TH

Protein identityUniProt · HPA

UniProt accession

P07101

Gene

TH

Ensembl

ENSG00000180176

Chromosome

11

Canonical length

528 aa

Protein class

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

Subcellular location

Cytosol

Quaternary structure

Homotetramer

OverviewNCBI Gene

The protein encoded by this gene is involved in the conversion of tyrosine to dopamine. It is the rate-limiting enzyme in the synthesis of catecholamines, hence plays a key role in the physiology of adrenergic neurons. Mutations in this gene have been associated with autosomal recessive Segawa syndrome. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

528 residues, UniProt reviewed canonical sequence.

>P07101|TH
     1  MPTPDATTPQ AKGFRRAVSE LDAKQAEAIM VRGQGAPGPS LTGSPWPGTA APAASYTPTP
    61  RSPRFIGRRQ SLIEDARKER EAAVAAAAAA VPSEPGDPLE AVAFEEKEGK AVLNLLFSPR
   121  ATKPSALSRA VKVFETFEAK IHHLETRPAQ RPRAGGPHLE YFVRLEVRRG DLAALLSGVR
   181  QVSEDVRSPA GPKVPWFPRK VSELDKCHHL VTKFDPDLDL DHPGFSDQVY RQRRKLIAEI
   241  AFQYRHGDPI PRVEYTAEEI ATWKEVYTTL KGLYATHACG EHLEAFALLE RFSGYREDNI
   301  PQLEDVSRFL KERTGFQLRP VAGLLSARDF LASLAFRVFQ CTQYIRHASS PMHSPEPDCC
   361  HELLGHVPML ADRTFAQFSQ DIGLASLGAS DEEIEKLSTL YWFTVEFGLC KQNGEVKAYG
   421  AGLLSSYGEL LHCLSEEPEI RAFDPEAAAV QPYQDQTYQS VYFVSESFSD AKDKLRSYAS
   481  RIQRPFSVKF DPYTLAIDVL DSPQAVRRSL EGVQDELDTL AHALSAIG

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TH 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)

0.33

Highest tissue expression

186 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TH.

Disease | AllUniProt

Conditions TH is implicated in, by any mechanism.

• Segawa syndrome autosomal recessive (ARSEGS) MIM:605407

Disease | GeneticClinVar

192 pathogenic / likely-pathogenic of 1,236 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Autosomal recessive DOPA responsive dystonia
• Dystonic disorder
• Inborn genetic diseases
• Dystonia 5
• Tyrosine hydroxylase deficiency

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)

0.79

gnomAD pLI

0

gnomAD missense Z

0.56

DepMap mean gene effect

-0.11

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• anatomical structure morphogenesis
• animal organ morphogenesis
• cognition
• dopamine biosynthetic process
• eating behavior
• embryonic camera-type eye morphogenesis
• epinephrine biosynthetic process
• eye photoreceptor cell development
• heart development
• heart morphogenesis
• hyaloid vascular plexus regression
• learning
• locomotory behavior
• mating behavior
• memory
• norepinephrine biosynthetic process
• pigmentation
• regulation of heart contraction
• response to ethanol
• response to hypoxia
• serotonin biosynthetic process
• synaptic transmission, dopaminergic
• visual perception
• dopamine biosynthetic process from tyrosine

Molecular functions

• enzyme binding
• identical protein binding
• iron ion binding
• tyrosine 3-monooxygenase activity

Cellular components

• axon
• cytoplasm
• cytoplasmic side of plasma membrane
• cytoplasmic vesicle
• cytosol
• melanosome membrane
• neuron projection
• nucleus
• perikaryon
• perinuclear region of cytoplasm
• smooth endoplasmic reticulum
• synaptic vesicle

Protein domainsUniProt · Pfam · InterPro

• Aromatic amino acid hydroxylase
• 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
• ACT-like domain
• Biopterin-dependent aromatic amino acid hydroxylase
• Tyrosine 3-monooxygenase
• Tyrosine hydroxylase, conserved site
• Tyrosine 3-monooxygenase, catalytic domain
• Tyrosine 3-monooxygenase-like, ACT domain
• Tyrosine hydroxylase N terminal
• Tyrosine 3-monooxygenase-like, ACT domain

KeywordsUniProt

• Catecholamine biosynthesis
• Cell projection
• Cytoplasm
• Cytoplasmic vesicle
• Dystonia
• Iron
• Metal-binding
• Monooxygenase
• Neurotransmitter biosynthesis
• Nucleus
• Oxidoreductase
• Parkinson disease
• Parkinsonism
• Phosphoprotein
• Synapse

InteractionsUniProt · HPA

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

• NT5DC2