1. DHI;dopaminochrome
2. aminochrome

1. Pavel S: A new possible pathogenesis of some gallstones. Med Hypotheses. 1984 Jul;14(3):285-92. [PubMed ]
2. Pavel S, Muskiet FA: Eumelanin (precursor) metabolites as markers for pigmented malignant melanoma: a preliminary report. Cancer Detect Prev. 1983;6(1-2):311-6. [PubMed ]
3. Pavel S, Boverhof R, Wolthers BG: Identification of 5-hydroxy-6-indolyl-O-sulfate in urine of patients with malignant melanoma. J Invest Dermatol. 1984 Jun;82(6):577-9. [PubMed ]

1. Tyrosinase precursor
2. L-dopachrome tautomerase precursor
3. D-dopachrome decarboxylase

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 ]

1. D-dopachrome tautomerase
2. Phenylpyruvate tautomerase II

MPFLELDTNLPANRVPAGLEKRLCAAAASILGKPADRVNVTVRPGLAMALSGSTEPCAQL
SISSIGVVGTAEDNRSHSAHFFEFLTKELALGQDRILIRFFPLESWQIGKIGTVMTFL

• MIF (PF01187 )

• None

• None

1. Nishihira J, Fujinaga M, Kuriyama T, Suzuki M, Sugimoto H, Nakagawa A, Tanaka I, Sakai M: Molecular cloning of human D-dopachrome tautomerase cDNA: N-terminal proline is essential for enzyme activation. Biochem Biophys Res Commun. 1998 Feb 13;243(2):538-44. [PubMed ]
2. Esumi N, Budarf M, Ciccarelli L, Sellinger B, Kozak CA, Wistow G: Conserved gene structure and genomic linkage for D-dopachrome tautomerase (DDT) and MIF. Mamm Genome. 1998 Sep;9(9):753-7. [PubMed ]
3. Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP, et al.: The DNA sequence of human chromosome 22. Nature. 1999 Dec 2;402(6761):489-95. [PubMed ]
4. Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J: Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat Biotechnol. 2003 May;21(5):566-9. Epub 2003 Mar 31. [PubMed ]
5. Hochstrasser DF, Frutiger S, Paquet N, Bairoch A, Ravier F, Pasquali C, Sanchez JC, Tissot JD, Bjellqvist B, Vargas R, et al.: Human liver protein map: a reference database established by microsequencing and gel comparison. Electrophoresis. 1992 Dec;13(12):992-1001. [PubMed ]
6. Sugimoto H, Taniguchi M, Nakagawa A, Tanaka I, Suzuki M, Nishihira J: Crystal structure of human D-dopachrome tautomerase, a homologue of macrophage migration inhibitory factor, at 1.54 A resolution. Biochemistry. 1999 Mar 16;38(11):3268-79. [PubMed ]