Sphingosine kinase 2

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).

Classification

Family (Pfam)

PF00781 DAGK_cat, PF19279 YegS_C

InterPro

ATP-NAD_kinase_N, Diacylglycerol_kinase_cat_dom, Lipid_Phosphate_FormReg, NAD/diacylglycerol_kinase_sf, YegS/DAGK_C

Functional cluster

Eukaryotic Transcription Factors & related

Gene Ontology · 38

• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0005783 endoplasmic reticulum
• GO:0005765 lysosomal membrane
• GO:0016020 membrane
• GO:0005743 mitochondrial inner membrane
• GO:0005739 mitochondrion
• GO:0005654 nucleoplasm
• GO:0000786 nucleosome
• GO:0005634 nucleus
• GO:0005886 plasma membrane
• GO:0005524 ATP binding
• GO:0042393 histone binding
• GO:0001727 lipid kinase activity
• GO:0031267 small GTPase binding
• GO:0008481 sphingosine kinase activity
• GO:0038036 sphingosine-1-phosphate receptor activity
• GO:1904628 cellular response to phorbol 13-acetate 12-myristate
• GO:0007565 female pregnancy
• GO:0035556 intracellular signal transduction
• GO:0030308 negative regulation of cell growth
• GO:0043065 positive regulation of apoptotic process
• GO:2000304 positive regulation of ceramide biosynthetic process
• GO:0002720 positive regulation of cytokine production involved in immune response
• GO:0032736 positive regulation of interleukin-13 production
• GO:0032755 positive regulation of interleukin-6 production
• GO:0033008 positive regulation of mast cell activation involved in immune response
• GO:0043306 positive regulation of mast cell degranulation
• GO:0032760 positive regulation of tumor necrosis factor production
• GO:2001169 regulation of ATP biosynthetic process
• GO:0043122 regulation of canonical NF-kappaB signal transduction
• GO:1904959 regulation of cytochrome-c oxidase activity
• GO:1903426 regulation of reactive oxygen species biosynthetic process
• GO:0006669 sphinganine-1-phosphate biosynthetic process
• GO:0030148 sphingolipid biosynthetic process
• GO:0046512 sphingosine biosynthetic process
• GO:0006670 sphingosine metabolic process
• GO:0045815 transcription initiation-coupled chromatin remodeling

Drugs targeting this protein · 1

• ABC-294640 inhibitor

Related proteins · sequence + function similarity

• Sphingosine kinase 2 0.98
• von Willebrand factor A domain-containing protein 5B2 0.83
• Pleckstrin homology domain-containing family H member 3 0.81
• von Willebrand factor A domain-containing protein 5B2 0.80
• Sharpin 0.80
• Pleckstrin homology domain-containing family H member 3 0.79
• Pleckstrin homology domain-containing family H member 3 0.79
• Docking protein 3 0.79
• Sharpin 0.78
• Ras and Rab interactor 1 0.78
• NADPH oxidase activator 1 0.77
• Structure-specific endonuclease ANKLE1 0.77

Co-cited proteins · studied together in the literature

• Sphingosine kinase 2 4 shared papers
• Ceramide kinase 1 shared papers
• Sphingosine kinase 1 2 shared papers
• Sphingosine kinase 1 1 shared papers
• Caspase-1 1 shared papers
• Elongation factor 1-alpha 1 1 shared papers
• Cytochrome c oxidase subunit 4 isoform 1, mitochondrial 1 shared papers
• Sphingosine kinase 1 1 shared papers
• Paired amphipathic helix protein Sin3a 1 shared papers
• Prohibitin 1 1 shared papers
• Methyl-CpG-binding domain protein 2 1 shared papers
• Prohibitin 1 1 shared papers

Literature · 20 cited papers

• Neuronal sphingosine kinase 2 subcellular localization is altered in Alzheimer's disease brain. Acta Neuropathol. Commun. · 2018
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• Sphingosine-1-phosphate produced by sphingosine kinase 2 in mitochondria interacts with prohibitin 2 to regulate complex IV assembly and respiration. FASEB J. · 2011
• Cleavage of sphingosine kinase 2 by caspase-1 provokes its release from apoptotic cells. Blood · 2010
• Regulation of histone acetylation in the nucleus by sphingosine-1-phosphate. Science · 2009
• A lipid binding domain in sphingosine kinase 2. Biochem. Biophys. Res. Commun. · 2009
• A quantitative atlas of mitotic phosphorylation. Proc. Natl. Acad. Sci. U.S.A. · 2008
• Eukaryotic elongation factor 1A interacts with sphingosine kinase and directly enhances its catalytic activity. J. Biol. Chem. · 2008
• Integral and associated lysosomal membrane proteins. Traffic · 2007
• Protein kinase D-mediated phosphorylation and nuclear export of sphingosine kinase 2. J. Biol. Chem. · 2007
• Sphingosine kinase type 2 activation by ERK-mediated phosphorylation. J. Biol. Chem. · 2007
• … and 8 more in the literature graph