Information on EC 2.7.1.107 - diacylglycerol kinase (ATP) and Organism(s) Homo sapiens

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria


The taxonomic range for the selected organisms is: Homo sapiens

EC NUMBER
COMMENTARY hide
2.7.1.107
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RECOMMENDED NAME
GeneOntology No.
diacylglycerol kinase (ATP)
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + 1,2-diacyl-sn-glycerol = ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
conserved residues in the extended cysteine-rich domain CRD are essential for activity. e.g. G236, P244, and P245
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
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-
-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
phosphatidate metabolism, as a signaling molecule
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type I lipoteichoic acid biosynthesis (S. aureus)
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Glycerolipid metabolism
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Glycerophospholipid metabolism
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Metabolic pathways
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Biosynthesis of secondary metabolites
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SYSTEMATIC NAME
IUBMB Comments
ATP:1,2-diacyl-sn-glycerol 3-phosphotransferase
Involved in synthesis of membrane phospholipids and the neutral lipid triacylglycerol. Activity is stimulated by certain phospholipids [4,7]. In plants and animals the product 1,2-diacyl-sn-glycerol 3-phosphate is an important second messenger. cf. EC 2.7.1.174, diacylglycerol kinase (CTP).
CAS REGISTRY NUMBER
COMMENTARY hide
60382-71-0
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
comprehensive analysis on the 1-monoacylglycerol kinase (1-MGK) and 2-monoacylglycerol kinase (2-MGK) activities, EC 2.7.1.94, of ten diacylglyceol kinase (DGK) isozymes, EC 2.7.1.107, from different organisms. Type I (alpha, beta, and gamma), type II (delta, eta, and kappa) and type III (epsilon) DGKs have 7.9-19.2% 2-MGK activity compared to their DGK activities, whereas their 1-MGK activities are below 3.0%. Both the 1-MGK and 2-MGK activities of the type IV DGKs (zeta and iota) are below 1% relative to their DGK activities. Type V DGKtheta has approximately 6% 1-MGK activity and below 2% 2-MGK activity compared to its DGK activity. Purified DGKtheta exhibits the same results, indicating that its 1-MGK activity is intrinsic. DGK isozymes are categorized into three types with respect to their 1-MGK and 2-MGK activities: those having (1) 2-MGK activity relatively stronger than their 1-MGK activity (types I-III), (2) only negligible 1-MGK and 2-MGK activities (type IV), and (3) 1-MGK activity stronger than its 2-MGK activity (type V). The 1-MGK activity of DGKtheta and the 2-MGK activity of DGKalpha are stronger than those of the acylglycerol kinase reported as 1-MGK and 2-MGK to date; comprehensive analysis on the 1-monoacylglycerol kinase (1-MGK) and 2-monoacylglycerol kinase (2-MGK) activities, EC 2.7.1.94, of ten diacylglyceol kinase (DGK) isozymes, EC 2.7.1.107, from different organisms. Type I (alpha, beta, and gamma), type II (delta, eta, and kappa) and type III (epsilon) DGKs have 7.9-19.2% 2-MGK activity compared to their DGK activities, whereas their 1-MGK activities are below 3.0%. Both the 1-MGK and 2-MGK activities of the type IV DGKs (zeta and iota) are below 1% relative to their DGK activities. Type V DGKtheta has approximately 6% 1-MGK activity and below 2% 2-MGK activity compared to its DGK activity. Purified DGKtheta exhibits the same results, indicating that its 1-MGK activity is intrinsic. DGK isozymes are categorized into three types with respect to their 1-MGK and 2-MGK activities: those having (1) 2-MGK activity relatively stronger than their 1-MGK activity (types I-III), (2) only negligible 1-MGK and 2-MGK activities (type IV), and (3) 1-MGK activity stronger than its 2-MGK activity (type V). The 1-MGK activity of DGKtheta and the 2-MGK activity of DGKalpha are stronger than those of the acylglycerol kinase reported as 1-MGK and 2-MGK to date; comprehensive analysis on the 1-monoacylglycerol kinase (1-MGK) and 2-monoacylglycerol kinase (2-MGK) activities, EC 2.7.1.94, of ten diacylglyceol kinase (DGK) isozymes, EC 2.7.1.107, from different organisms. Type I (alpha, beta, and gamma), type II (delta, eta, and kappa) and type III (epsilon) DGKs have 7.9-19.2% 2-MGK activity compared to their DGK activities, whereas their 1-MGK activities are below 3.0%. Both the 1-MGK and 2-MGK activities of the type IV DGKs (zeta and iota) are below 1% relative to their DGK activities. Type V DGKtheta has approximately 6% 1-MGK activity and below 2% 2-MGK activity compared to its DGK activity. Purified DGKtheta exhibits the same results, indicating that its 1-MGK activity is intrinsic. DGK isozymes are categorized into three types with respect to their 1-MGK and 2-MGK activities: those having (1) 2-MGK activity relatively stronger than their 1-MGK activity (types I-III), (2) only negligible 1-MGK and 2-MGK activities (type IV), and (3) 1-MGK activity stronger than its 2-MGK activity (type V). The 1-MGK activity of DGKtheta and the 2-MGK activity of DGKalpha are stronger than those of the acylglycerol kinase reported as 1-MGK and 2-MGK to date; comprehensive analysis on the 1-monoacylglycerol kinase (1-MGK) and 2-monoacylglycerol kinase (2-MGK) activities, EC 2.7.1.94, of ten diacylglyceol kinase (DGK) isozymes, EC 2.7.1.107, from different organisms. Type I (alpha, beta, and gamma), type II (delta, eta, and kappa) and type III (epsilon) DGKs have 7.9-19.2% 2-MGK activity compared to their DGK activities, whereas their 1-MGK activities are below 3.0%. Both the 1-MGK and 2-MGK activities of the type IV DGKs (zeta and iota) are below 1% relative to their DGK activities. Type V DGKtheta has approximately 6% 1-MGK activity and below 2% 2-MGK activity compared to its DGK activity. Purified DGKtheta exhibits the same results, indicating that its 1-MGK activity is intrinsic. DGK isozymes are categorized into three types with respect to their 1-MGK and 2-MGK activities: those having (1) 2-MGK activity relatively stronger than their 1-MGK activity (types I-III), (2) only negligible 1-MGK and 2-MGK activities (type IV), and (3) 1-MGK activity stronger than its 2-MGK activity (type V). The 1-MGK activity of DGKtheta and the 2-MGK activity of DGKalpha are stronger than those of the acylglycerol kinase reported as 1-MGK and 2-MGK to date; comprehensive analysis on the 1-monoacylglycerol kinase (1-MGK) and 2-monoacylglycerol kinase (2-MGK) activities, EC 2.7.1.94, of ten diacylglyceol kinase (DGK) isozymes, EC 2.7.1.107, from different organisms. Type I (alpha, beta, and gamma), type II (delta, eta, and kappa) and type III (epsilon) DGKs have 7.9-19.2% 2-MGK activity compared to their DGK activities, whereas their 1-MGK activities are below 3.0%. Both the 1-MGK and 2-MGK activities of the type IV DGKs (zeta and iota) are below 1% relative to their DGK activities. Type V DGKtheta has approximately 6% 1-MGK activity and below 2% 2-MGK activity compared to its DGK activity. Purified DGKtheta exhibits the same results, indicating that its 1-MGK activity is intrinsic. DGK isozymes are categorized into three types with respect to their 1-MGK and 2-MGK activities: those having (1) 2-MGK activity relatively stronger than their 1-MGK activity (types I-III), (2) only negligible 1-MGK and 2-MGK activities (type IV), and (3) 1-MGK activity stronger than its 2-MGK activity (type V). The 1-MGK activity of DGKtheta and the 2-MGK activity of DGKalpha are stronger than those of the acylglycerol kinase reported as 1-MGK and 2-MGK to date; comprehensive analysis on the 1-monoacylglycerol kinase (1-MGK) and 2-monoacylglycerol kinase (2-MGK) activities, EC 2.7.1.94, of ten diacylglyceol kinase (DGK) isozymes, EC 2.7.1.107, from different organisms. Type I (alpha, beta, and gamma), type II (delta, eta, and kappa) and type III (epsilon) DGKs have 7.9-19.2% 2-MGK activity compared to their DGK activities, whereas their 1-MGK activities are below 3.0%. Both the 1-MGK and 2-MGK activities of the type IV DGKs (zeta and iota) are below 1% relative to their DGK activities. Type V DGKtheta has approximately 6% 1-MGK activity and below 2% 2-MGK activity compared to its DGK activity. Purified DGKtheta exhibits the same results, indicating that its 1-MGK activity is intrinsic. DGK isozymes are categorized into three types with respect to their 1-MGK and 2-MGK activities: those having (1) 2-MGK activity relatively stronger than their 1-MGK activity (types I–III), (2) only negligible 1-MGK and 2-MGK activities (type IV), and (3) 1-MGK activity stronger than its 2-MGK activity (type V). The 1-MGK activity of DGKtheta and the 2-MGK activity of DGKalpha are stronger than those of the acylglycerol kinase reported as 1-MGK and 2-MGK to date; comprehensive analysis on the 1-monoacylglycerol kinase (1-MGK) and 2-monoacylglycerol kinase (2-MGK) activities, EC 2.7.1.94, of ten diacylglyceol kinase (DGK) isozymes, EC 2.7.1.107, from different organisms. Type I (alpha, beta, and gamma), type II (delta, eta, and kappa) and type III (epsilon) DGKs have 7.9-19.2% 2-MGK activity compared to their DGK activities, whereas their 1-MGK activities are below 3.0%. Both the 1-MGK and 2-MGK activities of the type IV DGKs (zeta and iota) are below 1% relative to their DGK activities. Type V DGKtheta has approximately 6% 1-MGK activity and below 2% 2-MGK activity compared to its DGK activity. Purified DGKtheta exhibits the same results, indicating that its 1-MGK activity is intrinsic. DGK isozymes are categorized into three types with respect to their 1-MGK and 2-MGK activities: those having (1) 2-MGK activity relatively stronger than their 1-MGK activity (types I–III), (2) only negligible 1-MGK and 2-MGK activities (type IV), and (3) 1-MGK activity stronger than its 2-MGK activity (type V). The 1-MGK activity of DGKtheta and the 2-MGK activity of DGKalpha are stronger than those of the acylglycerol kinase reported as 1-MGK and 2-MGK to date; comprehensive analysis on the 1-monoacylglycerol kinase (1-MGK) and 2-monoacylglycerol kinase (2-MGK) activities, EC 2.7.1.94, of ten diacylglyceol kinase (DGK) isozymes, EC 2.7.1.107, from different organisms. Type I (alpha, beta, and gamma), type II (delta, eta, and kappa) and type III (epsilon) DGKs have 7.9-19.2% 2-MGK activity compared to their DGK activities, whereas their 1-MGK activities are below 3.0%. Both the 1-MGK and 2-MGK activities of the type IV DGKs (zeta and iota) are below 1% relative to their DGK activities. Type V DGKtheta has approximately 6% 1-MGK activity and below 2% 2-MGK activity compared to its DGK activity. Purified DGKtheta exhibits the same results, indicating that its 1-MGK activity is intrinsic. DGK isozymes are categorized into three types with respect to their 1-MGK and 2-MGK activities: those having (1) 2-MGK activity relatively stronger than their 1-MGK activity (types I–III), (2) only negligible 1-MGK and 2-MGK activities (type IV), and (3) 1-MGK activity stronger than its 2-MGK activity (type V). The 1-MGK activity of DGKtheta and the 2-MGK activity of DGKalpha are stronger than those of the acylglycerol kinase reported as 1-MGK and 2-MGK to date
malfunction
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
ATP + 1,2-diarachidonoyl-sn-glycerol
ADP + 1,2-diarachidonoyl-sn-glycerol 3-phosphate
show the reaction diagram
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-
-
?
ATP + 1,2-dicapryl-sn-glycerol
ADP + 1,2-dicapryl-sn-glycerol 3-phosphate
show the reaction diagram
about 140% of the activity with sn-1,2-dioleoylglycerol
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-
?
ATP + 1,2-dilinoleoyl-sn-glycerol
ADP + 1,2-dilinoleoyl-sn-glycerol
show the reaction diagram
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-
-
?
ATP + 1,2-dioleoyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
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-
-
-
?
ATP + 1,2-dioleoyl-sn-glycerol
ADP + 1,2-dioleoyl-sn-glycerol 3-phosphate
show the reaction diagram
ATP + 1,2-dipalmitoyl-sn-glycerol
ADP + 1,2-dipalmitoyl-sn-glycerol 3-phosphate
show the reaction diagram
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15% of the activity with 1-stearoyl-2-arachidonoyl-sn-glycerol
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?
ATP + 1-arachidoyl-2-arachidonoyl-sn-glycerol
ADP + ?
show the reaction diagram
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isoform DGKepsilon shows about 70% activity with 0.38 mol% 1-arachidoyl-2-arachidonoyl-sn-glycerol compared to 1-stearoyl-2-arachidonoyl-sn-glycerol
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?
ATP + 1-O-hexadecyl-2-oleoyl-sn-glycerol
ADP + 1-O-hexadecyl-2-oleoyl-sn-glycerol 3-phosphate
show the reaction diagram
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45.4% of the activity with 1-stearoyl-2-arachidonoyl-sn-glycerol
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-
?
ATP + 1-O-hexadecyl-2-sn-acetyl glycerol
ADP + 1-O-hexadecyl-2-sn-acetyl glycerol 3-phosphate
show the reaction diagram
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about 12fold the rate of 1-O-hexadecyl-sn-glycerol phosphorylation, isoforms diacylglycerol kinase alpha, beta, gamma, delta1, delta1, zeta, jota, theta
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-
?
ATP + 1-O-hexadecyl-sn-glycerol
ADP + 1-O-hexadecyl-sn-glycerol 3-phosphate
show the reaction diagram
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-
-
-
?
ATP + 1-oleoyl-2-palmitoyl-sn-glycerol
ADP + 1-palmitoyl-2-oleoyl-sn-glycerol 3-phosphate
show the reaction diagram
about 85% of the activity with sn-1,2-dioleoylglycerol, DGKksi
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?
ATP + 1-palmitoyl-2-arachidonoyl-sn-glycerol
ADP + 1-palmitoyl-2-arachidonoyl-sn-glycerol 3-phosphate
show the reaction diagram
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isoform DGKepsilon shows about 90% activity with 0.38 mol% 1-palmitoyl-2-arachidonoyl-sn-glycerol compared to 1-stearoyl-2-arachidonoyl-sn-glycerol
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?
ATP + 1-palmitoyl-2-oleoyl-sn-glycerol
ADP + 1-palmitoyl-2-oleoyl-sn-glycerol 3-phosphate
show the reaction diagram
ATP + 1-stearoyl-2-arachidonoyl-sn-glycerol
ADP + 1-stearoyl-2-arachidonoyl-sn-glycerol 3-phosphate
show the reaction diagram
ATP + 1-stearoyl-2-docosahexaenoyl-sn-glycerol
ADP + 1-stearoyl-2-docosahexaenoyl-sn-glycerol
show the reaction diagram
no substrate for wild-type, but substrate for mutant R457Q
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?
ATP + 1-stearoyl-2-linoleoyl-sn-glycerol
ADP + 1-stearoyl-2-linoleoyl-sn-glycerol 3-phosphate
show the reaction diagram
ATP + 1-stearoyl-2-oleoyl-sn-glycerol
ADP + 1-stearoyl-2-oleoyl-sn-glycerol 3-phosphate
show the reaction diagram
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-
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?
ATP + 2,3-dioleoyl-sn-glycerol
ADP + 2,3-diacyl-sn-glycerol 1-phosphate
show the reaction diagram
ATP + 2-arachidonoyl-sn-glycerol
ADP + 2-arachidonoyl-sn-glycerol 3-phosphate
show the reaction diagram
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isoform DGKepsilon shows substrate specificity for sn-2 arachidonoyl-diacylglycerol
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?
ATP + 2-monooleoyl-rac-glycerol
ADP + 2-monooleoyl-rac-glycerol 3-phosphate
show the reaction diagram
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10.7% of the activity with 1-stearoyl-2-arachidonoyl-sn-glycerol
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?
ATP + sn-1,2-dioleoylglycerol
ADP + sn-1,2-dioleoylglycerol 3-phosphate
show the reaction diagram
ATP + sn-1,3-dioleoylglycerol
ADP + ?
show the reaction diagram
about 10% of the activity with sn-1,2-dioleoylglycerol
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?
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
ATP + 1-stearoyl-2-arachidonoyl-sn-glycerol
ADP + 1-stearoyl-2-arachidonoyl-sn-glycerol 3-phosphate
show the reaction diagram
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since diacylglycerol kinase is an enzyme of the phosphatidylinositol cycle, its natural substrate could be 1-stearoyl-2-arachidonoyl-sn-glycerol, thought to be the main diacylglycerol analog generated from phosphoinositide
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?
additional information
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,2-diarachidonoyl phosphatidic acid
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about 55% relative activity in the presence of 1.5 mol%
1-arachidoyl-2-arachidonoyl phosphatidic acid
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about 70% relative activity in the presence of 1.5 mol%
1-palmitoyl-2-arachidonoyl phosphatidic acid
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about 50% relative activity in the presence of 1.5 mol%
1-stearoyl-2-arachidonoyl phosphatidic acid
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about 48% relative activity in the presence of 1.5 mol%
1-stearoyl-2-oleoyl phosphatidic acid
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about 70% relative activity in the presence of 1.5 mol%
2,3-dioleoylglycerol
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uncompetitive inhibition of isoforms diacylglycerol kinase alpha and zeta, no inhibition of isoform epsilon. Binds to a site on the alpha and zeta isoforms that is exposed as a consequence of the substrate binding to the active site, the chiral specificity of the isoforms thus mimicks the substrate specificity
2-arachidonoyl glycerol
inhibitor for both of the epsilon or the zeta isoforms of diacylglycerol kinase; inhibitor for both of the epsilon or the zeta isoforms of diacylglycerol kinase
2-oleoyl glycerol
inhibits diacylglycerol kinase epsilon less than does 2-arachidonoyl glycerol; shows similar inhibitory potency for diacylglycerol kinase zeta as 2-arachidonoyl glycerol
alpha-thrombin
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apparent binding parameters of diacylglycerol kinase theta increase following alpha-thrombin stimulation
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antineutrophil cytoplasmic antibody
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selective activation of diacylglycerol kinase
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H2O2
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induces the interaction of diacylglycerol kinase gamma with beta2-chimaerin. Simultaneous addition of H2O2 and phorbol myristate acetate synergistically enhances the interaction with concomitant translocation of beta2-chimaerin from cytoplasm to the plasma membrane
octyl glucoside
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enzyme form DGK-I, DGK-II and DGK-III
phorbol ester
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activation of protein kinase C which inhibits diacylglycerol kinase epsilon binding to retinoblastoma protein. Mimicking of protein kinase C phosphorylation of serine residues by S/D mutations but not S/N mutations within the MARCKS phosphorylation site domain also prevents binding to retinoblastoma protein
phorbol myristate acetate
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induces the interaction of diacylglycerol kinase gamma with beta2-chimaerin. Simultaneous addition of H2O2 and phorbol myristate acetate synergistically enhances the interaction with concomitant translocation of beta2-chimaerin from cytoplasm to the plasma membrane
phosphatidic acid
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competitive inhibition
phosphatidylcholine
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enzyme form DGK-I, DGK-II and DGK-III
R59022
R59949
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pre-treatment increases both carbamoylcholine-induced and phytohemagglutinin-induced apoptosis due to an increase in the release of exosomes bearing non-processed pro-apoptotic protein FasL
RhoA
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V14-RhoA, strong binding to the C-terminal catalytic domain, negative regulation
thrombin
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stimulation results in an increase in the apparent KM of DGKtheta at low concentrations of substrate dioleoylglycerol. Increasing the bulk concentration of dioleoylglycerol returns the apparent KM to the basal value
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Triton N-101
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enzyme form DGK-I, DGK-II and DGK-III
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(S)-2-amino-2-((S)-6-octyl-1,2,3,4-tetrahydronaphthalen-2-yl)propan-1-ol
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analogue of FTY720, 0.01 mM increase phosphorylation of 1-O-hexadecyl-sn-2-acetyl glycerol by isoform diacylglycerol kinase alpha about 3.5fold.
cAMP
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stimulates nuclear diacylglycerol kinase catalytic activity
cholesterol
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DGKalpha can be activated in vitro in a Ca2+-independent manner by lipids such cholesterol
deoxycholate
FTY720
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in presence of 0.01 mM FTY720, phosphorylation of 1-O-hexadecyl-sn-2-acetyl glycerol by isoforms diacylglycerol kinase alpha, beta or gamma is 3fold increased
hepatocyte growth factor
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induces diaclyglycerol kinase activity, which is required for cell invasiveness
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P53
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p53 activates DGKalpha in response to DNA damage
phorbol-12-myristate-13-acetate
diacylglycerol kinase zeta activity at the T cell receptor is enhanced by phorbol-12-myristate-13-acetate cotreatment
phosphatidic acid
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more effective activator than phosphatidylserine. Phosphatidic acid decreases the apparent surface KM of DGKtheta for dioleoylglycerol and promotes binding to vesicles in a dose-dependent manner; phosphatidic acid is more effective than phosphatidiylserine. Both decreases the apparent surface KM value for dioleoylglycerol and promote binding to vesicles, but through different mechanisms
phosphatidylcholine
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the enzyme shows optimal activity in presence of phosphatidylserine or deoxycholate. Lower activity in presence of phosphatidylcholine
phosphatidylethanolamine
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DGKalpha can be activated in vitro in a Ca2+-independent manner by lipids such as phosphatidylethanolamine
phosphatidylserine
sphingosine
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in presence of 0.01 mM sphingosine, phosphorylation of 1-O-hexadecyl-sn-2-acetyl glycerol by isoforms diacylglycerol kinase alpha, beta or gamma is 7-9fold increased
additional information
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DGKzeta interacts with and is regulated by the retinoblastoma protein
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.45
1,2-diolein
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pH 7.5, 30°C
0.13 - 1.6
ATP
0.05 - 0.08
diolein
additional information
additional information
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.032 - 2.43
1,2-dioleoyl-sn-glycerol
0.162 - 5.7
1-stearoyl-2-arachidonoyl-sn-glycerol
0.087 - 2.8
1-stearoyl-2-linoleoyl-sn-glycerol
0.53 - 2.35
1-stearoyl-2-oleoyl-sn-glycerol
0.01 - 23
ATP
additional information
additional information
-
turnover numbers of full-length DGKepsilon with a C-terminal His tag, full-length FLAG-DGKepsilon and truncated FLAG-DGKepsilon
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
additional information
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Ki value in mol% for inhibitor 2,3-dioleoylglycerol is 1.7 for isoform alpha, 1.07 for isoform zeta, pH 7.2, 30°C
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
2.207
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enzyme form DGK-II
4.74
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enzyme form DGK-I
6.753
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enzyme form DGK-III
6.913
-
-
additional information
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the enzyme is assayed by using endogenous substrate
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7
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and a second optimum at pH 8
7.2
assay at; assay at; assay at; assay at; assay at; assay at; assay at; assay at
8
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and a second optimum at pH 7
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6 - 9
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about 50% of maximal activity at pH 6.0 and 9.0
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
assay at; assay at; assay at; assay at; assay at; assay at; assay at; assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
DGKeta1 and DGKeta2
Manually annotated by BRENDA team
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enzyme expression remained almost unchanged in granulocytic differentiation pathway; enzyme expression remains almost unchanged in granulocytic differentiation pathway
Manually annotated by BRENDA team
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DGK-IIdelta
Manually annotated by BRENDA team
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level of DGKgamma is rapidly and markedly decreased upon cellular differentiation into macrophages; levels of DGKgamma mRNA/protein is rapidly and markedly decreased upon cellular differentiation into macrophages
Manually annotated by BRENDA team
DGKeta1 and DGKeta2
Manually annotated by BRENDA team
DGKeta1
Manually annotated by BRENDA team
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mammary carcinoma
Manually annotated by BRENDA team
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breast cancer cell
Manually annotated by BRENDA team
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; expression of isoform diacylglycerol kinase alpha in several melanoma cell lines but not in noncancerous melanocytes
Manually annotated by BRENDA team
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diaclyglycerol kinase activity is reduced by oxidative stress in glomerular mesangial cells cultured under high glucose conditions. Antioxidants, including D-alpha-tocopherol and probucol may improve hyperglycemia-induced diacylglycerol-protein kinase C activation by enhancing diacylglycerol kinase activity
Manually annotated by BRENDA team
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activation of the adrenocorticotropin/cAMP signal transduction cascade rapidly increases nuclear diacylglycerol kinase activity and phosphatidic acid production. LXXLL motifs in diacylglycerol kinase theta mediate a direct interaction of nuclear receptor steroidogenic factor 1 with the kinase and may facilitate binding of phosphatidic acid to the receptor
Manually annotated by BRENDA team
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DGKalpha is expressed predominantly in oligodendrocytes
Manually annotated by BRENDA team
DGKeta1
Manually annotated by BRENDA team
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isoenzyme DGK-I, DGK-II and DGK-II
Manually annotated by BRENDA team
DGKeta1
Manually annotated by BRENDA team
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levels of DGKgamma mRNA/protein is rapidly and markedly decreased upon cellular differentiation into macrophages
Manually annotated by BRENDA team
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level of DGKgamma is rapidly and markedly decreased upon cellular differentiation into macrophages
Manually annotated by BRENDA team
DGKbeta
Manually annotated by BRENDA team
additional information
DGKeta1 is ubiquitously distributed in various tissues, DGKeta2 is detected only in testis, kidney and colon
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
-
-
Manually annotated by BRENDA team
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prior to cell attachment, phorbol ester induce translocation of DGKgamma from the cytoplasm to the cell periphery
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Manually annotated by BRENDA team
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trans-Golgi network
Manually annotated by BRENDA team
additional information
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subcellular localization of isozymes, overview, the enzyme must undergo membrane translocation for access of diacylglycerols
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Manually annotated by BRENDA team
PDB
SCOP
CATH
UNIPROT
ORGANISM
Homo sapiens;
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
58000
-
x * 58000, enzyme form DGK-III, SDS-PAGE
75000
-
enzyme form DGK-II, gel filtration
82700
-
x * 82700, DGK-Ialpha, calculation from amino acid sequence
86000
-
gel filtration
89000
-
x * 89000, DGK-Igamma, calculation from amino acid sequence
101400
-
x * 101400, DGK-Vtheta, calculation from amino acid sequence
103900
-
x * 103900, calculation from nucleotide sequence
104000
-
x * 104000, DGK-IVksi, calculation from amino acid sequence
108000
-
x * 108000, enzyme from Hela cells, SDS-PAGE
110000
-
x * 110000, enzyme from cell lines MDA-MB-453 and MCF-7, SDS-PAGE
128000
x * 128000 DGKeta1, calculation from nucleotide sequence
130000
-
x * 130000, DGK-IIdelta, calculation from amino acid sequence
135000
x * 135000, DGKeta2, calculation from nucleotide sequence
152000
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x * 152000, enzyme form DGK-I, SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
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upon stimulation of T lymphocytes, diacylglycerol kinase alpha is phosphorylated at residue Y335 by Src kinase p56lck. Phosphorylation regulates translocation of enzyme to cell membrane
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
42
-
5 min, complete loss of activity of DGK-II and DGK-III, about 10% loss of activity of enzyme form DGK-I
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
activation of tyrosine kinases is required for membrane stabilization of DGKalpha, phosphorylation of DGKalpha at Tyr335 appears to be essential for membrane localization
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
isoenzyme DGK-I and DGK-II, DGK-II only partially purified
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recombinant human His6-tagged DGK isozyme theta from COS-7 cells by nickel affinity chromatography
truncated protein lacking the 40 N-terminal amino acids may be extracted with 1.5 M KCl at neutral pH value, while wild-type protein remains fully membrane bound
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cDNA subcloned into the EcoRI site of the simian virus 40-based expression vector pSRE
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COS-7 cells transfected with DGKksi cDNA express a 117000 Da and a 114000 Da protein. The transfected cells also express increased diacylglycerol kinase activity, which is not altered in the presence of R59949
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COS-7 transfection
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expressed in COS-7 cells and in baculovirus-infected Sf21 insect cells
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expressed in HEK-293, U2OS, MCF-7, Swiss3-T3, MEF, and Phoenix cells
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expression in COS-7 cell
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expression in COS-7 cell and HeLa cell
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expression in COS-7 cell, with FLAG-tag
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expression in COS-7 cells
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expression in COS-7 cells; expression of truncated enzyme forms in COS-7 cells
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expression in IIC9 cells
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expression in lymphocyte
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expression in SF21 cells
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expression of GFP-tagged or FLAG-tagged wild-type and mutant isozymes theta in COS-7 cells
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expression of the isolated catalytic subunit of isozyme alpha shows 60% of maximal wild-type full length enzyme activity
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recombinant expression of human His6-tagged DGK isozyme theta from vector pSF-CMV-NH2-His-EKT3 in COS-7 cells; recombinant expression of human p3×FLAG-CMV-DGK isozyme delta2 in COS-7 cells; recombinant expression of human p3×FLAG-CMV-DGK isozyme epsilon in COS-7 cells; recombinant expression of human p3×FLAG-CMV-DGK isozyme eta1 in COS-7 cells; recombinant expression of human p3×FLAG-CMV-DGK isozyme gamma in COS-7 cells; recombinant expression of human p3×FLAG-CMV-DGK isozyme iota1 in COS-7 cells; recombinant expression of human p3×FLAG-CMV-DGK isozyme kappa in COS-7 cells; recombinant expression of human p3×FLAG-CMV-DGK isozyme zeta1 in COS-7 cells
subcloning into the expression vector pMT-2 and transfection in COS-7 cells results in a 6-7fold increase in diacylglycerol kinase activity
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the DGKbeta gene can generate several enzyme isoforms which can display different expression levels and subcellular localization but similar enzymatic activities in vitro
transfection of HEK-293 cells, COS-7 cells
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
p53-mediated upregulation of DGKalpha mRNA in human-derived cells, (PPAR)-gamma-dependent DGKalpha upregulation in endothelial cells, DMSO-based differentiation of promyelocytic HL-60 cells into a neutrophilic phenotype correlates with increase in the expression of DGKalpha, DGKalpha expression is upregulated in cancer
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C20A
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mutant shows diminished Zn occupancy
C60A
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mutant shows diminished Zn occupancy
E35G
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mutant exhibits greatly reduced polymerization. Samples of the mutant incubated with an excess of zinc are shifted entirely to the insoluble fraction. In absence of zinc, most of the mutant protein sample is monomeric. In the presence of added zinc, the mutant organizes into large sheet structures
F369A/F372A
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significant decrease in diacylglycerol kinase activity. Mutant cells display reduced uptake of transferrin
F369A/F372A/F748A
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significant decrease in diacylglycerol kinase activity. Mutant cells display reduced uptake of transferrin
F748A
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diacylglycerol kinase activity similar to that of wild-type. Mutant cells display reduced uptake of transferrin
G236R
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site-directed mutagenesis, highly reduced activity compared to the wild-type isozyme theta
G392D
activity of the mutant is less than 1% of the wild type enzyme
H16A
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mutant shows diminished Zn occupancy
H38A
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mutant shows diminished Zn occupancy
H3A
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mutant shows diminished Zn occupancy
H3A/C20A/H38A/C60A
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mutant shows a reduced zinc retention of 3%. Construct does not show any increase in turbidity after incubation with 50 microM zinc acetate. In the absence of zinc, short polymers are observed, much like the wild-type protein. When zinc is added, polymers increase in prevalence and length marginally but no large sheet structures are formed in 50 microM zinc. Mutant diminishes the formation of cytoplasmic puncta, shows partially impaired regulation of transport to the plasma membrane, and lacks the ability to inhibit the formation of CopII coated vesicles
L241V
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site-directed mutagenesis, slightly reduced activity compared to the wild-type isozyme theta
L447
residue is required for the cholesterol recognition/interaction amino acid consensus motif, mutation results in a loss of enzymatic activity
L447I
ratio of enzymic activity with substrates 1-stearoyl-2-linoleoyl-sn-glycerol to 1-stearoyl-2-arachidonoyl-sn-glycerol is 0.054
P244A
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site-directed mutagenesis, reduced activity compared to the wild-type isozyme theta
P244L
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site-directed mutagenesis, reduced activity compared to the wild-type isozyme theta
P245L
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site-directed mutagenesis, highly reduced activity compared to the wild-type isozyme theta
P32A
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redcution of both Km and kcat value, while maintianing the ratio kcat/Km constant. Specificity of mutant for substrates with polyunsaturated acyl chains is retained. Mutant has a higher affinity for membranes
R457K
ratio of enzymic activity with substrates 1-stearoyl-2-linoleoyl-sn-glycerol to 1-stearoyl-2-arachidonoyl-sn-glycerol is 0.217
R457Q
mutation results in the loss of the cholesterol recognition/interaction amino acid consensus motif and the loss of a positively charged residue, resulting in a higher enzymatic activity than wild-type. Ratio of enzymic activity with substrates 1-stearoyl-2-linoleoyl-sn-glycerol to 1-stearoyl-2-arachidonoyl-sn-glycerol is 0.099. Mutant gains preference for substrate 1-stearoyl-2-docosahexaenoyl-sn-glycerol
S240T
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site-directed mutagenesis, activity is unaltered compared to the wild-type isozyme theta
S258D/S265D/S270D/S271D
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mutation in diacylglycerol kinase zeta for mimicking of protein kinase C phosphorylation of serine residues within the MARCKS phosphorylation site domain. Mutations do prevent binding to retinoblastoma protein
S258N/S265N/S270N/S271N
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mutation in diacylglycerol kinase zeta for mimicking of protein kinase C phosphorylation of serine residues within the MARCKS phosphorylation site domain. Mutations do not prevent binding to retinoblastoma protein and subsequent stimulation of activity
V52E
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mutant exhibits greatly reduced polymerization, no polymers are visible in zinc-free conditions. After zinc addition, large sheet structures appear
Y335F
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expression of wild-type diacylglycerol kinase alpha markedly reduces ERK phosphorylation, whereas the effect of expressing the nonphosphorylatableY335F mutant is much less pronounced
Y451F
mutation results in a loss of a hydroxyl group and an essential residue of the cholesterol recognition/interaction amino acid consensus motif, leading to a higher activity than the wild-type protein. Ratio of enzymic activity with substrates 1-stearoyl-2-linoleoyl-sn-glycerol to 1-stearoyl-2-arachidonoyl-sn-glycerol is 0.107. Mutant gains preference for substrate 1,2-diarachidonoyl-sn-glycerol, with activities comparable to 1-stearoyl-2-arachidonoyl-sn-glycerol
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine