Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
11-cis-retinol + a fatty acid
all-trans-retinyl ester + H2O
-
the reverse isomerization occurs in vivo
-
-
r
2 all-trans-retinyl ester + 2 H2O
11-cis-retinol + 13-cis-retinol + 2 a fatty acid
intrinsic substrate for isoform RPE65c
-
-
?
all-trans-retinol
11-cis-retinol
all-trans-retinyl acetate + H2O
all-trans-retinol + acetate
-
-
-
-
?
all-trans-retinyl ester + H2O
11-cis-retinol + a fatty acid
all-trans-retinyl palmitate + H2O
11-cis-retinol + palmitate
all-trans-retinyl palmitate + H2O
all-trans-retinol + palmitate
an all-trans retinyl ester + H2O
13-cis-retinol + a fatty acid
specific substrate
-
-
?
an all-trans-retinyl ester + H2O
11-cis-retinol + a fatty acid
additional information
?
-
all-trans-retinol
11-cis-retinol
-
-
-
-
?
all-trans-retinol
11-cis-retinol
-
-
-
-
?
all-trans-retinyl ester + H2O
11-cis-retinol + a fatty acid
-
-
-
-
?
all-trans-retinyl ester + H2O
11-cis-retinol + a fatty acid
-
-
-
-
r
all-trans-retinyl ester + H2O
11-cis-retinol + a fatty acid
-
-
RPE65 does not specifically produce 11-cis-retinol only but also 13-cis-retinol
-
?
all-trans-retinyl ester + H2O
11-cis-retinol + a fatty acid
-
the forward reaction is not essential for the reverse isomerization
-
-
r
all-trans-retinyl ester + H2O
11-cis-retinol + a fatty acid
-
direct substrate
-
-
?
all-trans-retinyl ester + H2O
11-cis-retinol + a fatty acid
-
-
-
?
all-trans-retinyl ester + H2O
11-cis-retinol + a fatty acid
-
-
-
-
?
all-trans-retinyl ester + H2O
11-cis-retinol + a fatty acid
-
all-trans-retinyl ester must be incorporated into the phospholipid membrane to serve as a substrate for isomerohydrolase RPE65
-
-
?
all-trans-retinyl ester + H2O
11-cis-retinol + a fatty acid
-
direct substrate
-
-
?
all-trans-retinyl ester + H2O
11-cis-retinol + a fatty acid
-
-
-
-
?
all-trans-retinyl ester + H2O
11-cis-retinol + a fatty acid
-
direct substrate
-
-
?
all-trans-retinyl ester + H2O
11-cis-retinol + a fatty acid
-
-
-
-
?
all-trans-retinyl palmitate + H2O
11-cis-retinol + palmitate
-
-
-
-
?
all-trans-retinyl palmitate + H2O
11-cis-retinol + palmitate
-
-
-
?
all-trans-retinyl palmitate + H2O
11-cis-retinol + palmitate
-
high binding affinity
-
-
?
all-trans-retinyl palmitate + H2O
11-cis-retinol + palmitate
-
-
-
-
?
all-trans-retinyl palmitate + H2O
11-cis-retinol + palmitate
-
high affinity substrate
-
-
?
all-trans-retinyl palmitate + H2O
11-cis-retinol + palmitate
-
-
-
-
?
all-trans-retinyl palmitate + H2O
all-trans-retinol + palmitate
-
-
-
?
all-trans-retinyl palmitate + H2O
all-trans-retinol + palmitate
-
-
-
?
all-trans-retinyl palmitate + H2O
all-trans-retinol + palmitate
-
-
-
?
all-trans-retinyl palmitate + H2O
all-trans-retinol + palmitate
-
11-cis-retinyl palmitate is hydrolyzed with lower activity
-
?
all-trans-retinyl palmitate + H2O
all-trans-retinol + palmitate
-
-
-
?
all-trans-retinyl palmitate + H2O
all-trans-retinol + palmitate
-
-
-
?
an all-trans-retinyl ester + H2O
11-cis-retinol + a fatty acid
-
the enzyme generates predominantly 11-cis-retinol and a minor amount of 13-cis-retinol, from all-trans-retinyl ester
-
-
?
an all-trans-retinyl ester + H2O
11-cis-retinol + a fatty acid
-
the enzyme generates predominantly 11-cis-retinol (72.2%) and a minor amount of 13-cis-retinol (27.8%), from all-trans-retinyl ester
-
-
?
an all-trans-retinyl ester + H2O
11-cis-retinol + a fatty acid
-
the enzyme generates predominantly 11-cis-retinol and a minor amount of 13-cis-retinol, from all-trans-retinyl ester
-
-
?
an all-trans-retinyl ester + H2O
11-cis-retinol + a fatty acid
-
the enzyme generates predominantly 11-cis-retinol (87.3%) and a minor amount of 13-cis-retinol (12.7%), from all-trans-retinyl ester
-
-
?
an all-trans-retinyl ester + H2O
11-cis-retinol + a fatty acid
-
-
-
-
?
an all-trans-retinyl ester + H2O
11-cis-retinol + a fatty acid
-
the enzyme generates predominantly 11-cis-retinol (72.2%) and a minor amount of 13-cis-retinol (27.8%), from all-trans-retinyl ester
-
-
?
an all-trans-retinyl ester + H2O
11-cis-retinol + a fatty acid
-
-
-
?
an all-trans-retinyl ester + H2O
11-cis-retinol + a fatty acid
the enzyme generates 11-cis-retinol and 13-cis-retinol from all-trans-retinyl ester
-
-
?
additional information
?
-
-
all-trans-retinyl palmitate and cholesteryl oleate may be hydrolyzed at the same non-specific catalytic site, it is very likely that 11-cis-retinyl palmitate is hydrolyzed at a discrete catalytic site
-
-
?
additional information
?
-
-
the 11-cis-isomer is hydrolyzed at a much higher rate than the other isomers, 9-cis-retinyl palmitate, 13-cis-retinyl palmitate, and all-trans-retinyl palmitate
-
-
?
additional information
?
-
-
also hydrolyzes 11-cis-retinyl palmitate with higher activity. The hydrolysis of all-trans-retinyl palmitate and 11-cis-retinyl palmitate may occur at distinct catalytic sites
-
-
?
additional information
?
-
-
all-trans-9-des-methylretinol, retinyl acetate, retinyl heptanoate, all-trans-11-fluororetinol and all-trans-19,19,19-trifluororetinol are not isomerized
-
-
?
additional information
?
-
binding of Rpe65 to liposomes containing phosphatidylserine or phosphatidylglycerol, but not the basic or neutral phospholipids, allows the enzyme to extract its insoluble substrate, all-trans-retinyl palmitate, from the lipid bilayer for synthesis of 11-cis-retinol
-
-
?
additional information
?
-
isoform RPE65c does not generate any detectable 11-cis-retinol from all-trans-retinol
-
-
?
additional information
?
-
isoform RPE65c does not generate any detectable 11-cis-retinol from all-trans-retinol
-
-
?
additional information
?
-
-
isoform RPE65c does not generate any detectable 11-cis-retinol from all-trans-retinol
-
-
?
additional information
?
-
-
neither retinyl ester nor 11-cis-retinol is produced after incubation of all-trans-retinol with the purified RPE65 (not an intrinsic substrate for RPE65)
-
-
?
additional information
?
-
-
RPE65 is not inherently 11-cis-specific and can produce both 11- and 13-cis isomers
-
-
?
additional information
?
-
-
Rpe65 presents retinyl esters as substrate to the isomerase for synthesis of visual chromophore
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
1,10-phenanthroline
-
dose-dependent inhibition
10-N-acetamidodecyl chloromethyl ketone
2,2'-bipyridine
-
dose-dependent inhibition
2,2-dimethyl-4-phenyl-2H-imidazole-1-oxide
-
strong inhibition of isomerohydrolase activity (32% at 0.2 mM) in vitro
2-(2-carboxyethyl)-2-methyl-4-phenyl-2H-imidazole-1-oxide
-
moderate inhibitory effect at 0.2 mM
all-trans-retinyl bromoacetate
-
0.05 mM, 76% inhibition
apo-cellular retinol-binding protein type 1
-
CHAPS
-
the addition of 0.5% (w/v) CHAPS to the assay system almost completely abolishes the 11-cis-retinol formation
FATP1c
-
cytosolic C-terminal sequence from the fatty acid transport protein 1 (FATP1or SLC27A1, solute carrier family 27member1), interacts dose-dependently with the native RPE65 and markedly inhibits 11-cis retinol production by acting on the production of all-trans retinyl esters and the isomerase activity of RPE65
-
N-(12-chloro-11-oxododecyl)acetamide
n-benzylidene-tert-butylamine
-
14% inhibition at 0.2 mM
N-tert-butyl-alpha-phenylnitrone
-
strong uncompetitive inhibition (52%) of isomerohydrolase activity in vitro at 0.2 mM
NEM
-
inhibits all-trans retinyl-palmitate hydrolase and 11-cis-retinyl-palmitate hydrolase activity of the liver enzyme, inhibits all-trans-retinyl-palmitate hydrolase activity of the pigment epithelium, 11-cis-retinyl-palmitate hydrolase activity of the pigment epithelium is unaffected
nitrosobenzene
-
strong inhibition of isomerohydrolase activity in vitro at 0.2 mM
Triacsin C
inhibitor of fatty acyl:CoA ligases, potently inhibits RPE65 isomerase activity in cellulo, competitive inhibitor
triolein
-
inhibits all-trans retinyl-palmitate hydrolase and 11-cis-retinyl-palmitate hydrolase activity of the liver enzyme, inhibits all-trans-retinyl-palmitate hydrolase activity of the pigment epithelium, 11-cis-retinyl-palmitate hydrolase activity of the pigment epithelium is unaffected
10-N-acetamidodecyl chloromethyl ketone
-
-
10-N-acetamidodecyl chloromethyl ketone
-
-
apo-cellular retinol-binding protein type 1
-
-
-
apo-cellular retinol-binding protein type 1
-
-
-
apo-cellular retinol-binding protein type 1
-
-
-
bipyridine
in the presence of 1 mM of the metal chelator bipyridine the enzymatic activity of isoform RPE65c is almost completely abolished
bipyridine
the addition of 6 mM FeSO4 into the iron chelator reaction restores partial enzyme activity
N-(12-chloro-11-oxododecyl)acetamide
-
-
N-(12-chloro-11-oxododecyl)acetamide
-
-
N-(12-chloro-11-oxododecyl)acetamide
-
-
additional information
-
the distinctive apparent inhibition constants for NEM-induced inhibition of 11-cis retinyl-palmitate hydrolase and the all-trans-retinyl-palmitate hydrolase activity suggest a fundamental difference in the amino acid composition at the active site of the enzyme(s)
-
additional information
-
13,17,21-trimethyldocosa-12,16,20-trien-11-one and 3,7,11-trimethyldodeca-2,6,10-trienoic acid hexadecylamide are potent mRPE65 antagonists that inhibit 11-cis-retinal regeneration
-
additional information
-
not inhibited by N-tert-butyl-(2-sulfophenyl)nitrone, alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone, NXY059, tert-butylhydroxylamine, and 2-methyl-2-nitrosopropane
-
additional information
neither 8,11-eicosadiynoic acid nor 2-fluoropalmitic acid are selective or potent inhibitors of RPE65
-
additional information
-
in vitro, the dark-adapted form of RGR (retinal pigment epithelium-retinal G protein receptor-opsin) inhibits, but the light-adapted form has no effect on all-trans-REH
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
metabolism
-
the enzyme catalyzes the key reaction in the retinoid visual cycle
additional information
-
key residues determining the isomerization product specificity of the enzyme are Tyr58, Phe103, and Leu133
evolution
-
it is likely that the two novel homologues of RPE65 (13cIMH and RPE65c, EC 3.1.1.90 and EC 3.1.1.64, respectively) are generated through gene duplication after the separation of fish RPE65 from the ancestral RPE65, because they exhibit an extremely high level of sequence identity (97%) and are located in the same chromosome, but on a different chromosome from RPE65
evolution
the enzyme belongs to the RPE65/BCMO Superfamily. The crucial transition from the typical carotenoid double bond cleavage functionality to the isomerohydrolase functionality (RPE65), coupled with the origin of lecithin:retinol acyltransferase, occurred subsequent to divergence of the more primitive chordates (tunicates, etc.) in the last common ancestor of the jawless and jawed vertebrates
malfunction
-
outer segment discs of rod photoreceptors in Rpe65-deficient mice are disorganized, rod function is abolished although cone function remains. Rpe65-deficient mice lack rhodopsin, but not opsin apoprotein
malfunction
-
RPE65 mutations are associated with inherited retinal dystrophies
physiological function
13cIMH may play a key role in the modulation of neuronal functions in the brain
physiological function
isoform RPE65c is the alternative isomerohydrolase in the intra-retinal visual cycle, providing 11-cis retinal to cone photoreceptors in cone-dominant species
physiological function
-
RPE65 from the retinal pigment epithelium is a critical enzyme in the visual cycle for regeneration of 11-cis retinal
physiological function
-
RPE65 functions by binding to and mobilizing the highly hydrophobic all-trans-retinyl esters, allowing them to enter the visual cycle
physiological function
-
RPE65 is essential for the operation of the visual cycle. RPE65 is also on the rate-limiting pathway to fluorophore A2E (lipofuscin) formation
physiological function
-
RPE65 is important for vitamin A metabolism in melanoma cells and in keratinocytes. Activity of RPE65 is important for removal of all-trans retinal which is the substrate for retinoic acid production in skin cells
physiological function
-
RPE65 is involved not only for regeneration of rhodopsin but also plays an important role in regeneration of cone opsins and is critical for the health of cone photoreceptors. Interactions of RPE65 with an intact phospholipid bilayer are critical for its enzymatic activity
physiological function
-
Rpe65 is necessary for production of 11-cis-vitamin A in the retinal visual cycle
physiological function
-
RPE65 is the isomerohydrolase essential for regeneration of 11-cis retinal, the chromophore of visual pigments
physiological function
-
RPE65 is the isomerohydrolase of the visual cycle
physiological function
-
RPE65 operates in a multiprotein complex with retinol dehydrogenase 5 and retinal G protein-coupled receptor in RPE microsomes
physiological function
-
the enzyme is essential for the synthesis by isomerohydrolase of 11-cis-retinal, the chromophore of rod and cone opsins
physiological function
-
the efficient recycling of the chromophore of visual pigments, 11-cis-retinal, through the retinoid visual cycle is an essential process for maintaining normal vision. RPE65 is the isomerohydrolase in retinal pigment epithelium and generates predominantly 11-cis-retinol and a minor amount of 13-cis-retinol, from all-trans-retinyl ester
physiological function
-
the efficient recycling of the chromophore of visual pigments, 11-cis-retinal, through the retinoid visual cycle is an essential process for maintaining normal vision. RPE65 is the isomerohydrolase in retinal pigment epithelium and generates predominantly 11-cis-retinol and a minor amount of 13-cis-retinol, from all-trans-retinyl ester. Enzyme homologue RPE65c expressed in the inner retina may serve as an alternative isomerohydrolase in the inner retinal visual cycle to meet the high demand for recycling of the chromophore in the cone-dominant retina
physiological function
deletion of RPE65 partially suppresses cone dark adaptation. Transgenic mice expressing human RPE65 in the cones reveal no morphological or functional changes between control (RPE65-deficient) and transgenic cones, with only a slight delay in dark adaptation, possibly caused by the buffering of retinoids by RPE65
physiological function
large amounts of esters accumulate in Rpe65-/- mice. Retinyl ester levels in Sv/129 wild type mice that are dark adapted for various intervals are similar to those in mice raised in cyclic light. In C57BL/6 mice, which contain less Rpe65 protein, dark adaptation is accompanied by an increase in ester levels compared to cyclic light controls. Retinyl ester levels are much higher in Rpe65-/- mice compared to wild type and keep increasing with age
physiological function
RPE65 activity is reduced by coexpression of fatty acyl:CoA ligases or fatty acyl-CoA synthase FATP2
physiological function
transgenic mice expressing human RPE65 in the cones reveal no morphological or functional changes between control (RPE65-deficient) and transgenic cones, with only a slight delay in dark adaptation, possibly caused by the buffering of retinoids by RPE65
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
F103L
-
site-directed mutagenesis, the mutation reverses the enzyme isomerization product specificity from formation of 11-cis-retinol to 13-cis-retinol, product of EC 3.1.1.90. Formation of 95.7% 13-cis-retinol and 4.3% 11-cis-retinol
K222M
-
site-directed mutagenesis, the mutation reverses the enzyme isomerization product specificity from formation of 11-cis-retinol to 13-cis-retinol, product of EC 3.1.1.90. Formation of 55.1% 13-cis-retinol and 44.9% 11-cis-retinol
L133S
-
site-directed mutagenesis, the mutation reverses the enzyme isomerization product specificity from formation of 11-cis-retinol to 13-cis-retinol, product of EC 3.1.1.90. Formation of 71-3% 13-cis-retinol and 28.7% 11-cis-retinol
Y58N
-
site-directed mutagenesis, the mutation completely reverses the enzyme isomerization product specificity from formation of 11-cis-retinol to 13-cis-retinol, product of EC 3.1.1.90. Exclusive formation of 13-cis-retinol
A132T
-
50% activity compared to the wild type enzyme
A434V
-
55% activity compared to the wild type enzyme
C106A
-
the mutation does not affect the palmitylation status of the fragment 98-118, the mutant remains associated with the membrane. The mutant has an intact enzymatic activity similar to that of wild type enzyme
C106Y
-
site-directed mutagenesis, the mutant exhibits 16% reduced activity compared to the wild-type enzyme
C106Y/K297G
-
site-directed mutagenesis, the mutant exhibits 26% reduced activity compared to the wild-type enzyme
C112A
-
the mutation abolishes palmitylation in fragment 98-118 and dissociates RPE65 from the membrane. The mutant has no enzymatic activity
C231S
-
55% activity compared to the wild type enzyme
C329S
-
26% activity compared to the wild type enzyme
C329S/C330S
-
less than 2% activity compared to the wild type enzyme
C330Y
-
less than 2% activity compared to the wild type enzyme
E417A
-
less than 2% activity compared to the wild type enzyme
F61L
-
the mutant shows 1.02% activity compared to the wild type enzyme
F61W
-
the mutant shows 1.28% activity compared to the wild type enzyme
F61Y
-
the mutant shows 7.57% activity compared to the wild type enzyme
G40S
-
less than 2% activity compared to the wild type enzyme
G528V
-
less than 2% activity compared to the wild type enzyme
H182A
-
10% activity compared to the wild type enzyme
H182Y
-
10% activity compared to the wild type enzyme
H68A
-
less than 2% activity compared to the wild type enzyme
H68Y
-
less than 2% activity compared to the wild type enzyme
I220M
-
site-directed mutagenesis, the mutant exhibits 38% reduced activity compared to the wild-type enzyme
K294T
-
16% activity compared to the wild type enzyme
K297G
-
site-directed mutagenesis, the mutant exhibits 1.7fold increased activity compared to the wild-type enzyme
K297G/L510M
-
site-directed mutagenesis, the mutant exhibits 45% increased activity compared to the wild-type enzyme
K297G/N302I
-
site-directed mutagenesis, the mutant exhibits 7.7% increased activity compared to the wild-type enzyme
K297G/S533A
-
site-directed mutagenesis, the mutant exhibits 18% increased activity compared to the wild-type enzyme
L510M
-
site-directed mutagenesis, the mutant exhibits 29% reduced activity compared to the wild-type enzyme
N170K
-
site-directed mutagenesis, the mutant exhibits 1.6fold increased activity compared to the wild-type enzyme
N170K/C330T
-
site-directed mutagenesis, the mutant exhibits 15% reduced activity compared to the wild-type enzyme
N170K/I220M
-
site-directed mutagenesis, the mutant exhibits 69% reduced activity compared to the wild-type enzyme
N170K/K297G
-
site-directed mutagenesis, the mutant exhibits 67% increased activity compared to the wild-type enzyme
N170K/Q497P
-
site-directed mutagenesis, the mutant exhibits 16% increased activity compared to the wild-type enzyme
N302I
-
site-directed mutagenesis, the mutant exhibits 25% increased activity compared to the wild-type enzyme
P363T
-
the mutation is identified in patients with Leber's congenital amaurosis, significantly decreases the stability of the enzyme, alters subcellular localization mainly to the plasma membrane and abolishes its isomerohydrolase activity
Q497P
-
site-directed mutagenesis, the mutant exhibits 26% reduced activity compared to the wild-type enzyme
R44Q
-
less than 2% activity compared to the wild type enzyme
R91W
-
the mutation from patients with retinal dystrophies decreases the stability of RPE65 protein and abolishes its isomerohydrolase activity. The mutant shows significantly decreased protein levels but unchanged mRNA levels and has a half-life of less than 2 h when expressed in 293A cells compared with the wild type
S533A
-
site-directed mutagenesis, the mutant exhibits 23% increased activity compared to the wild-type enzyme
T147A
-
the mutant shows 12.63% activity compared to the wild type enzyme
T147C
-
the mutant shows 20.18% activity compared to the wild type enzyme
T147G
-
the mutant shows 30.02% activity compared to the wild type enzyme
T147S
-
the mutant shows 84% activity compared to the wild type enzyme
T39R
-
site-directed mutagenesis, the mutant exhibits 22% increased activity compared to the wild-type enzyme
T39R/N170K
-
site-directed mutagenesis, the mutant exhibits 39% increased activity compared to the wild-type enzyme
T39R/N170K/C330T
-
site-directed mutagenesis, the mutant exhibits 8.4% increased activity compared to the wild-type enzyme
T39R/N170K/C330T/Q497P
-
site-directed mutagenesis, the mutant exhibits 23% reduced activity compared to the wild-type enzyme
T39R/N170K/I220M
-
site-directed mutagenesis, the mutant exhibits 10% increased activity compared to the wild-type enzyme
T39R/N170K/I220M/Q497P
-
site-directed mutagenesis, the mutant exhibits 8.6% increased activity compared to the wild-type enzyme
T39R/N170K/Q497P
-
site-directed mutagenesis, the mutant exhibits 11% increased activity compared to the wild-type enzyme
W331F
-
the mutant shows 8.34% activity compared to the wild type enzyme
W331Y
-
the mutant shows 26.72% activity compared to the wild type enzyme
Y144D
-
the mutation is identified in patients with Leber's congenital amaurosis, significantly decreases the stability of the enzyme, alters subcellular localization mainly to the plasma membrane and abolishes its isomerohydrolase activity
Y275F
-
the mutant shows 14.44% activity compared to the wild type enzyme
Y368F
-
56% activity compared to the wild type enzyme
C330T
-
83% activity compared to the wild type enzyme
C330T
-
site-directed mutagenesis, the mutant exhibits 27% reduced activity compared to the wild-type enzyme
E417D
-
the mutation alters the sub-cellular localization of the protein from membrane to the cytosol. The mutant show 5fold reduced activity compared to the wild type enzyme
E417D
-
the mutation decreases the stability of RPE65 and alters its sub-cellular localization, the mutant retains partial enzymatic activity (the amount of 11-cis retinol generated by E417D is approximately 5fold lower than the amount generated by wild type RPE65)
E417Q
-
less than 2% activity compared to the wild type enzyme
E417Q
-
the mutation decreases the stability of RPE65 and alters its sub-cellular localization, the mutant abolishes isomerohydrolase activity. The mutation causes blindness in Leber congenital amaurosis patients
E417Q
-
the mutation is identified in patients with Leber congenital amaurosis, decreases the stability of RPE65, alters its sub-cellular localization from membrane to the cytosol and abolishes isomerohydrolase activity
H180A
-
less than 2% activity compared to the wild type enzyme
H180A
-
the mutant shows about 20% decreased protein levels and abolished enzymatic activity
H241A
-
less than 2% activity compared to the wild type enzyme
H241A
-
the mutant shows about 80% decreased protein levels and abolished enzymatic activity and significantly decreased protein stabilities in the presence of cycloheximide
H313A
-
less than 2% activity compared to the wild type enzyme
H313A
-
the mutant shows about 10% decreased protein levels and abolished enzymatic activity and significantly decreased protein stabilities in the presence of cycloheximide
H527A
-
less than 2% activity compared to the wild type enzyme
H527A
-
the mutant shows about 20% decreased protein levels and abolished enzymatic activity and significantly decreased protein stabilities in the presence of cycloheximide
Y368H
-
less than 3% activity compared to the wild type enzyme
Y368H
-
the mutation from patients with retinal dystrophies decreases the stability of RPE65 protein and abolishes its isomerohydrolase activity. The mutant shows significantly decreased protein levels but unchanged mRNA levels and has a half-life of less than 6 h when expressed in 293A cells compared with the wild type
additional information
-
mutant enzymes' recombinant expression levels, overview
additional information
-
rgt-/-knock-out mice, rpe65-/-knock-out mice
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Cooper, D.A.; Olson, J.A.
Hydrolysis of cis and trans isomers of retinyl palmitate by retinyl ester hydrolase of pig liver
Arch. Biochem. Biophys.
260
705-711
1988
Sus scrofa
brenda
Blaner, W.S.; Das, S.R.; Gouras, P.; Flood, M.T.
Hydrolysis of 11-cis- and all-trans-retinyl palmitate by homogenates of human retinal epithelial cells
J. Biol. Chem.
262
53-58
1987
Homo sapiens
brenda
Blaner W.S.; Prystowsky, J.H.; Smith, J.E.; Goodman, D.S.
Rat liver retinyl palmitate hydrolase activity. Relationship to cholesteryl oleate and triolein hydrolase activities
Biochim. Biophys. Acta
794
419-427
1984
Bos taurus
brenda
Bustamante, J.J.; Ziari, S.; Ramirez, R.D.; Tsin, A.T.C.
Retinyl ester hydrolase and the visual cycle in the chicken eye
Am. J. Physiol.
269
R1346-R1350
1995
Gallus gallus
brenda
Mata, J.R.; Mata, N.L.; Tsin, A.T.C.
Substrate specificity of retinyl ester hydrolase activity in retinal pigment epithelium
J. Lipid Res.
39
604-612
1998
Bos taurus
brenda
Mata, N.L.; Mata, J.R.; Tsin, A.T.C.
Comparison of retinyl ester hydrolase activities in bovine liver and retinal pigment epithelium
J. Lipid Res.
37
1947-1952
1996
Bos taurus
brenda
Jin, M.; Li, S.; Moghrabi, W.N.; Sun, H.; Travis, G.H.
Rpe65 is the retinoid isomerase in bovine retinal pigment epithelium
Cell
122
449-459
2005
Bos taurus
brenda
Chen, Y.; Moiseyev, G.; Takahashi, Y.; Ma, J.X.
Impacts of two point mutations of RPE65 from Lebers congenital amaurosis on the stability, subcellular localization and isomerohydrolase activity of RPE65
FEBS Lett.
580
4200-4204
2006
Homo sapiens
brenda
Takahashi, Y.; Chen, Y.; Moiseyev, G.; Ma, J.X.
Two point mutations of RPE65 from patients with retinal dystrophies decrease the stability of RPE65 protein and abolish its isomerohydrolase activity
J. Biol. Chem.
281
21820-21826
2006
Homo sapiens
brenda
Radu, R.A.; Hu, J.; Peng, J.; Bok, D.; Mata, N.L.; Travis, G.H.
Retinal pigment epithelium-retinal G protein receptor-opsin mediates light-dependent translocation of all-trans-retinyl esters for synthesis of visual chromophore in retinal pigment epithelial cells
J. Biol. Chem.
283
19730-19738
2008
Mus musculus
brenda
Guignard, T.J.; Jin, M.; Pequignot, M.O.; Li, S.; Chassigneux, Y.; Chekroud, K.; Guillou, L.; Richard, E.; Hamel, C.P.; Brabet, P.
FATP1 inhibits 11-cis retinol formation via interaction with the visual cycle retinoid isomerase RPE65 and LRAT
J. Biol. Chem.
285
18759-18768
2010
Homo sapiens
brenda
Redmond, T.M.; Poliakov, E.; Kuo, S.; Chander, P.; Gentleman, S.
RPE65, visual cycle retinol isomerase, is not inherently 11-cis-specific: support for a carbocation mechanism of retinol isomerization
J. Biol. Chem.
285
1919-1927
2010
Homo sapiens
brenda
Golczak, M.; Kiser, P.D.; Lodowski, D.T.; Maeda, A.; Palczewski, K.
Importance of membrane structural integrity for RPE65 retinoid isomerization activity
J. Biol. Chem.
285
9667-9682
2010
Homo sapiens
brenda
Kiser, P.D.; Golczak, M.; Lodowski, D.T.; Chance, M.R.; Palczewski, K.
Crystal structure of native RPE65, the retinoid isomerase of the visual cycle
Proc. Natl. Acad. Sci. USA
106
17325-17330
2009
Bos taurus (Q28175), Bos taurus
brenda
Kiser, P.D.; Palczewski, K.
Membrane-binding and enzymatic properties of RPE65
Prog. Retin. Eye Res.
29
428-442
2010
Bos taurus
brenda
Nikolaeva, O.; Takahashi, Y.; Moiseyev, G.; Ma, J.X.
Negative charge of the glutamic acid 417 residue is crucial for isomerohydrolase activity of RPE65
Biochem. Biophys. Res. Commun.
391
1757-1761
2010
Homo sapiens
brenda
Nikolaeva, O.; Moiseyev, G.; Rodgers, K.K.; Ma, J.X.
Binding to lipid membrane induces conformational changes in RPE65: implications for its isomerohydrolase activity
Biochem. J.
436
591-597
2011
Gallus gallus
brenda
Gollapalli, D.R.; Maiti, P.; Rando, R.R.
RPE65 operates in the vertebrate visual cycle by stereospecifically binding all-trans-retinyl esters
Biochemistry
42
11824-11830
2003
Bos taurus
brenda
Moiseyev, G.; Crouch, R.K.; Goletz, P.; Oatis, J.; Redmond, T.M.; Ma, J.X.
Retinyl esters are the substrate for isomerohydrolase
Biochemistry
42
2229-2238
2003
Bos taurus, Mus musculus
brenda
Lyubarsky, A.L.; Savchenko, A.B.; Morocco, S.B.; Daniele, L.L.; Redmond, T.M.; Pugh, E.N.
Mole quantity of RPE65 and its productivity in the generation of 11-cis-retinal from retinyl esters in the living mouse eye
Biochemistry
44
9880-9888
2005
Mus musculus
brenda
Maiti, P.; Kong, J.; Kim, S.R.; Sparrow, J.R.; Allikmets, R.; Rando, R.R.
Small molecule RPE65 antagonists limit the visual cycle and prevent lipofuscin formation
Biochemistry
45
852-860
2006
Bos taurus
brenda
Poliakov, E.; Parikh, T.; Ayele, M.; Kuo, S.; Chander, P.; Gentleman, S.; Redmond, T.M.
Aromatic lipophilic spin traps effectively inhibit RPE65 isomerohydrolase activity
Biochemistry
50
6739-6741
2011
Bos taurus
brenda
Nikolaeva, O.; Takahashi, Y.; Moiseyev, G.; Ma, J.X.
Purified RPE65 shows isomerohydrolase activity after reassociation with a phospholipid membrane
FEBS J.
276
3020-3030
2009
Gallus gallus
brenda
Takahashi, Y.; Moiseyev, G.; Chen, Y.; Nikolaeva, O.; Ma, J.X.
An alternative isomerohydrolase in the retinal Mueller cells of a cone-dominant species
FEBS J.
278
2913-2926
2011
Danio rerio (A9C3R8), Danio rerio (Q6PBW5), Danio rerio
brenda
Takahashi, Y.; Moiseyev, G.; Chen, Y.; Farjo, K.; Nikolaeva, O.; Ma, J.X.
An enzymatic mechanism for generating the precursor of endogenous 13-cis retinoic acid in the brain
FEBS J.
278
973-987
2011
Danio rerio (A9C3R9), Danio rerio
brenda
Takahashi, Y.; Moiseyev, G.; Chen, Y.; Ma, J.X.
Identification of conserved histidines and glutamic acid as key residues for isomerohydrolase activity of RPE65, an enzyme of the visual cycle in the retinal pigment epithelium
FEBS Lett.
579
5414-5418
2005
Homo sapiens
brenda
Lopes, V.S.; Gibbs, D.; Libby, R.T.; Aleman, T.S.; Welch, D.L.; Lillo, C.; Jacobson, S.G.; Radu, R.A.; Steel, K.P.; Williams, D.S.
The Usher 1B protein, MYO7A, is required for normal localization and function of the visual retinoid cycle enzyme, RPE65
Hum. Mol. Genet.
20
2560-2570
2011
Mus musculus
brenda
McBee, J.K.; Van Hooser, J.P.; Jang, G.F.; Palczewski, K.
Isomerization of 11-cis-retinoids to all-trans-retinoids in vitro and in vivo
J. Biol. Chem.
276
48483-48493
2001
Bos taurus
brenda
Mata, N.L.; Moghrabi, W.N.; Lee, J.S.; Bui, T.V.; Radu, R.A.; Horwitz, J.; Travis, G.H.
Rpe65 is a retinyl ester binding protein that presents insoluble substrate to the isomerase in retinal pigment epithelial cells
J. Biol. Chem.
279
635-643
2004
Mus musculus
brenda
Moiseyev, G.; Takahashi, Y.; Chen, Y.; Gentleman, S.; Redmond, T.M.; Crouch, R.K.; Ma, J.X.
RPE65 is an iron(II)-dependent isomerohydrolase in the retinoid visual cycle
J. Biol. Chem.
281
2835-2840
2006
Bos taurus
brenda
Moiseyev, G.; Takahashi, Y.; Chen, Y.; Kim, S.; Ma, J.X.
RPE65 from cone-dominant chicken is a more efficient isomerohydrolase compared with that from rod-dominant species
J. Biol. Chem.
283
8110-8117
2008
Bos taurus, Gallus gallus, Homo sapiens
brenda
Takahashi, Y.; Moiseyev, G.; Ablonczy, Z.; Chen, Y.; Crouch, R.K.; Ma, J.X.
Identification of a novel palmitylation site essential for membrane association and isomerohydrolase activity of RPE65
J. Biol. Chem.
284
3211-3218
2009
Bos taurus, Homo sapiens
brenda
Yuan, Q.; Kaylor, J.J.; Miu, A.; Bassilian, S.; Whitelegge, J.P.; Travis, G.H.
Rpe65 isomerase associates with membranes through an electrostatic interaction with acidic phospholipid headgroups
J. Biol. Chem.
285
988-999
2010
Gallus gallus, Bos taurus (Q28175)
brenda
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
brenda
Travis, G.H.; Kaylor, J.; Yuan, Q.
Analysis of the retinoid isomerase activities in the retinal pigment epithelium and retina
Methods Mol. Biol.
652
329-339
2010
Bos taurus, Gallus gallus
brenda
Redmond, T.M.; Yu, S.; Lee, E.; Bok, D.; Hamasaki, D.; Chen, N.; Goletz, P.; Ma, J.X.; Crouch, R.K.; Pfeifer, K.
Rpe65 is necessary for production of 11-cis-vitamin A in the retinal visual cycle
Nat. Genet.
20
344-351
1998
Mus musculus
brenda
Redmond, T.M.; Poliakov, E.; Yu, S.; Tsai, J.Y.; Lu, Z.; Gentleman, S.
Mutation of key residues of RPE65 abolishes its enzymatic role as isomerohydrolase in the visual cycle
Proc. Natl. Acad. Sci. USA
102
13658-13663
2005
Homo sapiens
brenda
Takahashi, Y.; Moiseyev, G.; Nikolaeva, O.; Ma, J.X.
Identification of the key residues determining the product specificity of isomerohydrolase
Biochemistry
51
4217-4225
2012
Danio rerio, Gallus gallus
brenda
Takahashi, Y.; Moiseyev, G.; Ma, J.X.
Identification of key residues determining isomerohydrolase activity of human RPE65
J. Biol. Chem.
289
6743-26751
2014
Homo sapiens
brenda
Poliakov, E.; Gubin, A.N.; Stearn, O.; Li, Y.; Campos, M.M.; Gentleman, S.; Rogozin, I.B.; Redmond, T.M.
Origin and evolution of retinoid isomerization machinery in vertebrate visual cycle: hint from jawless vertebrates
PLoS ONE
7
e49975
2012
no activity in tunicata, no activity in cephalochordata, Petromyzon marinus (L0ATZ0), Petromyzon marinus
brenda
Eroglu, A.; Gentleman, S.; Poliakov, E.; Redmond, T.M.
Inhibition of RPE65 retinol isomerase activity by inhibitors of lipid metabolism
J. Biol. Chem.
291
4966-4973
2016
Homo sapiens (Q16518)
brenda
Sheridan, C.; Boyer, N.P.; Crouch, R.K.; Koutalos, Y.
RPE65 and the accumulation of retinyl esters in mouse retinal pigment epithelium
Photochem. Photobiol.
93
844-848
2017
Mus musculus (Q91ZQ5), Mus musculus
brenda
Kolesnikov, A.; Tang, P.; Kefalov, V.
Examining the role of cone-expressed RPE65 in mouse cone function
Sci. Rep.
8
14201
2018
Homo sapiens (Q16518), Homo sapiens, Mus musculus (Q91ZQ5), Mus musculus
brenda