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Information on EC 2.7.8.41 - cardiolipin synthase (CMP-forming)
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2.7.8.41 cardiolipin synthase (CMP-forming)IUBMB Comments
The eukaryotic enzyme is involved in the biosynthesis of the mitochondrial phospholipid cardiolipin. It requires divalent cations for activity.
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Word Map
- 2.7.8.41
- phospholipid
- phosphatidylglycerol
- phosphatidylethanolamine
- phosphatidylglycerophosphate
-
cl-deficient
-
non-fermentable
-
cl-rich
- medicine
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Synonyms
hcls1, crls1, cls_cap, cls1p, cardiolipin synthase 1, sco1389, crcls1, cls 1, ydl142c, cardiolipin synthase-1, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
cardiolipin synthase
CHLREDRAFT_177689
CL synthase
CLS
CLS1
Cls1p
clsA
CLS_cap
CrCLS1
CRD1
Cre13.g604700
Crls1
Sco1389
YDL142c
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a CDP-diacylglycerol + a phosphatidylglycerol = a cardiolipin + CMP
-
-
-
-
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PATHWAY SOURCE
PATHWAYS
BRENDA
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SYSTEMATIC NAME
IUBMB Comments
CDP-diacylglycerol:L-1-phosphatidyl-glycerol diacylglycerolphosphotransferase (CMP-forming)
The eukaryotic enzyme is involved in the biosynthesis of the mitochondrial phospholipid cardiolipin. It requires divalent cations for activity.
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
a phosphatidylglycerol + a phosphatidylglycerol
a cardiolipin + glycerol
Cafeteria sp.
-
-
-
-
?
CDP-1,2-dimyristoylglycerol + egg yolk phosphatidylglycerol
a cardiolipin + CMP
-
-
-
-
?
CDP-dimyristoylglycerol + 1,2-dioleoylphosphatidylglycerol
1-(1-myristoyl-2-myristoyl-sn-glycero-3-phospho)-3-(1-oleoyl-2-oleoyl-sn-glycero-3-phospho)-sn-glycerol + CMP
competition experiments with [14C]-CDP-dioleoylglycerol show that the enzyme has similar activity with CDP-dimyristoylglycerol, CDP-diacylglycerol from egg yolk and CDP-dioleoylglycerol. CDP-dipalmitoylglycerol shows considerably less activity
-
-
?
CDP-dimyristoylglycerol + egg yolk phosphatidylglycerol
cardiolipin + CMP
-
-
-
-
?
CDP-dioleoylglycerol + 1,2-dilinoleoylphosphatidylglycerol
1-(1-linoleoyl-2-linoleoyl-sn-glycero-3-phospho)-3-(1-oleoyl-2-oleoyl-sn-glycero-3-phospho)-sn-glycerol + CMP
the enzyme is more active with dioleoyl and dilinoleoyl species of phosphatidylglycerol than with species with one or two palmitoyl groups
-
-
?
CDP-dioleoylglycerol + 1,2-dimyristoylphosphatidylglycerol
1-(1-oleoyl-2-oleoyl-sn-glycero-3-phospho)-3-(1-myristoyl-2-oleoyl-sn-glycero-3-phospho)-sn-glycerol + CMP
dimyristoyl phosphatidylglycerol is a very poor substrate
-
-
?
CDP-dioleoylglycerol + 1,2-dioleoylphosphatidylglycerol
1,3-bis(1,2-dioleoyl-sn-glycero-3-phospho)-sn-glycerol + CMP
CDP-dioleoylglycerol + 1,2-dipalmitoylphosphatidylglycerol
1-(1-oleoyl-2-oleoyl-sn-glycero-3-phospho)-3-(1-palmitoyl-2-palmitoyl-sn-glycero-3-phospho)-sn-glycerol + CMP
the enzyme is more active with dioleoyl and dilinoleoyl species of phosphatidylglycerol than with species with one or two palmitoyl groups
-
-
?
CDP-dioleoylglycerol + 1-oleoyl-2-linoleoyl phosphatidylglycerol
1-(1-oleoyl-2-oleoyl-sn-glycero-3-phospho)-3-(1-oleoyl-2-linoleoyl-sn-glycero-3-phospho)-sn-glycerol + CMP
the enzyme is more active with dioleoyl and dilinoleoyl species of phosphatidylglycerol than with species with one or two palmitoyl groups
-
-
?
CDP-dioleoylglycerol + 1-palmitoyl-2-oleoyl phosphatidylglycerol
1-(1-oleoyl-2-oleoyl-sn-glycero-3-phospho)-3-(1-palmitoyl-2-oleoyl-sn-glycero-3-phospho)-sn-glycerol + CMP
the enzyme is more active with dioleoyl and dilinoleoyl species of phosphatidylglycerol than with species with one or two palmitoyl groups
-
-
?
CDP-dioleoylglycerol + dioleoylphosphatidylglycerol
a cardiolipin + CMP
the enzyme is less active with phosphatidyl-glycerol species carrying one or two palmitoyl groups than with the dioleoyl species of phosphatidyl-glycerol. In addition, CDP-dipalmitoylglycerol hardly competes with CDP-dioleolyglycerol as substrate
-
-
?
CDP-dioleoylglycerol + dipalmitoylphosphatidylglycerol
a cardiolipin + CMP
the enzyme is less active with phosphatidyl-glycerol species carrying one or two palmitoyl groups than with the dioleoyl species of phosphatidyl-glycerol. In addition, CDP-dipalmitoylglycerol hardly competes with CDP-dioleolyglycerol as substrate
-
-
?
CDP-dipalmitoylglycerol + 1,2-dioleoylphosphatidylglycerol
1-(1-oleoyl-2-oleoyl-sn-glycero-3-phospho)-3-(1-palmitoyl-2-palmitoyl-sn-glycero-3-phospho)-sn-glycerol + CMP
competition experiments with [14C]-CDP-dioleoylglycerol show that the enzyme has similar activity with CDP-dimyristoylglycerol, CDP-diacylglycerol from egg yolk and CDP-dioleoylglycerol. CDP-dipalmitoylglycerol shows considerably less activity
-
-
?
egg yolk CDP-diacylglycerol + 1,2-dioleoylphosphatidylglycerol
a cardiolipin + CMP
CDP-diacylglycerol from egg lecithin is primarily CDP-1-palmitoyl-2-oleoylglycerol. Competition experiments with [14C]-CDP-dioleoylglycerol show that the enzyme has similar activity with CDP-dimyristoylglycerol, CDP-diacylglycerol from egg yolk and CDP-dioleoylglycerol. CDP-dipalmitoylglycerol shows considerably less activity
-
-
?
a CDP-diacylglycerol + a phosphatidyl-glycerol
a cardiolipin + CMP
-
-
-
-
?
a CDP-diacylglycerol + a phosphatidyl-glycerol
a cardiolipin + CMP
-
-
-
-
?
a CDP-diacylglycerol + a phosphatidylglycerol
a cardiolipin + CMP
-
-
-
-
?
a CDP-diacylglycerol + a phosphatidylglycerol
a cardiolipin + CMP
-
-
-
-
?
a CDP-diacylglycerol + a phosphatidylglycerol
a cardiolipin + CMP
-
-
-
?
a CDP-diacylglycerol + a phosphatidylglycerol
a cardiolipin + CMP
-
-
-
?
a CDP-diacylglycerol + a phosphatidylglycerol
a cardiolipin + CMP
-
-
-
-
?
a CDP-diacylglycerol + a phosphatidylglycerol
a cardiolipin + CMP
-
-
-
-
?
a CDP-diacylglycerol + a phosphatidylglycerol
a cardiolipin + CMP
-
-
-
-
?
a CDP-diacylglycerol + a phosphatidylglycerol
a cardiolipin + CMP
-
-
-
-
?
a CDP-diacylglycerol + a phosphatidylglycerol
a cardiolipin + CMP
-
-
-
?
a CDP-diacylglycerol + a phosphatidylglycerol
a cardiolipin + CMP
cardiolipin synthesis is a requirement for morphogenesis in Streptomyces
-
-
?
a CDP-diacylglycerol + a phosphatidylglycerol
a cardiolipin + CMP
-
-
-
?
a CDP-diacylglycerol + a phosphatidylglycerol
a cardiolipin + CMP
cardiolipin synthesis is a requirement for morphogenesis in Streptomyces
-
-
?
a CDP-diacylglycerol + a phosphatidylglycerol
a cardiolipin + CMP
-
-
-
-
?
CDP-dioleoylglycerol + 1,2-dioleoylphosphatidylglycerol
1,3-bis(1,2-dioleoyl-sn-glycero-3-phospho)-sn-glycerol + CMP
the enzyme is more active with dioleoyl and dilinoleoyl species of phosphatidylglycerol than with species with one or two palmitoyl groups. Competition experiments with [14C]-CDP-dioleoylglycerol show that the enzyme has similar activity with CDP-dimyristoylglycerol, CDP-diacylglycerol from egg yolk and CDP-dioleoylglycerol. CDP-dipalmitoylglycerol shows considerably less activity
-
-
?
CDP-dioleoylglycerol + 1,2-dioleoylphosphatidylglycerol
1,3-bis(1,2-dioleoyl-sn-glycero-3-phospho)-sn-glycerol + CMP
-
-
-
?
CDP-dioleoylglycerol + 1,2-dioleoylphosphatidylglycerol
1,3-bis(1,2-dioleoyl-sn-glycero-3-phospho)-sn-glycerol + CMP
-
-
-
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
a phosphatidylglycerol + a phosphatidylglycerol
a cardiolipin + glycerol
Cafeteria sp.
-
-
-
-
?
a CDP-diacylglycerol + a phosphatidyl-glycerol
a cardiolipin + CMP
-
-
-
-
?
a CDP-diacylglycerol + a phosphatidyl-glycerol
a cardiolipin + CMP
-
-
-
-
?
a CDP-diacylglycerol + a phosphatidylglycerol
a cardiolipin + CMP
-
-
-
-
?
a CDP-diacylglycerol + a phosphatidylglycerol
a cardiolipin + CMP
-
-
-
-
?
a CDP-diacylglycerol + a phosphatidylglycerol
a cardiolipin + CMP
-
-
-
?
a CDP-diacylglycerol + a phosphatidylglycerol
a cardiolipin + CMP
-
-
-
?
a CDP-diacylglycerol + a phosphatidylglycerol
a cardiolipin + CMP
-
-
-
-
?
a CDP-diacylglycerol + a phosphatidylglycerol
a cardiolipin + CMP
-
-
-
-
?
a CDP-diacylglycerol + a phosphatidylglycerol
a cardiolipin + CMP
-
-
-
-
?
a CDP-diacylglycerol + a phosphatidylglycerol
a cardiolipin + CMP
-
-
-
?
a CDP-diacylglycerol + a phosphatidylglycerol
a cardiolipin + CMP
cardiolipin synthesis is a requirement for morphogenesis in Streptomyces
-
-
?
a CDP-diacylglycerol + a phosphatidylglycerol
a cardiolipin + CMP
-
-
-
?
a CDP-diacylglycerol + a phosphatidylglycerol
a cardiolipin + CMP
cardiolipin synthesis is a requirement for morphogenesis in Streptomyces
-
-
?
a CDP-diacylglycerol + a phosphatidylglycerol
a cardiolipin + CMP
-
-
-
-
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Co2+
CoCl2
requires divalent cations for activity. Highest activities are measured in the presence of 20 mM MnCl2, while MgCl2 or CoCl2 stimulate the activity only slightly
Mg2+
MgCl2
requires divalent cations for activity. Highest activities are measured in the presence of 20 mM MnCl2, while MgCl2 or CoCl2 stimulate the activity only slightly
Mn2+
MnCl2
requires divalent cations for activity. Highest activities are measured in the presence of 20 mM MnCl2, while MgCl2 or CoCl2 stimulate the activity only slightly
Co2+
-
most efficient cation for the activation. Co2+ activates cardiolipin formation by increasing the maximal enzyme activity from 2.9 pmol/min/mg protein at low Co2+ concentration to 4.1 pmol/min/mg protein at high Co2+ concentration
Co2+
-
the enzyme displays an absolute requirement for divalent cations with Co2+ being more efficient than Mg2+ or Mn2+
Co2+
the enzyme is dependent on the presence of bivalent cations. The largest activity is found with Co2+, whereas Mn2+ supports a lower activity. No detectable cardiolipin synthase activity when using Ni2+, Ca2+, or Mg2+
Mg2+
-
the enzyme displays an absolute requirement for divalent cations with Co2+ being more efficient than Mg2+ or Mn2+
Mg2+
maximal activity is obtained in the presence of 20 mM Mg2+
Mn2+
-
the enzyme displays an absolute requirement for divalent cations with Co2+ being more efficient than Mg2+ or Mn2+
Mn2+
the enzyme is dependent on the presence of bivalent cations. The largest activity is found with Co2+, whereas Mn2+ supports a lower activity. No detectable cardiolipin synthase activity when using Ni2+, Ca2+, or Mg2+
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Triton X-100
0.2 mM, 50% inhibition. Concentrations higher than 0.6 mM result in an almost complete inhibition
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Triton
maximal activity is obtained with a Triton X-100:phospholipid ratio of 1:1
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Adenocarcinoma of Lung
Expression and potential mechanism of metabolism-related genes and CRLS1 in non-small cell lung cancer.
Carcinogenesis
Expression and potential mechanism of metabolism-related genes and CRLS1 in non-small cell lung cancer.
Carcinoma, Hepatocellular
Small regulatory polypeptide of amino acid response negatively relates to poor prognosis and controls hepatocellular carcinoma progression via regulating microRNA-5581-3p/human cardiolipin synthase 1.
Carcinoma, Non-Small-Cell Lung
Expression and potential mechanism of metabolism-related genes and CRLS1 in non-small cell lung cancer.
cardiolipin synthase (cmp-forming) deficiency
Cardiolipin Synthesis in Brown and Beige Fat Mitochondria Is Essential for Systemic Energy Homeostasis.
Cystic Fibrosis
Disease-associated mutations in cytoplasmic loops 1 and 2 of cystic fibrosis transmembrane conductance regulator impede processing or opening of the channel.
Essential Tremor
DRD3 Ser9Gly and HS1BP3 Ala265Gly are not associated with Parkinson disease.
Insulin Resistance
Cardiolipin Synthesis in Brown and Beige Fat Mitochondria Is Essential for Systemic Energy Homeostasis.
Insulin Resistance
CRLS1 ameliorates nonalcoholic steatohepatitis through ATF3 transcriptional inactivation.
Leukemia, Myeloid, Acute
Interactions among HCLS1, HAX1 and LEF-1 proteins are essential for G-CSF-triggered granulopoiesis.
Lung Neoplasms
Expression and potential mechanism of metabolism-related genes and CRLS1 in non-small cell lung cancer.
Neoplasms
Exome sequencing reveals recurrent germline variants in patients with familial Waldenstrom's macroglobulinemia.
Neoplasms
Expression and potential mechanism of metabolism-related genes and CRLS1 in non-small cell lung cancer.
Neoplasms
Growth-suppressive effects of BPOZ and EGR2, two genes involved in the PTEN signaling pathway.
Neoplasms
Identification Hub Genes in Colorectal Cancer by Integrating Weighted Gene Co-Expression Network Analysis and Clinical Validation in vivo and vitro.
Neoplasms
Retroviral integration mutagenesis in mice and comparative analysis in human AML identify reduced PTP4A3 expression as a prognostic indicator.
Neutropenia
Interactions among HCLS1, HAX1 and LEF-1 proteins are essential for G-CSF-triggered granulopoiesis.
Non-alcoholic Fatty Liver Disease
CRLS1 ameliorates nonalcoholic steatohepatitis through ATF3 transcriptional inactivation.
Osteosarcoma
Mesenchymal stromal cells of osteosarcoma patients do not show evidence of neoplastic changes during long-term culture.
Osteosarcoma
Ten-gene signature reveals the significance of clinical prognosis and immuno-correlation of osteosarcoma and study on novel skeleton inhibitors regarding MMP9.
Pneumonia
E3 Ligase Subunit Fbxo15 and PINK1 Kinase Regulate Cardiolipin Synthase 1 Stability and Mitochondrial Function in Pneumonia.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0016
CDP-dimyristoylglycerol
-
pH 8.5, 37°C, at optimal concentration of phospholipid activators
additional information
additional information
-
the two Km values for CDP-diacylglycerol, each estimated by nonlinear regression analysis of 18 kinetic points, are 0.02 and 0.03 mol% in the presence of 1 mM and 10 mM Mg2+ respectively, pH 9.0, 37°C
-
0.0024
CDP-1,2-dimyristoylglycerol
-
at low Co2+ concentration, pH pH 9.0, 37°C
0.0029
CDP-1,2-dimyristoylglycerol
-
at high Co2+ concentration, pH pH 9.0, 37°C
0.032
egg yolk phosphatidylglycerol
-
at high Co2+ concentration, pH pH 9.0, 37°C
-
0.045
egg yolk phosphatidylglycerol
-
pH 8.5, 37°C, at optimal concentration of phospholipid activators
-
0.0619
egg yolk phosphatidylglycerol
-
at low Co2+ concentration, pH pH 9.0, 37°C
-
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.000000373
-
pH and temperature not specified in the publication, activity in liver mitochondria
0.000000568
-
pH and temperature not specified in the publication, activity in thyroxine-treated liver mitochondria
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.5 - 8.5
pH 6.5: aboput 40% of maximal activity, pH 8.5: about 60%& of maximal activity
7.2 - 8.9
-
pH 7.2: about 40% of maximal activity, pH 8.9: about 75% of maximal activity
7.5 - 10
pH 7.5: about 45% of maximal activity, pH 10.0: about 85% of maximal activity
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
35 - 65
35°C: about 45% of maximal activity, 65°C: about 40% of maximal activity
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
additional information
the hCLS1 gene is predominantly expressed in tissues that require high levels of mitochondrial activities for energy metabolism
brenda
additional information
-
the hCLS1 gene is predominantly expressed in tissues that require high levels of mitochondrial activities for energy metabolism
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
the recombinant enzyme is exclusively localized in mitochondria when expressed in COS-7 cells
brenda