Tyrosine 3-monooxygenase - Rattus norvegicus (Rat)

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P04177 (TY3H_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 126. History...

Clusters with 100%, 90%, 50% identity |

Documents (3) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Tyrosine 3-monooxygenase
EC=1.14.16.2

Alternative name(s):
Tyrosine 3-hydroxylase
Short name=TH

Gene names

Name:

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	498 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 process	Catecholamine biosynthesis Neurotransmitter biosynthesis
Ligand	Iron Metal-binding
Molecular function	Monooxygenase Oxidoreductase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	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: Compara embryonic camera-type eye morphogenesis Inferred from electronic annotation. Source: Compara epinephrine biosynthetic process Inferred from electronic annotation. Source: Compara eye photoreceptor cell development Inferred from electronic annotation. Source: Compara 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: Compara locomotory behavior Inferred from electronic annotation. Source: Compara mating behavior Inferred from electronic annotation. Source: Compara memory Inferred from electronic annotation. Source: Compara 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: Compara 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: Compara 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 stimulus Inferred from expression pattern PubMed 19494803. Source: RGD response to electrical stimulus Inferred from expression pattern PubMed 21296669. Source: RGD response to estradiol stimulus 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 herbicide Inferred from expression pattern PubMed 20553223. Source: RGD response to hypoxia Inferred from direct assay PubMed 12692140. 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 nutrient levels Inferred from expression pattern PubMed 21364997. Source: RGD response to peptide hormone stimulus 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 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: Compara 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: Compara
Cellular_component	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 internal side of plasma membrane Inferred from electronic annotation. Source: Compara melanosome membrane Inferred from electronic annotation. Source: Compara mitochondrion Inferred from direct assay PubMed 11943812. Source: BHF-UCL nucleus Inferred from electronic annotation. Source: Compara perikaryon Inferred from direct assay PubMed 20434498. Source: RGD smooth endoplasmic reticulum Inferred from electronic annotation. Source: Compara synaptic vesicle Inferred from direct assay PubMed 15496595. Source: RGD terminal bouton Inferred from direct assay PubMed 14681933. Source: RGD
Molecular_function	amino acid binding Inferred from direct assay PubMed 19489646 PubMed 20025246. Source: RGD dopamine binding Inferred from physical interaction PubMed 15639226. Source: RGD ferric iron binding Inferred from direct assay PubMed 16475826 PubMed 19489646. Source: RGD ferrous iron binding Inferred from direct assay PubMed 16475826 PubMed 19489646. Source: RGD oxygen binding Inferred from direct assay PubMed 19489646 PubMed 20025246. Source: RGD tetrahydrobiopterin binding Inferred from direct assay PubMed 19489646 PubMed 20025246. Source: RGD tyrosine 3-monooxygenase activity Inferred from direct assay PubMed 19489646 PubMed 20025246 PubMed 20412389. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

Removed Ref.3

Chain

2 – 498

497

Tyrosine 3-monooxygenase

PRO_0000205564

Regions

Compositional bias

51 – 59

Poly-Ala

Sites

Metal binding

331

Iron

Metal binding

336

Iron

Metal binding

376

Iron

Amino acid modifications

Modified residue

Phosphoserine; by CaMK2 Ref.4 Ref.5

Modified residue

Phosphoserine Ref.4

Modified residue

Phosphoserine; by CaMK2 and PKA Ref.4 Ref.5

Secondary structure

498

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

P04177 [UniParc].

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

498

55,966

        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, 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, 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.

IPI

IPI00193259.

PIR

WHRTY. A00510.

RefSeq

NP_036872.1. NM_012740.3.

UniGene

Rn.11082.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1TOH	X-ray	2.30	A	156-498	[»]
2TOH	X-ray	2.30	A	156-498	[»]

DisProt

DP00094.

ProteinModelPortal

P04177.

SMR

P04177. Positions 160-498.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-4585867.

PTM databases

PhosphoSite

P04177.

Proteomic databases

PaxDb

P04177.

PRIDE

P04177.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSRNOT00000027682; ENSRNOP00000027682; ENSRNOG00000020410.

GeneID

25085.

KEGG

rno:25085.

UCSC

RGD:3853. rat.

Organism-specific databases

CTD

7054.

RGD

3853. Th.

Phylogenomic databases

eggNOG

COG3186.

GeneTree

ENSGT00390000010268.

HOGENOM

HOG000233373.

HOVERGEN

HBG006841.

InParanoid

P04177.

K00501.

OMA

SELDKCH.

OrthoDB

EOG43N7CM.

Enzyme and pathway databases

SABIO-RK

P04177.

UniPathway

UPA00747; UER00733.

Gene expression databases

ArrayExpress

P04177.

Genevestigator

P04177.

GermOnline

ENSRNOG00000020410. Rattus norvegicus.

Family and domain databases

Gene3D

1.10.800.10. 1 hit.

InterPro

IPR001273. 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]

PANTHER

PTHR11473. PTHR11473. 1 hit.

Pfam

PF00351. Biopterin_H. 1 hit.
PF12549. TOH_N. 2 hits.
[Graphical view]

PIRSF

PIRSF000336. TH. 1 hit.

PRINTS

PR00372. FYWHYDRXLASE.

SUPFAM

SSF56534. Aaa_hydroxylase. 1 hit.

TIGRFAMs

TIGR01269. Tyr_3_monoox. 1 hit.

PROSITE

PS00367. BH4_AAA_HYDROXYL_1. 1 hit.
PS51410. BH4_AAA_HYDROXYL_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P04177.

ChEMBL

CHEMBL2462.

EvolutionaryTrace

P04177.

NextBio

605346.

Entry information

Entry name

TY3H_RAT

Accession

Primary (citable) accession number: P04177

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 20, 1987
Last sequence update:	January 23, 2007
Last modified:	April 3, 2013
This is version 126 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

PATHWAY comments

Index of metabolic and biosynthesis pathways

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents