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Information on EC 2.7.8.41 - cardiolipin synthase (CMP-forming) and Organism(s) Homo sapiens
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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 taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Synonyms
hcls1, crls1, cls_cap, cls1p, cardiolipin synthase 1, cls 1, sco1389, crcls1, cardiolipin synthase-1, ydl142c, 
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topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-, -, -, -
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.
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
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-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
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-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-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
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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
additional information
-
the hCLS1 gene is predominantly expressed in tissues that require high levels of mitochondrial activities for energy metabolism
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
the recombinant enzyme is exclusively localized in mitochondria when expressed in COS-7 cells
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
physiological function
cardiolipin synthase is involved in maintaining physiologic membrane structure and function even under metabolic stress
physiological function
the enzyme catalyzes the terminal step in cardiolipin biosynthesis. Cardiolipin is essential for mitochondrial structure and function
physiological function
knockdown of cardiolipin synthase induces mitochondrial elongation in human cells. In cardiolipin synthase-knocked down cells a decreased amount of cardiolipin and an accumulation of phosphatidylglycerol is observed. Knockdown of other genes involved in cardiolipin synthesis does not influence mitochondrial morphology
physiological function
phosphatidylglycerophosphate synthase PGS1 and CLS1 are constituents of large protein complexes. PGS1 forms oligomers and associates with CLS1 and phosphatidylglycerophosphate phosphatase PTPMT1. Cardiolipin and CLS1 are not required for PGS1 to assemble in the complex. PGS1 and CLS1 interact with multiple cardiolipin-binding mitochondrial membrane proteins, including prohibitins, stomatin-like protein 2 and the MICOS components MIC60 and MIC19
physiological function
synthesis of cardiolipin is indispensable for stimulating and sustaining thermogenic fat function. Cardiolipin biosynthesis is robustly induced in brown and beige adipose upon cold exposure. Overexpression of cardiolipin synthase Crls1 enhances energy consumption in adipocytes, and adipose Crls1 levels positively correlate with insulin sensitivity
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). CRLS1_HUMAN
301
3
32593
Swiss-Prot
Mitochondrion (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
generation of transgenic mice selectively expressing human cardiolipin synthase 1 in cardiomyocytes
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
lipopolysaccharide treatment of HepG2 cells transiently expressing a histidine-tagged human cardiolipin synthase-1 (hCLS1) reduces hCLS1 mRNA and newly synthesized enzyme activity indicating that lipopolysaccharide inhibits production of newly synthesized hCLS1 via reduction in hCLS1 mRNA
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
cardiolipin synthase as a therapeutic target to attenuate mitochondrial dysfunction in diabetic myocardium
medicine
expression of Crls1 mRNA is significantly reduced in subcutaneous fat from diabetic subjects. The Crls1 mRNA levels in human subcutaneous white adipose tissue negatively correlate with HOMA2 measures of insulin resistance and positively correlate with HOMA2 measures of insulin sensitivity. Increased CRLS1 expression in human white adipocytes stimulates UCP1 expression and increases inducible uncoupled respiration
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Chen, D.; Zhang, X.Y.; Shi, Y.
Identification and functional characterization of hCLS1, a human cardiolipin synthase localized in mitochondria
Biochem. J.
398
169-176
2006
Homo sapiens (Q9UJA2), Homo sapiens
Houtkooper, R.H.; Akbari, H.; van Lenthe, H.; Kulik, W.; Wanders, R.J.; Frentzen, M.; Vaz, F.M.
Identification and characterization of human cardiolipin synthase
FEBS Lett.
580
3059-3064
2006
Homo sapiens (Q9UJA2), Homo sapiens
Lu, B.; Xu, F.Y.; Taylor, W.A.; Feingold, K.R.; Hatch, G.M.
Cardiolipin synthase-1 mRNA expression does not correlate with endogenous cardiolipin synthase enzyme activity in vitro and in vivo in mammalian lipopolysaccharide models of inflammation
Inflammation
34
247-254
2011
Homo sapiens (Q9UJA2), Homo sapiens, Mus musculus (Q80ZM8), Mus musculus
Kiebish, M.A.; Yang, K.; Sims, H.F.; Jenkins, C.M.; Liu, X.; Mancuso, D.J.; Zhao, Z.; Guan, S.; Abendschein, D.R.; Han, X.; Gross, R.W.
Myocardial regulation of lipidomic flux by cardiolipin synthase: setting the beat for bioenergetic efficiency
J. Biol. Chem.
287
25086-25097
2012
Homo sapiens (Q9UJA2)
Lu, B.; Xu, F.Y.; Jiang, Y.J.; Choy, P.C.; Hatch, G.M.; Grunfeld, C.; Feingold, K.R.
Cloning and characterization of a cDNA encoding human cardiolipin synthase (hCLS1)
J. Lipid Res.
47
1140-1145
2006
Homo sapiens (Q9UJA2), Homo sapiens
Serricchio, M.; Vissa, A.; Kim, P.; Yip, C.; McQuibban, G.
Cardiolipin synthesizing enzymes form a complex that interacts with cardiolipin-dependent membrane organizing proteins
Biochim. Biophys. Acta
1863
447-457
2018
Homo sapiens (Q9UJA2)
Sustarsic, E.; Ma, T.; Lynes, M.; Larsen, M.; Karavaeva, I.; Havelund, J.; Nielsen, C.; Jedrychowski, M.; Moreno-Torres, M.; Lundh, M.; Plucinska, K.; Jespersen, N.; Grevengoed, T.; Kramar, B.; Peics, J.; Hansen, J.; Shamsi, F.; Forss, I.; Neess, D.
Cardiolipin synthesis in brown and beige fat mitochondria is essential for systemic energy homeostasis
Cell Metab.
28
159-174.e11
2018
Homo sapiens (Q9UJA2), Homo sapiens, Mus musculus (Q80ZM8), Mus musculus
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