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Information on EC 1.14.16.4 - tryptophan 5-monooxygenase and Organism(s) Homo sapiens and UniProt Accession P17752
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1.14.16.4 tryptophan 5-monooxygenaseIUBMB Comments
The active centre contains mononuclear iron(II). The enzyme is activated by phosphorylation, catalysed by a Ca2+-activated protein kinase. The 4a-hydroxytetrahydropteridine formed can dehydrate to 6,7-dihydropteridine, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydropteridine must be enzymically reduced back to tetrahydropteridine, by EC 1.5.1.34, 6,7-dihydropteridine reductase, before it slowly rearranges into the more stable but inactive compound 7,8-dihydropteridine.
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Word Map
- 1.14.16.4
- serotonin
-
serotonergic
-
raphe
- 5-hydroxytryptamine
-
monoamine
-
dorsal
- dopamine
-
neurotransmitter
- hippocampus
-
antidepressant
-
reuptake
- 5-hydroxytryptophan
-
anxiety
-
psychiatric
- midbrain
- striatum
- hypothalamus
-
neurochemical
-
5-hydroxyindoleacetic
-
mood
-
enterochromaffin
-
neurotransmission
-
5-hiaa
- p-chlorophenylalanine
- fluoxetine
-
pineal
- brainstem
- alpha-methyl-p-tyrosine
-
monoaminergic
-
5,7-dihydroxytryptamine
- analysis
- methamphetamine
-
autoreceptors
-
slc6a4
-
immobility
- pargyline
- n-acetylserotonin
- neostriatal
-
5-httlpr
- medicine
- citalopram
-
antidepressant-like
- carcinoid
- biopterins
-
impulsivity
-
oxidase-a
- tetrahydropterins
- fenfluramine
-
impulsive
-
8-oh-dpat
- 5-hydroxyindole
- drug development
- 3,4-methylenedioxymethamphetamine
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
+
+
=
+
+
+
=
+
a 4a-hydroxy-5,6,7,8-tetrahydropteridine
Synonyms
tryptophan hydroxylase, tryptophan hydroxylase 2, tryptophan hydroxylase 1, tph-1, tryptophan hydroxylase-2, tryptophan hydroxylase-1, tph-2, tryptophan-5-hydroxylase, tryptophan 5-monooxygenase, htph2, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
indoleacetic acid-5-hydroxylase
-
-
-
-
L-tryptophan hydroxylase
-
-
-
-
oxygenase, tryptophan 5-mono-
-
-
-
-
TPH
TPH-2
TPH1
TPH2
tryptophan 5-hydroxylase
-
-
-
-
tryptophan hydroxylase
tryptophan hydroxylase 2
tryptophan hydroxylase-2
-
TPH2
-
-
TPH2
-
tryptophan hydroxylase
-
-
-
-
tryptophan hydroxylase 2
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-
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-hydroxytetrahydropteridine formed can dehydrate to 6,7-dihydropteridine, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydropteridine must be enzymically reduced back to tetrahydropteridine, by EC 1.5.1.34, 6,7-dihydropteridine reductase, before it slowly rearranges into the more stable but inactive compound 7,8-dihydropteridine.
CAS REGISTRY NUMBER
COMMENTARY
9037-21-2
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
L-tryptophan + (6R)-L-erytho-5,6,7,8-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + ?
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
rate-determining step of serotonin biosynthesis
-
-
?
L-phenylalanine + (7R)-5,6,7,8-tetrahydrobiopterine + O2
L-tyrosine + dihydropteridine + H2O
-
-
-
-
r
L-phenylalanine + tetrahydrobiopterin + O2
L-tyrosine + dihydropterin + H2O
-
-
-
-
r
L-tryptophan + (6R)-L-erytho-5,6,7,8-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + ?
-
-
-
-
?
L-tryptophan + (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
L-tryptophan + 2-amino-4-hydroxy-6,7-dimethyl-5,6,7,8-tetrahydropteridine + O2
?
-
-
-
-
r
L-tryptophan + 6-methyl-tetrahydropterin + O2
5-hydroxy-L-tryptophan + 6-methyl-4a-hydroxytetrahydropterin
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
low tryptophan levels are associated with depression and may arise because of stress, the hypothalamic and peripheral serotonin, i.e.5-hydroxytryptamine-system has a significant role in appetite regulation, possibly a homeostatic mechanism in regulating peripheral TRP levels, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
the enzyme is rate limiting in serotonin biosynthesis and important in serotonergic neurotransmission, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
TPH catalyzes the first step and rate-limiting reaction in the biosynthesis of 5-hydroxytryptamine, i.e. serotonin, and plays a role in brain development, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
TPH1 is the rate-limiting enzyme in serotonin biosynthesis
-
-
?
L-tryptophan + (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
-
?
L-tryptophan + (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
?
L-tryptophan + (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
-
?
L-tryptophan + (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
?
L-tryptophan + (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
over 300 single nucleotide polymorphisms have been identified and are associated with symptoms ranging from mild hyperphenylalaninemia to severe phenylketonuria
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
brain-specific isozyme TPH2 is the rate-limiting enzyme in serotonin biosynthesis, a truncated enzyme version occurs in brain tissues being the cause of impaired serotonin transmission
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
differences in the regulation of isozyme TPH2 versus isozyme TPH1, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
first and rate limiting step in the biosynthesis of the neurotransmitter serotonin
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
initial and rate-limiting enzyme in the biosynthesis of serotonin
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
rate-limiting step in the biosynthesis of serotonin, regulation of isozymes TPH1 and TPH2, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
rate-limiting step in the synthesis of serotonin
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
the enzyme is rate-limiting in neuronal serotonin biosynthesis, disturbances of the central serotonergic system, due to genetic variations in the TPH2 gene, are involved in the pathophysiology of alcohol dependence and suicidal behavior
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
the enzyme is rate-limiting in serotonin biosynthesis, deficient levels of serotonin are associated with suicide and depression
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
the enzyme is responsible for serotonin biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
TPH catalyzes the first step and rate-limiting reaction in the biosynthesis of 5-hydroxytryptamine, i.e. serotonin, and plays a role in brain development, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
TPH is rate-limiting in serotonin biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
TPH is rate-limiting in serotonin biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
TPH is the rate-limiting enzyme in the biosynthesis of 5-hydroxytryptamine, i.e. serotonin, possible involvement of the TPH1 218A allele in susceptibility to schizophrenia, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
TPH2 control 5-hydroxytryptamine, i.e. serotonin, biosynthesis and its deficiency is involved in affective disorders, pathophysiological mechanism, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
TPH2 is involved in serotonin biosynthesis, which is involved in behavioural processes, e.g. working memory, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
TPH2 is rate-limiting in serotonin, i.e. 5-hydroxytryptamine, biosynthesis, serotonin is involved in the pathophysiology of several psychiatric disorders including major depression, MD, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
TPH2 is the first and rate-limiting enzyme in the serotonin biosynthetic pathway
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
TPH2 is the rate-limiting enzyme during 5-hydroxytryptamine synthesis in the brain
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
TPH2 is the rate-limiting enzyme in brain serotonin/5-hydroxytryptamine biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
TPH2 is the rate-limiting enzyme in raphe serotonin biosynthesis, and polymorphisms of TPH2 are implicated in vulnerability to psychiatric disorders
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
-
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
-
initial and uncommited step in the biosynthesis of melatonin
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
-
rate-limiting step in biosynthesis of serotonin in brain
-
-
?
additional information
?
-
5-hydroxytryptamine is a major modulator of behavior in vertebrates and invertebrates, and deficiencies in the serotonergic system account for several behavioral disorders in humans, 5-hydroxyytryptamine is a major therapeutic target in patients with psychiatric disorders, overview, association of TPH1 with suicidal behavior, TPH1 is involved in brain and serotonergic neuron development, overview
-
-
?
additional information
?
-
5-hydroxytryptamine is a major modulator of behavior in vertebrates and invertebrates, and deficiencies in the serotonergic system account for several behavioral disorders in humans, 5-hydroxyytryptamine is a major therapeutic target in patients with psychiatric disorders, overview, association of TPH1 with suicidal behavior, TPH1 is involved in brain and serotonergic neuron development, overview
-
-
?
additional information
?
-
alcohol consumption may influence TPH1 and TPH2 expression and regulation
-
-
?
additional information
?
-
association between the tryptophan hydroxylase-1 gene A218C polymorphism and citalopram antidepressant response in a Korean population with major depressive disorder
-
-
?
additional information
?
-
-
association between the tryptophan hydroxylase-1 gene A218C polymorphism and citalopram antidepressant response in a Korean population with major depressive disorder
-
-
?
additional information
?
-
residue lying adjacent to substrate is F313, role of F313 in substrate specificity, residue is different from L-phenylalanine 4-hydroxylase
-
-
?
additional information
?
-
5-hydroxytryptamine is a major modulator of behavior in vertebrates and invertebrates, and deficiencies in the serotonergic system account for several behavioral disorders in humans, 5-hydroxyytryptamine is a major therapeutic target in patients with psychiatric disorders, overview
-
-
?
additional information
?
-
5-hydroxytryptamine is a major modulator of behavior in vertebrates and invertebrates, and deficiencies in the serotonergic system account for several behavioral disorders in humans, 5-hydroxyytryptamine is a major therapeutic target in patients with psychiatric disorders, overview
-
-
?
additional information
?
-
additive effects of serotonin transporter and tryptophan hydroxylase-2 gene variation on neural correlates of affective processing, serotonergic regulation of neural processing of affective stimuli with the striatum as a critical site where gene-gene regulation takes place, whole brain analysis for emotional word Stroop task, overview
-
-
?
additional information
?
-
localized changes in TPH2 expression in specific subnuclei of the dorsal raphe nucleus suggest that the serotonergic compensatory mechanism in depression and suicide is specifically regulated within the DRN and has implications for regions innervated by this subnucleus, overview
-
-
?
additional information
?
-
-
the borderline personality disorder might be partly due to serotonergic dysfunction
-
-
?
additional information
?
-
TPH2 expression is part of the developmental program regulated by REST, i.e. the RE-1 silencer of transcription, REST/NRSF is implicated in neurogenesis and transcriptionally regulates a network of genes, overview
-
-
?
additional information
?
-
-
TPH2 expression is part of the developmental program regulated by REST, i.e. the RE-1 silencer of transcription, REST/NRSF is implicated in neurogenesis and transcriptionally regulates a network of genes, overview
-
-
?
additional information
?
-
TPH2 gene and its 5' upstream region variants may be involved in the predisposition to suicide in major depression disorder, however, may not play a role in impulsive-aggressive behaviors as mediators, overview
-
-
?
additional information
?
-
-
TPH2 gene and its 5' upstream region variants may be involved in the predisposition to suicide in major depression disorder, however, may not play a role in impulsive-aggressive behaviors as mediators, overview
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
rate-determining step of serotonin biosynthesis
-
-
?
L-tryptophan + (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
over 300 single nucleotide polymorphisms have been identified and are associated with symptoms ranging from mild hyperphenylalaninemia to severe phenylketonuria
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
low tryptophan levels are associated with depression and may arise because of stress, the hypothalamic and peripheral serotonin, i.e.5-hydroxytryptamine-system has a significant role in appetite regulation, possibly a homeostatic mechanism in regulating peripheral TRP levels, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
the enzyme is rate limiting in serotonin biosynthesis and important in serotonergic neurotransmission, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
TPH catalyzes the first step and rate-limiting reaction in the biosynthesis of 5-hydroxytryptamine, i.e. serotonin, and plays a role in brain development, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
TPH1 is the rate-limiting enzyme in serotonin biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
brain-specific isozyme TPH2 is the rate-limiting enzyme in serotonin biosynthesis, a truncated enzyme version occurs in brain tissues being the cause of impaired serotonin transmission
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
differences in the regulation of isozyme TPH2 versus isozyme TPH1, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
first and rate limiting step in the biosynthesis of the neurotransmitter serotonin
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
initial and rate-limiting enzyme in the biosynthesis of serotonin
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
rate-limiting step in the biosynthesis of serotonin, regulation of isozymes TPH1 and TPH2, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
rate-limiting step in the synthesis of serotonin
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
the enzyme is rate-limiting in neuronal serotonin biosynthesis, disturbances of the central serotonergic system, due to genetic variations in the TPH2 gene, are involved in the pathophysiology of alcohol dependence and suicidal behavior
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
the enzyme is rate-limiting in serotonin biosynthesis, deficient levels of serotonin are associated with suicide and depression
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
the enzyme is responsible for serotonin biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
TPH catalyzes the first step and rate-limiting reaction in the biosynthesis of 5-hydroxytryptamine, i.e. serotonin, and plays a role in brain development, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
TPH is rate-limiting in serotonin biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
TPH is rate-limiting in serotonin biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
TPH is the rate-limiting enzyme in the biosynthesis of 5-hydroxytryptamine, i.e. serotonin, possible involvement of the TPH1 218A allele in susceptibility to schizophrenia, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
TPH2 control 5-hydroxytryptamine, i.e. serotonin, biosynthesis and its deficiency is involved in affective disorders, pathophysiological mechanism, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
TPH2 is involved in serotonin biosynthesis, which is involved in behavioural processes, e.g. working memory, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
TPH2 is rate-limiting in serotonin, i.e. 5-hydroxytryptamine, biosynthesis, serotonin is involved in the pathophysiology of several psychiatric disorders including major depression, MD, overview
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
TPH2 is the first and rate-limiting enzyme in the serotonin biosynthetic pathway
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
TPH2 is the rate-limiting enzyme during 5-hydroxytryptamine synthesis in the brain
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
-
TPH2 is the rate-limiting enzyme in brain serotonin/5-hydroxytryptamine biosynthesis
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
TPH2 is the rate-limiting enzyme in raphe serotonin biosynthesis, and polymorphisms of TPH2 are implicated in vulnerability to psychiatric disorders
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
-
initial and uncommited step in the biosynthesis of melatonin
-
-
?
L-tryptophan + tetrahydropteridine + O2
5-hydroxy-L-tryptophan + dihydropteridine + H2O
-
rate-limiting step in biosynthesis of serotonin in brain
-
-
?
additional information
?
-
5-hydroxytryptamine is a major modulator of behavior in vertebrates and invertebrates, and deficiencies in the serotonergic system account for several behavioral disorders in humans, 5-hydroxyytryptamine is a major therapeutic target in patients with psychiatric disorders, overview, association of TPH1 with suicidal behavior, TPH1 is involved in brain and serotonergic neuron development, overview
-
-
?
additional information
?
-
5-hydroxytryptamine is a major modulator of behavior in vertebrates and invertebrates, and deficiencies in the serotonergic system account for several behavioral disorders in humans, 5-hydroxyytryptamine is a major therapeutic target in patients with psychiatric disorders, overview, association of TPH1 with suicidal behavior, TPH1 is involved in brain and serotonergic neuron development, overview
-
-
?
additional information
?
-
alcohol consumption may influence TPH1 and TPH2 expression and regulation
-
-
?
additional information
?
-
association between the tryptophan hydroxylase-1 gene A218C polymorphism and citalopram antidepressant response in a Korean population with major depressive disorder
-
-
?
additional information
?
-
-
association between the tryptophan hydroxylase-1 gene A218C polymorphism and citalopram antidepressant response in a Korean population with major depressive disorder
-
-
?
additional information
?
-
5-hydroxytryptamine is a major modulator of behavior in vertebrates and invertebrates, and deficiencies in the serotonergic system account for several behavioral disorders in humans, 5-hydroxyytryptamine is a major therapeutic target in patients with psychiatric disorders, overview
-
-
?
additional information
?
-
5-hydroxytryptamine is a major modulator of behavior in vertebrates and invertebrates, and deficiencies in the serotonergic system account for several behavioral disorders in humans, 5-hydroxyytryptamine is a major therapeutic target in patients with psychiatric disorders, overview
-
-
?
additional information
?
-
additive effects of serotonin transporter and tryptophan hydroxylase-2 gene variation on neural correlates of affective processing, serotonergic regulation of neural processing of affective stimuli with the striatum as a critical site where gene-gene regulation takes place, whole brain analysis for emotional word Stroop task, overview
-
-
?
additional information
?
-
localized changes in TPH2 expression in specific subnuclei of the dorsal raphe nucleus suggest that the serotonergic compensatory mechanism in depression and suicide is specifically regulated within the DRN and has implications for regions innervated by this subnucleus, overview
-
-
?
additional information
?
-
-
the borderline personality disorder might be partly due to serotonergic dysfunction
-
-
?
additional information
?
-
TPH2 expression is part of the developmental program regulated by REST, i.e. the RE-1 silencer of transcription, REST/NRSF is implicated in neurogenesis and transcriptionally regulates a network of genes, overview
-
-
?
additional information
?
-
-
TPH2 expression is part of the developmental program regulated by REST, i.e. the RE-1 silencer of transcription, REST/NRSF is implicated in neurogenesis and transcriptionally regulates a network of genes, overview
-
-
?
additional information
?
-
TPH2 gene and its 5' upstream region variants may be involved in the predisposition to suicide in major depression disorder, however, may not play a role in impulsive-aggressive behaviors as mediators, overview
-
-
?
additional information
?
-
-
TPH2 gene and its 5' upstream region variants may be involved in the predisposition to suicide in major depression disorder, however, may not play a role in impulsive-aggressive behaviors as mediators, overview
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
residue Y235 is involved in cofactor binding, residue is different from L-phenylalanine 4-hydroxylase
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Fe2+
Fe2+
-
Fe2+ concentration for half-maximal activation of recombinant N-terminal truncated enzyme: 0.0013 mM
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4-(4-amino-6-[methyl[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)-L-phenylalanine
-
4-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)-L-phenylalanine
-
4-(4-amino-6-[[(1S)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)-L-phenylalanine
-
4-(4-amino-6-[[(4'-methylbiphenyl-4-yl)methyl]amino]-1,3,5-triazin-2-yl)-L-phenylalanine
-
4-(4-amino-6-[[4-(trifluoromethyl)benzyl]amino]-1,3,5-triazin-2-yl)-L-phenylalanine
-
4-[4-(methylamino)-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
4-[4-amino-6-(2,2,2-trifluoro-1-naphthalen-2-ylethoxy)-1,3,5-triazin-2-yl]-L-phenylalanine
-
4-[4-amino-6-([[4'-(trifluoromethyl)biphenyl-4-yl]methyl]amino)-1,3,5-triazin-2-yl]-L-phenylalanine
-
4-[4-amino-6-[(1-biphenyl-4-ylethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
4-[4-amino-6-[(1-methyl-1-naphthalen-2-ylethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
4-[4-amino-6-[(1-naphthalen-2-ylpropyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
4-[4-amino-6-[(1-tricyclo[3.3.1.1(3,7)]dec-1-ylethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
4-[4-amino-6-[(2,2,2-trifluoro-1-naphthalen-2-ylethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
4-[4-amino-6-[(2-methyl-1-naphthalen-2-ylpropyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
4-[4-amino-6-[(3,4-dimethylbenzyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
4-[4-amino-6-[(3-methyl-1-naphthalen-2-ylbutyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
4-[4-amino-6-[(4-phenoxybenzyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
4-[4-amino-6-[(biphenyl-2-ylmethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
4-[4-amino-6-[(biphenyl-3-ylmethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
4-[4-amino-6-[(biphenyl-4-ylmethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
4-[4-amino-6-[(cyclohexylmethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
4-[4-amino-6-[(naphthalen-2-ylmethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
4-[4-morpholin-4-yl-6-[(naphthalen-2-ylmethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
4-[4-[(1-naphthalen-2-ylethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
-
citalopram
selective serotonin reuptake inhibitors, like citalopram, exert their activity enhancing the general serotonergic tone, citalopram is the most selective one with little or no affinity for a variety of receptor types, association between gene TPH1 A218C polymorphism and citalopram antidepressant response in a Korean population, overview
(7R)-5,6,7,8-tetrahydrobiopterin
-
recombinant pinal enzyme, 2.1 mM, 50% inhibition
4-([(E)-amino[([1,1'-biphenyl]-2-yl)amino]methylidene]carbamoyl)-L-phenylalanine
-
-
4-([(E)-amino[([2-(piperidin-1-yl)-6-[(propan-2-yl)oxy]phenyl]methyl)amino]methylidene]carbamoyl)-L-phenylalanine
-
-
4-([(E)-amino[([2-(piperidin-1-yl)-6-[2-(trifluoromethyl)phenoxy]phenyl]methyl)amino]methylidene]carbamoyl)-L-phenylalanine
-
-
4-([(E)-amino[([2-(piperidin-1-yl)-6-[3-(trifluoromethyl)phenoxy]phenyl]methyl)amino]methylidene]carbamoyl)-L-phenylalanine
-
-
4-([(E)-amino[([2-(piperidin-1-yl)-6-[4-(trifluoromethyl)phenoxy]phenyl]methyl)amino]methylidene]carbamoyl)-L-phenylalanine
-
-
4-[[(E)-amino([[2-(1H-1,2,4-triazol-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(1H-pyrazol-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(2-azabicyclo[2.2.1]heptan-2-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(2-chlorophenoxy)-6-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(2-methoxyphenoxy)-6-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(2-methylphenoxy)-6-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(2-methylpiperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(2H-1,2,3-triazol-2-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(3,5-dimethylpiperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(3-azabicyclo[3.1.0]hexan-3-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(3-chlorophenoxy)-6-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(3-methoxyphenoxy)-6-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(3-methyl-1H-pyrazol-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(3-methylphenoxy)-6-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(3-methylpiperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(4-benzylpiperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(4-chlorophenoxy)-6-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(4-hydroxypiperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(4-methoxyphenoxy)-6-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(4-methoxypiperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(4-methyl-1H-imidazol-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(4-methylphenoxy)-6-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(4-phenylpiperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(azepan-1-yl)-6-methoxyphenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(azepan-1-yl)-6-phenoxyphenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(azepan-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(azetidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(cyclobutyloxy)-6-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(cyclohexyloxy)-6-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(diethylamino)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(morpholin-4-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(piperidin-1-yl)-5-(1,3-thiazol-2-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(piperidin-1-yl)-6-(trifluoromethyl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(pyrrolidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-(thiomorpholin-4-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-chloro-6-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-ethoxy-6-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-methoxy-6-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-methyl-6-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[2-phenoxy-6-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[3-(piperidin-1-yl)[1,1'-biphenyl]-2-yl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[3-chloro-2-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[3-methoxy-2-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[3-methyl-2-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[4-(piperidin-1-yl)[1,1'-biphenyl]-3-yl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[4-chloro-2-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[4-methoxy-2-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[4-methyl-2-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[5-chloro-2-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[5-methoxy-2-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino([[5-methyl-2-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino[[([1,1'-biphenyl]-2-yl)methyl](methyl)amino]methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino[[([1,1'-biphenyl]-2-yl)methyl]amino]methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino[[([1,1'-biphenyl]-3-yl)methyl]amino]methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino[[([1,1'-biphenyl]-4-yl)methyl]amino]methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino[[2-([1,1'-biphenyl]-2-yl)ethyl]amino]methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-amino[[3-([1,1'-biphenyl]-2-yl)propyl]amino]methylidene]carbamoyl]-L-phenylalanine
-
-
4-[[(E)-[[([1,1'-biphenyl]-2-yl)methyl]amino](methylamino)methylidene]carbamoyl]-L-phenylalanine
-
-
L-erythro-7,8-dihydrobiopterin
-
recombinant N-terminal truncated enzyme, competitive vs. (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
additional information
-
no substrate inhibition by (6R)-L-erytho-5,6,7,8-tetrahydrobiopterin
-
additional information
glucocorticoids inhibits TPH2 expression, the suppression is blocked by mifepristone, i.e. RU-486
-
additional information
-
glucocorticoids inhibits TPH2 expression, the suppression is blocked by mifepristone, i.e. RU-486
-
additional information
-
removal of 44 amino acids from the N-terminus of TPH2 results in a 3-4fold increased Vmax, which indicates a strong inhibitory function of this part on the enzymes activity
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
phosphorylation at Ser19 by protein kinase A or Ca2+/calmodulin dependent protein kinase II activates TPH2 by about 30%, high-affinity binding of purified PKA-phosphorylated TPH2 bound to the 14-3-3 proteins gamma , epsilon and BMH1 causes further increased enzyme activity, overview
-
additional information
-
phosphorylation at Ser19 by protein kinase A or Ca2+/calmodulin dependent protein kinase II activates TPH2 by about 30%, high-affinity binding of purified PKA-phosphorylated TPH2 bound to the 14-3-3 proteins gamma , epsilon and BMH1 causes further increased enzyme activity, overview
-
additional information
-
phosphorylation of TPH2 at Ser19 within the regulatory domain of the enzyme by calmodulin-dependent protein kinase II activates the enzyme
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0265
(6R)-L-erytho-5,6,7,8-tetrahydrobiopterin
doubly truncated enzyme form DELTANH102-DELTACOOH402
0.0128
(6R)-L-erytho-5,6,7,8-tetrahydrobiopterin
-
TPH2 fusion protein with maltose-binding protein
0.027
(6R)-L-erytho-5,6,7,8-tetrahydrobiopterin
-
TPH as fusion protein with maltose-binding protein expressed in Escherichia coli
0.027
(6R)-L-erytho-5,6,7,8-tetrahydrobiopterin
-
TPH1 fusion protein with maltose-binding protein
0.039
(6R)-L-erytho-5,6,7,8-tetrahydrobiopterin
-
TPH expressed in Pichia pastoris
0.146
(6R)-L-erytho-5,6,7,8-tetrahydrobiopterin
-
TPH1, in vitro transcription and translation product
0.281
(6R)-L-erytho-5,6,7,8-tetrahydrobiopterin
-
TPH2, in vitro transcription and translation product
0.0075
L-tryptophan
-
TPH as fusion protein with maltose-binding protein expressed in Escherichia coli
0.0132
L-tryptophan
0.02 mM ferrous ammonium, 0.5 mM (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin, 30°C
0.0282
L-tryptophan
pH 7.0, 30°C, recombinant wild-type TPH2 fusion enzyme
0.0449
L-tryptophan
pH 7.0, 30°C, recombinant phosphorylated wild-type TPH2
0.0545
L-tryptophan
pH 7.0, 30°C, recombinant non-phosphorylated wild-type TPH2
0.0147
tetrahydrobiopterin
pH 7.0, 30°C, recombinant mutant P449R fusion enzyme
0.0217
tetrahydrobiopterin
pH 7.0, 30°C, recombinant wild-type TPH2 fusion enzyme
0.0249
tetrahydrobiopterin
pH 7.0, 30°C, recombinant mutant R441H fusion enzyme
0.0289
tetrahydrobiopterin
pH 7.0, 30°C, recombinant detagged mutant R441H
0.0351
tetrahydrobiopterin
pH 7.0, 30°C, recombinant non-phosphorylated wild-type TPH2
0.0423
tetrahydrobiopterin
pH 7.0, 30°C, recombinant phosphorylated wild-type TPH2
0.0518
tetrahydrobiopterin
pH 7.0, 30°C, recombinant detagged mutant P449R
0.0684
tetrahydrobiopterin
pH 7.0, 30°C, recombinant detagged wild-type TPH2
additional information
additional information
kinetic mechanism of isozyme TPH1
-
additional information
additional information
kinetic mechanism of isozyme TPH1
-
additional information
additional information
-
1.2% O2 with 0.2 mM 2-amino-4-hydroxy-6-methyl-5,6,7,8-tetrahydropteridine, 7.1% O2 with 0.4 mM 2-amino-4-hydroxy-6,7-dimethyl-5,6,7,8-tetrahydropteridine
-
additional information
additional information
-
isozymes TPH1 and TPH2 kinetics, overview
-
additional information
additional information
isozymes TPH1 and TPH2 kinetics, overview
-
additional information
additional information
kinetic mechanism of isozyme TPH2
-
additional information
additional information
kinetic mechanism of isozyme TPH2
-
additional information
additional information
kinetics of phosphorylated and non-phosphorylated wild-type and mutant enzymes
-
additional information
additional information
-
kinetics of phosphorylated and non-phosphorylated wild-type and mutant enzymes
-
additional information
additional information
-
kinetics of wild-type isozyme TPH1, overview
-
additional information
additional information
-
kinetics of wild-type isozyme TPH2 and of TPH2 deletion mutants, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0727
L-phenylalanine
0.02 mM ferrous ammonium, 0.5 mM (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin, 30°C
0.0026
1,10-phenanthroline
-
vs. 2-amino-4-hydroxy-6-methyl-5,6,7,8-tetrahydropteridine
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00005
4-(4-amino-6-[methyl[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)-L-phenylalanine
Homo sapiens
-
0.000026
4-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)-L-phenylalanine
Homo sapiens
-
0.000044
4-(4-amino-6-[[(1S)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)-L-phenylalanine
Homo sapiens
-
0.000014
4-(4-amino-6-[[(4'-methylbiphenyl-4-yl)methyl]amino]-1,3,5-triazin-2-yl)-L-phenylalanine
Homo sapiens
-
0.00012
4-(4-amino-6-[[4-(trifluoromethyl)benzyl]amino]-1,3,5-triazin-2-yl)-L-phenylalanine
Homo sapiens
-
0.00061
4-[4-(methylamino)-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl]-L-phenylalanine
Homo sapiens
-
0.00032
4-[4-amino-6-(2,2,2-trifluoro-1-naphthalen-2-ylethoxy)-1,3,5-triazin-2-yl]-L-phenylalanine
Homo sapiens
-
0.00016
4-[4-amino-6-([[4'-(trifluoromethyl)biphenyl-4-yl]methyl]amino)-1,3,5-triazin-2-yl]-L-phenylalanine
Homo sapiens
-
0.000024
4-[4-amino-6-[(1-biphenyl-4-ylethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
Homo sapiens
-
0.000055
4-[4-amino-6-[(1-methyl-1-naphthalen-2-ylethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
Homo sapiens
-
0.00015
4-[4-amino-6-[(1-naphthalen-2-ylpropyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
Homo sapiens
-
0.000019
4-[4-amino-6-[(1-tricyclo[3.3.1.1(3,7)]dec-1-ylethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
Homo sapiens
-
0.00033
4-[4-amino-6-[(2,2,2-trifluoro-1-naphthalen-2-ylethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
Homo sapiens
-
0.00025
4-[4-amino-6-[(2-methyl-1-naphthalen-2-ylpropyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
Homo sapiens
-
0.0001
4-[4-amino-6-[(3,4-dimethylbenzyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
Homo sapiens
-
0.00012
4-[4-amino-6-[(3-methyl-1-naphthalen-2-ylbutyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
Homo sapiens
-
0.00015
4-[4-amino-6-[(4-phenoxybenzyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
Homo sapiens
-
0.000007
4-[4-amino-6-[(biphenyl-2-ylmethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
Homo sapiens
-
0.000038
4-[4-amino-6-[(biphenyl-3-ylmethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
Homo sapiens
-
0.00006
4-[4-amino-6-[(biphenyl-4-ylmethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
Homo sapiens
-
0.00012
4-[4-amino-6-[(cyclohexylmethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
Homo sapiens
-
0.000024
4-[4-amino-6-[(naphthalen-2-ylmethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
Homo sapiens
-
0.00156
4-[4-morpholin-4-yl-6-[(naphthalen-2-ylmethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
Homo sapiens
-
0.00019
4-[4-[(1-naphthalen-2-ylethyl)amino]-1,3,5-triazin-2-yl]-L-phenylalanine
Homo sapiens
-
0.000974
4-([(E)-amino[([1,1'-biphenyl]-2-yl)amino]methylidene]carbamoyl)-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000028
4-([(E)-amino[([2-(piperidin-1-yl)-6-[(propan-2-yl)oxy]phenyl]methyl)amino]methylidene]carbamoyl)-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.00001
4-([(E)-amino[([2-(piperidin-1-yl)-6-[2-(trifluoromethyl)phenoxy]phenyl]methyl)amino]methylidene]carbamoyl)-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000014
4-([(E)-amino[([2-(piperidin-1-yl)-6-[3-(trifluoromethyl)phenoxy]phenyl]methyl)amino]methylidene]carbamoyl)-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000006
4-([(E)-amino[([2-(piperidin-1-yl)-6-[4-(trifluoromethyl)phenoxy]phenyl]methyl)amino]methylidene]carbamoyl)-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.02
4-[(diaminomethylidene)carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.011036
4-[[(E)-amino(benzylamino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.001844
4-[[(E)-amino([[2-(1H-1,2,4-triazol-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000501
4-[[(E)-amino([[2-(1H-pyrazol-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000011
4-[[(E)-amino([[2-(2-azabicyclo[2.2.1]heptan-2-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000015
4-[[(E)-amino([[2-(2-chlorophenoxy)-6-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.00001
4-[[(E)-amino([[2-(2-methoxyphenoxy)-6-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000011
4-[[(E)-amino([[2-(2-methylphenoxy)-6-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000015
4-[[(E)-amino([[2-(2-methylpiperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000335
4-[[(E)-amino([[2-(2H-1,2,3-triazol-2-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000025
4-[[(E)-amino([[2-(3,5-dimethylpiperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000045
4-[[(E)-amino([[2-(3-azabicyclo[3.1.0]hexan-3-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000006
4-[[(E)-amino([[2-(3-chlorophenoxy)-6-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000006
4-[[(E)-amino([[2-(3-methoxyphenoxy)-6-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000666
4-[[(E)-amino([[2-(3-methyl-1H-pyrazol-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000008
4-[[(E)-amino([[2-(3-methylphenoxy)-6-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.00002
4-[[(E)-amino([[2-(3-methylpiperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000038
4-[[(E)-amino([[2-(4-benzylpiperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000011
4-[[(E)-amino([[2-(4-chlorophenoxy)-6-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000106
4-[[(E)-amino([[2-(4-hydroxypiperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000016
4-[[(E)-amino([[2-(4-methoxyphenoxy)-6-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000033
4-[[(E)-amino([[2-(4-methoxypiperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.005107
4-[[(E)-amino([[2-(4-methyl-1H-imidazol-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000015
4-[[(E)-amino([[2-(4-methylphenoxy)-6-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000054
4-[[(E)-amino([[2-(4-phenylpiperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000019
4-[[(E)-amino([[2-(azepan-1-yl)-6-methoxyphenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000013
4-[[(E)-amino([[2-(azepan-1-yl)-6-phenoxyphenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000016
4-[[(E)-amino([[2-(azepan-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000129
4-[[(E)-amino([[2-(azetidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000053
4-[[(E)-amino([[2-(cyclobutyloxy)-6-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.00003
4-[[(E)-amino([[2-(cyclohexyloxy)-6-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000099
4-[[(E)-amino([[2-(diethylamino)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000106
4-[[(E)-amino([[2-(morpholin-4-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000007
4-[[(E)-amino([[2-(piperidin-1-yl)-5-(1,3-thiazol-2-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000011 - 0.000017
4-[[(E)-amino([[2-(piperidin-1-yl)-6-(trifluoromethyl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
0.000022
4-[[(E)-amino([[2-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000032
4-[[(E)-amino([[2-(pyrrolidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000058
4-[[(E)-amino([[2-(thiomorpholin-4-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000033
4-[[(E)-amino([[2-chloro-6-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000043
4-[[(E)-amino([[2-ethoxy-6-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000018
4-[[(E)-amino([[2-methoxy-6-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000012
4-[[(E)-amino([[2-methyl-6-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000026
4-[[(E)-amino([[2-phenoxy-6-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000034
4-[[(E)-amino([[3-(piperidin-1-yl)[1,1'-biphenyl]-2-yl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000066
4-[[(E)-amino([[3-chloro-2-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000035
4-[[(E)-amino([[3-methoxy-2-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000046
4-[[(E)-amino([[3-methyl-2-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000014
4-[[(E)-amino([[4-(piperidin-1-yl)[1,1'-biphenyl]-3-yl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000074
4-[[(E)-amino([[4-chloro-2-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000061
4-[[(E)-amino([[4-methoxy-2-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000069
4-[[(E)-amino([[4-methyl-2-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000016
4-[[(E)-amino([[5-chloro-2-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000022
4-[[(E)-amino([[5-methoxy-2-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000025
4-[[(E)-amino([[5-methyl-2-(piperidin-1-yl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.001625
4-[[(E)-amino[[([1,1'-biphenyl]-2-yl)methyl](methyl)amino]methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000165
4-[[(E)-amino[[([1,1'-biphenyl]-2-yl)methyl]amino]methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000405
4-[[(E)-amino[[([1,1'-biphenyl]-3-yl)methyl]amino]methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.0022
4-[[(E)-amino[[([1,1'-biphenyl]-4-yl)methyl]amino]methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000061
4-[[(E)-amino[[2-([1,1'-biphenyl]-2-yl)ethyl]amino]methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000599
4-[[(E)-amino[[3-([1,1'-biphenyl]-2-yl)propyl]amino]methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.002014
4-[[(E)-[[([1,1'-biphenyl]-2-yl)methyl]amino](methylamino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000011
4-[[(E)-amino([[2-(piperidin-1-yl)-6-(trifluoromethyl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
0.000017
4-[[(E)-amino([[2-(piperidin-1-yl)-6-(trifluoromethyl)phenyl]methyl]amino)methylidene]carbamoyl]-L-phenylalanine
Homo sapiens
-
pH and temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.296
-
TPH as fusion protein with maltose-binding protein expressed in Escherichia coli
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
TPH1; North European Caucasians, healthy persons and major depression patients, isozyme TPH1
UniProt
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
in vivo predominantly localized to normal and malignant melanocytes
-
human small cell lung carcinoma cell line, SHP-77 cells preferentially express TPH1 over TPH2 mRNA
additional information
TPH1 is expressed predominantly during the late developmental stage in the brain
dorsal and median raphe nuclei, in the dorsal raphe nucleus there are more serotonin neurons and more neuronal TPH2 expression postmortem in depressed suicides. Depressed suicides have 26.5% more TPH2 grain density per neuron in the DRN compared with matched controls
additional information
TPH1 mRNA is mainly expressed in the pineal gland and the periphery
additional information
TPH1 mRNA is mainly expressed in the pineal gland and the periphery
additional information
analysis of TPH2 expression in brain tissues, overview
additional information
-
TPH1 is found in the periphery and pineal gland whereas TPH2 is expressed specifically in the central nervous system
additional information
TPH2 mRNA is preferentially expressed in the brain and in the peripheral myenteric neurons in the gut
additional information
TPH2 mRNA is preferentially expressed in the brain and in the peripheral myenteric neurons in the gut
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
serveral single nucleotide polymorphisms are associated with depression, suicidal behavior and bipolar disorder
metabolism
-
tryptophan hydroxylase 1 is the rate limiting enzyme in the biosynthesis off serotonin
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). TPH1_HUMAN
444
0
50985
Swiss-Prot
other Location (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
tetramer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
phosphoprotein
-
phosphorylation of TPH2 at Ser19 by calmodulin-dependent protein kinase II activates the enzyme
phosphoprotein
TPH2 is phosphorylated by protein kinase A at Ser19 and Ser104, and by Ca2+/calmodulin dependent protein kinase II at Ser19, phosphorylation at Ser19 activates TPH2 by about 30%, Ser19 is phosphorylated to a stoichiometry of up to 50% in HEK-293 cells expressing TPH2, overview, in vivo phosphorylation in transiently transfected HEK-293 cells occurs with Ser19 phosphorylation stoichiometry of maximally 0.5 mol of phosphate/mol of enzyme subunit in resting cells, which is increasable by cell activation with okadaic acid, overview
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
compound 4-(4-amino-6-[[(1R)-1-naphthalen-2-ylethyl]amino]-1,3,5-triazin-2-yl)-L-phenylalanine co-crystallized with TPH1
sitting drop vapor diffusion method, X-ray crystal structure of a truncated functional form of enzyme (DELTANH102-DELTACOOH402) with the bound cofactor analogue 7,8-dihydro-L-biopterin
modeled structure based on the known crystal structures of phenylalanine hydroxylase and tyrosine hydroxylase
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A218C
interaction between gene TPH1 218Ato C or rs1800532 polymorphism and gender in determining plasma TRP whereby presence of the 218C allele, in women, is associated with markedly reduced plasma tryptophan levels, overview
A328V
moderate loss-of-function effects in the catalytic and oligomerization domains
A779C
naturally occuring polymorphism in intron 7 of TPH1 is associated with alcoholic offenders
D479E
moderate loss-of-function effects in the catalytic and oligomerization domains
L36P
properties affecting the regulatory domain are indistinguishable from the wild-type, severe alterations in secondary structure
L36V
properties affecting the regulatory domain are indistinguishable from the wild-type
P206S
moderate loss-of-function effects in the catalytic and oligomerization domains, severe alterations in secondary structure, reduced stability
R303W
has severely reduced solubility and is completely inactive, alteration in net charge
R441H
moderate loss-of-function effects in the catalytic and oligomerization domains, alteration in net charge
R55C
properties affecting the regulatory domain are indistinguishable from the wild-type, alteration in net charge
S41Y
properties affecting the regulatory domain are indistinguishable from the wild-type
A218C
-
a naturally occuring polymorphism associated with borderline personality disorder diagnosis, but not with suicidal behaviour, genotyping, overview
C164A/G170A
-
mutations represent differences between the human and chimpanzee enzyme, activity similar to wild-type
C164A/G170A/Q468R
-
mutations represent differences between the human and chimpanzee enzyme and a polymorphism at position 468 present in chimpanzees but not in humans. 1.4fold activity compared to wild-type
delta1-150
-
deletion of the N-terminal regulatory domain. Increased solubility when expressed in Escherichia coli.
delta1-150/421-444
-
deletion of the N-terminal regulatory domain and the C-terminal tetramerisation domain. Increased solubility when expressed in Escherichia coli. The mutant protein shows a 2fold increase of the Km for L-tryptophan and a 3fold decrease of the Km for (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
F313W
P206S
a naturyll occuring rare, non-synonymous single nucleotide polymorphism rs17110563 showing significant association with bipolar disorder, reduced thermal stability and solubility of the mutated enzyme compared to the wild-type enzyme
P449R
R441H
S104A
site-directed mutagenesis of a phosphorylation site, the mutant is similarly activated by protein 14-3-3 as the wild-type enzyme
S104E
site-directed mutagenesis of a phosphorylation site, the mutant is not activated by protein 14-3-3 in contrast to the wild-type enzyme
S19A
S19E
site-directed mutagenesis of a phosphorylation site, the mutant is not activated by protein 14-3-3 in contrast to the wild-type enzyme
additional information
F313W
-
F313W mutant shows no preference for tryptophan over phenylalanine as a substrate
P449R
site-directed mutagenesis, the TPH2 genetic variant, shows comparable catalytic activity (Vmax) and solubility relative to the wild type, but has decreased thermal stability
R441H
reduced solubility compared to the wild-type enzyme and reduced thermal stability. The mutant shows a 2fold lower Km for (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
R441H
site-directed mutagenesis, the TPH2 genetic variant, shows had decreased activity, solubility and stability compared to the wild-type enzyme
S19A
site-directed mutagenesis of a phosphorylation site, the mutant is similarly activated by protein 14-3-3 as the wild-type enzyme
S19A
-
site-directed mutagenesis, the mutant is not phpsphorylated by calmodulin-dependent protein kinase II and not activates, but basal activity and catalytic function is unaltered
additional information
A218C is a naturally occuring polymorphism in TPH1, genotyping in Korean population with major depressive disorder patients, remission rate to citalopram treatment was worse in MDD subjects with the TPH1 A/A and A/C genotypes than in those with the TPH1 C/C genotype, overview
additional information
-
A218C is a naturally occuring polymorphism in TPH1, genotyping in Korean population with major depressive disorder patients, remission rate to citalopram treatment was worse in MDD subjects with the TPH1 A/A and A/C genotypes than in those with the TPH1 C/C genotype, overview
additional information
G703T and C218A are naturally occuring polymorphisms, genotyping of TPH1 and TPH2 in correlation to alcohol abuse, overview
additional information
genotyping, in a particular group of stress-induced depression patients isozyme TPH1 appears to be more relevant to MD pathogenesis than isozyme TPH2, overview
additional information
genotyping, in a particular group of stress-induced depression patients isozyme TPH1 appears to be more relevant to MD pathogenesis than isozyme TPH2, overview
additional information
-
genotyping, in a particular group of stress-induced depression patients isozyme TPH1 appears to be more relevant to MD pathogenesis than isozyme TPH2, overview
additional information
specific activity is decreased for all mutations in the catalytic and oligomerization domains of TPH2. All TPH2 mutants appear to be more soluble in HEK-293 cells than in Escherichia coli, all variants are expressed as intact fusion proteins at high levels in Escherichia coli and are cleaved by tobacco etch virus protease
additional information
-
specific activity is decreased for all mutations in the catalytic and oligomerization domains of TPH2. All TPH2 mutants appear to be more soluble in HEK-293 cells than in Escherichia coli, all variants are expressed as intact fusion proteins at high levels in Escherichia coli and are cleaved by tobacco etch virus protease
additional information
a naturally occuring mutation in exon 6, g.22879A-G, a single nucleotide polymorphism, causes truncation of the enzyme to the native short form of brain-specific isozyme TPH2, which causes impaired serotonin transmission and depression, phenotype, overview
additional information
-
a naturally occuring mutation in exon 6, g.22879A-G, a single nucleotide polymorphism, causes truncation of the enzyme to the native short form of brain-specific isozyme TPH2, which causes impaired serotonin transmission and depression, phenotype, overview
additional information
additive effects of serotonin transporter and tryptophan hydroxylase-2 gene variation on neural correlates of affective processing, isolation and analysis of a serotonergic gene polymorphism related to brain affective processing is the tryptophan hydroxylase-2 gene TPH2, TPH2 rs4570625 genotyping, behavioural phenotypes, overview
additional information
construction of a chimeric protein HA-TPH2-(1-41)-TPH1 composed of the first 41 amino acids of TPH2 appended to the N terminus of TPH1, the expression level of the chimeric protein is significantly decreased compared with TPH1 in HEK-293 and PC-12 cell lines and is more similar to that of TPH2
additional information
-
construction of various deletion mutants of TPH2: DN44, DC17, DC19,and DC51. Removal of 44 amino acids from the N-terminus of TPH2 results in a 3-4fold increased Vmax, which indicates a strong inhibitory function of this part on the enzymes activity. Deletion mutants DC17, DC19and DC51, which lack the putative C-terminal leucine zipper tetramerization domain, exist as monomeric enzymes
additional information
-
determination and analysis of single nucleotide polymorphisms in Japanese subjects, rs10741734, rs211102, rs10488683, rs9633898, rs1800532 and rs4537731, genotyping, analysis of correlations with schizophrenia in a case-control association study, and meta-analysis, no significant associations between the polymorphisms or haplotypes of TPH1 and schizophrenia in the Japanese subjects, but possible involvement of the TPH1 218A allele in susceptibility to schizophrenia, overview
additional information
determination and analysis of TPH2 polymorphisms rs10748185, rs2129575, rs1386495, rs1386494, and rs7305115 in terms of genotype, allele, and haplotype-based associations, neither single marker nor haplotype-based analysis shows significant associations between TPH2 and MD, genotyping, in this particular group of stress-induced depression patients TPH1 appears to be more relevant to MD pathogenesis than TPH2, overview
additional information
determination and analysis of TPH2 polymorphisms rs10748185, rs2129575, rs1386495, rs1386494, and rs7305115 in terms of genotype, allele, and haplotype-based associations, neither single marker nor haplotype-based analysis shows significant associations between TPH2 and MD, genotyping, in this particular group of stress-induced depression patients TPH1 appears to be more relevant to MD pathogenesis than TPH2, overview
additional information
-
determination and analysis of TPH2 polymorphisms rs10748185, rs2129575, rs1386495, rs1386494, and rs7305115 in terms of genotype, allele, and haplotype-based associations, neither single marker nor haplotype-based analysis shows significant associations between TPH2 and MD, genotyping, in this particular group of stress-induced depression patients TPH1 appears to be more relevant to MD pathogenesis than TPH2, overview
additional information
determination of several common and rare genetic variations, single nucleotide polymorphisms, in the TPH2 gene, e.g. of rs11178997 in the 5'-associated haplotype block, through a sequential sequencing and SNP-based genotyping, contribution of TPH2 genetic variability to the aetiology of bipolar affective disorder, BPAD, phenotypes, overview
additional information
-
determination of several common and rare genetic variations, single nucleotide polymorphisms, in the TPH2 gene, e.g. of rs11178997 in the 5'-associated haplotype block, through a sequential sequencing and SNP-based genotyping, contribution of TPH2 genetic variability to the aetiology of bipolar affective disorder, BPAD, phenotypes, overview
additional information
-
effects of TPH2 mutations on their heterologous expression levels, solubility, thermal stability, secondary structure, and catalytic properties, overview
additional information
effects of TPH2 mutations on their heterologous expression levels, solubility, thermal stability, secondary structure, and catalytic properties, overview
additional information
gene TPH2, screening for naturally occuring polymorphisms associated with behavioural properties, e.g. attention, and intelligence, overview
additional information
genotyping of naturally occuring single nucleotide polymorphisms of TPH2 in brain tissues, identification of 27 mutations, the mutations causing allelicexpression imbalance are associated with depressiona nd suicide, overview
additional information
-
genotyping of naturally occuring single nucleotide polymorphisms of TPH2 in brain tissues, identification of 27 mutations, the mutations causing allelicexpression imbalance are associated with depressiona nd suicide, overview
additional information
genotyping of TPH2 in depressive patients, the single nucleotide polymorphisms rs4448731 and rs4641527 significantly predict suicide, along with cluster B personality disorders and family history of suicide, overview
additional information
-
genotyping of TPH2 in depressive patients, the single nucleotide polymorphisms rs4448731 and rs4641527 significantly predict suicide, along with cluster B personality disorders and family history of suicide, overview
additional information
naturally occuring single nucleotide polymorphisms rs4570625, rs1386494, rs10897346 and rs1487278 are associated with major depression and the patients carrying these mutations respond to therapy, determination of clinical and molecular predictors, overview
additional information
-
naturally occuring single nucleotide polymorphisms rs4570625, rs1386494, rs10897346 and rs1487278 are associated with major depression and the patients carrying these mutations respond to therapy, determination of clinical and molecular predictors, overview
additional information
-
polymorphism rs11178997 of the TPH2 promoter significantly reduces TPH2 transcriptional activity by 7% in SHP-77 cells. In contrast, no significant differences in promoter activity are observed for the G- and T-alleles of rs4570625. Reduced binding of the transcription factor POU3F2, i.e. Brn-2 or N-Oct-3, to the A-allele occur with the polymorphism rs11178997, while overexpression of POU3F2 results in a robust activation of the TPH2 promoter by about 2.7fold, functional assays of TPH2 regulatory region variants, overview
additional information
screening for TPH2 polymorphisms in Han Chinese subjects, genotyping, haplotype frequency and association analysis, naturally occuring polymorphisms of TPH2 are A90G in the 5'-UTR of exon 1, C2755A in exon 2, C10662T in intron 4, G26270A in intron 5, G33775A in intron 6, G40237A in exon 7, A83610T in exon 9, and G93329A in the 3'-UTR of exon 11, overview
additional information
screening for TPH2 polymorphisms in Han Chinese subjects, genotyping, haplotype frequency and association analysis, naturally occuring polymorphisms of TPH2 are A90G in the 5'-UTR of exon 1, C2755A in exon 2, C10662T in intron 4, G26270A in intron 5, G33775A in intron 6, G40237A in exon 7, A83610T in exon 9, and G93329A in the 3'-UTR of exon 11, overview
additional information
-
screening for TPH2 polymorphisms in Han Chinese subjects, genotyping, haplotype frequency and association analysis, naturally occuring polymorphisms of TPH2 are A90G in the 5'-UTR of exon 1, C2755A in exon 2, C10662T in intron 4, G26270A in intron 5, G33775A in intron 6, G40237A in exon 7, A83610T in exon 9, and G93329A in the 3'-UTR of exon 11, overview
additional information
single nucleotide polymorphism, linkage disequilibrium, and haplotype studies on 353 alcohol-dependent patients of whom 102 individuals have a history of at least one suicide attempt and 305 healthy controls with 20 single nucleotide polymorphisms covering the entire gene region of TPH2. Neither single single nucleotide polymorphism nor haplotype analysis detect significant associations with alcohol dependence and/or suicidal behavior among alcohol-dependent patients, overview
additional information
-
single nucleotide polymorphism, linkage disequilibrium, and haplotype studies on 353 alcohol-dependent patients of whom 102 individuals have a history of at least one suicide attempt and 305 healthy controls with 20 single nucleotide polymorphisms covering the entire gene region of TPH2. Neither single single nucleotide polymorphism nor haplotype analysis detect significant associations with alcohol dependence and/or suicidal behavior among alcohol-dependent patients, overview
additional information
the naturally occuring functional promoter polymorphism TPH2-703 G/T of the tryptophan hydroxylase 2 gene is involved in prefrontal and parietal regions are activated during working memory tasks, genotype groups of the -703 G/T: a significantly stronger activation of the TT genotype carriers in BA 6, BA 46, and BA 40 is visible in contrast to the GTand GG groups, no significant differences between the genotype groups with respect to age or gender, overview
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
3-amino-2-benzyl-7-nitro-4-(2-quinolyl)-1,2-dihydroisoquinolin-1-one strongly stabilizes the protein during denaturation by heat. Half-denaturation temperature increases from 55.5°C to 64.4°C in the presence of 0.1 mM 3-amino-2-benzyl-7-nitro-4-(2-quinolyl)-1,2-dihydroisoquinolin-1-one.
-
high-affinity binding of purified PKA-phosphorylated TPH2 bound to the 14-3-3 proteins gamma , epsilon and BMH1 causes increased enzyme stability
in the presence of L-Phe, the enzyme dimer displays significantly increased half-life
-
The half-life of the protein is 30 min at 37°C, while the N-terminal and the N- and C-terminal truncated mutants exhibit half-lives of 203 min and 147 min, respectively
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant GST-tagged TPH2 from Escherichia coli by glutathione affinity chromatography
-
recombinant His6-MBP-fusion TPH2 wild-type and mutants from Escherichia coli by affinity chromatography, fusion protein cleavage, and gel filtration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
catalytic domain of TPH1 (DELTA1-99 TPH1 DELTA414-444) amplified, the cTPH/NdeI/XhoI gene cloned into the pET26 vector, expressed in Escherichia coli BL21(DE3) cells
gene TPH1 genotyping of female and male Caucasian patients with major depression
gene TPH1, DNA and amino acid sequence determination and analysis, genotyping in Han Chinese subjects
isozyme TPH1, DNA and amino acid sequence determination and analysis, TPH1 is located on chromosome 11, expression analysis
TPH1, genotyping in Korean population with major depressive disorder patients, overview
wild-type and missense mutants from vector pETM41 for 6 x His-MBP-TPH2 expression in Escherichia coli BL21-Codon Plus (DE3)-RIPL cells, and vector pcDNA5/FRT, for expression in a cell free expression system and in HEK-293 cells. Rabbit reticulocyte lysate used to express TPH2 wild-type and missense variants
a His-tagged version and a maltose binding protein-fusion protein are expressed in Escherichia coli
-
catalytic domain of TPH2 (DELTA1-145 TPH2 DELTA460-490) amplified, the cTPH/NdeI/XhoI gene cloned into the pET26 vector, expressed in Escherichia coli BL21(DE3) cells
DNA and amio acid sequence determination and analysis of short and long isozymes TPH2, expression analysis in brain
expression as maltose-binding protein fusion protein in Escherichia coli BL21 (DE3)
expression in escherichia coli and Pichia pastoris, His-Patch-thioredoxin-TPH, 6His-TPH or as a fusion protein with maltose-binding protein
-
expression in Escherichia coli BL21-CodonPlus(DE3)-RIL as His-tag fusion protein
-
expression in RN46A cells, transcriptional activity of the rat TPH2 promoter, overview
expression of wild-type and mutant isozymes TPH2 in Escherichia coli as His-tagged enzyme, and of wild-type TPH2 in HEK-293 cells
expression of wild-type isozyme TPH2, and of TPH2 deletion mutants in COS7 cells
-
gene TPH1, genotyping in Japanese population of healthy persons and shizophrenia patients
-
gene TPH2 is located on chromosome 12q15 comprising 11 exons, DNA and amino acid determination and analysis, genotyping of a population of alcohol-dependent patients of Caucasian origin from southern Germany
gene TPH2 located on the long arm of chromosome 12 at 12q21.1, DNA and amino acid sequence determination and analysis, genotyping
gene TPH2, DNA and amino acid sequence determination and analysis of wild-type and mutant genes, genotyping, overview
gene TPH2, DNA and amino acid sequence determination and analysis, genotyping
gene TPH2, DNA and amino acid sequence determination and analysis, genotyping in Han Chinese subjects
gene TPH2, DNA and amino acid sequence determination and analysis, genotyping, overview
gene TPH2, DNA and amino acid sequence determination, identification of a transcription element in the TPH2 promoter, a bipartite variant interrupted by a 6-base insertion, that resembles the binding motif for RE-1 silencer of transcription, i.e. REST, also known as NRSF transcription factor, permutations of the motif reveal considerable flexibility in the juxtaposition of the two halves of bipartite NRSE, expressionin rat C6-glioma cells, quantitative reverse transcription-PCR expression analysis, sequence comparisons
gene tph2, expression of TPH2 wild-type and mutants in Escherichia coli and in HEK-293 cells
genes TPH1 and TPH2, expression analysis, overview, expression of wild-type TPH1 and TPH2 in rat PC-12 cells, in vitro transcription and translation using reticulocyte lysate, the TPH2 extended N-terminal domain plays a role in modulating the enzyme expression, expression of mutant HA-TPH2-(1-41)-TPH1 in HEK-293 amd PC-12 cells, the expression level of the chimeric protein is significantly decreased compared with TPH1 in both cell lines and is more similar to that of TPH2, the N-terminal regulatory determinant is transferable, overview
isozyme TPH2, DNA and amino acid sequence determination and analysis, TPH2 is on chromosome 12, expression analysis
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
enzyme expression is reduced in ganglionic bowel in those affected by pre-operative Hirschsprung's-associated enterocolitis compared to those without Hirschsprung's-associated enterocolitis and healthy controls
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
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
medicine
additional information
enhancement of L-tryptophan hydroxylation activity of L-phenylalanine 4-hydroxylase from Chromobacterium violaceum using information on the crystal structures of aromatic amino acid hydroxylases including TPH
medicine
-
the two distinct serotonin systems in the brain (TPH2) and in the periphery (TPH1) can be targeted independently by pharmacological agents and new therapeutical options are available for psychiatric diseases on one side and disorders of haemostasis and the immune system on the other side
medicine
-
TPH2 is a good candidate gene for 5-hydroxytryptophan related psychiatric diseases such as bipolar affective disorders. The two distinnct serotonin systems in the brain (TPH2) and in the periphery (TPH1) can be targeted independently by pharmacological agents and new therapeutical options are available for psychiatric diseases on one side and disorders of haemostasis and the immune system on the other side
medicine
-
the serotonin transporter gene-linked promoter region 5-HTTLPR and tryptophan hydroxylase-2 genes act in concert to modulate the clinical response to citalopram among children and adolescents with depression and/or anxiety disorders
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Hosoda, S.; Nakamura, W.; Takatsuki, K.
Properties of tryptophan hydroxylase from human carcinoid tumor
Biochim. Biophys. Acta
482
27-34
1977
Homo sapiens
Kowlessur, D.; Kaufman, S.
Cloning and expression of recombinant human pineal tryptophan hydroxylase in Escherichia coli: purification and characterization of the cloned enzyme
Biochim. Biophys. Acta
1434
317-330
1999
Homo sapiens
McKinney, J.; Teigen, K.; Froystein, N.A.; Salauen, C.; Knappskog, P.M.; Haavik, J.; Martinez, A.
Conformation of the substrate and pterin cofactor bound to human tryptophan hydroxylase. Important role of Phe313 in substrate specificity
Biochemistry
40
15591-15601
2001
Homo sapiens
Martinez, A.; Knappskog, P.M.; Haavik, J.
A structural approach into human tryptophan hydroxylase and its implications for the regulation of serotonin biosynthesis
Curr. Med. Chem.
8
1077-1091
2001
Homo sapiens
Daubner, S.C.; Moran, G.R.; Fitzpatrick, P.F.
Role of tryptophan hydroxylase Phe313 in determining substrate specificity
Biochem. Biophys. Res. Commun.
292
639-641
2002
Homo sapiens
Walther, D.J.; Bader, M.
A unique central tryptophan hydroxylase isoform
Biochem. Pharmacol.
66
1673-1680
2003
Homo sapiens
Wang, L.; Erlandsen, H.; Haavik, J.; Knappskog, P.M.; Stevens, R.C.
Three-dimensional structure of human tryptophan hydroxylase and its implications for the biosynthesis of the neutrotransmitters serotonin and melatonin
Biochemistry
41
12569-12574
2002
Homo sapiens (P17752), Homo sapiens
Slominski, A.; Pisarchik, A.; Johansson, O.; Jing, C.; Semak, I.; Slugocki, G.; Wortsman, J.
Tryptophan hydroxylase expression in human skin cells
Biochim. Biophys. Acta
1639
80-86
2003
Homo sapiens
McKinney, J.; Knappskog, P.M.; Haavik, J.
Different properties of the central and peripheral forms of human tryptophan hydroxylase
J. Neurochem.
92
311-320
2005
Homo sapiens
McKinney, J.; Knappskog, P.M.; Pereira, J.; Ekern, T.; Toska, K.; Kuitert, B.B.; Levine, D.; Gronenborn, A.M.; Martinez, A.; Haavik, J.
Expression and purification of human tryptophan hydroxylase from Escherichia coli and Pichia pastoris
Protein Expr. Purif.
33
185-194
2004
Homo sapiens
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
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, Gallus gallus, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus
Winge, I.; McKinney, J.A.; Knappskog, P.M.; Haavik, J.
Characterization of wild-type and mutant forms of human tryptophan hydroxylase 2
J. Neurochem.
100
1648-1657
2007
Homo sapiens, Homo sapiens (Q8IWU9)
Ogawa, S.; Ichinose, H.
Effect of metals and phenylalanine on the activity of human tryptophan hydroxylase-2: comparison with that on tyrosine hydroxylase activity
Neurosci. Lett.
401
261-265
2006
Homo sapiens (Q8IWU9), Homo sapiens
Hong, K.W.; Sugawara, Y.; Hasegawa, H.; Hayasaka, I.; Hashimoto, R.; Ito, S.; Inoue-Murayama, M.
A new gain-of-function allele in chimpanzee tryptophan hydroxylase 2 and the comparison of its enzyme activity with that in humans and rats
Neurosci. Lett.
412
195-200
2007
Callithrix jacchus, Gorilla gorilla, Homo sapiens, Macaca fuscata, Pan troglodytes, Pongo pygmaeus, Rattus norvegicus, Cephalopachus bancanus, Otolemur crassicaudatus, Hylobates agilis, Mandrillus sphinx
Gacek, P.; Conner, T.S.; Tennen, H.; Kranzler, H.R.; Covault, J.
Tryptophan hydroxylase 2 gene and alcohol use among college students
Addict. Biol.
13
440-448
2008
Homo sapiens (P17752)
Wilson, S.T.; Stanley, B.; Brent, D.A.; Oquendo, M.A.; Huang, Y.Y.; Mann, J.J.
The tryptophan hydroxylase-1 A218C polymorphism is associated with diagnosis, but not suicidal behavior, in borderline personality disorder
Am. J. Med. Genet.
150B
202-208
2008
Homo sapiens
Lin, Y.M.; Chao, S.C.; Chen, T.M.; Lai, T.J.; Chen, J.S.; Sun, H.S.
Association of functional polymorphisms of the human tryptophan hydroxylase 2 gene with risk for bipolar disorder in Han Chinese
Arch. Gen. Psychiatry
64
1015-1024
2007
Homo sapiens (P17752), Homo sapiens (Q8IWU9), Homo sapiens
Winge, I.; McKinney, J.A.; Ying, M.; DSantos, C.S.; Kleppe, R.; Knappskog, P.M.; Haavik, J.
Activation and stabilization of human tryptophan hydroxylase 2 by phosphorylation and 14-3-3 binding
Biochem. J.
410
195-204
2008
Homo sapiens (Q8IWU9), Homo sapiens
Scheuch, K.; Lautenschlager, M.; Grohmann, M.; Stahlberg, S.; Kirchheiner, J.; Zill, P.; Heinz, A.; Walther, D.J.; Priller, J.
Characterization of a functional promoter polymorphism of the human tryptophan hydroxylase 2 gene in serotonergic raphe neurons
Biol. Psychiatry
62
1288-1294
2007
Homo sapiens, Rattus norvegicus (Q8CGU9)
Lopez de Lara, C.; Brezo, J.; Rouleau, G.; Lesage, A.; Dumont, M.; Alda, M.; Benkelfat, C.; Turecki, G.
Effect of tryptophan hydroxylase-2 gene variants on suicide risk in major depression
Biol. Psychiatry
62
72-80
2007
Homo sapiens (Q8IWU9), Homo sapiens
Reuter, M.; Esslinger, C.; Montag, C.; Lis, S.; Gallhofer, B.; Kirsch, P.
A functional variant of the tryptophan hydroxylase 2 gene impacts working memory: A genetic imaging study
Biol. Psychol.
79
111-117
2008
Homo sapiens (Q8IWU9)
Canli, T.; Congdon, E.; Todd Constable, R.; Lesch, K.P.
Additive effects of serotonin transporter and tryptophan hydroxylase-2 gene variation on neural correlates of affective processing
Biol. Psychol.
79
118-125
2008
Homo sapiens (Q8IWU9)
Cichon, S.; Winge, I.; Mattheisen, M.; Georgi, A.; Karpushova, A.; Freudenberg, J.; Freudenberg-Hua, Y.; Babadjanova, G.; Van Den Bogaert, A.; Abramova, L.I.; Kapiletti, S.; Knappskog, P.M.; McKinney, J.; Maier, W.; Jamra, R.A.; Schulze, T.G.; Schumacher, J.; Propping, P.; Rietschel, M.; Haavik, J.
Brain-specific tryptophan hydroxylase 2 (TPH2): a functional Pro206Ser substitution and variation in the 5'-region are associated with bipolar affective disorder
Hum. Mol. Genet.
17
87-97
2008
Homo sapiens (Q8IWU9), Homo sapiens
Gizatullin, R.; Zaboli, G.; Joensson, E.G.; Asberg, M.; Leopardi, R.
The tryptophan hydroxylase (TPH) 2 gene unlike TPH-1 exhibits no association with stress-induced depression
J. Affect. Disord.
107
175-179
2008
Homo sapiens (P17752), Homo sapiens (Q8IWU9), Homo sapiens
Porter, R.J.; Mulder, R.T.; Joyce, P.R.; Miller, A.L.; Kennedy, M.
Tryptophan hydroxylase gene (TPH1) and peripheral tryptophan levels in depression
J. Affect. Disord.
109
209-212
2008
Homo sapiens (P17752), Homo sapiens
Patel, P.D.; Bochar, D.A.; Turner, D.L.; Meng, F.; Mueller, H.M.; Pontrello, C.G.
Regulation of tryptophan hydroxylase-2 gene expression by a bipartite RE-1 silencer of transcription/neuron restrictive silencing factor (REST/NRSF) binding motif
J. Biol. Chem.
282
26717-26724
2007
Rattus norvegicus (Q8CGU9), Homo sapiens (Q8IWU9), Homo sapiens
Murphy, K.L.; Zhang, X.; Gainetdinov, R.R.; Beaulieu, J.M.; Caron, M.G.
A regulatory domain in the N terminus of tryptophan hydroxylase 2 controls enzyme expression
J. Biol. Chem.
283
13216-13224
2008
Homo sapiens (Q8IWU9)
Reuter, M.; Ott, U.; Vaitl, D.; Hennig, J.
Impaired executive control is associated with a variation in the promoter region of the tryptophan hydroxylase 2 gene
J. Cogn. Neurosci.
19
401-408
2007
Homo sapiens (Q8IWU9)
Tenner, K.; Walther, D.; Bader, M.
Influence of human tryptophan hydroxylase 2 N- and C-terminus on enzymatic activity and oligomerization
J. Neurochem.
102
1887-1894
2007
Homo sapiens
Kuhn, D.M.; Sakowski, S.A.; Geddes, T.J.; Wilkerson, C.; Haycock, J.W.
Phosphorylation and activation of tryptophan hydroxylase 2: identification of serine-19 as the substrate site for calcium, calmodulin-dependent protein kinase II
J. Neurochem.
103
1567-1573
2007
Homo sapiens
Lenicov, F.R.; Lemonde, S.; Czesak, M.; Mosher, T.M.; Albert, P.R.
Cell-type specific induction of tryptophan hydroxylase-2 transcription by calcium mobilization
J. Neurochem.
103
2047-2057
2007
Rattus norvegicus, Homo sapiens (Q8IWU9)
Nakamura, K.; Hasegawa, H.
Developmental role of tryptophan hydroxylase in the nervous system
Mol. Neurobiol.
35
45-54
2007
Mus musculus (P17532), Mus musculus (Q8CGV2), Homo sapiens (P17752), Homo sapiens (Q8IWU9)
Lim, J.E.; Pinsonneault, J.; Sadee, W.; Saffen, D.
Tryptophan hydroxylase 2 (TPH2) haplotypes predict levels of TPH2 mRNA expression in human pons
Mol. Psychiatry
12
491-501
2007
Homo sapiens (Q8IWU9), Homo sapiens
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 (Q8IWU9), Homo sapiens, Mus musculus, Mus musculus C57BL/6, Rattus norvegicus (Q8CGU9)
Bach-Mizrachi, H.; Underwood, M.D.; Tin, A.; Ellis, S.P.; Mann, J.J.; Arango, V.
Elevated expression of tryptophan hydroxylase-2 mRNA at the neuronal level in the dorsal and median raphe nuclei of depressed suicides
Mol. Psychiatry
13
507-13, 465
2008
Homo sapiens (Q8IWU9)
Haghighi, F.; Bach-Mizrachi, H.; Huang, Y.Y.; Arango, V.; Shi, S.; Dwork, A.J.; Rosoklija, G.; Sheng, H.T.; Morozova, I.; Ju, J.; Russo, J.J.; Mann, J.J.
Genetic architecture of the human tryptophan hydroxylase 2 gene: existence of neural isoforms and relevance for major depression
Mol. Psychiatry
13
813-820
2008
Homo sapiens (Q8IWU9), Homo sapiens
Zill, P.; Preuss, U.W.; Koller, G.; Bondy, B.; Soyka, M.
SNP- and haplotype analysis of the tryptophan hydroxylase 2 gene in alcohol-dependent patients and alcohol-related suicide
Neuropsychopharmacology
32
1687-1694
2007
Homo sapiens (Q8IWU9), Homo sapiens
Watanabe, Y.; Nunokawa, A.; Kaneko, N.; Someya, T.
The tryptophan hydroxylase 1 (TPH1) gene and risk of schizophrenia: a moderate-scale case-control study and meta-analysis
Neurosci. Res.
59
322-326
2007
Homo sapiens
Tzvetkov, M.V.; Brockmoeller, J.; Roots, I.; Kirchheiner, J.
Common genetic variations in human brain-specific tryptophan hydroxylase-2 and response to antidepressant treatment
Pharmacogenet. Genomics
18
495-506
2008
Homo sapiens (Q8IWU9), Homo sapiens
Ham, B.; Lee, B.; Paik, J.; Kang, R.; Choi, M.; Choi, I.; Lee, M.
Association between the tryptophan hydroxylase-1 gene A218C polymorphism and citalopram antidepressant response in a Korean population
Prog. Neuropsychopharmacol. Biol. Psychiatry
31
104-107
2007
Homo sapiens (P17752), Homo sapiens
Kino, K.; Hara, R.; Nozawa, A.
Enhancement of L-tryptophan 5-hydroxylation activity by structure-based modification of L-phenylalanine 4-hydroxylase from Chromobacterium violaceum
J. Biosci. Bioeng.
108
184-189
2009
Homo sapiens (P17752)
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
Mus musculus, Homo sapiens (P17752)
McKinney, J.A.; Turel, B.; Winge, I.; Knappskog, P.M.; Haavik, J.
Functional properties of missense variants of human tryptophan hydroxylase 2
Hum. Mutat.
30
787-794
2009
Homo sapiens (P17752), Homo sapiens
Windahl, M.; Boesen, J.; Karlsen, P.; Christensen, H.
Expression, purification and enzymatic characterization of the catalytic domains of human tryptophan hydroxylase isoforms
Protein J.
28
400-406
2009
Homo sapiens (P17752), Homo sapiens (Q8IWU9), Homo sapiens
Calvo, A.C.; Scherer, T.; Pey, A.L.; Ying, M.; Winge, I.; McKinney, J.; Haavik, J.; Thoeny, B.; Martinez, A.
Effect of pharmacological chaperones on brain tyrosine hydroxylase and tryptophan hydroxylase 2
J. Neurochem.
114
853-863
2010
Homo sapiens
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
Rotberg, B.; Kronenberg, S.; Carmel, M.; Frisch, A.; Brent, D.; Zalsman, G.; Apter, A.; Weizman, A.
Additive effects of 5-HTTLPR (serotonin transporter) and tryptophan hydroxylase 2 G-703T gene polymorphisms on the clinical response to citalopram among children and adolescents with depression and anxiety disorders
J. Child Adolesc. Psychopharmacol.
23
117-122
2013
Homo sapiens
Zhang, S.; Hinck, C.S.; Fitzpatrick, P.F.
The regulatory domain of human tryptophan hydroxylase 1 forms a stable dimer
Biochem. Biophys. Res. Commun.
476
457-461
2016
Homo sapiens
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
Goldberg, D.R.; De Lombaert, S.; Aiello, R.; Bourassa, P.; Barucci, N.; Zhang, Q.; Paralkar, V.; Stein, A.J.; Valentine, J.; Zavadoski, W.
Discovery of acyl guanidine tryptophan hydroxylase-1 inhibitors
Bioorg. Med. Chem. Lett.
26
2855-2860
2016
Homo sapiens
Tidemand, K.; Christensen, H.; Hoeck, N.; Harris, P.; Boesen, J.; Peters, G.
Stabilization of tryptophan hydroxylase 2 by L-phenylalanine-induced dimerization
FEBS Open Bio
6
987-999
2016
Homo sapiens
Petrassi, M.; Barber, R.; Be, C.; Beach, S.; Cox, B.; DSouza, A.M.; Duggan, N.; Hussey, M.; Fox, R.; Hunt, P.; Jarai, G.; Kosaka, T.; Oakley, P.; Patel, V.; Press, N.; Rowlands, D.; Scheufler, C.; Schmidt, O.; Srinivas, H.; Turner, M.; Turner, R.; Westwick, J.; Wolfreys, A.; Pathan, N.; Watson, S.; Thomas, M.
Identification of a novel allosteric inhibitory site on tryptophan hydroxylase 1 enabling unprecedented selectivity over all related hydroxylases
Front. Pharmacol.
8
240
2017
Homo sapiens
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