[1]	NUCLEOTIDE SEQUENCE [MRNA]. PubMed=2857492 [NCBI, ExPASy, EBI, Israel, Japan] Grima B., Lamouroux A., Blanot F., Faucon Biguet N., Mallet J.; "Complete coding sequence of rat tyrosine hydroxylase mRNA."; Proc. Natl. Acad. Sci. U.S.A. 82:617-621(1985).
[2]	NUCLEOTIDE SEQUENCE [MRNA]. Anton X.X., Manaster J.S., Kordower X.X., Markham X.X., Bredesen D.E.; Submitted (JUL-1993) to the EMBL/GenBank/DDBJ databases.
[3]	PROTEIN SEQUENCE OF 2-12; 284-298 AND 452-459, CLEAVAGE OF INITIATOR METHIONINE, AND MASS SPECTROMETRY. TISSUE=Pheochromocytoma; Bienvenut W.V., von Kriegsheim A.F., Kolch W.; Submitted (AUG-2006) to UniProtKB.
[4]	PHOSPHORYLATION AT SER-19; SER-31 AND SER-40. PubMed=1672315 [NCBI, ExPASy, EBI, Israel, Japan] Haycock J.W., Haycock D.A.; "Tyrosine hydroxylase in rat brain dopaminergic nerve terminals. Multiple-site phosphorylation in vivo and in synaptosomes."; J. Biol. Chem. 266:5650-5657(1991).
[5]	PHOSPHORYLATION AT SER-19 AND SER-40, AND MASS SPECTROMETRY. DOI=10.1074/jbc.M105280200; PubMed=11502746 [NCBI, ExPASy, EBI, Israel, Japan] Bevilaqua L.R., Graham M.E., Dunkley P.R., von Nagy-Felsobuki E.I., Dickson P.W.; "Phosphorylation of Ser(19) alters the conformation of tyrosine hydroxylase to increase the rate of phosphorylation of Ser(40)."; J. Biol. Chem. 276:40411-40416(2001).
[6]	X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 164-498. DOI=10.1038/nsb0797-578; PubMed=9228951 [NCBI, ExPASy, EBI, Israel, Japan] Goodwill K.E., Sabatier C., Marks C., Raag R., Fitzpatrick P.F., Stevens R.C.; "Crystal structure of tyrosine hydroxylase at 2.3 A and its implications for inherited neurodegenerative diseases."; Nat. Struct. Biol. 4:578-585(1997).
[7]	X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 160-498. DOI=10.1021/bi981462g; PubMed=9753429 [NCBI, ExPASy, EBI, Israel, Japan] Goodwill K.E., Sabatier C., Stevens R.C.; "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."; Biochemistry 37:13437-13445(1998).

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: Fe(2+) 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: Homotetramer.
PTM: In vitro, phosphorylation of Ser-19 increases the rate of Ser-40 phosphorylation, which results in enzyme opening and activation.
SIMILARITY: Belongs to the biopterin-dependent aromatic amino acid hydroxylase family.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

M10244; AAA42257.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
L22651; AAA42258.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

A00510; WHRTY.

NP_036872.1; -.

3D structure databases

PDB

1TOH; X-ray; 2.30 A; A=156-498.	[ExPASy / RCSB / EBI]
2TOH; X-ray; 2.30 A; A=156-498.	[ExPASy / RCSB / EBI]

Detailed list of linked structures.

1TOH; -.
2TOH; -.

DP00094; -.

PTM databases

P04177; -.

Organism-specific databases

RGD

3853; Th.

Gene expression databases

ArrayExpress

P04177; -.

GermOnline

ENSRNOG00000020410; Rattus norvegicus.

Ontologies

GO:0030659;	Cellular component: cytoplasmic vesicle membrane (inferred from direct assay from UniProtKB).
GO:0005739;	Cellular component: mitochondrion (inferred from direct assay from UniProtKB).
GO:0004497;	Molecular function: monooxygenase activity (inferred from direct assay from UniProtKB).
GO:0006585;	Biological process: dopamine biosynthetic process from tyrosine (inferred from mutant phenotype from UniProtKB).
QuickGo view.

Family and domain databases

InterPro

IPR001273; Aaa_hydroxylase.
IPR005962; Tyr_3_mOase.
Graphical view of domain structure.

Gene3D

G3DSA:1.10.800.10; Aaa_hydroxylase; 1.

PANTHER

PTHR11473; Aaa_hydroxylase; 1.

Pfam

PF00351; Biopterin_H; 1.
Pfam graphical view of domain structure.

PRINTS

PR00372; FYWHYDRXLASE.

ProDom

PD002559; Aaa_hydroxylase; 1.
[Domain structure / List of seq. sharing at least 1 domain]

TIGRFAMs

TIGR01269; Tyr_3_monoox; 1.

PROSITE

PS00367; BIOPTERIN_HYDROXYL; 1.

Genome annotation databases

Ensembl

ENSRNOG00000020410; Rattus norvegicus. [Contig view]

GeneID

25085; -.

KEGG

rno:25085; -.

Phylogenomic databases

HOVERGEN

P04177; -.

Other

LinkHub

P04177; -.

NextBio

605346; -.

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Catecholamine biosynthesis; Direct protein sequencing; Iron; Metal-binding; Monooxygenase; Neurotransmitter biosynthesis; Oxidoreductase; Phosphoprotein.

Features

Feature table viewer

`Key`	`From To`	`Length`	`Description`	`FTId`
`INIT_MET`	`1 1`		`Removed.`
`CHAIN`	`2 498`	`497`	`Tyrosine 3-monooxygenase.`	`PRO_0000205564`
`COMPBIAS`	`51 59`	`9`	`Poly-Ala.`
`METAL`	`331 331`		`Iron.`
`METAL`	`336 336`		`Iron.`
`METAL`	`376 376`		`Iron.`
`MOD_RES`	`19 19`		`Phosphoserine; by CaMK2.`
`MOD_RES`	`31 31`		`Phosphoserine.`
`MOD_RES`	`40 40`		`Phosphoserine; by PKA.`
`HELIX`	`171 176`	`6`
`TURN`	`193 196`	`4`
`HELIX`	`198 213`	`16`
`HELIX`	`227 247`	`21`
`HELIX`	`250 262`	`13`
`HELIX`	`273 283`	`11`
`STRAND`	`287 290`	`4`
`HELIX`	`297 304`	`8`
`TURN`	`305 307`	`3`
`STRAND`	`308 311`	`4`
`HELIX`	`329 335`	`7`
`HELIX`	`337 340`	`4`
`HELIX`	`343 356`	`14`
`HELIX`	`361 372`	`12`
`TURN`	`373 377`	`5`
`STRAND`	`379 382`	`4`
`STRAND`	`385 388`	`4`
`HELIX`	`391 394`	`4`
`HELIX`	`397 403`	`7`
`STRAND`	`405 412`	`8`
`HELIX`	`415 419`	`5`
`STRAND`	`425 427`	`3`
`STRAND`	`430 436`	`7`
`HELIX`	`438 450`	`13`
`STRAND`	`457 461`	`5`
`TURN`	`462 465`	`4`
`STRAND`	`466 470`	`5`
`HELIX`	`473 496`	`24`

Sequence information

Length: 498 AA [This is the length of the unprocessed precursor]

Molecular weight: 55966 Da [This is the MW of the unprocessed precursor]

CRC64: 17F7E003D29218C5 [This is a checksum on the sequence]

        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

P04177 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools