2.3.1.43: phosphatidylcholine-sterol O-acyltransferase
This is an abbreviated version!
For detailed information about phosphatidylcholine-sterol O-acyltransferase, go to the full flat file.
Word Map on EC 2.3.1.43
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2.3.1.43
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lipoprotein
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hdl
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apolipoproteins
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cholesteryl
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high-density
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triglyceride
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esterification
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apoa-i
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atherosclerosis
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lipase
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esterify
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low-density
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coronary
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cardiovascular
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hdl-cholesterol
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unesterified
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opacity
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apoproteins
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hypercholesterolemia
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corneal
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discoidal
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atherogenic
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subfractions
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hdl-associated
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triglyceride-rich
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apoc-iii
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postheparin
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synthesis
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hyperlipoproteinemia
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lysolecithin
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vldl-c
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tg-rich
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dimyristoyl
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antiatherogenic
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b-containing
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normolipidemic
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cholesterol-loaded
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xanthoma
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medicine
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lipoprotein-cholesterol
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chylomicron
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acyl-coa:cholesterol
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lipid-free
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paraoxonase
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apob-containing
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hdl-mediated
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3hcholesterol
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drug development
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lipid-poor
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hypertriglyceridemia
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tangier
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very-low-density
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non-hdl
- 2.3.1.43
- lipoprotein
- hdl
-
apolipoproteins
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cholesteryl
-
high-density
- triglyceride
- esterification
- apoa-i
- atherosclerosis
- lipase
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esterify
-
low-density
- coronary
- cardiovascular
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hdl-cholesterol
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unesterified
- opacity
- apoproteins
- hypercholesterolemia
- corneal
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discoidal
-
atherogenic
-
subfractions
-
hdl-associated
-
triglyceride-rich
- apoc-iii
-
postheparin
- synthesis
- hyperlipoproteinemia
- lysolecithin
-
vldl-c
-
tg-rich
-
dimyristoyl
-
antiatherogenic
-
b-containing
-
normolipidemic
-
cholesterol-loaded
-
xanthoma
- medicine
-
lipoprotein-cholesterol
- chylomicron
-
acyl-coa:cholesterol
-
lipid-free
- paraoxonase
-
apob-containing
-
hdl-mediated
-
3hcholesterol
- drug development
-
lipid-poor
- hypertriglyceridemia
- tangier
-
very-low-density
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non-hdl
Reaction
Synonyms
acyltransferase, lecithin-cholesterol, cholesterol transacyltransferase, LAT, LCAT, lecithin cholesterol acyl transferase, lecithin cholesterol acyltransferase, lecithin-cholesterol acyl transferase, lecithin-cholesterol acyltransferase, lecithin/cholesterol acyltransferase, lecithin: cholesterol acyltransferase, lecithin:cholesterol acyl-transferase, lecithin:cholesterol acyltransferase, lysolecithin acyltransferase, phospholipid-cholesterol acyltransferase, plasma lecithin-cholesterol acyltransferase, TgLCAT, TGME49_272420
ECTree
2.3.1.43 phosphatidylcholine-sterol O-acyltransferaseAdvanced search results
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results (Engineering
Engineering on EC 2.3.1.43 - phosphatidylcholine-sterol O-acyltransferase
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PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
C31Y
E149A
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site-directed mutagenesis, mutation alters the human enzyme residue to the corresponding residue of the rat sequence, 2.9fold increased cholesteryl ester formation activity, 5.5fold increased phospholipase A2 activity in the mutant compared to the wild-type enzyme
E149A/Y292H/W294F
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site-directed mutagenesis, mutation alters the human enzyme residues to the corresponding residues of the rat sequence, increased cholesteryl ester formation activity and phospholipase A2 activity with 1-palmitoyl-2-20:4-sn-glycero-3-phosphocholine, decreased activities with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine compared to the wild-type enzyme
P274S
the homozygous mutation causes familial lecithin-cholesterol acyltransferase deficiency with renal involvement
T123I
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naturally occuring mutation involved in the fish eye disease, conformational changes upon substrate binding is altered in mutant T123I compared to the wild-type enzyme, overview
V309M
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naturally occuring mutation in exon 6, the rare enzyme genetic disorder, familial LCAT deficiency, leads to corneal opacities and proteinuria with renal failure, phenotype analysis of a Polish family, the patients show 10% of control enzyme activity and highly reduced enzyme concentrations, low total HDL-cholesterol and cholesteryl ester concentrations, decreased apo AI and apo AII serum levels, low LDL-cholesterol and apoB and Lp levels, and increased oleate/linoleate ratios, in cholestryl esters, phenotype, overview
Y292H/W294F
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site-directed mutagenesis, mutation alters the human enzyme residues to the corresponding residues of the rat sequence, 1.4fold increased cholesteryl ester formation activity, 2.8fold increased phospholipase A2 activity in the mutant compared to the wild-type enzyme
additional information
C31Y
site-directed mutagenesis, the mutation renders the enzyme more stable and active than the native form
C31Y
the mutant has an about 10fold higher cholesterol esterification activity compared with wild type
additional information
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deletion of the first residue of the enzyme's N-terminus lead to 95% reduced alpha-enzyme activity and slightly increased beta-enzyme activity, deletion of the first 2 residues lead to abolished alpha-enzyme activity and reduced beta-enzyme activity, respectively, but the mutant enzymes are still able to bind the substrates, mutants with deletion of 3-5 N-terminal residues show no alpha-enzyme activity and residual or no beta-enzyme activity, overview
additional information
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a frameshift mutation, insertion of an adenine identified at codon 178 generating a Tsp 509 I restriction site, s AATT, in exon 5 of the LCAT gene is associated with renal failure with proteinuria, corneal opacity, and anemia in familial LCAT deficiency
additional information
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using adenovirus-mediated gene transfer of the mutants apoA-I(R151C), apoA-I(R160L) and apoA-I(R149A) in apoA-I-/- mice, a common feature of the three mutations are observed: low HDL levels and the presence of discoidal particles in plasma. These defects can be corrected by coinfection of apoA-I-/- mice with adenoviruses expressing the mutant proteins along with human LCAT, indicating that the endogenous LCAT is rate limiting in the conversion of discoidal into spherical HDL
additional information
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deleterious LCAT mutants show low HDL-cholesterol levels
additional information
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enzyme deficiency phenotypes, overview. Generation of transgenic mice, monkeys, or rabbits overexpressing the human LCAT
additional information
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HDL2 and HDL3-phospholipids, HDL2-cholesterol concentrations and LCAT activity are reduced in preganancy-induced hypertension and in chronic hypertensive mothers, as well as in their small for gestational age, SGA, newborns. Maternal hypertension and foetal intrauterine growth retardation are associated with profound abnormalities in HDL metabolism, consistent with an atherogenic risk, phenotype, overview
additional information
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LCAT overexpression in transgenic wild-type and human-apolipoprotein A-I-transgenic mice does not promote macrophage reverse cholesterol transport, even in the setting of hepatic SR-BI overexpression or CETP expression, overview
additional information
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loss-of-function LCAT mutants show highly decreased HDL-cholesteryl ester plasma levels and inability to form mature HDL particles, leading to progressive renal insufficiency, up to end-stage renal disease A, and corneal opacification, as well as to hemolytic anemia, phenotype of heterozygotes and homozygotes
additional information
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reduced LCAT expression can cause reduction of plasma HDL cholesterol concentration, impaired HDL maturation, altered HDL composition and increased plasma concentration of lipid-poor pre-beta HDL particles, overview
additional information
construction of a recombinant human lecithin-cholesterol acyltransferase Fc fusion (huLCAT-Fc), a chimeric protein produced by fusing human Fc to the C-terminus of the human enzyme via a linker sequence. The huLCAT-Fc homodimer contains five N-linked glycosylation sites per monomer. The heterogeneity and site-specific distribution of the various glycans are examined using enzymatic digestion and LC-MS/MS, followed by automatic processing. Almost all of the N-linked glycans in human LCAT are fucosylated and sialylated. The predominant LCAT N-linked glycoforms are biantennary glycans, followed by triantennary sugars, whereas the level of tetraantennary glycans is much lower. Glycans at the Fc N-linked site exclusively contain typical asialobiantennary structures. HuLCAT-Fc is also confirmed to have mucin-type glycans attached at T407 and S409. When LCAT-Fc fusions are constructed using a G-S-G-G-G-G linker, an unexpected 1632 Da xylose-based glycosaminoglycan (GAG) tetrasaccharide core of Xyl-Gal-Gal-GlcA is attached to S418. Several minor intermediate species including Xyl, Xyl-Gal, Xyl-Gal-Gal, and a phosphorylated GAG core are also present. GAG incorporation can be eliminated through engineering by shifting the linker Ser residue downstream in the linker sequence
additional information
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construction of a recombinant human lecithin-cholesterol acyltransferase Fc fusion (huLCAT-Fc), a chimeric protein produced by fusing human Fc to the C-terminus of the human enzyme via a linker sequence. The huLCAT-Fc homodimer contains five N-linked glycosylation sites per monomer. The heterogeneity and site-specific distribution of the various glycans are examined using enzymatic digestion and LC-MS/MS, followed by automatic processing. Almost all of the N-linked glycans in human LCAT are fucosylated and sialylated. The predominant LCAT N-linked glycoforms are biantennary glycans, followed by triantennary sugars, whereas the level of tetraantennary glycans is much lower. Glycans at the Fc N-linked site exclusively contain typical asialobiantennary structures. HuLCAT-Fc is also confirmed to have mucin-type glycans attached at T407 and S409. When LCAT-Fc fusions are constructed using a G-S-G-G-G-G linker, an unexpected 1632 Da xylose-based glycosaminoglycan (GAG) tetrasaccharide core of Xyl-Gal-Gal-GlcA is attached to S418. Several minor intermediate species including Xyl, Xyl-Gal, Xyl-Gal-Gal, and a phosphorylated GAG core are also present. GAG incorporation can be eliminated through engineering by shifting the linker Ser residue downstream in the linker sequence
additional information
generation of human LCAT transgenic mice that are apoA-I deficient by breeding hLCATTg/Tg mice on C57Bl/6J background with apoA-I-/- mice on C57Bl/6J background, both over more than 10 generations
additional information
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generation of human LCAT transgenic mice that are apoA-I deficient by breeding hLCATTg/Tg mice on C57Bl/6J background with apoA-I-/- mice on C57Bl/6J background, both over more than 10 generations
additional information
removal of a proline rich region (residues 402 to 416) on the C-terminus
additional information
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LCAT deficiency significantly decreases the cholesteryl ester percentage and significantly increases the phospholipid percentage of LDL, overview
additional information
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mice deficient in apo A-I and especially in apoE lipoproteins show reduced plasma enzyme activity, overview
additional information
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overexpression of human LCAT in transgenic wild-type and human-apolipoprotein A-I-transgenic mice does not promote macrophage reverse cholesterol transport, even in the setting of hepatic SR-BI overexpression or CETP expression, overview. LCAT heterozygous and homozygous deficient mice mutants, phenotypes, detailed overview
additional information
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overexpression of LCAT does not protect against diet-induced atherosclerosis, but in contrary does increase the atherosclerosis risk. LCAT knockout mice show markedly reduced plasma total cholesterol, cholesteryl esters, HDL-C, apolipoprotein A-I, and an increase in plasma triglycerides, the amount of alpha-HDl is decreased compared to wild-type mice
additional information
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mice deficient in apo A-I and especially in apoE lipoproteins show reduced plasma enzyme activity, overview
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additional information
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hepatocyte-directed adenoviral gene transfer of LCAT or apolipoprotein A-I to LDLr+/- rabbits with 0.15% cholesterol-diet-induced hyperlipidemia increases the HDL cholesterol in these rabbits, intimal lesions in organs of the LDL+/- heterozygous rabbits, overview
additional information
construction of enzyme knockout and overexpressing strains, the loss of TgLCAT expression leads to an egress defect, and its overexpression confers an egress advantage, phenotype, overview
additional information
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construction of enzyme knockout and overexpressing strains, the loss of TgLCAT expression leads to an egress defect, and its overexpression confers an egress advantage, phenotype, overview
additional information
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construction of enzyme knockout and overexpressing strains, the loss of TgLCAT expression leads to an egress defect, and its overexpression confers an egress advantage, phenotype, overview
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