TPH1

Last updated
TPH1
PBB Protein TPH1 image.jpg
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases TPH1 , TPRH, TRPH, tryptophan hydroxylase 1
External IDs OMIM: 191060 MGI: 98796 HomoloGene: 121565 GeneCards: TPH1
Orthologs
SpeciesHumanMouse
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

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

Contents

TPH1 was first discovered to synthesize serotonin in 1988 [6] 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. [7]

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. [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

Related Research Articles

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Aromatic L-amino acid decarboxylase, also known as DOPA decarboxylase (DDC), tryptophan decarboxylase, and 5-hydroxytryptophan decarboxylase, is a lyase enzyme, located in region 7p12.2-p12.1.

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<span class="mw-page-title-main">Tryptophan hydroxylase</span> Class of enzymes

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<span class="mw-page-title-main">TPH2</span> Protein-coding gene in the species Homo sapiens

Tryptophan hydroxylase 2 (TPH2) is an isozyme of tryptophan hydroxylase found in vertebrates. In humans, TPH2 is primarily expressed in the serotonergic neurons of the brain, with the highest expression in the raphe nucleus of the midbrain. Until the discovery of TPH2 in 2003, serotonin levels in the central nervous system were believed to be regulated by serotonin synthesis in peripheral tissues, in which tryptophan hydroxylase is the dominant form.

<span class="mw-page-title-main">Neuropeptide FF receptor 2</span> Protein-coding gene in the species Homo sapiens

Neuropeptide FF receptor 2, also known as NPFF2 is a human protein encoded by the NPFFR2 gene.

<span class="mw-page-title-main">MARK1</span> Protein-coding gene in the species Homo sapiens

Serine/threonine-protein kinase MARK1 is an enzyme that in humans is encoded by the MARK1 gene.

<span class="mw-page-title-main">PHKG1</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Visinin-like protein 1</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">PHOX2A</span> Protein-coding gene in humans

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<span class="mw-page-title-main">SLC22A3</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">ADCY9</span> Protein-coding gene in the species Homo sapiens

Adenylyl cyclase type 9 is an enzyme that in humans is encoded by the ADCY9 gene.

<span class="mw-page-title-main">OMG (gene)</span> Protein-coding gene in the species Homo sapiens

Oligodendrocyte-myelin glycoprotein is a protein that in humans is encoded by the OMG gene.

<span class="mw-page-title-main">Vesicular glutamate transporter 1</span> Protein-coding gene in the species Homo sapiens

Vesicular glutamate transporter 1 (VGLUT1) is a protein that in humans is encoded by the SLC17A7 gene.

<span class="mw-page-title-main">COX6C</span> Protein-coding gene in the species Homo sapiens

Cytochrome c oxidase subunit 6C is an enzyme that in humans is encoded by the COX6C gene.

In genetics, rs1799913, also called A779C, is a gene variation—a single nucleotide polymorphism (SNP)— in the TPH1 gene. It is located in intron 7.

In genetics, rs1800532 (A218C) is a genetic variant. It is a single nucleotide polymorphism in the TPH1 gene and located in intron 7.

<span class="mw-page-title-main">GLUD2</span> Protein-coding gene in humans

Glutamate dehydrogenase 2, mitochondrial, also known as GDH 2, is an enzyme that in humans is encoded by the GLUD2 gene. This dehydrogenase is one of the family of glutamate dehydrogenases that are ubiquitous in life.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000129167 - Ensembl, May 2017
  2. 1 2 3 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.
  5. 1 2 "Entrez Gene: TPH1 tryptophan hydroxylase 1 (tryptophan 5-monooxygenase)".
  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.
  7. 1 2 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.
  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.
  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.
  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.

Further reading

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