Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

1.14.16.4

Official Name

tryptophan 5-monooxygenase

Name from literature

Tryptophan hydroxylase

Pathway from literature

the biosynthesis of serotonin (5-HT)/ melatonin biosynthesis

Pathway from KEGG

Amino Acid Metabolism; Tryptophan metabolism; map00380

Organisms

Human (9606)

Genome localization

11p15.3-p14[7166 ], 12q21.1[121278 ],

Comments

The active centre contains mononuclear iron(II). The enzyme is activated by phosphorylation, catalysed by a Ca2+-activated protein kinase. The 4a-hydroxytetrahydrobiopterin formed can dehydrate to 6,7-dihydrobiopterin, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydrobiopterin can be enzymically reduced back to tetrahydrobiopterin, by EC 1.5.1.34 (6,7-dihydropteridine reductase), or slowly rearranges into the more stable compound 7,8-dihydrobiopterin.

Rate-limiting Description

"OBJECTIVE: Tryptophan hydroxylase is the rate-limiting enzyme in the biosynthesis of serotonin." (10327914)

"Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of serotonin, however functional variants have not been reported from the coding sequence of this gene." (10483053)

Regulatory Information

Upstream transcription factor

5978;7534;5568

Regulatory type

Detail

key enzyme;

"The expression of serta in raphe and ventral posterior tuberculum overlapped with the location of serotonin and expression of tryptophan hydroxylase, which is a key enzyme for serotonin synthesis." (16498236)

phosphorylation;PKA(5568)

"purified TPH2 WT (wild-type) was activated by 30% after PKA phosphorylation and studies of the mutant enzymes showed that enzyme activation was mainly due to phosphorylation at Ser(19)" (17973628)

phosphorylation;PKA(5568)

"purified TPH2 WT (wild-type) was activated by 30% after PKA phosphorylation and studies of the mutant enzymes showed that enzyme activation was mainly due to phosphorylation at Ser(19)" (17973628#18339632)

transcriptional factor;REST(5978)

"This sequence census method was then used to map in vivo binding of the neuron-restrictive silencer factor (NRSF; also known as REST, for repressor element-1 silencing transcription factor) to 1946 locations in the human genome." (17540862)

phosphorylation;

P17752

phosphorylation;

Q8IWU9

phosphorylation;

P17752:from_uniprot:58_Phosphoserine; by PKA

phosphorylation;

Q8IWU9:from_uniprot:382_Phosphoserine

phosphorylation;

Q8IWU9:from_uniprot:392_Phosphoserine

transcriptional factor;YWHAZ(7534)

"Demonstration of the phosphorylation-dependent interaction of tryptophan hydroxylase with the 14-3-3 protein." (8101440)

Gene ontology

Gene ontology

GO:0016597 (F) amino acid binding [Q8IWU9, P17752 ];
GO:0004510 (F) tryptophan 5-monooxygenase activity [Q8IWU9, P17752 ];
GO:0055114 (P) oxidation reduction [Q8IWU9, P17752 ];
GO:0006587 (P) serotonin biosynthetic process from tryptophan [Q8IWU9, P17752 ];
GO:0005506 (F) iron ion binding [Q8IWU9, P17752 ];

Tissue expression

Tissue From HPRD

Pons [01846 ];
Pineal gland [01846 ];
Uterine myometrium [01846 ];
Adrenal gland [01846 ];
Gastric mucosa [01846 ];
Skin fibroblast [01846 ];
Skin [01846 ];
Enteroendocrine cell [01846 ];
Ileum [01846 ];
Melanocyte [01846 ];
Mast cell [01846 ];
Brain [09594 ];
Keratinocyte [01846 ];
Muscle [01846 ];
Pituitary gland [01846 ];

Tissue specificity

Brain specific [Q8IWU9 ];

Isoform 2 seems to be less widely expressed than isoform 1 [P17752 ];

Disease relevance

Disease

Genetic variation in TPH2 may influence susceptibility to major depressive disorder (MDD) [MIM:608516] [Q8IWU9 ];

Links

SwissProt

P17752; Q8IWU9

Entrez Gene

121278; 7166

HPRD

01846; 09594



  Copyright 2009, Center for Bioinformatics 
  Last Modified: 2009-03-24  
  Design by Zhao Min