrane in a CIB1-dependent manner . Binds to membranes containing negatively charged lipids but not neutral lipids . Recruited to endocytic membranes by sphingosine where promotes membrane fusion (By similarity).
Widely expressed with highest levels in adult liver, kidney, heart and skeletal muscle. Expressed in brain cortex (at protein level) .