Tyrosine 3-monooxygenase

Details

Name
Tyrosine 3-monooxygenase
Synonyms
  • 1.14.16.2
  • TH
  • TYH
  • Tyrosine 3-hydroxylase
Gene Name
TH
Organism
Humans
Amino acid sequence
>lcl|BSEQ0037053|Tyrosine 3-monooxygenase
MPTPDATTPQAKGFRRAVSELDAKQAEAIMVRGQGAPGPSLTGSPWPGTAAPAASYTPTP
RSPRFIGRRQSLIEDARKEREAAVAAAAAAVPSEPGDPLEAVAFEEKEGKAVLNLLFSPR
ATKPSALSRAVKVFETFEAKIHHLETRPAQRPRAGGPHLEYFVRLEVRRGDLAALLSGVR
QVSEDVRSPAGPKVPWFPRKVSELDKCHHLVTKFDPDLDLDHPGFSDQVYRQRRKLIAEI
AFQYRHGDPIPRVEYTAEEIATWKEVYTTLKGLYATHACGEHLEAFALLERFSGYREDNI
PQLEDVSRFLKERTGFQLRPVAGLLSARDFLASLAFRVFQCTQYIRHASSPMHSPEPDCC
HELLGHVPMLADRTFAQFSQDIGLASLGASDEEIEKLSTLYWFTVEFGLCKQNGEVKAYG
AGLLSSYGELLHCLSEEPEIRAFDPEAAAVQPYQDQTYQSVYFVSESFSDAKDKLRSYAS
RIQRPFSVKFDPYTLAIDVLDSPQAVRRSLEGVQDELDTLAHALSAIG
Number of residues
528
Molecular Weight
58599.545
Theoretical pI
6.25
GO Classification
Functions
amino acid binding / dopamine binding / enzyme binding / ferric iron binding / ferrous iron binding / oxygen binding / tetrahydrobiopterin binding / tyrosine 3-monooxygenase activity
Processes
anatomical structure morphogenesis / catecholamine biosynthetic process / cellular nitrogen compound metabolic process / cellular response to drug / cellular response to glucose stimulus / cellular response to growth factor stimulus / cellular response to manganese ion / cellular response to nicotine / cerebral cortex development / circadian sleep/wake cycle / dopamine biosynthetic process / dopamine biosynthetic process from tyrosine / eating behavior / embryonic camera-type eye morphogenesis / epinephrine biosynthetic process / eye photoreceptor cell development / fatty acid metabolic process / glycoside metabolic process / heart development / heart morphogenesis / isoquinoline alkaloid metabolic process / learning / locomotory behavior / mating behavior / memory / multicellular organismal aging / neurotransmitter biosynthetic process / norepinephrine biosynthetic process / organ morphogenesis / phthalate metabolic process / phytoalexin metabolic process / pigmentation / regulation of heart contraction / response to activity / response to amphetamine / response to corticosterone / response to electrical stimulus / response to estradiol / response to ethanol / response to ether / response to herbicide / response to hypoxia / response to immobilization stress / response to isolation stress / response to light stimulus / response to lipopolysaccharide / response to nutrient levels / response to peptide hormone / response to pyrethroid / response to salt stress / response to water deprivation / response to zinc ion / sensory perception of sound / small molecule metabolic process / social behavior / sphingolipid metabolic process / synaptic transmission, dopaminergic / synaptic vesicle amine transport / terpene metabolic process / visual perception
Components
cytoplasm / cytoplasmic side of plasma membrane / cytoplasmic vesicle / cytosol / dendrite / melanosome membrane / mitochondrion / neuron projection / nucleus / perikaryon / smooth endoplasmic reticulum / synaptic vesicle / terminal bouton
General Function
Tyrosine 3-monooxygenase activity
Specific Function
Plays an important role in the physiology of adrenergic neurons.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Not Available
Gene sequence
>lcl|BSEQ0016153|Tyrosine 3-monooxygenase (TH)
ATGCCCACCCCCGACGCCACCACGCCACAGGCCAAGGGCTTCCGCAGGGCCGTGTCTGAG
CTGGACGCCAAGCAGGCAGAGGCCATCATGTCCCCGCGGTTCATTGGGCGCAGGCAGAGC
CTCATCGAGGACGCCCGCAAGGAGCGGGAGGCGGCGGTGGCAGCAGCGGCCGCTGCAGTC
CCCTCGGAGCCCGGGGACCCCCTGGAGGCTGTGGCCTTTGAGGAGAAGGAGGGGAAGGCC
GTGCTAAACCTGCTCTTCTCCCCGAGGGCCACCAAGCCCTCGGCGCTGTCCCGAGCTGTG
AAGGTGTTTGAGACGTTTGAAGCCAAAATCCACCATCTAGAGACCCGGCCCGCCCAGAGG
CCGCGAGCTGGGGGCCCCCACCTGGAGTACTTCGTGCGCCTCGAGGTGCGCCGAGGGGAC
CTGGCCGCCCTGCTCAGTGGTGTGCGCCAGGTGTCAGAGGACGTGCGCAGCCCCGCGGGG
CCCAAGGTCCCCTGGTTCCCAAGAAAAGTGTCAGAGCTGGACAAGTGTCATCACCTGGTC
ACCAAGTTCGACCCTGACCTGGACTTGGACCACCCGGGCTTCTCGGACCAGGTGTACCGC
CAGCGCAGGAAGCTGATTGCTGAGATCGCCTTCCAGTACAGGCACGGCGACCCGATTCCC
CGTGTGGAGTACACCGCCGAGGAGATTGCCACCTGGAAGGAGGTCTACACCACGCTGAAG
GGCCTCTACGCCACGCACGCCTGCGGGGAGCACCTGGAGGCCTTTGCTTTGCTGGAGCGC
TTCAGCGGCTACCGGGAAGACAATATCCCCCAGCTGGAGGACGTCTCCCGCTTCCTGAAG
GAGCGCACGGGCTTCCAGCTGCGGCCTGTGGCCGGCCTGCTGTCCGCCCGGGACTTCCTG
GCCAGCCTGGCCTTCCGCGTGTTCCAGTGCACCCAGTATATCCGCCACGCGTCCTCGCCC
ATGCACTCCCCTGAGCCGGACTGCTGCCACGAGCTGCTGGGGCACGTGCCCATGCTGGCC
GACCGCACCTTCGCGCAGTTCTCGCAGGACATTGGCCTGGCGTCCCTGGGGGCCTCGGAT
GAGGAAATTGAGAAGCTGTCCACGCTGTACTGGTTCACGGTGGAGTTCGGGCTGTGTAAG
CAGAACGGGGAGGTGAAGGCCTATGGTGCCGGGCTGCTGTCCTCCTACGGGGAGCTCCTG
CACTGCCTGTCTGAGGAGCCTGAGATTCGGGCCTTCGACCCTGAGGCTGCGGCCGTGCAG
CCCTACCAAGACCAGACGTACCAGTCAGTCTACTTCGTGTCTGAGAGCTTCAGTGACGCC
AAGGACAAGCTCAGGAGCTATGCCTCACGCATCCAGCGCCCCTTCTCCGTGAAGTTCGAC
CCGTACACGCTGGCCATCGACGTGCTGGACAGCCCCCAGGCCGTGCGGCGCTCCCTGGAG
GGTGTCCAGGATGAGCTGGACACCCTTGCCCATGCGCTGAGTGCCATTGGCTAG
Chromosome Location
11
Locus
11p15.5
External Identifiers
ResourceLink
UniProtKB IDP07101
UniProtKB Entry NameTY3H_HUMAN
GenBank Protein ID37127
GenBank Gene IDY00414
GenAtlas IDTH
HGNC IDHGNC:11782
General References
  1. Kaneda N, Kobayashi K, Ichinose H, Kishi F, Nakazawa A, Kurosawa Y, Fujita K, Nagatsu T: Isolation of a novel cDNA clone for human tyrosine hydroxylase: alternative RNA splicing produces four kinds of mRNA from a single gene. Biochem Biophys Res Commun. 1987 Aug 14;146(3):971-5. [Article]
  2. Grima B, Lamouroux A, Boni C, Julien JF, Javoy-Agid F, Mallet J: A single human gene encoding multiple tyrosine hydroxylases with different predicted functional characteristics. Nature. 1987 Apr 16-22;326(6114):707-11. [Article]
  3. Kobayashi K, Kaneda N, Ichinose H, Kishi F, Nakazawa A, Kurosawa Y, Fujita K, Nagatsu T: Isolation of a full-length cDNA clone encoding human tyrosine hydroxylase type 3. Nucleic Acids Res. 1987 Aug 25;15(16):6733. [Article]
  4. Kobayashi K, Kaneda N, Ichinose H, Kishi F, Nakazawa A, Kurosawa Y, Fujita K, Nagatsu T: Structure of the human tyrosine hydroxylase gene: alternative splicing from a single gene accounts for generation of four mRNA types. J Biochem. 1988 Jun;103(6):907-12. [Article]
  5. Roma J, Saus E, Cuadros M, Reventos J, Sanchez de Toledo J, Gallego S: Characterisation of novel splicing variants of the tyrosine hydroxylase C-terminal domain in human neuroblastic tumours. Biol Chem. 2007 Apr;388(4):419-26. [Article]
  6. Taylor TD, Noguchi H, Totoki Y, Toyoda A, Kuroki Y, Dewar K, Lloyd C, Itoh T, Takeda T, Kim DW, She X, Barlow KF, Bloom T, Bruford E, Chang JL, Cuomo CA, Eichler E, FitzGerald MG, Jaffe DB, LaButti K, Nicol R, Park HS, Seaman C, Sougnez C, Yang X, Zimmer AR, Zody MC, Birren BW, Nusbaum C, Fujiyama A, Hattori M, Rogers J, Lander ES, Sakaki Y: Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature. 2006 Mar 23;440(7083):497-500. [Article]
  7. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  8. Le Bourdelles B, Boularand S, Boni C, Horellou P, Dumas S, Grima B, Mallet J: Analysis of the 5' region of the human tyrosine hydroxylase gene: combinatorial patterns of exon splicing generate multiple regulated tyrosine hydroxylase isoforms. J Neurochem. 1988 Mar;50(3):988-91. [Article]
  9. Ginns EI, Rehavi M, Martin BM, Weller M, O'Malley KL, LaMarca ME, McAllister CG, Paul SM: Expression of human tyrosine hydroxylase cDNA in invertebrate cells using a baculovirus vector. J Biol Chem. 1988 May 25;263(15):7406-10. [Article]
  10. Le Bourdelles B, Horellou P, Le Caer JP, Denefle P, Latta M, Haavik J, Guibert B, Mayaux JF, Mallet J: Phosphorylation of human recombinant tyrosine hydroxylase isoforms 1 and 2: an additional phosphorylated residue in isoform 2, generated through alternative splicing. J Biol Chem. 1991 Sep 15;266(26):17124-30. [Article]
  11. Bademci G, Edwards TL, Torres AL, Scott WK, Zuchner S, Martin ER, Vance JM, Wang L: A rare novel deletion of the tyrosine hydroxylase gene in Parkinson disease. Hum Mutat. 2010 Oct;31(10):E1767-71. doi: 10.1002/humu.21351. [Article]
  12. Ludecke B, Dworniczak B, Bartholome K: A point mutation in the tyrosine hydroxylase gene associated with Segawa's syndrome. Hum Genet. 1995 Jan;95(1):123-5. [Article]
  13. Ludecke B, Bartholome K: Frequent sequence variant in the human tyrosine hydroxylase gene. Hum Genet. 1995 Jun;95(6):716. [Article]
  14. Knappskog PM, Flatmark T, Mallet J, Ludecke B, Bartholome K: Recessively inherited L-DOPA-responsive dystonia caused by a point mutation (Q381K) in the tyrosine hydroxylase gene. Hum Mol Genet. 1995 Jul;4(7):1209-12. [Article]
  15. Ludecke B, Knappskog PM, Clayton PT, Surtees RA, Clelland JD, Heales SJ, Brand MP, Bartholome K, Flatmark T: Recessively inherited L-DOPA-responsive parkinsonism in infancy caused by a point mutation (L205P) in the tyrosine hydroxylase gene. Hum Mol Genet. 1996 Jul;5(7):1023-8. [Article]
  16. Kunugi H, Kawada Y, Hattori M, Ueki A, Otsuka M, Nanko S: Association study of structural mutations of the tyrosine hydroxylase gene with schizophrenia and Parkinson's disease. Am J Med Genet. 1998 Mar 28;81(2):131-3. [Article]
  17. Ishiguro H, Arinami T, Saito T, Akazawa S, Enomoto M, Mitushio H, Fujishiro H, Tada K, Akimoto Y, Mifune H, Shiozuka S, Hamaguchi H, Toru M, Shibuya H: Systematic search for variations in the tyrosine hydroxylase gene and their associations with schizophrenia, affective disorders, and alcoholism. Am J Med Genet. 1998 Sep 7;81(5):388-96. [Article]
  18. van den Heuvel LP, Luiten B, Smeitink JA, de Rijk-van Andel JF, Hyland K, Steenbergen-Spanjers GC, Janssen RJ, Wevers RA: A common point mutation in the tyrosine hydroxylase gene in autosomal recessive L-DOPA-responsive dystonia in the Dutch population. Hum Genet. 1998 Jun;102(6):644-6. [Article]
  19. Brautigam C, Steenbergen-Spanjers GC, Hoffmann GF, Dionisi-Vici C, van den Heuvel LP, Smeitink JA, Wevers RA: Biochemical and molecular genetic characteristics of the severe form of tyrosine hydroxylase deficiency. Clin Chem. 1999 Dec;45(12):2073-8. [Article]
  20. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [Article]
  21. Swaans RJ, Rondot P, Renier WO, Van Den Heuvel LP, Steenbergen-Spanjers GC, Wevers RA: Four novel mutations in the tyrosine hydroxylase gene in patients with infantile parkinsonism. Ann Hum Genet. 2000 Jan;64(Pt 1):25-31. [Article]
  22. DE Lonlay P, Nassogne MC, van Gennip AH, van Cruchten AC, Billatte de Villemeur T, Cretz M, Stoll C, Launay JM, Steenberger-Spante GC, van den Heuvel LP, Wevers RA, Saudubray JM, Abeling NG: Tyrosine hydroxylase deficiency unresponsive to L-dopa treatment with unusual clinical and biochemical presentation. J Inherit Metab Dis. 2000 Dec;23(8):819-25. [Article]
  23. Schiller A, Wevers RA, Steenbergen GC, Blau N, Jung HH: Long-term course of L-dopa-responsive dystonia caused by tyrosine hydroxylase deficiency. Neurology. 2004 Oct 26;63(8):1524-6. [Article]
  24. Diepold K, Schutz B, Rostasy K, Wilken B, Hougaard P, Guttler F, Romstad A, Birk Moller L: Levodopa-responsive infantile parkinsonism due to a novel mutation in the tyrosine hydroxylase gene and exacerbation by viral infections. Mov Disord. 2005 Jun;20(6):764-7. [Article]
  25. Moller LB, Romstad A, Paulsen M, Hougaard P, Ormazabal A, Pineda M, Blau N, Guttler F, Artuch R: Pre- and postnatal diagnosis of tyrosine hydroxylase deficiency. Prenat Diagn. 2005 Aug;25(8):671-5. [Article]
  26. Verbeek MM, Steenbergen-Spanjers GC, Willemsen MA, Hol FA, Smeitink J, Seeger J, Grattan-Smith P, Ryan MM, Hoffmann GF, Donati MA, Blau N, Wevers RA: Mutations in the cyclic adenosine monophosphate response element of the tyrosine hydroxylase gene. Ann Neurol. 2007 Oct;62(4):422-6. [Article]
  27. Giovanniello T, Leuzzi V, Carducci C, Carducci C, Sabato ML, Artiola C, Santagata S, Pozzessere S, Antonozzi I: Tyrosine hydroxylase deficiency presenting with a biphasic clinical course. Neuropediatrics. 2007 Aug;38(4):213-5. [Article]
  28. Wu ZY, Lin Y, Chen WJ, Zhao GX, Xie H, Murong SX, Wang N: Molecular analyses of GCH-1, TH and parkin genes in Chinese dopa-responsive dystonia families. Clin Genet. 2008 Dec;74(6):513-21. doi: 10.1111/j.1399-0004.2008.01039.x. Epub 2008 Jun 11. [Article]
  29. Clot F, Grabli D, Cazeneuve C, Roze E, Castelnau P, Chabrol B, Landrieu P, Nguyen K, Ponsot G, Abada M, Doummar D, Damier P, Gil R, Thobois S, Ward AJ, Hutchinson M, Toutain A, Picard F, Camuzat A, Fedirko E, San C, Bouteiller D, LeGuern E, Durr A, Vidailhet M, Brice A: Exhaustive analysis of BH4 and dopamine biosynthesis genes in patients with Dopa-responsive dystonia. Brain. 2009 Jul;132(Pt 7):1753-63. doi: 10.1093/brain/awp084. Epub 2009 Jun 2. [Article]
  30. Willemsen MA, Verbeek MM, Kamsteeg EJ, de Rijk-van Andel JF, Aeby A, Blau N, Burlina A, Donati MA, Geurtz B, Grattan-Smith PJ, Haeussler M, Hoffmann GF, Jung H, de Klerk JB, van der Knaap MS, Kok F, Leuzzi V, de Lonlay P, Megarbane A, Monaghan H, Renier WO, Rondot P, Ryan MM, Seeger J, Smeitink JA, Steenbergen-Spanjers GC, Wassmer E, Weschke B, Wijburg FA, Wilcken B, Zafeiriou DI, Wevers RA: Tyrosine hydroxylase deficiency: a treatable disorder of brain catecholamine biosynthesis. Brain. 2010 Jun;133(Pt 6):1810-22. doi: 10.1093/brain/awq087. Epub 2010 Apr 29. [Article]
  31. Mak CM, Lam CW, Siu TS, Chan KY, Siu WK, Yeung WL, Hui J, Wong VC, Low LC, Ko CH, Fung CW, Chen SP, Yuen YP, Lee HC, Yau E, Chan B, Tong SF, Tam S, Chan YW: Biochemical and molecular characterization of tyrosine hydroxylase deficiency in Hong Kong Chinese. Mol Genet Metab. 2010 Apr;99(4):431-3. doi: 10.1016/j.ymgme.2009.12.011. Epub 2009 Dec 21. [Article]
  32. Haugarvoll K, Bindoff LA: A novel compound heterozygous tyrosine hydroxylase mutation (p.R441P) with complex phenotype. J Parkinsons Dis. 2011;1(1):119-22. doi: 10.3233/JPD-2011-11006. [Article]
  33. Giovanniello T, Claps D, Carducci C, Carducci C, Blau N, Vigevano F, Antonozzi I, Leuzzi V: A new tyrosine hydroxylase genotype associated with early-onset severe encephalopathy. J Child Neurol. 2012 Apr;27(4):523-5. doi: 10.1177/0883073811420717. Epub 2011 Sep 22. [Article]
  34. Stamelou M, Mencacci NE, Cordivari C, Batla A, Wood NW, Houlden H, Hardy J, Bhatia KP: Myoclonus-dystonia syndrome due to tyrosine hydroxylase deficiency. Neurology. 2012 Jul 31;79(5):435-41. doi: 10.1212/WNL.0b013e318261714a. Epub 2012 Jul 18. [Article]
  35. Chi CS, Lee HF, Tsai CR: Tyrosine hydroxylase deficiency in Taiwanese infants. Pediatr Neurol. 2012 Feb;46(2):77-82. doi: 10.1016/j.pediatrneurol.2011.11.012. [Article]
  36. Cai C, Shi W, Zeng Z, Zhang M, Ling C, Chen L, Cai C, Zhang B, Li WD: GTP cyclohydrolase I and tyrosine hydroxylase gene mutations in familial and sporadic dopa-responsive dystonia patients. PLoS One. 2013 Jun 6;8(6):e65215. doi: 10.1371/journal.pone.0065215. Print 2013. [Article]
  37. Fossbakk A, Kleppe R, Knappskog PM, Martinez A, Haavik J: Functional studies of tyrosine hydroxylase missense variants reveal distinct patterns of molecular defects in Dopa-responsive dystonia. Hum Mutat. 2014 Jul;35(7):880-90. doi: 10.1002/humu.22565. Epub 2014 Jun 3. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00135Tyrosineapproved, investigational, nutraceuticalunknownbinderDetails
DB00765MetyrosineapprovedyesbinderDetails
DB00120Phenylalanineapproved, investigational, nutraceuticalunknownbinderDetails
DB00360Sapropterinapproved, investigationalyescofactorDetails
DB035523-TyrosineexperimentalunknownDetails
DB04400L-erythro-7,8-dihydrobiopterinexperimentalunknownDetails