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Literature summary for 2.7.1.91 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

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

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

Cloned(Commentary)

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

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 [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

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/ Products (Substrates)

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

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

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

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

Source Tissue

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 [micromol/min/mg]

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

Substrates and Products (Substrate)

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

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

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

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