Information on EC 1.14.18.1 - tyrosinase and Organism(s) Mus musculus and UniProt Accession P11344

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Mus musculus
UNIPROT: P11344
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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota


The taxonomic range for the selected organisms is: Mus musculus

EC NUMBER
COMMENTARY hide
1.14.18.1
-
RECOMMENDED NAME
GeneOntology No.
tyrosinase
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
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reduction
-
-
-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Betalain biosynthesis
-
-
Biosynthesis of secondary metabolites
-
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Isoquinoline alkaloid biosynthesis
-
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L-dopachrome biosynthesis
-
-
Metabolic pathways
-
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Tyrosine metabolism
-
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SYSTEMATIC NAME
IUBMB Comments
L-tyrosine,L-dopa:oxygen oxidoreductase
A type III copper protein found in a broad variety of bacteria, fungi, plants, insects, crustaceans, and mammals, which is involved in the synthesis of betalains and melanin. The enzyme, which is activated upon binding molecular oxygen, can catalyse both a monophenolase reaction cycle (reaction 1) or a diphenolase reaction cycle (reaction 2). During the monophenolase cycle, one of the bound oxygen atoms is transferred to a monophenol (such as L-tyrosine), generating an o-diphenol intermediate, which is subsequently oxidized to an o-quinone and released, along with a water molecule. The enzyme remains in an inactive deoxy state, and is restored to the active oxy state by the binding of a new oxygen molecule. During the diphenolase cycle the enzyme binds an external diphenol molecule (such as L-dopa) and oxidizes it to an o-quinone that is released along with a water molecule, leaving the enzyme in the intermediate met state. The enzyme then binds a second diphenol molecule and repeats the process, ending in a deoxy state [7]. The second reaction is identical to that catalysed by the related enzyme catechol oxidase (EC 1.10.3.1). However, the latter can not catalyse the hydroxylation or monooxygenation of monophenols.
CAS REGISTRY NUMBER
COMMENTARY hide
9002-10-2
not distinguished from EC 1.10.3.1
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
-
tyrosinases are essential enzymes in melanin biosynthesis and therefore responsible for pigmentation of skin and hair
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
L-tyrosine + O2 + AH2
L-dopa + H2O + A
show the reaction diagram
radioactive substrate L-[3,5-3H]-tyrosine, specific activity 50 Ci/mmol
-
-
?
2,4,5-trihydroxyphenethylamine + O2
?
show the reaction diagram
-
-
-
-
?
3,4,6-trihydroxyphenylalanine + O2
?
show the reaction diagram
-
-
-
-
?
3,4-dihydroxyphenethylamine + O2
?
show the reaction diagram
-
-
-
-
?
3,4-dihydroxyphenylalanine methyl ester + O2
?
show the reaction diagram
-
-
-
-
?
3,4-dihydroxyphenylserine + O2
?
show the reaction diagram
-
-
-
-
?
3-(3,4-dihydroxyphenyl)-2-methylalanine + O2
?
show the reaction diagram
-
-
-
-
?
4-methylcatechol + O2
4-methyl-o-benzoquinone + H2O
show the reaction diagram
dopa + 1/2 O2
dopaquinone + H2O
show the reaction diagram
L-3,4-dihydroxyphenylalanine + 1/2 O2
L-dopaquinone + H2O
show the reaction diagram
L-dopa + 1/2 O2
dopachrome + H2O
show the reaction diagram
-
-
-
-
?
L-dopa + 1/2 O2
L-dopaquinone + H2O
show the reaction diagram
-
-
-
-
?
L-tyrosine + L-dopa + O2
L-dopa + dopaquinone + H2O
show the reaction diagram
-
-
-
-
?
L-tyrosine + O2
L-DOPA + H2O
show the reaction diagram
-
-
-
-
?
L-tyrosine + O2 + AH2
L-3,4-dihydroxyphenylalanine + H2O + A
show the reaction diagram
N-acetyl-3,4-dihydroxyphenethylamine + O2
?
show the reaction diagram
-
-
-
-
?
N-methyl-3,4-dihydroxyphenethylamine + O2
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
catalyzing the rate-limiting step for melanin biosynthesis
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
L-3,4-dihydroxyphenylalanine + 1/2 O2
L-dopaquinone + H2O
show the reaction diagram
-
-
-
-
-
L-tyrosine + O2 + AH2
L-3,4-dihydroxyphenylalanine + H2O + A
show the reaction diagram
additional information
?
-
-
catalyzing the rate-limiting step for melanin biosynthesis
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
copper
the active site of the tyrosinase model shows the same structural conformation as in sTyr and ibCO, where two copper ions are coordinated by three histidines each, forming a binuclear type 3 copper site similar to that of the template structure
copper
-
copper transporter ATP7A localizes to melanosomes in wildtype melanocytes. Copper restores in vitro tyrosinase activity in melanosomes of BLOC-1-deficient melanocytes, immunofluorescence microscopy
Cu2+
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tyrosinases is a copper-containing enzyme belonging to the type 3 copper protein family
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2E)-3-(3,4-dihydroxyphenyl)-N-[2-(1H-indol-3-yl)ethyl]prop-2-enamide
-
14% inhibition at 0.1 mM; 2% inhibition at 0.1 mM
(2E)-3-(3,4-dihydroxyphenyl)-N-[2-(4-hydroxyphenyl)ethyl]prop-2-enamide
-
15% inhibition at 0.1 mM; 30% inhibition at 0.1 mM
(2E)-3-(3,4-dihydroxyphenyl)-N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]prop-2-enamide
-
55% inhibition at 0.1 mM; 73% inhibition at 0.1 mM
(2E)-3-(3,4-dihydroxyphenyl)-N-[2-(5-methoxy-1H-indol-3-yl)ethyl]prop-2-enamide
-
1% inhibition at 0.1 mM; 4% inhibition at 0.1 mM
(2E)-3-(4-hydroxy-3-methoxyphenyl)-N-[2-(1H-indol-3-yl)ethyl]prop-2-enamide
-
13% inhibition at 0.1 mM; 4% inhibition at 0.1 mM
(2E)-N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]-3-(4-hydroxy-3-methoxyphenyl)prop-2-enamide
-
29% inhibition at 0.1 mM; 48% inhibition at 0.1 mM
1-(2,4-dihydroxyphenyl)-3-(2,4-dimethoxy-3-methylphenyl)propane
-
tyrosinase inhibitor with strong depigmenting effects, found in the medicinal plant Dianella ensifolia. 22times more potent than kojic acid
1-Phenyl-2-thiourea
-
-
1H-indol-5-ol
-
54% inhibition at 0.1 mM; 62% inhibition at 0.1 mM
2,4-dihydroxy-N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]benzamide
-
39% inhibition at 0.1 mM; 50% inhibition at 0.1 mM
2-butyl-5-hydroxyphenyl 3-(3,4-dihydroxyphenyl)propanoate
-
KI-063
3,4-dihydroxy-N-[2-(1H-indol-3-yl)ethyl]benzamide
-
2% inhibition at 0.1 mM; 7% inhibition at 0.1 mM
3,4-dihydroxy-N-[2-(4-hydroxyphenyl)ethyl]benzamide
-
6% inhibition at 0.1 mM; 9% inhibition at 0.1 mM
3,4-dihydroxy-N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]benzamide
-
43% inhibition at 0.1 mM; 48% inhibition at 0.1 mM
3-(2-aminoethyl)-1H-indol-5-ol
-
15% inhibition at 0.1 mM; 22% inhibition at 0.1 mM
4-hydroxy-N-[2-(1H-indol-3-yl)ethyl]benzamide
-
0% inhibition at 0.1 mM
4-hydroxy-N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]-3-methoxybenzamide
-
16% inhibition at 0.1 mM; 32% inhibition at 0.1 mM
4-hydroxy-N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]benzamide
-
31% inhibition at 0.1 mM; 9% inhibition at 0.1 mM
gallic acid
-
significantly inhibited tyrosinase. Isolated from Radix polygoni multiflori, a herb used effectively to prevent graying and to treat skin depigmentation diseases in traditional Chinese medicine
kojic acid
N-caffeoylserotonin
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73% inhibition at 0.1 mM
N-protocatechuoylserotonin
-
48% inhibition at 0.1 mM
N-[2-(1H-indol-3-yl)ethyl]benzamide
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0% inhibition at 0.1 mM; 1% inhibition at 0.1 mM
N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]acetamide
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18% inhibition at 0.1 mM; 23% inhibition at 0.1 mM
N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]benzamide
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22% inhibition at 0.1 mM; 23% inhibition at 0.1 mM
p-hydroxybenzyl alcohol
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p-hydroxybenzyl alcohol, inhibitory effect on tyrosinase activity and melanogenesis. p-hydroxybenzyl alcohol exhibits an inhibitory effect on melanogenesis in mouse melanocytes at noncytotoxic concentrations. The results indicate that no significant difference is observed in tyrosinase gene expression between the p-hydroxybenzyl alcohol-treated and non-treated cells. Thus, it is concluded that no repression of tyrosinase gene is induced by p-hydroxybenzyl alcohol
paeonol
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effects of paeonol on cell growth of B16F10 melanoma cells are shown. The effect of a high dose of paeonol (200 microM) is better than that of 2 microM hydroquinone (HQ), which acts as a positive agent. Paeonol down-regulates tyrosinase expression at mRNA and protein level. And paeonol inhibits MITF mRNA expression in B16F10 melanoma cells und the phosphorylation of CREB
terrein
-
examines the effects of a combination of 2-butyl-5-hydroxyphenyl 3-(3,4-dihydroxyphenyl)propanoate with terrein, an agent that down-regulates microphthalmia-associated transcription factor. Cells co-treated with 2-butyl-5-hydroxyphenyl 3-(3,4-dihydroxyphenyl)propanoate and terrein show much less pigmentation than cells treated with 2-butyl-5-hydroxyphenyl 3-(3,4-dihydroxyphenyl)propanoate or terrein alone
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside
8-MOP
-
shows significant activation effects on B16 cell tyrosinase
Aloe-emodin
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isolated from Radix polygoni multiflori, a herb used effectively to prevent graying and to treat skin depigmentation diseases in traditional Chinese medicine. Shows slightly melanogenesis stimulation activities
Anionic detergents
-
activation
-
chrysophanol
emodin
gallic acid
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-
L-Dopa
Organic solvents
-
activation
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physcion
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.102
2,4,5-trihydroxyphenethylamine
-
-
0.094
3,4,5-trihydroxyphenethylamine
-
-
0.305
3,4,6-trihydroxyphenylalanine
-
-
0.047
3,4-Dihydroxyphenethylamine
-
-
0.046
3,4-dihydroxyphenylalanine methyl ester
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-
0.02
3,4-dihydroxyphenylethanol
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-
0.23
3,4-dihydroxyphenylglycol
-
-
0.145
3,4-dihydroxyphenylserine
-
-
0.194
3-(3,4-Dihydroxyphenyl)-2-methylalanine
-
-
0.026
D-Dopa
-
-
0.022
DL-dopa
-
-
0.016 - 1.9
L-Dopa
0.12 - 0.23
L-tyrosine
0.014
N-acetyl-3,4-dihydroxyphenethylamine
-
-
0.024
N-methyl-3,4-dihydroxyphenethylamine
-
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0117 - 0.0217
tyrosine
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.028
(2E)-3-(3,4-dihydroxyphenyl)-N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]prop-2-enamide
Mus musculus
-
-
0.216
(2E)-N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]-3-(4-hydroxy-3-methoxyphenyl)prop-2-enamide
Mus musculus
-
-
0.012
1-(2,4-dihydroxyphenyl)-3-(2,4-dimethoxy-3-methylphenyl)propane
Mus musculus
-
-
0.068
1H-indol-5-ol
Mus musculus
-
-
0.042
2,4-dihydroxy-N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]benzamide
Mus musculus
-
-
0.073
3,4-dihydroxy-N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]benzamide
Mus musculus
-
-
0.55
3-(2-aminoethyl)-1H-indol-5-ol
Mus musculus
-
-
0.211
4-hydroxy-N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]-3-methoxybenzamide
Mus musculus
-
-
0.233
4-hydroxy-N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]benzamide
Mus musculus
-
-
0.061 - 0.273
kojic acid
0.028
N-caffeoylserotonin
Mus musculus
-
in 50 mM phosphate buffer (pH 6.8), at 37°C
0.073
N-protocatechuoylserotonin
Mus musculus
-
in 50 mM phosphate buffer (pH 6.8), at 37°C
0.311
N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]acetamide
Mus musculus
-
-
0.333
N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]benzamide
Mus musculus
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.032
-
-
2.5
-
dopa oxidation
6889
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.8
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
mouse melanoma cell
Manually annotated by BRENDA team
-
B16F10 melanoma cell
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
; to catalyse melanin synthesis, tyrosinase is subsequently reloaded with copper within specialized organelles called melanosomes, immunofluorescence microscopy
Manually annotated by BRENDA team
additional information
-
tryrosinase is present but inactive in BLOC-1-deficient melanocytes
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
58000
corresponds to the fully deglycosylated protein backbone. Western blot analysis
66000
-
x * 66000, isoenzyme 1, immunoblot
68000
-
x * 68000, isoenzyme 2, immunoblot
70000
-
x * 70000, isoenzyme 4, immunoblot
80000
-
x * 80000, isoenzyme 4, immunoblot
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
-
x * 66000, isoenzyme 1, immunoblot; x * 68000, isoenzyme 2, immunoblot; x * 70000, isoenzyme 4, immunoblot; x * 80000, isoenzyme 4, immunoblot
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
additional information
-
isoenzymes with molecular weights of 58000 Da and 68000 Da are highly resistant to proteinase K digestion
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
highly resistant to SDS and proteinase K
-
maximal stability in Tween 20, 0.25 mg/ml melanosomal lipids stabilize
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ammonium sulfate, S-300 chromatography, preparative PAGE
-
high-mobility tyrosinase form, ammonium sulfate, hydroxyapatite, gel filtration, low-mobility tyrosinase form, DEAE-Sephadex, partial purification
-
preparative PAGE
-
proteinase K digest, DEAE-52 cellulose, 4 isozymes
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
the wild-type Tyr and mutant constructs are transiently expressed in human embryonic kidney (HEK) 293T cells for functional analysis
high molecular weight isoenzyme
-
in vitro transcription translation of 2 different cDNA clones encoding tyrosinase 1 and 2
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
M374G
potential to delete the enzymatic activity of Tyr. Major effect on the active site: the packing density of this normally rigid environment is significantly lowered when the original amino acid is mutated to the smaller glycine because the missing side chain of G374 can neither anchor the loop nor orient the side chain of H367
M374G/S375G
Tyr-GG double mutant, potential to delete the enzymatic activity of Tyr. The M374G/S375G mutation, designated Tyr-GG, replaces two residues present in mTyr by the equivalent residues in mTyrp1 and could potentially modify the enzymatic properties of the protein, when compared with wild-type Tyr. Analysis of the behaviour of the individual mutants M374G and S374G indicates that loss of enzymatic activity in Tyr-GG is mostly because of the M374G mutation
S375G
potential to delete the enzymatic activity of Tyr
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
pharmacology
-
results of low cytotoxicity, high inhibition of melanin synthesis and lack of effect on gene expression suggest that p-hydroxybenzyl alcohol can be a potential agent for skin lightening to be used in cosmetic products