1.14.16.4: tryptophan 5-monooxygenase
This is an abbreviated version!
For detailed information about tryptophan 5-monooxygenase, go to the full flat file.
Word Map on EC 1.14.16.4
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1.14.16.4
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serotonin
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serotonergic
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raphe
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5-hydroxytryptamine
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monoamine
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dorsal
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dopamine
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neurotransmitter
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hippocampus
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antidepressant
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reuptake
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5-hydroxytryptophan
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anxiety
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psychiatric
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midbrain
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striatum
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hypothalamus
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neurochemical
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5-hydroxyindoleacetic
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mood
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enterochromaffin
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neurotransmission
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5-hiaa
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p-chlorophenylalanine
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fluoxetine
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pineal
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brainstem
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alpha-methyl-p-tyrosine
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monoaminergic
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5,7-dihydroxytryptamine
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analysis
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methamphetamine
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autoreceptors
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slc6a4
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immobility
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pargyline
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n-acetylserotonin
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neostriatal
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5-httlpr
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medicine
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citalopram
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antidepressant-like
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carcinoid
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biopterins
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impulsivity
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oxidase-a
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tetrahydropterins
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fenfluramine
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impulsive
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8-oh-dpat
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5-hydroxyindole
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drug development
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3,4-methylenedioxymethamphetamine
- 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
Reaction
Synonyms
hTPH2, indoleacetic acid-5-hydroxylase, L-tryptophan 5-hydroxylase, L-tryptophan hydroxylase, oxygenase, tryptophan 5-mono-, peripheral tryptophan hydroxylase, PTMO, putative tryptophan monooxygenase, TH2, TPH, TPH-1, TPH-2, TPH1, TPH2, TRpOH, tryptophan 5-hydroxylase, tryptophan 5-monooxygenase, tryptophan hydroxylase, tryptophan hydroxylase 1, tryptophan hydroxylase 2, tryptophan hydroxylase I, tryptophan hydroxylase isoform 1, tryptophan hydroxylase isoform 2, tryptophan hydroxylase isoform2, tryptophan hydroxylase type I, tryptophan hydroxylase-1, tryptophan hydroxylase-2, tryptophan-5-hydroxylase
ECTree
1.14.16.4 tryptophan 5-monooxygenaseAdvanced search results
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results (Engineering
Engineering on EC 1.14.16.4 - tryptophan 5-monooxygenase
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PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
A218C
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
C164A/G170A
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mutations represent differences between the human and chimpanzee enzyme, activity similar to wild-type
C164A/G170A/Q468R
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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
D479E
moderate loss-of-function effects in the catalytic and oligomerization domains
delta1-150
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deletion of the N-terminal regulatory domain. Increased solubility when expressed in Escherichia coli.
delta1-150/421-444
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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
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
P449R
R303W
has severely reduced solubility and is completely inactive, alteration in net charge
R441H
R55C
properties affecting the regulatory domain are indistinguishable from the wild-type, alteration in net charge
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
S41Y
properties affecting the regulatory domain are indistinguishable from the wild-type
C110S/C112S/C162S/C234S/C248S/C296S/C315S/C355S/C365S/C394S/C404S/C408S/C476S
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all 13 cysteine residues mutated
C110S/C162S/C234S/C248S/C296S/C355S/C365S/C394S/C404S/C408S/C476S
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mutant protein containing a single cysteine residue within the regulatory domain (Cys112) and within the catalytic core domain (Cys315)
C1473G
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naturally occuring polymorphism of gene Tph2, C57Bl/6 and 129X1/SvJ mice are homozygous for the 1473C allele, whereas DBA/2 and BALB/cJ mice are homozygous for the 1473G allele, comparison of pulmonary hypertension and vascular remodeling of haplotypes, overview
C162S/C234S/C248S/C296S/C315S/C355S/C365S/C394S/C404S/C408S/C476S
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all cysteine residues of the catalytic core domain mutated
C315S/C355S/C365S/C394S/C404S/C408S/C476S
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seven C-terminal-most cysteines mutated
G1473C
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naturally occuring polymorphism, citalopram raises basal extracellular serotonin levels in DBA/2J, DBA/2N and BALB/c mice carrying the 1473G allele, but not in C57BL/6J and C57BL/6N mice carrying the 1473C allele, overview
P447R
the C1473G naturally occuring polymorphism in gene tph2 is the main factor mediating the genetically defined variability of tryptophan hydroxylase-2 activity in the mouse brain, phenotypes, overview
Q486R
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determination of a naturally occuring single nucleotide polymorphism at the exon 11 coding region that resulted in amino acid substitutions in the C-terminal domain, determination of allele frequency, the mutation is a gain -of-function mutation leading to 20% increased activity, comparison to rat and human TPH2s, overview
F241I
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drop in interaction energy of 4%, reduction in interaction for the isoleucine mutation may cause a reduction in the production of 5-hydroxy-L-tryptophan, and in turn, a reduction in serotonin. This may lead to onset of symptoms, such as anxiety, depression, and OCD
F241L
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retains the interaction energy necessary to keep protein function
F241Q
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retains the interaction energy necessary to keep protein function
F241Y
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retains the interaction energy necessary to keep protein function
additional information
A218C
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a naturally occuring polymorphism associated with borderline personality disorder diagnosis, but not with suicidal behaviour, genotyping, overview
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
F313W
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F313W mutant shows no preference for tryptophan over phenylalanine as a substrate
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
P206S
moderate loss-of-function effects in the catalytic and oligomerization domains, severe alterations in secondary structure, reduced stability
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
R441H
moderate loss-of-function effects in the catalytic and oligomerization domains, alteration in net charge
S19A
site-directed mutagenesis of a phosphorylation site, the mutant is similarly activated by protein 14-3-3 as the wild-type enzyme
S19A
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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
TPH knockout, by RNAi, animals shows reduced serotonin levels compared to wild-type animals
additional information
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TPH knockout, by RNAi, animals shows reduced serotonin levels compared to wild-type animals
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
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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
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
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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
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
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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
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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
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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
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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
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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
G703T and C218A are naturally occuring polymorphisms, genotyping of TPH1 and TPH2 in correlation to alcohol abuse, 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
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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
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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, 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
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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
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
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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
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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
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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
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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
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
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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
C74A and G223A are naturally occuring, nonsynonymous single nucleotide polymorphisms
additional information
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C74A and G223A are naturally occuring, nonsynonymous single nucleotide polymorphisms
additional information
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construction of Tph1 knockout mutant mice, distal pulmonary vessel muscularization is less marked in Tph1-/- than in wild-type mice
additional information
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generation of Tph1 homozygous null mice from a 129S5/SvEvBrd and C57BL/6J hybrid background
additional information
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mice deficient in TPH1 and serotonin exhibit a reduced risk of thrombosis and thromboembolism, development of antithrombotic hammerhead miniribozymes with site-specific cleavage activity against short synthetic Tph1 RNA substrates targeting peripheral tryptophan hydroxylase, method development and evaluation, overview
additional information
polymorphism rs11178997 of the TPH2 promoter significantly reduces TPH2 transcriptional activity by 22% in primary serotonergic neurons. 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. The human TPH2 promoter is active in rat serotonergic raphe neurons
