Mouse Anti-SPHK2 Recombinant Antibody (CBT3925) (V2LY-0625-LY319)

Sphingosine Kinase 2

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-dihydrosphingosine, D-erythro-sphingosine and L-threo-dihydrosphingosine. Binds phosphoinositides (PubMed:19168031, PubMed:12954646).
In contrast to prosurvival SPHK1, has a positive effect on intracellular ceramide levels, inhibits cells growth and enhances apoptosis (PubMed:16118219).
In mitochondria, is important for cytochrome-c oxidase assembly and mitochondrial respiration. The SPP produced in mitochondria binds PHB2 and modulates the regulation via PHB2 of complex IV assembly and respiration (PubMed:20959514).
In nucleus, plays a role in epigenetic regulation of gene expression. Interacts with HDAC1 and HDAC2 and, through SPP production, inhibits their enzymatic activity, preventing the removal of acetyl groups from lysine residues with histones. Up-regulates acetylation of histone H3-K9, histone H4-K5 and histone H2B-K12 (PubMed:19729656).
In nucleus, may have an inhibitory effect on DNA synthesis and cell cycle (PubMed:12954646, PubMed:16103110).
In mast cells, is the main regulator of SPP production which mediates calcium influx, NF-kappa-B activation, cytokine production, such as TNF and IL6, and degranulation of mast cells (By similarity).
In dopaminergic neurons, is involved in promoting mitochondrial functions regulating ATP and ROS levels (By similarity).
Also involved in the regulation of glucose and lipid metabolism (By similarity).

Biological Process blood vessel developmentIEA:Ensembl
Biological Process brain developmentIEA:Ensembl
Biological Process cell population proliferationIEA:Ensembl
Biological Process cellular response to phorbol 13-acetate 12-myristateManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process epigenetic maintenance of chromatin in transcription-competent conformationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process female pregnancyIEA:Ensembl
Biological Process histone H2A-K5 acetylationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process histone H2B-K12 acetylationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process negative regulation of cell growthISS:UniProtKB
Biological Process negative regulation of histone deacetylase activityManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process negative regulation of histone deacetylationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process phosphorylationManual Assertion Based On ExperimentIBA:GO_Central
Biological Process positive regulation of apoptotic processManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of calcium ion importISS:UniProtKB
Biological Process positive regulation of cell population proliferationIEA:Ensembl
Biological Process positive regulation of ceramide biosynthetic processManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of cytokine production involved in immune responseISS:UniProtKB
Biological Process positive regulation of histone H3-K9 acetylationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of interleukin-13 productionISS:UniProtKB
Biological Process positive regulation of interleukin-6 productionISS:UniProtKB
Biological Process positive regulation of mast cell activation involved in immune responseISS:UniProtKB
Biological Process positive regulation of mast cell degranulationISS:UniProtKB
Biological Process positive regulation of protein kinase C signalingISS:UniProtKB
Biological Process positive regulation of tumor necrosis factor productionISS:UniProtKB
Biological Process regulation of ATP biosynthetic processISS:UniProtKB
Biological Process regulation of cytochrome-c oxidase activityManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process regulation of I-kappaB kinase/NF-kappaB signalingISS:UniProtKB
Biological Process regulation of reactive oxygen species biosynthetic processISS:UniProtKB
Biological Process sphinganine-1-phosphate biosynthetic processManual Assertion Based On ExperimentIDA: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 processISS:UniProtKB

Cytoplasm
Nucleus
Endoplasmic reticulum
Mitochondrion inner membrane
In nucleus, located in nucleosomes where it associates with core histone proteins such as histone 3 (PubMed:19729656).
In brains of patients with Alzheimer's disease, may be preferentially localized in the nucleus. Cytosolic expression decrease correlates with the density of amyloid deposits (PubMed:29615132).
In apoptotic cells, colocalizes with CASP1 in cell membrane where is cleaved and released from cells in an active form (PubMed:20197547).
Isoform 2
Lysosome membrane

In patients with Alzheimer's disease brains, may be preferentially localized in the nucleus. Cytosolic expression decrease correlates with the density of amyloid deposits.

Phosphorylated by PKD on Ser-419 and Ser-421 upon PMA treatment. Phosphorylation induces export from the nucleus to the cytoplasm (PubMed:17635916).
Phosphorylated by MAPK1 and MAPK2 at Ser-387 and Thr-614, phosphorylation is induced by agonists such as EGF and PMA and increases kinase activity (PubMed:17311928).
Cleaved by CASP1 in apoptotic cells. The truncated form is released from cells.