TPH1

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

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)[1] Band 11p15.1 Start 18,017,555 bp[1] End 18,046,269 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7 B3|7 30.43 cM Start 46,294,065 bp[2] End 46,321,961 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) 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 BioGPS 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 Species Human Mouse Entrez 7166 21990 Ensembl ENSG00000129167 ENSMUSG00000040046 UniProt P17752 P17532 RefSeq (mRNA) NM_004179 NM_001136084 NM_001276372 NM_009414 RefSeq (protein) NP_004170 NP_001129556 NP_001263301 NP_033440 Location (UCSC) Chr 11: 18.02 – 18.05 Mb Chr 7: 46.29 – 46.32 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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.

See also

• Tryptophan hydroxylase
• TPH2
• Rs1799913 (A779C): intron related to figural and numeric creativity
• rs1800532 (A218C)