P17289 · TY3H_BOVIN

  • Protein
    Tyrosine 3-monooxygenase
  • Gene
    TH
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Catalyzes the conversion of L-tyrosine to L-dihydroxyphenylalanine (L-Dopa), the rate-limiting step in the biosynthesis of cathecolamines, dopamine, noradrenaline, and adrenaline. Uses tetrahydrobiopterin and molecular oxygen to convert tyrosine to L-Dopa (By similarity).
In addition to tyrosine, is able to catalyze the hydroxylation of phenylalanine and tryptophan with lower specificity (By similarity).
Positively regulates the regression of retinal hyaloid vessels during postnatal development (By similarity).

Catalytic activity

Cofactor

Fe2+ (UniProtKB | Rhea| CHEBI:29033 )

Activity regulation

Inhibited in feedback fashion by the catecholamine neurotransmitters, especially by dopamine in competition with tetrahydrobiopterin. Phosphorylation of several Ser/Thr residues in the N-terminus regulates the catalytic activity. Ser-31 and Ser-40 are readily phosphorylated to activate the catalytic activity. A Cysteine modification induced by N-ethylmaleimide (NEM), inhibits tyrosine 3-monooxygenase activity through the modification of the Cys-170.

Pathway

Catecholamine biosynthesis; dopamine biosynthesis; dopamine from L-tyrosine: step 1/2.

Features

Showing features for binding site, site.

TypeIDPosition(s)Description
Binding site324Fe cation (UniProtKB | ChEBI)
Binding site329Fe cation (UniProtKB | ChEBI)
Binding site369Fe cation (UniProtKB | ChEBI)
Site418Important for substrate specificity

GO annotations

AspectTerm
Cellular Componentaxon
Cellular Componentcytoplasm
Cellular Componentnucleus
Cellular Componentperikaryon
Cellular Componentperinuclear region of cytoplasm
Cellular Componentsynaptic vesicle
Molecular Functioniron ion binding
Molecular Functiontyrosine 3-monooxygenase activity
Biological Processdopamine biosynthetic process from tyrosine
Biological Processheart development
Biological Processhyaloid vascular plexus regression
Biological Processresponse to ethanol
Biological Processresponse to hypoxia

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Tyrosine 3-monooxygenase
  • EC number
  • Alternative names
    • Tyrosine 3-hydroxylase (TH)

Gene names

    • Name
      TH

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Artiodactyla > Ruminantia > Pecora > Bovidae > Bovinae > Bos

Accessions

  • Primary accession
    P17289

Proteomes

Subcellular Location

Nucleus
Cell projection, axon
Cytoplasm
Note: When phosphorylated at Ser-19 shows a nuclear distribution and when phosphorylated at Ser-31 as well at Ser-40 shows a cytosolic distribution (By similarity).
Expressed in dopaminergic axons and axon terminals (By similarity).

Keywords

Phenotypes & Variants

PTM/Processing

Features

Showing features for initiator methionine, chain, modified residue.

TypeIDPosition(s)Description
Initiator methionine1Removed
ChainPRO_00002055602-491Tyrosine 3-monooxygenase
Modified residue19Phosphoserine; by CaMK2
Modified residue31Phosphoserine
Modified residue40Phosphoserine; by CaMK2 and PKA
Modified residue465Phosphoserine

Post-translational modification

Phosphorylated on Ser-19, Ser-31 and Ser-40 by several protein kinases with different site specificities. Phosphorylation at Ser-31 and Ser-40 leads to an increase of TH activity. Phosphorylation at Ser-40 activates the enzyme and also counteracts the feedback inhibition of TH by catecholamines (By similarity).
Phosphorylation of Ser-19 and Ser-31 triggers the proteasomal degradation of TH through the ubiquitin-proteasome pathway (By similarity).
Phosphorylation at Ser-31 facilitates transport of TH from the soma to the nerve terminals via the microtubule network (By similarity).
Phosphorylation at Ser-19 induces the high-affinity binding to the 14-3-3 protein YWHAG; this interaction may influence the phosphorylation and dephosphorylation of other sites (By similarity).
Ser-19 increases the phosphorylation at Ser-40 in a hierarchical manner, leading to increased activity (By similarity).

Keywords

Proteomic databases

PTM databases

Interaction

Subunit

Homotetramer (By similarity).
Interacts (when phosphorylated at Ser-19) with YWHAG; one YWHAG dimer bounds to one TH tetramer this interaction may influence the phosphorylation and dephosphorylation of other sites (By similarity).

Protein-protein interaction databases

Chemistry

Structure

Family & Domains

Sequence similarities

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    491
  • Mass (Da)
    55,123
  • Last updated
    2007-01-23 v5
  • Checksum
    86707712238F12F2
MPTPNAASPQAKGFRRAVSELDAKQAEAIMSPRFVGRRQSLIQDARKEREKAEAAASSSESAEAAAWLERDGEAVLTLLFALPPTRPPALTRAIKVFETFEAHLHHLETRPAQPLRAGSPPLECFVRCEVPGPVVPALLSALRRVAEDVRAAGESKVLWFPRKVSELDKCHHLVTKFDPDLDLDHPGFSDQAYRQRRKLIAEIAFQYKQGDPIPHVEYTAEETATWKEVYSTLRGLYPTHACREHLEAFELLERFCGYREDRIPQLEDVSRFLKERTGFQLRPAAGLLSARDFLASLAFRVFQCTQYIRHASSPMHSPEPECCHELLGHVPMLADRTFAQFSQDIGLASLGVSDEEIEKLSTLYWFTVEFGLCKQNGEVKAYGAGLLSSYGELLHSLSEEPEIRAFDPDAAAVQPYQDQTYQPVYFVSESFSDAKDKLRSYASRIQRPFSVKFDPYTLAIDVLDSPHAIRHALDGVQDEMQALAHALNAIS

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict65-68in Ref. 2; AAA30798
Sequence conflict73in Ref. 2; AAA30798
Sequence conflict83in Ref. 2; AAA30798
Sequence conflict86in Ref. 2; AAA30798
Sequence conflict284in Ref. 2; AAA30798
Sequence conflict321in Ref. 2; AAA30798
Sequence conflict328-330in Ref. 2; AAA30798
Sequence conflict380in Ref. 2; AAA30798
Sequence conflict471in Ref. 2; AAA30798

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
M36794
EMBL· GenBank· DDBJ
AAA30779.1
EMBL· GenBank· DDBJ
mRNA
M36705
EMBL· GenBank· DDBJ
AAA30798.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

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