1. 2-L-carboxy-2,3-dihydroindole-5,6-quinone
2. L-dopachrome

• Cytoplasm (Predicted from LogP)

1. Tyrosinase precursor
2. L-dopachrome tautomerase precursor
3. Tyrosinase-related protein 2

1. Monophenol monooxygenase
2. Tumor rejection antigen AB
3. SK29-AB
4. LB24-AB

MLLAVLYCLLWSFQTSAGHFPRACVSSKNLMEKECCPPWSGDRSPCGQLSGRGSCQNILL
SNAPLGPQFPFTGVDDRESWPSVFYNRTCQCSGNFMGFNCGNCKFGFWGPNCTERRLLVR
RNIFDLSAPEKDKFFAYLTLAKHTISSDYVIPIGTYGQMKNGSTPMFNDINIYDLFVWMH
YYVSMDALLGGSEIWRDIDFAHEAPAFLPWHRLFLLRWEQEIQKLTGDENFTIPYWDWRD
AEKCDICTDEYMGGQHPTNPNLLSPASFFSSWQIVCSRLEEYNSHQSLCNGTPEGPLRRN
PGNHDKSRTPRLPSSADVEFCLSLTQYESGSMDKAANFSFRNTLEGFASPLTGIADASQS
SMHNALHIYMNGTMSQVQGSANDPIFLLHHAFVDSIFEQWLRRHRPLQEVYPEANAPIGH
NRESYMVPFIPLYRNGDFFISSKDLGYDYSYLQDSDPDSFQDYIKSYLEQASRIWSWLLG
AAMVGAVLTALLAGLVSLLCRHKRKQLPEEKQPLLMEKEDYHSLYQSHL

• Riboflavin Metabolism (map00740 )
• Stilbene, coumarine and lignin biosynthesis (map00940 )
• Tyrosine Metabolism (map00350 )

• L-tyrosine + L-dopa + O2 = L-dopa + dopaquinone + H2O

• Tyrosinase (PF00264 )

• 1-18

• 477-497

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

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. [PubMed ]
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. [PubMed ]
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. [PubMed ]
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. [PubMed ]
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. [PubMed ]
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. [PubMed ]
7. 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 ]
8. 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 ]
9. 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 ]
10. 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 ]
11. 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 ]
12. 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 ]
13. 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 ]
14. 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 ]
15. 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 ]
16. 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 ]
17. 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 ]
18. 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 ]
19. Oetting WS, King RA: Molecular analysis of type I-A (tyrosinase negative) oculocutaneous albinism. Hum Genet. 1992 Nov;90(3):258-62. [PubMed ]
20. 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 ]
21. 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 ]
22. 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 ]
23. Summers CG, Oetting WS, King RA: Diagnosis of oculocutaneous albinism with molecular analysis. Am J Ophthalmol. 1996 Jun;121(6):724-6. [PubMed ]
24. 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 ]
25. 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 ]
26. 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. [PubMed ]
27. 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. [PubMed ]
28. 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. [PubMed ]
29. 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 ]

1. DT
2. DCT
3. L- dopachrome Delta-isomerase
4. Tyrosinase-related protein 2
5. TRP-2
6. TRP2

MSPLWWGFLLSCLGCKILPGAQGQFPRVCMTVDSLVNKECCPRLGAESANVCGSQQGRGQ
CTEVRADTRPWSGPYILRNQDDRELWPRKFFHRTCKCTGNFAGYNCGDCKFGWTGPNCER
KKPPVIRQNIHSLSPQEREQFLGALDLAKKRVHPDYVITTQHWLGLLGPNGTQPQFANCS
VYDFFVWLHYYSVRDTLLGPGRPYRAIDFSHQGPAFVTWHRYHLLCLERDLQRLIGNESF
ALPYWNFATGRNECDVCTDQLFGAARPDDPTLISRNSRFSSWETVCDSLDDYNHLVTLCN
GTYEGLLRRNQMGRNSMKLPTLKDIRDCLSLQKFDNPPFFQNSTFSFRNALEGFDKADGT
LDSQVMSLHNLVHSFLNGTNALPHSAANDPIFVVLHSFTDAIFDEWMKRFNPPADAWPQE
LAPIGHNRMYNMVPFFPPVTNEELFLTSDQLGYSYAIDLPVSVEETPGWPTTLLVVMGTL
VALVGLFVLLAFLQYRRLRKGYTPLMETHLSSKRYTEEA

• Tyrosine Metabolism (map00350 )

• L-dopachrome = 5,6-dihydroxyindole-2-carboxylate

• Tyrosinase (PF00264 )

• 1-23

• 473-493

ATGAGCCCCCTTTGGTGGGGGTTTCTGCTCAGTTGCTTGGGCTGCAAAATCCTGCCAGGA
GCCCAGGGTCAGTTCCCCCGAGTCTGCATGACGGTGGACAGCCTAGTGAACAAGGAGTGC
TGCCCACGCCTGGGTGCAGAGTCGGCCAATGTCTGTGGCTCTCAGCAAGGCCGGGGGCAG
TGCACAGAGGTGCGAGCCGACACAAGGCCCTGGAGTGGTCCCTACATCCTACGAAACCAG
GATGACCGTGAGCTGTGGCCAAGAAAATTCTTCCACCGGACCTGCAAGTGCACAGGAAAC
TTTGCCGGCTATAATTGTGGAGACTGCAAGTTTGGCTGGACCGGTCCCAACTGCGAGCGG
AAGAAACCACCAGTGATTCGGCAGAACATCCATTCCTTGAGTCCTCAGGAAAGAGAGCAG
TTCTTGGGCGCCTTAGATCTCGCGAAGAAGAGAGTACACCCCGACTACGTGATCACCACA
CAACACTGGCTGGGCCTGCTTGGGCCCAATGGAACCCAGCCGCAGTTTGCCAACTGCAGT
GTTTATGATTTTTTTGTGTGGCTCCATTATTATTCTGTTAGAGATACATTATTAGGACCA
GGACGCCCCTACAGGGCCATAGATTTCTCACATCAAGGACCTGCATTTGTTACCTGGCAC
CGGTACCATTTGTTGTGTCTGGAAAGAGATCTCCAGCGACTCATTGGCAATGAGTCTTTT
GCTTTGCCCTACTGGAACTTTGCCACTGGGAGGAACGAGTGTGATGTGTGTACAGACCAG
CTGTTTGGGGCAGCGAGACCAGACGATCCGACTCTGATTAGTCGGAACTCAAGATTCTCC
AGCTGGGAAACTGTCTGTGATAGCTTGGATGACTACAACCACCTGGTCACCTTGTGCAAT
GGAACCTATGAAGGTTTGCTGAGAAGAAATCAAATGGGAAGAAACAGCATGAAATTGCCA
ACCTTAAAAGACATACGAGATTGCCTGTCTCTCCAGAAGTTTGACAATCCTCCCTTCTTC
CAGAACTCTACCTTCAGTTTCAGGAATGCTTTGGAAGGGTTTGATAAAGCAGATGGGACT
CTGGATTCTCAAGTGATGAGCCTTCATAATTTGGTTCATTCCTTCCTGAACGGGACAAAC
GCTTTGCCACATTCAGCCGCCAATGATCCCATTTTTGTGGTTCTTCATTCCTTTACTGAT
GCCATCTTTGATGAGTGGATGAAAAGATTTAATCCTCCTGCAGATGCCTGGCCTCAGGAG
CTGGCCCCTATTGGTCACAATCGGATGTACAACATGGTTCCTTTCTTCCCTCCAGTGACT
AATGAAGAACTCTTTTTAACCTCAGACCAACTTGGCTACAGCTATGCCATCGATCTGCCA
GTTTCAGTTGAAGAAACTCCAGGTTGGCCCACAACTCTCTTAGTAGTCATGGGAACACTG
GTGGCTTTGGTTGGTCTTTTTGTGCTGTTGGCTTTTCTTCAATATAGAAGACTTCGAAAA
GGATATACACCCCTAATGGAGACACATTTAAGCAGCAAGAGATACACAGAAGAAGCCTAG

1. Yokoyama K, Suzuki H, Yasumoto K, Tomita Y, Shibahara S: Molecular cloning and functional analysis of a cDNA coding for human DOPAchrome tautomerase/tyrosinase-related protein-2. Biochim Biophys Acta. 1994 Apr 6;1217(3):317-21. [PubMed ]
2. Cassady JL, Sturm RA: Sequence of the human dopachrome tautomerase-encoding TRP-2 cDNA. Gene. 1994 Jun 10;143(2):295-8. [PubMed ]
3. Bouchard B, Del Marmol V, Jackson IJ, Cherif D, Dubertret L: Molecular characterization of a human tyrosinase-related-protein-2 cDNA. Patterns of expression in melanocytic cells. Eur J Biochem. 1994 Jan 15;219(1-2):127-34. [PubMed ]
4. Sturm RA, O'Sullivan BJ, Box NF, Smith AG, Smit SE, Puttick ER, Parsons PG, Dunn IS: Chromosomal structure of the human TYRP1 and TYRP2 loci and comparison of the tyrosinase-related protein gene family. Genomics. 1995 Sep 1;29(1):24-34. [PubMed ]
5. Yokoyama K, Yasumoto K, Suzuki H, Shibahara S: Cloning of the human DOPAchrome tautomerase/tyrosinase-related protein 2 gene and identification of two regulatory regions required for its pigment cell-specific expression. J Biol Chem. 1994 Oct 28;269(43):27080-7. [PubMed ]

MSPLWWGFLLSCLGCKILPGAQGQFPRVCMTVDSLVNKECCPRLGAESANVCGSQQGRGQ
CTEVRADTRPWSGPYILRNQDDRELWPRKFFHRTCKCTGNFAGYNCGDCKFGWTGPNCER
KKPPVIRQNIHSLSPQEREQFLGALDLAKKRVHPDYVITTQHWLGLLGPNGTQPQFANCS
VYDFFVWLHYYSVRDTLLGPGRPYRAIDFSHQGPAFVTWHRYHLLCLERDLQRLIGNESF
ALPYWNFATGRNECDVCTDQLFGAARPDDPTLISRNSRFSSWETVCDSLDDYNHLVTLCN
GTYEGLLRRNQMGRNSMKLPTLKDIRDCLSLQKFDNPPFFQNSTFSFRNALEGFDKADGT
LDSQVMSLHNLVHSFLNGTNALPHSAANDPIFVVISNRLLYNATTNILEHVRKEKATKEL
PSLHVLVLHSFTDAIFDEWMKRFNPPADAWPQELAPIGHNRMYNMVPFFPPVTNEELFLT
SDQLGYSYAIDLPVSVEETPGWPTTLLVVMGTLVALVGLFVLLAFLQYRRLRKGYTPLME
THLSSKRYTEEA

• Tyrosinase (PF00264 )

• None

• None

1. Khong HT, Rosenberg SA: Pre-existing immunity to tyrosinase-related protein (TRP)-2, a new TRP-2 isoform, and the NY-ESO-1 melanoma antigen in a patient with a dramatic response to immunotherapy. J Immunol. 2002 Jan 15;168(2):951-6. [PubMed ]
2. Liu G, Khong HT, Wheeler CJ, Yu JS, Black KL, Ying H: Molecular and functional analysis of tyrosinase-related protein (TRP)-2 as a cytotoxic T lymphocyte target in patients with malignant glioma. J Immunother. 2003 Jul-Aug;26(4):301-12. [PubMed ]