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P04177

- TY3H_RAT

UniProt

P04177 - TY3H_RAT

Protein

Tyrosine 3-monooxygenase

Gene

Th

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 136 (01 Oct 2014)
      Sequence version 3 (23 Jan 2007)
      Previous versions | rss
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    Functioni

    Plays an important role in the physiology of adrenergic neurons.

    Catalytic activityi

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

    Cofactori

    Fe2+ ion.

    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 binding Source: RGD
    8. protein domain specific binding Source: RGD
    9. tetrahydrobiopterin binding Source: RGD
    10. 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 light stimulus Source: RGD
    45. response to lipopolysaccharide Source: RGD
    46. response to metal ion Source: RGD
    47. response to nicotine Source: RGD
    48. response to nutrient levels Source: RGD
    49. response to organic cyclic compound Source: RGD
    50. response to peptide hormone Source: RGD
    51. response to pyrethroid Source: RGD
    52. response to salt stress Source: RGD
    53. response to steroid hormone Source: RGD
    54. response to water deprivation Source: RGD
    55. response to zinc ion Source: RGD
    56. sensory perception of sound Source: RGD
    57. social behavior Source: RGD
    58. sphingolipid metabolic process Source: RGD
    59. synaptic transmission, dopaminergic Source: Ensembl
    60. synaptic vesicle amine transport Source: RGD
    61. terpene metabolic process Source: RGD
    62. visual perception Source: Ensembl

    Keywords - Molecular functioni

    Monooxygenase, Oxidoreductase

    Keywords - Biological processi

    Catecholamine biosynthesis, Neurotransmitter biosynthesis

    Keywords - Ligandi

    Iron, Metal-binding

    Enzyme and pathway databases

    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: 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

    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

    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 – 773
    Beta strandi80 – 856
    Beta strandi91 – 933
    Helixi98 – 1069
    Beta strandi110 – 1167
    Beta strandi119 – 1224
    Beta strandi133 – 1386
    Helixi141 – 15010
    Beta strandi162 – 1643
    Helixi171 – 1766
    Beta strandi177 – 1793
    Turni193 – 1964
    Helixi198 – 21316
    Helixi227 – 24721
    Helixi250 – 26213
    Helixi273 – 28311
    Beta strandi287 – 2904
    Helixi297 – 3048
    Turni305 – 3073
    Beta strandi308 – 3114
    Helixi329 – 3357
    Helixi337 – 3404
    Helixi343 – 35614
    Helixi361 – 37212
    Turni373 – 3775
    Beta strandi379 – 3824
    Beta strandi385 – 3884
    Helixi391 – 3944
    Helixi397 – 4037
    Beta strandi405 – 4128
    Helixi415 – 4195
    Beta strandi425 – 4273
    Beta strandi430 – 4367
    Helixi438 – 45013
    Beta strandi457 – 4615
    Turni462 – 4654
    Beta strandi466 – 4705
    Helixi473 – 49624

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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.
    OMAiELDKCHH.
    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

    MPTPSAPSPQ PKGFRRAVSE QDAKQAEAVT SPRFIGRRQS LIEDARKERE    50
    AAAAAAAAAV ASSEPGNPLE AVVFEERDGN AVLNLLFSLR GTKPSSLSRA 100
    VKVFETFEAK IHHLETRPAQ RPLAGSPHLE YFVRFEVPSG DLAALLSSVR 150
    RVSDDVRSAR EDKVPWFPRK VSELDKCHHL VTKFDPDLDL DHPGFSDQVY 200
    RQRRKLIAEI AFQYKHGEPI PHVEYTAEEI ATWKEVYVTL KGLYATHACR 250
    EHLEGFQLLE RYCGYREDSI PQLEDVSRFL KERTGFQLRP VAGLLSARDF 300
    LASLAFRVFQ CTQYIRHASS PMHSPEPDCC HELLGHVPML ADRTFAQFSQ 350
    DIGLASLGAS DEEIEKLSTV YWFTVEFGLC KQNGELKAYG AGLLSSYGEL 400
    LHSLSEEPEV RAFDPDTAAV QPYQDQTYQP VYFVSESFND AKDKLRNYAS 450
    RIQRPFSVKF DPYTLAIDVL DSPHTIQRSL EGVQDELHTL AHALSAIS 498
    Length:498
    Mass (Da):55,966
    Last modified:January 23, 2007 - v3
    Checksum:i17F7E003D29218C5
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M10244 mRNA. Translation: AAA42257.1 .
    L22651 mRNA. Translation: AAA42258.1 .
    PIRi A00510. WHRTY.
    RefSeqi NP_036872.1. NM_012740.3.
    UniGenei Rn.11082.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1TOH X-ray 2.30 A 156-498 [» ]
    2MDA NMR - A/B 65-159 [» ]
    2TOH X-ray 2.30 A 156-498 [» ]
    DisProti DP00094.
    ProteinModelPortali P04177.
    SMRi P04177. Positions 160-498.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 247158. 1 interaction.
    IntActi P04177. 4 interactions.
    MINTi MINT-4585867.

    Chemistry

    BindingDBi P04177.
    ChEMBLi CHEMBL2462.

    PTM databases

    PhosphoSitei P04177.

    Proteomic databases

    PaxDbi P04177.
    PRIDEi P04177.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000027682 ; ENSRNOP00000027682 ; ENSRNOG00000020410 .
    GeneIDi 25085.
    KEGGi rno:25085.
    UCSCi RGD:3853. rat.

    Organism-specific databases

    CTDi 7054.
    RGDi 3853. Th.

    Phylogenomic databases

    eggNOGi COG3186.
    GeneTreei ENSGT00390000010268.
    HOGENOMi HOG000233373.
    HOVERGENi HBG006841.
    InParanoidi P04177.
    KOi K00501.
    OMAi ELDKCHH.
    OrthoDBi EOG7KM5T1.
    PhylomeDBi P04177.
    TreeFami TF313327.

    Enzyme and pathway databases

    UniPathwayi UPA00747 ; UER00733 .
    SABIO-RK P04177.

    Miscellaneous databases

    EvolutionaryTracei P04177.
    NextBioi 605346.
    PROi P04177.

    Gene expression databases

    Genevestigatori P04177.

    Family and domain databases

    Gene3Di 1.10.800.10. 1 hit.
    InterProi 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 ]
    PANTHERi PTHR11473. PTHR11473. 1 hit.
    Pfami PF00351. Biopterin_H. 1 hit.
    PF12549. TOH_N. 2 hits.
    [Graphical view ]
    PIRSFi PIRSF000336. TH. 1 hit.
    PRINTSi PR00372. FYWHYDRXLASE.
    SUPFAMi SSF56534. SSF56534. 1 hit.
    TIGRFAMsi TIGR01269. Tyr_3_monoox. 1 hit.
    PROSITEi PS00367. BH4_AAA_HYDROXYL_1. 1 hit.
    PS51410. BH4_AAA_HYDROXYL_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    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: October 1, 2014
    This is version 136 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