Information on EC 2.7.1.107 - diacylglycerol kinase (ATP)

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

EC NUMBER
COMMENTARY
2.7.1.107
-
RECOMMENDED NAME
GeneOntology No.
diacylglycerol kinase (ATP)
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + 1,2-diacyl-sn-glycerol = ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
-
-
-
ATP + 1,2-diacyl-sn-glycerol = ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
random equilibrium mechanism
-
ATP + 1,2-diacyl-sn-glycerol = ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
C-terminal active site comprises residues 371-501, the C1 domain is absolutely required for catalytic activity, residues Asp434, Asp650, Asp465, and Asp497 are involved
-
ATP + 1,2-diacyl-sn-glycerol = ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
catalytic and regulatory mechanisms
-
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
-
ATP + 1,2-diacyl-sn-glycerol = ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
catalytic and regulatory mechanisms
Dictyostelium discoideum HL5
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Biosynthesis of secondary metabolites
-
-
Glycerolipid metabolism
-
-
Glycerophospholipid metabolism
-
-
Metabolic pathways
-
-
phosphatidate metabolism, as a signaling molecule
-
-
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).
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
1,2-diacylglycerol kinase
-
-
-
-
adenosine 5'-triphosphate:1,2-diacylglycerol 3-phosphotransferase
-
-
-
-
arachidonoyl-specific diacylglycerol kinase
-
-
-
-
ATP:diacylglycerol phosphotransferase
-
-
-
-
DAGK
-
-
-
-
DAGKalpha
-
-
-
-
DG kinase
-
-
-
-
DGK
-
-
-
-
DGK-alpha
-
-
-
-
DGK-theta
-
-
-
-
DGKbeta
-
-
-
-
DGKdelta
-
-
-
-
DGKgamma
-
-
-
-
DGKiota
-
-
-
-
DGKksi
-
-
-
-
diacylglycerol kinase
-
-
-
-
diacylglycerol kinase (ATP dependent)
-
-
-
-
diacylglycerol:ATP kinase
-
-
-
-
diglyceride kinase
-
-
-
-
kinase (phosphorylating), 1,2-diacylglycerol
-
-
-
-
kinase, 1,2-diacylglycerol (phosphorylating)
-
-
-
-
sn-1,2-diacylglycerol kinase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
60382-71-0
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
2 isozymes DGK1 and DGK2
SwissProt
Manually annotated by BRENDA team
different splice forms
-
-
Manually annotated by BRENDA team
DGKtheta and DGKdelta
-
-
Manually annotated by BRENDA team
Dictyostelium discoideum HL5
strain HL5
-
-
Manually annotated by BRENDA team
9 different isozymes divided into 5 subtypes, alternative splicing of isozymes
-
-
Manually annotated by BRENDA team
; DGKgamma
-
-
Manually annotated by BRENDA team
DGK-theta
-
-
Manually annotated by BRENDA team
DGKbeta
Uniprot
Manually annotated by BRENDA team
DGKeta1 and DGKeta2
UniProt
Manually annotated by BRENDA team
DGKgamma
-
-
Manually annotated by BRENDA team
diacylglycerol kinase delta2
-
-
Manually annotated by BRENDA team
diacylglycerol kinase epsilon
UniProt
Manually annotated by BRENDA team
isoform diacalglycerol kinase alpha
UniProt
Manually annotated by BRENDA team
isoform diacalglycerol kinase zeta
UniProt
Manually annotated by BRENDA team
isoform diaclyglycerol kinase epsilon
UniProt
Manually annotated by BRENDA team
isoform diacylglycerol kinase delta
-
-
Manually annotated by BRENDA team
isoform diacylglycerol kinase delta
UniProt
Manually annotated by BRENDA team
isoform diacylglycerol kinase delta. Female patient with a de novo balanced translocation, 46,X,t(X,2)(p11.2,q37)dn, who exhibits seizures, capillary abnormality, developmental delay, infantile hypotonia, and obesity
UniProt
Manually annotated by BRENDA team
isoform diacylglycerol kinase epsilon
UniProt
Manually annotated by BRENDA team
isoform diacylglycerolkinase epsilon
UniProt
Manually annotated by BRENDA team
isoform diacylglycerolkinase zeta
UniProt
Manually annotated by BRENDA team
isozyme theta
-
-
Manually annotated by BRENDA team
patients with bipolar disorder
-
-
Manually annotated by BRENDA team
9 different isozymes
-
-
Manually annotated by BRENDA team
9 different isozymes divided into 5 subtypes, alternative splicing of isozymes
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
DGKalpha isoform
UniProt
Manually annotated by BRENDA team
DGKepsilon isoform
SwissProt
Manually annotated by BRENDA team
DGKzeta isoform
UniProt
Manually annotated by BRENDA team
diacylglycerol kinase alpha
UniProt
Manually annotated by BRENDA team
diacylglycerol kinase zeta
UniProt
Manually annotated by BRENDA team
no activity in Saccharomyces cerevisiae
-
-
-
Manually annotated by BRENDA team
DGK-I, DGK-II and DGK-III
-
-
Manually annotated by BRENDA team
DGK-theta
-
-
Manually annotated by BRENDA team
isoform alpha
UniProt
Manually annotated by BRENDA team
isoform beta
UniProt
Manually annotated by BRENDA team
isoform zeta
SwissProt
Manually annotated by BRENDA team
isoforms gamma, epsilon
-
-
Manually annotated by BRENDA team
isozymes DGKalpha, DGKzeta, and DGKepsilon
-
-
Manually annotated by BRENDA team
neuron-specific isozymes DGKbeta and DGKgamma
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
DGKalpha
-
-
Manually annotated by BRENDA team
Sus scrofa DGKalpha
DGKalpha
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
knockdown of DGKfzeta in cultured neurons decreases spine density
malfunction
Q86XP1
small interfering RNA-dependent knockdown of diacylglycerol kinase eta impairs the Ras/B-Raf/C-Raf/MEK/ERK pathway activated by epidermal growth factor in HeLa cells and inhibits cell proliferation
physiological function
O88673, Q80UP3, Q9R1C6
DGKalpha has a central role in modulating T cell anergy through its ability to control DAG levels, which likely activates RasGRP1 and possibly other proteins
physiological function
Q9R1C6
DGKepsilon prevents cardiac hypertrophy and progression to heart failure under chronic pressure overload
physiological function
-
DGKs broadly regulate signaling events by virtue of their ability to provide 1,2-diacyl-sn-glycerol 3-phosphate (phosphatidic acid) for the synthesis of phosphatidylinositols
physiological function
-
DGKs broadly regulate signaling events by virtue of their ability to provide 1,2-diacyl-sn-glycerol 3-phosphate (phosphatidic acid) for the synthesis of phosphatidylinositols, isoform DGKzeta activates phosphatidylinositol-4-phosphate 5-kinase type Ialpha, DGKzeta modulates Rac1 activation to influence neurite outgrowth, DGKzeta modulates mTor activation and immune cell signaling
physiological function
O88673, Q80UP3, Q9R1C6
DGKzeta has an important biological function in the nucleus where it appears to modulate the cell cycle by metabolizing 1,2-diacylglycerol
physiological function
-
diacylglycerol kinase beta promotes dendritic outgrowth and spine maturation in developing hippocampal neurons
physiological function
-
diacylglycerol kinase zeta regulates actin cytoskeleton reorganization through dissociation of Rac1 from RhoGDI
physiological function
-
isoform DGKalpha positively regulates tumor nuclear factor-alpha-dependent necrosis factor-kappaB activation via the protein kinase Czeta-mediated Ser311 phosphorylation of p65/RelA, isoform DGKalpha does not affect phosphorylation of IkappaB, DGKalpha enhances phosphorylation of p65 at Ser311 but not at Ser468 or Ser536
physiological function
P20192
isoform DGKalpha positively regulates tumor nuclear factor-alpha-dependent necrosis factor-kappaB activation via the protein kinase Czeta-mediated Ser311 phosphorylation of p65/RelA, isoform DGKalpha does not affect phosphorylation of IkappaB, DGKalpha enhances phosphorylation of p65 at Ser311 but not at Ser468 or Ser536
physiological function
-
isoform DGKbeta is provided to perisynaptic sites of medium spiny neurons so that it can effectively produce 1,2-diacyl-sn-glycerol 3-phosphate upon activation of Gq protein-coupled receptors and modulate the cellular state of striatal output neurons
physiological function
-
isoform DGKepsilon interacts with actin stress fibers and is involved in their stability in vascular smooth muscle cells
physiological function
-
isoform DGKf appears to form a multi-protein complex with functionally related proteins to organize efficient 1,2-diacylglycerol and 1,2-diacyl-sn-glycerol 3-phosphate signaling pathways at excitatory synapses, the DGKzeta isoform at excitatory postsynaptic sites is critically involved in spine maintenance, DGKzeta promotes neurite outgrowth
physiological function
-
membrane localization of DGKalpha acts as a switch-off signal for Ras activation, mediated by localization to the membrane of Ras-GRP1, DGKalpha is a negative regulator of the T cell activation program, DGKalpha activity is required for optimal chemotactic response of neutrophils, whereas it halts their oxidative burst, DGKalpha is a negative modulator of diacylglycerol signaling, DGKalpha activity modulates the mTOR pathway to prevent cell cycle transition, DGKalpha is an indicator of cell quiescence, DGKalpha is a positive regulator of cell proliferation and migration
physiological function
O88673
membrane localization of DGKalpha acts as a switch-off signal for Ras activation, mediated by localization to the membrane of Ras-GRP1, DGKalpha is a negative regulator of the T cell activation program, DGKalpha activity is required for optimal chemotactic response of neutrophils, whereas it halts their oxidative burst, DGKalpha is a negative modulator of diacylglycerol signaling, DGKalpha activity modulates the mTOR pathway to prevent cell cycle transition, DGKalpha is an indicator of cell quiescence, DGKalpha is a positive regulator of cell proliferation and migration
physiological function
-
neither overexpression of wild type nor kinase-inactive DGKzeta affects cell cycle distribution
physiological function
-
nuclear DGK-zeta downregulates the expression of cyclin D1 and increased the expression of TIS21/BTG2/PC3
physiological function
Q86XP1
overexpression of DGKeta1 can activate the Ras/B-Raf/C-Raf/MEK/ERK pathway in a DGK activity-independent manner, suggesting that DGKeta serves as a scaffold/adaptor protein, DGKeta activates C-Raf but not B-Raf
physiological function
P23743, Q13574
endogenous isoform diacylglycerol kinase alpha is recruited to the T cell receptor complex following T cell receptor/CD28 engagement
physiological function
P23743, Q13574
endogenous isoform diacylglycerol kinase zeta is recruited to the T cell receptor complex following T cell receptor/CD28 engagement. Specific diacylglycerol kinase gene silencing shows that phosphatidic acid production at the activated complex depends mainly on diacylglycerol kinase zeta. At early stages of T cell immunological synapse formation, isoform zeta translocates rapidly to the plasma membrane, where rapid, sustained diacylglycerol accumulation is found
physiological function
-
in response to cold temperatures, there is a very fast accumulation of phosphatidic acid in Arabidopsis seedlings and leaf discs. Radiolabeling studies indicate a dominant role of diacylglycerol kinase under these conditions
physiological function
-
treating SKOV-3 ovarian cancer cell with a sphingosine analogue stimulates conversion of exogenous 1-alkyl-2-acetyl glycerol to alkyl-lysophosphatidic acid. Diacylglycerol kinase alpha may contribute significantly to the production of alkyl-lysophosphatidic acid in SKOV-3 cells, showing cross-talk between the sphingolipid and glycerol lipid pathways
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
1,2-dipalmitoyl-sn-glycerol + GTP
GDP + 1,2-dipalmitoyl-sn-glycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
1,2-dipalmitoyl-sn-glycerol + GTP
GDP + 1,2-dipalmitoyl-sn-glycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
2'-deoxy-ATP + sn-1,2-dihexanoylglycerol
2'-deoxy-ADP + sn-1,2-dihexanoylglycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
ADP + sn-1,2-dihexanoylglycerol
AMP + sn-1,2-dihexanoylglycerol 3-phosphate
show the reaction diagram
-
MgADP- is a very poor phosphoryl donor
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
P19638
-
enzyme is more active toward long-chain diacylglycerol compared with short-chain diacylglycerol
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
the enzyme functions to recycle diacylglycerol which is generated largely as a by-product of membrane-derived oligosaccharide biosynthesis
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
the enzyme may regulate the intracellular concentration of diacylglycerol
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
the enzyme is involved in resynthesis of phosphatidylinositol by converting a second messenger diacylglycerol to phosphatidic acid
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
DGKiota may have important cellular functions in retina and brain
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
DAGKalpha is stimulated vby Src-like kinase-dependent phosphoinositide 3 kinase activation in lymphocytes. In vivo the increase in cellular levels of Src-like kinase-dependent phosphoinositide 3 kinase products is sufficient to induce DAGKalpha activation, allowing DAGKalpha relocation to the intact lymphocyte
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
nuclear DGK-theta is activated in response to alpha-thrombin
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
Q64398
the enzyme plays a role in cellular processes by regulating the intracellular concentration of the second messenger diacylglycerol. DGKeta may play a more general role in regulating cellular diacylglycerol levels
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
Q86XP1
the expression of DGKeta2 is suppressed by glucocorticoid in contrast to the marked induction of DGKeta1
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
high level expression of DGKalpha is induced following a signal transmitted through the pre-T-cell-receptor and the protein tyrosine kinase lck. Activity of DGKalpha contributes to survival in CD4+ 8+ double positive thymocytes as pharmacological inhibition of DGK activity results in death of this cell population both in cell suspension and thymic explants. DGKalpha promotes survival in theses thymocytes through a Bcl-regulated pathway
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
Q01583
the enzyme may have an important function in the adult nervous system and muscle and during the development of the embryonic nervous system
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
DGK-Ialpha is involved in IL-2-mediated lymphocyte proliferation
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
the 80000 Da and the 150000 Da enzyme form do not possess specificity towards diacylglycerol molecular species
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
DGKgamma negatively regulates macrophage differentiation through its catalytic action operating on the cytoskeleton
-
-
?
ATP + 1,2-diacylglycerol
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
P0ABN1
-
-
-
?
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
-
-
-
r
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
-
-
-
r
ATP + 1,2-diacylglycerol
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-diacylglycerol
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-diacylglycerol
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
Q9FFN7
-
-
-
?
ATP + 1,2-diacylglycerol
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-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
O88673, Q80UP3, Q9R1C6
-
-
-
?
ATP + 1,2-diacylglycerol
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
O88673
-
-
-
?
ATP + 1,2-diacylglycerol
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-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
P49621
-
-
-
?
ATP + 1,2-diacylglycerol
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
P20192
-
-
-
?
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
Q86XP1
-
-
-
?
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
-
i.e. phosphatidic acid
-
?
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
-
i.e. phosphatidic acid
-
r
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
-
i.e. phosphatidic acid
-
?
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
-
i.e. phosphatidic acid
-
?
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
-
i.e. phosphatidic acid
-
?
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
Q9FFN7
-
i.e. phosphatidic acid
-
?
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
-
1,2-diacyl-sn-glycerol 3-phosphate is phosphatidic acid
-
ir
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
reaction takes place during stimulated phosphatidylinositol turnover
-
-
?
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
second messenger and intermediate in lipid synthesis
-
-
?
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
termination of diacylglycerol signaling, isozymes DGKalpha, DGKbeta, and DGKgamma play a pivotal role in development and metabolism of brain
-
-
?
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
the enzyme binds and regulates signalling proteins which are activated by either diacylglycerol or phosphatidic acid
-
-
?
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
the enzyme binds and regulates signalling proteins which are activated by either diacylglycerol or phosphatidic acid, isozyme dgk-1 regulates diacylglycerol signalling required for acetylcholine release
-
-
?
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
1,2-diacylglycerol is a second messenger
i.e. phosphatidic acid
-
?
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
O88673, Q80UP3, Q9R1C6
DGKepsilon exhibits specificity for diacylglcerol substrates containing an arachidonoyl chain in the sn-2 position
-
-
?
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
Dictyostelium discoideum HL5
-
-
-
-
?
ATP + 1,2-diarachidonoyl-glycerol
ADP + 1,2-diarachidonoyl-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
P52429
-
-
-
?
ATP + 1,2-dicapryl-sn-glycerol
ADP + 1,2-dicapryl-sn-glycerol 3-phosphate
show the reaction diagram
Q13574
about 140% of the activity with sn-1,2-dioleoylglycerol
-
-
?
ATP + 1,2-didecanoylglycerol
ADP + 1,2-didecanoylglycerol 3-phosphate
show the reaction diagram
-
enzyme type I: activity is 157% of the activity with rac-1,2-dioleoylglycerol, enzyme type II: activity is 141% of the activity with rac-1,2-dioleoylglycerol
-
-
?
ATP + 1,2-didodecanoylglycerol
ADP + 1,2-didodecanoylglycerol 3-phosphate
show the reaction diagram
-
enzyme type I: activity is 107% of the activity with rac-1,2-dioleoylglycerol, enzyme type II: activity is 227% of the activity with rac-1,2-dioleoylglycerol
-
-
-
ATP + 1,2-dihexadecanoylglycerol
ADP + 1,2-dihexadecanoylglycerol 3-phosphate
show the reaction diagram
-
enzyme type I: activity is 198% of the activity with rac-1,2-dioleoylglycerol, enzyme type II: activity is 231% of the activity with rac-1,2-dioleoylglycerol
-
-
?
ATP + 1,2-dihexanoyl-sn-glycerol
ADP + 1,2-dihexanoyl-sn-glycerol 3-phosphate
show the reaction diagram
Dictyostelium discoideum, Dictyostelium discoideum HL5
-
-
-
-
?
ATP + 1,2-dihexanoylglycerol
ADP + 1,2-dihexanoylglycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 1,2-dilinoleoyl-sn-glycerol
ADP + 1,2-dilinoleoyl-sn-glycerol
show the reaction diagram
P52429
-
-
-
?
ATP + 1,2-dioctanoyl-sn-glycerol
ADP + 1,2-dioctanoyl-sn-glycerol 3-phosphate
show the reaction diagram
P19638
-
-
-
?
ATP + 1,2-dioctanoyl-sn-glycerol
ADP + 1,2-dioctanoyl-sn-glycerol 3-phosphate
show the reaction diagram
Dictyostelium discoideum, Dictyostelium discoideum HL5
-
preferred substrate
-
-
?
ATP + 1,2-dioctanoylglycerol
ADP + 1,2-dioctanoylglycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 1,2-dioctanoylglycerol
ADP + 1,2-dioctanoylglycerol 3-phosphate
show the reaction diagram
-
enzyme type I: activity is 149% of the activity with rac-1,2-dioleoylglycerol, enzyme type II: activity is 114% of the activity with rac-1,2-dioleoylglycerol
-
-
?
ATP + 1,2-dioleoyl-sn-glycerol
ADP + 1,2-dioleoyl-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-dioleoyl-sn-glycerol
ADP + 1,2-dioleoyl-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-dioleoyl-sn-glycerol
ADP + 1,2-dioleoyl-sn-glycerol 3-phosphate
show the reaction diagram
Q9FFN7
-
-
-
?
ATP + 1,2-dioleoyl-sn-glycerol
ADP + 1,2-dioleoyl-sn-glycerol 3-phosphate
show the reaction diagram
P52429
-
-
-
?
ATP + 1,2-dioleoyl-sn-glycerol
ADP + 1,2-dioleoyl-sn-glycerol 3-phosphate
show the reaction diagram
P19638
-
-
-
?
ATP + 1,2-dioleoyl-sn-glycerol
ADP + 1,2-dioleoyl-sn-glycerol 3-phosphate
show the reaction diagram
-
isoform DGKepsilon shows about 7% activity with 0.38 mol% 1,2-dioleoyl-sn-glycerol compared to 1-stearoyl-2-arachidonoyl-sn-glycerol
-
-
?
ATP + 1,2-dioleoyl-sn-glycerol
ADP + 1,2-dioleoyl-sn-glycerol 3-phosphate
show the reaction diagram
-
about 15fold the rate of 1-O-hexadecyl-sn-glycerol phosphorylation, isoforms diacylglycerol kinase alpha, beta, gamma, delta1, delta1, zeta, jota, theta
-
-
?
ATP + 1,2-dioleoyl-sn-glycerol
ADP + 1,2-dioleoyl-sn-glycerol 3-phosphate
show the reaction diagram
Dictyostelium discoideum HL5
-
-
-
-
?
ATP + 1,2-dioleoyl-sn-glycerol
ADP + 1,2-diacyl-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-dipalmitoyl-sn-glycerol
ADP + 1,2-dipalmitoyl-sn-glycerol 3-phosphate
show the reaction diagram
-
15% of the activity with 1-stearoyl-2-arachidonoyl-sn-glycerol
-
-
?
ATP + 1,2-ditetradecanoylglycerol
ADP + 1,2-ditetradecanoylglycerol 3-phosphate
show the reaction diagram
-
enzyme type I: activity is 200% of the activity with rac-1,2-dioleoylglycerol, enzyme type II: activity is 262% of the activity with rac-1,2-dioleoylglycerol
-
-
-
ATP + 1,3-dioleoyl-sn-glycerol
ADP + 1,3-dioleoyl-sn-glycerol 2-phosphate
show the reaction diagram
-
low activity, about 4% of the activity with 1,2-dioleoyl-sn-glycerol
-
-
?
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-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-O-hexanoyl-2-arachidonoyl-sn-glycerol
ADP + 1-O-hexanoyl-2-arachidonoyl-sn-glycerol 3-phosphate
show the reaction diagram
-
preferred by isozyme DGKzeta and isozyme DGKalpha
-
-
?
ATP + 1-O-hexanoyl-2-oleoyl-sn-glycerol
ADP + 1-O-hexanoyl-2-oleoyl-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
Q13574
about 85% of the activity with sn-1,2-dioleoylglycerol, DGKksi
-
-
?
ATP + 1-palmitoyl-2-arachidonoyl-sn-glycerol
ADP + 1-palmitoyl-2-arachidonoyl-sn-glycerol 3-phosphate
show the reaction diagram
-
enzyme type I: activity is 181% of the activity with rac-1,2-dioleoylglycerol, enzyme type II: activity is 116% of the activity with rac-1,2-dioleoylglycerol
-
-
?
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-palmitoyl-2-linoleoyl-sn-glycerol
ADP + 1-palmitoyl-2-linoleoyl-sn-glycerol 3-phosphate
show the reaction diagram
-
enzyme type I: activity is 116% of the activity with rac-1,2-dioleoylglycerol, enzyme type II: activity is 86% of the activity with rac-1,2-dioleoylglycerol
-
-
?
ATP + 1-palmitoyl-2-oleoyl-sn-glycerol
ADP + 1-palmitoyl-2-oleoyl-sn-glycerol 3-phosphate
show the reaction diagram
-
about 60% of the activity with 1-palmitoyl-2-arachidonoyl-sn-glycerol
-
-
?
ATP + 1-palmitoyl-2-oleoyl-sn-glycerol
ADP + 1-palmitoyl-2-oleoyl-sn-glycerol 3-phosphate
show the reaction diagram
-
96.5% of the activity with 1-stearoyl-2-arachidonoyl-sn-glycerol
-
-
?
ATP + 1-palmitoyl-2-oleoyl-sn-glycerol
ADP + 1-palmitoyl-2-oleoyl-sn-glycerol 3-phosphate
show the reaction diagram
Q13574
about 80% of the activity with sn-1,2-dioleoylglycerol, about 80% of the activity with sn-1,2-dioleoylglycerol, DGKksi
-
-
?
ATP + 1-stearoyl-2-arachidonoyl-sn-glycerol
ADP + 1-stearoyl-2-arachidonoyl-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-arachidonoyl-sn-glycerol
ADP + 1-stearoyl-2-arachidonoyl-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
Q9FFN7
-
-
-
?
ATP + 1-stearoyl-2-arachidonoyl-sn-glycerol
ADP + 1-stearoyl-2-arachidonoyl-sn-glycerol 3-phosphate
show the reaction diagram
P52429
-
-
-
?
ATP + 1-stearoyl-2-arachidonoyl-sn-glycerol
ADP + 1-stearoyl-2-arachidonoyl-sn-glycerol 3-phosphate
show the reaction diagram
Q13574
108% of the activity with sn-1,2-dioleoylglycerol
-
-
?
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
-
-
?
ATP + 1-stearoyl-2-arachidonoyl-sn-glycerol
ADP + 1-stearoyl-2-arachidonoyl-sn-glycerol 3-phosphate
show the reaction diagram
-
about 110% of the activity with 1,2-dioleoyl-sn-glycerol
-
-
?
ATP + 1-stearoyl-2-arachidonoyl-sn-glycerol
ADP + 1-stearoyl-2-arachidonoyl-sn-glycerol 3-phosphate
show the reaction diagram
-
preferred substrate of isoform diacylglycerol kinase epsilon
-
-
?
ATP + 1-stearoyl-2-arachidonoyl-sn-glycerol
ADP + 1-stearoyl-2-arachidonoyl-sn-glycerol 3-phosphate
show the reaction diagram
-
isoform DGKepsilon shows 100% activity with 0.38 mol% 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
P52429
in wild-type, ratio of enzymic activity of substrates 1-stearoyl-2-linoleoyl-sn-glycerol to 1-stearoyl-2-arachidonoyl-sn-glycerol is 0.109
-
-
?
ATP + 1-stearoyl-2-docosahexaenoyl-sn-glycerol
ADP + 1-stearoyl-2-docosahexaenoyl-sn-glycerol
show the reaction diagram
P52429
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-linoleoyl-sn-glycerol
ADP + 1-stearoyl-2-linoleoyl-sn-glycerol 3-phosphate
show the reaction diagram
P52429
-
-
-
?
ATP + 1-stearoyl-2-linoleoyl-sn-glycerol
ADP + 1-stearoyl-2-linoleoyl-sn-glycerol 3-phosphate
show the reaction diagram
P52429
in wild-type, ratio of enzymic activity of substrates 1-stearoyl-2-linoleoyl-sn-glycerol to 1-stearoyl-2-arachidonoyl-sn-glycerol is 0.109
-
-
?
ATP + 1-stearoyl-2-oleoyl-sn-glycerol
ADP + 1-stearoyl-2-oleoyl-sn-glycerol 3-phosphate
show the reaction diagram
P52429
-
-
-
?
ATP + 2,3-dioleoyl-sn-glycerol
ADP + 2,3-diacyl-sn-glycerol 1-phosphate
show the reaction diagram
-
-
-
-
-
ATP + 2,3-dioleoyl-sn-glycerol
ADP + 2,3-diacyl-sn-glycerol 1-phosphate
show the reaction diagram
-
-
isoform diacylglycerol kinase alpha 8.5%, zeta, 12%, epsilon 6% of the activity with 1,2-dioleoyl-sn-glycerol, respectively
-
?
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 + 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 + ceramide
ADP + ceramide 3-phosphate
show the reaction diagram
-
-
-
-
?
ATP + ceramide
ADP + ceramide 3-phosphate
show the reaction diagram
-
no activity
-
-
-
ATP + ceramide
ADP + ceramide 3-phosphate
show the reaction diagram
-
hardly utilized
-
-
-
ATP + rac-1,2-dioleoylglycerol
ADP + rac-1,2-dioleoylglycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
ATP + sn-1,2-dihexanoylglycerol
ADP + sn-1,2-dihexanoylglycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
ATP + sn-1,2-dioctanoylglycerol
ADP + sn-1,2-dioctanoylglycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
ATP + sn-1,2-dioleoylglycerol
ADP + sn-1,2-dioleoylglycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
ATP + sn-1,2-dioleoylglycerol
ADP + sn-1,2-dioleoylglycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
ATP + sn-1,2-dioleoylglycerol
ADP + sn-1,2-dioleoylglycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
ATP + sn-1,2-dioleoylglycerol
ADP + sn-1,2-dioleoylglycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
ATP + sn-1,2-dioleoylglycerol
ADP + sn-1,2-dioleoylglycerol 3-phosphate
show the reaction diagram
-
-
-
-
-
ATP + sn-1,2-dioleoylglycerol
ADP + sn-1,2-dioleoylglycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
ATP + sn-1,2-dioleoylglycerol
ADP + sn-1,2-dioleoylglycerol 3-phosphate
show the reaction diagram
Q13574
recombinant DGKksi
-
-
?
ATP + sn-1,2-dioleoylglycerol
ADP + sn-1,2-dioleoylglycerol 3-phosphate
show the reaction diagram
-
enzyme type I: activity is 18% of the activity with rac-1,2-dioleoylglycerol, enzyme type II: activity is 19% of the activity with rac-1,2-dioleoylglycerol
-
-
?
ATP + sn-1,3-dioleoylglycerol
ADP + ?
show the reaction diagram
Q13574
about 10% of the activity with sn-1,2-dioleoylglycerol
-
-
?
GTP + dioleoylglycerol
GDP + dioleoylglycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
GTP + sn-1,2-dihexanoylglycerol
GDP + sn-1,2-dihexanoylglycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
ITP + sn-1,2-dihexanoylglycerol
IDP + sn-1,2-dihexanoylglycerol 3-phosphate
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
sn-1,3-dioleoylglycerol is not a substrate
-
-
-
additional information
?
-
-
enzyme form I and II show a preference for diacylglycerol substrates with saturated acyl chains of 10-12 carbon atoms
-
-
-
additional information
?
-
-
no activity with ficaprenol
-
-
-
additional information
?
-
-
diacylglycerol emulsion
-
-
-
additional information
?
-
-
the enzyme is active in mixed micelles containing octyl glucoside and dioleoylglycerol
-
-
-
additional information
?
-
-
complex enzyme regulation involving alternative splicing, overview, the enzyme is involved in several processes such as cell growth, neuronal transmission, and cytoskeleton remodeling
-
-
-
additional information
?
-
-
complex enzyme regulation, overview, the enzyme is involved in several processes such as cell growth, neuronal transmission, and cytoskeleton remodeling
-
-
-
additional information
?
-
-
the enzyme inhibits neurotransmission to control behaviour by terminating diacylglycerol signaling, probably independent of Galpha0 signaling
-
-
-
additional information
?
-
Q9FFN7
the isozyme DGK2 is involved in cold signal transduction
-
-
-
additional information
?
-
-
the isozyme zeta interacts with phosphoinositol phosphate 5-kinase activating it via phosphatidic acid, isozyme theta associates with RhoA, complex enzyme regulation involving alternative splicing, overview, the enzyme is involved in several processes such as cell growth, neuronal transmission, and cytoskeleton remodeling
-
-
-
additional information
?
-
-
1-oleoyl-rac-glycerol is a poor substrate
-
-
-
additional information
?
-
-
isozymes DGKzeta, DGKalpha, and DGKepsilon utilize 1-alkyl-2-acyl-glycerols as substrates, addition of cholesterol and/or phosphatidylethanolamine reduce the substrate specificity
-
-
-
additional information
?
-
-
DGK-3 affects the resetting of the thermal memory by altering plasticity in the temperature range of AFD synaptic output, without detectably affecting plasticity in the temperature range of AFD temperature sensitivity
-
-
-
additional information
?
-
-
DGKzeta blocks cardiac hypertrophic programs in response to endothelin-1 in neonatal rat cardiomyocytes. DGKzeta blocks cardiac hypertrophy induced by G protein-coupled receptor agonists and pressure overload in vivo. DGKzeta attenuates ventricular remodeling and improves survival after myocardial infarction
-
-
-
additional information
?
-
P23743
diacylglycerol kinase alpha suppresses tumor necrosis factor-alpha-induced apoptosis of human melanoma cells through NF-kappaB activation
-
-
-
additional information
?
-
-
diacylglycerol kinase delta regulates protein kinase C and epidermal growth factor receptor signaling
-
-
-
additional information
?
-
-
diacylglycerol kinase gamma interacts with and activates beta2-chimaerin, a Rac-specific GAP, in response to epidermal growth factor
-
-
-
additional information
?
-
-
diacylglycerol kinase zeta plays a role in modulation of membrane trafficking. DGKzeta depletion in JURKAT cells accelerates transferrin receptor exit from the endocytic recycling compartment
-
-
-
additional information
?
-
Q80UP3
diacylglycerol kinase zeta regulates microbial recognition and host resistance to Toxoplasma gondii
-
-
-
additional information
?
-
-
nuclear DGKgamma regulates cell cycle
-
-
-
additional information
?
-
Q80UP3
nuclear diacylglycerol kinase-zeta is a negative regulator of cell cycle progression in C2C12 mouse myoblasts
-
-
-
additional information
?
-
Q307R0
phospholipase C/diacylglycerol kinase-mediated signalling is required for benzothiadiazole-induced oxidative burst and hypersensitive cell death in rice suspension-cultured cells
-
-
-
additional information
?
-
-
Rv2252 encodes a diacylglycerol kinase involved in the biosynthesis of phosphatidylinositol mannosides
-
-
-
additional information
?
-
-
T cell anergy is reversed by active Ras and is regulated by diacylglycerol kinase-alpha
-
-
-
additional information
?
-
-
the enzyme plays a role in the secretion of lethal exosomes bearing Fas ligand during activation-induced cell death of T lymphocytes
-
-
-
additional information
?
-
P19638
the soluble diacylglycerol kinase DgkB is required for lipoteichoic acid production in Bacillus subtilis
-
-
-
additional information
?
-
-
activation of a Ca2+-independent protein kinase C isozyme by 1,2-diacylglycerol, which is generated by phospholipase Cbeta and phospholipase D activation and inactivated by phosphorylation via diacylglycerol kinase, is responsible for the endothelin-1-induced decreases in Ca2+ transients and cell shortening
-
-
-
additional information
?
-
-
diacylglycerol kinase alpha is involved in secretion of pro-apoptotic protein Fas ligand by T-lymphocytes via the regulation of the release of lethal exosomes by the exocytic pathway
-
-
-
additional information
?
-
P49619
diacylglycerol kinase gamma regulates beta2-chimaerin, a GTPase-activating protein for Rac
-
-
-
additional information
?
-
-
diacylglycerol kinase is involved in the regulation of oxidative stress-induced intestinal cell injury
-
-
-
additional information
?
-
-
diacylglycerol kinase zeta and syntrophins play a role at multiple stages of the cell fusion process. Potential link between changes in the lipid content of the membranebilayer and reorganization of the actin cytoskeleton during myoblast fusion
-
-
-
additional information
?
-
Q80UP3
diacylglycerol kinase zeta is a key determinant of cell cycle progression and differentiation of C2C12 cells
-
-
-
additional information
?
-
-
diacylglycerol kinase zeta is involved in control of vesicle trafficking
-
-
-
additional information
?
-
-
diacylglycerol kinases alpha and zeta synergistically promote T cell maturation in the thymus
-
-
-
additional information
?
-
-
diacylglycerol kinases are required for anchorage-independent growth in MDA-MB-231 cells
-
-
-
additional information
?
-
P19638
no substrate: monoacylglycerol, ceramide, or undecaprenol
-
-
-
additional information
?
-
-
1,2-diacylglycerol embedded in unilamellar dioleoyl-phosphatidylcholine vesicles is not a substrate for DgkB
-
-
-
additional information
?
-
P52429, Q13574
2-arachidonoyl glycerol is a very poor substrate for the epsilon isoform of diacylglycerol kinases. 2-Oleoyl glycerol is also a poor substrate for this isoform of diacylglycerol kinases
-
-
-
additional information
?
-
P52429, Q13574
2-arachidonoyl glycerol is a very poor substrate for the zeta isoforms of diacylglycerol kinases. 2-Oleoyl glycerol is also a poor substrate for this isoform
-
-
-
additional information
?
-
-
alkyl-lysophosphatidic acid can be produced in SKOV-3 cells by diacylglycerol kinase-mediated phosphorylation of 1-O-hexadecyl-sn-2-acetyl glycerol followed by deacetylation of 1-O-hexadecyl-sn-2-acetyl glycerol 3-phosphate. Production of alkyl-lysophosphatidic acid is stimulated by sphingosine and its analogues
-
-
-
additional information
?
-
P52429
the cholesterol recognition/interaction amino acid consensus domain adjacent to the lipoxygenase-like motif plays a role in acyl-chain selectivity. Despite the high degree of conservation of the amino acid sequence in this region of the protein, certain mutations result in proteins with higher activity than the wild-type protein. These mutations also result in a selective gain of acyl-chain preferences for diacylglycerols with different acyl-chain profiles. In addition to the lipoxygenase-like motif, adjacent residues also contribute to selectivity for diacylglycerols with specific acyl-chain compositions
-
-
-
additional information
?
-
P52429
water does not compete with diacylglycerol as an acceptor of the gamma-phosphate of ATP. Neither with the highly specific substrate, 1-stearoyl-2-arachidonoyl-sn-glycerol, nor with a less specific substrate, 1-stearoyl-2-linoleoyl-sn-glycerol, is there any evidence for ATP hydrolysis accompanying substrate phosphorylation
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
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-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
the enzyme functions to recycle diacylglycerol which is generated largely as a by-product of membrane-derived oligosaccharide biosynthesis
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
the enzyme may regulate the intracellular concentration of diacylglycerol
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
the enzyme is involved in resynthesis of phosphatidylinositol by converting a second messenger diacylglycerol to phosphatidic acid
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
DGKiota may have important cellular functions in retina and brain
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
DAGKalpha is stimulated vby Src-like kinase-dependent phosphoinositide 3 kinase activation in lymphocytes. In vivo the increase in cellular levels of Src-like kinase-dependent phosphoinositide 3 kinase products is sufficient to induce DAGKalpha activation, allowing DAGKalpha relocation to the intact lymphocyte
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
nuclear DGK-theta is activated in response to alpha-thrombin
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
Q64398
the enzyme plays a role in cellular processes by regulating the intracellular concentration of the second messenger diacylglycerol. DGKeta may play a more general role in regulating cellular diacylglycerol levels
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
Q86XP1
the expression of DGKeta2 is suppressed by glucocorticoid in contrast to the marked induction of DGKeta1
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
high level expression of DGKalpha is induced following a signal transmitted through the pre-T-cell-receptor and the protein tyrosine kinase lck. Activity of DGKalpha contributes to survival in CD4+ 8+ double positive thymocytes as pharmacological inhibition of DGK activity results in death of this cell population both in cell suspension and thymic explants. DGKalpha promotes survival in theses thymocytes through a Bcl-regulated pathway
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
Q01583
the enzyme may have an important function in the adult nervous system and muscle and during the development of the embryonic nervous system
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
DGK-Ialpha is involved in IL-2-mediated lymphocyte proliferation
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
the 80000 Da and the 150000 Da enzyme form do not possess specificity towards diacylglycerol molecular species
-
-
?
ATP + 1,2-diacyl-sn-glycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
DGKgamma negatively regulates macrophage differentiation through its catalytic action operating on the cytoskeleton
-
-
?
ATP + 1,2-diacylglycerol
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
P0ABN1
-
-
-
?
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
-
-
-
r
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
-
-
-
r
ATP + 1,2-diacylglycerol
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-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
Q9FFN7
-
-
-
?
ATP + 1,2-diacylglycerol
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-diacylglycerol
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
P20192
-
-
-
?
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
reaction takes place during stimulated phosphatidylinositol turnover
-
-
?
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
second messenger and intermediate in lipid synthesis
-
-
?
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
termination of diacylglycerol signaling, isozymes DGKalpha, DGKbeta, and DGKgamma play a pivotal role in development and metabolism of brain
-
-
?
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
the enzyme binds and regulates signalling proteins which are activated by either diacylglycerol or phosphatidic acid
-
-
?
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
-
the enzyme binds and regulates signalling proteins which are activated by either diacylglycerol or phosphatidic acid, isozyme dgk-1 regulates diacylglycerol signalling required for acetylcholine release
-
-
?
ATP + 1,2-diacylglycerol
ADP + 1,2-diacyl-sn-glycerol 3-phosphate
show the reaction diagram
Dictyostelium discoideum HL5
-
-
-
-
?
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
?
-
-
complex enzyme regulation involving alternative splicing, overview, the enzyme is involved in several processes such as cell growth, neuronal transmission, and cytoskeleton remodeling
-
-
-
additional information
?
-
-
complex enzyme regulation, overview, the enzyme is involved in several processes such as cell growth, neuronal transmission, and cytoskeleton remodeling
-
-
-
additional information
?
-
-
the enzyme inhibits neurotransmission to control behaviour by terminating diacylglycerol signaling, probably independent of Galpha0 signaling
-
-
-
additional information
?
-
Q9FFN7
the isozyme DGK2 is involved in cold signal transduction
-
-
-
additional information
?
-
-
the isozyme zeta interacts with phosphoinositol phosphate 5-kinase activating it via phosphatidic acid, isozyme theta associates with RhoA, complex enzyme regulation involving alternative splicing, overview, the enzyme is involved in several processes such as cell growth, neuronal transmission, and cytoskeleton remodeling
-
-
-
additional information
?
-
-
DGK-3 affects the resetting of the thermal memory by altering plasticity in the temperature range of AFD synaptic output, without detectably affecting plasticity in the temperature range of AFD temperature sensitivity
-
-
-
additional information
?
-
-
DGKzeta blocks cardiac hypertrophic programs in response to endothelin-1 in neonatal rat cardiomyocytes. DGKzeta blocks cardiac hypertrophy induced by G protein-coupled receptor agonists and pressure overload in vivo. DGKzeta attenuates ventricular remodeling and improves survival after myocardial infarction
-
-
-
additional information
?
-
P23743
diacylglycerol kinase alpha suppresses tumor necrosis factor-alpha-induced apoptosis of human melanoma cells through NF-kappaB activation
-
-
-
additional information
?
-
-
diacylglycerol kinase delta regulates protein kinase C and epidermal growth factor receptor signaling
-
-
-
additional information
?
-
-
diacylglycerol kinase gamma interacts with and activates beta2-chimaerin, a Rac-specific GAP, in response to epidermal growth factor
-
-
-
additional information
?
-
-
diacylglycerol kinase zeta plays a role in modulation of membrane trafficking. DGKzeta depletion in JURKAT cells accelerates transferrin receptor exit from the endocytic recycling compartment
-
-
-
additional information
?
-
Q80UP3
diacylglycerol kinase zeta regulates microbial recognition and host resistance to Toxoplasma gondii
-
-
-
additional information
?
-
-
nuclear DGKgamma regulates cell cycle
-
-
-
additional information
?
-
Q80UP3
nuclear diacylglycerol kinase-zeta is a negative regulator of cell cycle progression in C2C12 mouse myoblasts
-
-
-
additional information
?
-
Q307R0
phospholipase C/diacylglycerol kinase-mediated signalling is required for benzothiadiazole-induced oxidative burst and hypersensitive cell death in rice suspension-cultured cells
-
-
-
additional information
?
-
-
Rv2252 encodes a diacylglycerol kinase involved in the biosynthesis of phosphatidylinositol mannosides
-
-
-
additional information
?
-
-
T cell anergy is reversed by active Ras and is regulated by diacylglycerol kinase-alpha
-
-
-
additional information
?
-
-
the enzyme plays a role in the secretion of lethal exosomes bearing Fas ligand during activation-induced cell death of T lymphocytes
-
-
-
additional information
?
-
P19638
the soluble diacylglycerol kinase DgkB is required for lipoteichoic acid production in Bacillus subtilis
-
-
-
additional information
?
-
-
activation of a Ca2+-independent protein kinase C isozyme by 1,2-diacylglycerol, which is generated by phospholipase Cbeta and phospholipase D activation and inactivated by phosphorylation via diacylglycerol kinase, is responsible for the endothelin-1-induced decreases in Ca2+ transients and cell shortening
-
-
-
additional information
?
-
-
diacylglycerol kinase alpha is involved in secretion of pro-apoptotic protein Fas ligand by T-lymphocytes via the regulation of the release of lethal exosomes by the exocytic pathway
-
-
-
additional information
?
-
P49619
diacylglycerol kinase gamma regulates beta2-chimaerin, a GTPase-activating protein for Rac
-
-
-
additional information
?
-
-
diacylglycerol kinase is involved in the regulation of oxidative stress-induced intestinal cell injury
-
-
-
additional information
?
-
-
diacylglycerol kinase zeta and syntrophins play a role at multiple stages of the cell fusion process. Potential link between changes in the lipid content of the membranebilayer and reorganization of the actin cytoskeleton during myoblast fusion
-
-
-
additional information
?
-
Q80UP3
diacylglycerol kinase zeta is a key determinant of cell cycle progression and differentiation of C2C12 cells
-
-
-
additional information
?
-
-
diacylglycerol kinase zeta is involved in control of vesicle trafficking
-
-
-
additional information
?
-
-
diacylglycerol kinases alpha and zeta synergistically promote T cell maturation in the thymus
-
-
-
additional information
?
-
-
diacylglycerol kinases are required for anchorage-independent growth in MDA-MB-231 cells
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
-
absolute requirement for a divalent ion. Mg2+ is more effective than Mn2+ or Ca2+
Ca2+
-
2 mol of Ca2+ per mol of enzyme. Ca2+ plus phosphatidylserine markedly activates by reducing the Km value for ATP
Ca2+
-
DGK I: good activator, DGK IV: activation with 1 mM CaCl2 is comparable to that obtained on presence of MgCl2
Ca2+
-
plus phosphatidylserine, activates enzyme DGK-Igamma
Ca2+
-
plus phosphatidylserine, activates enzyme DGK-Ibeta
Ca2+
-
plus phosphatidylserine, activates enzyme DGK-Ialpha
Ca2+
-
activity is independent of Ca2+, dissociation constant is 0.00044 mM, hydrophobic region of the enzyme is masked by addition of Ca2+; enzyme can bind approximately 2 mol of Ca2+ per mol
Ca2+
-
activity is independent of Ca2+, dissociation constant is 0.00089 mM, binding of Ca2+ results in exposure of hydrophobic amino acids; enzyme can bind approximately 2 mol of Ca2+ per mol
Ca2+
-
enzyme can bind approximately 2 mol of Ca2+ per mol; enzyme requires Ca2+, dissociation constant is 0.0099 mM, hydrophobic region of the enzyme is masked by addition of Ca2+
Ca2+
-
activates in vitro, interacts via N-terminal RVH motif and EF hands
Ca2+
-
dependent on, maximal below 0.01 mM
Ca2+
-
dependent on, isozymes DGKalpha, DGKbeta, and DGKgamma
Ca2+
-
isoform diacylglycerol kinase alpha requires Ca2+
Ca2+
-
Ca2+ requirement in DGKalpha activation
Ca2+
O88673
Ca2+ requirement in DGKalpha activation
Ca2+
O88673, Q80UP3, Q9R1C6
activates; activates; activates
Cd2+
-
enzyme requires a free divalent metal cation: Mg2+, Mn2+, Co2+, Cd2+ or Zn2+
Cd2+
-
when Mg2+ is excluded from the assay, Cd2+ supports activity to lesser extent
Co2+
-
enzyme requires a free divalent metal cation: Mg2+, Mn2+, Co2+, Cd2+ or Zn2+
Co2+
-
when Mg2+ is excluded from the assay, Co2+ supports activity to lesser extent
Mg2+
-
absolute requirement for a divalent ion. Mg2+ is more effective than Mn2+ or Ca2+. 50% stimulation by 0.4 mM Mg2+, maximal activity at 5-40 mM
Mg2+
-
enzyme requires a free divalent metal cation: Mg2+, Mn2+, Co2+, Cd2+ or Zn2+
Mg2+
-
divalent cation is required for activity. Mg2+ is most effective, maximal activation at about 10 mM
Mg2+
-
the enzyme is dependent on
Mg2+
-
required
Mg2+
-
DGK I: maximal activation at 20 mM. DGK IV: maximal activation at 5 mM
Mg2+
-
required, optimal activity at 2.5 mM for DGK-I, 5.0 mM for DGK-II and 10.0 mM for DGK-III
Mg2+
-
required, maximal activity at 3 mM MgCl2, half-maximal activity at around 1 mM
Mg2+
-
required, optimal activity of microsomal enzyme at 2 mM, optimal activity of soluble enzyme at 10 mM
Mg2+
-
a second Mg2+ in addition to MgATP is required for activity
Mg2+
-
coordidating bivalent metal ion is involved in substrate binding
Mg2+
Q9FFN7
dependent on
Mg2+
-
at 10 mM MgCl2
Mg2+
-
structure reveals a Mg2+ site and an associated Asp-water-Mg2+ network
Mg2+
-
required for activity, interfacial binding of DgkB requires a Mg2+-dependent conformational change
Mg2+
P0ABN1
required for activity
Mn2+
-
absolute requirement for a divalent ion. Mg2+ is more effective than Mn2+ or Ca2+. Mn2+ is more effective on the enzyme from microtubule than on the enzyme from supernatant
Mn2+
-
enzyme requires a free divalent metal cation: Mg2+, Mn2+, Co2+, Cd2+ or Zn2+. Ka for Mg2+ is 3.4 mM
Mn2+
-
slight activation at 5 mM
Mn2+
-
DGK I: activation is not so great as with MgCl2. Maximal stimulation at 0.1 mM. DGK IV: activation is 10fold less than with MgCl2
Mn2+
-
Mg2+ requirement can be partially substituted by Mn2+
Zinc
-
the enzyme contains two zinc fingers
Zinc
-
the sterile alpha motif domain of diacylglycerol kinase delta binds zinc at multiple sites, driving the organization of the enzyme into large sheets of polymers. A mutant enzyme containing a sterile alpha motif domain refractory to zinc binding 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
Zn2+
-
enzyme requires a free divalent metal cation: Mg2+, Mn2+, Co2+, Cd2+ or Zn2+
Zn2+
-
when Mg2+ is excluded from the assay, Zn2+ supports activity to lesser extent
Mn2+
-
when Mg2+ is excluded from the assay, Mn2+ supports activity to lesser extent
additional information
-
effects of liposome composition on substrate specificity and catalytic activity level of the isozymes
additional information
-
neither Ca2+, Mn2+, nor Zn2+ is able to effectively replace Mg2+, although Ca2+ and Mn2+ support a few percent activity
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
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%
2,3-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
P52429, Q13574
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
P52429, Q13574
inhibits diacylglycerol kinase epsilon less than does 2-arachidonoyl glycerol; shows similar inhibitory potency for diacylglycerol kinase zeta as 2-arachidonoyl glycerol
adenosine
-
0.5 mM, 5% inhibition of DGK I and 28% inhibition of DGK IV
adenosine 5'-tetraphosphoryl-3-O-(1,2-dihexanoyl)-sn-glycerol
-
-
ADP
-
0.5 mM, 77% inhibition of DGK I and 66% inhibition of DGK IV
alpha-thrombin
-
apparent binding parameters of diacylglycerol kinase theta increase following alpha-thrombin stimulation
-
AMP
-
0.5 mM, 18% inhibition of DGK I and 14% inhibition of DGK IV
antineutrophil cytoplasmic antibody
-
selective activation of diacylglycerol kinase
-
ATPgammaS
-
-
ATPgammaS
-
0.5 mM, 93% inhibition of DGK I and 71% inhibition of DGK IV
cAMP
-
0.5 mM, 20% inhibition of DGK I and 15% inhibition of DGK IV
CDP
-
0.5 mM, 43% inhibition of DGK I and 28% inhibition of DGK IV
ceramide
-
-
CTP
-
0.5 mM, 42% inhibition of DGK I and 9% inhibition of DGK IV
deoxycholate
-
0.5%, 30% inhibition
deoxycholate
-
1 mM, about 50% inhibition
diacylglycerol
-
above 3.4 mol%, substrate inhibition
dioctanoylglycerol
-
above 3.4 mol%
dioleoylglycerol
-
above 3.4 mol%
ethanol
-
0.5%, 20% inhibition
GDP
-
0.5 mM, 74% inhibition of DGK I and 72% inhibition of DGK IV
GTP
-
0.5 mM, 74% inhibition of DGK I and 56% inhibition of DGK IV
GTPgammaS
-
0.5 mM, 37% inhibition of DGK I and 32% inhibition of DGK IV
H2O2
-
endogenous nuclear diacylglycerol kinase zeta rapidly translocates to the cytoplasm following H2O2 treatment
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
NaCl
Q9FFN7
more than 50% inhibition at above 200 mM
Nonidet
-
0.5%, 45% inhibition
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
phosphate
-
-
phosphatidate
-
moderate
phosphatidic acid
-
competitive inhibition
phosphatidylcholine
-
enzyme form DGK-I, DGK-II and DGK-III
phosphatidylglycerol
-
inhibits phosphatidylcholine-dependent kinase activity
phosphatidylinositol
-
2.5 mol% results in 50% inhibition of the phosphatidylcholine-dependent kinase activity
phosphatidylinositol 4,5-bisphosphate
O88673, Q80UP3, Q9R1C6
potent inhibitor
phosphatidylinositol-(4,5)-bisphosphate
O88673, Q80UP3, Q9R1C6
potent inhibitor; potent inhibitor
quercetin
-
0.1 mM, 41% inhibition of DGK I and 15% inhibition of DGK IV
R59022
-
inhibits the 80000 Da enzyme form but not the 150000 Da enzyme form
R59022
-
inhibits DGK-II and to a lesser extent DGK-III, but little affects DGK-I
R59022
-
-
R59022
Q9FFN7
specific inhibitor
R59022
-
specifc inhibitor of diacylglycerol kinase. Treatment significantly increases glucose transport, p38 and MKK3/6 activation in myotubes. The R59022-induced glucose transport is blocked by SB203580, a specific p38 inhibitor. R59022 fails to stimulate both possible known mechanisms to enhance glucose transport, an IRS1-PI3K-Akt pathway, muscle contraction signaling or GLUT1 and GLUT4 expression
R59022
-
inhibition of diacylglycerol kinase decreases H2O2-induced RIE-1 cell apoptosis
R59022
-
decrease in total diacylglycerol kinase activity and increases in diacylglycerol levels upon incubation of skeletal muscle, with parallel increase in protein kinase C activity and isoform-specific phosphorylation of protein kinase Cdelta. Diacylglycerol kinase inhibition also reduces insulin-stimulated glucose transport
R59949
-
DGKalpha
R59949
-
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
R59949
-
decrease in total diacylglycerol kinase activity and increases in diacylglycerol levels upon incubation of skeletal muscle, with parallel increase in protein kinase C activity and isoform-specific phosphorylation of protein kinase Cdelta. Diacylglycerol kinase inhibition also reduces insulin-stimulated glucose transport
R59949
-
inhibition of diacylglycerol kinase activity accompanied by increased protein kinase Calpha activity, reduced glucose-induced insulin receptor activation, and GLUT4 translocation. Inhibition of decrease in the intracellular levels of diacylglycerol upon exposure of L6 cells to glucose
R59949
-
specific inhibition of diacylglycerol kinase alpha. Inhibition impairs impairs hepatocyte growth factor- and v-Src-induced cell scatter and migration, without affecting the loss of intercellular adhesions, impairs hepatocyre growth factor-induced cell spreading, lamellipodia formation, membrane ruffling, and focal adhesions remodeling and impairs hepatocyte growth factor-induced Rac activation and membrane targeting
R59949
O88673, Q80UP3, Q9R1C6
DGKalpha inhibitor
RhoA
-
V14-RhoA, strong binding to the C-terminal catalytic domain, negative regulation
Sodium deoxycholate
Q9FFN7
at 5 mM
sphingosine
-
inhibits the 150000 Da enzyme
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
-
0.5%, 45% inhibition
-
Triton N-101
-
enzyme form DGK-I, DGK-II and DGK-III
-
Triton N-101
-
-
-
Triton X-100
-
extremely inhibitory to the 80000 Da enzyme and the 150000 Da enzyme form
Triton X-100
-
0.5 mM, 50% inhibition
Triton X-100
Q9FFN7
strong inhibition at up to 2%
LiCl
Q9FFN7
more than 50% inhibition at above 200 mM
additional information
-
addition of cholesterol and/or phosphatidylethanolamine reduce the substrate specificity
-
additional information
Q9FFN7
isozyme DGK2 activity is affected by salts and detergents, no inhibition by Ca2+
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(S)-2-amino-20-((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.
-
1,3-dioleoylglycerol
-
activates
1-monooleoylglycerol
-
activates
1-O-alkylphosphatidylcholine
-
half-maximal activation at 21.9 mol%
1-palmitoyl-2-oleoylglycerophosphocholine
-
activates
4beta-phorbol-12-myristate-13-acetate
Q7ZYJ3
enhances voltage-dependent opening of wild-type and cAMP/H+-uncoupled hyperpolarization activated, cyclic nucleotide-regulated channels. 4beta-Phorbol-12-myristate-13-acetate exerts its effects on channel gating via sequential activation ofprotein kinase C and diacylglycerol kinase coupled with upregulation of mitogen-activated protein kinase and phospholipase A2
acidic phospholipids
-
activation in vitro
-
benzothiadiazole
-
activation of the expression of diacylglycerol kinase OsDAGK1
bis-phosphatidic acid
-
half-maximal activation at 3.9 mol%
-
cAMP
-
stimulates nuclear diacylglycerol kinase catalytic activity
cardiolipin
-
mitochondrial, half-maximal activation at 2.3 mol%
cardiolipin
-
good activator
cardiolipin
-
activates
cardiolipin
-
half-maximal activation by 1 mol%
cholesterol
-
DGKalpha can be activated in vitro in a Ca2+-independent manner by lipids such cholesterol
cholesterol
O88673
DGKalpha can be activated in vitro in a Ca2+-independent manner by lipids such cholesterol
cholesterol 3-sulfate
-
activates
D-glucose
-
exposure of L6 cell myotubes overexpressing human insulin receptors to 25 mM glucose for 5 min decreases the intracellular levels of diacylglycerol, paralleled by transient activation of diacylglycerol kinase and of insulin receptor signaling. Following 30-min exposure, both diacylglycerol levels and diacylglycerol kinase activity return close to basal levels. Glucose exposure redistributes diacylglycerol kinase isoforms alpha and delta, from the prevalent cytosolic localization to the plasma membrane fraction
deoxycholate
-
purified enzyme is completely devoid of activity without addition of phospholipid or deoxycholate
deoxycholate
-
stimulation
deoxycholate
-
the enzyme shows optimal activity in presence of phosphatidylserine or deoxycholate. Lower activity in presence of phosphatidylcholine. Diacylglycerol analogs containing an unsaturated fatty acid at the sn-2 position give optimal enzyme activity irrespective of the presence of deoxycholate
deoxycholate
-
enhances activity of enzyme form DGK-II and DGK-III, enzyme form DGK-I is not much affected
deoxycholate
-
enhances activity
Detergent
-
no activity in absence of detergent
-
di-O-hexadecylphosphatidylcholine
-
half-maximal activation at 13.5 mol%
diacylglycerol 3-phosphate
-
the enzyme apoprotein is attributed to a novel feedback activation involving diacylglycerol 3-phosphate
dilauroyl-N,N-dimethylglycerophosphoethanolamine
-
activates
dilauroyl-N-methylglycerophosphoethanolamine
-
activates
dilauroylglycerophosphocholine
-
activates
dilauroylglycerophosphoethanolamine
-
activates
dilauroylphosphatidylcholine
-
half-maximal activation at 11.9 mol%
dimethylmyristamide
-
activates
dioleoyl ethylene glycol
-
activates
dioleoyl-phosphatidylglycerol
-
-
dioleoylphosphatidylcholine
-
half-maximal activation at 10.4 mol%
dioleoylphosphatidylglycerol
-
half-maximal activation at 6.3 mol%
dipalmitoylphosphatidic acid
-
activates only in presence of Triton X-100
endothelin-1
-
activates diacylglycerol kinase in caveolae/rafts and noncaveolae/rafts of mesenteric arteries. Activation does not depend on phosphatidylinositol 3-kinase. In response to norepinephrin, but not to epithelin-1, protein kinase PKB translocates to caveolae/rafts
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
H2O2
-
endogenous nuclear diacylglycerol kinase zeta rapidly translocates to the cytoplasm following H2O2 treatment
hepatocyte growth factor
-
induces diaclyglycerol kinase activity, which is required for cell invasiveness
-
hexadecanol
-
activates
hexadecyl phosphorylcholine
-
half-maximal activation at 17.3 mol%
hexadecylphosphorylcholine
-
activates
lauryl maltoside
-
activates in presence of 11 mM Triton X-100
Lipid
-
purified enzyme is completely inactive unless a lipid is added to the assay buffer containing Triton X-100
lysophosphatidylcholine
-
activation of phospholipids in the order of decreasing efficiency: phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, sphingomyelin
lysophosphatidylethanolamine
-
activates
myristoylcholine chloride
-
activates
myristyl acetate
-
activates
n-hexyl beta-D-glucoside
-
activates in presence of 11 mM Triton X-100
nitrododecane
-
activates
norepinephrine
-
stimulates an increase in diacylglycerol kinase activity in caveolae/rafts of mesenteric arteries. Activation depends on phosphatidylinositol 3-kinase. In response to norepinephrin, but not to epithelin-1, protein kinase PKB translocates to caveolae/rafts
octyl acetate
-
activates
octyl beta-glucoside
-
activates in presence of 11 mM Triton X-100
oleic acid
-
activates only in presence of Triton X-100
oleoylcholine chloride
-
activates
-
P53
-
p53 activates DGKalpha in response to DNA damage
P53
O88673
p53 activates DGKalpha in response to DNA damage
palmitic acid
-
activates only in presence of Triton X-100
phorbol-12-myristate-13-acetate
P23743, Q13574
diacylglycerol kinase zeta activity at the T cell receptor is enhanced by phorbol-12-myristate-13-acetate cotreatment
phosphatidic acid
-
activates only in presence of Triton X-100
phosphatidic acid
-
good activator of DGK IV, no effect on DGK I activity
phosphatidic acid
-
highly stimulating
phosphatidic acid
-
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
phosphatidic acid
-
production of oxidative burst and hypersensitive cell death. Activation of the epxression of diacylglycerol kinase and transcritional factor gene OsBIERF3. Neomycin partially inhibits the poduction of oxidatve burst, hypersensitive cell death, and expression of both genes
phosphatidyl glycerol
-
good activator
phosphatidylcholine
-
-
phosphatidylcholine
-
the enzyme shows optimal activity in presence of phosphatidylserine or deoxycholate. Lower activity in presence of phosphatidylcholine
phosphatidylcholine
-
activates
phosphatidylcholine
-
moderate enhancement of DGK IV, no effect on DGK I activity
phosphatidylcholine
-
enzyme type II has a preference for phosphatidylcholine as cofactor, enzyme type I can utilize both phosphatidylserine and phosphatidylinositol, but has a lower preference for phosphatidylcholine
phosphatidylcholine
-
activation of phospholipids in the order of decreasing efficiency: phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, sphingomyelin
phosphatidylcholine plasmalogen
-
half-maximal activation at 7.3 mol%
-
phosphatidylethanolamine
-
activates only in presence of Triton X-100
phosphatidylethanolamine
-
plus cardiolipin, activates
phosphatidylethanolamine
-
activation of phospholipids in the order of decreasing efficiency: phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, sphingomyelin
phosphatidylethanolamine
-
DGKalpha can be activated in vitro in a Ca2+-independent manner by lipids such as phosphatidylethanolamine
phosphatidylethanolamine
O88673
DGKalpha can be activated in vitro in a Ca2+-independent manner by lipids such as phosphatidylethanolamine
phosphatidylglycerol
-
effective stimulation
phosphatidylinositol
-
effective stimulation
phosphatidylinositol
-
enhances activity of DGK I and DGK IV
phosphatidylinositol
-
enzyme type II has a preference for phosphatidylcholine as cofactor, enzyme type I can utilize both phosphatidylserine and phosphatidylinositol, but has a lower preference for phosphatidylcholine
phosphatidylinositol 4,5-bisphosphate
-
highly stimulating
phosphatidylserine
-
activates
phosphatidylserine
-
activates
phosphatidylserine
-
-
phosphatidylserine
-
the enzyme shows optimal activity in presence of phosphatidylserine or deoxycholate. Lower activity in presence of phosphatidylcholine
phosphatidylserine
-
good activator
phosphatidylserine
-
enhances activity of DGK I and DGK IV
phosphatidylserine
-
enzyme type II has a preference for phosphatidylcholine as cofactor, enzyme type I can utilize both phosphatidylserine and phosphatidylinositol, but has a lower preference for phosphatidylcholine
phosphatidylserine
-
activation of phospholipids in the order of decreasing efficiency: phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, sphingomyelin
phosphatidylserine
-
10-20 mol% result in 7.5-7.8fold activation of the recombinant wild-type enzyme, 3.8fold of the recombinant mutant DELTA196, and 6.5fold of the recombinant mutant DELTA332
phosphatidylserine
-
strong activation
phosphatidylserine
-
less effective activator than phosphatidic acid. Phosphatidylserine decreases the apparent surface KM of DGKtheta for dioleoylglycerol; 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
Phospholipid
-
purified enzyme is completely devoid of activity without addition of phospholipid or deoxycholate
Phospholipid
-
activation by phospholipid is not stereospecific and is mimicked partially by fatty acids
Phospholipid
-
enhances activity. Activation of phospholipids in the order of decreasing efficiency: phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, sphingomyelin
Phospholipid
-
a combination of diacylglycerol and phospholipid exclusively leads to full activation
Platelet-activating factor
-
half-maximal activation at 22.4 mol%
rac-1,2-dioleoylglycero-3-sulfate
-
half-maximal activation at 2.7 mol%
sn-1,2-dioleoylglycerol
-
activates
sn-1,3-dioleoylglycerol
-
activates
Sodium cholate
-
enhances activity of DGK I and DGK IV
Sodium deoxycholate
-
enhances activity of DGK I and DGK IV
Sodium dodecyl sulfate
-
activates
sodium hexadecyl sulfate
-
half-maximal activation at 9.8 mol%
Span-20
-
activates
sphingomyelin
-
activation of phospholipids in the order of decreasing efficiency: phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, sphingomyelin
sphingosine
-
potently activates the 80000 Da enzyme
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
stearic acid
-
activates only in presence of Triton X-100
stearoyllysophosphatidylcholine
-
half-maximal activation at 15.8 mol%
Triton X-100
-
activates
methyl myristate
-
activates
additional information
-
serotonin signalling activates the enzyme
-
additional information
Q9FFN7
the isozyme DGK2 is induced by exposure to low temperatures, e.g. 4C
-
additional information
-
DGKzeta interacts with and is regulated by the retinoblastoma protein
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.09
1,2-diarachidonoyl-glycerol
-
pH 7.4, 30C, enzyme form DGK I
0.14
1,2-diarachidonoyl-glycerol
-
pH 7.4, 30C, enzyme form DGK IV
0.45
1,2-diolein
-
pH 7.5, 30C
0.125
1,2-dioleoyl-sn-glycerol
Q9FFN7
pH 7.5, 25C
0.07
1-stearoyl-2-arachidonoyl-glycerol
-
pH 7.4, 30C, enzyme form DGK I
0.09
1-stearoyl-2-arachidonoyl-glycerol
-
pH 7.4, 30C, enzyme form DGK IV
4.2
2'-Deoxy-ATP
-
pH 6.8, 30C, reaction with sn-2,3-dihexanoylglycerol
1
ADP
-
about, pH 6.8, 30C, reaction with sn-2,3-dihexanoylglycerol
0.1
ATP
-
pH 7.5, 25C
0.102
ATP
-
pH 7.5, 25C
0.105
ATP
-
pG 7.4, 30C, enzyme type I
0.125
ATP
-
pH 7.4, 30C, in presence of 1,2-dioleoylglycerol, enzyme form DGK I
0.13
ATP
-
wild-type protein, FLAG-tag, pH 7.2, 25C
0.13
ATP
-
mutant C46A/C113A, pH 6.9, 25C
0.135
ATP
-
N-terminally trucated protein, FLAG-tag, pH 7.2, 25C
0.15
ATP
-
pH 7.4, 30C, enzyme form DGK-I
0.16
ATP
-
pH 6.6, 30C
0.16
ATP
-
pH 7.0, 37C, microsomal enzyme
0.17
ATP
-
pH 7.0, 37C, soluble enzyme
0.2
ATP
-
wild-type protein with C-terminal His-tag, pH 7.2, 25C
0.245
ATP
-
pH 7.4, 30C, enzyme form DGK-II
0.25
ATP
-
pH 7.4, 30C, in presence of 1,2-dioleoylglycerol, enzyme form DGK IV
0.3
ATP
-
pH 7.4, 30C
0.34
ATP
-
wild-type, pH 6.9, 25C
0.4
ATP
-
mutant C46A/C113A/Q33C, pH 6.9, 25C
0.45
ATP
-
pH 7.4, 30C, enzyme form DGK-III
0.5
ATP
-
pH 7.5, 30C, without deoxycholate
0.506
ATP
-
pG 7.4, 30C, enzyme type II
0.6
ATP
-
mutant C46A/C113A/E34C, pH 6.9, 25C
1
ATP
-
mutant C46A/C113A/A29C, pH 6.9, 25C
1.3
ATP
-
mutant C46A/C113A/E28C, pH 6.9, 25C
1.4
ATP
-
pH 6.6, 25C
1.6
ATP
-
pH 7.5, 30C, with 1 mM deoxycholate
2.1
ATP
-
mutant C46A/C113A/F31C, pH 6.9, 25C
2.6
ATP
-
pH 6.8, 30C, reaction with sn-2,3-dihexanoylglycerol
3.3
ATP
-
mutant C46A/C113AA30C, pH 6.9, 25C
4.8
ATP
-
mutant C46A/C113A/R32C, pH 6.9, 25C
0.23
ceramide
-
pH 6.6, 25C
0.25
diacylglycerol
-
pH 7.5, 25C
0.05
diolein
-
pH 7.4, 30C, enzyme form DGK-I
0.065
diolein
-
pH 7.4, 30C, enzyme form DGK-II
0.08
diolein
-
pH 7.4, 30C, enzyme form DGK-III
0.9
dioleoylglycerol
-
pH 7.5, 25C
0.03
GTP
-
pH 6.6, 30C
0.104
GTP
-
pH 7.5, 25C
0.42
GTP
-
pH 7.0, 37C, soluble enzyme
0.63
GTP
-
pH 7.0, 37C, microsomal enzyme
8.7
GTP
-
pH 6.8, 30C, reaction with sn-2,3-dihexanoylglycerol
5.9
ITP
-
pH 6.8, 30C, reaction with sn-2,3-dihexanoylglycerol
0.12
MgATP2-
-
wild-type enzyme
0.14
MgATP2-
-
mutant enzyme E76L
0.33
MgATP2-
-
mutant enzyme E69C
0.44
MgATP2-
-
mutant enzyme N72S
0.91
MgATP2-
-
mutant enzyme A14Q
1.5
MgATP2-
-
mutant enzyme K94V
0.1
sn-1,2-dioleoylglycerol
-
pH 7.4, 30C, enzyme form DGK IV
0.125
sn-1,2-dioleoylglycerol
-
pH 7.4, 30C, enzyme form DGK I
2.1
MgATP2-
-
mutant enzyme D95N
additional information
additional information
-
Km for dioleoylglycerol is 0.92 mol%
-
additional information
additional information
-
in presence of Triton X-100, used for purification, a biphasic dependency upon diacylglycerol is observed and the apparent Michaelis constant values for diacylglycerol decreases with decreasing Triton concentration
-
additional information
additional information
-
-
-
additional information
additional information
-
Km-values are 0.92 mol% for dioleoylglycerol and 3.6 mol% for dioctanoylglycerol
-
additional information
additional information
-
-
-
additional information
additional information
-
kinetics, recombinant wild-type and mutant enzymes
-
additional information
additional information
-
Km values of isozymes DGKzeta, DGKepsilon, and DGKalpha with different substrates in mol%
-
additional information
additional information
-
kinetics, follow a Michaelis-Menten mechanism in case of medium-chain diacylglycerols, and are strongly dependent on detergent concentration and sort used in the micelles in the assay in case of longer-chain substrates showing sigmoidal kinetics, overview
-
additional information
additional information
-
turnover numbers of full-length DGKepsilon with a C-terminal His tag, full-length FLAG-DGKepsilon and truncated FLAG-DGKepsilon
-
additional information
additional information
-
KMapp for substrate 1,2-dioleoyl-sn-glycerol is 0.9 mol% in presence of 1% phosphatidic acid, 0.6 mol% in presence of 9% phosphatidylserine, and 8.0 mol% without additive
-
additional information
additional information
-
Km-value in mol% for wild-type 9.2, mutant C46A/C113A 4.9, mutant C46A/C113A/E28C 5.7, mutant C46A/C113A/A29C 7.4, mutant C46A/C113AA30C 27.2, mutant C46A/C113A/F31C 17.2, mutant C46A/C113A/R32C 12.9, mutant C46A/C113A/Q33C 12.1, mutant C46A/C113A/E34C 13.7
-
additional information
additional information
-
Km value in mol% for substrate 1,2-dioleoylglycerol is 0.8 for isoform alpha, 0.52 for isoform zeta, pH 7.2, 30C
-
additional information
additional information
-
Km value for wild-type is 0.59 mol%, for mutant P32A 0.13 mol%, using substrate 1-stearoyl-2-oleoyl-sn-glycerol
-
additional information
additional information
P52429
Km value of wild-type, 2.35, mutant Y451, 2.07, mutant R457Q, 1.71 mol% 1-stearoyl-2-arachidonoyl-sn-glycerol, respectively, pH 7.2, 22C
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.032
1,2-dioleoyl-sn-glycerol
-
wild-type protein with C-terminal His-tag, pH 7.2, 25C
1.2
1,2-dioleoyl-sn-glycerol
-
wild-type protein, FLAG-tag, pH 7.2, 25C
2.43
1,2-dioleoyl-sn-glycerol
-
N-terminally trucated protein, FLAG-tag, pH 7.2, 25C
0.162
1-stearoyl-2-arachidonoyl-sn-glycerol
-
wild-type protein with C-terminal His-tag, pH 7.2, 25C
1.7
1-stearoyl-2-arachidonoyl-sn-glycerol
-
wild-type protein, FLAG-tag, pH 7.2, 25C
5.7
1-stearoyl-2-arachidonoyl-sn-glycerol
-
N-terminally trucated protein, FLAG-tag, pH 7.2, 25C
0.087
1-stearoyl-2-linoleoyl-sn-glycerol
-
wild-type protein with C-terminal His-tag, pH 7.2, 25C
1.23
1-stearoyl-2-linoleoyl-sn-glycerol
-
wild-type protein, FLAG-tag, pH 7.2, 25C
2.8
1-stearoyl-2-linoleoyl-sn-glycerol
-
N-terminally trucated protein, FLAG-tag, pH 7.2, 25C
0.53
1-stearoyl-2-oleoyl-sn-glycerol
-
mutant P32A
2.35
1-stearoyl-2-oleoyl-sn-glycerol
-
wild-type
0.01
ATP
-
wild-type protein with C-terminal His-tag, pH 7.2, 25C
8.2
ATP
-
wild-type protein, FLAG-tag, pH 7.2, 25C
23
ATP
-
N-terminally trucated protein, FLAG-tag, pH 7.2, 25C
additional information
additional information
-
-
-
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
LITERATURE
IMAGE
0.095
ADP
-
pH 7.5, 25C
0.102
ATP
-
pH 7.5, 25C
0.06
CDP
-
pH 7.5, 25C
0.48
CTP
-
pH 7.5, 25C
0.058
GDP
-
pH 7.5, 25C
0.123
GDPbetaS
-
pH 7.5, 25C
0.081
GTP
-
pH 7.5, 25C
0.038
IDP
-
pH 7.5, 25C
2.5
phosphate
-
pH 7.5, 25C
0.043
UDP
-
pH 7.5, 25C
0.26
UTP
-
pH 7.5, 25C
0.51
ITP
-
pH 7.5, 25C
additional information
additional information
-
Ki-value for adenosine 5'-tetraphosphoryl-3-O-(1,2-dihexanoyl)-sn-glycerol is 0.036 mol%
-
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, 30C
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.00001
-
recombinant MBP-fusion enzyme in recombinant insect cell extract, substrate 1-oleoyl-rac-glycerol
0.0002 - 0.018
-
substrate specificity and catalytic activity level of the isozymes at different liposome compositions
0.0004
-
mutant enzyme D271A, specific activity is less than 0.0004 micromol/min/mg, in 50 mM HEPES, pH 7.4, 150 mM LiCl, 10 mM MgCl2, 5 mM ATP, and lipid vesicles; mutant enzyme D68A, specific activity is less than 0.0004 micromol/min/mg, in 50 mM HEPES, pH 7.4, 150 mM LiCl, 10 mM MgCl2, 5 mM ATP, and lipid vesicles; mutant enzyme E273A, specific activity is less than 0.0004 micromol/min/mg, in 50 mM HEPES, pH 7.4, 150 mM LiCl, 10 mM MgCl2, 5 mM ATP, and lipid vesicles
0.0008
-
recombinant MBP-fusion enzyme in recombinant insect cell extract, substrate 1,3-dioleoyl-sn-glycerol
0.0019
-
recombinant MBP-fusion enzyme in recombinant insect cell extract, substrate 1,2-dioleoyl-sn-glycerol
0.0021
-
recombinant MBP-fusion enzyme in recombinant insect cell extract, substrate 1-stearoyl-2-arachidonoyl-sn-glycerol
0.0023
-
mutant enzyme N96A, in 50 mM HEPES, pH 7.4, 150 mM LiCl, 10 mM MgCl2, 5 mM ATP, and lipid vesicles
0.0024
-
mutant enzyme D124A, in 50 mM HEPES, pH 7.4, 150 mM LiCl, 10 mM MgCl2, 5 mM ATP, and lipid vesicles
0.0028
-
mutant enzyme K15A/K165A, in 50 mM HEPES, pH 7.4, 150 mM LiCl, 10 mM MgCl2, 5 mM ATP, and lipid vesicles
0.0031
-
mutant enzyme T94A, in 50 mM HEPES, pH 7.4, 150 mM LiCl, 10 mM MgCl2, 5 mM ATP, and lipid vesicles
0.0036
-
mutant enzyme D97A, in 50 mM HEPES, pH 7.4, 150 mM LiCl, 10 mM MgCl2, 5 mM ATP, and lipid vesicles
0.0062
-
mutant enzyme D216A, in 50 mM HEPES, pH 7.4, 150 mM LiCl, 10 mM MgCl2, 5 mM ATP, and lipid vesicles
0.0122
-
mutant enzyme K15A, in 50 mM HEPES, pH 7.4, 150 mM LiCl, 10 mM MgCl2, 5 mM ATP, and lipid vesicles
0.0139
-
mutant enzyme K165A, in 50 mM HEPES, pH 7.4, 150 mM LiCl, 10 mM MgCl2, 5 mM ATP, and lipid vesicles
0.0168
-
mutant enzyme R100A, in 50 mM HEPES, pH 7.4, 150 mM LiCl, 10 mM MgCl2, 5 mM ATP, and lipid vesicles
0.0249
-
wild type enzyme, in 50 mM HEPES, pH 7.4, 150 mM LiCl, 10 mM MgCl2, 5 mM ATP, and lipid vesicles
0.0256
-
mutant enzyme R20A, in 50 mM HEPES, pH 7.4, 150 mM LiCl, 10 mM MgCl2, 5 mM ATP, and lipid vesicles
2.207
-
enzyme form DGK-II
4.74
-
enzyme form DGK-I
4.8
P19638
substrate 1,2-dioctanoyl-sn-glycerol, pH 7.0, 25C
5.187
-
enzyme form DGK IV
6.753
-
enzyme form DGK-III
6.913
-
-
7.5
-
purified solubilized MBP-fusion wild-type enzyme
7.7
-
1500000 Da enzyme
11.5
-
enzyne form DGK I
15
-
80000 Da enzyme
23
-
purified recombinant mutant W25L
26
-
purified recombinant mutant W18L/W25L/W47L
36
-
purified recombinant mutant W18L/W25L/W47L/W117L
42
-
purified recombinant mutant W18L/W25L
61
-
purified recombinant mutant W18L
77
-
purified recombinant mutant W18L/W47L/W117L
89
P19638
substrate 1,2-dioleoyl-sn-glycerol, pH 7.0, 25C
102
-
purified recombinant wild-type enzyme
additional information
-
the enzyme is assayed by using endogenous substrate
additional information
-
activity measurment of enzyme solubilized in liposomes consisting different amounts of 1,2-dioleoylphosphatidylcholine, 1,2-dioleoylphosphatidylethanolamine, and 1,2-dioleoylphosphatidylserine, overview
additional information
Q9FFN7
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.1
-
enzyme from supernantant fraction
6.3 - 8.3
-
-
6.4
-
enzyme from microtubule
6.9
-
assay at
7
-
and a second optimum at pH 8
7
-
broad around, enzyme in plasma membrane vesicles from shoots
7.4
-
DGK I and DGK IV
7.4
-
phosphatidylcholine-dependent activity
7.5 - 8
-
assay at
8
-
and a second optimum at pH 7
8
-
broad, deoxycholate-dependent or phosphatidylcholine-dependent activity
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4.5 - 7.5
-
pH 4.5: about 50% of maximal activity, pH 7.5: about 45% of maximal activity, enzyme from supernatant. pH 4.5: about 55% of maximal activity, pH 7.5: about 45% of maximal activity, enzyme from microtubuli
6 - 8.5
-
pH 6.0: about 40% of maximal activity, pH 8.5: about 50% of maximal activity
6 - 9
-
about 50% of maximal activity at pH 6.0 and 9.0
6.5 - 7
-
rapid decrease of activity below pH 6.5, pH 7: optimum
6.5 - 7.8
Q9FFN7
rapid decrease below pH 6.5 and above pH 7.8
6.5 - 8.5
-
pH 6.5: about 45% of maximal activity, pH 8.5: about 45% of maximal activity
6.5 - 9
-
pH 6.5: about 35% of maximal activity, pH 9.0: about 65% of maximal activity, phosphatidylcholine-dependent activity
6.8 - 9
-
pH 6.5: about 85% of maximal activity pH 9.0: about 50% of maximal activity, enzyme form DGK I
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
-
assay at
25
-
assay at
25
Q9FFN7
assay at
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4
-
isoelectric focusing
additional information
-
it remains unclear whether the multiple species, observed by isoelectric focusing represent distinct isoforms of the enzyme, or are modified versions of the type I and type II enzyme
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
isozymes DGKalpha and DGKzeta
Manually annotated by BRENDA team
O88673
high expression
Manually annotated by BRENDA team
-
Purkinje cells, DGK-Igamma
Manually annotated by BRENDA team
-
DGK-Vtheta, cerebellar cortex and hippocampus
Manually annotated by BRENDA team
-
the enzyme is highly expressed in hippocampus, caudate nucleus, occipital pole, cerebral cortex and cerebellum
Manually annotated by BRENDA team
Q86XP1
DGKeta1
Manually annotated by BRENDA team
-
neuron, DGK-Ibeta
Manually annotated by BRENDA team
-
DGK-Ialpha
Manually annotated by BRENDA team
-
DGK-IVksi, oligodendrocyte, DGK-Ialpha
Manually annotated by BRENDA team
-
DGKksi mRNA is expressed at high level
Manually annotated by BRENDA team
-
post-natal, developing, neuron-specific isozymes DGKbeta and DGKgamma, and isozyme DGKalpha, isozymes alpha and gamma appear at birth and then decline, while isozyme beta appears about 14 days after birth and reaches a maximum at day 28, overview
Manually annotated by BRENDA team
A9YTL2
and olfactory sensilla trichodea, main localization in male adult
Manually annotated by BRENDA team
-
nuclear DGKzeta increases during myogenic differentiation of mouse C2C12 myoblasts
Manually annotated by BRENDA team
-
nuclear diacylglycerol kinase-zeta is a negative regulator of cell cycle progression in C2C12 mouse myoblasts
Manually annotated by BRENDA team
-
diacylglycerol kinase zeta and syntrophins, scaffold proteins of the dystrophin glycoprotein complex that bind directly to diacylglycerol kinase zeta, are spatially regulated during fusion of cultured cells. Both proteins accumulate with the GTPase Rac1 at sites where fine filopodia mediate the initial contact between myoblasts. Diacylglycerol kinase zeta codistributes with the Ca2+-dependent cell adhesion molecule N-cadherin at nascent cell contacts
Manually annotated by BRENDA team
-
treated with benzothiadiazole and infected by Xanthomonas oryza pv. oryza. Treatment activates expression of a diacylglycerol kinase gene, OsDAGK1, and a phosphoinositide-specific phospholipase C gene, OsPI-PLC1, and a defence-related EREBP transcriptional factor gene, OsBIERF3
Manually annotated by BRENDA team
Q86XP1
DGKeta1 and DGKeta2
Manually annotated by BRENDA team
-
ras-transformed
Manually annotated by BRENDA team
-
enzyme expression remains almost unchanged in granulocytic differentiation pathway, enzyme expression remained almost unchanged in granulocytic differentiation pathway
Manually annotated by BRENDA team
-
low activity
Manually annotated by BRENDA team
O88673
low expression
Manually annotated by BRENDA team
-
pyramidal cells, isozymes DGKbeta and DGKgamma
Manually annotated by BRENDA team
-
moderate labeling in the hippocampus
Manually annotated by BRENDA team
-
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
-
a subclone of embryo fibroblasts
Manually annotated by BRENDA team
-
DGKalpha expression in T cells inhibits secretion of FasL-bearing exosomes triggered by receptor stimulation, and subsequent acivation-induced cell death is impaired. Conversely, the inhibition of DGKalpha enhances the secretion of these lethal exosomes carrying mFasL and enhances acivation-induced cell death
Manually annotated by BRENDA team
-
DGKzeta depletion in JURKAT cells accelerates transferrin receptor exit from the endocytic recycling compartment
Manually annotated by BRENDA team
O88673
low expression
Manually annotated by BRENDA team
Q86XP1
DGKeta1 and DGKeta2
Manually annotated by BRENDA team
Q9FFN7
especially cauline
Manually annotated by BRENDA team
-
low activity
Manually annotated by BRENDA team
O88673
low expression
Manually annotated by BRENDA team
Q86XP1
DGKeta1
Manually annotated by BRENDA team
O88673
high expression
Manually annotated by BRENDA team
-
at different developmental stages, isozyme spatiotemporal expression pattern, changes during development, overview
Manually annotated by BRENDA team
-
alveolar, isozymes DGKalpha and DGKzeta
Manually annotated by BRENDA team
-
mammary carcinoma
Manually annotated by BRENDA team
-
breast cancer cell
Manually annotated by BRENDA team
-
mammary carcinoma
Manually annotated by BRENDA team
-
isozyme DGKgamma, day 3-14 after birth
Manually annotated by BRENDA team
-
DGKbeta is expressed in medium spiny neurons constituting the striatonigral and striatopallidal pathways, whereas striatal interneurons are below the detection threshold
Manually annotated by BRENDA team
-
expression of isoform diacylglycerol kinase alpha in several melanoma cell lines but not in noncancerous melanocytes
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
Q01583
tubular muscle
Manually annotated by BRENDA team
-
ventricular myocyte
Manually annotated by BRENDA team
-
expression of diacylglycerol kinase isoform alpha, delta, epsilon, zeta, or theta mRNA
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
-
weak labeling in the neocortex
Manually annotated by BRENDA team
-
of accumbens nucleus, caudate-putamen and olfactory tubercle, DGK-II
Manually annotated by BRENDA team
-
of the brain, DGK-Ibeta
Manually annotated by BRENDA team
-
neuron-specific isozymes DGKbeta and DGKgamma having a spatio-temporally different function in the neuron
Manually annotated by BRENDA team
-
dendritic spines on neuronal dendrites
Manually annotated by BRENDA team
-
weak labeling in the olfactory bulb
Manually annotated by BRENDA team
-
of the brain, DGK-Ialpha
Manually annotated by BRENDA team
-
DGKalpha is expressed predominantly in oligodendrocytes
Manually annotated by BRENDA team
O88673
DGKalpha is expressed predominantly in oligodendrocytes
Manually annotated by BRENDA team
Q86XP1
DGKeta1
Manually annotated by BRENDA team
Q86XP1
DGKeta1
Manually annotated by BRENDA team
-
selective increase in nuclear DGK-theta activity in response to nerve growth factor stimulation
Manually annotated by BRENDA team
-
DGKbeta is the major isozyme in the pituitary gland, the signals are also detected intensely for isoform DGKzeta, moderately for DGKepsilon and faintly for DGKalpha, the signals for isoforms DGKgamma and DGKiota are below the detection level
Manually annotated by BRENDA team
-
isoenzyme DGK-I, DGK-II and DGK-II
Manually annotated by BRENDA team
Q86XP1
DGKeta1
Manually annotated by BRENDA team
-
delay of isozyme DGKgamma
Manually annotated by BRENDA team
-
DGK-Igamma
Manually annotated by BRENDA team
-
expression is induced by benzothiadiazole, and by infection with Magnaporthe grisea. In benzothiadiazole-treated rice seedlings, expression is induced earlier and at a higher level than in water-treated control seedlings after inoculation with Magnaporthe grisea
Manually annotated by BRENDA team
A9YTL2
and brain, main localization in male adult
Manually annotated by BRENDA team
-
short term exposure of skeletal muscle cells to glucose causes a rapid induction of DGK, followed by a reduction of protein kinase C-alpha activity and transactivation of the insulin receptor signaling
Manually annotated by BRENDA team
Q16760
patients with type 2 diabetes mellitus display reduced diacylglycerol kinase delta expression and activity in skeletal muscle
Manually annotated by BRENDA team
-
DGKiota immunoreactivity is distributed solely in the cytoplasm of most of the dorsal root ganglion, DGKzeta is detected heterogeneously in the nucleus and cytoplasm of small neurons of the dorsal root ganglion with variable levels of distribution, whereas it is detected exclusively in the cytoplasm of large neurons
Manually annotated by BRENDA team
O88673
high expression
Manually annotated by BRENDA team
Q86XP1
DGKeta1
Manually annotated by BRENDA team
-
DGKbeta is strongly detected in the striatum, DGKbeta is expressed not only in projection neurons but also in interneurons and is concentrated at perisynaptic sites of asymmetrical synapses
Manually annotated by BRENDA team
-
diacylglycerol kinase beta accumulates on the perisynaptic site of medium spiny neurons in the striatum
Manually annotated by BRENDA team
-
particularly enriched in peripheral T lymphocytes
Manually annotated by BRENDA team
O88673
particularly enriched in peripheral T lymphocytes
Manually annotated by BRENDA team
O88673
high expression
Manually annotated by BRENDA team
Q86XP1
DGKeta1 and DGKeta2
Manually annotated by BRENDA team
-
DGK-IIdelta and DGK-IIIepsilon
Manually annotated by BRENDA team
Q86XP1
DGKeta1
Manually annotated by BRENDA team
-
DGK-IVksi
Manually annotated by BRENDA team
-
particularly enriched in thymus
Manually annotated by BRENDA team
O88673
particularly enriched in thymus
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
Q9Y6T7
DGKbeta
Manually annotated by BRENDA team
-
DGKzeta-immunoreactivity is clearly detected in Iba1-immunoreactive cells of an oval or ameboid shape in the scar region, which represent activated microglia and/or macrophages. DGKzeta-immunoreactivity is not detected in Iba1-immunoreactive, resting microglia of ramified and dendritic configuration in the intact cortex
Manually annotated by BRENDA team
additional information
Q86XP1
DGKeta1 is ubiquitously distributed in various tissues, DGKeta2 is detected only in testis, kidney and colon
Manually annotated by BRENDA team
additional information
-
expression profile of isozymes during development
Manually annotated by BRENDA team
additional information
Q9FFN7
isozyme DGK2 expression in various tissues, expression pattern
Manually annotated by BRENDA team
additional information
-
tissue-specific expression of isozymes
Manually annotated by BRENDA team
additional information
A9YTL2
expression is first detected at day 3 of the pupal stage, then reaches a maximum at the end of the pupal stage, and is maintained at this level during the adult period
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
DGKepsilon is detected in a filamentous pattern, parallel to the long axis of cell, and on actin stress fibers
Manually annotated by BRENDA team
O08560, P49621, P51556
-
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
Q86XP1
DGKeta1 and DGKeta2 are rapidly translocated from the cytoplasm to endosomes in response to stress stimuli. DGKeta1 is rapidly relocated back to the cytoplasm upon removal of stress stimuli. DGKeta2 exhibits sustained endosomal association
Manually annotated by BRENDA team
Q9Y6T7
one variant of DGKbeta is associated with the plasma membrane, the other isoform is predominantly localized within the cytoplasm
Manually annotated by BRENDA team
-
cytoplasm at the early stage of culture, indicating that DGKgamma is transported from the cytoplasm to the nucleus
Manually annotated by BRENDA team
-
DGKiota immunoreactivity is distributed solely in the cytoplasm of most of the dorsal root ganglion
Manually annotated by BRENDA team
O08560, P49621, P51556
co-localizes with actin filaments
Manually annotated by BRENDA team
-
DGK-zeta export from nucleus to cytoplasm is regulated by a leucine-rich nuclear export signal through the exportin chromosome regional maintenance protein 1
Manually annotated by BRENDA team
O88673, Q80UP3, Q9R1C6
in the basal state, DGKzeta resides in the cytoplasm, but upon appropriate cellular events, it translocates to different parts of the cell in order to perform its biological role
Manually annotated by BRENDA team
-
isoform DGKalpha is detected sparsely in the cytoplasm, in aortic smooth muscle cell contracted by serotonin DGKepsilon is detected diffusely in the cytoplasm without a filamentous stress fiber pattern
Manually annotated by BRENDA team
-
localized in the narrow cytoplasmic space between smooth endoplasmic reticulum and plasma membrane
Manually annotated by BRENDA team
Q16760
isoform diacylglycerol kinase delta-1, but not a splice variant isoform diacylglycerol kinase delta-2 or the other type II isoform diacylglycerol kinase ny-1/2, translocates from the cytoplasm to the plasma membrane in HEK-293 and mouse myoblast C2C12 cells within 5 min in response to high glucose levels. The translocation is inhibited by phosphatidylinositol 3-kinase inhibitors, LY294002 and GDC-0941. The PH and C1 domains are responsible for the plasma membrane translocation and the sterile alpha-motif domain negatively regulates the translocation
Manually annotated by BRENDA team
-
isoenzyme DGK-I, DGK-II and DGK-II
Manually annotated by BRENDA team
-
no activity in cytosol
Manually annotated by BRENDA team
-
in lymphocytes the basal activity is 1.6fold higher in the membrane fraction than in cytosol. In neutrophils the basal activity is identical in cytosol and mambrane-fraction
Manually annotated by BRENDA team
-
isozyme DGKgamma in hippocampal pyriamidal cells and proximal dendrites
Manually annotated by BRENDA team
-
DGKalpha is a cytosolic enzyme that must relocate to the membrane in response to receptor stimulation to exercise its function
Manually annotated by BRENDA team
O88673
DGKalpha is a cytosolic enzyme that must relocate to the membrane in response to receptor stimulation to exercise its function
Manually annotated by BRENDA team
-
fusion constructs of Green Fluorescent Protein to truncated forms of diacylglycerol kinase 1 and diacylglycerol kinase 2 missing the catalytic and accessory domains
Manually annotated by BRENDA team
Q86XP1
DGKeta1 and DGKeta2 are rapidly translocated from the cytoplasm to endosomes in response to stress stimuli. DGKeta1 is rapidly relocated back to the cytoplasm upon removal of stress stimuli. DGKeta2 exhibits sustained endosomal association. Oligomerization of DGKeta2 mediated by its SAM domain is largely responsible for its sustained endosomal localization
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
-
trans-Golgi network
Manually annotated by BRENDA team
O08560, P49621, P51556
diacylglacerol kinase isoform gamma
Manually annotated by BRENDA team
-
integral membrane protein
Manually annotated by BRENDA team
-
integral membrane protein
Manually annotated by BRENDA team
-
intrinsic membrane-protein
Manually annotated by BRENDA team
-
in lymphocytes the basal activity is 1.6fold higher in the membrane fraction than in cytosol. In neutrophils the basal activity is identical in cytosol and membrane-fraction
Manually annotated by BRENDA team
-
tightly associated with the inner membrane
Manually annotated by BRENDA team
-
the hydrophobic domain of DGKepsilo does not contribute to substrate specificity but plays a role in permanently sequestering the enzyme to a membrane
Manually annotated by BRENDA team
-
mainly associated with internal membranes
Manually annotated by BRENDA team
-
recruitment of diacylglycerol kinase alpha to the membrane is mediated both via its proline-rich sequence and phosphorylation of Y335
Manually annotated by BRENDA team
-
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
-
sterile alpha-motif of diacylglycerol kinase delta1 forms helical polymers through a head-to-tail interaction. Disruption of polymerization by mutations constitutively localizes the enzyme to the plasma membrane
Manually annotated by BRENDA team
-
the region of transmembrane helix 1 spanning the hydrophobic core of the bilayer runs from Glu28 on the cytoplasmic side to Asp49 or Val50 on the periplasmic side. This locates the charged/polar cluster 32RQE34 within the hydrophobic core of the bilayer. Hydrophobic matching between the protein and the surrounding lipid bilayer is highly efficient
Manually annotated by BRENDA team
-
upon activation of T lymphocytes, diacylglycerol kinase alpha is phosphorylated, and the phosphoprotein is located at the plasma membrane
Manually annotated by BRENDA team
-
DGKalpha is a cytosolic enzyme that must relocate to the membrane in response to receptor stimulation to exercise its function
Manually annotated by BRENDA team
O88673
DGKalpha is a cytosolic enzyme that must relocate to the membrane in response to receptor stimulation to exercise its function
Manually annotated by BRENDA team
P23743, Q13574
at early stages of T cell immunological synapse formation, isoform zeta translocates rapidly to the plasma membrane
Manually annotated by BRENDA team
-
DGK-theta is localized in the speckle domain of the nucleus
Manually annotated by BRENDA team
-
agonist-induced activity of nuclear DGKthata activity, nuclear localization of DGKdelta
Manually annotated by BRENDA team
-
DGKzeta is detected heterogeneously in the nucleus and cytoplasm of small neurons of the dorsal root ganglion with variable levels of distribution, whereas it is detected exclusively in the cytoplasm of large neurons
Manually annotated by BRENDA team
-
involvement of isoform diacylglycerol kinase zeta in cell-cycle progression
Manually annotated by BRENDA team
-
isoform diacylglycerol kinase zeta localizes to the nucleus during interphase including G1, S, and G2 phases in NIH-3T3 cells and in proliferating spermatogonia in the testis. Enzyme is associated with chromatin and dissociates from chromatin during mitotic phase
Manually annotated by BRENDA team
-
a portion of intracellular DGKzeta protein is localized to the nucleus
Manually annotated by BRENDA team
-
DGK-zeta displays a functional independent nuclear export signal sequence between the amino acid residues 362-370
Manually annotated by BRENDA team
-
isoform DGKzeta is observed as a granular pattern in the nucleus, isoform DGKalpha is detected sparsely in the nucleus
Manually annotated by BRENDA team
-
activity of DGK-I is recovered dominantly in the soluble fraction, that for DGK-II in the particulate fraction and that for DGK-III in soluble and particulate fraction
-
Manually annotated by BRENDA team
Q9Y6T7
one variant of DGKbeta is associated with the plasma membrane, the other isoform is predominantly localized within the cytoplasm
Manually annotated by BRENDA team
-
active site of the enzyme is localized to the inner cytoplasmic surface
Manually annotated by BRENDA team
-
activation and relocalization to plasma membrane of DGKalpha is a direct consequence of PI3K activation
Manually annotated by BRENDA team
-
isozyme DGKbeta predominantly, in hippocampal pyriamidal neurons including perikarya and the peripheral dendrites, dendrit cell body
Manually annotated by BRENDA team
Q16760
isoform diacylglycerol kinase delta-1, but not a splice variant isoform diacylglycerol kinase delta-2 or the other type II isoform diacylglycerol kinase ny-1/2, translocates from the cytoplasm to the plasma membrane in HEK-293 and mouse myoblast C2C12 cells within 5 min in response to high glucose levels. The translocation is inhibited by phosphatidylinositol 3-kinase inhibitors, LY294002 and GDC-0941. The PH and C1 domains are responsible for the plasma membrane translocation and the sterile alpha-motif domain negatively regulates the translocation
Manually annotated by BRENDA team
-
activity of DGK-I is recovered dominantly in the soluble fraction, that for DGK-II in the particulate fraction and that for DGK-III in soluble and particulate fraction
-
Manually annotated by BRENDA team
additional information
-
no isozyme DGKgamma in the nucleus, subcellular localization of isozymes in neurons
-
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
additional information
O08560, P49621, P51556
diacylglacerol kinase isoform epsilon is distributed around the perinuclear region
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Staphylococcus aureus (strain MRSA252)
Staphylococcus aureus (strain MRSA252)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
15400
-
gel filtration
640362
64000
O88673, Q80UP3, Q9R1C6
isoform DGKepsilon
702424
68000
-
less than, sucrose density gradient centrifugation
640354
75000
-
microtubular enzyme, sucrose density gradient centrifugation
640351
75000
-
enzyme form DGK-II, gel filtration
640365
76000
-
gel filtration
640370
80000
-
SDS-PAGE
702437
86000
-
gel filtration
640357
90000
-
isoform DGKbeta, SDS-PAGE
702913, 703560
95000
-
gel filtration
640366
104000
-
isoform DGK-zeta, SDS-PAGE
703142
250000
-
gel filtration
640354
additional information
-
the molecular weight of the peak fraction of enzyme from supernatant is 125000 Da and the average molecular weight is 160000 Da, suggesting that more than one species might be present
640351
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
Q86XP1
x * 128000 DGKeta1, calculation from nucleotide sequence
?
-
x * 104000, DGK-IVksi, calculation from amino acid sequence
?
Q86XP1
x * 135000, DGKeta2, calculation from nucleotide sequence
?
-
x * 101400, DGK-Vtheta, calculation from amino acid sequence, x * 130000, DGK-IIdelta, calculation from amino acid sequence
?
-
x * 108000, enzyme from Hela cells, SDS-PAGE
?
-
x * 152000, enzyme form DGK-I, SDS-PAGE
?
-
x * 90300, DGK-Ibeta, calculation from amino acid sequence
?
-
x * 89000, DGK-Igamma, calculation from amino acid sequence
?
-
1 * 110000, enzyme from cell line PC12, SDS-PAGE
?
-
x * 103900, calculation from nucleotide sequence
?
-
x * 110000, enzyme from cell lines MDA-MB-453 and MCF-7, SDS-PAGE
?
-
x * 82700, DGK-Ialpha, calculation from amino acid sequence
?
-
x * 126800, DGK-IIeta, calculation from amino acid sequence
?
-
x * 88500, DGK-Igamma, calculation from amino acid sequence
?
-
x * 13245, calculation from nucleotide sequence, x * 14300, SDS-PAGE
?
-
x * 58000, enzyme form DGK-III, SDS-PAGE
?
-
x *63900, DGK-IIIepsilon, calculation from amino acid sequence
?
-
x * 82600, DGK-Ialpha, calculation from amino acid sequence
?
-
x * 14000 Da, SDS-PAGE
?
-
x * 82200, DGK-Ialpha, calculation from amino acid sequence
?
Q9FFN7
x * 79400, about, sequence calculation, x * 140000, about, recombinant NusA/His6-tagged isozyme DGK2, SDS-PAGE
?
-
x * 88000-90000, isozymes DGKalpha, DGKbeta, and DGKgamma, SDS-PAGE
?
A9YTL2
x * 109500, calculated
?
P19638
x * 34000, calculated and SDS-PAGE
?
-
x * 37333, calculated, x * 42000, SDS-PAGE
homotrimer
P0ABN1
solution nuclear magnetic resonance method
monomer
-
-
monomer
-
1 * 78000, SDS-PAGE
monomer
-
1 * 51000, SDS-PAGE
monomer
-
1 * 86000, SDS-PAGE
monomer
-
1 * 15000, SDS-PAGE
monomer
-
GKepsilon is monomeric on SDS-PAGE but exhibits partial dimerization with low concentrations of perfluorooctanoic acid
additional information
-
isozyme theta is the only one of 9 isozyme forms, that possesses three instead of two cysteine-rich domains at the N-terminal regulatory region
additional information
Q9FFN7
structural organization of isozymes containing a 1,2-diacylglycerol/phorbolester-binding domain 1, a zinc-finger dependent C1 domain, and a 1,2-diacylglycerol accessory domain, overview
additional information
-
structure-function relationships of isozyme domain motifs, e.g. the C1 domain, the EF hand, and the pleckstrin homology, structural motifs and their organization, mammalian isozymes require other domain in addition to the catalytic domain for activity, overview
additional information
-
structure-function relationships of isozyme domain motifs, overview
additional information
-
association of diacylglycerol kinase zeta with sorting nexin 27 via postsynaptic density protein-domain. The sorting nexin 27 postsynaptic density protein-domain contributes to its vesicle localization, interaction with diacylglycerol kinase zeta may regulate localization
additional information
-
diacylglycerol kinase delta2 interacts with the platform subdomain of adaptor protein AP2alpha through its DXF-type binding motif. Binding is involved in the transferrin internalization
additional information
-
diacylglycerol kinase zeta is associated with chromatin and dissociates from chromatin during mitotic phase
additional information
-
interaction with SH3 and SH2 domains of Src are mediated both via its proline-rich sequence and phosphorylation of Y335
additional information
-
nuclear receptor steroidogenic factor 1 binds to diacylglycerol kinase zeta and diacylglycerol kinase theta in vitro and in vivo
additional information
-
sterile alpha-motif of diacylglycerol kinase delta1 forms helical polymers through a head-to-tail interaction. Disruption of polymerization by mutations constitutively localizes the enzyme to the plasma membrane
additional information
-
the N-terminal half of the catalytic region of diacylglycerol kinase gamma interacts with the Src homology 2 and C1 domains of beta-chimaerin. The Src homology 2 domain contributes to the interaction independently of phosphotyrosine
additional information
-
wild-type protein has a weak tendency to oligomerize in presence of weak detergents
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
-
both hepatocytes growth factor stimulation and v-Src transformation induce tyrosine phosphorylation of diacylglycerol kinase alpha on Y335, through a mechanism requiring its proline-rich C-terminal sequence. Both proline-rich sequence and phosphorylation of Y335 mediate its enzymatic activation, its ability to interact respectively with SH3 and SH2 domains of Src, its recruitment to the membrane. Phosphorylation is required for hepatocyte growth factor-induced motility
phosphoprotein
-
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
phosphoprotein
-
the 80000 Da enzyme form is phosphorylated by an unidentified protein kinase
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
sitting-drop vapour-diffusion method. Crystals belong to space group P2(1), with unit-cell parameters a = 42.4, b = 166.1, c = 48.5 A, beta = 96.97
-
isoform DgkB, both as free enzyme and in complex with ADP, 2.4 and 2.3 A resolution, respectively. Enzyme is a tight homodimer, and each monomer comprises two domains with the catalytic center located within the interdomain cleft
-
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
42
-
5 min, complete loss of activity of DGK-II and DGK-III, about 10% loss of activity of enzyme form DGK-I
640365
43 - 45
-
preincubation of microtubules, 10 min, 50% loss of activity
640351
57
-
Triton-solubilized preparation, t1/2: 12 min
640352
100
-
enzyme activity of membranes, t1/2: 20 min
640352
100
-
the membrane preparation shows a threefold stimulation by heating for 5 min followed by a gradual loss of activity, half-life: about 1 h. Butane-1-ol-dissolved enzyme has a half-life of about 45 min
640360
additional information
-
addition of phospholipids provides some protection from thermal inactivation
640352
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
enzyme is unstable in membrane extract, upon storage overnight at 4C 90% of the activity is lost
-
lipid activators stabilize the enzyme agisnt inactivation induced by diacylglycerol. Mg2+ and Mn2+ show only a small stabilization effect both in presence and in absence of 10 mol% phosphatidylglycerol
-
when cosolubilized with diacylglycerol in octylglucoside micelles, the enzyme undergoes rapid irreversible inactivation
-
enzyme activity is destroyed by trypsin, no protection by substrate
-
activation of tyrosine kinases is required for membrane stabilization of DGKalpha, phosphorylation of DGKalpha at Tyr335 appears to be essential for membrane localization
-
activation of tyrosine kinases is required for membrane stabilization of DGKalpha, phosphorylation of DGKalpha at Tyr335 appears to be essential for membrane localization
O88673
DGKalpha is also activated when it binds to membranes
O88673, Q80UP3, Q9R1C6
microsomal activity is more unstable on storage at 0C than the soluble enzyme
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4C, -20C or -70C, more than 50% of the activity is lost after overnight storage in presence of 10 or 20% glycerol
Q64398
-20C, in presence of 1 mM dithiothreitol, microsomal and soluble enzyme stable for about 1 week
-
4C, enzyme concentrated by polyethyleneglycol 6000, stable for 1 week
-
4C, purified enzyme, 50% loss of activity after 3 days
-
the 150000 Da enzyme is very unstable but can be stored at -80C in presence of bovine serum albumin
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
CHAPS is the most effective detergent for isozyme DGK2 solubilization, NusA/His6-tagged fusion isozyme DGK2 from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
Q9FFN7
recombinant protein
P19638
recombinant N-terminally His-tagged wild-type and mutant enzymes or MBP-fusion protein from insect cells by nickel affinity chromatography
-
native enzyme, by ultracentrifugation, gel filtration, and antibody affinity chromatography
-
apoprotein
-
recombinant HIs-tagged wild-type and mutant enzymes
-
isoenzyme DGK-I and DGK-II, DGK-II only partially purified
-
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
-
DGK I and DGK IV
-
recombinant GST-fusion isozymes DGKalpha, DGKgamma, and DGKbeta from Escherichia coli, and Sf9 cells, respectively, and from COS-7 cells, by glutathione affinity chromatography
-
Ni-NTA column chromatography
-
a heat-labile 80000 Da enzyme and a heat-stable 150000 Da enzyme
-
partially, recombinant wild-type and point mutant enzymes from yeast by ion exchange chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
AtDGK2, DNA and amino acid sequence determination and analysis, phylogenetic analysis, expression as NusA/His6-tagged isozyme DGK2 in Escherichia coli strain BL21(DE3)
Q9FFN7
expression in Arabidopsis thaliana protoplasts
-
expression as His-tagged protein, Escherichia coli; expression in Escherichia coli
P19638
gene dgk-1alpha, DNA and amino acid sequence determination and analysis of wild-type and mutant enzymes, expression of N-terminally His-tagged wild-type and mutant enzymes and of wild-type enzyme enzyme fused to the maltose binding protein in insect cells via the baculovirus infection system, enzyme is found to 95% in aggregated form
-
expression in COS-7 and HEK-293T cells
-
a 100fold overproduction is obtained when dgkA is placed on a hybrid plasmid under control of the lambdapl promoter
-
expression of His-tagged wild-type and mutant enzymes
-
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 and in baculovirus-infected Sf21 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 cell, with FLAG-tag
-
expression in COS-7 cells
-
expression in COS-7 cells; expression of truncated enzyme forms 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
-
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
Q9Y6T7
transfection of HEK-293 cells, COS-7 cells
-
insect cells infected with recombinant baculovirus containing the cDNA
Q64398
expression in T lymphocyte and COS-7 cells
O88673
expression in Escherichia coli
-
expression in tobacco
-
cDNA subcloned into the EcoRI site of the simian virus 40-based expression vector pSRE
-
expression in COS-7 cell; expression in COS-7 cell; expression in COS-7 cell; expression in COS-7 cell
O08560, P49621, P51556
expression in NIH 3T3 cells
-
GFP-tagged DGKh and DGKg co-expressed in human neuroblastoma cells SH-SY5Y, expression of GST-fusion isozyme DGKalpha and DGKgamma in Escherichia coli strain DH5alpha, expression of GST-fusion isozyme DGKbeta in Spodoptera frugiperda Sf9 cells via baculovirus infection system, expression of GST-fusion isozymes DGKalpha, DGKbeta, and DGKgamma in COS-7 cells
-
high kinase activity is shown in COS cells transfected with either one of the three cDNAs for DGK-I, DGK-II or DGK-III
-
expressed in Escherichia coli BL21(DE3) cells
-
-
P20192
cDNA subcloned into the EcoRI site of the simian virus 40-based expression vector pSRE
-
expression of wild-type and deletion mutant enzymes in COS-1 cells, expression of wild-type and point mutant enzymes in the enzyme-deficient Saccharomyces cerevisiae strain WY294
-
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
-
DGKzeta mRNA levels are increased in mice on a high-fat diet, but are lower in those that become obese by a high-fat diet
-
p53-mediated upregulation of DGKalpha mRNA in mouse-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
O88673
as early as 1h after cryoinjury, DGKzeta-immunoreactivity is greatly decreased in the afflicted cerebral cortex and almost disappears in the necrotic core. On day 7 after cryoinjury, however, DGKzeta-immunoreactivity reappears in this area
-
DGKzeta is induced in activated microglia in brain trauma
-
DGKzeta mRNA levels are increased in rats on a high-fat diet, but are lower in those that become obese by a high-fat diet
-
protein and mRNA expression of isoform DGKepsilon in aortic smooth muscle cells is significantly increased by stimulation with serotonin
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A722V
-
mutant isolated due to defects in DGK-1 controlled behaviour, altered behaviour compared to the wild-type enzyme, overview
C115Y
-
mutant isolated due to defects in DGK-1 controlled behaviour, altered behaviour compared to the wild-type enzyme, overview
C184Y
-
mutant isolated due to defects in DGK-1 controlled behaviour, altered behaviour compared to the wild-type enzyme, overview
G606E
-
mutant isolated due to defects in DGK-1 controlled behaviour, altered behaviour compared to the wild-type enzyme, overview
G609E
-
mutant isolated due to defects in DGK-1 controlled behaviour, altered behaviour compared to the wild-type enzyme, overview
N745I
-
mutant isolated due to defects in DGK-1 controlled behaviour, altered behaviour compared to the wild-type enzyme, overview
P736S
-
mutant isolated due to defects in DGK-1 controlled behaviour, altered behaviour compared to the wild-type enzyme, overview
Q246stop
-
mutant isolated due to defects in DGK-1 controlled behaviour, altered behaviour compared to the wild-type enzyme, overview
Q422stop
-
mutant isolated due to defects in DGK-1 controlled behaviour, altered behaviour compared to the wild-type enzyme, overview
R167stop
-
mutant isolated due to defects in DGK-1 controlled behaviour, altered behaviour compared to the wild-type enzyme, overview
R180stop
-
mutant isolated due to defects in DGK-1 controlled behaviour, altered behaviour compared to the wild-type enzyme, overview
S880L
-
mutant isolated due to defects in DGK-1 controlled behaviour, altered behaviour compared to the wild-type enzyme, overview
W646stop
-
mutant isolated due to defects in DGK-1 controlled behaviour, altered behaviour compared to the wild-type enzyme, overview
W674stop
-
mutant isolated due to defects in DGK-1 controlled behaviour, altered behaviour compared to the wild-type enzyme, overview
W767stop
-
mutant isolated due to defects in DGK-1 controlled behaviour, altered behaviour compared to the wild-type enzyme, overview
A14Q
-
significantly impaired catalytic function, without evidence of gross structural alterations, subunit mixing experiments of mutant enzymes, subunit mixing experiments of mutant enzymes
C46A/C113A
-
mutant lacking all Cys residues. Activity is slightly higher than wild-type
C46A/C113A/A29C
-
introduction of Cys residue at transmembrane helix 1 into mutant lacking the native Cys residues. Low activity mutant, 64% trimer formation compared to wild-type
C46A/C113A/A30C
-
introduction of Cys residue at transmembrane helix 1 into mutant lacking the native Cys residues. Low activity mutant, 79% trimer formation compared to wild-type
C46A/C113A/E28C
-
introduction of Cys residue at transmembrane helix 1 into mutant lacking the native Cys residues. Low activity mutant, 93% trimer formation compared to wild-type
C46A/C113A/Q33C
-
introduction of Cys residue at transmembrane helix 1 into mutant lacking the native Cys residues. Low activity mutant, 77% trimer formation compared to wild-type
C46A/C113A/R32C
-
introduction of Cys residue at transmembrane helix 1 into mutant lacking the native Cys residues. Low activity mutant, 63% trimer formation compared to wild-type
C46A/C113AE34C
-
introduction of Cys residue at transmembrane helix 1 into mutant lacking the native Cys residues. Low activity mutant, 100% trimer formation compared to wild-type
C46A/C113AF31C
-
introduction of Cys residue at transmembrane helix 1 into mutant lacking the native Cys residues. Low activity mutant, 72% trimer formation compared to wild-type
D95N
-
significantly impaired catalytic function, without evidence of gross structural alterations. Km-value for MgATP2- raises 18fold, subunit mixing experiments of mutant enzymes
E69C
-
mutant enzyme has an altered structure even in SDS
E76L
-
significantly impaired catalytic function, without evidence of gross structural alterations, subunit mixing experiments of mutant enzymes
I110P
-
mutant enzyme can not be purified because its expression is toxic to the Escherichia coli host
I110R
-
mutant enzyme can not be purified because its expression is toxic to the Escherichia coli host
I110W
-
mutant is highly misfolding while at the same time being more stable than the wild-type protein
I110Y
-
mutant exhibits enhanced stability but folds with an efficiency similar to that of the wild type
K94L
-
significantly impaired catalytic function, without evidence of gross structural alterations. Km-value for MgATP2- raises 13fold, subunit mixing experiments of mutant enzymes
N72S
-
significantly impaired catalytic function, without evidence of gross structural alterations, subunit mixing experiments of mutant enzymes
W112L
-
site-directed mutagenesis, inactive mutant
W117L
-
site-directed mutagenesis, inactive mutant
W18L
-
site-directed mutagenesis, reduced activity compared to the wild-type enzyme
W18L/W25L
-
site-directed mutagenesis, reduced activity compared to the wild-type enzyme
W18L/W25L/W112L/W117L
-
site-directed mutagenesis, inactive mutant
W18L/W25L/W47L
-
site-directed mutagenesis, reduced activity compared to the wild-type enzyme
W18L/W25L/W47L/W112L
-
site-directed mutagenesis, inactive mutant
W18L/W25L/W47L/W117L
-
site-directed mutagenesis, reduced activity compared to the wild-type enzyme
W18L/W47L/W112L/W117L
-
site-directed mutagenesis, inactive mutant
W18L/W47L/W117L
-
site-directed mutagenesis, reduced activity compared to the wild-type enzyme
W25L
-
site-directed mutagenesis, reduced activity compared to the wild-type enzyme
W25L/W47L/W112L/W117L
-
site-directed mutagenesis, inactive mutant
C20A
-
mutant shows diminished Zn occupancy
C60A
-
mutant shows diminished Zn occupancy
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
Q86XP1
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
L447
P52429
residue is required for the cholesterol recognition/interaction amino acid consensus motif, mutation results in a loss of enzymatic activity
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
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
P52429
ratio of enzymic activity with substrates 1-stearoyl-2-linoleoyl-sn-glycerol to 1-stearoyl-2-arachidonoyl-sn-glycerol is 0.217
R457Q
P52429
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
-
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
C20S
-
mutation in sterile alpha-motif, mutant forms an oligomer
D43G
-
mutation in sterile alpha-motif, mutant is largely monomeric in solution
E35G
-
mutation in sterile alpha-motif, mutant is largely monomeric in solution
G53D
-
mutation in sterile alpha-motif, mutant is largely monomeric in solution
K45E
-
mutation in sterile alpha-motif, mutant forms an oligomer
T57P
-
mutant with reduced activity, used for construcution of fusion protein for genetic selection of soluble mutants
G279D
O08560, P49621, P51556
inactive mutant of diacylglycerol kinase epsilon due to replacement of ATP-binding domain GxGxxG with GxDxxG. Similar subcellular localization as wild type
G356D
O08560, P49621, P51556
inactive mutant of diacylglycerol kinase zeta due to replacement of ATP-binding domain GxGxxG with GxDxxG. Similar subcellular localization as wild type
G428D
O08560, P49621, P51556
inactive mutant of diacylglycerol kinase alpha due to replacement of ATP-binding domain GxGxxG with GxDxxG. Similar subcellular localization as wild type
G491D
O08560, P49621, P51556
inactive mutant of diacylglycerol kinase gamma due to replacement of ATP-binding domain GxGxxG with GxDxxG. Similar subcellular localization as wild type
D124A
-
residue involved in the Mg1-water network, no catalytic acitivity
D124A
-
mutant shows strongly reduced activity
D216A
-
mutant shows strongly reduced activity
D271A
-
mutant shows almost no activity
D271A
-
residue involved in the Mg1-water network, no catalytic acitivity
D68A
-
mutant shows almost no activity
D68A
-
no catalytic activity. Role of D68 in mediating the interaction of Mg2+ with the gamma-phosphate of ATP
D97A
-
mutant shows strongly reduced activity
E273A
-
no catalytic activity
E273A
-
mutant shows almost no activity
K15A
-
mutant shows reduced activity
K15A/K165A
-
mutant shows strongly reduced activity
K165A
-
mutant shows reduced activity
N96A
-
mutant shows strongly reduced activity
R100A
-
mutant shows reduced activity
R20A
-
mutant shows wild type activity
T94A
-
mutant shows strongly reduced activity
D434A
-
site-directed mutagenesis, inactive mutant
D434N
-
site-directed mutagenesis, inactive mutant
D465A
-
site-directed mutagenesis, inactive mutant
D465N
-
site-directed mutagenesis, 0.1% of wild-type activity
D497A
-
site-directed mutagenesis, inactive mutant
D497N
-
site-directed mutagenesis, 0.9% of wild-type activity, reduced stimulation by Ca2+ and phosphatidylserine compared to the wild-type enzyme
D529A
-
site-directed mutagenesis, 1.1% of wild-type activity
D529N
-
site-directed mutagenesis, 5.5% of wild-type activity, unaltered stimulation by Ca2+ and phosphatidylserine compared to the wild-type enzyme
D650A
-
site-directed mutagenesis, inactive mutant
D650N
-
site-directed mutagenesis, inactive mutant
D697A
-
site-directed mutagenesis, 1.4% of wild-type activity
additional information
-
expression of fusion constructs of Green Fluorescent Protein to truncated forms of diacylglycerol kinase 1 and diacylglycerol kinase 2 missing the catalytic and accessory domains. Fusion proteins are localized to the endoplasmic reticulum. Fusion constructs of N-terminal 50 amino acid residues of diacylglycerol kinase 1 and the 43 residues of diacylglycerol kinase 2 to the Yellow Fluorescent Protein alos localize to the endoplasmic reticulum
additional information
P19638
functional complementation of Escherichia coli dgkA mutant. Conditional inactivation of gene expression leads to the accumulation of diacylglycerol and the cessation of lipoteichoic acid formation in Bacillus subtilis
G796R
-
mutant isolated due to defects in DGK-1 controlled behaviour, altered behaviour compared to the wild-type enzyme, overview
additional information
-
determination of mutational defects/molecular lesions affecting the enzyme activity and splice forms of the enzyme, overview
G434D
-
kinase-defective dominant-negative mutant , impairs hepatocyte growth factor- and v-Src-induced cell scatter and migration, without affecting the loss of intercellular adhesions, impairs hepatocyre growth factor-induced cell spreading, lamellipodia formation, membrane ruffling, and focal adhesions remodeling and impairs hepatocyte growth factor-induced Rac activation and membrane targeting
additional information
-
deletion mutants lacking respectively the entire C-terminal half of diacylglycerol kinase alpha or the last 13 amino acids PPPRSTNFFGFLS. Contrary to wild-type, mutants are not pulled down by immobilized GST-Src-SH3 fusion protein
additional information
-
downregulation of diacylglycerol kinase alpha by siRNA impairs hepatocyte growth factor- and v-Src-induced cell scatter and migration, without affecting the loss of intercellular adhesions, impairs hepatocyre growth factor-induced cell spreading, lamellipodia formation, membrane ruffling, and focal adhesions remodeling and impairs hepatocyte growth factor-induced Rac activation and membrane targeting
Y335F
-
mutants is not tyrosine phosphorylated upon coexpression with activated Src mutant Y527F. Enzymatic activity is not stimulated by hepatocyte growth factor cell stimulation
additional information
-
the ATP binding sequence of isozyme DGK2in strain rdgA contains the mutant GXDXXG motif leading to rapid retinal degeneration after birth
L447I
P52429
ratio of enzymic activity with substrates 1-stearoyl-2-linoleoyl-sn-glycerol to 1-stearoyl-2-arachidonoyl-sn-glycerol is 0.054
additional information
-
construction of deletion mutants, N- or C-terminal truncations inactivate the isozyme theta
additional information
-
mutation of the second glycine in the binding sequence motif GXGXXG of the ATP-binding site to aspartate or alanine renders the mutant enzymes catalytically inactive
additional information
-
truncated form of the protein (DGKDELTAepsilon) lacking the 40 N-terminal amino acids. Full-length FLAG-DGKepsilon and truncated FLAG-DGKepsilon are both more specific for 1-stearoyl-2-arachidonoyl-sn-glycerol than for 1,2-dioleoyl-sn-glycerol. 1-Stearoyl-2-linoleoyl-sn-glycerol exhibits intermediate specificity for both forms of the enzyme. The truncated form of the enzyme maintains substrate specificity for lipids with an arachidonoyl moiety present at the sn-2 position. The truncation increases the catalytic rate constant for all three substrates and may suggest a role in the negative regulation of this enzyme
additional information
-
diacylglycerol kinase delta has alternative splicing variants, type 1 DGKdelta1 and type 2 DGKdelta2, with calculated molecular masses of 130 and 134 kDa, respectively. HeLa cells express both type 1 and 2 DGKdelta, and COS7 cells express only type 2 DGKdelta. In DGKdelta-knockdown cells uptake of transferrin is reduced. DGKdelta2 is partially co-localized with clathrin or adaptor protein AP2alpha in COS7 cells. Mutants lacking binding ability to AP2alpha as well as kinase-negative mutants cannot compensate for the uptake of transferrin inhibited by siRNA treatment. Overexpression of wild-type diacylglycerol kinase delta2 completely recovers the transferrin uptake
additional information
P52429
expression of a peptide corresponding to a putative transmembrane segment which comprises approximately residues 20-40 and is found in all forms of mammalian diacylglycerol kinase epsilon. Peptide KKKKLILWTLCSVLLPVFITFWKKKKK-NH2 has increased helical content and significant blue shifts in the presence of anionic but not zwitterionic bilayer membranes. Peptide dimerizes and preferentially interacts with cholesterol in lipid films comprised of homogeneous mixtures of cholesterol and phosphatidylcholine, yet the presence of cholesterol in hydrated vesicle bilayers decreases its helical content
additional information
-
expression of truncated FLAG-tagged protein lacking the 40 N-terminal amino acids, which includes the hydrophobic segment. Truncated protein maintains substrate specificity and increases catalytic rate constant. Truncated protein may be extracted with 1.5 M KCl at neutral pH value, while wild-type protein remains fully membrane bound
additional information
P49619
heterologous expression of diacylglycerol kinase gamma in COS-7 cells. Upon stimulation with epidermal growth factor, enzyme specifically interacts and co-localizes at the plasma membrane with beta2-chimaerin. Enzyme enhances epidermal growth factor-dependent translocation of beta2-chimaerin to the plasma membrane and markedly augments epidermal growth factor-dependent GTPase-activating protein activity of beta2-chimaerin
additional information
Q16760
in a female patient with a de novo balanced translocation, 46,X,t(X,2)(p11.2,q37)dn, who exhibits seizures, capillary abnormality, developmental delay, infantile hypotonia, and obesity, diacylglycerol kinase delta is disrupted at 2q37. Diacylglycerol kinase delta is involved in the etiology of seizures
additional information
-
overexpression of wild-type diacylglycerol kinase alpha, but not of its kinase-dead mutant, markedly suppresses tumor necrosis factor alpha-induced apoptosis of AKI human melanoma cells and enhances the tumor necrosis factor alpha-stimulated transcriptional activity of transcription factor NF-kappaB. siRNA-mediated knock-down of diacylglycerol kinase alpha enhances the apoptosis. Overexpression of isoforms beta and gamma has no detectable effect on apoptosis
additional information
-
RNA interference-mediated knockdown of diacylglycerol kinase zeta leads to accelerated transferrin receptor exit from the lymphocyte endocytic recycling compartment back to the plasma membrane
additional information
-
silencing of diacylglycerol kinase theta by siRNA expression inhibits cAMP-dependent CYP17 transcription. LXXLL motifs in diacylglycerol kinase theta mediate a direct interaction of steroidogenic factor 1 with the kinase and may facilitate binding of phosphatidic acid to the receptor
Y451F
P52429
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
-
mutation of the second glycine in the binding sequence motif GXGXXG of the ATP-binding site to aspartate or alanine renders the mutant enzymes catalytically inactive
K56E
-
mutation in sterile alpha-motif, mutant is largely monomeric in solution
additional information
O88673
construction of mutant protein lacking the regulatory N-terminus and both C1 domains. Mutant is enzymatically active. deletion analysis reveals that the C1 domains are essential for plasma membrane targeting in intact cells but unnecessary for catalytic activity. The C-terminal sequence is required for membrane-binding in a phosphatidic acid-dependent manner. In the absence of the calcium binding domain, receptor-dependent translocation of the truncated protein is regulated by phosphorylation of residue Y335
additional information
-
creation of thoracic transverse aortic constriction in transgenic mice with cardiac-specific overexpression of diacylglycerol kinase zeta and wild-type mice. Increases in heart weight at 4 weeks after thoracic transverse aortic constriction are attenuated in diacylglycerol kinase zeta transgenic mice compared with wild-type mice. Increases in interventricular septal thickness, dilatation of the left ventricular cavity, and decreases in left ventricular systolic function in wild-type mice are observed at 4 weeks after surgery and are attenuated in diacylglycerol kinase zetatransgenic mice. Contrary to wild-type, cardiac fibrosis and gene induction of type I and type III collagens, but not transforming growth factor are blocked in diacylglycerol kinase zeta transgenic mice
additional information
Q80UP3
deficiency for diacylglycerol kinase zeta results in impaired interleukin 12 and tumor necrosis factor alpha production following toll-like receptor stimulation in vitro and in vivo, increased resistance to endotoxin shock, and enhanced susceptibility to Toxoplasma gondii infection. Deficiency results in increased activation of the phosphatidylinositol 3-kinase-Akt pathway. Inhibition of phosphatidylinositol 3-kinase activity or treatment with phosphatidic acid can restore lipopolysaccharide-induced interleukin 12 production by diacylglycerol kinase zeta-deficient mice
additional information
-
diacylglycerol kinase delta knock-down mice reveal abnormal epiletic discharges and electrographic seizures in three out of six homozygotes
additional information
-
expression of isolated His-tagged sterile alpha-motif domain of diacylglycerol kinase delta1, comprised of residues 1097-1164. The domain forms large aggregates with a molecular weight of 250000 Dalton or greater, while calculated monomer molecular weight is 9500 Dalton
additional information
-
generation of double transgenic mice with cardiac-specific overexpression of both diacylglycerol kinase zeta and G-protein subunit alphaq. Diacylglycerol kinase zeta prevents cardiac dysfunction, determined by dilatation of left ventricular dimensions, reduction of left ventricular fractional shortening, and marked increases in left ventricular end-diastolic pressure in G-protein subunit alphaq transgenic mice. Translocation of protein kinase C isoforms, phosphorylation activity of c-jun N-terminal kinase and p38 mitogen-activated protein kinase in G-protein subunit alphaq transgenic mice are attenuated by diacylglycerol kinase zeta?. Diacylglycerol kinase zeta improves the survival rate of G-protein subunit alphaq transgenic mice
additional information
-
generation of heterozygous diacylglycerol kinase delta whole-body knockout mice. Diacylglycerol kinase delta haploinsufficiency increases diacylglycerol content, reduces peripheral insulin sensitivity, insulin signaling, and glucose transport, and leads to age-dependent obesity. Metabolic flexibility is impaired
additional information
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generation of mice lacking both diacylglycerol kinase alpha and zeat. Absence of both diacylglycerol kinases results in a severe decrease in the number of CD4+CD8- and CD4-CD8+ single-positive thymocytes correlating with increased diacylglycerol kinase-mediated signaling. Positive selection, but not negative selection, is impaired in diacylglycerol kinase alpha-/- zeta -/- mice. The developmental blockage in diacylglycerol kinase alpha-/- zeta -/- mice can be partially overcome by treatment with phosphatidic acid. Decreased diacylglycerol kinase activity also promotes thymic lymphomagenesis accompanying elevated Ras and Erk1/2 activation
additional information
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in mouse ventricular myocytes overexpressing diaclyglycerol kinase zeta, the effect induced by endothelin-1 on Ca2+ transients and cell shortening are abolished
additional information
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overexpression of diacylglycerol kinase zeta blocks cells in G1 phase of cell cycle. Cell cycle arrest is accompanied by decreased levels of retinoblastoma protein phosphorylated on Ser-807/811. Down-regulation by siRNA increases the number of cells in both the S and G2/M phases of the cell cycle and prevents the cell cycle block characterizing C2C12 cell myogenic differentiation
additional information
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transgenic mice with cardiac-specific overexpression of diacylglycerol kinase zeta. Left ventricular chamber dilatation, reduction of left ventricular systolic function and increases in left ventricular weight and lung weight at 4 weeks after myocardial infarction are attenuated in transgenic mice compared with wild-type mice. In the noninfarct area, fibrosis fraction and upregulation of profibrotic genes, such as transforming growth factor-1, collagen type I, and collagen type III, are blocked in transgenic mice. Survival rate at 4 weeks after myocardial infarction is higher in transgenic mice than in wild-type
additional information
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nuclear export signal mutant forms of DGK-zeta accumulate in the nucleus to a much greater extent than wild type DGK-zeta
V52E
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mutation in sterile alpha-motif, mutant is largely monomeric in solution
additional information
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generation of transgenic tobacco plants constitutively expressing rice diacylglycerol kinase. Overexpression results in enhanced resistance against infection by tobacco mosaic virus and Phytophthora parasitica var. nicotianae
G495D
O08560, P49621, P51556
inactive mutant of diacylglycerol kinase beta due to replacement of ATP-binding domain GxGxxG with GxDxxG. In contrast to the filamentous image of the wild type, mutant is diffusely distributed throughout the cytoplasm
additional information
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antisense silencing of diacylglacerol kinase isoform delta, but not alpha, expression is sufficient to prevent the effect of high glucose on protein kinase alpha activity, insulin receptor signaling, and glucose uptake
additional information
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diacylglycerol kinase zeta siRNA tranfection decreases H2O2-induced apoptosis. Overexpression of kinase-dead diacylglycerol kinase zeta significantly increases protein kinase D phosphorylation
D697N
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site-directed mutagenesis, 4.0% of wild-type activity, reduced stimulation by Ca2+ and phosphatidylserine compared to the wild-type enzyme
additional information
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construction of deletion mutants DELTA196, lacking the RVH motif and the EF hand, and DELTA332, lacking the RVH motif, the EF hand, and the C1 domain, mutant DELTA332 shows 50% of wild-type activity
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
solubilization of the active enzyme from aggregates after recombinant expression in yeast
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
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diacylglycerol kinases are required for anchorage-independent growth in MDA-MB-231 cells. Activity is induced by hepatocyte growth factor
medicine
Q16760
in a female patient with a de novo balanced translocation, 46,X,t(X,2)(p11.2,q37)dn, who exhibits seizures, capillary abnormality, developmental delay, infantile hypotonia, and obesity, diacylglycerol kinase delta is disrupted at 2q37.Diacylglycerol kinase delta is involved in the etiology of seizures
medicine
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overexpression of wild-type diacylglycerol kinase alpha, but not of its kinase-dead mutant, markedly suppresses tumor necrosis factor alpha-induced apoptosis of AKI human melanoma cells and enhances the tumor necrosis factor alpha-stimulated transcriptional activity of transcription factor NF-kappaB. siRNA-mediated knock-down of diacylglycerol kinase alpha enhances the apoptosis. Overexpression of isoforms beta and gamma has no detectable effect on apoptosis
medicine
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patients with certain forms of systematic vasculitis, such as Wegeners granulomatosis, have circulating antineutrophil cytoplasmic antibodies. Diacylglycerol kinase is selectively activated by circulating antineutrophil cytoplasmic antibodies and the generated phosphatidic acid is responsible for promoting neutrophil adhesion, in part through integrin activation
medicine
Q16760
patients with type 2 diabetes mellitus display reduced diacylglycerol kinase delta expression and activity in skeletal muscle
medicine
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study on genetic basis of bipolar disorder. Of 37 single nucleotide polymorphisms selected for individual genotyping, the strongest association signal is detected at a marker within the diacylglycerol kinase eta. Several genes, each of modest effect, reproducibly influence disease risk. Bipolar disorder may be a polygenic disease
medicine
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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
medicine
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enzyme is able to remove 1-stearoyl-2-arachidonoylglycerol, the precursor of the endocannabinoid 2-arachidonoyl glycerol
analysis
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generation of a soluble mutant selection assay based on a library of random diacylglycerol kinase delta1 mutants of sterile alpha-motif and murine dihydrofolate reductase as the selectable marker
medicine
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comparison of transgenic mice with cardiac-specific overexpression of diacylglycerol kinase zeta and wild-type mice in streptozotocin-induced diabetic and non-diabetic conditions. After 8 weeks, decreases in heart weight and heart weight/body weight ratio in diabetic wild-type mice are inhibited in transgenic mice. Decreases in left ventricular end-diastolic diameter and fractional shortening observed in wild-type mice are attenuated in transgenic mice. Thinning of the interventricular septum and the posterior wall in diabetic wild-type hearts are blocked in transgenic mice. Reduction of transverse diameter of cardiomyocytes isolated from the left ventricle in diabetic wild-type mice is attenuated in transgenic mice. Cardiac fibrosis was much less in diabetic transgenic than in diabetic wild-type mice
medicine
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creation of thoracic transverse aortic constriction in transgenic mice with cardiac-specific overexpression of diacylglycerol kinase zeta and wild-type mice. Increases in heart weight at 4 weeks after thoracic transverse aortic constriction are attenuated in diacylglycerol kinase zeta transgenic mice compared with wild-type mice. Increases in interventricular septal thickness, dilatation of the left ventricular cavity, and decreases in left ventricular systolic function in wild-type mice are observed at 4 weeks after surgery and are attenuated in diacylglycerol kinase zetatransgenic mice. Contrary to wild-type, cardiac fibrosis and gene induction of type I and type III collagens, but not transforming growth factor are blocked in diacylglycerol kinase zeta transgenic mice
medicine
Q80UP3
deficiency for diacylglycerol kinase zeta results in impaired interleukin 12 and tumor necrosis factor alpha production following toll-like receptor stimulation in vitro and in vivo, increased resistance to endotoxin shock, and enhanced susceptibility to Toxoplasma gondii infection
medicine
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diacylglycerol kinase delta haploinsufficiency increases diacylglycerol content, reduces peripheral insulin sensitivity, insulin signaling, and glucose transport, and leads to age-dependent obesity. Metabolic flexibility is impaired
medicine
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diacylglycerol kinase delta knock-down mice reveal abnormal epiletic discharges and electrographic seizures in three out of six homozygotes
medicine
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diacylglycerol kinase zeta blocks cardiac dysfunction and progression to lethal heart failure by activated G-protein subunit alphaq protein without detectable adverse effects in the in-vivo heart
medicine
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transgenic mice with cardiac-specific overexpression of diacylglycerol kinase zeta. Left ventricular chamber dilatation, reduction of left ventricular systolic function and increases in left ventricular weight and lung weight at 4 weeks after myocardial infarction are attenuated in transgenic mice compared with wild-type mice. In the noninfarct area, fibrosis fraction and upregulation of profibrotic genes, such as transforming growth factor-1, collagen type I, and collagen type III, are blocked in transgenic mice. Survival rate at 4 weeks after myocardial infarction is higher in transgenic mice than in wild-type
medicine
Q9R1C6
DGKepsilon is a therapeutic target to prevent cardiac hypertrophy and progression to heart failure
agriculture
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generation of transgenic tobacco plants constitutively expressing rice diacylglycerol kinase. Overexpression results in enhanced resistance against infection by tobacco mosaic virus and Phytophthora parasitica var. nicotianae
medicine
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DGKzeta may be a therapeutic target to prevent cardiac hypertrophy and progression to heart failure