TPH1

Tryptophan hydroxylase 1
PDB rendering based on 1mlw.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1IN9, 1MLW, 3HF6, 3HF8, 3HFB
Identifiers
Symbols	TPH1 ; TPRH; TRPH
External IDs	OMIM: 191060 MGI: 98796 HomoloGene: 121565 ChEMBL: 5689 GeneCards: TPH1 Gene
EC number	1.14.16.4
Gene ontology Molecular function • tryptophan 5-monooxygenase activity • iron ion binding • amino acid binding Cellular component • cytosol • neuron projection Biological process • circadian rhythm • aromatic amino acid family metabolic process • negative regulation of ossification • cellular nitrogen compound metabolic process • response to immobilization stress • serotonin biosynthetic process • small molecule metabolic process • positive regulation of fat cell differentiation • indolalkylamine biosynthetic process • bone remodeling • oxidation-reduction process • mammary gland alveolus development Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7166	21990
Ensembl	ENSG00000129167	ENSMUSG00000040046
UniProt	P17752	P17532
RefSeq (mRNA)	NM_004179	NM_001136084
RefSeq (protein)	NP_004170	NP_001129556
Location (UCSC)	Chr 11: 18.02 – 18.04 Mb	Chr 7: 46.65 – 46.67 Mb
PubMed search	[1]	[2]

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

TPH1 was first discovered to synthesize serotonin in 1988 and was thought that there only was a single TPH gene until 2003, while a second form was found in the mouse (Tph2), rat and human brain (TPH2) and the original TPH was then renamed to TPH1.

Function

Tryptophan hydroxylases catalyze the biopterin-dependent monooxygenation of tryptophan to 5-hydroxytryptophan (5-HTP), which is subsequently decarboxylated 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.

Clinical significance

Tryptophan hydroxylase is important for synthesizing indoleamine neurotransmitters and related compounds in the body and brain, including serotonin, melatonin, tryptamine, N-methyltryptamine, and N,N-dimethyltryptamine. TPH1 is expressed in the body, but not the brain. 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, while a case-control study (2001) could find no association between polymorphisms and Alzheimer's Disease.

One human mutant of TPH1, A218C found in intron 7, is highly associated with schizophrenia. 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.

See also

• Tryptophan hydroxylase
• TPH2
• Rs1799913 (A779C)
• rs1800532 (A218C)