Information on EC 2.7.7.41 - phosphatidate cytidylyltransferase and Organism(s) Homo sapiens and UniProt Accession Q92903

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Homo sapiens
UNIPROT: Q92903


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


The taxonomic range for the selected organisms is: Homo sapiens

EC NUMBER
COMMENTARY hide
2.7.7.41
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RECOMMENDED NAME
GeneOntology No.
phosphatidate cytidylyltransferase
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
nucleotidyl group transfer
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-
-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
CDP-diacylglycerol biosynthesis I
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CDP-diacylglycerol biosynthesis II
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CDP-diacylglycerol biosynthesis III
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type I lipoteichoic acid biosynthesis (S. aureus)
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CDP-diacylglycerol biosynthesis
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Glycerophospholipid metabolism
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Metabolic pathways
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Biosynthesis of secondary metabolites
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SYSTEMATIC NAME
IUBMB Comments
CTP:phosphatidate cytidylyltransferase
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CAS REGISTRY NUMBER
COMMENTARY hide
9067-83-8
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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knocking down CDS1 results in the formation of giant or supersized lipid droplets in cultured cells. The levels of many phosphatidate species are significantly increased upon knocking down CDS1, the amount of phosphatidate in the endoplasmic reticulum is dramatically increased upon knocking down CDS1, overview. The changes in phosphatidate level and localization may underlie the formation of giant lipid droplets as well as the block in adipogenesis in CDS-deficient cells
metabolism
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the two isoforms of human CDS, CDS1 and CDS2, show different acyl chain specificities for its lipid substrate. CDS1 and CDS2 can create different CDP-DAG pools that may serve to enrich different phospholipid species with specific acyl chains
physiological function
malfunction
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knocking down CDS2 results in the formation of giant or supersized lipid droplets in cultured cells. Only a small number of phosphatidate species are increased upon depleting CDS2, the amount of phosphatidate in the endoplasmic reticulum is dramatically increased upon knocking down CDS2, overview. The changes in phosphatidate level and localization may underlie the formation of giant lipid droplets as well as the block in adipogenesis in CDS-deficient cells
metabolism
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the two isoforms of human CDS, CDS1 and CDS2, show different acyl chain specificities for its lipid substrate. CDS1 and CDS2 can create different CDP-DAG pools that may serve to enrich different phospholipid species with specific acyl chains
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
CTP + 1,2-diarachidonoyl-sn-phosphatidic acid
diphosphate + CDP-1,2-diarachidonoylglycerol
show the reaction diagram
-
-
-
?
CTP + 1,2-dilinoleoyl-sn-phosphatidic acid
diphosphate + CDP-1,2-dilinoleoylglycerol
show the reaction diagram
-
-
-
?
CTP + 1,2-dioleoyl-sn-phosphatidic acid
diphosphate + CDP-1,2-dioleoylglycerol
show the reaction diagram
-
-
-
?
CTP + 1,2-diolinoleoyl-sn-phosphatidic acid
diphosphate + CDP-1,2-diolinoleoylglycerol
show the reaction diagram
-
-
-
?
CTP + 1-palmitoyl-2-arachidonoyl-sn-phosphatidic acid
diphosphate + CDP-1-palmitoyl-2-arachidonoylglycerol
show the reaction diagram
-
-
-
?
CTP + 1-stearoyl-2-arachidonoyl-sn-phosphatidic acid
diphosphate + CDP-1-stearoyl-2-arachidonoyl-glycerol
show the reaction diagram
-
-
-
?
CTP + 1-stearoyl-2-arachidonoyl-sn-phosphatidic acid
diphosphate + CDP-1-stearoyl-2-arachidonoylglycerol
show the reaction diagram
-
-
-
?
CTP + 1-stearoyl-2-docosahexaenoyl-sn-phosphatidic acid
diphosphate + CDP-1-stearoyl-2-docosahexaenoylglycerol
show the reaction diagram
-
-
-
?
CTP + 1-stearoyl-2-linoleoyl-sn-phosphatidic acid
diphosphate + CDP-1-stearoyl-2-linoleoyl-glycerol
show the reaction diagram
-
-
-
-
CTP + 1-stearoyl-2-linoleoyl-sn-phosphatidic acid
diphosphate + CDP-1-stearoyl-2-linoleoylglycerol
show the reaction diagram
-
-
-
?
CTP + 1-stearoyl-2-oleoyl-sn-phosphatidic acid
diphosphate + CDP-1-stearoyl-2-oleoylglycerol
show the reaction diagram
-
-
-
?
CTP + phosphatidate
diphosphate + CDP-diacylglycerol
show the reaction diagram
CTP + 1,2-diarachidonoyl-sn-phosphatidic acid
diphosphate + CDP-1,2-diarachidonoylglycerol
show the reaction diagram
50% of the activity with 1-stearoyl-2-arachidonoyl-sn-phosphatidic acid
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-
?
CTP + 1,2-dilinoleoyl-sn-phosphatidic acid
diphosphate + CDP-1,2-dilinoleoylglycerol
show the reaction diagram
20% of the activity with 1-stearoyl-2-arachidonoyl-sn-phosphatidic acid
-
-
?
CTP + 1,2-dioleoyl-sn-phosphatidic acid
diphosphate + CDP-1,2-dioleoylglycerol
show the reaction diagram
less than 5% of the activity with 1-stearoyl-2-arachidonoyl-sn-phosphatidic acid
-
-
?
CTP + 1,2-diolinoleoyl-sn-phosphatidic acid
diphosphate + CDP-1,2-diolinoleoylglycerol
show the reaction diagram
-
-
-
?
CTP + 1-palmitoyl-2-arachidonoyl-sn-phosphatidic acid
diphosphate + CDP-1-palmitoyl-2-arachidonoylglycerol
show the reaction diagram
65% of the activity with 1-stearoyl-2-arachidonoyl-sn-phosphatidic acid
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-
?
CTP + 1-stearoyl-2-arachidonoyl-sn-phosphatidic acid
diphosphate + CDP-1-stearoyl-2-arachidonoyl-glycerol
show the reaction diagram
-
-
-
?
CTP + 1-stearoyl-2-arachidonoyl-sn-phosphatidic acid
diphosphate + CDP-1-stearoyl-2-arachidonoylglycerol
show the reaction diagram
-
-
-
?
CTP + 1-stearoyl-2-docosahexaenoyl-sn-phosphatidic acid
diphosphate + CDP-1-stearoyl-2-docosahexaenoylglycerol
show the reaction diagram
-
-
-
?
CTP + 1-stearoyl-2-linoleoyl-sn-phosphatidic acid
diphosphate + CDP-1-stearoyl-2-linoleoyl-glycerol
show the reaction diagram
-
-
-
-
CTP + 1-stearoyl-2-linoleoyl-sn-phosphatidic acid
diphosphate + CDP-1-stearoyl-2-linoleoylglycerol
show the reaction diagram
20% of the activity with 1-stearoyl-2-arachidonoyl-sn-phosphatidic acid
-
-
?
CTP + 1-stearoyl-2-oleoyl-sn-phosphatidic acid
diphosphate + CDP-1-stearoyl-2-oleoylglycerol
show the reaction diagram
20% of the activity with 1-stearoyl-2-arachidonoyl-sn-phosphatidic acid
25% of the activity with 1-stearoyl-2-arachidonoyl-sn-phosphatidic acid
-
?
CTP + phosphatidate
diphosphate + CDP-diacylglycerol
show the reaction diagram
CTP + phosphatidate
diphosphate + CDPdiacylglycerol
show the reaction diagram
dCTP + phosphatidate
diphosphate + dCDPdiacylglycerol
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
CTP + 1-stearoyl-2-arachidonoyl-sn-phosphatidic acid
diphosphate + CDP-1-stearoyl-2-arachidonoyl-glycerol
show the reaction diagram
O95674
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-
-
?
CTP + 1-stearoyl-2-linoleoyl-sn-phosphatidic acid
diphosphate + CDP-1-stearoyl-2-linoleoyl-glycerol
show the reaction diagram
O95674
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-
-
-
CTP + phosphatidate
diphosphate + CDP-diacylglycerol
show the reaction diagram
CTP + 1-stearoyl-2-arachidonoyl-sn-phosphatidic acid
diphosphate + CDP-1-stearoyl-2-arachidonoyl-glycerol
show the reaction diagram
O95674
-
-
-
?
CTP + 1-stearoyl-2-linoleoyl-sn-phosphatidic acid
diphosphate + CDP-1-stearoyl-2-linoleoyl-glycerol
show the reaction diagram
O95674
-
-
-
-
CTP + phosphatidate
diphosphate + CDP-diacylglycerol
show the reaction diagram
CTP + phosphatidate
diphosphate + CDPdiacylglycerol
show the reaction diagram
dCTP + phosphatidate
diphosphate + dCDPdiacylglycerol
show the reaction diagram
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mammalian enzymes show similar efficacy for CTP and dCTP, however CTP is the preferred substrate in vivo, since dCDP-diacylglycerol is not detectable in mammalian tissues. In Escherichia coli equivalent amounts of CDP-diacylglycerol and dCDP-diacylglycerol are detected. Arabinofuranosylcytosine is also found to be incorporated into lipid in mammalian cells, suggesting that it is a substrate for the enzyme
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?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mg2+
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required
Mg2+
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required
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
L-alpha-phosphatidylinositol 4,5-bisphosphate
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strongest inhibitor among the phosphatidylinositols tested
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phosphatidylinositol
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CDS1 shows no acyl chain-dependent inhibition
phosphatidylinositol 4-phosphate
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phosphatidylinositol-(4,5)-bisphosphate
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CDS1 is inhibited by their anionic phospholipid end products, with phosphatidylinositol-(4,5)-bisphosphate showing the strongest inhibition
L-alpha-phosphatidylinositol 4,5-bisphosphate
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1 mol%, 80% inhibition
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L-alpha-phosphatidylinositol 4-phosphate
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1 mol%, 50% inhibition
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phosphatidylinositol
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15-20% inhibition by soybean and liver phosphatidylinositol, inhibition of CDS2 by phosphatidylinositol is acyl chain-dependent, with the strongest inhibition seen with the 1-stearoyl-2-arachidonoyl species; significant inhibition of isoform CDS2 by both soybean and liver PI, with 15?20% residual activity
phosphatidylinositol 4-phosphate
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55% inhibition at 1 mol%
phosphatidylinositol-(4,5)-bisphosphate
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80% inhibition at 1 mol%, CDS2 is inhibited by its anionic phospholipid end products, with phosphatidylinositol-(4,5)-bisphosphate showing the strongest inhibition
additional information
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no significant inhibition in activity when either soybean or liver phosphatidylinositol is used at equimolar concentrations with respect to substrate. Neither soy nor egg phosphatidylglycerol has any significant inhibitory effect when used at equimolar concentrations with respect to substrate. Isoform CDS1 shows no acyl chain-dependent inhibition for 1-stearoyl-2-arachidonoyl-snphosphatidylinositol, 1-stearoyl-2-linoleoyl-sn-phosphatidylinositol, or 1,2-diolinoleoyl-sn-phosphatidylinositol
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
GTP
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small stimulation
GTP
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small stimulation
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
1-stearoyl-2-arachidonoyl-sn-phosphatidic acid
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2.9
1-stearoyl-2-arachidonoyl-sn-phosphatidic acid
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pH 8.0, 22°C; pH 8.0, 22°C, recombinant CDS1
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3.2
1-stearoyl-2-linoleoyl-sn-phosphatidic acid
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pH 8.0, 22°C; pH 8.0, 22°C, recombinant CDS1
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8
1-stearoyl-2-arachidonoyl-sn-phosphatidic acid
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pH 8.0, 22°C; pH 8.0, 22°C, recombinant CDS2
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2.9
1-stearoyl-2-linoleoyl-sn-phosphatidic acid
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pH 8.0, 22°C; pH 8.0, 22°C, recombinant CDS2
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
2.4
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substrate 1-stearoyl-2-arachidonoyl-sn-phosphatidic acid, pH 8.0, 22°C
4.5
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substrate 1-stearoyl-2-arachidonoyl-sn-phosphatidic acid, pH 8.0, 22°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8
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assay at
8
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assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22
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assay at room temperature
22
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assay at room temperature
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.57
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calculated from nucleotide sequence
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
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ER tubular localization; GFP-tagged CDS1 shows a typical ER tubular localization when it is expressed in COS7 cells
Manually annotated by BRENDA team
PDB
SCOP
CATH
UNIPROT
ORGANISM
-
-
-
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
53226
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x * 53226, calculation from nucleotide sequence
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
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x * 53226, calculation from nucleotide sequence
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in COS-7 cell; recombinant expression of C-terminally myc-tagged and GFP-tagged CDS1 in COS7 cells
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expression in COS cells
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expression in COS-7 cell; recombinant expression of C-terminally myc-tagged and GFP-tagged CDS2 in COS7 cells
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expression under the control of a GAL1 promoter in a null cds1 mutant yeast strain complements its growth defect and produces enzyme activity when induced with galactose
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information