Tyrosine 3-monooxygenase - Rattus norvegicus (Rat)

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P04177 (TY3H_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified November 16, 2011. Version 115. 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)

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 = 3,4-dihydroxy-L-phenylalanine + 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	O-glycoside metabolic process Inferred from expression pattern. Source: RGD cellular response to drug Inferred from expression pattern. Source: RGD cellular response to glucose stimulus Inferred from expression pattern. Source: RGD cellular response to growth factor stimulus Inferred from expression pattern. Source: RGD cellular response to manganese ion Inferred from expression pattern. Source: RGD cellular response to nicotine Inferred from expression pattern. Source: RGD cerebral cortex development Inferred from expression pattern. Source: RGD circadian sleep/wake cycle Inferred from expression pattern. Source: RGD dopamine biosynthetic process from tyrosine Inferred from mutant phenotype. Source: BHF-UCL fatty acid metabolic process Inferred from expression pattern. Source: RGD heart development Inferred from direct assay. Source: RGD isoquinoline alkaloid metabolic process Inferred from expression pattern. Source: RGD multicellular organismal aging Inferred from expression pattern. Source: RGD neurotransmitter biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW phthalate metabolic process Inferred from expression pattern. Source: RGD phytoalexin metabolic process Inferred from expression pattern. Source: RGD protein homotetramerization Traceable author statement. Source: RGD response to activity Inferred from expression pattern. Source: RGD response to amphetamine Inferred from expression pattern. Source: RGD response to corticosterone stimulus Inferred from expression pattern. Source: RGD response to electrical stimulus Inferred from expression pattern. Source: RGD response to estradiol stimulus Inferred from expression pattern. Source: RGD response to ethanol Inferred from expression pattern. Source: RGD response to ether Inferred from expression pattern. Source: RGD response to herbicide Inferred from expression pattern. Source: RGD response to hypoxia Inferred from direct assay. Source: RGD response to light stimulus Inferred from expression pattern. Source: RGD response to lipopolysaccharide Inferred from expression pattern. Source: RGD response to nutrient levels Inferred from expression pattern. Source: RGD response to peptide hormone stimulus Inferred from expression pattern. Source: RGD response to pyrethroid Inferred from expression pattern. Source: RGD response to salt stress Inferred from expression pattern. Source: RGD response to water deprivation Inferred from expression pattern. Source: RGD response to zinc ion Inferred from expression pattern. Source: RGD sensory perception of sound Inferred from expression pattern. Source: RGD social behavior Inferred from expression pattern. Source: RGD sphingolipid metabolic process Inferred from expression pattern. Source: RGD synaptic vesicle amine transport Inferred from direct assay. Source: RGD terpene metabolic process Inferred from expression pattern. Source: RGD
Cellular component	cytosol Inferred from direct assay. Source: RGD dendrite Inferred from direct assay. Source: RGD mitochondrion Inferred from direct assay. Source: BHF-UCL perikaryon Inferred from direct assay. Source: RGD synaptic vesicle Inferred from direct assay. Source: RGD synaptosome Inferred from direct assay. Source: RGD terminal button Inferred from direct assay. Source: RGD
Molecular function	amino acid binding Inferred from direct assay. Source: RGD dopamine binding Inferred from physical interaction. Source: RGD ferric iron binding Inferred from direct assay. Source: RGD ferrous iron binding Inferred from direct assay. Source: RGD oxygen binding Inferred from direct assay. Source: RGD protein domain specific binding Inferred from physical interaction. Source: RGD tetrahydrobiopterin binding Inferred from direct assay. Source: RGD tyrosine 3-monooxygenase activity Inferred from direct assay. 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 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
Show »

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: 2857492] [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: 1672315] [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: 11502746] [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: 9228951] [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: 9753429] [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	[»]

ProteinModelPortal

P04177.

SMR

P04177. Positions 160-498.

DisProt

DP00094.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-4585867.

STRING

P04177.

PTM databases

PhosphoSite

P04177.

Proteomic databases

PRIDE

P04177.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSRNOT00000027682; ENSRNOP00000027682; ENSRNOG00000020410.

GeneID

25085.

KEGG

rno:25085.

UCSC

M10244. rat.

Organism-specific databases

CTD

7054.

RGD

3853. Th.

Phylogenomic databases

eggNOG

roNOG12445.

HOVERGEN

HBG006841.

InParanoid

P04177.

OMA

PKVPWFP.

OrthoDB

EOG43N7CM.

PhylomeDB

P04177.

Gene expression databases

ArrayExpress

P04177.

Genevestigator

P04177.

GermOnline

ENSRNOG00000020410. Rattus norvegicus.

Family and domain databases

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]

Gene3D

G3DSA:1.10.800.10. Aaa_hydroxylase. 1 hit.

K00501.

PANTHER

PTHR11473. Aaa_hydroxylase. 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

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:	November 16, 2011
This is version 115 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

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents