Human Recombinant SPHK1 protein (V2LY-0526-LY6928)

Sphingosine Kinase 1

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 (PubMed:20577214, PubMed:23602659, PubMed:29662056, PubMed:24929359, PubMed:11923095).
In contrast to proapoptotic SPHK2, has a negative effect on intracellular ceramide levels, enhances cell growth and inhibits apoptosis (PubMed:16118219).
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 (PubMed:20577214).
In response to TNF and in parallel to NF-kappa-B activation, negatively regulates RANTES induction through p38 MAPK signaling pathway (PubMed:23935096).
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 (PubMed:28049734, PubMed:24929359).
In Purkinje cells, seems to be also involved in the regulation of autophagosome-lysosome fusion upon VEGFA (PubMed:25417698).
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.

Biological Process blood vessel developmentIEA:Ensembl
Biological Process brain developmentIEA:Ensembl
Biological Process calcium-mediated signalingManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process cell population proliferationIEA:Ensembl
Biological Process cellular response to growth factor stimulusManual Assertion Based On ExperimentIBA:GO_Central
Biological Process cellular response to hydrogen peroxideIEA:Ensembl
Biological Process cellular response to vascular endothelial growth factor stimulusManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process DNA biosynthetic processIEA:Ensembl
Biological Process inflammatory responseIEA:Ensembl
Biological Process intracellular signal transductionManual Assertion Based On ExperimentTAS:UniProtKB
Biological Process negative regulation of apoptotic processManual Assertion Based On ExperimentIDA:MGI
Biological Process negative regulation of ceramide biosynthetic processManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process phosphorylationManual Assertion Based On ExperimentIBA:GO_Central
Biological Process positive regulation of angiogenesisManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of cell growthManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of cell migrationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of fibroblast proliferationManual Assertion Based On ExperimentIDA:MGI
Biological Process positive regulation of interleukin-17 productionISS:UniProtKB
Biological Process positive regulation of mitotic cell cycleManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of mitotic nuclear divisionIEA:Ensembl
Biological Process positive regulation of NF-kappaB transcription factor activityManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of NIK/NF-kappaB signalingManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of p38MAPK cascadeManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of peptidyl-threonine phosphorylationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of protein ubiquitinationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of smooth muscle contractionManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process protein acetylationISS:UniProtKB
Biological Process regulation of endocytosisManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of endosomal vesicle fusionISS:UniProtKB
Biological Process regulation of interleukin-1 beta productionIEA:Ensembl
Biological Process regulation of microglial cell activationISS:UniProtKB
Biological Process regulation of neuroinflammatory responseISS:UniProtKB
Biological Process regulation of phagocytosisISS:UniProtKB
Biological Process regulation of tumor necrosis factor-mediated signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process response to tumor necrosis factorManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process sphingoid catabolic process1 PublicationNAS:UniProtKB
Biological Process sphingolipid biosynthetic processTAS:Reactome
Biological Process sphingolipid metabolic processManual Assertion Based On ExperimentIBA:GO_Central
Biological Process sphingosine biosynthetic processManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process sphingosine metabolic processManual Assertion Based On ExperimentIDA:UniProtKB

Cytoplasm
Nucleus
Cell membrane
Endosome membrane
Membrane, clathrin-coated pit
Synapse
Translocated from the cytoplasm to the plasma membrane in a CIB1-dependent manner (PubMed:19854831).
Binds to membranes containing negatively charged lipids but not neutral lipids (PubMed:24929359).
Recruited to endocytic membranes by sphingosine where promotes membrane fusion (By similarity).