Reviewed, UniProtKB/Swiss-Prot P04177 (TY3H_RAT)

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:

Th

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 Direct protein sequencing
Gene Ontology (GO)
Biological process	dopamine biosynthetic process from tyrosine Inferred from mutant phenotype. Source: UniProtKB neurotransmitter biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW protein homotetramerization Traceable author statement. Source: RGD response to hypoxia Inferred from direct assay. Source: RGD response to steroid hormone stimulus Inferred from expression pattern. Source: RGD
Cellular component	cytosol Inferred from direct assay. Source: RGD mitochondrion Inferred from direct assay. Source: UniProtKB synaptic vesicle Inferred from direct assay. Source: RGD terminal button Inferred from direct assay. Source: RGD
Molecular function	amino acid binding Inferred from physical interaction. 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 tyrosine 3-monooxygenase activity Traceable author statement. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.3

Chain

2 – 498

497

Tyrosine 3-monooxygenase

PRO_0000205564

Regions

Compositional bias

51 – 59

9

Poly-Ala

Sites

Metal binding

331

1

Iron

Metal binding

336

1

Iron

Metal binding

376

1

Iron

Amino acid modifications

Modified residue

19

1

Phosphoserine; by CaMK2 Ref.4 Ref.5

Modified residue

31

1

Phosphoserine Ref.4

Modified residue

40

1

Phosphoserine; by PKA Ref.4 Ref.5

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

498

Helix Strand Turn

Details...

Helix

171 – 176

6

Turn

193 – 196

4

Helix

198 – 213

16

Helix

227 – 247

21

Helix

250 – 262

13

Helix

273 – 283

11

Beta strand

287 – 290

4

Helix

297 – 304

8

Turn

305 – 307

3

Beta strand

308 – 311

4

Helix

329 – 335

7

Helix

337 – 340

4

Helix

343 – 356

14

Helix

361 – 372

12

Turn

373 – 377

5

Beta strand

379 – 382

4

Beta strand

385 – 388

4

Helix

391 – 394

4

Helix

397 – 403

7

Beta strand

405 – 412

8

Helix

415 – 419

5

Beta strand

425 – 427

3

Beta strand

430 – 436

7

Helix

438 – 450

13

Beta strand

457 – 461

5

Turn

462 – 465

4

Beta strand

466 – 470

5

Helix

473 – 496

24

Sequences

	Sequence		Length	Mass (Da)
	P04177-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 17F7E003D29218C5	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

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.

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.

ModBase

Search...

Protein-protein interaction databases

STRING

P04177.

PTM databases

PhosphoSite

P04177.

Genome annotation databases

Ensembl

ENSRNOT00000027682; ENSRNOP00000027682; ENSRNOG00000020410; Rattus norvegicus. [Genome view]

GeneID

25085.

KEGG

rno:25085.

UCSC

M10244. rat.

Organism-specific databases

CTD

25085.

RGD

3853. Th.

Phylogenomic databases

eggNOG

roNOG12445.

HOVERGEN

HBG006841.

InParanoid

P04177.

OMA

ELDKCHH.

OrthoDB

EOG94BDNR.

PhylomeDB

P04177.

Enzyme and pathway databases

BRENDA

1.14.16.2. 248.

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_N.
[Graphical view]

Gene3D

G3DSA:1.10.800.10. Aaa_hydroxylase. 1 hit.

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. BIOPTERIN_HYDROXYL. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

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:	March 2, 2010
This is version 101 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)