NameTyrosinase
Synonyms
  • 1.14.18.1
  • LB24-AB
  • Monophenol monooxygenase
  • SK29-AB
  • Tumor rejection antigen AB
Gene NameTYR
OrganismHuman
Amino acid sequence
>lcl|BSEQ0000503|Tyrosinase
MLLAVLYCLLWSFQTSAGHFPRACVSSKNLMEKECCPPWSGDRSPCGQLSGRGSCQNILL
SNAPLGPQFPFTGVDDRESWPSVFYNRTCQCSGNFMGFNCGNCKFGFWGPNCTERRLLVR
RNIFDLSAPEKDKFFAYLTLAKHTISSDYVIPIGTYGQMKNGSTPMFNDINIYDLFVWMH
YYVSMDALLGGSEIWRDIDFAHEAPAFLPWHRLFLLRWEQEIQKLTGDENFTIPYWDWRD
AEKCDICTDEYMGGQHPTNPNLLSPASFFSSWQIVCSRLEEYNSHQSLCNGTPEGPLRRN
PGNHDKSRTPRLPSSADVEFCLSLTQYESGSMDKAANFSFRNTLEGFASPLTGIADASQS
SMHNALHIYMNGTMSQVQGSANDPIFLLHHAFVDSIFEQWLRRHRPLQEVYPEANAPIGH
NRESYMVPFIPLYRNGDFFISSKDLGYDYSYLQDSDPDSFQDYIKSYLEQASRIWSWLLG
AAMVGAVLTALLAGLVSLLCRHKRKQLPEEKQPLLMEKEDYHSLYQSHL
Number of residues529
Molecular Weight60392.69
Theoretical pI6.05
GO Classification
Functions
  • monophenol monooxygenase activity
  • protein homodimerization activity
  • protein heterodimerization activity
  • monooxygenase activity
  • copper ion binding
Processes
  • visual perception
  • melanin biosynthetic process from tyrosine
  • cell proliferation
  • eye pigment biosynthetic process
  • cellular nitrogen compound metabolic process
  • small molecule metabolic process
  • response to cAMP
  • melanin biosynthetic process
  • response to UV
  • response to vitamin D
  • thymus development
Components
  • melanosome membrane
  • integral component of membrane
  • cytosol
  • perinuclear region of cytoplasm
  • melanosome
  • cytoplasm
  • nucleus
  • Golgi-associated vesicle
  • lysosome
General FunctionProtein homodimerization activity
Specific FunctionThis is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the rate-limiting conversions of tyrosine to DOPA, DOPA to DOPA-quinone and possibly 5,6-dihydroxyindole to indole-5,6 quinone.
Pfam Domain Function
Transmembrane Regions477-497
GenBank Protein ID340037
UniProtKB IDP14679
UniProtKB Entry NameTYRO_HUMAN
Cellular LocationMelanosome membrane
Gene sequence
>lcl|BSEQ0021257|Tyrosinase (TYR)
ATGCTCCTGGCTGTTTTGTACTGCCTGCTGTGGAGTTTCCAGACCTCCGCTGGCCATTTC
CCTAGAGCCTGTGTCTCCTCTAAGAACCTGATGGAGAAGGAATGCTGTCCACCGTGGAGC
GGGGACAGGAGTCCCTGTGGCCAGCTTTCAGGCAGAGGTTCCTGTCAGAATATCCTTCTG
TCCAATGCACCACTTGGGCCTCAATTTCCCTTCACAGGGGTGGATGACCGGGAGTCGTGG
CCTTCCGTCTTTTATAATAGGACCTGCCAGTGCTCTGGCAACTTCATGGGATTCAACTGT
GGAAACTGCAAGTTTGGCTTTTGGGGACCAAACTGCACAGAGAGACGACTCTTGGTGAGA
AGAAACATCTTCGATTTGAGTGCCCCAGAGAAGGACAAATTTTTTGCCTACCTCACTTTA
GCAAAGCATACCATCAGCTCAGACTATGTCATCCCCATAGGGACCTATGGCCAAATGAAA
AATGGATCAACACCCATGTTTAACGACATCAATATTTATGACCTCTTTGTCTGGATGCAT
TATTATGTGTCAATGGATGCACTGCTTGGGGGATCTGAAATCTGGAGAGACATTGATTTT
GCCCATGAAGCACCAGCTTTTCTGCCTTGGCATAGACTCTTCTTGTTGCGGTGGGAACAA
GAAATCCAGAAGCTGACAGGAGATGAAAACTTCACTATTCCATATTGGGACTGGCGGGAT
GCAGAAAAGTGTGACATTTGCACAGATGAGTACATGGGAGGTCAGCACCCCACAAATCCT
AACTTACTCAGCCCAGCATCATTCTTCTCCTCTTGGCAGATTGTCTGTAGCCGATTGGAG
GAGTACAACAGCCATCAGTCTTTATGCAATGGAACGCCCGAGGGACCTTTACGGCGTAAT
CCTGGAAACCATGACAAATCCAGAACCCCAAGGCTCCCCTCTTCAGCTGATGTAGAATTT
TGCCTGAGTTTGACCCAATATGAATCTGGTTCCATGGATAAAGCTGCCAATTTCAGCTTT
AGAAATACACTGGAAGGATTTGCTAGTCCACTTACTGGGATAGCGGATGCCTCTCAAAGC
AGCATGCACAATGCCTTGCACATCTATATGAATGGAACAATGTCCCAGGTACAGGGATCT
GCCAACGATCCTATCTTCCTTCTTCACCATGCATTTGTTGACAGTATTTTTGAGCAGTGG
CTCCGAAGGCACCGTCCTCTTCAAGAAGTTTATCCAGAAGCCAATGCACCCATTGGACAT
AACCGGGAATCCTACATGGTTCCTTTTATACCACTGTACAGAAATGGTGATTTCTTTATT
TCATCCAAAGATCTGGGCTATGACTATAGCTATCTACAAGATTCAGACCCAGACTCTTTT
CAAGACTACATTAAGTCCTATTTGGAACAAGCGAGTCGGATCTGGTCATGGCTCCTTGGG
GCGGCGATGGTAGGGGCCGTCCTCACTGCCCTGCTGGCAGGGCTTGTGAGCTTGCTGTGT
CGTCACAAGAGAAAGCAGCTTCCTGAAGAAAAGCAGCCACTCCTCATGGAGAAAGAGGAT
TACCACAGCTTGTATCAGAGCCATTTATAA
GenBank Gene IDM27160
GeneCard IDNot Available
GenAtlas IDTYR
HGNC IDHGNC:12442
Chromosome Location11
Locus11q14-q21
References
  1. Giebel LB, Strunk KM, Spritz RA: Organization and nucleotide sequences of the human tyrosinase gene and a truncated tyrosinase-related segment. Genomics. 1991 Mar;9(3):435-45. 1903356
  2. Kwon BS, Haq AK, Pomerantz SH, Halaban R: Isolation and sequence of a cDNA clone for human tyrosinase that maps at the mouse c-albino locus. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7473-7. 2823263
  3. Bouchard B, Fuller BB, Vijayasaradhi S, Houghton AN: Induction of pigmentation in mouse fibroblasts by expression of human tyrosinase cDNA. J Exp Med. 1989 Jun 1;169(6):2029-42. 2499655
  4. Chintamaneni CD, Halaban R, Kobayashi Y, Witkop CJ Jr, Kwon BS: A single base insertion in the putative transmembrane domain of the tyrosinase gene as a cause for tyrosinase-negative oculocutaneous albinism. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5272-6. 1711223
  5. Brichard V, Van Pel A, Wolfel T, Wolfel C, De Plaen E, Lethe B, Coulie P, Boon T: The tyrosinase gene codes for an antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J Exp Med. 1993 Aug 1;178(2):489-95. 8340755
  6. Martinez-Arias R, Comas D, Andres A, Abello MT, Domingo-Roura X, Bertranpetit J: The tyrosinase gene in gorillas and the albinism of 'Snowflake'. Pigment Cell Res. 2000 Dec;13(6):467-70. 11153699
  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. 15489334
  8. Kikuchi H, Miura H, Yamamoto H, Takeuchi T, Dei T, Watanabe M: Characteristic sequences in the upstream region of the human tyrosinase gene. Biochim Biophys Acta. 1989 Dec 22;1009(3):283-6. 2480811
  9. Takeda A, Tomita Y, Okinaga S, Tagami H, Shibahara S: Functional analysis of the cDNA encoding human tyrosinase precursor. Biochem Biophys Res Commun. 1989 Aug 15;162(3):984-90. 2504160
  10. Murphy WJ, Eizirik E, Johnson WE, Zhang YP, Ryder OA, O'Brien SJ: Molecular phylogenetics and the origins of placental mammals. Nature. 2001 Feb 1;409(6820):614-8. 11214319
  11. Oetting WS, King RA: Molecular basis of type I (tyrosinase-related) oculocutaneous albinism: mutations and polymorphisms of the human tyrosinase gene. Hum Mutat. 1993;2(1):1-6. 8477259
  12. Oetting WS, King RA: Molecular basis of albinism: mutations and polymorphisms of pigmentation genes associated with albinism. Hum Mutat. 1999;13(2):99-115. 10094567
  13. Basrur V, Yang F, Kushimoto T, Higashimoto Y, Yasumoto K, Valencia J, Muller J, Vieira WD, Watabe H, Shabanowitz J, Hearing VJ, Hunt DF, Appella E: Proteomic analysis of early melanosomes: identification of novel melanosomal proteins. J Proteome Res. 2003 Jan-Feb;2(1):69-79. 12643545
  14. Chi A, Valencia JC, Hu ZZ, Watabe H, Yamaguchi H, Mangini NJ, Huang H, Canfield VA, Cheng KC, Yang F, Abe R, Yamagishi S, Shabanowitz J, Hearing VJ, Wu C, Appella E, Hunt DF: Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes. J Proteome Res. 2006 Nov;5(11):3135-44. 17081065
  15. Spritz RA, Strunk KM, Giebel LB, King RA: Detection of mutations in the tyrosinase gene in a patient with type IA oculocutaneous albinism. N Engl J Med. 1990 Jun 14;322(24):1724-8. 2342539
  16. Giebel LB, Strunk KM, King RA, Hanifin JM, Spritz RA: A frequent tyrosinase gene mutation in classic, tyrosinase-negative (type IA) oculocutaneous albinism. Proc Natl Acad Sci U S A. 1990 May;87(9):3255-8. 1970634
  17. Giebel LB, Tripathi RK, Strunk KM, Hanifin JM, Jackson CE, King RA, Spritz RA: Tyrosinase gene mutations associated with type IB ("yellow") oculocutaneous albinism. Am J Hum Genet. 1991 Jun;48(6):1159-67. 1903591
  18. Tripathi RK, Strunk KM, Giebel LB, Weleber RG, Spritz RA: Tyrosinase gene mutations in type I (tyrosinase-deficient) oculocutaneous albinism define two clusters of missense substitutions. Am J Med Genet. 1992 Jul 15;43(5):865-71. 1642278
  19. Spritz RA, Strunk KM, Hsieh CL, Sekhon GS, Francke U: Homozygous tyrosinase gene mutation in an American black with tyrosinase-negative (type IA) oculocutaneous albinism. Am J Hum Genet. 1991 Feb;48(2):318-24. 1899321
  20. Giebel LB, Tripathi RK, King RA, Spritz RA: A tyrosinase gene missense mutation in temperature-sensitive type I oculocutaneous albinism. A human homologue to the Siamese cat and the Himalayan mouse. J Clin Invest. 1991 Mar;87(3):1119-22. 1900309
  21. King RA, Mentink MM, Oetting WS: Non-random distribution of missense mutations within the human tyrosinase gene in type I (tyrosinase-related) oculocutaneous albinism. Mol Biol Med. 1991 Feb;8(1):19-29. 1943686
  22. Oetting WS, King RA: Molecular analysis of type I-A (tyrosinase negative) oculocutaneous albinism. Hum Genet. 1992 Nov;90(3):258-62. 1487241
  23. Tripathi RK, Bundey S, Musarella MA, Droetto S, Strunk KM, Holmes SA, Spritz RA: Mutations of the tyrosinase gene in Indo-Pakistani patients with type I (tyrosinase-deficient) oculocutaneous albinism (OCA). Am J Hum Genet. 1993 Dec;53(6):1173-9. 7902671
  24. Gershoni-Baruch R, Rosenmann A, Droetto S, Holmes S, Tripathi RK, Spritz RA: Mutations of the tyrosinase gene in patients with oculocutaneous albinism from various ethnic groups in Israel. Am J Hum Genet. 1994 Apr;54(4):586-94. 8128955
  25. Breimer LH, Winder AF, Jay B, Jay M: Initiation codon mutation of the tyrosinase gene as a cause of human albinism. Clin Chim Acta. 1994 Jun;227(1-2):17-22. 7955413
  26. Summers CG, Oetting WS, King RA: Diagnosis of oculocutaneous albinism with molecular analysis. Am J Ophthalmol. 1996 Jun;121(6):724-6. 8644824
  27. Morell R, Spritz RA, Ho L, Pierpont J, Guo W, Friedman TB, Asher JH Jr: Apparent digenic inheritance of Waardenburg syndrome type 2 (WS2) and autosomal recessive ocular albinism (AROA). Hum Mol Genet. 1997 May;6(5):659-64. 9158138
  28. Spritz RA, Oh J, Fukai K, Holmes SA, Ho L, Chitayat D, France TD, Musarella MA, Orlow SJ, Schnur RE, Weleber RG, Levin AV: Novel mutations of the tyrosinase (TYR) gene in type I oculocutaneous albinism (OCA1). Hum Mutat. 1997;10(2):171-4. 9259202
  29. Oetting WS, Fryer JP, King RA: Mutations of the human tyrosinase gene associated with tyrosinase related oculocutaneous albinism (OCA1). Mutations in brief no. 204. Online. Hum Mutat. 1998;12(6):433-4. 10671066
  30. Passmore LA, Kaesmann-Kellner B, Weber BH: Novel and recurrent mutations in the tyrosinase gene and the P gene in the German albino population. Hum Genet. 1999 Sep;105(3):200-10. 10987646
  31. Tsai CH, Tsai FJ, Wu JY, Lin SP, Chang JG, Yang CF, Lee CC: Insertion/deletion mutations of type I oculocutaneous albinism in chinese patients from Taiwan. Hum Mutat. 1999 Dec;14(6):542. 10571953
  32. Camand O, Marchant D, Boutboul S, Pequignot M, Odent S, Dollfus H, Sutherland J, Levin A, Menasche M, Marsac C, Dufier JL, Heon E, Abitbol M: Mutation analysis of the tyrosinase gene in oculocutaneous albinism. Hum Mutat. 2001 Apr;17(4):352. 11295837
  33. Nakamura E, Miyamura Y, Matsunaga J, Kano Y, Dakeishi-Hara M, Tanita M, Kono M, Tomita Y: A novel mutation of the tyrosinase gene causing oculocutaneous albinism type 1 (OCA1). J Dermatol Sci. 2002 Feb;28(2):102-5. 11858948
  34. Opitz S, Kasmann-Kellner B, Kaufmann M, Schwinger E, Zuhlke C: Detection of 53 novel DNA variations within the tyrosinase gene and accumulation of mutations in 17 patients with albinism. Hum Mutat. 2004 Jun;23(6):630-1. 15146472
  35. Stokowski RP, Pant PV, Dadd T, Fereday A, Hinds DA, Jarman C, Filsell W, Ginger RS, Green MR, van der Ouderaa FJ, Cox DR: A genomewide association study of skin pigmentation in a South Asian population. Am J Hum Genet. 2007 Dec;81(6):1119-32. Epub 2007 Oct 15. 17999355
  36. Sulem P, Gudbjartsson DF, Stacey SN, Helgason A, Rafnar T, Magnusson KP, Manolescu A, Karason A, Palsson A, Thorleifsson G, Jakobsdottir M, Steinberg S, Palsson S, Jonasson F, Sigurgeirsson B, Thorisdottir K, Ragnarsson R, Benediktsdottir KR, Aben KK, Kiemeney LA, Olafsson JH, Gulcher J, Kong A, Thorsteinsdottir U, Stefansson K: Genetic determinants of hair, eye and skin pigmentation in Europeans. Nat Genet. 2007 Dec;39(12):1443-52. Epub 2007 Oct 21. 17952075
  37. Chong JX, Ouwenga R, Anderson RL, Waggoner DJ, Ober C: A population-based study of autosomal-recessive disease-causing mutations in a founder population. Am J Hum Genet. 2012 Oct 5;91(4):608-20. doi: 10.1016/j.ajhg.2012.08.007. Epub 2012 Sep 13. 22981120
  38. Simeonov DR, Wang X, Wang C, Sergeev Y, Dolinska M, Bower M, Fischer R, Winer D, Dubrovsky G, Balog JZ, Huizing M, Hart R, Zein WM, Gahl WA, Brooks BP, Adams DR: DNA variations in oculocutaneous albinism: an updated mutation list and current outstanding issues in molecular diagnostics. Hum Mutat. 2013 Jun;34(6):827-35. doi: 10.1002/humu.22315. Epub 2013 Apr 30. 23504663
  39. Shah SA, Din SU, Raheem N, Daud S, Mubeen J, Nadeem A, Tayyab M, Baloch DM, Babar ME, Ahmad J: Identification of a novel mutation (p.Ile198Thr) in gene TYR in a Pakistani family with nonsyndromic oculocutaneous albinism. Clin Exp Dermatol. 2014 Jul;39(5):646-8. doi: 10.1111/ced.12382. 24934919