SPHK1

The protein encoded by this gene catalyzes the phosphorylation of sphingosine to form sphingosine-1-phosphate (S1P), a lipid mediator with both intra- and extracellular functions. Intracellularly, S1P regulates proliferation and survival, and extracellularly, it is a ligand for cell surface G protein-coupled receptors. This protein, and its product S1P, play a key role in TNF-alpha signaling and the NF-kappa-B activation pathway important in inflammatory, antiapoptotic, and immune processes. Phosphorylation of this protein alters its catalytic activity and promotes its translocation to the plasma membrane. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2017]

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).