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Information on EC 1.14.16.4 - tryptophan 5-monooxygenase and Organism(s) Mus musculus and UniProt Accession P17532

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IUBMB Comments
The active centre contains mononuclear iron(II). The enzyme is activated by phosphorylation, catalysed by a Ca2+-activated protein kinase. The 4a-hydroxytetrahydrobiopterin formed can dehydrate to 6,7-dihydrobiopterin, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydrobiopterin can be enzymically reduced back to tetrahydrobiopterin, by EC 1.5.1.34 (6,7-dihydropteridine reductase), or slowly rearranges into the more stable compound 7,8-dihydrobiopterin.
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Mus musculus
UNIPROT: P17532
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Word Map
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The taxonomic range for the selected organisms is: Mus musculus
Synonyms
tryptophan hydroxylase, tryptophan hydroxylase 2, tryptophan hydroxylase 1, tph-1, tryptophan hydroxylase-2, tph-2, tryptophan hydroxylase-1, tryptophan-5-hydroxylase, htph2, tryptophan 5-hydroxylase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
indoleacetic acid-5-hydroxylase
-
-
-
-
L-tryptophan hydroxylase
-
-
-
-
oxygenase, tryptophan 5-mono-
-
-
-
-
peripheral tryptophan hydroxylase
244
-
TPH-1
244
-
tryptophan 5-hydroxylase
-
-
-
-
tryptophan 5-monooxygenase
244
-
tryptophan hydroxylase
tryptophan hydroxylase 1
244
-
tryptophan hydroxylase 2
244
-
tryptophan hydroxylase isoform2
244
-
tryptophan hydroxylase type I
244
-
tryptophan hydroxylase-1
244
-
tryptophan hydroxylase-2
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
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reduction
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
L-tryptophan,tetrahydrobiopterin:oxygen oxidoreductase (5-hydroxylating)
The active centre contains mononuclear iron(II). The enzyme is activated by phosphorylation, catalysed by a Ca2+-activated protein kinase. The 4a-hydroxytetrahydrobiopterin formed can dehydrate to 6,7-dihydrobiopterin, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydrobiopterin can be enzymically reduced back to tetrahydrobiopterin, by EC 1.5.1.34 (6,7-dihydropteridine reductase), or slowly rearranges into the more stable compound 7,8-dihydrobiopterin.
CAS REGISTRY NUMBER
COMMENTARY hide
9037-21-2
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
L-phenylalanine + tetrahydropteridine + O2
tyrosine + dihydropteridine + H2O
show the reaction diagram
L-tryptophan + (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + 6-methyl-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 6-methyl-4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
L-tyrosine + tetrahydropteridine + O2
?
show the reaction diagram
-
1% of activity with L-tryptophan
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
P17532, Q8CGV2
TPH catalyzes the first step and rate-limiting reaction in the biosynthesis of 5-hydroxytryptamine, i.e. serotonin, and plays a role in brain and serotonergic neuron development, also TPH1 is involved in behavioural disorders, overview
-
-
?
L-tryptophan + (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
tetrahydrobiopterin
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-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,10-phenanthroline
-
-
2,2'-dipyridyl
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-
3,4-dihydroxyphenylalanine
-
-
3,4-Dihydroxyphenylethylamine
-
-
3-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)phenylalanine
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3-amino-3-[4-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)phenyl]propanoic acid
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3-[1-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)piperidin-4-yl]alanine
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3-[3-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)-1H-pyrazol-1-yl]alanine
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3-[5-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)pyridin-2-yl]alanine
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4-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)-2-fluorophenylalanine
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4-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)-a-methylphenylalanine
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4-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)-L-phenylalanine
4-(5-[[(1-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)methyl]amino]pyrazin-2-yl)-L-phenylalanine
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4-(5-[[(1-hydroxynaphthalen-2-yl)methyl]amino]pyrazin-2-yl)-L-phenylalanine
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4-(5-[[(2'-methylbiphenyl-2-yl)methyl]amino]pyrazin-2-yl)-L-phenylalanine
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4-(5-[[(9-ethyl-9H-carbazol-3-yl)methyl]amino]pyrazin-2-yl)-L-phenylalanine
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4-(5-[[3-(cyclopentyloxy)-4-methoxybenzyl]amino]pyrazin-2-yl)-L-phenylalanine
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4-chloro-L-phenylalanine
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irreversible inhibitor
4-Chlorophenylalanine
4-ethynylphenylalanine
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4-Fluorotryptophan
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4-[4-amino-6-(1-naphthalen-2-ylethoxy)-1,3,5-triazin-2-yl]-L-phenylalanine
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4-[4-amino-6-(2,2,2-trifluoro-1-naphthalen-2-ylethoxy)-1,3,5-triazin-2-yl]-L-phenylalanine
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4-[4-amino-6-(2,2,2-trifluoro-1-[2-[3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl]ethoxy)-1,3,5-triazin-2-yl]-L-phenylalanine
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4-[4-amino-6-[2,2,2-trifluoro-1-(2-furan-2-ylphenyl)ethoxy]-1,3,5-triazin-2-yl]-L-phenylalanine
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4-[4-amino-6-[2,2,2-trifluoro-1-(3'-methylbiphenyl-2-yl)ethoxy]-1,3,5-triazin-2-yl]-L-phenylalanine
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4-[4-amino-6-[2,2,2-trifluoro-1-(5-furan-2-ylthiophen-2-yl)ethoxy]-1,3,5-triazin-2-yl]-L-phenylalanine
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4-[5-[(3,4-dimethoxybenzyl)amino]pyrazin-2-yl]-L-phenylalanine
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4-[5-[(4-cyanobenzyl)amino]pyrazin-2-yl]-L-phenylalanine
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4-[5-[(biphenyl-4-ylmethyl)amino]pyrazin-2-yl]-L-phenylalanine
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4-[5-[(cyclohexylmethyl)amino]pyrazin-2-yl]-L-phenylalanine
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4-[5-[(furan-3-ylmethyl)amino]pyrazin-2-yl]-L-phenylalanine
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4-[5-[(pyridin-3-ylmethyl)amino]pyrazin-2-yl]-L-phenylalanine
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4-[5-[(quinolin-3-ylmethyl)amino]pyrazin-2-yl]-L-phenylalanine
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5-Fluorotryptophan
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5-hydroxytryptophan
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6-Fluorotryptophan
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8-hydroxyquinoline
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D-Dopa
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noncompetitive vs. L-tryptophan and (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
dopamine
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noncompetitive vs. L-tryptophan and (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
L-4-chlorophenylalanine
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L-Dopa
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noncompetitive vs. L-tryptophan and (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
L-p-Chlorophenylalanine
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L-phenylalanine
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competitive vs. tryptophan
L-tryptophan
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competitive to L-phenylalanine
L-tyrosine
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noncompetitive vs. L-tryptophan and (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
LP-533401
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LP-615819
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serotonin
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1 mM, 7.5% inhibition, 10 mM, 70% inhibition
additional information
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-mercaptoethanol
2-mercaptoethylamine
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30 mM, 93.8% activity compared to activation with dithiothreitol
2-mercaptopropionate
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30 mM, 11.7% activity compared to activation with dithiothreitol
3-Mercaptopropionate
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30 mM, 22% activity compared to activation with dithiothreitol
dithiothreitol
Fe(NH4)2(SO4)2
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-
glutathione
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30 mM, 16.1% activity compared to activation with dithiothreitol
L-cysteine
N-acetylcysteine
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30 mM, 31.2% activity compared to activation with dithiothreitol
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0075 - 0.0166
L-tryptophan
0.0344 - 0.796
(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
0.055 - 0.0752
2-amino-4-hydroxy-6-methyltetrahydropteridine
0.1
L-phenylalanine
-
cofactor 2-amino-4-hydroxy-6-methyltetrahydropteridine
0.0075 - 0.355
L-tryptophan
0.294
tetrahydrobiopterin
-
activated enzyme in desalted extracts
additional information
additional information
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0761 - 0.609
D-Dopa
0.007 - 0.0943
dopamine
0.026
L-4-chlorophenylalanine
-
-
0.017 - 0.0887
L-Dopa
0.0162 - 0.306
L-tyrosine
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.011
3-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)phenylalanine
Mus musculus
-
-
0.00377
3-amino-3-[4-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)phenyl]propanoic acid
Mus musculus
-
-
0.00077
3-[1-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)piperidin-4-yl]alanine
Mus musculus
-
-
0.0126
3-[3-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)-1H-pyrazol-1-yl]alanine
Mus musculus
-
-
0.00089
3-[5-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)pyridin-2-yl]alanine
Mus musculus
-
-
0.0002
4-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)-2-fluorophenylalanine
Mus musculus
-
-
0.0111
4-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)-a-methylphenylalanine
Mus musculus
-
-
0.000026 - 0.000032
4-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)-L-phenylalanine
0.000046
4-(5-[[(1-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)methyl]amino]pyrazin-2-yl)-L-phenylalanine
Mus musculus
-
-
0.000013
4-(5-[[(1-hydroxynaphthalen-2-yl)methyl]amino]pyrazin-2-yl)-L-phenylalanine
Mus musculus
-
-
0.00004
4-(5-[[(2'-methylbiphenyl-2-yl)methyl]amino]pyrazin-2-yl)-L-phenylalanine
Mus musculus
-
-
0.000031
4-(5-[[(9-ethyl-9H-carbazol-3-yl)methyl]amino]pyrazin-2-yl)-L-phenylalanine
Mus musculus
-
-
0.000045
4-(5-[[3-(cyclopentyloxy)-4-methoxybenzyl]amino]pyrazin-2-yl)-L-phenylalanine
Mus musculus
-
-
0.092
4-Chlorophenylalanine
Mus musculus
-
-
0.03
4-ethynylphenylalanine
Mus musculus
-
-
0.00038
4-[4-amino-6-(1-naphthalen-2-ylethoxy)-1,3,5-triazin-2-yl]-L-phenylalanine
Mus musculus
-
-
0.00018
4-[4-amino-6-(2,2,2-trifluoro-1-naphthalen-2-ylethoxy)-1,3,5-triazin-2-yl]-L-phenylalanine
Mus musculus
-
-
0.000029
4-[4-amino-6-(2,2,2-trifluoro-1-[2-[3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl]ethoxy)-1,3,5-triazin-2-yl]-L-phenylalanine
Mus musculus
-
-
0.000024
4-[4-amino-6-[2,2,2-trifluoro-1-(2-furan-2-ylphenyl)ethoxy]-1,3,5-triazin-2-yl]-L-phenylalanine
Mus musculus
-
-
0.00007
4-[4-amino-6-[2,2,2-trifluoro-1-(3'-methylbiphenyl-2-yl)ethoxy]-1,3,5-triazin-2-yl]-L-phenylalanine
Mus musculus
-
-
0.000054
4-[4-amino-6-[2,2,2-trifluoro-1-(5-furan-2-ylthiophen-2-yl)ethoxy]-1,3,5-triazin-2-yl]-L-phenylalanine
Mus musculus
-
-
0.000069
4-[5-[(3,4-dimethoxybenzyl)amino]pyrazin-2-yl]-L-phenylalanine
Mus musculus
-
-
0.00011
4-[5-[(4-cyanobenzyl)amino]pyrazin-2-yl]-L-phenylalanine
Mus musculus
-
-
0.000044
4-[5-[(biphenyl-4-ylmethyl)amino]pyrazin-2-yl]-L-phenylalanine
Mus musculus
-
-
0.00024
4-[5-[(cyclohexylmethyl)amino]pyrazin-2-yl]-L-phenylalanine
Mus musculus
-
-
0.00096
4-[5-[(furan-3-ylmethyl)amino]pyrazin-2-yl]-L-phenylalanine
Mus musculus
-
-
0.00615
4-[5-[(pyridin-3-ylmethyl)amino]pyrazin-2-yl]-L-phenylalanine
Mus musculus
-
-
0.00019
4-[5-[(quinolin-3-ylmethyl)amino]pyrazin-2-yl]-L-phenylalanine
Mus musculus
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.434
-
recombinant enzyme, activity in cell extracts
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6 - 8.7
-
about 50% activity at pH 6.0 and 8.7
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
TPH1; isozyme TPH1
UniProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
temporal expression pattern of TPH1
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
-
enzyme-deficient mice have elevated serum tryptophan levels, a normal mast cell compartment and enhanced signaling of mammalian target of rapamycin. Enzyme deficiency exacerbates experimental autoimmune encephalomyelitis
metabolism
-
rate-limiting enzyme in the serotonin biosynthesis
physiological function
-
the enzyme is a potent regulator of immunity regulating immune tolerance and inflammation. The enzyme is essential for the generation of protective T cell–mediated antitumor immunity
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
Sequence
TPH1_MOUSE
447
0
51343
Swiss-Prot
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
47000
-
x * 47000, recombinant enzyme, SDS-PAGE
53000
-
4 * 53000, enzyme from mastocytoma cells, SDS-PAGE
56000
-
4 * 56000, SDS-PAGE
270000
-
enzyme from mastocytoma cells, gel filtration
280000
-
enzyme from mastocytoma cells, gradient PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
-
x * 47000, recombinant enzyme, SDS-PAGE
homotetramer
-
4 * 56000, SDS-PAGE
tetramer
-
4 * 53000, enzyme from mastocytoma cells, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
-
tryptophan hydroxylase becomes phosphorylated at Ser58 in brain stem of 1-month-old SAMP6
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C110S/C112S
-
all cysteine residues of the regulatory domain mutated
C110S/C112S/C162S/C234S/C248S/C296S
-
six N-terminal-most cysteines mutated
C110S/C112S/C162S/C234S/C248S/C296S/C315S/C355S/C365S/C394S/C404S/C408S/C476S
-
all 13 cysteine residues mutated
C110S/C162S/C234S/C248S/C296S/C355S/C365S/C394S/C404S/C408S/C476S
-
mutant protein containing a single cysteine residue within the regulatory domain (Cys112) and within the catalytic core domain (Cys315)
C1473G
-
naturally occuring polymorphism of gene Tph2, C57Bl/6 and 129X1/SvJ mice are homozygous for the 1473C allele, whereas DBA/2 and BALB/cJ mice are homozygous for the 1473G allele, comparison of pulmonary hypertension and vascular remodeling of haplotypes, overview
C162S/C234S/C248S/C296S/C315S/C355S/C365S/C394S/C404S/C408S/C476S
-
all cysteine residues of the catalytic core domain mutated
C315S/C355S/C365S/C394S/C404S/C408S/C476S
-
seven C-terminal-most cysteines mutated
C476S
-
residue of the tetramerization domain
DELTA1-40
-
simulates tyrosine hydroxylase 1
DELTA-C-terminal 24 residues
-
removed tetramerization domain
G1473C
-
naturally occuring polymorphism, citalopram raises basal extracellular serotonin levels in DBA/2J, DBA/2N and BALB/c mice carrying the 1473G allele, but not in C57BL/6J and C57BL/6N mice carrying the 1473C allele, overview
P447R
the C1473G naturally occuring polymorphism in gene tph2 is the main factor mediating the genetically defined variability of tryptophan hydroxylase-2 activity in the mouse brain, phenotypes, overview
additional information
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4
-
complete loss of activity in absence of stabilizing agents after 20 h
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
catalase at a concentration of more than 1 mg/ml is required for stability during reaction at aerobic conditiones
-
EDTA stabilizes
-
EDTA: 0.05 mM stabilizes
-
ethylene glycol, 50%, stabilizes
-
NaCl: 1 M, in addition to other stabilizing agents brings a great improvement in stabilization
-
Tween 20 stabilizes
-
Tween 20: 0.06% stabilizes
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 10% glycerol, 0.05 mM EDTA, 0.06% Tween 20, 28 d, 69% loss of activity
-
-80°C, 1 month, 30% loss of activity
-
4°C, 0.06% Tween 20, 0.05 mM EDTA, 50% ethylene glycol, 1 M NaCl, 5 days, no loss of activity
-
4°C, 10% glycerol, 0.05 mM EDTA, 0.06% Tween 20, 28 d, 34% loss of activity
-
PURIFICATION/commentary
ORGANISM
UNIPROT
LITERATURE
2-amino-4-hydroxy-6,7-dimethyltetrahydropteridine-agarose
-
one chromatography step, 98% homogeneity
-
purified and cleaved from its fusion tag
-
recombinant isozymes TPH1 and TPH2 from Escherichia coli by pterin affinity chromatography
-
CLONED/commentary
ORGANISM
UNIPROT
LITERATURE
isozyme TPH1, DNA and amino acid sequence determination and analysis, tissue-specific and developmental expression analysis, expression of His6-tagged TPH1 in COS7 cells
expression in Escherichia coli
-
expression of isozymes TPH1 and TPH2 in Escherichia coli
-
expression of TPH2 in COS cells
-
genes Tph1 and Tph2, expression analysis in wild-type and mutant mice, overview
-
glutathione S-transferase-fusion protein expressed in Escherichia coli, expressed in HEK293-cell, eGFP-fusion protein expressed in HEK293-cell
-
into pT vector and linearized with Nco I prior to antisense transcription with SP6
-
isozyme TPH2, DNA and amino acid sequence determination and analysis, tissue-specific and developmental expression analysis, expression of His6-tagged TPH2 in COS7 cells
secondary structure of TPH1 RNA, overview
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
enzyme expression is induced by prolactin
-
enzyme expression is inhibited by a Jak2 inhibitor and partially inhibited by MEK1/2 inhibitor U0126 or PI3K inhibitor LY-294002
-
imipramine increases dorsal raphe TPH2 gene expression in a glucocorticoid-dependent manner, increases are due to relief of inhibitory glucocorticoid signaling
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
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substituted 3-(4-(1,3,5-triazin-2-yl)-phenyl)-2-aminopropanoic acids as novel TPH1 inhibitors may provide novel treatments for gastrointestinal disorders associated with dysregulation of the serotonergic system, such as chemotherapy-induced emesis and irritable bowel syndrome
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Hasegawa, H.; Ichiyama, A.
Tryptophan 5-monooxygenase from mouse mastocytoma: high-performance liquid chromatography assay
Methods Enzymol.
142
88-92
1987
Mus musculus
Manually annotated by BRENDA team
Fujisawa, H.; Nakata, H.
Tryptophan 5-monooxygenase from mouse mastocytoma clone P815
Methods Enzymol.
142
93-96
1987
Mus musculus
Manually annotated by BRENDA team
Nakata, H.; Fujisawa, H.
Tryptophan 5-monooxygenase from mouse mastocytoma P815. A simple purification and general properties
Eur. J. Biochem.
124
595-601
1982
Mus musculus
Manually annotated by BRENDA team
Naoi, M.; Maruyama, W.; Takahashi, T.; Ota, M.; Parvez, H.
Inhibition of tryptophan hydroxylase by dopamine and the precursor amino acids
Biochem. Pharmacol.
48
207-211
1994
Mus musculus
Manually annotated by BRENDA team
Park, D.H.; Stone, D.M.; Kim, K.S.; Joh, T.H.
Characterization of recombinant mouse tryptophan hydroxylase expressed in Escherichia coli
Mol. Cell. Neurosci.
5
87-93
1994
Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Yohrling, I.G.; Jiang, G.C.; DeJohn, M.M.; Robertson, D.J.; Vrana, K.E.; Cha, J.H.
Inhibition of tryptophan hydroxylase activity and decreased 5-HT1A receptor binding in a mouse model of Huntington's disease
J. Neurochem.
82
1416-1423
2002
Mus musculus
Manually annotated by BRENDA team
Walther, D.J.; Peter, J.U.; Bashammakh, S.; Hortnagl, H.; Voits, M.; Fink, H.; Bader, M.
Synthesis of serotonin by a second tryptophan hydroxylase isoform
Science
299
76
2003
Mus musculus (Q8CGV2)
Manually annotated by BRENDA team
Zhang, X.; Beaulieu, J.M.; Sotnikova, T.D.; Gainetdinov, R.R.; Caron, M.G.
Tryptophan hydroxylase-2 controls brain serotonin synthesis
Science
305
217
2004
Mus musculus, Mus musculus (Q8CGV2)
Manually annotated by BRENDA team
Hasegawa, H.; Ichiyama, A.
Distinctive iron requirement of tryptophan 5-monooxygenase: TPH1 requires dissociable ferrous iron
Biochem. Biophys. Res. Commun.
338
277-284
2005
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Zhang, X.; Beaulieu, J.M.; Gainetdinov, R.R.; Caron, M.G.
Functional polymorphisms of the brain serotonin synthesizing enzyme tryptophan hydroxylase-2
Cell. Mol. Life Sci.
63
6-11
2006
Danio rerio, Drosophila melanogaster, Gallus gallus, Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Cervo, L.; Canetta, A.; Calcagno, E.; Burbassi, S.; Sacchetti, G.; Caccia, S.; Fracasso, C.; Albani, D.; Forloni, G.; Invernizzi, R.W.
Genotype-dependent activity of tryptophan hydroxylase-2 determines the response to citalopram in a mouse model of depression
J. Neurosci.
25
8165-8172
2005
Mus musculus
Manually annotated by BRENDA team
Izikki, M.; Hanoun, N.; Marcos, E.; Savale, L.; Barlier-Mur, A.M.; Saurini, F.; Eddahibi, S.; Hamon, M.; Adnot, S.
Tryptophan hydroxylase 1 knockout and tryptophan hydroxylase 2 polymorphism: effects on hypoxic pulmonary hypertension in mice
Am. J. Physiol. Lung Cell. Mol. Physiol.
293
L1045-L1052
2007
Mus musculus
Manually annotated by BRENDA team
Niimi, K.; Takahashi, E.; Itakura, C.
Emotional behavior and expression patterns of tyrosine hydroxylase and tryptophan hydroxylase in senescence-accelerated mouse (SAM) P6 mice
Behav. Brain Res.
188
329-336
2008
Mus musculus
Manually annotated by BRENDA team
Shi, Z.C.; Devasagayaraj, A.; Gu, K.; Jin, H.; Marinelli, B.; Samala, L.; Scott, S.; Stouch, T.; Tunoori, A.; Wang, Y.; Zang, Y.; Zhang, C.; Kimball, S.D.; Main, A.J.; Sun, W.; Yang, Q.; Nouraldeen, A.; Yu, X.Q.; Buxton, E.; Patel, S.; Nguyen, N.; Swaffield, J.; Powell, D.R.; Wilson, A.; Liu, Q.
Modulation of peripheral serotonin levels by novel tryptophan hydroxylase inhibitors for the potential treatment of functional gastrointestinal disorders
J. Med. Chem.
51
3684-3687
2008
Mus musculus
Manually annotated by BRENDA team
Calcagno, E.; Canetta, A.; Guzzetti, S.; Cervo, L.; Invernizzi, R.W.
Strain differences in basal and post-citalopram extracellular 5-HT in the mouse medial prefrontal cortex and dorsal hippocampus: relation with tryptophan hydroxylase-2 activity
J. Neurochem.
103
1111-1120
2007
Mus musculus
Manually annotated by BRENDA team
Liu, Q.; Yang, Q.; Sun, W.; Vogel, P.; Heydorn, W.; Yu, X.Q.; Hu, Z.; Yu, W.; Jonas, B.; Pineda, R.; Calderon-Gay, V.; Germann, M.; ONeill, E.; Brommage, R.; Cullinan, E.; Platt, K.; Wilson, A.; Powell, D.; Sands, A.; Zambrowicz, B.; Shi, Z.C.
Discovery and characterization of novel tryptophan hydroxylase inhibitors that selectively inhibit serotonin synthesis in the gastrointestinal tract
J. Pharmacol. Exp. Ther.
325
47-55
2008
Mus musculus
Manually annotated by BRENDA team
Peter, J.; Alenina, N.; Bader, M.; Walther, D.J.
Development of antithrombotic miniribozymes that target peripheral tryptophan hydroxylase
Mol. Cell. Biochem.
295
205-215
2007
Mus musculus
Manually annotated by BRENDA team
Nakamura, K.; Hasegawa, H.
Developmental role of tryptophan hydroxylase in the nervous system
Mol. Neurobiol.
35
45-54
2007
Homo sapiens (P17752), Homo sapiens (Q8IWU9), Mus musculus (P17532), Mus musculus (Q8CGV2)
Manually annotated by BRENDA team
Clark, J.A.; Flick, R.B.; Pai, L.Y.; Szalayova, I.; Key, S.; Conley, R.K.; Deutch, A.Y.; Hutson, P.H.; Mezey, E.
Glucocorticoid modulation of tryptophan hydroxylase-2 protein in raphe nuclei and 5-hydroxytryptophan concentrations in frontal cortex of C57/Bl6 mice
Mol. Psychiatry
13
498-506
2008
Homo sapiens, Homo sapiens (Q8IWU9), Mus musculus, Mus musculus C57BL/6, Rattus norvegicus (Q8CGU9)
Manually annotated by BRENDA team
Kulikov, A.V.; Osipova, D.V.; Popova, N.K.
The C1473G polymorphism in gene tph2 is the main factor mediating the genetically defined variability of tryptophan hydroxylase-2 activity in the mouse brain
Russ. J. Genet.
43
1408-1412
2007
Mus musculus (Q8CGV2)
-
Manually annotated by BRENDA team
Jin, H.; Cianchetta, G.; Devasagayaraj, A.; Gu, K.; Marinelli, B.; Samala, L.; Scott, S.; Stouch, T.; Tunoori, A.; Wang, Y.; Zang, Y.; Zhang, C.; David Kimball, S.; Main, A.J.; Ding, Z.M.; Sun, W.; Yang, Q.; Yu, X.Q.; Powell, D.R.; Wilson, A.; Liu, Q.; Shi, Z.C.
Substituted 3-(4-(1,3,5-triazin-2-yl)-phenyl)-2-aminopropanoic acids as novel tryptophan hydroxylase inhibitors
Bioorg. Med. Chem. Lett.
19
5229-5232
2009
Homo sapiens (P17752), Mus musculus
Manually annotated by BRENDA team
Heydendael, W.; Jacobson, L.
Glucocorticoid status affects antidepressant regulation of locus coeruleus tyrosine hydroxylase and dorsal raphe tryptophan hydroxylase gene expression
Brain Res.
1288
69-78
2009
Mus musculus
Manually annotated by BRENDA team
Kuhn, D.M.; Sykes, C.E.; Geddes, T.J.; Jaunarajs, K.L.; Bishop, C.
Tryptophan hydroxylase 2 aggregates through disulfide cross-linking upon oxidation: possible link to serotonin deficits and non-motor symptoms in Parkinsons disease
J. Neurochem.
116
426-437
2011
Mus musculus
Manually annotated by BRENDA team
Matthes, S.; Mosienko, V.; Bashammakh, S.; Alenina, N.; Bader, M.
Tryptophan hydroxylase as novel target for the treatment of depressive disorders
Pharmacology
85
95-109
2010
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Nowak, E.C.; de Vries, V.C.; Wasiuk, A.; Ahonen, C.; Bennett, K.A.; Le Mercier, I.; Ha, D.G.; Noelle, R.J.
Tryptophan hydroxylase-1 regulates immune tolerance and inflammation
J. Exp. Med.
209
2127-2135
2012
Mus musculus
Manually annotated by BRENDA team
Laurent, L.; Deroy, K.; St-Pierre, J.; Cote, F.; Sanderson, J.T.; Vaillancourt, C.
Human placenta expresses both peripheral and neuronal isoform of tryptophan hydroxylase
Biochimie
140
159-165
2017
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Iida, H.; Ogihara, T.; Min, M.K.; Hara, A.; Kim, Y.G.; Fujimaki, K.; Tamaki, M.; Fujitani, Y.; Kim, H.; Watada, H.
Expression mechanism of tryptophan hydroxylase 1 in mouse islets during pregnancy
J. Mol. Endocrinol.
55
41-53
2015
Mus musculus
Manually annotated by BRENDA team
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