Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P04177 (TY3H_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 135. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tyrosine 3-monooxygenase

EC=1.14.16.2
Alternative name(s):
Tyrosine 3-hydroxylase
Short name=TH
Gene names
Name:Th
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length498 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Plays an important role in the physiology of adrenergic neurons.

Catalytic activity

L-tyrosine + tetrahydrobiopterin + O2 = L-dopa + 4a-hydroxytetrahydrobiopterin.

Cofactor

Fe2+ ion.

Enzyme regulation

Phosphorylation leads to an increase in the catalytic activity.

Pathway

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

Subunit structure

Homotetramer.

Post-translational modification

In vitro, phosphorylation of Ser-19 increases the rate of Ser-40 phosphorylation, which results in enzyme opening and activation.

Sequence similarities

Belongs to the biopterin-dependent aromatic amino acid hydroxylase family.

Ontologies

Keywords
   Biological processCatecholamine biosynthesis
Neurotransmitter biosynthesis
   LigandIron
Metal-binding
   Molecular functionMonooxygenase
Oxidoreductase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcatecholamine biosynthetic process

Inferred from direct assay PubMed 20025246. Source: RGD

cellular response to alkaloid

Inferred from expression pattern PubMed 18696327. Source: RGD

cellular response to drug

Inferred from expression pattern PubMed 18602388. Source: RGD

cellular response to glucose stimulus

Inferred from expression pattern PubMed 21217063. Source: RGD

cellular response to growth factor stimulus

Inferred from expression pattern PubMed 17306206. Source: RGD

cellular response to manganese ion

Inferred from expression pattern PubMed 19781568. Source: RGD

cellular response to nicotine

Inferred from expression pattern PubMed 20827341. Source: RGD

cerebral cortex development

Inferred from expression pattern PubMed 21295554. Source: RGD

circadian sleep/wake cycle

Inferred from expression pattern PubMed 20980612. Source: RGD

cognition

Inferred from expression pattern PubMed 20096955. Source: RGD

dopamine biosynthetic process from tyrosine

Inferred from mutant phenotype PubMed 11943812. Source: BHF-UCL

eating behavior

Inferred from electronic annotation. Source: Ensembl

embryonic camera-type eye morphogenesis

Inferred from electronic annotation. Source: Ensembl

epinephrine biosynthetic process

Inferred from electronic annotation. Source: Ensembl

eye photoreceptor cell development

Inferred from electronic annotation. Source: Ensembl

fatty acid metabolic process

Inferred from expression pattern PubMed 21071351. Source: RGD

glycoside metabolic process

Inferred from expression pattern PubMed 20183248. Source: RGD

heart development

Inferred from direct assay PubMed 21280046. Source: RGD

isoquinoline alkaloid metabolic process

Inferred from expression pattern PubMed 18305432. Source: RGD

learning

Inferred from electronic annotation. Source: Ensembl

locomotory behavior

Inferred from electronic annotation. Source: Ensembl

mating behavior

Inferred from electronic annotation. Source: Ensembl

memory

Inferred from electronic annotation. Source: Ensembl

multicellular organismal aging

Inferred from expression pattern PubMed 17112516. Source: RGD

neurotransmitter biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-KW

norepinephrine biosynthetic process

Inferred from electronic annotation. Source: Ensembl

phthalate metabolic process

Inferred from expression pattern PubMed 21145954. Source: RGD

phytoalexin metabolic process

Inferred from expression pattern PubMed 19185027. Source: RGD

protein homotetramerization

Traceable author statement PubMed 2427363. Source: RGD

regulation of heart contraction

Inferred from electronic annotation. Source: Ensembl

response to activity

Inferred from expression pattern PubMed 21276429. Source: RGD

response to amphetamine

Inferred from expression pattern PubMed 21078367. Source: RGD

response to corticosterone

Inferred from expression pattern PubMed 19494803. Source: RGD

response to drug

Inferred from expression pattern PubMed 21396352. Source: RGD

response to electrical stimulus

Inferred from expression pattern PubMed 21296669. Source: RGD

response to estradiol

Inferred from expression pattern PubMed 11914591. Source: RGD

response to ethanol

Inferred from expression pattern PubMed 16713504. Source: RGD

response to ether

Inferred from expression pattern PubMed 15896472. Source: RGD

response to growth factor

Inferred from expression pattern PubMed 21236244. Source: RGD

response to herbicide

Inferred from expression pattern PubMed 20553223. Source: RGD

response to hypoxia

Inferred from direct assay PubMed 12692140. Source: RGD

response to immobilization stress

Inferred from expression pattern PubMed 11858766. Source: RGD

response to insecticide

Inferred from expression pattern PubMed 21277943. Source: RGD

response to light stimulus

Inferred from expression pattern PubMed 21185915. Source: RGD

response to lipopolysaccharide

Inferred from expression pattern PubMed 21239462. Source: RGD

response to metal ion

Inferred from expression pattern PubMed 20224926. Source: RGD

response to nicotine

Inferred from expression pattern PubMed 17437548. Source: RGD

response to nutrient levels

Inferred from expression pattern PubMed 21364997. Source: RGD

response to organic cyclic compound

Inferred from expression pattern PubMed 20951685. Source: RGD

response to peptide hormone

Inferred from expression pattern PubMed 21129429. Source: RGD

response to pyrethroid

Inferred from expression pattern PubMed 16229977. Source: RGD

response to salt stress

Inferred from expression pattern PubMed 21113619. Source: RGD

response to steroid hormone

Inferred from expression pattern PubMed 11883789. Source: RGD

response to water deprivation

Inferred from expression pattern PubMed 15637337. Source: RGD

response to zinc ion

Inferred from expression pattern PubMed 20553223. Source: RGD

sensory perception of sound

Inferred from expression pattern PubMed 16080996. Source: RGD

social behavior

Inferred from expression pattern PubMed 15345906. Source: RGD

sphingolipid metabolic process

Inferred from expression pattern PubMed 21076868. Source: RGD

synaptic transmission, dopaminergic

Inferred from electronic annotation. Source: Ensembl

synaptic vesicle amine transport

Inferred from direct assay PubMed 19903816. Source: RGD

terpene metabolic process

Inferred from expression pattern PubMed 20934257. Source: RGD

visual perception

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentaxon

Inferred from direct assay PubMed 14681933. Source: RGD

cytoplasm

Inferred from direct assay PubMed 14681933. Source: RGD

cytoplasmic side of plasma membrane

Inferred from electronic annotation. Source: Ensembl

cytoplasmic vesicle membrane

Inferred from direct assay PubMed 11943812. Source: BHF-UCL

cytosol

Inferred from direct assay PubMed 15496595. Source: RGD

dendrite

Inferred from direct assay PubMed 21362438. Source: RGD

melanosome membrane

Inferred from electronic annotation. Source: Ensembl

mitochondrion

Inferred from direct assay PubMed 11943812. Source: BHF-UCL

neuron projection

Inferred from direct assay PubMed 20412389. Source: RGD

neuronal cell body

Inferred from direct assay PubMed 21325515. Source: RGD

nucleus

Inferred from electronic annotation. Source: Ensembl

perikaryon

Inferred from direct assay PubMed 20434498. Source: RGD

smooth endoplasmic reticulum

Inferred from electronic annotation. Source: Ensembl

synaptic vesicle

Inferred from direct assay PubMed 15496595. Source: RGD

terminal bouton

Inferred from direct assay PubMed 14681933. Source: RGD

   Molecular_functionamino acid binding

Inferred from direct assay PubMed 19489646PubMed 20025246. Source: RGD

dopamine binding

Inferred from physical interaction PubMed 15639226. Source: RGD

ferric iron binding

Inferred from direct assay PubMed 16475826PubMed 19489646. Source: RGD

ferrous iron binding

Inferred from direct assay PubMed 16475826PubMed 19489646. Source: RGD

monooxygenase activity

Inferred from direct assay PubMed 33381. Source: BHF-UCL

oxygen binding

Inferred from direct assay PubMed 19489646PubMed 20025246. Source: RGD

protein binding

Inferred from physical interaction PubMed 11943812PubMed 19903816. Source: RGD

protein domain specific binding

Inferred from physical interaction PubMed 19903816. Source: RGD

tetrahydrobiopterin binding

Inferred from direct assay PubMed 19489646PubMed 20025246. Source: RGD

tyrosine 3-monooxygenase activity

Inferred from direct assay PubMed 19489646PubMed 20025246PubMed 20412389. Source: RGD

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.3
Chain2 – 498497Tyrosine 3-monooxygenase
PRO_0000205564

Regions

Compositional bias51 – 599Poly-Ala

Sites

Metal binding3311Iron
Metal binding3361Iron
Metal binding3761Iron

Amino acid modifications

Modified residue191Phosphoserine; by CaMK2 Ref.4 Ref.5
Modified residue311Phosphoserine Ref.4
Modified residue401Phosphoserine; by CaMK2 and PKA Ref.4 Ref.5

Secondary structure

....................................................................... 498
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P04177 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 17F7E003D29218C5

FASTA49855,966
        10         20         30         40         50         60 
MPTPSAPSPQ PKGFRRAVSE QDAKQAEAVT SPRFIGRRQS LIEDARKERE AAAAAAAAAV 

        70         80         90        100        110        120 
ASSEPGNPLE AVVFEERDGN AVLNLLFSLR GTKPSSLSRA VKVFETFEAK IHHLETRPAQ 

       130        140        150        160        170        180 
RPLAGSPHLE YFVRFEVPSG DLAALLSSVR RVSDDVRSAR EDKVPWFPRK VSELDKCHHL 

       190        200        210        220        230        240 
VTKFDPDLDL DHPGFSDQVY RQRRKLIAEI AFQYKHGEPI PHVEYTAEEI ATWKEVYVTL 

       250        260        270        280        290        300 
KGLYATHACR EHLEGFQLLE RYCGYREDSI PQLEDVSRFL KERTGFQLRP VAGLLSARDF 

       310        320        330        340        350        360 
LASLAFRVFQ CTQYIRHASS PMHSPEPDCC HELLGHVPML ADRTFAQFSQ DIGLASLGAS 

       370        380        390        400        410        420 
DEEIEKLSTV YWFTVEFGLC KQNGELKAYG AGLLSSYGEL LHSLSEEPEV RAFDPDTAAV 

       430        440        450        460        470        480 
QPYQDQTYQP VYFVSESFND AKDKLRNYAS RIQRPFSVKF DPYTLAIDVL DSPHTIQRSL 

       490 
EGVQDELHTL AHALSAIS 

« Hide

References

[1]"Complete coding sequence of rat tyrosine hydroxylase mRNA."
Grima B., Lamouroux A., Blanot F., Faucon Biguet N., Mallet J.
Proc. Natl. Acad. Sci. U.S.A. 82:617-621(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]Anton X.X., Manaster J.S., Kordower X.X., Markham X.X., Bredesen D.E.
Submitted (JUL-1993) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]Bienvenut W.V., von Kriegsheim A.F., Kolch W.
Submitted (AUG-2006) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 2-12; 284-298 AND 452-459, CLEAVAGE OF INITIATOR METHIONINE, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Pheochromocytoma.
[4]"Tyrosine hydroxylase in rat brain dopaminergic nerve terminals. Multiple-site phosphorylation in vivo and in synaptosomes."
Haycock J.W., Haycock D.A.
J. Biol. Chem. 266:5650-5657(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-19; SER-31 AND SER-40.
[5]"Phosphorylation of Ser(19) alters the conformation of tyrosine hydroxylase to increase the rate of phosphorylation of Ser(40)."
Bevilaqua L.R., Graham M.E., Dunkley P.R., von Nagy-Felsobuki E.I., Dickson P.W.
J. Biol. Chem. 276:40411-40416(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-19 AND SER-40, IDENTIFICATION BY MASS SPECTROMETRY.
[6]"Crystal structure of tyrosine hydroxylase at 2.3 A and its implications for inherited neurodegenerative diseases."
Goodwill K.E., Sabatier C., Marks C., Raag R., Fitzpatrick P.F., Stevens R.C.
Nat. Struct. Biol. 4:578-585(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 164-498.
[7]"Crystal structure of tyrosine hydroxylase with bound cofactor analogue and iron at 2.3 A resolution: self-hydroxylation of Phe300 and the pterin-binding site."
Goodwill K.E., Sabatier C., Stevens R.C.
Biochemistry 37:13437-13445(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 160-498.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M10244 mRNA. Translation: AAA42257.1.
L22651 mRNA. Translation: AAA42258.1.
PIRWHRTY. A00510.
RefSeqNP_036872.1. NM_012740.3.
UniGeneRn.11082.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1TOHX-ray2.30A156-498[»]
2MDANMR-A/B65-159[»]
2TOHX-ray2.30A156-498[»]
DisProtDP00094.
ProteinModelPortalP04177.
SMRP04177. Positions 160-498.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid247158. 1 interaction.
IntActP04177. 4 interactions.
MINTMINT-4585867.

Chemistry

BindingDBP04177.
ChEMBLCHEMBL2462.

PTM databases

PhosphoSiteP04177.

Proteomic databases

PaxDbP04177.
PRIDEP04177.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000027682; ENSRNOP00000027682; ENSRNOG00000020410.
GeneID25085.
KEGGrno:25085.
UCSCRGD:3853. rat.

Organism-specific databases

CTD7054.
RGD3853. Th.

Phylogenomic databases

eggNOGCOG3186.
GeneTreeENSGT00390000010268.
HOGENOMHOG000233373.
HOVERGENHBG006841.
InParanoidP04177.
KOK00501.
OMAELDKCHH.
OrthoDBEOG7KM5T1.
PhylomeDBP04177.
TreeFamTF313327.

Enzyme and pathway databases

SABIO-RKP04177.
UniPathwayUPA00747; UER00733.

Gene expression databases

GenevestigatorP04177.

Family and domain databases

Gene3D1.10.800.10. 1 hit.
InterProIPR001273. ArAA_hydroxylase.
IPR018301. ArAA_hydroxylase_Fe/CU_BS.
IPR019774. Aromatic-AA_hydroxylase_C.
IPR005962. Tyr_3_mOase.
IPR019773. Tyrosine_3-monooxygenase-like.
IPR021164. Tyrosine_hydroxylase_CS.
[Graphical view]
PANTHERPTHR11473. PTHR11473. 1 hit.
PfamPF00351. Biopterin_H. 1 hit.
PF12549. TOH_N. 2 hits.
[Graphical view]
PIRSFPIRSF000336. TH. 1 hit.
PRINTSPR00372. FYWHYDRXLASE.
SUPFAMSSF56534. SSF56534. 1 hit.
TIGRFAMsTIGR01269. Tyr_3_monoox. 1 hit.
PROSITEPS00367. BH4_AAA_HYDROXYL_1. 1 hit.
PS51410. BH4_AAA_HYDROXYL_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP04177.
NextBio605346.
PROP04177.

Entry information

Entry nameTY3H_RAT
AccessionPrimary (citable) accession number: P04177
Entry history
Integrated into UniProtKB/Swiss-Prot: March 20, 1987
Last sequence update: January 23, 2007
Last modified: June 11, 2014
This is version 135 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways