Activating Compound | Comment | Organism | Structure |
---|---|---|---|
G-protein-coupled receptor agonists | - |
Homo sapiens | |
growth factors | platelet- and nerve-derived growth factors | Homo sapiens | |
immunoglobulins E and G | - |
Homo sapiens | |
additional information | selective activation mechanism of isozymes, overview, isozyme SPHK2 is activated by high ionic strength | Homo sapiens | |
muscarinic acetylcholine agonists | - |
Homo sapiens | |
sphingosine 1-phosphate | - |
Homo sapiens | |
TNF-alpha | - |
Homo sapiens | |
Triton X-100 | isozyme SPHK1 | Homo sapiens |
Application | Comment | Organism |
---|---|---|
medicine | isozyme SPHK1 is a potential therapeutic target in the treatment of inflammatory and autoimmune diseases | Homo sapiens |
Cloned (Comment) | Organism |
---|---|
isozymes SPHK1 and SPHK2, DNA and amino acid sequence determination and analysis | Homo sapiens |
overexpression of isozymes SPHK1 and SPHK2 in cytosol of HEK293 cells | Mus musculus |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
additional information | isozyme SPHK2 is inhibited by high ionic strength | Homo sapiens | |
Triton X-100 | isozyme SPHK2 | Homo sapiens |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.0034 | 0.0138 | D-erythro-sphingosine | isozyme SPHK2 | Homo sapiens | |
0.005 | 0.0156 | D-erythro-sphingosine | isozyme SPHK1 | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
membrane | subcellular localization depends on the tissue type | Mus musculus | 16020 | - |
membrane | subcellular localization depends on the tissue type | Homo sapiens | 16020 | - |
nucleus | isozyme SPHK2 | Mus musculus | 5634 | - |
nucleus | isozyme SPHK2 | Homo sapiens | 5634 | - |
soluble | subcellular localization depends on the tissue type | Mus musculus | - |
- |
soluble | subcellular localization depends on the tissue type | Homo sapiens | - |
- |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + D-erythro-sphingosine | Homo sapiens | major substrate of isozyme SPHK1, also active with isozyme SPHK2 | ADP + D-erythro-sphingosine 1-phosphate | - |
? | |
ATP + sphinganine | Homo sapiens | the lipid phosphate acts as a pleiotropic agent in cell signalling pathways, acts often in concert with ceramide 1-phosphate, enzyme is involved in the sphingomyelid pathway, overview | ADP + sphinganine 1-phosphate | - |
? | |
ATP + sphinganine | Mus musculus | the lipid phosphate acts as a pleiotropic agent in cell signalling pathways, enzyme is involved in the sphingomyelid pathway, overview | ADP + sphinganine 1-phosphate | - |
? | |
additional information | Homo sapiens | isozyme SPHK1 is involved in responses to macrophages, the enzyme is involved in mast cell signalling, in neutrophil priming, and in prostaglandin biosynthesis via arachidonic acid production, overview, sphinganine 1-phosphate acts as an extracellular mediator by binding to specific members of the EDG-family of G-protein coupled receptors, and intracellularly as a messenger | ? | - |
? | |
additional information | Mus musculus | sphinganine 1-phosphate acts as an extracellular mediator by binding to specific members of the EDG-family of G-protein coupled receptors, and intracellularly as a messenger | ? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
2 isozymes SPHK1 and SPHK2, several splicing variants exist, overview | - |
Mus musculus | - |
2 isozymes SPHK1 and SPHK2 | - |
Posttranslational Modification | Comment | Organism |
---|---|---|
phosphoprotein | isozyme SPHK1 is phosphorylated at Ser225 by extracellular signal-regulated kinases 1 and 2, i.e. ERK1 and 2, and by cyclin dependent kinase 2, i.e. CDK2, recombinant isozyme SPHK1 in HEK293 cells is phosphorylated by ERK1 after stimulation with TNF-alpha, mechanism, overview, phosphorylation activates the enzyme by up to 14fold | Homo sapiens |
Reaction | Comment | Organism | Reaction ID |
---|---|---|---|
ATP + a sphingoid base = ADP + a sphingoid base 1-phosphate | Lys103 is important in catalysis | Homo sapiens |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
blood | isozymes SPHK1 and SPHK2 | Mus musculus | - |
blood platelet | secretion of sphinganine 1-phosphate | Homo sapiens | - |
brain | isozymes SPHK1 and SPHK2 | Mus musculus | - |
kidney | isozymes SPHK1 and SPHK2 | Mus musculus | - |
liver | low activity of isozyme SPHK1, high activity of isozyme SPHK2 | Mus musculus | - |
lung | high activity, isozymes SPHK1 and SPHK2 | Mus musculus | - |
lymph node | isozymes SPHK1 and SPHK2 | Mus musculus | - |
mast cell | secretion of sphinganine 1-phosphate | Homo sapiens | - |
monocyte | secretion of sphinganine 1-phosphate | Homo sapiens | - |
skeletal muscle | low activity, isozymes SPHK1 and SPHK2 | Mus musculus | - |
small intestine | low activity, isozymes SPHK1 and SPHK2 | Mus musculus | - |
spleen | high activity, isozymes SPHK1 and SPHK2 | Mus musculus | - |
Specific Activity Minimum [µmol/min/mg] | Specific Activity Maximum [µmol/min/mg] | Comment | Organism |
---|---|---|---|
additional information | - |
- |
Homo sapiens |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + 1-O-hexadecyl-2-deoxy-2-amino-sn-glycerol | isozyme SPHK2, 10fold lower activity with isozyme SPHK1 | Homo sapiens | ADP + 1-O-hexadecyl-2-deoxy-2-amino-sn-glycerol 3-phosphate | - |
? | |
ATP + D-erythro-sphingosine | - |
Homo sapiens | ADP + D-erythro-sphingosine 1-phosphate | - |
? | |
ATP + D-erythro-sphingosine | major substrate of isozyme SPHK1, also active with isozyme SPHK2 | Homo sapiens | ADP + D-erythro-sphingosine 1-phosphate | - |
? | |
ATP + DL-threo-dihydrosphingosine | isozyme SPHK2, no activity with isozyme SPHK1 | Homo sapiens | ADP + DL-threo-dihydrosphingosine 1-phosphate | - |
? | |
ATP + phytosphingosine | isozyme SPHK2, no activity with isozyme SPHK1 | Homo sapiens | ADP + phytosphingosine 1-phosphate | - |
? | |
ATP + sphinganine | - |
Mus musculus | ADP + sphinganine 1-phosphate | - |
? | |
ATP + sphinganine | - |
Homo sapiens | ADP + sphinganine 1-phosphate | - |
? | |
ATP + sphinganine | the lipid phosphate acts as a pleiotropic agent in cell signalling pathways, acts often in concert with ceramide 1-phosphate, enzyme is involved in the sphingomyelid pathway, overview | Homo sapiens | ADP + sphinganine 1-phosphate | - |
? | |
ATP + sphinganine | the lipid phosphate acts as a pleiotropic agent in cell signalling pathways, enzyme is involved in the sphingomyelid pathway, overview | Mus musculus | ADP + sphinganine 1-phosphate | - |
? | |
GTP + sphinganine | isozyme SPHK1 | Homo sapiens | GDP + sphinganine 1-phosphate | - |
? | |
additional information | isozyme SPHK1 is involved in responses to macrophages, the enzyme is involved in mast cell signalling, in neutrophil priming, and in prostaglandin biosynthesis via arachidonic acid production, overview, sphinganine 1-phosphate acts as an extracellular mediator by binding to specific members of the EDG-family of G-protein coupled receptors, and intracellularly as a messenger | Homo sapiens | ? | - |
? | |
additional information | sphinganine 1-phosphate acts as an extracellular mediator by binding to specific members of the EDG-family of G-protein coupled receptors, and intracellularly as a messenger | Mus musculus | ? | - |
? | |
additional information | no activity with ceramide | Mus musculus | ? | - |
? | |
additional information | no activity with ceramide, the 2 isozymes interact with a number of proteins, overview | Homo sapiens | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
More | structure analysis of the 2 isozymes, schematic map, the enzyme contains 5 sequences stretches C1-C5 typical for lipid kinases, but the enzyme does not contain distinct domains for catalysis or substrate binding, overview | Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
More | the enzyme belongs to the subfamily of diacylglyceride kinases DAGKs | Mus musculus |
More | the enzyme belongs to the subfamily of diacylglyceride kinases DAGKs | Homo sapiens |
sphinganine kinase | - |
Mus musculus |
sphinganine kinase | - |
Homo sapiens |
SPHK | - |
Mus musculus |
SPHK | - |
Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Mus musculus | |
ATP | binding site of SPHK1: involves Gly82, nucleotide binding also involved the SGDGX17-21K motif in the C2-region | Homo sapiens | |
GTP | utilized by isozyme SPHK1 | Homo sapiens |