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Showing Protein Tyrosinase (HMDBP00087)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 27 metabolites
Identification
HMDB Protein ID HMDBP00087
Secondary Accession Numbers
  • 5319
  • HMDBP03837
Name Tyrosinase
Synonyms
  1. LB24-AB
  2. Monophenol monooxygenase
  3. SK29-AB
  4. Tumor rejection antigen AB
Gene Name TYR
Protein Type Unknown
Biological Properties
General Function Involved in oxidoreductase activity
Specific Function This 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.
Pathways
  • Alkaptonuria
  • Disulfiram Action Pathway
  • Dopamine beta-hydroxylase deficiency
  • Hawkinsinuria
  • Melanogenesis
  • Monoamine oxidase-a deficiency (MAO-A)
  • Riboflavin metabolism
  • Riboflavin Metabolism
  • Tyrosine metabolism
  • Tyrosine metabolism
  • Tyrosinemia Type I
  • Tyrosinemia, transient, of the newborn
Reactions
L-Dopa + Oxygen → Dopaquinone + Water details
L-Tyrosine + Oxygen → Dopaquinone + Water details
L-Tyrosine + Oxygen → L-Dopa + Water details
L-Dopa + L-Tyrosine + Oxygen → Dopaquinone + L-Dopa + Water details
Hydroquinone + Oxygen → Quinone + Water details
Tyramine + Oxygen + NADH + Hydrogen Ion → Dopamine + NAD + Water details
(S)-N-Methylcoclaurine + Oxygen + Reduced acceptor → (S)-3-Hydroxy-N-methylcoclaurine + Water + Acceptor details
5,6-Dihydroxyindole + Oxygen → Indole-5,6-quinone + Water details
GO Classification
Biological Process
thymus development
cell proliferation
eye pigment biosynthetic process
melanin biosynthetic process from tyrosine
visual perception
Cellular Component
Golgi-associated vesicle
perinuclear region of cytoplasm
melanosome membrane
melanosome
lysosome
integral to membrane
Function
catalytic activity
oxidoreductase activity
Molecular Function
monophenol monooxygenase activity
protein homodimerization activity
copper ion binding
protein heterodimerization activity
Process
metabolic process
Cellular Location
  1. Melanosome membrane
  2. Single-pass type I membrane protein
Gene Properties
Chromosome Location 11
Locus 11q14-q21
SNPs TYR
Gene Sequence 
>1590 bp
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
Protein Properties
Number of Residues 529
Molecular Weight 60392.69
Theoretical pI 6.118
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence 
>Tyrosinase
MLLAVLYCLLWSFQTSAGHFPRACVSSKNLMEKECCPPWSGDRSPCGQLSGRGSCQNILL
SNAPLGPQFPFTGVDDRESWPSVFYNRTCQCSGNFMGFNCGNCKFGFWGPNCTERRLLVR
RNIFDLSAPEKDKFFAYLTLAKHTISSDYVIPIGTYGQMKNGSTPMFNDINIYDLFVWMH
YYVSMDALLGGSEIWRDIDFAHEAPAFLPWHRLFLLRWEQEIQKLTGDENFTIPYWDWRD
AEKCDICTDEYMGGQHPTNPNLLSPASFFSSWQIVCSRLEEYNSHQSLCNGTPEGPLRRN
PGNHDKSRTPRLPSSADVEFCLSLTQYESGSMDKAANFSFRNTLEGFASPLTGIADASQS
SMHNALHIYMNGTMSQVQGSANDPIFLLHHAFVDSIFEQWLRRHRPLQEVYPEANAPIGH
NRESYMVPFIPLYRNGDFFISSKDLGYDYSYLQDSDPDSFQDYIKSYLEQASRIWSWLLG
AAMVGAVLTALLAGLVSLLCRHKRKQLPEEKQPLLMEKEDYHSLYQSHL
GenBank ID Protein 340037
UniProtKB/Swiss-Prot ID P14679
UniProtKB/Swiss-Prot Entry Name TYRO_HUMAN
PDB IDs Not Available
GenBank Gene ID M27160
GeneCard ID TYR
GenAtlas ID TYR
HGNC ID HGNC:12442
References
General References
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  2. 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. [PubMed:17081065 ]
  3. 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. [PubMed:1903356 ]
  4. 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. [PubMed:2823263 ]
  5. 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. [PubMed:2499655 ]
  6. 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. [PubMed:1711223 ]
  7. 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. [PubMed:8340755 ]
  8. 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. [PubMed:11153699 ]
  9. 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. [PubMed:2480811 ]
  10. 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. [PubMed:2504160 ]
  11. 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. [PubMed:11214319 ]
  12. 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. [PubMed:8477259 ]
  13. Oetting WS, King RA: Molecular basis of albinism: mutations and polymorphisms of pigmentation genes associated with albinism. Hum Mutat. 1999;13(2):99-115. [PubMed:10094567 ]
  14. 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. [PubMed:12643545 ]
  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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:1943686 ]
  22. Oetting WS, King RA: Molecular analysis of type I-A (tyrosinase negative) oculocutaneous albinism. Hum Genet. 1992 Nov;90(3):258-62. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:7955413 ]
  26. Summers CG, Oetting WS, King RA: Diagnosis of oculocutaneous albinism with molecular analysis. Am J Ophthalmol. 1996 Jun;121(6):724-6. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:10671066 ]
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  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. [PubMed: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. [PubMed: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. [PubMed:17999355 ]
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