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Literature summary for 1.14.16.4 extracted from
- Activation and stabilization of human tryptophan hydroxylase 2 by phosphorylation and 14-3-3 binding (2008), Biochem. J., 410, 195-204.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| 14-3-3 protein | activates the phosphorylated TPH2 | Homo sapiens | |
| DTT | - |
Homo sapiens |  |
| 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 | Homo sapiens |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| expression of wild-type and mutant isozymes TPH2 in Escherichia coli as His-tagged enzyme, and of wild-type TPH2 in HEK-293 cells | Homo sapiens |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| S104A | site-directed mutagenesis of a phosphorylation site, the mutant is similarly activated by protein 14-3-3 as the wild-type enzyme | Homo sapiens |
| 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 | Homo sapiens |
| S19A | site-directed mutagenesis of a phosphorylation site, the mutant is similarly activated by protein 14-3-3 as the wild-type enzyme | Homo sapiens |
| 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 | Homo sapiens |
| S306A | site-directed mutagenesis of a putative phosphorylation site | Homo sapiens |
| S306E | site-directed mutagenesis of a putative phosphorylation site | Homo sapiens |
| S99A | site-directed mutagenesis of a putative phosphorylation site | Homo sapiens |
| S99E | site-directed mutagenesis of a putative phosphorylation site | Homo sapiens |
General Stability
| General Stability | Organism |
|---|---|
| high-affinity binding of purified PKA-phosphorylated TPH2 bound to the 14-3-3 proteins gamma , epsilon and BMH1 causes increased enzyme stability | Homo sapiens |
KM Value [mM]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| additional information | - |
additional information | kinetics of phosphorylated and non-phosphorylated wild-type and mutant enzymes | Homo sapiens | |
| 0.0351 | - |
tetrahydrobiopterin | pH 7.0, 30°C, recombinant non-phosphorylated wild-type TPH2 | Homo sapiens | |
| 0.0423 | - |
tetrahydrobiopterin | pH 7.0, 30°C, recombinant phosphorylated wild-type TPH2 | Homo sapiens | |
| 0.0449 | - |
L-tryptophan | pH 7.0, 30°C, recombinant phosphorylated wild-type TPH2 | Homo sapiens | |
| 0.0545 | - |
L-tryptophan | pH 7.0, 30°C, recombinant non-phosphorylated wild-type TPH2 | Homo sapiens | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| L-tryptophan + tetrahydrobiopterin + O2 | Homo sapiens | rate-limiting step in the synthesis of serotonin | 5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | Q8IWU9 | isozyme TPH2 | - |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| 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 | Homo sapiens |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| recombinant His-tagged wild-type and mutant TPH2s from Escherichia coli | Homo sapiens |
Specific Activity [micromol/min/mg]
| Specific Activity Minimum [µmol/min/mg] | Specific Activity Maximum [µmol/min/mg] | Comment | Organism |
|---|---|---|---|
| additional information | - |
- |
Homo sapiens |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| L-tryptophan + tetrahydrobiopterin + O2 | - |
Homo sapiens | 5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin | - |
? | |
| L-tryptophan + tetrahydrobiopterin + O2 | rate-limiting step in the synthesis of serotonin | Homo sapiens | 5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| TPH2 | - |
Homo sapiens |
| tryptophan hydroxylase 2 | - |
Homo sapiens |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 30 | - |
assay at | Homo sapiens |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 7 | - |
assay at | Homo sapiens |
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