TPH2

Protein identityUniProt · HPA

UniProt accession

Q8IWU9

Gene

TPH2

Ensembl

ENSG00000139287

Chromosome

12

Canonical length

490 aa

Protein class

Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Predicted intracellular proteins

OverviewNCBI Gene

This gene encodes a member of the pterin-dependent aromatic 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 may be associated with psychiatric diseases such as bipolar affective disorder and major depression. [provided by RefSeq, Feb 2016]

Canonical amino-acid sequenceUniProt

490 residues, UniProt reviewed canonical sequence.

>Q8IWU9|TPH2
     1  MQPAMMMFSS KYWARRGFSL DSAVPEEHQL LGSSTLNKPN SGKNDDKGNK GSSKREAATE
    61  SGKTAVVFSL KNEVGGLVKA LRLFQEKRVN MVHIESRKSR RRSSEVEIFV DCECGKTEFN
   121  ELIQLLKFQT TIVTLNPPEN IWTEEEELED VPWFPRKISE LDKCSHRVLM YGSELDADHP
   181  GFKDNVYRQR RKYFVDVAMG YKYGQPIPRV EYTEEETKTW GVVFRELSKL YPTHACREYL
   241  KNFPLLTKYC GYREDNVPQL EDVSMFLKER SGFTVRPVAG YLSPRDFLAG LAYRVFHCTQ
   301  YIRHGSDPLY TPEPDTCHEL LGHVPLLADP KFAQFSQEIG LASLGASDED VQKLATCYFF
   361  TIEFGLCKQE GQLRAYGAGL LSSIGELKHA LSDKACVKAF DPKTTCLQEC LITTFQEAYF
   421  VSESFEEAKE KMRDFAKSIT RPFSVYFNPY TQSIEILKDT RSIENVVQDL RSDLNTVCDA
   481  LNKMNQYLGI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TPH2 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)

0.29

Highest tissue expression

0.5 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TPH2.

Disease | AllUniProt

Conditions TPH2 is implicated in, by any mechanism.

• Major depressive disorder (MDD) MIM:608516
• Attention deficit-hyperactivity disorder 7 (ADHD7) MIM:613003

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)

0.85

gnomAD pLI

0

gnomAD missense Z

1

DepMap mean gene effect

-0.16

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• aromatic amino acid metabolic process
• serotonin biosynthetic process

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
• RNA editing
• Serotonin biosynthesis

InteractionsUniProt · HPA

Protein binding partners of TPH2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• DNAJC12