Target General Infomation
Target ID
T62390
Former ID
TTDS00365
Target Name
Tyrosine 3-monooxygenase
Gene Name
TH
Synonyms
Tyrosine 3-hydroxylase; TH
Target Type
Successful
Disease Dietary shortage [ICD9: 260-269; ICD10: E40-E46]
Parkinson's disease [ICD9: 332; ICD10: G20]
Pheochromocytoma [ICD9: 194.0, 227.0, 255.6; ICD10: C74.1, D35.0]
Function
Plays an important role in the physiology of adrenergic neurones.
BioChemical Class
Oxidoreductases acting on paired donors
UniProt ID
EC Number
EC 1.14.16.2
Sequence
MPTPDATTPQAKGFRRAVSELDAKQAEAIMVRGQGAPGPSLTGSPWPGTAAPAASYTPTP
RSPRFIGRRQSLIEDARKEREAAVAAAAAAVPSEPGDPLEAVAFEEKEGKAVLNLLFSPR
ATKPSALSRAVKVFETFEAKIHHLETRPAQRPRAGGPHLEYFVRLEVRRGDLAALLSGVR
QVSEDVRSPAGPKVPWFPRKVSELDKCHHLVTKFDPDLDLDHPGFSDQVYRQRRKLIAEI
AFQYRHGDPIPRVEYTAEEIATWKEVYTTLKGLYATHACGEHLEAFALLERFSGYREDNI
PQLEDVSRFLKERTGFQLRPVAGLLSARDFLASLAFRVFQCTQYIRHASSPMHSPEPDCC
HELLGHVPMLADRTFAQFSQDIGLASLGASDEEIEKLSTLYWFTVEFGLCKQNGEVKAYG
AGLLSSYGELLHCLSEEPEIRAFDPEAAAVQPYQDQTYQSVYFVSESFSDAKDKLRSYAS
RIQRPFSVKFDPYTLAIDVLDSPQAVRRSLEGVQDELDTLAHALSAIG
Drugs and Mode of Action
Drug(s) L-Phenylalanine Drug Info Approved Dietary shortage [540274], [550111]
L-Tyrosine Drug Info Approved Dietary shortage [468020], [550756]
Metyrosine Drug Info Approved Pheochromocytoma [538495], [541992]
Tetrahydrobiopterin Drug Info Approved Dietary shortage [537637], [540739]
ProSavin Drug Info Phase 1/2 Parkinson's disease [524296]
Inhibitor 3-chlorotyrosine Drug Info [543389]
3-iodotyrosine Drug Info [543389]
7,8-dihydrobiopterin Drug Info [551393]
alpha-propyldopacetamide Drug Info [543389]
Meta-Tyrosine Drug Info [551393]
Binder L-Phenylalanine Drug Info [535693], [536211], [536359]
L-Tyrosine Drug Info [535693], [536211]
Metyrosine Drug Info [536239]
Modulator ProSavin Drug Info [551478]
Cofactor Tetrahydrobiopterin Drug Info [536529]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
BioCyc Pathway Catecholamine biosynthesis
KEGG Pathway Tyrosine metabolism
Metabolic pathways
Dopaminergic synapse
Prolactin signaling pathway
Parkinson&#039
s disease
Cocaine addiction
Amphetamine addiction
Alcoholism
PANTHER Pathway Adrenaline and noradrenaline biosynthesis
Parkinson disease
Dopamine receptor mediated signaling pathway
Nicotine pharmacodynamics pathway
Pathway Interaction Database ATF-2 transcription factor network
AP-1 transcription factor network
p38 signaling mediated by MAPKAP kinases
Alpha-synuclein signaling
PathWhiz Pathway Catecholamine Biosynthesis
WikiPathways Monoamine Transport
SIDS Susceptibility Pathways
Biogenic Amine Synthesis
Dopaminergic Neurogenesis
Metabolism of amino acids and derivatives
Dopamine metabolism
Parkinsons Disease Pathway
Nicotine Activity on Dopaminergic Neurons
References
Ref 468020(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4791).
Ref 524296ClinicalTrials.gov (NCT01856439) Long Term Safety and Efficacy Study of ProSavin in Parkinson's Disease. U.S. National Institutes of Health.
Ref 537637Sapropterin: A New Therapeutic Agent for Phenylketonuria (September) (CE). Ann Pharmacother. 2009 Aug 4.
Ref 538495FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 017871.
Ref 540274(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 3313).
Ref 540739(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5276).
Ref 541992(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6956).
Ref 550111Drug information of L-Alanine, Health Canada, 2008. (drugid: 1025)
Ref 550756Drug information of L-Phenylalanine, 2008. eduDrugs.
Ref 535693In situ and in vitro evidence for DCoH/HNF-1 alpha transcription of tyrosinase in human skin melanocytes. Biochem Biophys Res Commun. 2003 Feb 7;301(2):610-6.
Ref 536211Effect of metals and phenylalanine on the activity of human tryptophan hydroxylase-2: comparison with that on tyrosine hydroxylase activity. Neurosci Lett. 2006 Jul 3;401(3):261-5. Epub 2006 Apr 11.
Ref 536239Dopamine beta-hydroxylase deficiency. A genetic disorder of cardiovascular regulation. Hypertension. 1991 Jul;18(1):1-8.
Ref 536359Selectivity and affinity determinants for ligand binding to the aromatic amino acid hydroxylases. Curr Med Chem. 2007;14(4):455-67.
Ref 536529Biochemistry of postmortem brains in Parkinson's disease: historical overview and future prospects. J Neural Transm Suppl. 2007;(72):113-20.
Ref 543389(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1243).
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
Ref 551478Clinical pipeline report, company report or official report of Oxford BioMedica.

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