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Literature summary extracted from

  • Baumruker, T.; Bornancin, F.; Billich, A.
    The role of sphingosine and ceramide kinases in inflammatory responses (2005), Immunol. Lett., 96, 175-185.
    View publication on PubMed

Activating Compound

EC Number Activating Compound Comment Organism Structure
2.7.1.91 G-protein-coupled receptor agonists
-
 Homo sapiens
2.7.1.91 growth factors platelet- and nerve-derived growth factors Homo sapiens
2.7.1.91 immunoglobulins E and G
-
 Homo sapiens
2.7.1.91 additional information selective activation mechanism of isozymes, overview, isozyme SPHK2 is activated by high ionic strength Homo sapiens
2.7.1.91 muscarinic acetylcholine agonists
-
 Homo sapiens
2.7.1.91 sphingosine 1-phosphate
-
 Homo sapiens
2.7.1.91 TNF-alpha
-
 Homo sapiens
2.7.1.91 Triton X-100 isozyme SPHK1 Homo sapiens
2.7.1.138 additional information the enzyme is induced by the calcium triggers interleukin-1beta and IgE/Ag due to calcium mobilization Homo sapiens
2.7.1.138 Phorbol esters e.g. PMA Homo sapiens

Application

EC Number Application Comment Organism
2.7.1.91 medicine isozyme SPHK1 is a potential therapeutic target in the treatment of inflammatory and autoimmune diseases Homo sapiens

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.7.1.91 isozymes SPHK1 and SPHK2, DNA and amino acid sequence determination and analysis Homo sapiens
2.7.1.91 overexpression of isozymes SPHK1 and SPHK2 in cytosol of HEK293 cells Mus musculus
2.7.1.138 DNA and amino acid sequence determination, expression in HeLa and COS-1 cells, expression of GFP-tagged enzyme in HUVEC and COS-1 cells Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
2.7.1.138 additional information siRNA to the gene encoding the enzyme for downregulation blocks arachidonic acid release and subsequent prostaglandin E2 production after stimulation Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.7.1.91 additional information isozyme SPHK2 is inhibited by high ionic strength Homo sapiens
2.7.1.91 Triton X-100 isozyme SPHK2 Homo sapiens
2.7.1.138 C2-ceramide
-
 Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.7.1.91 0.0034 0.0138 D-erythro-sphingosine isozyme SPHK2 Homo sapiens
2.7.1.91 0.005 0.0156 D-erythro-sphingosine isozyme SPHK1 Homo sapiens
2.7.1.138 0.032
-
 ATP recombinant enzyme Homo sapiens
2.7.1.138 0.187
-
 ceramide recombinant enzyme Homo sapiens

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
2.7.1.91 membrane subcellular localization depends on the tissue type Mus musculus 16020
-
2.7.1.91 membrane subcellular localization depends on the tissue type Homo sapiens 16020
-
2.7.1.91 nucleus isozyme SPHK2 Mus musculus 5634
-
2.7.1.91 nucleus isozyme SPHK2 Homo sapiens 5634
-
2.7.1.91 soluble subcellular localization depends on the tissue type Mus musculus
-
-
2.7.1.91 soluble subcellular localization depends on the tissue type Homo sapiens
-
-
2.7.1.138 cytosol
-
 Homo sapiens 5829
-
2.7.1.138 Golgi apparatus
-
 Homo sapiens 5794
-
2.7.1.138 membrane bound Homo sapiens 16020
-
2.7.1.138 additional information subcellular localization may be dependent on the cell type Homo sapiens
-
-
2.7.1.138 synaptic vesicle
-
 Homo sapiens 8021
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.7.1.138 Ca2+ activation Homo sapiens
2.7.1.138 Mg2+ activation Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.7.1.91 ATP + D-erythro-sphingosine Homo sapiens major substrate of isozyme SPHK1, also active with isozyme SPHK2 ADP + D-erythro-sphingosine 1-phosphate
-
 ?
2.7.1.91 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
-
 ?
2.7.1.91 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
-
 ?
2.7.1.91 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 ?
-
 ?
2.7.1.91 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 ?
-
 ?
2.7.1.138 ATP + ceramide Homo sapiens
-
 ADP + ceramide 1-phosphate ceramide 1-phosphate is a lipid signalling molecule involved in regulation of many physiological processes related to cell proliferation, apoptosis, and inflammation, most of them in concert with sphingosine 1-phosphate, ceramide 1-phosphate might act via extracellular cell surface receptors or intracellularly as second messenger ?
2.7.1.138 additional information Homo sapiens the enzyme does not play a role in neutrophil priming, the enzyme regulates the activity and translocalization of cytosolic phospholipase isozyme A2alpha, overview, the enzyme is involved in prostaglandin biosynthesis, i.e. intracellular arachidonic acid production, which is blocked by enzyme gene silencing ?
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.7.1.91 Homo sapiens
-
 2 isozymes SPHK1 and SPHK2, several splicing variants exist, overview
-
2.7.1.91 Mus musculus
-
 2 isozymes SPHK1 and SPHK2
-
2.7.1.138 Homo sapiens
-
-
-

Posttranslational Modification

EC Number Posttranslational Modification Comment Organism
2.7.1.91 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
2.7.1.138 lipoprotein the enzyme is myristoylated at the N-terminus within the pleckstrin homology PH domain, required for activity Homo sapiens

Reaction

EC Number Reaction Comment Organism Reaction ID
2.7.1.91 ATP + a sphingoid base = ADP + a sphingoid base 1-phosphate Lys103 is important in catalysis Homo sapiens
a

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.7.1.91 blood isozymes SPHK1 and SPHK2 Mus musculus
-
2.7.1.91 blood platelet secretion of sphinganine 1-phosphate Homo sapiens
-
2.7.1.91 brain isozymes SPHK1 and SPHK2 Mus musculus
-
2.7.1.91 kidney isozymes SPHK1 and SPHK2 Mus musculus
-
2.7.1.91 liver low activity of isozyme SPHK1, high activity of isozyme SPHK2 Mus musculus
-
2.7.1.91 lung high activity, isozymes SPHK1 and SPHK2 Mus musculus
-
2.7.1.91 lymph node isozymes SPHK1 and SPHK2 Mus musculus
-
2.7.1.91 mast cell secretion of sphinganine 1-phosphate Homo sapiens
-
2.7.1.91 monocyte secretion of sphinganine 1-phosphate Homo sapiens
-
2.7.1.91 skeletal muscle low activity, isozymes SPHK1 and SPHK2 Mus musculus
-
2.7.1.91 small intestine low activity, isozymes SPHK1 and SPHK2 Mus musculus
-
2.7.1.91 spleen high activity, isozymes SPHK1 and SPHK2 Mus musculus
-
2.7.1.138 brain
-
 Homo sapiens
-
2.7.1.138 additional information the enzyme is expressed in all or nearly all tissues and cell types Homo sapiens
-

Specific Activity [micromol/min/mg]

EC Number Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
2.7.1.91 additional information
-
-
 Homo sapiens

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.1.91 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
-
 ?
2.7.1.91 ATP + D-erythro-sphingosine
-
 Homo sapiens ADP + D-erythro-sphingosine 1-phosphate
-
 ?
2.7.1.91 ATP + D-erythro-sphingosine major substrate of isozyme SPHK1, also active with isozyme SPHK2 Homo sapiens ADP + D-erythro-sphingosine 1-phosphate
-
 ?
2.7.1.91 ATP + DL-threo-dihydrosphingosine isozyme SPHK2, no activity with isozyme SPHK1 Homo sapiens ADP + DL-threo-dihydrosphingosine 1-phosphate
-
 ?
2.7.1.91 ATP + phytosphingosine isozyme SPHK2, no activity with isozyme SPHK1 Homo sapiens ADP + phytosphingosine 1-phosphate
-
 ?
2.7.1.91 ATP + sphinganine
-
 Mus musculus ADP + sphinganine 1-phosphate
-
 ?
2.7.1.91 ATP + sphinganine
-
 Homo sapiens ADP + sphinganine 1-phosphate
-
 ?
2.7.1.91 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
-
 ?
2.7.1.91 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
-
 ?
2.7.1.91 GTP + sphinganine isozyme SPHK1 Homo sapiens GDP + sphinganine 1-phosphate
-
 ?
2.7.1.91 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 ?
-
 ?
2.7.1.91 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 ?
-
 ?
2.7.1.91 additional information no activity with ceramide Mus musculus ?
-
 ?
2.7.1.91 additional information no activity with ceramide, the 2 isozymes interact with a number of proteins, overview Homo sapiens ?
-
 ?
2.7.1.138 ATP + C16-ceramide lower activity Homo sapiens ADP + C16-ceramide 1-phosphate
-
 ?
2.7.1.138 ATP + C18-ceramide lower activity Homo sapiens ADP + C18-ceramide 1-phosphate
-
 ?
2.7.1.138 ATP + C8-ceramide best substrate Homo sapiens ADP + C8-ceramide 1-phosphate
-
 ?
2.7.1.138 ATP + C8-dihydroceramide high activity Homo sapiens ADP + C8-dihydroceramide 1-phosphate
-
 ?
2.7.1.138 ATP + C8-phytoceramide high activity Homo sapiens ADP + C8-phytoceramide 1-phosphate
-
 ?
2.7.1.138 ATP + ceramide
-
 Homo sapiens ADP + ceramide 1-phosphate ceramide 1-phosphate is a lipid signalling molecule involved in regulation of many physiological processes related to cell proliferation, apoptosis, and inflammation, most of them in concert with sphingosine 1-phosphate, ceramide 1-phosphate might act via extracellular cell surface receptors or intracellularly as second messenger ?
2.7.1.138 ATP + ceramide the enzyme is specific for the cramide backbone, acylation of amino group in position 2 is required Homo sapiens ADP + ceramide 1-phosphate
-
 ?
2.7.1.138 additional information the enzyme does not play a role in neutrophil priming, the enzyme regulates the activity and translocalization of cytosolic phospholipase isozyme A2alpha, overview, the enzyme is involved in prostaglandin biosynthesis, i.e. intracellular arachidonic acid production, which is blocked by enzyme gene silencing Homo sapiens ?
-
 ?
2.7.1.138 additional information no activity with GTP, no activity with sphingosine and sphinganine, and with diacylglycerol Homo sapiens ?
-
 ?

Subunits

EC Number Subunits Comment Organism
2.7.1.91 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
2.7.1.138 More the enzyme possesses an N-terminal pleckstrin homology PH domain, residues 32-121, and a C-terminal region which contains a Ca2+/calmodulin binding domain, residues 378-455, that flanks the catalytic domain, residues 124-433, the enzyme also contains 5 sequences stretches C1-C5 typical for lipid kinases Homo sapiens

Synonyms

EC Number Synonyms Comment Organism
2.7.1.91 More the enzyme belongs to the subfamily of diacylglyceride kinases DAGKs Mus musculus
2.7.1.91 More the enzyme belongs to the subfamily of diacylglyceride kinases DAGKs Homo sapiens
2.7.1.91 sphinganine kinase
-
 Mus musculus
2.7.1.91 sphinganine kinase
-
 Homo sapiens
2.7.1.91 SPHK
-
 Mus musculus
2.7.1.91 SPHK
-
 Homo sapiens
2.7.1.138 CERK
-
 Homo sapiens
2.7.1.138 More the enzyme belongs to the subfamily of diacylglyceride kinases DAGKs Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.7.1.138 6.5
-
 sharp optimum Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
2.7.1.91 ATP
-
 Mus musculus
2.7.1.91 ATP binding site of SPHK1: involves Gly82, nucleotide binding also involved the SGDGX17-21K motif in the C2-region Homo sapiens
2.7.1.91 GTP utilized by isozyme SPHK1 Homo sapiens
2.7.1.138 ATP GGDG motif binding site is located in the C2-subdomain Homo sapiens
2.7.1.138 additional information no activity with GTP Homo sapiens