2.7.1.91: sphingosine kinase
This is an abbreviated version!
For detailed information about sphingosine kinase, go to the full flat file.
Word Map on EC 2.7.1.91
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2.7.1.91
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sphingosine-1-phosphate
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1-phosphate
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sphingolipids
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ceramide
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endothelial
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sirnas
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necrosis
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agonist
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metastasis
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artery
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erk
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phospholipase
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fingolimod
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fibrosis
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lymphocyte
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protein-coupled
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sphingomyelinase
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tnf
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pulmonary
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leukemia
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sphingomyelin
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anti-apoptotic
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s1p-induced
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stat3
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pertussis
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mapks
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pro-apoptotic
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mitogen
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sclerosis
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pkc
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rheostat
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signal-regulated
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caspase-3
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pro-survival
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platelet-derived
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lysophospholipids
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cardioprotective
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phytosphingosine
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drug development
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lymphopenia
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egress
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glucosylceramide
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medicine
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fumonisins
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s1p-mediated
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dihydroceramide
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mitogenesis
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pdgf-induced
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ceramide-induced
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lysophosphatidic
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fcepsilonri
- 2.7.1.91
- sphingosine-1-phosphate
- 1-phosphate
- sphingolipids
- ceramide
- endothelial
- sirnas
- necrosis
- agonist
- metastasis
- artery
- erk
- phospholipase
- fingolimod
- fibrosis
- lymphocyte
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protein-coupled
- sphingomyelinase
- tnf
- pulmonary
- leukemia
- sphingomyelin
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anti-apoptotic
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s1p-induced
- stat3
- pertussis
- mapks
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pro-apoptotic
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mitogen
- sclerosis
- pkc
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rheostat
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signal-regulated
- caspase-3
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pro-survival
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platelet-derived
- lysophospholipids
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cardioprotective
- phytosphingosine
- drug development
- lymphopenia
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egress
- glucosylceramide
- medicine
- fumonisins
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s1p-mediated
- dihydroceramide
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mitogenesis
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pdgf-induced
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ceramide-induced
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lysophosphatidic
- fcepsilonri
Reaction
Synonyms
dihydrosphingosine kinase, kinase, dihydrosphingosine (phosphorylating), kinase, sphingosine (phosphorylating), More, SGK, SK, SK-1, SK-2, SK1, SK2, sphinganine kinase, sphingoid base kinase, sphingosine kinase, sphingosine kinase 1, sphingosine kinase 2, sphingosine kinase type 1, sphingosine kinase type 2, sphingosine kinase-1, sphingosine kinase-2, SPHK, SPHK-1, SPHK1, SPHK1a, SPHK1b, SPHK2, SPK
ECTree
2.7.1.91 sphingosine kinaseAdvanced search results
results (
results (Engineering
Engineering on EC 2.7.1.91 - sphingosine kinase
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PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
D176N
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type
D176N/D178N
site-directed mutagenesis, the mutant shows 90% reduced activity compared to the wild-type
D176N/E180Q
site-directed mutagenesis, the mutant shows 90% reduced activity compared to the wild-type
D81A
site-directed mutagenesis, the mutant shows essentially no activity for phosphoryl transfer and ADP formation
D81N
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
D89A
site-directed mutagenesis, the mutation significantly reduces the preferred binding to plasma over nuclear membrane
E180Q
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type
E182Q
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type
F197A
site-directed mutagenesis, the mutant shows 25% reduced activity compared to the wild-type
F197A/L198Q
site-directed mutagenesis, the mutant shows 25% reduced activity compared to the wild-type
F303H
G111A
site-directed mutagenesis, the mutant is catalytically inactive
G111D
site-directed mutagenesis, the mutant is catalytically inactive
G113A
G113D
site-directed mutagenesis, the mutant is catalytically inactive
G212E
site-directed mutagenesis, the mutant is catalytically inactive
G212E/L218A
site-directed mutagenesis, the mutant is catalytically inactive
G26A
site-directed mutagenesis, the mutant shows unaltered kinetics compared to the wild-type
G26D
site-directed mutagenesis, the mutant is catalytically inactive
G80A
site-directed mutagenesis, the mutant is catalytically inactive
G80D
site-directed mutagenesis, the mutant is catalytically inactive
G82A
site-directed mutagenesis, the mutant shows a 44.7fold increase in Km compared to the wild-type
G82D
H122A
the mutation reduces cleavage by cathepsin B at the mutation site, reduced activity by 60%
K103A
site-directed mutagenesis, the mutant is catalytically inactive
K103R
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type
K27A
site-directed mutagenesis, the mutant shows unaltered kinetics compared to the wild-type
K29A
site-directed mutagenesis, the mutant shows unaltered kinetics compared to the wild-type
L134Q
L147Q
L153Q
L187Q
site-directed mutagenesis, the mutant shows 95% reduced activity compared to the wild-type
L194Q
site-directed mutagenesis, the mutant shows 75% reduced activity compared to the wild-type
L198Q
site-directed mutagenesis, the mutant shows 25% reduced activity compared to the wild-type
L200Q
L218A
site-directed mutagenesis, the mutant shows about 38% of wild-type activity
N121E
the mutation reduces cleavage by cathepsin B at the mutation site, reduced activity by 20%
N89A
site-directed mutagenesis, the mutant loses 50% activity compared to the wild-type, and loses selective binding to vesicles comprised of phosphatidylcholine and phosphatidylserine over those comprised of phosphatidylcholine and phosphatidylglycerol
R185A/R186A
site-directed mutagenesis, the mutant shows 75% reduced activity compared to the wild-type
R56A/R57A/H59A/R61A
the mutations of isoform SphK1 reduce the phorbol 12-myristate 13-acetate- and ceramide 1-phosphate-induced translocation of isoform SphK1 to the plasma membrane, however, the capacity of ceramide 1-phosphate to bind with and activate isoform SphK1 is not affected by the mutations
S168A
site-directed mutagenesis, the mutant maintains the selectivity of selective binding to vesicles comprised of phosphatidylcholine and phosphatidylserine over those comprised of phosphatidylcholine and phosphatidylglycerol, as shown by the wild-type
S225A
S225D
site-directed mutagenesis, mutation of S225 to aspartic and glutamic acids, mimicing serine phosphorylation, does not alter SK1 activity but maintains preferred binding of SK1 to plasma membrane over nuclear membrane
S225E
site-directed mutagenesis, mutation of S225 to aspartic and glutamic acids, mimicing serine phosphorylation, does not alter SK1 activity but maintains preferred binding of SK1 to plasma membrane over nuclear membrane
S351A
site-directed mutagenesis, the mutant shows about 115% of wild-type activity
S401A
site-directed mutagenesis, the mutant shows about 109% of wild-type activity
S430A
site-directed mutagenesis, the mutant shows about 124% of wild-type activity
S441A
site-directed mutagenesis, the mutant shows about 35% of wild-type activity
S79A
site-directed mutagenesis, the mutant shows a 1.5fold increase in Km compared to the wild-type
S79D
site-directed mutagenesis, the mutant is catalytically inactive
T54A
T578A
site-directed mutagenesis, the mutant shows about 56% of wild-type activity
T74A
site-directed mutagenesis, the mutation significantly reduces the preferred binding to plasma over nuclear membrane
V290N
V327A/L328Q
site-directed mutagenesis, the mutant shows about 75% of wild-type activity
S225A
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expression in resistance artery smooth muscle cells reduces resting and myogenic tone, resting Ca2+, pressure-induced Ca2+ elevations, and Ca2+ sensitivity. Lack of function of S225A can only partly be overcome by forced localization to the plasma membrane
D175N/D177N
site-directed mutagenesis, less than 5% of wild-type enzyme activity
D177N
site-directed mutagenesis, less than 10% of wild-type enzyme activity
G213E/L219A
site-directed mutagenesis, the mutant is catalytically inactive
G82D
L219A
site-directed mutagenesis, the mutant shows about 38% of wild-type activity
S225A
the mutation prevents ERK1/2-mediated phosphorylation and membrane localization of SK1
G82D
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dominant-negative mutant, calcium entry to cells is decreased in mutant lines. Exogenous sphingosine 1-phosphate restores calcium entry
H122Y
no detectable difference in activity compared to the wild type enzyme
additional information
F303H
site-directed mutagenesis, the mutant shows 95% reduced activity compared to the wild-type
F303H
site-directed mutagenesis, the mutant shows highly reduced activity compared to the wild-type
G113A
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type
G82D
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dominant-negative SK1 mutant, removes the capacity of Ang-1 to inhibit endothelial cell permeability
G82D
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dominant-negative SK1mutant, displays substantially attenuated 11,12-epoxy-(5Z,8Z,14Z)-eicosatrienoic acid-induced endothelial cell proliferation, migration, and tube formation in vitro and Matrigel plug angiogenesis in vivo
G82D
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over-expression inhibits the TNF-induced vascular cell adhesion molecule VCAM-1 and E selectin and inhibits PMN adhesion
G82D
site-directed mutagenesis, the mutant is catalytically inactive
L134Q
site-directed mutagenesis, the mutant shows highly reduced activity compared to the wild-type
L147Q
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type
L147Q
site-directed mutagenesis, the mutant shows 75% reduced activity compared to the wild-type
L153Q
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type
L153Q
site-directed mutagenesis, the mutant shows 25% reduced activity compared to the wild-type
L200Q
site-directed mutagenesis, the mutant shows 95% reduced activity compared to the wild-type
L200Q
site-directed mutagenesis, the mutant shows highly reduced activity compared to the wild-type
S225A
the mutation prevents ERK1/2-mediated phosphorylation and membrane localization of SK1
S225A
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transfection with S225A, a nonphosphorylatable mutant of SK1, inhibits basal leakiness, and both S225A and a dominant-negative SK1 mutant remove the capacity of Ang-1 to inhibit endothelial cell permeability
S225A
site-directed mutagenesis, the mutation significantly reduces the preferred binding to plasma over nuclear membrane, the mutant shows 39% reduced activity compared to the wild-type
T54A
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type
T54A
site-directed mutagenesis, the mutant loses selective binding to vesicles comprised of phosphatidylcholine and phosphatidylserine over those comprised of phosphatidylcholine and phosphatidylglycerol
T54A
site-directed mutagenesis, the mutant shows 55% reduced activity compared to the wild-type
V290N
site-directed mutagenesis, the mutant shows highly reduced activity compared to the wild-type
G82D
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catalytically inactive. Overexpression in myoblast cells significantly increases cell growth and delays the beginning of myogenesis
additional information
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disruption mutants of genes sgkA and sgkB, single mutants with reduced activity, or double mutants nearly inactive, show increased sensitivity to the anticancer drug cisplatin and altered growth behaviour
additional information
complementation of yeast enzyme-deficient mutant strain by both Sk1 and Sk2
additional information
complementation of yeast enzyme-deficient mutant strain by both Sk1 and Sk2
additional information
complementation of yeast enzyme-deficient mutant strain by both Sk1 and Sk2, a Drosophila melanogaster null Sk2 transposon insertion mutant shows elevated long chain base levels, impaired flight performance, and diminished ovulation, phenotype analysis
additional information
complementation of yeast enzyme-deficient mutant strain by both Sk1 and Sk2, a Drosophila melanogaster null Sk2 transposon insertion mutant shows elevated long chain base levels, impaired flight performance, and diminished ovulation, phenotype analysis
additional information
deletion mutants in highly conserved regions, truncation mutants
additional information
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deletion mutants in highly conserved regions, truncation mutants
additional information
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isoform SphK2 contains a lipid binding domain at the N-terminal residues 1-175, a region of sequence that is absent in Sphk1. Deleting the N-terminal domain reduces Sphk2 membrane localisation in cells
additional information
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deletion of 21 amino acids from the COOH-terminus of isoform SphK1, expression of residues 1-363, results in about 2.2fold increase in catalytic activity relative to wild-type SphK1, which is independent of the phosphorylation state of Serine 225 and stimulation by phorbol-12,13-myristic acid. HEK-293 cells stably expressing the truncated protein exhibit enhanced cell growth under serum-deprived cell culture conditions. A further truncated mutant, residues 1-315, displays about 20% of wild-type activity
additional information
construction of an N- and C-terminally truncated enzyme form comprising residues 9-364 of full-length 368 residues, the mutant is catalytically active
additional information
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construction of an N- and C-terminally truncated enzyme form comprising residues 9-364 of full-length 368 residues, the mutant is catalytically active
additional information
construction of catalytically inactive deletion mutants DELTA1226 and DELTA226-619
additional information
construction of catalytically inactive deletion mutants DELTA1226 and DELTA226-619
additional information
deletion of any one of the conserved domains hSK1DELTA17-36, hSK1DELTA72-96, hSK1DELTA107-119, hSK1DELTA165-198, or hSK1DELTA338-344 results in loss of interaction with calcium-loaded, sepharose-bound calmodulin, presumably due to improper protein folding, and sphingosine kinase activity. Truncation of the C-terminal 41 residues (hSK1DELTA344-384) also results in misfolded, inactive protein. In contrast, deletion of 17 residues (hSK1 DELTA368-384) yields a protein with affinity for calcium-calmodulin with activity equivalent to the wild-type enzyme. Deletion of 21 residues from the C-terminus (hSK1DELTA364-384) results in a protein that is constitutively and 2.2times more active than the wild-type. No significant change enzyme affinity for ATP but a slightly higher Vmax of 1.3fold are observed. Construction of mutations in domain 4 focusing primarily on SPH and calcium-calmodulin/CIB1 interactions
additional information
deletion of any one of the conserved domains hSK1DELTA17-36, hSK1DELTA72-96, hSK1DELTA107-119, hSK1DELTA165-198, or hSK1DELTA338-344 results in loss of interaction with calcium-loaded, sepharose-bound calmodulin, presumably due to improper protein folding, and sphingosine kinase activity. Truncation of the C-terminal 41 residues (hSK1DELTA344-384) also results in misfolded, inactive protein. In contrast, deletion of 17 residues (hSK1 DELTA368-384) yields a protein with affinity for calcium-calmodulin with activity equivalent to the wild-type enzyme. Deletion of 21 residues from the C-terminus (hSK1DELTA364-384) results in a protein that is constitutively and 2.2times more active than the wild-type. No significant change enzyme affinity for ATP but a slightly higher Vmax of 1.3fold are observed. Construction of mutations in domain 4 focusing primarily on SPH and calcium-calmodulin/CIB1 interactions
additional information
enzyme knockdown in HeLa cells using siRNA cell treatment. Enzyme knockdown significantly enhances RANTES induction in response to TNF with no statistically significant effect on unstimulated levels. RANTES induction is highly NF-kappaB-dependent as shown using NF-kappaB inhibitor BAY 11-7082
additional information
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site-directed mutagenesis at Cys-4 and Cys-5 residues results in increased sphingosine kinase activity
additional information
site-directed mutagenesis at Cys-4 and Cys-5 residues results in increased sphingosine kinase activity
additional information
construction of catalytically inactive deletion mutants DELTA1-227 and DELTA227-618
additional information
construction of catalytically inactive deletion mutants DELTA1-227 and DELTA227-618
additional information
generation of enzyme-deficient sphk1-/- mice, platelets from sphk1-/- mice do not show spontaneous or activation-dependent formation of platelet-leukocyte aggregates and a significantly increased activation-dependent ATP release and in vitro thrombus formation compared with the wild-type
additional information
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generation of enzyme-deficient sphk1-/- mice, platelets from sphk1-/- mice do not show spontaneous or activation-dependent formation of platelet-leukocyte aggregates and a significantly increased activation-dependent ATP release and in vitro thrombus formation compared with the wild-type
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additional information
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spontaneous mutants with reduced enzyme activity
