TPH1

Protein identityUniProt · HPA

UniProt accession

P17752

Gene

TPH1

Ensembl

ENSG00000129167

Chromosome

11

Canonical length

444 aa

Protein class

Enzymes, FDA approved drug targets, Metabolic proteins, Predicted intracellular proteins

Subcellular location

Cytosol

Quaternary structure

Homotetramer

OverviewNCBI Gene

This gene encodes a member of the aromatic amino acid hydroxylase family. The encoded protein catalyzes the first and rate limiting step in the biosynthesis of serotonin, an important hormone and neurotransmitter. Mutations in this gene have been associated with an elevated risk for a variety of diseases and disorders, including schizophrenia, somatic anxiety, anger-related traits, bipolar disorder, suicidal behavior, addictions, and others.[provided by RefSeq, Apr 2009]

Canonical amino-acid sequenceUniProt

444 residues, UniProt reviewed canonical sequence.

>P17752|TPH1
     1  MIEDNKENKD HSLERGRASL IFSLKNEVGG LIKALKIFQE KHVNLLHIES RKSKRRNSEF
    61  EIFVDCDINR EQLNDIFHLL KSHTNVLSVN LPDNFTLKED GMETVPWFPK KISDLDHCAN
   121  RVLMYGSELD ADHPGFKDNV YRKRRKYFAD LAMNYKHGDP IPKVEFTEEE IKTWGTVFQE
   181  LNKLYPTHAC REYLKNLPLL SKYCGYREDN IPQLEDVSNF LKERTGFSIR PVAGYLSPRD
   241  FLSGLAFRVF HCTQYVRHSS DPFYTPEPDT CHELLGHVPL LAEPSFAQFS QEIGLASLGA
   301  SEEAVQKLAT CYFFTVEFGL CKQDGQLRVF GAGLLSSISE LKHALSGHAK VKPFDPKITC
   361  KQECLITTFQ DVYFVSESFE DAKEKMREFT KTIKRPFGVK YNPYTRSIQI LKDTKSITSA
   421  MNELQHDLDV VSDALAKVSR KPSI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TPH1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.27

Highest tissue expression

19 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TPH1.

Disease | AutoantibodyPubMed

Conditions in which antibodies against TPH1 are reported. Each links to that disease's full target list.

• Polyendocrinopathies, Autoimmune 3

ReferencesPubMed · IEDB

Publications for TPH1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.93

gnomAD pLI

0

gnomAD missense Z

0.73

DepMap mean gene effect

-0.08

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• bone remodeling
• mammary gland alveolus development
• platelet degranulation
• positive regulation of fat cell differentiation
• serotonin biosynthetic process
• regulation of hemostasis
• serotonin biosynthetic process from tryptophan

Molecular functions

• iron ion binding
• tryptophan 5-monooxygenase activity

Cellular components

• cytosol
• neuron projection

Protein domainsUniProt · Pfam · InterPro

• Aromatic amino acid hydroxylase
• ACT domain
• Tryptophan 5-monooxygenase
• Aromatic amino acid hydroxylase, iron/copper binding site
• Tyrosine 3-monooxygenase-like
• Aromatic amino acid hydroxylase, C-terminal
• Aromatic amino acid monoxygenase, C-terminal domain superfamily
• Aromatic amino acid hydroxylase superfamily
• Tryptophan 5-hydroxylase, catalytic domain
• ACT-like domain
• Biopterin-dependent aromatic amino acid hydroxylase

KeywordsUniProt

• Iron
• Metal-binding
• Monooxygenase
• Oxidoreductase
• Phosphoprotein
• Serotonin biosynthesis
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of TPH1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• DNAJC12