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Protein

Tyrosine 3-monooxygenase

Gene

Th

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi331 – 3311Iron
Metal bindingi336 – 3361Iron
Metal bindingi376 – 3761Iron

GO - Molecular functioni

  1. amino acid binding Source: RGD
  2. dopamine binding Source: RGD
  3. ferric iron binding Source: RGD
  4. ferrous iron binding Source: RGD
  5. monooxygenase activity Source: BHF-UCL
  6. oxygen binding Source: RGD
  7. protein domain specific binding Source: RGD
  8. tetrahydrobiopterin binding Source: RGD
  9. tyrosine 3-monooxygenase activity Source: RGD

GO - Biological processi

  1. catecholamine biosynthetic process Source: RGD
  2. cellular response to alkaloid Source: RGD
  3. cellular response to drug Source: RGD
  4. cellular response to glucose stimulus Source: RGD
  5. cellular response to growth factor stimulus Source: RGD
  6. cellular response to manganese ion Source: RGD
  7. cellular response to nicotine Source: RGD
  8. cerebral cortex development Source: RGD
  9. circadian sleep/wake cycle Source: RGD
  10. cognition Source: RGD
  11. dopamine biosynthetic process from tyrosine Source: BHF-UCL
  12. eating behavior Source: Ensembl
  13. embryonic camera-type eye morphogenesis Source: Ensembl
  14. epinephrine biosynthetic process Source: Ensembl
  15. eye photoreceptor cell development Source: Ensembl
  16. fatty acid metabolic process Source: RGD
  17. glycoside metabolic process Source: RGD
  18. heart development Source: RGD
  19. isoquinoline alkaloid metabolic process Source: RGD
  20. learning Source: Ensembl
  21. locomotory behavior Source: Ensembl
  22. mating behavior Source: Ensembl
  23. memory Source: Ensembl
  24. multicellular organismal aging Source: RGD
  25. neurotransmitter biosynthetic process Source: UniProtKB-KW
  26. norepinephrine biosynthetic process Source: Ensembl
  27. phthalate metabolic process Source: RGD
  28. phytoalexin metabolic process Source: RGD
  29. protein homotetramerization Source: RGD
  30. regulation of heart contraction Source: Ensembl
  31. response to activity Source: RGD
  32. response to amphetamine Source: RGD
  33. response to corticosterone Source: RGD
  34. response to drug Source: RGD
  35. response to electrical stimulus Source: RGD
  36. response to estradiol Source: RGD
  37. response to ethanol Source: RGD
  38. response to ether Source: RGD
  39. response to growth factor Source: RGD
  40. response to herbicide Source: RGD
  41. response to hypoxia Source: RGD
  42. response to immobilization stress Source: RGD
  43. response to insecticide Source: RGD
  44. response to isolation stress Source: RGD
  45. response to light stimulus Source: RGD
  46. response to lipopolysaccharide Source: RGD
  47. response to metal ion Source: RGD
  48. response to nicotine Source: RGD
  49. response to nutrient levels Source: RGD
  50. response to organic cyclic compound Source: RGD
  51. response to peptide hormone Source: RGD
  52. response to pyrethroid Source: RGD
  53. response to salt stress Source: RGD
  54. response to steroid hormone Source: RGD
  55. response to water deprivation Source: RGD
  56. response to zinc ion Source: RGD
  57. sensory perception of sound Source: RGD
  58. social behavior Source: RGD
  59. sphingolipid metabolic process Source: RGD
  60. synaptic transmission, dopaminergic Source: Ensembl
  61. synaptic vesicle amine transport Source: RGD
  62. terpene metabolic process Source: RGD
  63. visual perception Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Monooxygenase, Oxidoreductase

Keywords - Biological processi

Catecholamine biosynthesis, Neurotransmitter biosynthesis

Keywords - Ligandi

Iron, Metal-binding

Enzyme and pathway databases

BRENDAi1.14.16.2. 5301.
ReactomeiREACT_295841. Catecholamine biosynthesis.
SABIO-RKP04177.
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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi3853. Th.

Subcellular locationi

GO - Cellular componenti

  1. axon Source: RGD
  2. cytoplasm Source: RGD
  3. cytoplasmic side of plasma membrane Source: Ensembl
  4. cytoplasmic vesicle membrane Source: BHF-UCL
  5. cytosol Source: RGD
  6. dendrite Source: RGD
  7. melanosome membrane Source: Ensembl
  8. mitochondrion Source: BHF-UCL
  9. neuronal cell body Source: RGD
  10. neuron projection Source: RGD
  11. nucleus Source: Ensembl
  12. perikaryon Source: RGD
  13. smooth endoplasmic reticulum Source: Ensembl
  14. synaptic vesicle Source: RGD
  15. terminal bouton Source: RGD
Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed1 Publication
Chaini2 – 498497Tyrosine 3-monooxygenasePRO_0000205564Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei19 – 191Phosphoserine; by CaMK22 Publications
Modified residuei31 – 311Phosphoserine1 Publication
Modified residuei40 – 401Phosphoserine; by CaMK2 and PKA2 Publications

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

PhosphoSiteiP04177.

Expressioni

Gene expression databases

ExpressionAtlasiP04177. baseline and differential.
GenevestigatoriP04177.

Interactioni

Subunit structurei

Homotetramer.

Protein-protein interaction databases

BioGridi247158. 1 interaction.
IntActiP04177. 4 interactions.
MINTiMINT-4585867.

Structurei

Secondary structure

1
498
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi75 – 773Combined sources
Beta strandi80 – 856Combined sources
Beta strandi91 – 933Combined sources
Helixi98 – 1069Combined sources
Beta strandi110 – 1167Combined sources
Beta strandi119 – 1224Combined sources
Beta strandi133 – 1386Combined sources
Helixi141 – 15010Combined sources
Beta strandi162 – 1643Combined sources
Helixi171 – 1766Combined sources
Beta strandi177 – 1793Combined sources
Turni193 – 1964Combined sources
Helixi198 – 21316Combined sources
Helixi227 – 24721Combined sources
Helixi250 – 26213Combined sources
Helixi273 – 28311Combined sources
Beta strandi287 – 2904Combined sources
Helixi297 – 3048Combined sources
Turni305 – 3073Combined sources
Beta strandi308 – 3114Combined sources
Helixi329 – 3357Combined sources
Helixi337 – 3404Combined sources
Helixi343 – 35614Combined sources
Helixi361 – 37212Combined sources
Turni373 – 3775Combined sources
Beta strandi379 – 3824Combined sources
Beta strandi385 – 3884Combined sources
Helixi391 – 3944Combined sources
Helixi397 – 4037Combined sources
Beta strandi405 – 4128Combined sources
Helixi415 – 4195Combined sources
Beta strandi425 – 4273Combined sources
Beta strandi430 – 4367Combined sources
Helixi438 – 45013Combined sources
Beta strandi457 – 4615Combined sources
Turni462 – 4654Combined sources
Beta strandi466 – 4705Combined sources
Helixi473 – 49624Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1TOHX-ray2.30A156-498[»]
2MDANMR-A/B65-159[»]
2TOHX-ray2.30A156-498[»]
DisProtiDP00094.
ProteinModelPortaliP04177.
SMRiP04177. Positions 160-498.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP04177.

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi51 – 599Poly-Ala

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG3186.
GeneTreeiENSGT00390000010268.
HOGENOMiHOG000233373.
HOVERGENiHBG006841.
InParanoidiP04177.
KOiK00501.
OMAiYATHACG.
OrthoDBiEOG7KM5T1.
PhylomeDBiP04177.
TreeFamiTF313327.

Family and domain databases

Gene3Di1.10.800.10. 1 hit.
InterProiIPR001273. 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]
PANTHERiPTHR11473. PTHR11473. 1 hit.
PfamiPF00351. Biopterin_H. 1 hit.
PF12549. TOH_N. 2 hits.
[Graphical view]
PIRSFiPIRSF000336. TH. 1 hit.
PRINTSiPR00372. FYWHYDRXLASE.
SUPFAMiSSF56534. SSF56534. 1 hit.
TIGRFAMsiTIGR01269. Tyr_3_monoox. 1 hit.
PROSITEiPS00367. BH4_AAA_HYDROXYL_1. 1 hit.
PS51410. BH4_AAA_HYDROXYL_2. 1 hit.
[Graphical view]

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.

Cross-referencesi

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1TOHX-ray2.30A156-498[»]
2MDANMR-A/B65-159[»]
2TOHX-ray2.30A156-498[»]
DisProtiDP00094.
ProteinModelPortaliP04177.
SMRiP04177. Positions 160-498.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247158. 1 interaction.
IntActiP04177. 4 interactions.
MINTiMINT-4585867.

Chemistry

BindingDBiP04177.
ChEMBLiCHEMBL2462.

PTM databases

PhosphoSiteiP04177.

Proteomic databases

PaxDbiP04177.
PRIDEiP04177.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi7054.
RGDi3853. Th.

Phylogenomic databases

eggNOGiCOG3186.
GeneTreeiENSGT00390000010268.
HOGENOMiHOG000233373.
HOVERGENiHBG006841.
InParanoidiP04177.
KOiK00501.
OMAiYATHACG.
OrthoDBiEOG7KM5T1.
PhylomeDBiP04177.
TreeFamiTF313327.

Enzyme and pathway databases

UniPathwayiUPA00747; UER00733.
BRENDAi1.14.16.2. 5301.
ReactomeiREACT_295841. Catecholamine biosynthesis.
SABIO-RKP04177.

Miscellaneous databases

EvolutionaryTraceiP04177.
NextBioi605346.
PROiP04177.

Gene expression databases

ExpressionAtlasiP04177. baseline and differential.
GenevestigatoriP04177.

Family and domain databases

Gene3Di1.10.800.10. 1 hit.
InterProiIPR001273. 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]
PANTHERiPTHR11473. PTHR11473. 1 hit.
PfamiPF00351. Biopterin_H. 1 hit.
PF12549. TOH_N. 2 hits.
[Graphical view]
PIRSFiPIRSF000336. TH. 1 hit.
PRINTSiPR00372. FYWHYDRXLASE.
SUPFAMiSSF56534. SSF56534. 1 hit.
TIGRFAMsiTIGR01269. Tyr_3_monoox. 1 hit.
PROSITEiPS00367. BH4_AAA_HYDROXYL_1. 1 hit.
PS51410. BH4_AAA_HYDROXYL_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. 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, IDENTIFICATION BY 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, IDENTIFICATION BY 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.

Entry informationi

Entry nameiTY3H_RAT
AccessioniPrimary (citable) accession number: P04177
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 20, 1987
Last sequence update: January 23, 2007
Last modified: April 1, 2015
This is version 141 of the entry and version 3 of the sequence. [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

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.