SPHK2
SPHK2 (sphingosine kinase 2) is a lipid kinase that catalyses the phosphorylation of sphingosine to form sphingosine-1-phosphate (SPP), a lipid mediator with intracellular and extracellular functions. It is one of two sphingosine kinase isozymes encoded in the human genome. Browse Assay Genie's current range of SPHK2 research reagents below, or read on for the biology behind the target.
SPHK2 catalyses the phosphorylation of sphingosine to sphingosine-1-phosphate (SPP). It also acts on D-erythro-dihydrosphingosine, D-erythro-sphingosine and L-threo-dihydrosphingosine, and binds phosphoinositides. In contrast to the prosurvival enzyme SPHK1, SPHK2 has a positive effect on intracellular ceramide levels, inhibits cell growth and enhances apoptosis. It is also involved in the regulation of glucose and lipid metabolism.
The enzyme acts in several cellular compartments, and its role depends on where the SPP is produced. In mitochondria, SPHK2 is important for cytochrome-c oxidase assembly and mitochondrial respiration: the SPP formed there binds PHB2 and modulates, via PHB2, the assembly of complex IV and respiration. In dopaminergic neurons it promotes mitochondrial function by regulating ATP and ROS levels. In the nucleus, SPHK2 interacts with HDAC1 and HDAC2, and SPP inhibits their enzymatic activity. This prevents removal of acetyl groups from histone lysine residues and raises acetylation of histone H3-K9, histone H4-K5 and histone H2B-K12, linking the enzyme to epigenetic regulation of gene expression. Nuclear SPHK2 may also inhibit DNA synthesis and the cell cycle. In mast cells it is the main regulator of SPP production, which mediates calcium influx, NF-kappa-B activation, cytokine production (including TNF and IL-6) and degranulation.
The human SPHK2 gene belongs to the sphingosine kinase family. SPP mediates processes including migration, proliferation and apoptosis, and has been linked to several cancers through angiogenesis and tumorigenesis. The encoded protein may play a role in breast cancer proliferation and chemoresistance. Alternatively spliced transcript variants encoding multiple isoforms have been observed. The mouse ortholog is Sphk2.
SPHK2 produces SPP, a lipid mediator with intracellular and extracellular functions, and acts alongside SPHK1 with contrasting effects on ceramide and cell survival.
SPP influences migration, proliferation and apoptosis, and SPHK2 may contribute to breast cancer proliferation and chemoresistance.
Nuclear SPHK2 interacts with HDAC1 and HDAC2, and SPP inhibits their activity, increasing histone acetylation at specific lysine residues.
SPHK2 supports complex IV assembly and respiration via PHB2, and regulates SPP-driven cytokine production and degranulation in mast cells.
SPHK2 phosphorylates sphingosine to sphingosine-1-phosphate. Depending on its compartment, it supports mitochondrial respiration, inhibits HDAC1 and HDAC2 in the nucleus, and drives SPP-dependent signalling in mast cells. Unlike SPHK1, it increases ceramide levels, inhibits cell growth and enhances apoptosis.
The HGNC-approved symbol is SPHK2 and the full name is sphingosine kinase 2, with no other aliases or previous symbols listed. NCBI Gene reports that alternatively spliced transcript variants encode multiple isoforms. It is one of two sphingosine kinase isozymes, the other being SPHK1.
The mouse ortholog is Sphk2, so the enzyme can be studied in mouse models; check the datasheet of any product for its validated reactivity. NCBI Gene notes that SPP signalling is implicated in several cancers, and that SPHK2 may play a role in breast cancer proliferation and chemoresistance.
The other sphingosine kinase isozyme and related sphingolipid pathway targets with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q9NRA0; product specifications from Assay Genie datasheets.