TPH1

TPH1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1MLW, 3HF6, 3HF8, 3HFB, 5J6D
Identifiers
Aliases	TPH1, TPRH, TRPH, tryptophan hydroxylase 1
External IDs	OMIM: 191060; MGI: 98796; HomoloGene: 121565; GeneCards: TPH1; OMA:TPH1 - orthologs
Gene location (Human)
Chr.	Chromosome 11 (human)
End	18,046,269 bp
Gene location (Mouse)
Chr.	Chromosome 7 (mouse)
End	46,321,961 bp
RNA expression pattern
	Top expressed in
	buccal mucosa cell; ; rectum; ; ascending aorta; ; Descending thoracic aorta; ; mucosa of sigmoid colon; ; testicle; ; pylorus; ; tibial arteries; ; jejunal mucosa; ; duodenum;
	Top expressed in
	pineal gland; ; duodenum; ; lactiferous gland; ; pyloric antrum; ; embryo; ; embryo; ; jejunum; ; muscle of thigh; ; left colon; ; extraocular muscle;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	iron ion binding; metal ion binding; monooxygenase activity; tryptophan 5-monooxygenase activity; oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced pteridine as one donor, and incorporation of one atom of oxygen; oxidoreductase activity;
Cellular component	cytoplasm; cytosol; neuron projection;
Biological process	response to immobilization stress; mammary gland alveolus development; serotonin biosynthetic process; negative regulation of ossification; aromatic amino acid family metabolic process; bone remodeling; circadian rhythm; positive regulation of fat cell differentiation; indolalkylamine biosynthetic process;
	Sources:Amigo / QuickGO
Orthologs
	7166
	21990
	ENSG00000129167
	ENSMUSG00000040046
	P17752
	P17532
	NM_004179
	NM_001136084; NM_001276372; NM_009414
	NP_004170
	NP_001129556; NP_001263301; NP_033440
	Wikidata
View/Edit Human	View/Edit Mouse

Tryptophan hydroxylase 1 (TPH1) is an isoenzyme of tryptophan hydroxylase which in humans is encoded by the TPH1 gene.^[5]

TPH1 was first discovered to support serotonin synthesis in 1988 by converting tryptophan into 5-hydroxytryptophan.^[6] It was thought that there only was a single TPH gene until 2003. A second form was found in the mouse (Tph2), rat and human brain (TPH2) and the original TPH was then renamed to TPH1.^[7]

Function

Tryptophan hydroxylases catalyze the biopterin-dependent monooxygenation of tryptophan to 5-hydroxytryptophan (5-HTP), which is subsequently decarboxylated by aromatic amino acid decarboxylase to form the neurotransmitter serotonin (5-hydroxytryptamine or 5-HT). It is the rate-limiting enzyme in the biosynthesis of serotonin.

TPH expression is limited to a few specialized tissues: raphe neurons, pinealocytes, mast cells, mononuclear leukocytes, beta-cells of the islets of Langerhans, and intestinal and pancreatic enterochromaffin cells.^[5]^{[citation needed]}

Clinical significance

Tryptophan hydroxylase is important for synthesizing indoleamine neurotransmitters and related compounds in the body and brain, including serotonin and melatonin. TPH1 is expressed in the body, but not the brain.^[7] Nevertheless, the effect of variations in the TPH1 gene on brain-related variables, such as personality traits and neuropsychiatric disorders, has been studied. For example, one study (1998) found an association between a polymorphism in the gene with impulsive-aggression measures,^[8] while a case-control study (2001) could find no association between polymorphisms and Alzheimer's disease.^[9]

One human mutant of TPH1, A218C found in intron 7, is highly associated with schizophrenia.^[10] Introns are regions of DNA that do not code for the amino acid sequence of a protein and were long considered to be 'junk DNA' lacking purpose. The correlation of an intron mutation with schizophrenia is significant because it suggests that introns have an important role in translation, transcription, or another, possibly unknown, aspect of the production of proteins from DNA.

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000129167 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000040046 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b "Entrez Gene: TPH1 tryptophan hydroxylase 1 (tryptophan 5-monooxygenase)".
^ Finocchiaro LM, Arzt ES, Fernández-Castelo S, Criscuolo M, Finkielman S, Nahmod VE (December 1988). "Serotonin and melatonin synthesis in peripheral blood mononuclear cells: stimulation by interferon-gamma as part of an immunomodulatory pathway". J. Interferon Res. 8 (6): 705–16. doi:10.1089/jir.1988.8.705. PMID 3148005.
^ ^a ^b Walther DJ, Peter JU, Bashammakh S, Hörtnagl H, Voits M, Fink H, Bader M (January 2003). "Synthesis of serotonin by a second tryptophan hydroxylase isoform". Science. 299 (5603): 76. doi:10.1126/science.1078197. PMID 12511643. S2CID 7095712.
^ New AS, Gelernter J, Yovell Y, Trestman RL, Nielsen DA, Silverman J, Mitropoulou V, Siever LJ (1998). "Tryptophan hydroxylase genotype is associated with impulsive-aggression measures: a preliminary study". Am. J. Med. Genet. 81 (1): 13–7. doi:10.1002/(SICI)1096-8628(19980207)81:1<13::AID-AJMG3>3.0.CO;2-O. PMID 9514581.
^ Wang YC, Tsai SJ, Liu TY, Liu HC, Hong CJ (January 2001). "No association between tryptophan hydroxylase gene polymorphism and Alzheimer's disease". Neuropsychobiology. 43 (1): 1–4. doi:10.1159/000054856. PMID 11150890. S2CID 39712696.
^ Allen NC, Bagade S, McQueen MB, Ioannidis JP, Kavvoura FK, Khoury MJ, Tanzi RE, Bertram L (July 2008). "Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database". Nat. Genet. 40 (7): 827–34. doi:10.1038/ng.171. PMID 18583979. S2CID 21772210.

External links

Overview of all the structural information available in the PDB for UniProt: P17752 (Tryptophan 5-hydroxylase 1) at the PDBe-KB.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000129167 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000040046 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] "Entrez Gene: TPH1 tryptophan hydroxylase 1 (tryptophan 5-monooxygenase)".

[pmid3148005-6] Finocchiaro LM, Arzt ES, Fernández-Castelo S, Criscuolo M, Finkielman S, Nahmod VE (December 1988). "Serotonin and melatonin synthesis in peripheral blood mononuclear cells: stimulation by interferon-gamma as part of an immunomodulatory pathway". J. Interferon Res. 8 (6): 705–16. doi:10.1089/jir.1988.8.705. PMID 3148005.

[Walther_2003-7] Walther DJ, Peter JU, Bashammakh S, Hörtnagl H, Voits M, Fink H, Bader M (January 2003). "Synthesis of serotonin by a second tryptophan hydroxylase isoform". Science. 299 (5603): 76. doi:10.1126/science.1078197. PMID 12511643. S2CID 7095712.

[pmid9514581-8] New AS, Gelernter J, Yovell Y, Trestman RL, Nielsen DA, Silverman J, Mitropoulou V, Siever LJ (1998). "Tryptophan hydroxylase genotype is associated with impulsive-aggression measures: a preliminary study". Am. J. Med. Genet. 81 (1): 13–7. doi:10.1002/(SICI)1096-8628(19980207)81:1<13::AID-AJMG3>3.0.CO;2-O. PMID 9514581.

[pmid11150890-9] Wang YC, Tsai SJ, Liu TY, Liu HC, Hong CJ (January 2001). "No association between tryptophan hydroxylase gene polymorphism and Alzheimer's disease". Neuropsychobiology. 43 (1): 1–4. doi:10.1159/000054856. PMID 11150890. S2CID 39712696.

[pmid18583979-10] Allen NC, Bagade S, McQueen MB, Ioannidis JP, Kavvoura FK, Khoury MJ, Tanzi RE, Bertram L (July 2008). "Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database". Nat. Genet. 40 (7): 827–34. doi:10.1038/ng.171. PMID 18583979. S2CID 21772210.

[5]

[1]

[2]

[3]

[4]

[6]

[7]

[8]

[9]

[10]

TPH1

Contents

Function

Clinical significance

See also

References

Further reading

External links