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Information on EC 2.3.1.135 - phosphatidylcholine-retinol O-acyltransferase and Organism(s) Homo sapiens
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2.3.1.135 phosphatidylcholine-retinol O-acyltransferaseIUBMB Comments
A key enzyme in retinoid metabolism, catalysing the transfer of an acyl group from the sn-1 position of phosphatidylcholine to retinol, forming retinyl esters which are then stored. Recognizes the substrate both in free form and when bound to cellular-retinol-binding-protein, but has higher affinity for the bound form. Can also esterify 11-cis-retinol.
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Word Map
- 2.3.1.135
-
retinoids
- retinal
-
all-trans-retinyl
- opsin
- 11-cis-retinol
-
isomerohydrolase
- amaurosis
-
leber
-
s-opsins
-
11-cis-retinoids
- medicine
-
crbp-i
- diagnostics
- analysis
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
Synonyms
lecithin retinol acyltransferase, lecithin-retinol acyltransferase, lecithin retinol acyl transferase, lecithin:retinol acyl transferase, retinyl ester synthase, lecithin/retinol acyltransferase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
acyltransferase, lecithin-retinol
-
-
-
-
lecithin retinol acyl transferase
-
-
-
-
lecithin retinol acyltransferase
lecithin-retinol acyltransferase
lecithin:retinol acyltransferase
LRAT
retinyl ester synthase
-
-
-
-
additional information
enzyme is the founder of a novel Cys-His enzyme family
lecithin-retinol acyltransferase
-
-
-
-
lecithin:retinol acyltransferase
-
-
-
-
lecithin:retinol acyltransferase
-
-
LRAT
-
-
-
-
LRAT
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
phosphatidylcholine + retinol-[cellular-retinol-binding-protein] = 2-acylglycerophosphocholine + retinyl-ester-[cellular-retinol-binding-protein]
phosphatidylcholine + retinol-[cellular-retinol-binding-protein] = 2-acylglycerophosphocholine + retinyl-ester-[cellular-retinol-binding-protein]
C161 and H60 form a catalytic dyad essential for activity, Q177 and D67 may play a non-essential role in catalysis, identification of the active site, reaction mechanism
phosphatidylcholine + retinol-[cellular-retinol-binding-protein] = 2-acylglycerophosphocholine + retinyl-ester-[cellular-retinol-binding-protein]
mechanism, Cys161 and Tyr154 are essential for activity
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Acyl group transfer
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
phosphatidylcholine:retinol---[cellular-retinol-binding-protein] O-acyltransferase
A key enzyme in retinoid metabolism, catalysing the transfer of an acyl group from the sn-1 position of phosphatidylcholine to retinol, forming retinyl esters which are then stored. Recognizes the substrate both in free form and when bound to cellular-retinol-binding-protein, but has higher affinity for the bound form. Can also esterify 11-cis-retinol.
CAS REGISTRY NUMBER
COMMENTARY
117444-03-8
-
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
didecanoylphosphatidylcholine + all-trans-retinol
all-trans-retinyl decanoate + 2-decanoylglycerophosphocholine
-
activity is about 10% of that with diheptanoylphosphatidylcholine
-
?
diheptanoylphosphatidylcholine + all-trans-retinol
all-trans-retinyl heptanoate + 2-heptanoylglycerophosphocholine
-
-
-
?
dilauroylphosphatidylcholine + all-trans-retinol
all-trans-retinyl laurate + 2-lauroylglycerophosphocholine
-
activity is about 4% of that with diheptanoylphosphatidylcholine
-
?
dimyristoylphosphatidylcholine + all-trans-retinol
all-trans-retinyl myristate + 2-myristoylglycerophosphocholine
activity is about 3% of that with diheptanoylphosphatidylcholine
-
-
?
dioctanoylphosphatidylcholine + all-trans-retinol
all-trans-retinyl octanoate + 2-octanoylglycerophosphocholine
activity is less than 15% of that with diheptanoylphosphatidylcholine
-
-
?
dioleoylphosphatidylcholine + all-trans-retinol
all-trans-retinyl oleate + 2-oleoylglycerophosphocholine
-
-
-
?
dipalmitoylphosphatidylcholine + all-trans-retinol
all-trans-retinyl palmitate + 2-palmitoylglycerophosphocholine
lecithin + retinol-[cellular retinol-binding protein]
2-acylglycerophosphocholine + retinyl ester-[cellular retinol-binding protein]
-
-
-
-
?
phosphatidylcholine + 11-cis-retinol
2-acylglycerophosphocholine + 11-cis-retinyl acyl ester
phosphatidylcholine + 11-cis-retinol-[cellular-retinol-binding-protein]
2-acylglycerophosphocholine + 11-cis-retinyl-ester-[cellular-retinol-binding-protein]
phosphatidylcholine + all-trans-retinol
2-acylglycerophosphocholine + all-trans-retinyl acyl ester
phosphatidylcholine + all-trans-retinol
2-acylglycerophosphocholine + all-trans-retinyl acylester
phosphatidylcholine + all-trans-retinol
all-trans-retinyl acyl esters + 2-acylglycerophosphocholine
phosphatidylcholine + all-trans-retinol-(bovine serum albumin)
all-trans-retinyl acyl ester-(bovine serum albumin) + 2-acylglycerophosphocholine
-
-
?
phosphatidylcholine + all-trans-retinol-[cellular-retinol-binding-protein]
2-acylglycerophosphocholine + all-trans-retinyl-ester-[cellular-retinol-binding-protein]
phosphatidylcholine + retinol-(cellular-retinol-binding-protein)
2-acylglycerophosphocholine + retinyl ester-(cellular-retinol-binding-protein)
phosphatidylcholine + retinol-[cellular-retinol-binding-protein]
2-acylglycerophosphocholine + retinyl-ester-[cellular-retinol-binding-protein]
dipalmitoylphosphatidylcholine + all-trans-retinol
all-trans-retinyl palmitate + 2-palmitoylglycerophosphocholine
-
-
-
?
dipalmitoylphosphatidylcholine + all-trans-retinol
all-trans-retinyl palmitate + 2-palmitoylglycerophosphocholine
-
mechanistic hypothesis
-
?
dipalmitoylphosphatidylcholine + all-trans-retinol
all-trans-retinyl palmitate + 2-palmitoylglycerophosphocholine
-
mechanistic hypothesis
-
?
dipalmitoylphosphatidylcholine + all-trans-retinol
all-trans-retinyl palmitate + 2-palmitoylglycerophosphocholine
mechanistic hypothesis
-
r
dipalmitoylphosphatidylcholine + all-trans-retinol
all-trans-retinyl palmitate + 2-palmitoylglycerophosphocholine
activity is about 2% of that with diheptanoylphosphatidylcholine
-
-
?
phosphatidylcholine + 11-cis-retinol
2-acylglycerophosphocholine + 11-cis-retinyl acyl ester
-
-
-
?
phosphatidylcholine + 11-cis-retinol
2-acylglycerophosphocholine + 11-cis-retinyl acyl ester
-
low activity
-
-
?
phosphatidylcholine + 11-cis-retinol
2-acylglycerophosphocholine + 11-cis-retinyl acyl ester
essential for generation of the precursor for 11-cis-retinal, the visual chromophore in the eye
-
-
?
phosphatidylcholine + 11-cis-retinol-[cellular-retinol-binding-protein]
2-acylglycerophosphocholine + 11-cis-retinyl-ester-[cellular-retinol-binding-protein]
-
trans-esterification reaction is reversible, however in the presence of the isomerase, all-trans-retinyl esters are converted to 11-cis-retinol which is enzymatically oxidized to 11-cis-retinal, the chromophore of vision. Both all-trans-retinol and 11-cis-retinol are substrates for LRAT esterification, although all-transretinol is the preferred substrate.
-
-
r
phosphatidylcholine + 11-cis-retinol-[cellular-retinol-binding-protein]
2-acylglycerophosphocholine + 11-cis-retinyl-ester-[cellular-retinol-binding-protein]
-
both all-trans-retinol and 11-cis-retinol are substrates for LRAT esterification, although all-transretinol is the preferred substrate.
-
-
r
phosphatidylcholine + all-trans-retinol
2-acylglycerophosphocholine + all-trans-retinyl acyl ester
enzyme is involved in vitamin A storage and mobilization
-
-
r
phosphatidylcholine + all-trans-retinol
2-acylglycerophosphocholine + all-trans-retinyl acyl ester
all-trans-retinol is vitamin A, phosphatidylcholine is lecithin
-
-
r
phosphatidylcholine + all-trans-retinol
2-acylglycerophosphocholine + all-trans-retinyl acylester
-
-
-
-
?
phosphatidylcholine + all-trans-retinol
2-acylglycerophosphocholine + all-trans-retinyl acylester
transfer of acyl moiety from sn-1 position of lecithin, i.e. phosphatidylcholine, to vitamin A, i.e. all-trans-retinol
-
-
?
phosphatidylcholine + all-trans-retinol
all-trans-retinyl acyl esters + 2-acylglycerophosphocholine
-
-
-
-
?
phosphatidylcholine + all-trans-retinol
all-trans-retinyl acyl esters + 2-acylglycerophosphocholine
-
-
-
r
phosphatidylcholine + all-trans-retinol
all-trans-retinyl acyl esters + 2-acylglycerophosphocholine
-
-
-
r
phosphatidylcholine + all-trans-retinol
all-trans-retinyl acyl esters + 2-acylglycerophosphocholine
-
-
-
?
phosphatidylcholine + all-trans-retinol-[cellular-retinol-binding-protein]
2-acylglycerophosphocholine + all-trans-retinyl-ester-[cellular-retinol-binding-protein]
-
-
-
-
?
phosphatidylcholine + all-trans-retinol-[cellular-retinol-binding-protein]
2-acylglycerophosphocholine + all-trans-retinyl-ester-[cellular-retinol-binding-protein]
-
-
-
?
phosphatidylcholine + all-trans-retinol-[cellular-retinol-binding-protein]
2-acylglycerophosphocholine + all-trans-retinyl-ester-[cellular-retinol-binding-protein]
-
enzyme is involved in the visual cycle in the eye
-
-
?
phosphatidylcholine + all-trans-retinol-[cellular-retinol-binding-protein]
2-acylglycerophosphocholine + all-trans-retinyl-ester-[cellular-retinol-binding-protein]
transfer of acyl moiety from sn-1 position of lecithin, i.e. phosphatidylcholine, to vitamin A, i.e. all-trans-retinol
-
-
?
phosphatidylcholine + all-trans-retinol-[cellular-retinol-binding-protein]
2-acylglycerophosphocholine + all-trans-retinyl-ester-[cellular-retinol-binding-protein]
-
trans-esterification reaction is reversible, however in the presence of the isomerase, all-trans-retinyl esters are converted to 11-cis-retinol which is enzymatically oxidized to 11-cis-retinal, the chromophore of vision. Both all-trans-retinol and 11-cis-retinol are substrates for LRAT esterification, although all-transretinol is the preferred substrate.
-
-
r
phosphatidylcholine + all-trans-retinol-[cellular-retinol-binding-protein]
2-acylglycerophosphocholine + all-trans-retinyl-ester-[cellular-retinol-binding-protein]
-
both all-trans-retinol and 11-cis-retinol are substrates for LRAT esterification, although all-transretinol is the preferred substrate.
-
-
r
phosphatidylcholine + retinol-(cellular-retinol-binding-protein)
2-acylglycerophosphocholine + retinyl ester-(cellular-retinol-binding-protein)
-
-
-
?
phosphatidylcholine + retinol-(cellular-retinol-binding-protein)
2-acylglycerophosphocholine + retinyl ester-(cellular-retinol-binding-protein)
-
-
-
?
phosphatidylcholine + retinol-[cellular-retinol-binding-protein]
2-acylglycerophosphocholine + retinyl-ester-[cellular-retinol-binding-protein]
-
-
-
-
?
phosphatidylcholine + retinol-[cellular-retinol-binding-protein]
2-acylglycerophosphocholine + retinyl-ester-[cellular-retinol-binding-protein]
-
renal cell carcinomata contain greatly reduced levels of retinol and retinyl esters relative to healthy kidney tissue
-
-
?
phosphatidylcholine + retinol-[cellular-retinol-binding-protein]
2-acylglycerophosphocholine + retinyl-ester-[cellular-retinol-binding-protein]
-
esterification of all-trans-retinol
-
-
?
additional information
?
-
-
little or no ability to transfer acyl groups from lysophosphatidylcholine, phosphatidylethanolamine or phosphatidic acid to retinol-(cellular-retinol-binding protein)
-
-
?
additional information
?
-
-
only fatty acyl group at the sn-1 is transferred
-
-
?
additional information
?
-
-
only fatty acyl group at the sn-1 is transferred
-
-
?
additional information
?
-
only fatty acyl group at the sn-1 is transferred
-
-
?
additional information
?
-
-
only fatty acyl group at the sn-1 is transferred
-
-
?
additional information
?
-
-
the fatty acid in the 2-position is important in substrate recognition
-
-
?
additional information
?
-
-
low prevalence of lecithin retinol acyltransferase mutations in patients with Leber congenital amaurosis and autosomal recessive retinitis pigmentosa
-
-
?
additional information
?
-
-
retinoids, vitamin A, i.e.retinol, and related metabolites, have been shown to be important in regulating cell growth and differentiation, retinoid signaling, overview, expression of LRAT, which converts retinol to retinyl esters, is reduced in several human carcinomas as compared with adjacent normal tissue from the same organs, LRAT protein progressively decreases with a reduction in the degree of tumor differentiation in invasive breast carcinomas, overview
-
-
?
additional information
?
-
-
the enzyme performs formation of all-trans retinyl heptanoate from all-trans-retinol and 1,2-diheptanoyl-sn-glycero-3-phosphocholine, DHPC
-
-
?
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
lecithin + retinol-[cellular retinol-binding protein]
2-acylglycerophosphocholine + retinyl ester-[cellular retinol-binding protein]
-
-
-
-
?
phosphatidylcholine + 11-cis-retinol
2-acylglycerophosphocholine + 11-cis-retinyl acyl ester
essential for generation of the precursor for 11-cis-retinal, the visual chromophore in the eye
-
-
?
phosphatidylcholine + 11-cis-retinol-[cellular-retinol-binding-protein]
2-acylglycerophosphocholine + 11-cis-retinyl-ester-[cellular-retinol-binding-protein]
-
trans-esterification reaction is reversible, however in the presence of the isomerase, all-trans-retinyl esters are converted to 11-cis-retinol which is enzymatically oxidized to 11-cis-retinal, the chromophore of vision. Both all-trans-retinol and 11-cis-retinol are substrates for LRAT esterification, although all-transretinol is the preferred substrate.
-
-
r
phosphatidylcholine + all-trans-retinol
2-acylglycerophosphocholine + all-trans-retinyl acyl ester
enzyme is involved in vitamin A storage and mobilization
-
-
r
phosphatidylcholine + all-trans-retinol
all-trans-retinyl acyl esters + 2-acylglycerophosphocholine
phosphatidylcholine + all-trans-retinol-[cellular-retinol-binding-protein]
2-acylglycerophosphocholine + all-trans-retinyl-ester-[cellular-retinol-binding-protein]
phosphatidylcholine + retinol-[cellular-retinol-binding-protein]
2-acylglycerophosphocholine + retinyl-ester-[cellular-retinol-binding-protein]
phosphatidylcholine + all-trans-retinol
all-trans-retinyl acyl esters + 2-acylglycerophosphocholine
-
-
-
-
?
phosphatidylcholine + all-trans-retinol
all-trans-retinyl acyl esters + 2-acylglycerophosphocholine
-
-
-
?
phosphatidylcholine + all-trans-retinol-[cellular-retinol-binding-protein]
2-acylglycerophosphocholine + all-trans-retinyl-ester-[cellular-retinol-binding-protein]
-
-
-
?
phosphatidylcholine + all-trans-retinol-[cellular-retinol-binding-protein]
2-acylglycerophosphocholine + all-trans-retinyl-ester-[cellular-retinol-binding-protein]
-
enzyme is involved in the visual cycle in the eye
-
-
?
phosphatidylcholine + all-trans-retinol-[cellular-retinol-binding-protein]
2-acylglycerophosphocholine + all-trans-retinyl-ester-[cellular-retinol-binding-protein]
-
trans-esterification reaction is reversible, however in the presence of the isomerase, all-trans-retinyl esters are converted to 11-cis-retinol which is enzymatically oxidized to 11-cis-retinal, the chromophore of vision. Both all-trans-retinol and 11-cis-retinol are substrates for LRAT esterification, although all-transretinol is the preferred substrate.
-
-
r
phosphatidylcholine + retinol-[cellular-retinol-binding-protein]
2-acylglycerophosphocholine + retinyl-ester-[cellular-retinol-binding-protein]
-
-
-
-
?
phosphatidylcholine + retinol-[cellular-retinol-binding-protein]
2-acylglycerophosphocholine + retinyl-ester-[cellular-retinol-binding-protein]
-
renal cell carcinomata contain greatly reduced levels of retinol and retinyl esters relative to healthy kidney tissue
-
-
?
additional information
?
-
-
low prevalence of lecithin retinol acyltransferase mutations in patients with Leber congenital amaurosis and autosomal recessive retinitis pigmentosa
-
-
?
additional information
?
-
-
retinoids, vitamin A, i.e.retinol, and related metabolites, have been shown to be important in regulating cell growth and differentiation, retinoid signaling, overview, expression of LRAT, which converts retinol to retinyl esters, is reduced in several human carcinomas as compared with adjacent normal tissue from the same organs, LRAT protein progressively decreases with a reduction in the degree of tumor differentiation in invasive breast carcinomas, overview
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
N-ethylmaleimide
-
0.001 mM, complete inhibition of retinol-(cellular-retinol-binding-protein)type II esterification
phenylmethylsulfonyl fluoride
-
2 mM, 90% inhibition of retinol-(cellular-retinol-binding-protein)type II esterification
additional information
-
mutant C161S is not significantly inactivated by N-Boc-L-biocytinyl-11-aminoundecan chloromethylketone
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SDS
SDS is necessary for tLRAT extraction from cell lysates. tLRAT enzymatic activity drastically diminishes at SDS concentrations below 0.05% and remains unchanged when SDS concentration is increased from 0.05 to 1%. SDS is very important for tLRAT stability
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00024
all-trans-retinol-[cellular-retinol-binding-protein]
-
pH and temperature not specified in the publication
-
0.0005
retinol-(cellular-retinol-binding-protein)
-
reaction with phosphatidylcholine
-
0.00036
all-trans-retinol
-
with dipalmitoylphosphatidylcholine, cloned enzyme, expressed in HEK-293T cells
0.00094
all-trans-retinol
-
with dipalmitoylphosphatidylcholine, cloned enzyme, expressed in HEK-296T cells
additional information
additional information
-
steady-state kinetic analysis using purified truncated mutant tLRAT
-
additional information
additional information
the water-soluble phospholipid:retinol molar ratio is very critical in the assay. It should be equal to at least 12.5:1 to allow proper solubilization of retinol by water-soluble phospholipid. A water-soluble phospholipid:tLRAT molar ratio of 4200000:1 should not be exceeded, otherwise a large decrease in activity occurs
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
activity of recombinant mutant enzymes and recombinant truncated wild-type, overview
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
pH profile of recombinant mutant enzymes and recombinant truncated wild-type
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
neoplastic and adjacent, non-neoplastic glandular breast tissue specimens from human patients, expression analysis, reduced enzyme expression, LRAT protein progressively decreases with a reduction in the degree of tumor differentiation in invasive breast carcinomas, overview
hepatic stellate cells shift their retinyl ester synthesizing capacity from LRAT to acyl-CoA:diacylglycerol acyltransferase DGAT1 during activation
additional information
the enzyme is distributed in both hepatic stellate cells and endothelial cells of normal rodent and human liver
-
GATA transcription factors are involved in the transcriptional activation of LRAT in normal human prostate epithelial cells
-
adenocarcinoma, LRAT is downregulated as a result of oncogenic transformation
-
transcriptional regulation of the human LRAT gene is aberrant in human prostate cancer cells
additional information
expression of multiple mRNAs in a tissue-specific manner
additional information
-
renal tissue expression pattern, expression is higher in renal tumor than in normal tissue
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
before initiation of retinyl ester biosynthesis, LRAT distributes throughout the endoplasmic reticulum, and Crpb1 localizes with mitochondria associated membranes, surrounded by LRAT. Upon initiating retinyl ester biosynthesis in cells, Crpb1 remains with MAM, and both Crbp1 and MAM re-localize with LRAT. LRAT formed rings around the growing lipid droplets
-
upon initiating retinyl ester biosynthesis in cells, Crpb1 remains with MAM, and both Crbp1 and MAM re-localize with LRAT. LRAT formed rings around the growing lipid droplets. LRAT-containing rings colocalize with the lipid-droplet surface proteins, desnutrin/adipose triglyceride lipase and perilipin 2. Colocalization with lipid droplets requires the 38 N-terminal amino acid residues of LRAT, and specifically K36 and R38. Formation of rings around the growing lipid droplets does not require functional microtubules
-
bound, membrane topology model of LRAT using I-TASSER, membrane interaction probes of LRAT and truncated LRAT with phospholipid monolayers, circular dichroism, overview
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
-
based on its secondary structure LRAT belongs to a superfamily of enzymes generically referred as NIpC/P60. Within this superfamily, a multiple sequence alignment of LRAT and LRAT-like family members shows that they share three conserved amino acid residues; cysteine, histidine and a polar residue that is thought to complete a catalytic triad similar to the papain-like thiol peptidases
malfunction
metabolism
-
the key step of vitamin A metabolism is the esterification of all-trans retinol, catalyzed by lecithin/retinol acyltransferase, LRAT. Vitamin A metabolism in benign and malignant melanocytic skin cells with regard to expression, functional activity of LRAT, RPE65, and cRBP2 and their regulation, overview
physiological function
additional information
malfunction
-
a truncated form of LRAT as well as its S175R mutant lead to retinis pigmentosa, a severe form of retinal dystrophy
malfunction
-
homozygous mutation S175R occurs in two patients diagnosed with severe early-onset retinal degeneration
physiological function
-
activities of LRAT and RPE65 may be important for removal of all-trans retinal which is the substrate for retinoic acid production in skin cells. Decreasing cellular amount of retinoic acid and its precursor molecules might result in a change of gene regulation
physiological function
-
function of LRAT is to catalyze a trans-esterification reaction that occurs between the sn-1 position of lecithin molecules in the lipid bilayer of the smooth endoplasmic reticulum and all-trans-retinol in the formation of all-trans-retinyl esters. Functional role of LRAT in the visual cycle
physiological function
-
lecithin:retinol acyltransferase, LRAT, is a membrane-bound protein that plays an essential function in the visual cycle. It catalyzes the esterification of retinol into retinyl esters in the retinal pigment epithelium as well as in other tissues including testis, liver, and intestine
physiological function
-
relationship between LRAT and Crbp1 during retinyl ester biosynthesis in which mitochondria associated membranes-associated Crpb1 and LRAT colocalize, and both surround the growing retinyl ester-containing lipid droplet. The N-terminus of LRAT, especially K36 and R38, is essential to colocalization with the lipid droplet
physiological function
quiescent LRAT knockout hepatic stellate cells retain the capacity to synthesize retinyl esters and to store neutral lipids in lipid droplets ex vivo. The median lipid droplet size in LRAT knockout hepatic stellate cells (1080 nm) is significantly smaller than in wild-type stellate cells (1618 nm). Upon prolonged (24h) incubation, the amounts of small (less than 700 nm) lipid droplets strongly increases both in wild type and in LRAT knockout hepatic stellate cells
additional information
-
malignant melanoma cells are able to esterify all-trans retinol and subsequently isomerize all-trans retinyl esters into 11-cis retinol, whereas their benign counterpart melanocytes are not able to catalyze these reactions
additional information
-
the catalytic triad includes histidine 60, tyrosine 154 and cysteine 161 in the LRAT structure
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). LRAT_HUMAN
230
1
25703
Swiss-Prot
Secretory Pathway (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
20000
25000
40000
-
nonreducing PAGE, higher aggregation, up to pentamers, occurs in absence of denaturing agents
20000
-
1 * 25000, full-length wild-type enzyme, SDS-PAGE, 1 * 20000, recombinant truncated enzyme, SDS-PAGE
20000
-
2 * 25000, full-length wild-type enzyme, SDS-PAGE, 2 * 20000, recombinant truncated enzyme, SDS-PAGE
25000
-
1 * 25000, full-length wild-type enzyme, SDS-PAGE, 1 * 20000, recombinant truncated enzyme, SDS-PAGE
25000
-
2 * 25000, full-length wild-type enzyme, SDS-PAGE, 2 * 20000, recombinant truncated enzyme, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
-
2 * 25000, full-length wild-type enzyme, SDS-PAGE, 2 * 20000, recombinant truncated enzyme, SDS-PAGE
monomer
additional information
-
the enzyme exists as a mixture of monomer and dimer, determined by sedimentation equilibrium analysis and mass spectrometry, higher aggregation, up to pentamers, occurs in absence of denaturing agents
monomer
-
1 * 25000, full-length wild-type enzyme, SDS-PAGE, 1 * 20000, recombinant truncated enzyme, SDS-PAGE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E14L
naturally occuring substitution localized in an N-terminal alpha-helix. The mutant protein is instable and shows accelerated proteosomal degradation. The instability of E14L does not abrogate the production of the visual chromophore in a cell-based assay. Eexpression of E14L leads to a rapid increase in cellular levels of retinoic acid upon retinoid supplementation
K104A
site-directed mutagenesis, reduced activity compared to the truncated wild-type enzyme
K133A
site-directed mutagenesis, increased activity compared to the truncated wild-type enzyme
K133A/K134A
site-directed mutagenesis, slightly increased activity compared to the truncated wild-type enzyme
K134A
site-directed mutagenesis, increased activity compared to the truncated wild-type enzyme
K147A
site-directed mutagenesis, reduced activity compared to the truncated wild-type enzyme
K180R
site-directed mutagenesis, reduced activity compared to the truncated wild-type enzyme
K186R
site-directed mutagenesis, reduced activity compared to the truncated wild-type enzyme
K90A
site-directed mutagenesis, highly reduced activity compared to the truncated wild-type enzyme
K95A
site-directed mutagenesis, highly reduced activity compared to the truncated wild-type enzyme
P173L
mutation caused night blindness in a patient. The enzymatic activity of truncated mutant P173L LRAT is 6.3fold lower compared to that of truncated wild-type (P173)
S175R
Y118F
site-directed mutagenesis, activity similar to the truncated wild-type enzyme
Y167F
site-directed mutagenesis, activity similar to the truncated wild-type enzyme
Y64F
site-directed mutagenesis, highly increased activity compared to the truncated wild-type enzyme
additional information
S175R
-
naturally occurring missense mutation, causing recessive earlyonset severe retinal dystrophy, the mutant enzyme shows highly reduced activity
S175R
-
site-directed mutagenesis, the mutation in the truncated LRAT results in an inactive enzyme. The S175R mutation has no effect on the membrane binding properties of tLRAT, the global secondary structure of tLRAT remains almost unchanged with the S175R mutation. The loss of enzymatic activity associated with the S175R mutant is related to loss of an essential nucleophile near the active site, or alternatively to steric obstruction of the active site that impedes substrate binding
additional information
-
screening for and analysis of naturally occurring mutants, low prevalence of lecithin retinol acyltransferase mutations in patients with Leber congenital amaurosis and autosomal recessive retinitis pigmentosa, overview
additional information
-
ectopic expression of human lecithin:retinol acyltransferase in murine basal layer of mouse skin and oral cavity epithelia
additional information
-
construction of a truncated enzyme version, tLRAT, that shows enzyme activity, but leads to physiological dysfunction of the protein by causing retinis pigmentosa
additional information
-
construction of a truncated enzyme version, tLRAT, that shows enzyme activity, but leads to physiological dysfunction of the protein by causing retinis pigmentosa
additional information
human and mouse enzyme differ in residue 173. A significant difference is observed between the intrinsic fluorescence emission as well as between the circular dichroism spectra of a truncated mouse LRAT (R173) and truncated human LRAT (P173). Truncated mouse LRAT is less thermostable than truncated human LRAT
additional information
-
human and mouse enzyme differ in residue 173. A significant difference is observed between the intrinsic fluorescence emission as well as between the circular dichroism spectra of a truncated mouse LRAT (R173) and truncated human LRAT (P173). Truncated mouse LRAT is less thermostable than truncated human LRAT
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
10.4
inactivation of recombinant truncated wild-type enzyme, reversible by dialysis against a buffer with pH 8.4
658075
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
enzyme transfected in HEK-293T cells partially purificated by solubilization and centrifugation
-
recombinant His-tagged truncated wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by nickel affinity chromatography in presence of 1% SDS
recombinant truncated enzyme from Escherichia coli in presence of 1% SDS, by nickel affinity chromatography to homogeneity
-
SDS is necessary for tLRAT extraction from cell lysates. tLRAT enzymatic activity drastically diminishes at SDS concentrations below 0.05% and remains unchanged when SDS concentration is increased from 0.05 to 1%. SDS is very important for tLRAT stability. Detergents such as 0.2% Triton X-100, 0.7% CHAPSO,and 1.2 mM n-dodecyl-beta-D-maltoside and sodium are not effective
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
DNA sequence determination and analysis of the full length gene including the 3'- and 5'-ends, genetic organization analysis, at least 2 splicing variants, the second of which lacks a 103 nt polynucleotide in the 5'-UTR of the full length transcript
expression in HEK-293T cells
expression of a truncated enzyme form lacking the transmembrane N- and C-termini in Escherichia coli as His-tagged protein, which is insoluble in absence of detergents
-
expression of His-tagged truncated wild-type enzyme and His-tagged mutant enzymes in Escherichia coli strain BL21(DE3)
LRAT, quantitative real-time RT-PCR expression analysis in melanoma cell lines
-
stable expression of GFP-tagged LRAT in CHO cells and of GFP-tagged LRAT in COS7 cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
-
ARPE-19 cell system is appropriate for studying the visual cycle enzymes
diagnostics
-
enzyme might be a prognostic or therapeutic marker in renal cancer
medicine
medicine
-
LRAT mutations are likely a rare cause of Leber congenital amaurosis among patients from North America
medicine
-
study on the effects of ectopic expression of human lecithin:retinol acyltransferase on murine oral cavity carcinogenesis induced by the carcinogen 4-nitroquinoline 1-oxide. In transgenic mice with targeted human LRAT expression to the basal layer of mouse skin and oral cavity epithelia, the retinyl ester levels in skin are 32% greater than those in wild-type mice, and topical treatment of the back skin with retinol results in greater increases in retinyl esters than in wild-type mouse skin. While 4-nitroquinoline 1-oxide treatment induces multifocal precancerous and cancer lesions in the tongues of both transgene positive and negative mice, higher percentages of transgene positive mice develop more severe tongue lesions of grades 3 and 4 than transgene negative mice after 4-nitroquinoline 1-oxide treatment. Carcinogen treatment also results in greater percentages of transgene positive mouse tongues with hyperplasia, dysplasia, and carcinoma than transgene negative mouse tongues. There are higher cyclooxygenase-2 and lower RARbeta(2) mRNA levels in transgene positive mouse tongues as compared to wild-type mouse tongues after 4-nitroquinoline 1-oxide treatment
medicine
-
expression of RPE65 involved in vitamin A metabolism is downregulated in malignant melanoma compared with benign melanocytic nevi. In contrast, expression of LRAT is not significantly different. High LRAT expression in melanoma metastases is inversely correlated with patient survival, Kaplan-Meier analysis reveals earlier melanoma-related death
medicine
among overweight/obese and lean children (aged 6-12 years), LRAT expression is remarkably lower in the overweight/obese group than in the lean group. Compared with the lean group, the overweight/obese group has elevated vitamin A level. The levels of 25-hydroxyvitamin D and its receptor are lower in overweight/obese subjects than in lean subjects. LRAT is negatively correlated with body mass index and waist circumference and positively correlated with high-density lipoprotein
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
MacDonald, P.N.; Ong, D.E.
A lecithin:retinol acyltransferase activity in human and rat liver
Biochem. Biophys. Res. Commun.
156
157-163
1988
Homo sapiens, Rattus norvegicus
Ruiz, A.; Winston, A.; Lim, Y.H.; Gilbert, B.A.; Rando, R.R.; Bok, D.
Molecular and biochemical characterization of lecithin retinol acyltransferase
J. Biol. Chem.
274
3834-3841
1999
Bos taurus, Homo sapiens (O95237), Homo sapiens
Mondal, M.S.; Ruiz, A.; Bok, D.; Rando, R.R.
Lecithin retinol acyltransferase contains cysteine residues essential for catalysis
Biochemistry
39
5215-5220
2000
Homo sapiens
Ruiz, A.; Bok, D.
Molecular characterization of lecithin-retinol acyltransferase
Methods Enzymol.
316
400-413
2000
Bos taurus, Homo sapiens
Mondal, M.S.; Ruiz, A.; Hu, J.; Bok, D.; Rando, R.R.
Two histidine residues are essential for catalysis by lecithin retinol acyl transferase
FEBS Lett.
489
14-18
2001
Bos taurus, Homo sapiens
Guo, X.; Knudsen, B.S.; Peehl, D.M.; Ruiz, A.; Bok, D.; Rando, R.R.; Rhim, J.S.; Nanus, D.M.; Gudas, L.J.
Retinol metabolism and lecithin:retinol acyltransferase levels are reduced in cultured human prostate cancer cells and tissue specimens
Cancer Res.
62
1654-1661
2002
Homo sapiens
Rando, R.R.
Membrane-bound lecithin-retinol acyltransferase
Biochem. Biophys. Res. Commun.
292
1243-1250
2002
Bos taurus, Homo sapiens, Rattus norvegicus
Jahng, W.J.; Xue, L.; Rando, R.R.
Lecithin retinol acyltransferase is a founder member of a novel family of enzymes
Biochemistry
42
12805-12812
2003
Homo sapiens (O95237)
Bok, D.; Ruiz, A.; Yaron, O.; Jahng, W.J.; Ray, A.; Xue, L.; Rando, R.R.
Purification and characterization of a transmembrane domain-deleted form of lecithin retinol acyltransferase
Biochemistry
42
6090-6098
2003
Homo sapiens
Xue, L.; Rando, R.R.
Roles of cysteine 161 and tyrosine 154 in the lecithin-retinol acyltransferase mechanism
Biochemistry
43
6120-6126
2004
Homo sapiens (O95237)
Zhan, H.C.; Gudas, L.J.; Bok, D.; Rando, R.; Nanus, D.M.; Tickoo, S.K.
Differential expression of the enzyme that esterifies retinol, lecithin:retinol acyltransferase, in subtypes of human renal cancer and normal kidney
Clin. Cancer Res.
9
4897-4905
2003
Homo sapiens
Trevino, S.G.; Schuschereba, S.T.; Bowman, P.D.; Tsin, A.
Lecithin:retinol acyltransferase in ARPE-19
Exp. Eye Res.
80
897-900
2005
Homo sapiens, no activity in Gallus gallus
Zolfaghari, R.; Ross, A.C.
Cloning, gene organization and identification of an alternative splicing process in lecithin:retinol acyltransferase cDNA from human liver
Gene
341
181-188
2004
Homo sapiens (O95237)
Sheren-Manoff, M.; Shin, S.J.; Su, D.; Bok, D.; Rando, R.R.; Gudas, L.J.
Reduced lecithin:retinol acyltransferase expression in human breast cancer
Int. J. Oncol.
29
1193-1199
2006
Homo sapiens
Sweeney, M.O.; McGee, T.L.; Berson, E.L.; Dryja, T.P.
Low prevalence of lecithin retinol acyltransferase mutations in patients with Leber congenital amaurosis and autosomal recessive retinitis pigmentosa
Mol. Vis.
13
588-593
2007
Homo sapiens
Cai, K.; Gudas, L.J.
Retinoic acid receptors and GATA transcription factors activate the transcription of the human lecithin:retinol acyltransferase gene
Int. J. Biochem. Cell Biol.
41
546-553
2009
Homo sapiens
Nagatsuma, K.; Hayashi, Y.; Hano, H.; Sagara, H.; Murakami, K.; Saito, M.; Masaki, T.; Lu, T.; Tanaka, M.; Enzan, H.; Aizawa, Y.; Tajiri, H.; Matsuura, T.
Lecithin: retinol acyltransferase protein is distributed in both hepatic stellate cells and endothelial cells of normal rodent and human liver
Liver Int.
29
47-54
2009
Homo sapiens (O95237), Homo sapiens, Mus musculus
Tang, X.H.; Su, D.; Albert, M.; Scognamiglio, T.; Gudas, L.J.
Overexpression of lecithin:retinol acyltransferase in the epithelial basal layer makes mice more sensitive to oral cavity carcinogenesis induced by a carcinogen
Cancer Biol. Ther.
8
1212-1213
2009
Homo sapiens
Amann, P.M.; Luo, C.; Owen, R.W.; Hofmann, C.; Freudenberger, M.; Schadendorf, D.; Eichmueller, S.B.; Bazhin, A.V.
Vitamin A metabolism in benign and malignant melanocytic skin cells: importance of lecithin/retinol acyltransferase and RPE65
J. Cell. Physiol.
227
718-728
2012
Homo sapiens
Jiang, W.; Napoli, J.L.
Reorganization of cellular retinol-binding protein type 1 and lecithin:retinol acyltransferase during retinyl ester biosynthesis
Biochim. Biophys. Acta
1820
859-869
2012
Homo sapiens
Ruiz, A.; Bok, D.
Focus on molecules: lecithin retinol acyltransferase
Exp. Eye Res.
90
186-187
2010
Homo sapiens, Mus musculus
Bussieres, S.; Cantin, L.; Salesse, C.
Lecithin retinol acyltransferase and its S175R mutant have a similar secondary structure content and maximum insertion pressure but different enzyme activities
Exp. Eye Res.
93
778-781
2011
Homo sapiens
Bussieres, S.; Cantin, L.; Desbat, B.; Salesse, C.
Binding of a truncated form of lecithin:retinol acyltransferase and its N- and C-terminal peptides to lipid monolayers
Langmuir
28
3516-3523
2012
Homo sapiens
Horchani, H.; Bussires, S.; Cantin, L.; Lhor, M.; Lalibert-Gemme, J.S.; Breton, R.; Salesse C.
Enzymatic activity of lecithin:retinol acyltransferase: a thermostable and highly active enzyme with a likely mode of interfacial activation
Biochim. Biophys. Acta
1844
1128-1836
2014
Homo sapiens (O95237)
Hassel, J.C.; Amann, P.M.; Schadendorf, D.; Eichmueller, S.B.; Nagler, M.; Bazhin, A.V.
Lecithin retinol acyltransferase as a potential prognostic marker for malignant melanoma
Exp. Dermatol.
22
757-759
2013
Homo sapiens
Gauthier, M.E.; Roy, S.; Cantin, L.; Salesse, C.
Comparison between the enzymatic activity, structure and substrate binding of mouse and human lecithin retinol acyltransferase
Biochem. Biophys. Res. Commun.
519
832-837
2019
Homo sapiens (O95237), Homo sapiens, Mus musculus (Q9JI60), Mus musculus
Chelstowska, S.; Widjaja-Adhi, M.A.K.; Silvaroli, J.A.; Golczak, M.
Impact of LCA-associated E14L LRAT mutation on protein stability and retinoid homeostasis
Biochemistry
56
4489-4499
2017
Homo sapiens (O95237)
Ajat, M.; Molenaar, M.; Brouwers, J.F.H.M.; Vaandrager, A.B.; Houweling, M.; Helms, J.B.
Hepatic stellate cells retain the capacity to synthesize retinyl esters and to store neutral lipids in small lipid droplets in the absence of LRAT
Biochim. Biophys. Acta
1862
176-187
2017
Homo sapiens (O95237), Mus musculus (Q9JI60)
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