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Protein

Tyrosine 3-monooxygenase

Gene

Th

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Plays an important role in the physiology of adrenergic neurons.

Catalytic activityi

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

Cofactori

Enzyme regulationi

Phosphorylation leads to an increase in the catalytic activity.

Pathwayi: dopamine biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes dopamine from L-tyrosine.
Proteins known to be involved in the 2 steps of the subpathway in this organism are:
  1. Tyrosine 3-monooxygenase (Th)
  2. Aromatic-L-amino-acid decarboxylase (Ddc)
This subpathway is part of the pathway dopamine biosynthesis, which is itself part of Catecholamine biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes dopamine from L-tyrosine, the pathway dopamine biosynthesis and in Catecholamine biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi331Iron1
Metal bindingi336Iron1
Metal bindingi376Iron1

GO - Molecular functioni

  • amino acid binding Source: RGD
  • dopamine binding Source: RGD
  • enzyme binding Source: Ensembl
  • ferric iron binding Source: RGD
  • ferrous iron binding Source: RGD
  • monooxygenase activity Source: BHF-UCL
  • oxygen binding Source: RGD
  • tetrahydrobiopterin binding Source: RGD
  • tyrosine 3-monooxygenase activity Source: RGD

GO - Biological processi

  • aminergic neurotransmitter loading into synaptic vesicle Source: RGD
  • catecholamine biosynthetic process Source: RGD
  • cellular response to alkaloid Source: RGD
  • cellular response to drug Source: RGD
  • cellular response to glucose stimulus Source: RGD
  • cellular response to growth factor stimulus Source: RGD
  • cellular response to manganese ion Source: RGD
  • cellular response to nicotine Source: RGD
  • cerebral cortex development Source: RGD
  • circadian sleep/wake cycle Source: RGD
  • cognition Source: RGD
  • dopamine biosynthetic process from tyrosine Source: RGD
  • eating behavior Source: Ensembl
  • embryonic camera-type eye morphogenesis Source: Ensembl
  • epinephrine biosynthetic process Source: Ensembl
  • eye photoreceptor cell development Source: Ensembl
  • fatty acid metabolic process Source: RGD
  • glycoside metabolic process Source: RGD
  • heart development Source: RGD
  • isoquinoline alkaloid metabolic process Source: RGD
  • learning Source: Ensembl
  • locomotory behavior Source: Ensembl
  • mating behavior Source: Ensembl
  • memory Source: Ensembl
  • multicellular organism aging Source: RGD
  • neurotransmitter biosynthetic process Source: UniProtKB-KW
  • norepinephrine biosynthetic process Source: Ensembl
  • phthalate metabolic process Source: RGD
  • phytoalexin metabolic process Source: RGD
  • protein homotetramerization Source: RGD
  • regulation of heart contraction Source: Ensembl
  • response to activity Source: RGD
  • response to amphetamine Source: RGD
  • response to corticosterone Source: RGD
  • response to drug Source: RGD
  • response to electrical stimulus Source: RGD
  • response to estradiol Source: RGD
  • response to ethanol Source: RGD
  • response to ether Source: RGD
  • response to growth factor Source: RGD
  • response to herbicide Source: RGD
  • response to hypoxia Source: RGD
  • response to immobilization stress Source: RGD
  • response to insecticide Source: RGD
  • response to isolation stress Source: RGD
  • response to light stimulus Source: RGD
  • response to lipopolysaccharide Source: RGD
  • response to metal ion Source: RGD
  • response to nicotine Source: RGD
  • response to nutrient levels Source: RGD
  • response to organic cyclic compound Source: RGD
  • response to peptide hormone Source: RGD
  • response to pyrethroid Source: RGD
  • response to salt stress Source: RGD
  • response to steroid hormone Source: RGD
  • response to water deprivation Source: RGD
  • response to zinc ion Source: RGD
  • sensory perception of sound Source: RGD
  • social behavior Source: RGD
  • sphingolipid metabolic process Source: RGD
  • synaptic transmission, dopaminergic Source: Ensembl
  • terpene metabolic process Source: RGD
  • visual perception Source: Ensembl

Keywordsi

Molecular functionMonooxygenase, Oxidoreductase
Biological processCatecholamine biosynthesis, Neurotransmitter biosynthesis
LigandIron, Metal-binding

Enzyme and pathway databases

BRENDAi1.14.16.2 5301
ReactomeiR-RNO-209905 Catecholamine biosynthesis
SABIO-RKiP04177
UniPathwayiUPA00747; UER00733

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine 3-monooxygenase (EC:1.14.16.2)
Alternative name(s):
Tyrosine 3-hydroxylase
Short name:
TH
Gene namesi
Name:Th
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi3853 Th

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2462

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00002055642 – 498Tyrosine 3-monooxygenaseAdd BLAST497

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei19Phosphoserine; by CaMK22 Publications1
Modified residuei31Phosphoserine1 Publication1
Modified residuei40Phosphoserine; by CaMK2 and PKA2 Publications1
Modified residuei472PhosphoserineBy similarity1

Post-translational modificationi

In vitro, phosphorylation of Ser-19 increases the rate of Ser-40 phosphorylation, which results in enzyme opening and activation.2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP04177
PRIDEiP04177

PTM databases

iPTMnetiP04177
PhosphoSitePlusiP04177

Expressioni

Gene expression databases

BgeeiENSRNOG00000020410
GenevisibleiP04177 RN

Interactioni

Subunit structurei

Homotetramer.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi247158, 1 interactor
IntActiP04177, 4 interactors
MINTiP04177
STRINGi10116.ENSRNOP00000027682

Chemistry databases

BindingDBiP04177

Structurei

Secondary structure

1498
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi75 – 77Combined sources3
Beta strandi80 – 85Combined sources6
Beta strandi91 – 93Combined sources3
Helixi98 – 106Combined sources9
Beta strandi110 – 116Combined sources7
Beta strandi119 – 122Combined sources4
Beta strandi133 – 138Combined sources6
Helixi141 – 150Combined sources10
Beta strandi162 – 164Combined sources3
Helixi171 – 176Combined sources6
Beta strandi177 – 179Combined sources3
Turni193 – 196Combined sources4
Helixi198 – 213Combined sources16
Helixi227 – 247Combined sources21
Helixi250 – 262Combined sources13
Helixi273 – 283Combined sources11
Beta strandi287 – 290Combined sources4
Helixi297 – 304Combined sources8
Turni305 – 307Combined sources3
Beta strandi308 – 311Combined sources4
Helixi329 – 335Combined sources7
Helixi337 – 340Combined sources4
Helixi343 – 356Combined sources14
Helixi361 – 372Combined sources12
Turni373 – 377Combined sources5
Beta strandi379 – 382Combined sources4
Beta strandi385 – 388Combined sources4
Helixi391 – 394Combined sources4
Helixi397 – 403Combined sources7
Beta strandi405 – 412Combined sources8
Helixi415 – 419Combined sources5
Beta strandi425 – 427Combined sources3
Beta strandi430 – 436Combined sources7
Helixi438 – 450Combined sources13
Beta strandi457 – 461Combined sources5
Turni462 – 465Combined sources4
Beta strandi466 – 470Combined sources5
Helixi473 – 496Combined sources24

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1TOHX-ray2.30A156-498[»]
2MDANMR-A/B65-159[»]
2TOHX-ray2.30A156-498[»]
DisProtiDP00094
ProteinModelPortaliP04177
SMRiP04177
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP04177

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi51 – 59Poly-Ala9

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG3820 Eukaryota
COG3186 LUCA
GeneTreeiENSGT00390000010268
HOGENOMiHOG000233373
HOVERGENiHBG006841
InParanoidiP04177
KOiK00501
OMAiPHLEYFV
OrthoDBiEOG091G05MZ
PhylomeDBiP04177
TreeFamiTF313327

Family and domain databases

Gene3Di1.10.800.10, 1 hit
InterProiView protein in InterPro
IPR001273 ArAA_hydroxylase
IPR018301 ArAA_hydroxylase_Fe/CU_BS
IPR036951 ArAA_hydroxylase_sf
IPR036329 Aro-AA_hydroxylase_C_sf
IPR019774 Aromatic-AA_hydroxylase_C
IPR005962 Tyr_3_mOase
IPR019773 Tyrosine_3-monooxygenase-like
IPR021164 Tyrosine_hydroxylase_CS
PANTHERiPTHR11473 PTHR11473, 1 hit
PfamiView protein in Pfam
PF00351 Biopterin_H, 1 hit
PF12549 TOH_N, 2 hits
PIRSFiPIRSF000336 TH, 1 hit
PRINTSiPR00372 FYWHYDRXLASE
SUPFAMiSSF56534 SSF56534, 1 hit
TIGRFAMsiTIGR01269 Tyr_3_monoox, 1 hit
PROSITEiView protein in PROSITE
PS00367 BH4_AAA_HYDROXYL_1, 1 hit
PS51410 BH4_AAA_HYDROXYL_2, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P04177-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPTPSAPSPQ PKGFRRAVSE QDAKQAEAVT SPRFIGRRQS LIEDARKERE
60 70 80 90 100
AAAAAAAAAV ASSEPGNPLE AVVFEERDGN AVLNLLFSLR GTKPSSLSRA
110 120 130 140 150
VKVFETFEAK IHHLETRPAQ RPLAGSPHLE YFVRFEVPSG DLAALLSSVR
160 170 180 190 200
RVSDDVRSAR EDKVPWFPRK VSELDKCHHL VTKFDPDLDL DHPGFSDQVY
210 220 230 240 250
RQRRKLIAEI AFQYKHGEPI PHVEYTAEEI ATWKEVYVTL KGLYATHACR
260 270 280 290 300
EHLEGFQLLE RYCGYREDSI PQLEDVSRFL KERTGFQLRP VAGLLSARDF
310 320 330 340 350
LASLAFRVFQ CTQYIRHASS PMHSPEPDCC HELLGHVPML ADRTFAQFSQ
360 370 380 390 400
DIGLASLGAS DEEIEKLSTV YWFTVEFGLC KQNGELKAYG AGLLSSYGEL
410 420 430 440 450
LHSLSEEPEV RAFDPDTAAV QPYQDQTYQP VYFVSESFND AKDKLRNYAS
460 470 480 490
RIQRPFSVKF DPYTLAIDVL DSPHTIQRSL EGVQDELHTL AHALSAIS
Length:498
Mass (Da):55,966
Last modified:January 23, 2007 - v3
Checksum:i17F7E003D29218C5
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M10244 mRNA Translation: AAA42257.1
L22651 mRNA Translation: AAA42258.1
PIRiA00510 WHRTY
RefSeqiNP_036872.1, NM_012740.3
UniGeneiRn.11082

Genome annotation databases

EnsembliENSRNOT00000027682; ENSRNOP00000027682; ENSRNOG00000020410
GeneIDi25085
KEGGirno:25085
UCSCiRGD:3853 rat

Similar proteinsi

Entry informationi

Entry nameiTY3H_RAT
AccessioniPrimary (citable) accession number: P04177
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 20, 1987
Last sequence update: January 23, 2007
Last modified: May 23, 2018
This is version 161 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

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