Protein: Sphingosine kinase 2 (SK 2) (SPK 2) (EC 2.7.1.91) (Q9NRA0)
Organism: Homo sapiens (Human)
Function: 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. In contrast to prosurvival SPHK1, has a positive effect on intracellular ceramide levels, inhibits cells growth and enhances apoptosis. 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. 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. In nucleus, may have an inhibitory effect on DNA synthesis and cell cycle. 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).
Subcellular location: Cytoplasm {ECO:0000269|PubMed:12954646, ECO:0000269|PubMed:16103110, ECO:0000269|PubMed:17635916, ECO:0000269|PubMed:20197547, ECO:0000269|PubMed:29615132}. Nucleus {ECO:0000269|PubMed:12954646, ECO:0000269|PubMed:16103110, ECO:0000269|PubMed:17635916, ECO:0000269|PubMed:19729656, ECO:0000269|PubMed:20197547, ECO:0000269|PubMed:29615132}. Endoplasmic reticulum {ECO:0000250|UniProtKB:Q9JIA7}. Mitochondrion inner membrane {ECO:0000250|UniProtKB:Q9JIA7}. Note=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). {ECO:0000269|PubMed:19729656, ECO:0000269|PubMed:20197547, ECO:0000269|PubMed:29615132}.; SUBCELLULAR LOCATION: [Isoform 2]: Lysosome membrane {ECO:0000269|PubMed:17897319}.
Interaction partners:
- Sphingosine-1-phosphate lyase 1
- Sphingosine-1-phosphate phosphatase 1
- Neutral ceramidase
- Acid ceramidase
- Sphingosine-1-phosphate phosphatase 2
- Alkaline ceramidase 2
- Alkaline ceramidase 1
- Histone H3.3
- Histone H3.3C
- Alkaline ceramidase 3
Sequence:
MNGHLEAEEQQDQRPDQELTGSWGHGPRSTLVRAKAMAPPPPPLAASTPLLHGEFGSYPARGPRFALTLTSQALHIQRLRPKPEARPRGGLVPLAEVSGCCTLRSRSPSDSAAYFCIYTYPRGRRGARRRATRTFRADGAATYEENRAEAQRWATALTCLLRGLPLPGDGEITPDLLPRPPRLLLLVNPFGGRGLAWQWCKNHVLPMISEAGLSFNLIQTERQNHARELVQGLSLSEWDGIVTVSGDGLLHEVLNGLLDRPDWEEAVKMPVGILPCGSGNALAGAVNQHGGFEPALGLDLLLNCSLLLCRGGGHPLDLLSVTLASGSRCFSFLSVAWGFVSDVDIQSERFRALGSARFTLGTVLGLATLHTYRGRLSYLPATVEPASPTPAHSLPRAKSELTLTPDPAPPMAHSPLHRSVSDLPLPLPQPALASPGSPEPLPILSLNGGGPELAGDWGGAGDAPLSPDPLLSSPPGSPKAALHSPVSEGAPVIPPSSGLPLPTPDARVGASTCGPPDHLLPPLGTPLPPDWVTLEGDFVLMLAISPSHLGADLVAAPHARFDDGLVHLCWVRSGISRAALLRLFLAMERGSHFSLGCPQLGYAAARAFRLEPLTPRGVLTVDGEQVEYGPLQAQMHPGIGTLLTGPPGCPGREP