UniProtKB - P17289 (TY3H_BOVIN)
Tyrosine 3-monooxygenase
TH
Functioni
Catalyzes the conversion of L-tyrosine to L-dihydroxyphenylalanine (L-Dopa), the rate-limiting step in the biosynthesis of cathecolamines, dopamine, noradrenaline, and adrenaline. Uses tetrahydrobiopterin and molecular oxygen to convert tyrosine to L-Dopa (By similarity).
In addition to tyrosine, is able to catalyze the hydroxylation of phenylalanine and tryptophan with lower specificity (By similarity).
Positively regulates the regression of retinal hyaloid vessels during postnatal development (By similarity).
By similarityCatalytic activityi
- (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + L-tyrosine + O2 = (4aS,6R)-4a-hydroxy-L-erythro-5,6,7,8-tetrahydrobiopterin + L-dopaBy similarityEC:1.14.16.2By similarityThis reaction proceeds in the forwardBy similarity direction.
Cofactori
Activity regulationi
: dopamine biosynthesis Pathwayi
This protein is involved in step 1 of the subpathway that synthesizes dopamine from L-tyrosine.By similarity 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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 324 | Iron; via tele nitrogenBy similarity | 1 | |
Metal bindingi | 329 | Iron; via tele nitrogenBy similarity | 1 | |
Metal bindingi | 369 | IronBy similarity | 1 | |
Sitei | 418 | Important for substrate specificityBy similarity | 1 |
GO - Molecular functioni
- iron ion binding Source: InterPro
- tyrosine 3-monooxygenase activity Source: GO_Central
GO - Biological processi
- dopamine biosynthetic process from tyrosine Source: GO_Central
- heart development Source: GO_Central
- hyaloid vascular plexus regression Source: UniProtKB
- neurotransmitter biosynthetic process Source: UniProtKB-KW
- response to ethanol Source: GO_Central
- response to hypoxia Source: GO_Central
Keywordsi
Molecular function | Monooxygenase, Oxidoreductase |
Biological process | Catecholamine biosynthesis, Neurotransmitter biosynthesis |
Ligand | Iron, Metal-binding |
Enzyme and pathway databases
SABIO-RKi | P17289 |
UniPathwayi | UPA00747;UER00733 |
Names & Taxonomyi
Protein namesi | Recommended name: Tyrosine 3-monooxygenase (EC:1.14.16.2By similarity)Alternative name(s): Tyrosine 3-hydroxylase Short name: TH |
Gene namesi | Name:TH |
Organismi | Bos taurus (Bovine) |
Taxonomic identifieri | 9913 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Artiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos |
Proteomesi |
|
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm By similarity
Nucleus
- Nucleus By similarity
Other locations
- perinuclear region By similarity
- axon By similarity
- synaptic vesicle By similarity
Note: When phosphorylated at Ser-19 shows a nuclear distribution and when phsphorylated at Ser-31 as well at Ser-40 shows a cytosolic distribution (By similarity). Expressed in dopaminergic axons and axon terminals (By similarity).By similarity
Other locations
- axon Source: GO_Central
- cytoplasm Source: GO_Central
- perikaryon Source: GO_Central
- perinuclear region of cytoplasm Source: UniProtKB
Keywords - Cellular componenti
Cell junction, Cell projection, Cytoplasm, Cytoplasmic vesicle, Nucleus, SynapsePTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | Removed1 Publication | |||
ChainiPRO_0000205560 | 2 – 491 | Tyrosine 3-monooxygenaseAdd BLAST | 490 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 19 | Phosphoserine; by CaMK21 Publication | 1 | |
Modified residuei | 31 | Phosphoserine1 Publication | 1 | |
Modified residuei | 40 | Phosphoserine; by CaMK2 and PKA1 Publication | 1 | |
Modified residuei | 465 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
PhosphoproteinProteomic databases
PaxDbi | P17289 |
PTM databases
iPTMneti | P17289 |
Interactioni
Subunit structurei
Homotetramer (By similarity).
Interacts (when phosphorylated at Ser-19) with YWHAG; one YWHAG dimer bounds to one TH tetramer this interaction may influence the phosphorylation and dephosphorylation of other sites (By similarity).
By similarityProtein-protein interaction databases
STRINGi | 9913.ENSBTAP00000038050 |
Chemistry databases
BindingDBi | P17289 |
Family & Domainsi
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG3820, Eukaryota |
InParanoidi | P17289 |
OrthoDBi | 614557at2759 |
Family and domain databases
CDDi | cd03345, eu_TyrOH, 1 hit |
Gene3Di | 1.10.800.10, 1 hit |
InterProi | View protein in InterPro IPR045865, ACT-like_dom_sf IPR001273, ArAA_hydroxylase IPR036951, ArAA_hydroxylase_sf IPR036329, Aro-AA_hydroxylase_C_sf IPR019774, Aromatic-AA_hydroxylase_C IPR041903, Eu_TyrOH_cat IPR005962, Tyr_3_mOase IPR019773, Tyrosine_3-monooxygenase-like IPR021164, Tyrosine_hydroxylase_CS |
PANTHERi | PTHR11473, PTHR11473, 1 hit |
Pfami | View protein in Pfam PF00351, Biopterin_H, 1 hit PF12549, TOH_N, 2 hits |
PIRSFi | PIRSF000336, TH, 1 hit |
PRINTSi | PR00372, FYWHYDRXLASE |
SUPFAMi | SSF55021, SSF55021, 1 hit SSF56534, SSF56534, 1 hit |
TIGRFAMsi | TIGR01269, Tyr_3_monoox, 1 hit |
PROSITEi | View protein in PROSITE PS51410, BH4_AAA_HYDROXYL_2, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MPTPNAASPQ AKGFRRAVSE LDAKQAEAIM SPRFVGRRQS LIQDARKERE
60 70 80 90 100
KAEAAASSSE SAEAAAWLER DGEAVLTLLF ALPPTRPPAL TRAIKVFETF
110 120 130 140 150
EAHLHHLETR PAQPLRAGSP PLECFVRCEV PGPVVPALLS ALRRVAEDVR
160 170 180 190 200
AAGESKVLWF PRKVSELDKC HHLVTKFDPD LDLDHPGFSD QAYRQRRKLI
210 220 230 240 250
AEIAFQYKQG DPIPHVEYTA EETATWKEVY STLRGLYPTH ACREHLEAFE
260 270 280 290 300
LLERFCGYRE DRIPQLEDVS RFLKERTGFQ LRPAAGLLSA RDFLASLAFR
310 320 330 340 350
VFQCTQYIRH ASSPMHSPEP ECCHELLGHV PMLADRTFAQ FSQDIGLASL
360 370 380 390 400
GVSDEEIEKL STLYWFTVEF GLCKQNGEVK AYGAGLLSSY GELLHSLSEE
410 420 430 440 450
PEIRAFDPDA AAVQPYQDQT YQPVYFVSES FSDAKDKLRS YASRIQRPFS
460 470 480 490
VKFDPYTLAI DVLDSPHAIR HALDGVQDEM QALAHALNAI S
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 65 – 68 | AAWL → GSLV in AAA30798 (PubMed:2899135).Curated | 4 | |
Sequence conflicti | 73 | E → K in AAA30798 (PubMed:2899135).Curated | 1 | |
Sequence conflicti | 83 | P → R in AAA30798 (PubMed:2899135).Curated | 1 | |
Sequence conflicti | 86 | R → K in AAA30798 (PubMed:2899135).Curated | 1 | |
Sequence conflicti | 284 | A → V in AAA30798 (PubMed:2899135).Curated | 1 | |
Sequence conflicti | 321 | E → D in AAA30798 (PubMed:2899135).Curated | 1 | |
Sequence conflicti | 328 – 330 | GHV → AHG in AAA30798 (PubMed:2899135).Curated | 3 | |
Sequence conflicti | 380 | K → N in AAA30798 (PubMed:2899135).Curated | 1 | |
Sequence conflicti | 471 | H → R in AAA30798 (PubMed:2899135).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M36794 mRNA Translation: AAA30779.1 M36705 mRNA Translation: AAA30798.1 |
PIRi | I45983 JL0039 |
RefSeqi | NP_776309.1, NM_173884.2 |
Genome annotation databases
GeneIDi | 280707 |
KEGGi | bta:280707 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M36794 mRNA Translation: AAA30779.1 M36705 mRNA Translation: AAA30798.1 |
PIRi | I45983 JL0039 |
RefSeqi | NP_776309.1, NM_173884.2 |
3D structure databases
AlphaFoldDBi | P17289 |
SMRi | P17289 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 9913.ENSBTAP00000038050 |
Chemistry databases
BindingDBi | P17289 |
ChEMBLi | CHEMBL3713 |
PTM databases
iPTMneti | P17289 |
Proteomic databases
PaxDbi | P17289 |
Genome annotation databases
GeneIDi | 280707 |
KEGGi | bta:280707 |
Organism-specific databases
CTDi | 7054 |
Phylogenomic databases
eggNOGi | KOG3820, Eukaryota |
InParanoidi | P17289 |
OrthoDBi | 614557at2759 |
Enzyme and pathway databases
UniPathwayi | UPA00747;UER00733 |
SABIO-RKi | P17289 |
Miscellaneous databases
PROi | PR:P17289 |
Family and domain databases
CDDi | cd03345, eu_TyrOH, 1 hit |
Gene3Di | 1.10.800.10, 1 hit |
InterProi | View protein in InterPro IPR045865, ACT-like_dom_sf IPR001273, ArAA_hydroxylase IPR036951, ArAA_hydroxylase_sf IPR036329, Aro-AA_hydroxylase_C_sf IPR019774, Aromatic-AA_hydroxylase_C IPR041903, Eu_TyrOH_cat IPR005962, Tyr_3_mOase IPR019773, Tyrosine_3-monooxygenase-like IPR021164, Tyrosine_hydroxylase_CS |
PANTHERi | PTHR11473, PTHR11473, 1 hit |
Pfami | View protein in Pfam PF00351, Biopterin_H, 1 hit PF12549, TOH_N, 2 hits |
PIRSFi | PIRSF000336, TH, 1 hit |
PRINTSi | PR00372, FYWHYDRXLASE |
SUPFAMi | SSF55021, SSF55021, 1 hit SSF56534, SSF56534, 1 hit |
TIGRFAMsi | TIGR01269, Tyr_3_monoox, 1 hit |
PROSITEi | View protein in PROSITE PS51410, BH4_AAA_HYDROXYL_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | TY3H_BOVIN | |
Accessioni | P17289Primary (citable) accession number: P17289 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 1, 1990 |
Last sequence update: | January 23, 2007 | |
Last modified: | May 25, 2022 | |
This is version 144 of the entry and version 5 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families