1.14.16.2: tyrosine 3-monooxygenase
This is an abbreviated version!
For detailed information about tyrosine 3-monooxygenase, go to the full flat file.
Word Map on EC 1.14.16.2
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1.14.16.2
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dopamine
-
dopaminergic
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parkinsonism
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nigra
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striatum
-
catecholamine
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substantia
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nerve
-
ventral
-
fiber
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sympathetic
-
innervation
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adrenal
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noradrenergic
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neurotransmitter
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6-hydroxydopamine
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ganglia
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th-positive
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catecholaminergic
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neuropeptide
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norepinephrine
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nigrostriatal
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midbrain
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monoamine
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neurotrophic
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compacta
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coeruleus
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hypothalamus
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tegmental
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mesencephalic
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1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
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l-dopa
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6-ohda
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neurochemical
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accumbens
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noradrenaline
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rostrally
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dopac
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apomorphine
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perikarya
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intrastriatal
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beta-hydroxylase
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mptp-induced
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varicosity
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ventrolateral
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dopamine-beta-hydroxylase
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preoptic
-
npy
-
phenylethanolamine
-
analysis
-
diagnostics
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homovanillic
-
synthesis
- 1.14.16.2
- dopamine
-
dopaminergic
- parkinsonism
- nigra
- striatum
- catecholamine
-
substantia
- nerve
-
ventral
- fiber
-
sympathetic
-
innervation
- adrenal
-
noradrenergic
-
neurotransmitter
- 6-hydroxydopamine
- ganglia
-
th-positive
-
catecholaminergic
-
neuropeptide
- norepinephrine
-
nigrostriatal
- midbrain
-
monoamine
-
neurotrophic
- compacta
- coeruleus
- hypothalamus
- tegmental
-
mesencephalic
- 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
- l-dopa
-
6-ohda
-
neurochemical
- accumbens
- noradrenaline
-
rostrally
-
dopac
- apomorphine
- perikarya
-
intrastriatal
- beta-hydroxylase
-
mptp-induced
-
varicosity
-
ventrolateral
- dopamine-beta-hydroxylase
-
preoptic
- npy
- phenylethanolamine
- analysis
- diagnostics
-
homovanillic
- synthesis
Reaction
Synonyms
CAT-2, DTH1, DTH2, hTH2, L-tyrosine hydroxylase, monophenol monooxygenase, oxygenase, tyrosine 3-mono-, TH, TH1, TH2, TyrH, tyrosinase, tyrosine 3-hydroxylase, tyrosine 3-monooxygenase, tyrosine hydroxylase, tyrosine hydroxylase type 1, tyrosine-3-mono-oxygenase, tyrosine-3-monooxygenase
ECTree
1.14.16.2 tyrosine 3-monooxygenaseAdvanced search results
results (
results (Engineering
Engineering on EC 1.14.16.2 - tyrosine 3-monooxygenase
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PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
E434A
-
the mutant shows 35.6% of wild type activity. Furthermore, the mutation dramatically reduces its substrate affinity for tetrahydrobiopterin and decreases its activation by Fe2+
A297L
D361N
reductions in Vmax are not significantly different from the wild type enzyme
E332A
-
the mutant has 10fold higher Km for 6-methyltetrahydropterin, but reduction of the enzyme by 6-methyltetrahydropterin is similar to the wild type
E332D
active site residue, 10fold reduction in activity, close to the catalytic iron
E362Q
reductions in Vmax are not significantly different from the wild type enzyme
E362R/E365R
the Vmax is significantly less reduced by dopamine than for the wild type enzyme
E365Q
the Vmax is significantly less reduced by dopamine than for the wild type enzyme
F184W/W372F
-
4fold lower Km for L-tyrosine compared to the wild-type enzyme. Similar Km for 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine compared to wild-type enzyme
K170E/L480A
the mutant is inhibited over the same range of dopamine like the wild type enzyme
K366L
reductions in Vmax are not significantly different from the wild type enzyme
L205P
R306H
-
1.2fold decrease in Km-value for L-tyrosine compared to wild-type enzyme, Ki-value for L-tyrosine is nearly identical to wild-type value, 1.3fold decrease in KM-value for tetrahydrobiopterin compared to wild-type enzyme, 1.2fold increase of turnover-number compared to wild-type enzyme. 8.2°C increase in Tm-value compared to wild-type enzyme
R37E/R38E
S368A
the Vmax is significantly less reduced by dopamine than for the wild type enzyme
S40E
-
the mutant mimics a phosphorylation of S40. The kinetics of reduction and oxidation of the enzyme are similar to the wild type
T245P
-
1.4fold increase in Km-value for L-tyrosine compared to wild-type enzyme, 1.6fold increase in Ki-value for L-tyrosine compared to wild-type enzyme, 1.1fold increase in KM-value for tetrahydrobiopterin compared to wild-type enzyme, 1.6fold increase of turnover-number compared to wild-type enzyme. 3.9°C increase in Tm-value compared to wild-type enzyme
T283M
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1.2fold decrease in Km-value for L-tyrosine compared to wild-type enzyme, 1.2fold decrease in Ki-value for L-tyrosine compared to wild-type enzyme, 1.3fold decrease in KM-value for tetrahydrobiopterin compared to wild-type enzyme, 4.2fold decrease of turnover-number compared to wild-type enzyme
T463M
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1.1fold decrease in Km-value for L-tyrosine compared to wild-type enzyme, Ki-value for L-tyrosine is nearly identical to wild-type value compared to wild-type enzyme, 1.4fold decrease in KM-value for tetrahydrobiopterin compared to wild-type enzyme, 1.2fold increase of turnover-number compared to wild-type enzyme. 7.7°C increase in Tm-value compared to wild-type enzyme
W166F/F184W/W233F/W372F
-
mutant protein contains one tryptophan at residue 184 in the middle of a mobile active-site loop. The mutant was generated to perform steady-state fluorescence anisotropy measurements and shows kinetic properties similar to the wild-type enzyme
W166F/F184W/W372F
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Km for L-tyrosine similar to the wild-type enzyme. 3fold higher Km for 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine compared to wild-type enzyme
W166F/W233F/W372F
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Km for L-tyrosine similar to the wild-type enzyme. 4fold higher Km for 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine compared to wild-type enzyme
W166F/W372F
-
Km for L-tyrosine similar to the wild-type enzyme. 3fold higher Km for 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine compared to wild-type enzyme
W372F
-
10fold lower Km for L-tyrosine compared to the wild-type enzyme. Similar Km for 6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydopteridine compared to wild-type enzyme
A297L
the mutation mediates high affinity dopamine inhibition through Vmax reduction and increasing the Km value for the cofactor
D361N
the mutant shows increased Vmax compared to the wild type enzyme
D425A
the mutant shows strongly reduced activity compared to the wild type enzyme
D425C
the mutant shows strongly reduced activity compared to the wild type enzyme
D425E
the mutant shows strongly reduced activity compared to the wild type enzyme
D425F
the mutant shows strongly reduced activity compared to the wild type enzyme
D425G
the mutant shows strongly reduced activity compared to the wild type enzyme
D425H
the mutant shows strongly reduced activity compared to the wild type enzyme
D425I
the mutant shows strongly reduced activity compared to the wild type enzyme
D425K
the mutant shows strongly reduced activity compared to the wild type enzyme
D425L
the mutant shows strongly reduced activity compared to the wild type enzyme
D425M
the mutant shows strongly reduced activity compared to the wild type enzyme
D425N
the mutant shows strongly reduced activity compared to the wild type enzyme
D425Q
the mutant shows strongly reduced activity compared to the wild type enzyme
D425R
the mutant shows strongly reduced activity compared to the wild type enzyme
D425S
the mutant shows strongly reduced activity compared to the wild type enzyme
D425T
the mutant shows strongly reduced activity compared to the wild type enzyme
D425V
D425Y
the mutant shows strongly reduced activity compared to the wild type enzyme
E332A
-
the E332A mutant hydroxylates less than 1% L-tyrosine compared to wild type and does not produce 4a-hydroxytetrahydrobiopterin
E362Q
the mutant shows reduced Vmax compared to the wild type enzyme
E362R/E365R
the mutation mediates high affinity dopamine inhibition through Vmax reduction and increasing the Km value for the cofactor
E365Q
the mutant shows reduced Vmax compared to the wild type enzyme
E376H
-
iron content is not significantly altered. Pterin oxidation at 1.2% of the wild-type activity. Tyrosine hydroxylation is less than 0.4% of the wild-type value
E376Q
-
iron content is not significantly altered. Pterin oxidation at 0.4% of the wild-type activity. Tyrosine hydroxylation is 0.39% of the wild-type value
H323Y
enhanced Km for tyrosine, 4.5fold enhanced phenylalanine hydroxylation activity, active site mutant
H331E/E376H
-
mutant enzyme contains significantly less iron than the wild-type enzyme. Pterin oxidation at 0.21% of the wild-type activity. Tyrosine hydroxylation is less than 0.4% of the wild-type value
H331Q
-
mutant enzyme is not successfully expressed. Pterin oxidation at 2.4% of the wild-type activity. Tyrosine hydroxylation is less than 0.002% of the wild-type value
H336E
-
significant decrease in iron content. Pterin oxidation at 6.3% of the wild-type activity. Tyrosine hydroxylation is 0.78% of the wild-type value
H336Q
-
iron-free mutant enzyme. Pterin oxidation at 11.9% of the wild-type activity. Tyrosine hydroxylation is 3.7% of the wild-type value
K366L
the mutant shows reduced Vmax compared to the wild type enzyme
Q310H
4fold reduced tyrosine hydroxylation/dopa formation activity, slightly enhanced phenylalanine hydroxylation activity, active site mutant
Q424A
the mutant shows reduced activity compared to the wild type enzyme
Q426A
the mutant strongly reduced activity compared to the wild type enzyme
R37E/R38E
the Km value for tetrahydrobiopterin measured for the mutant is approximately half that of the wild type enzyme
S19E
S19E/S40E
S31E
S368A
the mutation mediates high affinity dopamine inhibition through Vmax reduction and increasing the Km value for the cofactor
S395A
-
the S395A mutant produces 4a-hydroxytetrahydrobiopterin at the same rate as wild type, but does so in predominantly uncoupled reaction (2% of wild type enzyme L-tyrosine hydroxylation)
S40E
S8E
T427A
the mutant shows reduced activity compared to the wild type enzyme
W166F/W233F/W372F/F14W
-
introduced tryptophan residue in regulatory domain
W166F/W233F/W372F/F34W
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introduced tryptophan residue in regulatory domain
W166F/W233F/W372F/F74W
-
introduced tryptophan residue in regulatory domain
Y371F
increased Km for tyrosine and pterin cosubstrates, highly decreased Km for phenylalanine
Y423A
the mutant shows reduced activity compared to the wild type enzyme
additional information
A297L
the Vmax is significantly less reduced by dopamine than for the wild type enzyme
L205P
-
the mutant is associated with recessively inherited L-DOPA-responsive infantile parkinsonism, the mutation reduces the activity and stability of the protein in cells and in vitro expression systems, being considered a misfolding mutation
R37E/R38E
-
the point mutation increases the binding capacity of 5,6,7,8,-tetrahydrobiopterin to tyrosine hydroxylase molecule to increase the activity and possibly to increase the stability
R37E/R38E
the KM for tetrahydrobiopterin measured for the mutant is approximately half that of the wild type enzyme and the Vmax is significantly less reduced by dopamine than for the wild type enzyme
D425V
335fold reduced tyrosine hydroxylation/dopa formation activity, 120fold reduced reaction velocity with tyrosine, 3fold enhanced phenylalanine hydroxylation activity, active site mutant
D425V
the mutant shows strongly reduced activity compared to the wild type enzyme
S19E
-
similar steady-state parameters and similar binding affinity for catecholamines to wild-type enzyme. Inactivated 1.8fold slower than the wild-type enzyme at 42°C in presence of 2% glycerol
S19E/S40E
-
investigation of regulation by phosphorylation, slight decrease in KM value for tetrahydrobiopterin, slight increase in Vmax value
S31E
-
similar steady-state parameters and similar binding affinity for catecholamines to wild-type enzyme. Inactivated 1.8fold slower than the wild-type enzyme at 42°C in presence of 2% glycerol
S40E
-
inactivated 1.6fold faster than the wild-type enzyme at 42°C in presence of 2% glycerol
S8E
-
similar steady-state parameters and similar binding affinity for catecholamines to wild-type enzyme. More stable than wild-type enzyme at 42°C in presence of 2% glycerol
additional information
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truncated hTH1 isoform lacking the 150 N-terminal amino acids
additional information
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construction of a truncation enzyme mutant lacking exons 2, 8, and 9 and showing reduced enzyme activity
additional information
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detection of single nucleotide polymorphisms in the local genomic region, systematic polymorphism discovery at the TH locus and analysis for contributions to sympathetic function and blood pressure, i.e. 4 common TH promoter polymorphisms C-824T, G-801C, A-581G, and G-494A, overview
additional information
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deletion of the N-terminus of tyrosine hydroxylase removes the high affinity dopamine binding site, but does not affect dopamine binding to the low affinity site
additional information
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the deletion mutation of N-terminal 38-amino acids increases the binding capacity of 5,6,7,8,-tetrahydrobiopterin to tyrosine hydroxylase molecule to increase the activity and possibly to increase the stability
additional information
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construction of neurokinin 3 receptor knockout mice, the mutant mice do not show altered tyrosine hydroxylase levels in the caudate putamen or nucleus accumbens, but show decreased enzyme levels in the olfactory tuberculum, phenotype, overview
additional information
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increased TH-Ser40 phosphorylation in primary mesencephalic dopaminergic neurons from PKCdelta knock-out mice, overview
additional information
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reduction of high-level tyrosine hydroxylase dopaminergic alpha-Syn-deficient cells by infection with wild-type alpha-Syn human lentivirus, overview
additional information
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silencing alpha-synuclein gene expression by short hairpin RNA expression does not affect tyrosine hydroxylase expression but enhance tyrosine hydroxylase activity in MN9D cells by increasing TH Ser40 phosphorylation, overview
additional information
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the pogo/pogo mouse phenotype of ataxic mice shows upregulation of tyrosine hydroxylase expression induced by enzyme phosphorylation via cyclin-dependent kinase 5, reduced Cdk5 activity in both p35-/- and p39-/- cerebellum do not correspond to defects in tyrosine hydroxylase expression, overview
additional information
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silencing alpha-synuclein gene expression by short hairpin RNA expression does not affect tyrosine hydroxylase expression but enhance tyrosine hydroxylase activity in MN9D cells by increasing TH Ser40 phosphorylation, overview
-
additional information
active site mutants of phenylalanine hydroxylase lead to highly increased tyrosine hydroxylation activity of the enzyme mutants
additional information
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investigation of the role of several amino acid residues in binding of substrate and ligands by site-specific mutagenesis
