SPHK2 phospho T578

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:12954646, PubMed:19168031). 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).

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.

Mainly expressed in adult kidney, liver, and brain (PubMed:10751414). Expressed in cerebral cortex and hippocampus (at protein level) (PubMed:29615132). Isoform 1 is the predominant form expressed in most tissues (PubMed:16103110).

• 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

SK2, SPHK2, Sphingosine kinase 2, SK 2, SPK 2

• swissprot:Q9NRA0

Proteins

Epigenetics

69217Da