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Information on EC 2.7.1.107 - diacylglycerol kinase (ATP) and Organism(s) Homo sapiens and UniProt Accession P52429

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IUBMB Comments
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).
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Homo sapiens
UNIPROT: P52429
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
dgk, diacylglycerol kinase, dag kinase, dg kinase, dgkzeta, dagk, dgkalpha, dgk-zeta, diglyceride kinase, dgkepsilon, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
DGKepsilon
diacylglycerol kinase epsilon
diacylglycerol kinase-epsilon
-
1,2-diacylglycerol kinase
-
-
-
-
adenosine 5'-triphosphate:1,2-diacylglycerol 3-phosphotransferase
-
-
-
-
arachidonoyl-specific diacylglycerol kinase
-
-
-
-
ATP:diacylglycerol phosphotransferase
-
-
-
-
DAGK
-
-
-
-
DAGKalpha
-
-
-
-
DG kinase
-
-
-
-
DGK-alpha
-
-
-
-
DGK-theta
-
-
-
-
DGKA
isoform
DGKalpha
DGKbeta
DGKdelta
DGKepsilon
-
-
DGKeta
isoform
DGKeta1
isoform
DGKeta2
isoform
DGKeta3
splice variant
DGKeta4
splice variant
DGKgamma
DGKiota
DGKkappa
isoform
DGKksi
-
-
-
-
DGKtheta
isoform
DGKzeta
diacylglycerol kinase
diacylglycerol kinase (ATP dependent)
-
-
-
-
diacylglycerol kinase alpha
diacylglycerol kinase eta
isoform
diacylglycerol kinase zeta
diacylglycerol kinase-zeta
-
diacylglycerol:ATP kinase
-
-
-
-
diglyceride kinase
-
-
-
-
epsilonDGK
-
-
kinase (phosphorylating), 1,2-diacylglycerol
-
-
-
-
kinase, 1,2-diacylglycerol (phosphorylating)
-
-
-
-
sn-1,2-diacylglycerol kinase
-
-
-
-
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
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
-
-
-
-
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
-
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-diarachidonoyl-sn-glycerol
ADP + 1,2-diarachidonoyl-sn-glycerol 3-phosphate
show the reaction diagram
-
-
-
?
ATP + 1,2-dilinoleoyl-sn-glycerol
ADP + 1,2-dilinoleoyl-sn-glycerol
show the reaction diagram
-
-
-
?
ATP + 1,2-dioleoyl-sn-glycerol
ADP + 1,2-dioleoyl-sn-glycerol 3-phosphate
show the reaction diagram
ATP + 1-arachidoyl-2-arachidonoyl-sn-glycerol
ADP + ?
show the reaction diagram
isoform DGKepsilon shows about 70% activity with 0.38 mol% 1-arachidoyl-2-arachidonoyl-sn-glycerol compared to 1-stearoyl-2-arachidonoyl-sn-glycerol
-
-
?
ATP + 1-palmitoyl-2-arachidonoyl-sn-glycerol
ADP + 1-palmitoyl-2-arachidonoyl-sn-glycerol 3-phosphate
show the reaction diagram
isoform DGKepsilon shows about 90% activity with 0.38 mol% 1-palmitoyl-2-arachidonoyl-sn-glycerol compared to 1-stearoyl-2-arachidonoyl-sn-glycerol
-
-
?
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 3-phosphate
show the reaction diagram
no substrate for wild-type, but substrate for mutant R457Q
-
-
?
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
-
-
-
?
ATP + 2-arachidonoyl-sn-glycerol
ADP + 2-arachidonoyl-sn-glycerol 3-phosphate
show the reaction diagram
isoform DGKepsilon shows substrate specificity for sn-2 arachidonoyl-diacylglycerol
-
-
?
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-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
-
-
?
ATP + 1,2-dilauroyl-sn-glycerol
ADP + 1,2-dilauroyl-sn-glycerol 3-phosphate
show the reaction diagram
high activity
-
-
?
ATP + 1,2-dioleolyl-sn-glycerol
ADP + 1,2-dioleolyl-sn-glycerol 3-phosphate
show the reaction diagram
-
-
-
?
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
ATP + 1,2-distearoyl-sn-glycerol
ADP + 1,2-distearoyl-sn-glycerol 3-phosphate
show the reaction diagram
high activity
-
-
?
ATP + 1-O-hexadecyl-2-oleoyl-sn-glycerol
ADP + 1-O-hexadecyl-2-oleoyl-sn-glycerol 3-phosphate
show the reaction diagram
-
45.4% of the activity with 1-stearoyl-2-arachidonoyl-sn-glycerol
-
-
?
ATP + 1-O-hexadecyl-2-sn-acetyl glycerol
ADP + 1-O-hexadecyl-2-sn-acetyl glycerol 3-phosphate
show the reaction diagram
-
about 12fold the rate of 1-O-hexadecyl-sn-glycerol phosphorylation, isoforms diacylglycerol kinase alpha, beta, gamma, delta1, delta1, zeta, jota, theta
-
-
?
ATP + 1-O-hexadecyl-sn-glycerol
ADP + 1-O-hexadecyl-sn-glycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
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
-
-
?
ATP + 1-palmitoyl-2-oleolyl-sn-glycerol
ADP + 1-palmitoyl-2-oleolyl-sn-glycerol 3-phosphate
show the reaction diagram
high activity
-
-
?
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 3-phosphate
show the reaction diagram
high activity
-
-
?
ATP + 1-stearoyl-2-eicosatetraenoyl-sn-glycerol
ADP + 1-stearoyl-2-eicosatetraenoyl-sn-glycerol 3-phosphate
show the reaction diagram
high activity
-
-
?
ATP + 1-stearoyl-2-linoleoyl-sn-glycerol
ADP + 1-stearoyl-2-linoleoyl-sn-glycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 2,3-dioleoyl-sn-glycerol
ADP + 2,3-diacyl-sn-glycerol 1-phosphate
show the reaction diagram
ATP + 2-monooleoyl-rac-glycerol
ADP + 2-monooleoyl-rac-glycerol 3-phosphate
show the reaction diagram
-
10.7% of the activity with 1-stearoyl-2-arachidonoyl-sn-glycerol
-
-
?
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
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL 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-stearoyl-2-arachidonoyl-sn-glycerol
ADP + 1-stearoyl-2-arachidonoyl-sn-glycerol 3-phosphate
show the reaction diagram
specific substrate of isoform DGKepsilon
-
-
?
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
-
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
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,2-diarachidonoyl phosphatidic acid
about 55% relative activity in the presence of 1.5 mol%
1-arachidoyl-2-arachidonoyl phosphatidic acid
about 70% relative activity in the presence of 1.5 mol%
1-palmitoyl-2-arachidonoyl phosphatidic acid
about 50% relative activity in the presence of 1.5 mol%
1-stearoyl-2-arachidonoyl phosphatidic acid
about 48% relative activity in the presence of 1.5 mol%
1-stearoyl-2-oleoyl phosphatidic acid
about 70% relative activity in the presence of 1.5 mol%
2-arachidonoyl glycerol
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
phosphatidic acid
competitive inhibition
phosphatidylinositol-4,5-bisphosphate
noncompetitive inhibitor with respect to 1-stearoyl-2-arachidonoyl-sn-glycerol but a competitive inhibitor with respect to ATP
2,3-dioleoylglycerol
-
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
2-oleoyl glycerol
shows similar inhibitory potency for diacylglycerol kinase zeta as 2-arachidonoyl glycerol
4-[bis(4-fluorophenyl)methylidene]piperidine
-
-
5-[(2E)-3-(2-furyl)prop-2-enylidene]-3-[(phenylsulfonyl)amino]2-thioxo-1,3-thiazolidin-4-one
-
alpha-thrombin
-
apparent binding parameters of diacylglycerol kinase theta increase following alpha-thrombin stimulation
-
antineutrophil cytoplasmic antibody
-
selective activation of diacylglycerol kinase
-
H2O2
-
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
N-[7-[cyclopropyl(hydroxy)methyl]-2,3-dihydro-1,4-benzodioxin-6-yl]cyclopropanecarboxamide
-
octyl glucoside
-
enzyme form DGK-I, DGK-II and DGK-III
phorbol ester
-
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
-
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
phosphatidylcholine
-
enzyme form DGK-I, DGK-II and DGK-III
R59022
R59949
RhoA
-
V14-RhoA, strong binding to the C-terminal catalytic domain, negative regulation
ritanserin
thrombin
-
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
-
Triton N-101
-
enzyme form DGK-I, DGK-II and DGK-III
-
additional information
isoform DGKalpha is not inhibited by ketanserin
-
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
-
analogue of FTY720, 0.01 mM increase phosphorylation of 1-O-hexadecyl-sn-2-acetyl glycerol by isoform diacylglycerol kinase alpha about 3.5fold.
4-(2,4-dimethylphenoxy)-N-hydroxybutanamide
0.1 mM KU-10 activates isoform DGKalpha by about 10%
-
cAMP
-
stimulates nuclear diacylglycerol kinase catalytic activity
cholesterol
DGKalpha can be activated in vitro in a Ca2+-independent manner by lipids such cholesterol
deoxycholate
FTY720
-
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
-
induces diaclyglycerol kinase activity, which is required for cell invasiveness
-
N-[7-[cyclopropyl(hydroxy)methyl]-2,3-dihydro-1,4-benzodioxin-6-yl]cyclopropanecarboxamide
0.1 mM KU-8 activates isoform DGKalpha by 19%
-
P53
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
phosphatidylcholine
-
the enzyme shows optimal activity in presence of phosphatidylserine or deoxycholate. Lower activity in presence of phosphatidylcholine
phosphatidylethanolamine
DGKalpha can be activated in vitro in a Ca2+-independent manner by lipids such as phosphatidylethanolamine
phosphatidylserine
sphingosine
-
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
DGKzeta interacts with and is regulated by the retinoblastoma protein
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.45
1,2-diolein
-
pH 7.5, 30°C
0.05 - 1.6
ATP
0.05 - 0.08
diolein
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.53 - 2.35
1-stearoyl-2-oleoyl-sn-glycerol
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
0.01 - 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
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
additional information
-
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
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.223
4-[bis(4-fluorophenyl)methylidene]piperidine
Homo sapiens
isoform DGKalpha, pH and temperature not specified in the publication
-
0.00034
5-[(2E)-3-(2-furyl)prop-2-enylidene]-3-[(phenylsulfonyl)amino]2-thioxo-1,3-thiazolidin-4-one
Homo sapiens
isoform DGKalpha, at pH 7.4 and 30°C
-
0.025
ritanserin
Homo sapiens
isoform DGKalpha, pH and temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
2.207
-
enzyme form DGK-II
4.74
-
enzyme form DGK-I
6.753
-
enzyme form DGK-III
6.913
-
-
additional information
-
the enzyme is assayed by using endogenous substrate
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7
-
and a second optimum at pH 8
8
-
and a second optimum at pH 7
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6 - 9
-
about 50% of maximal activity at pH 6.0 and 9.0
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
DGKeta1 and DGKeta2
Manually annotated by BRENDA team
-
DGK-IIdelta
Manually annotated by BRENDA team
DGKeta1 and DGKeta2
Manually annotated by BRENDA team
DGKeta1
Manually annotated by BRENDA team
-
mammary carcinoma
Manually annotated by BRENDA team
-
breast cancer cell
Manually annotated by BRENDA team
-
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
-
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
DGKalpha is expressed predominantly in oligodendrocytes
Manually annotated by BRENDA team
DGKeta1
Manually annotated by BRENDA team
-
isoenzyme DGK-I, DGK-II and DGK-II
Manually annotated by BRENDA team
expressed in round spermatids
Manually annotated by BRENDA team
expressed in the secondary spermatocytes
Manually annotated by BRENDA team
DGKeta1
Manually annotated by BRENDA team
-
levels of DGKgamma mRNA/protein is rapidly and markedly decreased upon cellular differentiation into macrophages
Manually annotated by BRENDA team
-
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
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
segment from amino acid residues 18 to 42 forms a bent helix that enters and leaves the same side of the membrane
Manually annotated by BRENDA team
-
prior to cell attachment, phorbol ester induce translocation of DGKgamma from the cytoplasm to the cell periphery
-
Manually annotated by BRENDA team
additional information
-
subcellular localization of isozymes, overview, the enzyme must undergo membrane translocation for access of diacylglycerols
-
Manually annotated by BRENDA team
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
malfunction
metabolism
1-stearoyl-2-arachidonoyl-sn-glycerol phosphorylation to phosphatidic acid catalyzed by isoform DGKepsilon is one of the key steps of the phosphoinositide cycle. Enhanced isoform DGKepsilon activity plays a role in Huntingtons disease pathogenesis
physiological function
enzyme isoforms control cancer cell survival, proliferation, and angiogenesis by regulating Akt/mTOR and MAPK/ERK pathways. In addition, some enzyme isoforms control cancer cell migration by regulating the activities of the Rho GTPases Rac1 and RhoA
evolution
malfunction
physiological function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
DGKE_HUMAN
567
1
63927
Swiss-Prot
Secretory Pathway (Reliability: 5)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
120000
gel filtration
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
-
x * 152000, enzyme form DGK-I, SDS-PAGE
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
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 64000, His6-tagged enzyme lacking the first 40 residues, SDS-PAGE
monomer
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Ca2+-bound EF-hand domain of isoform DGKalpha, sitting drop vapor diffusion method, using 0.1 M HEPES, pH 7.0, 1.0 M succinic acid, and 1% (w/v) PEG monomethyl ether 2000
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
P32A
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
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
C20A
-
mutant shows diminished Zn occupancy
C60A
-
mutant shows diminished Zn occupancy
E134Q
the mutant shows impaired Ca2+ binding
E179Q
the mutant is not able to bind Ca2+
E35G
-
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
-
significant decrease in diacylglycerol kinase activity. Mutant cells display reduced uptake of transferrin
F369A/F372A/F748A
-
significant decrease in diacylglycerol kinase activity. Mutant cells display reduced uptake of transferrin
F748A
-
diacylglycerol kinase activity similar to that of wild-type. Mutant cells display reduced uptake of transferrin
G236R
-
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
-
mutant shows diminished Zn occupancy
H38A
-
mutant shows diminished Zn occupancy
H3A
-
mutant shows diminished Zn occupancy
H3A/C20A/H38A/C60A
-
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
-
site-directed mutagenesis, slightly reduced activity compared to the wild-type isozyme theta
P244A
-
site-directed mutagenesis, reduced activity compared to the wild-type isozyme theta
P244L
-
site-directed mutagenesis, reduced activity compared to the wild-type isozyme theta
P245L
-
site-directed mutagenesis, highly reduced activity compared to the wild-type isozyme theta
S240T
-
site-directed mutagenesis, activity is unaltered compared to the wild-type isozyme theta
S258D/S265D/S270D/S271D
-
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
-
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
-
mutant exhibits greatly reduced polymerization, no polymers are visible in zinc-free conditions. After zinc addition, large sheet structures appear
Y335F
expression of wild-type diacylglycerol kinase alpha markedly reduces ERK phosphorylation, whereas the effect of expressing the nonphosphorylatableY335F mutant is much less pronounced
additional information
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
recombinant purified isoform DGKepsilon and DGKepsilonDELTA40 are largely inactivated after being stored at room temperature for 7.5 h. After incubation at room temperature for 2 h, the proportions of activity that isoforms DGKepsilon and DGKepsilonDELTA40 retain are 35.2 and 50.3%, respectively
4
after 6.5 h at 4°C, isoform DGKepsilon and DGKepsilonDELTA40 retain 19.1% and 15.8% of their initial activities, respectively, and 48.2% and 38.1% when stored in 50% glycerol, respectively
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
the recombinant isoform DGKepsilon and a truncated version lacking the first 40 residues lose activity upon being stored, particularly upon freezing and thawing, which is minimized by the addition of glycerol.
activation of tyrosine kinases is required for membrane stabilization of DGKalpha, phosphorylation of DGKalpha at Tyr335 appears to be essential for membrane localization
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-80°C, purified isoform DGKepsilon and DGKepsilonDELTA40, 14 weeks, no significant loss of activity
4°C, purified enzyme in 20 mM Tris-HCl, pH 7.4 with 200 mM NaCl, 3 mM CaCl2, 3 mM MgCl2, 0.5 mM dithiothreitol, and 5% (v/v) glycerol, at least 3 months, no loss of activity
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Ni-NTA resin column chromatography
isoenzyme DGK-I and DGK-II, DGK-II only partially purified
-
Ni-NTA agarose column chromatography and Superdex S200 gel filtration
Ni-NTA agarose column chromatography, Superdex 200 gel filtration or Superdex 75 gel filtration
Ni-NTA agarose column chromatography, Superdex 75 gel filtration and Superdex 200 gel filtration
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
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in COS-7 cells and in baculovirus-infected Sf21 insect cells
expressed in Sf21 insect cells
expression in COS-7 cell, with FLAG-tag
recombinant expression of human p3×FLAG-CMV-DGK isozyme epsilon in COS-7 cells
cDNA subcloned into the EcoRI site of the simian virus 40-based expression vector pSRE
-
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
COS-7 transfection
-
expressed in COS-7 cells
expressed in Escherichia coli Rosetta2 (DE3) cells
expressed in Escherichia coli strain Rosetta2 (DE3) and baculovirus-infected Sf9 insect cells
expressed in HEK-293, U2OS, MCF-7, Swiss3-T3, MEF, and Phoenix cells
expression in COS-7 cell
-
expression in COS-7 cell and HeLa cell
-
expression in COS-7 cells
expression in IIC9 cells
-
expression in lymphocyte
expression in SF21 cells
-
expression of GFP-tagged or FLAG-tagged wild-type and mutant isozymes theta in COS-7 cells
-
expression of the isolated catalytic subunit of isozyme alpha shows 60% of maximal wild-type full length enzyme activity
-
expression of truncated enzyme forms in COS-7 cells
-
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 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
-
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
-
using a baculovirus-Sf9 insect cell expression system
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
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
enzyme is able to remove 1-stearoyl-2-arachidonoylglycerol, the precursor of the endocannabinoid 2-arachidonoyl glycerol
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Schaap, D.; de Widt, J.; van der Wal, J.; Vandekerckhove, J.; van Damme, J.; Gussow, D.; Ploegh, H.L.; van Blitterswijk, W.J.; van der Bend, R.L.
Purification, cDNA-cloning and expression of human diacylglycerol kinase
FEBS Lett.
275
151-158
1990
Escherichia coli, Homo sapiens
Manually annotated by BRENDA team
Allan, D.; Thomas, P.; Gatt, S.
1,2-diacylglycerol kinase of human erythrocyte membranes. Assay with endogenously generated substrate
Biochem. J.
191
669-672
1980
Homo sapiens
Manually annotated by BRENDA team
Yada, Y.; Ozeki, T.; Kanoh, H.; Nozawa, Y.
Purification and characterization of cytosolic diacylglycerol kinases of human platelets
J. Biol. Chem.
265
19237-19243
1990
Homo sapiens
Manually annotated by BRENDA team
Yamada, K.; Sakane, F.; Imai, S.; Tsushima, S.; Murakami, T.; Kanoh, H.
Regulatory role of diacylglycerol kinase gamma in macrophage differentiation of leukemia cells
Biochem. Biophys. Res. Commun.
305
101-107
2003
Homo sapiens
Manually annotated by BRENDA team
Hurttia, H.; Leino, L.
Subcellular localization of diacylglycerol kinase activity in stimulated and unstimulated human peripheral blood lymphocytes and neutrophils
Biochem. Mol. Biol. Int.
40
579-585
1996
Homo sapiens
Manually annotated by BRENDA team
Tabellini, G.; Bortul, R.; Santi, S.; Riccio, M.; Baldini, G.; Cappellini, A.; Billi, A.M.; Berezney, R.; Ruggeri, A.; Cocco, L.; Martelli, A.M.
Diacylglycerol kinase-theta is localized in the speckle domains of the nucleus
Exp. Cell Res.
287
143-154
2003
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Sakane, F.; Kanoh, H.
Molecules in focus: diacylglycerol kinase
Int. J. Biochem. Cell Biol.
29
1139-1143
1997
Homo sapiens, Mesocricetus auratus, Rattus norvegicus, Sus scrofa
Manually annotated by BRENDA team
Caricasole, A.; Bettini, E.; Sala, C.; Roncarati, R.; Kobayashi, N.; Caldara, F.; Goto, K.; Terstappen, G.C.
Molecular cloning and characterization of the human diacylglycerol kinase beta (DGKbeta) gene: alternative splicing generates DGKbeta isotypes with different properties
J. Biol. Chem.
277
4790-4796
2002
Homo sapiens (Q9Y6T7), Homo sapiens
Manually annotated by BRENDA team
Bunting, M.; Tang, W.; Zimmerman, G.A.; McIntyre, T.M.; Prescott, S.M.
Molecular cloning and characterization of a novel human diacylglycerol kinase zeta
J. Biol. Chem.
271
10230-10236
1996
Homo sapiens (Q13574), Homo sapiens
Manually annotated by BRENDA team
Yamada, K.; Sakane, F.; Matsushima, N.; Kanoh, H.
EF-hand motifs of alpha, beta and gamma isoforms of diacylglycerol kinase bind calcium with different affinities and conformational changes
Biochem. J.
321
59-64
1997
Homo sapiens, Rattus norvegicus, Sus scrofa, Sus scrofa DGKalpha
Manually annotated by BRENDA team
Ding, L.; Traer, E.; McIntyre, T.M.; Zimmerman, G.A.; Prescott, S.M.
The cloning and characterization of a novel human diacylglycerol kinase, DGKiota
J. Biol. Chem.
273
32746-32752
1998
Homo sapiens
Manually annotated by BRENDA team
Murakami, T.; Sakane, F.; Imai, S.; Houkin, K.; Kanoh, H.
Identification and characterization of two splice variants of human diacylglycerol kinase eta
J. Biol. Chem.
278
34364-34372
2003
Homo sapiens (Q86XP1), Homo sapiens
Manually annotated by BRENDA team
Los, A.P.; van Baal, J.; de Widt, J.; Divecha, N.; van Blitterswijk, W.J.
Structure-activity relationship of diacylglycerol kinase theta
Biochim. Biophys. Acta
1636
169-174
2004
Homo sapiens
Manually annotated by BRENDA team
Luo, B.; Regier, D.S.; Prescott, S.M.; Topham, M.K.
Diacylglycerol kinases
Cell. Signal.
16
983-989
2004
Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mammalia, no activity in Saccharomyces cerevisiae
Manually annotated by BRENDA team
Dicu, A.O.; Matthew, K.; Topham, K.; Ottaway, L.; Epand, R.M.
Role of the hydrophobic segment of diacylglycerol kinase epsilon
Biochemistry
46
6109-6117
2007
Homo sapiens
Manually annotated by BRENDA team
Tu-Sekine, B.; Ostroski, M.; Raben, D.M.
Modulation of diacylglycerol kinase theta activity by alpha-thrombin and phospholipids
Biochemistry
46
924-932
2007
Homo sapiens
Manually annotated by BRENDA team
Yanagisawa, K.; Yasuda, S.; kai, M.; Imai, S.i.; Yamada, K.; Yamashita, T.; JImbow, K.; Kanoh, H.; Sakane, F.
Diacylglycerol kinase alpha suppresses tumor necrosis factor-alpha-induced apoptosis of human melanoma cells through NF-kappaB activation
Biochim. Biophys. Acta
1771
462-474
2007
Homo sapiens, Homo sapiens (P23743)
Manually annotated by BRENDA team
Los, A.P.; de Widt, J.; Topham, M.K.; van Blitterswijk, W.J.; Divecha, N.
Protein kinase C inhibits binding of diacylglycerol kinase-zeta to the retinoblastoma protein
Biochim. Biophys. Acta
1773
352-357
2007
Homo sapiens
Manually annotated by BRENDA team
Alonso, R.; Mazzeo, C.; Merida, I.; Izquierdo, M.
: A new role of diacylglycerol kinase alpha on the secretion of lethal exosomes bearing Fas ligand during activation-induced cell death of T lymphocytes
Biochimie
89
213-221
2007
Homo sapiens, Homo sapiens (P23743)
Manually annotated by BRENDA team
Yasuda, S.; Kai, M.; Imai, S.; Kanoh, H.; Sakane, F.
Diacylglycerol kinase gamma interacts with and activates beta2-chimaerin, a Rac-specific GAP, in response to epidermal growth factor
FEBS Lett.
581
551-557
2007
Chlorocebus aethiops, Homo sapiens (P49619)
Manually annotated by BRENDA team
Evangelisti, C.; Bortul, R.; Fala, F.; Tabellini, G.; Goto, K.; Martelli, A.M.
Nuclear diacylglycerol kinases: emerging downstream regulators in cell signalling networks
Histol. Histopathol.
22
573-579
2007
Chlorocebus aethiops, Cricetulus griseus, Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Miele, C.; Paturzo, F.; Teperino, R.; Sakane, F.; Fiory, F.; Oriente, F.; Ungaro, P.; Valentino, R.; Beguinot, F.; Formisano, P.
Glucose regulates diacylglycerol intracellular levels and protein kinase C activity by modulating diacylglycerol kinase subcellular localization
J. Biol. Chem.
282
3185-3143
2007
Homo sapiens
Manually annotated by BRENDA team
Rincon, E.; Santos, T.; Avila-Flores, A.; Albar, J.P.; Lalioti, V.; Lei, C.; Hong, W.; Merida, I.
Proteomics identification of sorting nexin 27 as a diacylglycerol kinase zeta-associated protein
Mol. Cell. Proteomics
6
1073-1087
2007
Homo sapiens, Homo sapiens (Q13574)
Manually annotated by BRENDA team
Leach, N.T.; Sun, Y.; Michaud, S.; Zheng, Y.; Ligon, K.L.; Ligon, A.H.; Sander, T.; Korf, B.R.; Lu, W.; Harris, D.J.; Gusella, J.F.; Maas, R.L.; Quade, B.J.; Cole, A.J.; Kelz, M.B.; Morton, C.C.
Disruption of diacylglycerol kinase delta (DGKD) associated with seizures in humans and mice
Am. J. Hum. Genet.
80
792-799
2007
Mus musculus, Homo sapiens (Q16760), Homo sapiens
Manually annotated by BRENDA team
Filigheddu, N.; Cutrupi, S.; Porporato, P.E.; Riboni, F.; Baldanzi, G.; Chianale, F.; Fortina, E.; Piantanida, P.; De Bortoli, M.; Vacca, G.; Graziani, A.; Surico, N.
Diacylglycerol kinase is required for HGF-induced invasiveness and anchorage-independent growth of MDA-MB-231 breast cancer cells
Anticancer Res.
27
1489-1492
2007
Homo sapiens
Manually annotated by BRENDA team
Kawasaki, T.; Kobayashi, T.; Ueyama, T.; Shirai, Y.; Saito, N.
Regulation of clathrin-dependent endocytosis by diacylglycerol kinase delta: importance of kinase activity and binding to AP2alpha
Biochem. J.
409
471-479
2008
Homo sapiens
Manually annotated by BRENDA team
Yasuda, S.; Kai, M.; Imai, S.; Kanoh, H.; Sakane, F.
Phorbol ester and hydrogen peroxide synergistically induce the interaction of diacylglycerol kinase gamma with the Src homology 2 and C1 domains of beta2-chimaerin
Biochem. J.
409
95-106
2008
Homo sapiens
Manually annotated by BRENDA team
Epand, R.M.; Shulga, Y.V.; Timmons, H.C.; Perri, A.L.; Belani, J.D.; Perinpanathan, K.; Johnson-McIntire, L.B.; Bajjalieh, S.; Dicu, A.O.; Elias, C.; Rychnovsky, S.D.; Topham, M.K.
Substrate chirality and specificity of diacylglycerol kinases and the multisubstrate lipid kinase
Biochemistry
46
14225-14231
2007
Homo sapiens
Manually annotated by BRENDA team
Glukhov, E.; Shulga, Y.V.; Epand, R.F.; Dicu, A.O.; Topham, M.K.; Deber, C.M.; Epand, R.M.
Membrane interactions of the hydrophobic segment of diacylglycerol kinase epsilon
Biochim. Biophys. Acta
1768
2549-2558
2007
Homo sapiens (P52429)
Manually annotated by BRENDA team
Chibalin, A.V.; Leng, Y.; Vieira, E.; Krook, A.; Bjoernholm, M.; Long, Y.C.; Kotova, O.; Zhong, Z.; Sakane, F.; Steiler, T.; Nylen, C.; Wang, J.; Laakso, M.; Topham, M.K.; Gilbert, M.; Wallberg-Henriksson, H.; Zierath, J.R.
Downregulation of diacylglycerol kinase delta contributes to hyperglycemia-induced insulin resistance
Cell
132
375-386
2008
Mus musculus, Rattus norvegicus, Homo sapiens (Q16760), Homo sapiens
Manually annotated by BRENDA team
Williams, J.M.; Pettitt, T.R.; Powell, W.; Grove, J.; Savage, C.O.; Wakelam, M.J.
Antineutrophil cytoplasm antibody-stimulated neutrophil adhesion depends on diacylglycerol kinase-catalyzed phosphatidic acid formation
J. Am. Soc. Nephrol.
18
1112-1120
2007
Homo sapiens
Manually annotated by BRENDA team
Merino, E.; Avila-Flores, A.; Shirai, Y.; Moraga, I.; Saito, N.; Merida, I.
Lck-dependent tyrosine phosphorylation of diacylglycerol kinase alpha regulates its membrane association in T cells
J. Immunol.
180
5805-5815
2008
Homo sapiens (P23743)
Manually annotated by BRENDA team
Decaffmeyer, M.; Shulga, Y.V.; Dicu, A.O.; Thomas, A.; Truant, R.; Topham, M.K.; Brasseur, R.; Epand, R.M.
Determination of the topology of the hydrophobic segment of mammalian diacylglycerol kinase epsilon in a cell membrane and its relationship to predictions from modeling
J. Mol. Biol.
383
797-809
2008
Homo sapiens (P52429)
Manually annotated by BRENDA team
Li, D.; Urs, A.N.; Allegood, J.; Leon, A.; Merrill, A.H.; Sewer, M.B.
Cyclic AMP-stimulated interaction between steroidogenic factor 1 and diacylglycerol kinase theta facilitates induction of CYP17
Mol. Cell. Biol.
27
6669-6685
2007
Homo sapiens
Manually annotated by BRENDA team
Baum, A.E.; Akula, N.; Cabanero, M.; Cardona, I.; Corona, W.; Klemens, B.; Schulze, T.G.; Cichon, S.; Rietschel, M.; Noethen, M.M.; Georgi, A.; Schumacher, J.; Schwarz, M.; Abou Jamra, R.; Hoefels, S.; Propping, P.; Satagopan, J.; Detera-Wadleigh, S.D.; Hardy, J.; McMahon, F.J.
A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder
Mol. Psychiatry
13
197-207
2008
Homo sapiens
Manually annotated by BRENDA team
Los, A.; de Widt, J.; van Blitterswijk, W.; Divecha, N.
Is there a role for diacylglycerol kinase-zeta in cell cycle regulation?
Adv. Enzyme Regul.
48
31-39
2008
Homo sapiens (Q13574)
Manually annotated by BRENDA team
Merida, I.; Avila-Flores, A.; Garcia, J.; Merino, E.; Almena, M.; Torres-Ayuso, P.
Diacylglycerol kinase alpha, from negative modulation of T cell activation to control of cancer progression
Adv. Enzyme Regul.
49
174-188
2009
Mus musculus (O88673), Homo sapiens (P23743)
Manually annotated by BRENDA team
Kai, M.; Yasuda, S.; Imai, S.; Toyota, M.; Kanoh, H.; Sakane, F.
Diacylglycerol kinase alpha enhances protein kinase Czeta-dependent phosphorylation at Ser311 of p65/RelA subunit of nuclear factor-kappaB
FEBS Lett.
583
3265-3268
2009
Sus scrofa (P20192), Homo sapiens (P23743)
Manually annotated by BRENDA team
Yasuda, S.; Kai, M.; Imai, S.; Takeishi, K.; Taketomi, A.; Toyota, M.; Kanoh, H.; Sakane, F.
Diacylglycerol kinase eta augments C-Raf activity and B-Raf/C-Raf heterodimerization
J. Biol. Chem.
284
29559-29570
2009
Homo sapiens (Q86XP1)
Manually annotated by BRENDA team
Lung, M.; Shulga, Y.V.; Ivanova, P.T.; Myers, D.S.; Milne, S.B.; Brown, H.A.; Topham, M.K.; Epand, R.M.
Diacylglycerol kinase epsilon is selective for both acyl chains of phosphatidic acid or diacylglycerol
J. Biol. Chem.
284
31062-31073
2009
Homo sapiens (P52429)
Manually annotated by BRENDA team
Gellett, A.M.; Kharel, Y.; Sunkara, M.; Morris, A.J.; Lynch, K.R.
Biosynthesis of alkyl lysophosphatidic acid by diacylglycerol kinases
Biochem. Biophys. Res. Commun.
422
758-763
2012
Homo sapiens
Manually annotated by BRENDA team
Knight, M.J.; Joubert, M.K.; Plotkowski, M.L.; Kropat, J.; Gingery, M.; Sakane, F.; Merchant, S.S.; Bowie, J.U.
Zinc binding drives sheet formation by the SAM domain of diacylglycerol kinase delta
Biochemistry
49
9667-9676
2010
Homo sapiens
Manually annotated by BRENDA team
Gantayet, A.; Jegatheswaran, J.; Jayakumaran, G.; Topham, M.K.; Epand, R.M.
Endocannabinoids and diacylglycerol kinase activity
Biochim. Biophys. Acta
1808
1050-1053
2011
Homo sapiens (P52429), Homo sapiens (Q13574)
Manually annotated by BRENDA team
Takeuchi, M.; Sakiyama, S.; Usuki, T.; Sakai, H.; Sakane, F.
Diacylglycerol kinase delta1 transiently translocates to the plasma membrane in response to high glucose
Biochim. Biophys. Acta
1823
2210-2216
2012
Homo sapiens (Q16760), Homo sapiens
Manually annotated by BRENDA team
Prodeus, A.; Berno, B.; Topham, M.K.; Epand, R.M.
The basis of the substrate specificity of the epsilon isoform of human diacylglycerol kinase is not a consequence of competing hydrolysis of ATP
Chem. Phys. Lipids
166
26-30
2013
Homo sapiens (P52429), Homo sapiens
Manually annotated by BRENDA team
DSouza, K.; Epand, R.M.
Catalytic activity and acyl-chain selectivity of diacylglycerol kinase epsilon are modulated by residues in and near the lipoxygenase-like motif
J. Mol. Biol.
416
619-628
2012
Homo sapiens (P52429)
Manually annotated by BRENDA team
Gharbi, S.I.; Rincon, E.; Avila-Flores, A.; Torres-Ayuso, P.; Almena, M.; Cobos, M.A.; Albar, J.P.; Merida, I.
Diacylglycerol kinase zeta controls diacylglycerol metabolism at the immunological synapse
Mol. Biol. Cell
22
4406-4414
2011
Homo sapiens (P23743), Homo sapiens (Q13574)
Manually annotated by BRENDA team
Atsumi, H.; Kitada, M.; Kanasaki, K.; Koya, D.
Reversal of redox-dependent inhibition of diacylglycerol kinase by antioxidants in mesangial cells exposed to high glucose
Mol. Med. Rep.
4
923-927
2011
Homo sapiens
Manually annotated by BRENDA team
Sato, Y.; Murakami, C.; Yamaki, A.; Mizuno, S.; Sakai, H.; Sakane, F.
Distinct 1-monoacylglycerol and 2-monoacylglycerol kinase activities of diacylglycerol kinase isozymes
Biochim. Biophys. Acta
1864
1170-1176
2016
Homo sapiens (O75912), Homo sapiens (P49619), Homo sapiens (P52429), Homo sapiens (P52824), Homo sapiens (Q13574), Homo sapiens (Q16760), Homo sapiens (Q5KSL6), Homo sapiens (Q86XP1), Sus scrofa (P20192), Rattus norvegicus (P68403)
Manually annotated by BRENDA team
Saito, T.; Takahashi, D.; Sakane, F.
Expression, purification, and characterization of human diacylglycerol kinase zeta
ACS Omega
4
5540-5546
2019
Homo sapiens (Q13574), Homo sapiens
Manually annotated by BRENDA team
Merida, I.; Arranz-Nicolas, J.; Rodriguez-Rodriguez, C.; Avila-Flores, A.
Diacylglycerol kinase control of protein kinase C
Biochem. J.
476
1205-1219
2019
Homo sapiens (Q13574)
Manually annotated by BRENDA team
Jennings, W.; Doshi, S.; Hota, P.K.; Prodeus, A.; Black, S.; Epand, R.M.
Expression, purification, and properties of a human arachidonoyl-specific isoform of diacylglycerol kinase
Biochemistry
56
1337-1347
2017
Homo sapiens (P52429), Homo sapiens
Manually annotated by BRENDA team
Franks, C.E.; Campbell, S.T.; Purow, B.W.; Harris, T.E.; Hsu, K.L.
The ligand binding landscape of diacylglycerol kinases
Cell Chem. Biol.
24
870-880.e5
2017
Homo sapiens (P23743)
Manually annotated by BRENDA team
Epand, R.M.; So, V.; Jennings, W.; Khadka, B.; Gupta, R.S.; Lemaire, M.
Diacylglycerol kinase-epsilon properties and biological roles
Front. Cell Dev. Biol.
4
112
2016
Homo sapiens (P52429), Homo sapiens
Manually annotated by BRENDA team
Fazio, A.; Obeng, E.; Rusciano, I.; Marvi, M.; Zoli, M.; Mongiorgi, S.; Ramazzotti, G.; Follo, M.; McCubrey, J.; Cocco, L.; Manzoli, L.; Ratti, S.
Subcellular localization relevance and cancer-associated mechanisms of diacylglycerol kinases
Int. J. Mol. Sci.
21
1-19
2020
Homo sapiens (O75912), Homo sapiens (P23743), Homo sapiens (P49619), Homo sapiens (P52429), Homo sapiens (P52824), Homo sapiens (Q13574), Homo sapiens (Q16760), Homo sapiens (Q5KSL6), Homo sapiens (Q86XP1), Homo sapiens (Q9Y6T7)
Manually annotated by BRENDA team
Hayashi, D.; Tsumagari, R.; Liu, K.; Ueda, S.; Yamanoue, M.; Sakane, F.; Shirai, Y.
Screening of subtype-specific activators and inhibitors for diacylglycerol kinase
J. Biochem.
165
517-522
2019
Homo sapiens (O75912), Homo sapiens (P23743), Homo sapiens (P49619), Homo sapiens (P52824), Homo sapiens (Q13574), Homo sapiens (Q16760), Homo sapiens (Q5KSL6), Homo sapiens (Q86XP1), Homo sapiens (Q9Y6T7)
Manually annotated by BRENDA team
Poli, A.; Fiume, R.; Baldanzi, G.; Capello, D.; Ratti, S.; Gesi, M.; Manzoli, L.; Graziani, A.; Suh, P.G.; Cocco, L.; Follo, M.Y.
Nuclear localization of diacylglycerol kinase alpha in K562 cells is involved in cell cycle progression
J. Cell. Physiol.
232
2550-2557
2017
Homo sapiens (P23743), Homo sapiens
Manually annotated by BRENDA team
Takahashi, D.; Sakane, F.
Expression and purification of human diacylglycerol kinase alpha from baculovirus-infected insect cells for structural studies
PeerJ
6
e5449
2018
Homo sapiens (P23743), Homo sapiens
Manually annotated by BRENDA team
Murakami, E.; Shionoya, T.; Komenoi, S.; Suzuki, Y.; Sakane, F.
Cloning and characterization of novel testis-specific diacylglycerol kinase eta splice variants 3 and 4
PLoS ONE
11
e0162997
2016
Homo sapiens (Q86XP1)
Manually annotated by BRENDA team
Takahashi, D.; Suzuki, K.; Sakamoto, T.; Iwamoto, T.; Murata, T.; Sakane, F.
Crystal structure and calcium-induced conformational changes of diacylglycerol kinase alpha EF-hand domains
Protein Sci.
28
694-706
2019
Homo sapiens (P23743)
Manually annotated by BRENDA team