The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

TYR  -  tyrosinase

Homo sapiens

Synonyms: ATN, CMM8, LB24-AB, Monophenol monooxygenase, OCA1, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of TYR


Psychiatry related information on TYR


High impact information on TYR

  • We have previously shown that MITF transactivates the gene for tyrosinase, a key enzyme for melanogenesis, and is critically involved in melanocyte differentiation [11].
  • These two patients were each a compound heterozygote for a different pathologic mutant allele and an allele containing a 'normal' polymorphism, Arg402Gln, which results in a tyrosinase polypeptide with reduced thermal stability [12].
  • Autosomal recessive ocular albinism associated with a functionally significant tyrosinase gene polymorphism [12].
  • In these patients, AROA thus appears to represent a clinically mild form of OCA1, with a fixed visual deficit resulting from low tyrosinase activity during fetal development but with normal pigmentation of the skin and hair postnatally [12].
  • One of the two major autosomal recessive forms involves the tyrosinase gene (OCA1), while the other form (OCA2) has recently been associated with alterations of the P gene on chromosome 15 [13].

Chemical compound and disease context of TYR


Biological context of TYR

  • High-level expression of TYR produced newly synthesized melanin and induced cell death in all of these cells [19].
  • We show that TYR and OCA2 have measurable effects on skin pigmentation differences between the west African and west European parental populations [20].
  • The evidence also suggests that at least some of the introns within the TYR, TYRP1, and TYRP2 coding regions were gained after duplication and that intron slippage is unlikely to have occurred [21].
  • These results suggest that hinokitiol-induced ERK phosphorylation reduces MITF and TYR transcription, and mediates the action of hinokitiol on melanogenesis [22].
  • In time-course experiments, the increase in cell number and tyrosinase activity became evident after one treatment of the melanocytes with 100 nM alpha-MSH for 48 hr [23].

Anatomical context of TYR


Associations of TYR with chemical compounds


Physical interactions of TYR


Enzymatic interactions of TYR


Regulatory relationships of TYR


Other interactions of TYR

  • We conclude that this mutation of the human TRP-1 gene affects its interaction with tyrosinase, resulting in dysregulation of tyrosinase activity, promotes the synthesis of brown versus black melanin, and is responsible for a third genetic type of OCA in humans, which we classify as "OCA3."[3]
  • Tyrosinase-positive OCA (OCA2), which is the most common, affects approximately 1/3,900 newborns and has a carrier frequency of approximately 1/33 [42].
  • Functional analysis of microphthalmia-associated transcription factor in pigment cell-specific transcription of the human tyrosinase family genes [43].
  • The DT gene is a member of the tyrosinase gene family and specifically expressed in melanin-producing cells [44].
  • In five out of six cases high numbers of CD8(+)/tetramer(+) cells could be detected by flow cytometry, and in four patients lymphocyte populations specific for two different melanoma antigens (Melan-A/MART1 and tyrosinase) were contemporaneously present [45].

Analytical, diagnostic and therapeutic context of TYR

  • Western blot analysis and measurement of enzyme activity revealed that the expression of TYRP1 or DCT had little effect on the amount or activity of cointroduced TYR in either the melanocytic or nonmelanocytic cells [19].
  • RESULTS: the nested RT-PCR amplified the TYR and TYRP1 sequences from 14 and 2 of the 30 healthy bloods, respectively [46].
  • With the recent availability of novel antibodies against melanoma antigens tyrosinase and MART-1, it is important to validate their usefulness in pathology practice and in screening patients for immunotherapy treatment [5].
  • A decreasing CTL response against the internal tyrosinase peptide was documented in 1 patient through the course of vaccination and a decrease in DTH reactions [47].
  • Immunoblotting analysis with anti-tyrosinase antibody (alpha Ty-SP) demonstrated the amount of tyrosinase was slightly increased in TRP-1 overexpressing cells but slightly decreased in anti-sense infectant cells [48].


  1. Microphthalmia transcription factor in the immunohistochemical diagnosis of metastatic melanoma: comparison with four other melanoma markers. Miettinen, M., Fernandez, M., Franssila, K., Gatalica, Z., Lasota, J., Sarlomo-Rikala, M. Am. J. Surg. Pathol. (2001) [Pubmed]
  2. Prostate cancer risk: associations with ultraviolet radiation, tyrosinase and melanocortin-1 receptor genotypes. Luscombe, C.J., French, M.E., Liu, S., Saxby, M.F., Jones, P.W., Fryer, A.A., Strange, R.C. Br. J. Cancer (2001) [Pubmed]
  3. Mutation in and lack of expression of tyrosinase-related protein-1 (TRP-1) in melanocytes from an individual with brown oculocutaneous albinism: a new subtype of albinism classified as "OCA3". Boissy, R.E., Zhao, H., Oetting, W.S., Austin, L.M., Wildenberg, S.C., Boissy, Y.L., Zhao, Y., Sturm, R.A., Hearing, V.J., King, R.A., Nordlund, J.J. Am. J. Hum. Genet. (1996) [Pubmed]
  4. Immunophenotyping of melanomas for tyrosinase: implications for vaccine development. Chen, Y.T., Stockert, E., Tsang, S., Coplan, K.A., Old, L.J. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  5. Expression of gp100, MART-1, tyrosinase, and S100 in paraffin-embedded primary melanomas and locoregional, lymph node, and visceral metastases: implications for diagnosis and immunotherapy. A study conducted by the EORTC Melanoma Cooperative Group. de Vries, T.J., Smeets, M., de Graaf, R., Hou-Jensen, K., Bröcker, E.B., Renard, N., Eggermont, A.M., van Muijen, G.N., Ruiter, D.J. J. Pathol. (2001) [Pubmed]
  6. The genetic susceptibility to Gilles de la Tourette syndrome in a large multiple affected British kindred: linkage analysis excludes a role for the genes coding for dopamine D1, D2, D3, D4, D5 receptors, dopamine beta hydroxylase, tyrosinase, and tyrosine hydroxylase. Brett, P.M., Curtis, D., Robertson, M.M., Gurling, H.M. Biol. Psychiatry (1995) [Pubmed]
  7. Oculocutaneous albinism, immunodeficiency, hematological disorders, and minor anomalies: a new autosomal recessive syndrome? Kotzot, D., Richter, K., Gierth-Fiebig, K. Am. J. Med. Genet. (1994) [Pubmed]
  8. Schizophrenia-associated chromosome 11q21 translocation: identification of flanking markers and development of chromosome 11q fragment hybrids as cloning and mapping resources. Fletcher, J.M., Evans, K., Baillie, D., Byrd, P., Hanratty, D., Leach, S., Julier, C., Gosden, J.R., Muir, W., Porteous, D.J. Am. J. Hum. Genet. (1993) [Pubmed]
  9. The effects of tyrosine depletion in normal healthy volunteers: implications for unipolar depression. McLean, A., Rubinsztein, J.S., Robbins, T.W., Sahakian, B.J. Psychopharmacology (Berl.) (2004) [Pubmed]
  10. Familial association of albinism and schizophrenia. Clarke, D.J., Buckley, M.E. The British journal of psychiatry : the journal of mental science. (1989) [Pubmed]
  11. Epistatic relationship between Waardenburg syndrome genes MITF and PAX3. Watanabe, A., Takeda, K., Ploplis, B., Tachibana, M. Nat. Genet. (1998) [Pubmed]
  12. Autosomal recessive ocular albinism associated with a functionally significant tyrosinase gene polymorphism. Fukai, K., Holmes, S.A., Lucchese, N.J., Siu, V.M., Weleber, R.G., Schnur, R.E., Spritz, R.A. Nat. Genet. (1995) [Pubmed]
  13. African origin of an intragenic deletion of the human P gene in tyrosinase positive oculocutaneous albinism. Durham-Pierre, D., Gardner, J.M., Nakatsu, Y., King, R.A., Francke, U., Ching, A., Aquaron, R., del Marmol, V., Brilliant, M.H. Nat. Genet. (1994) [Pubmed]
  14. Human melanoma patients recognize an HLA-A1-restricted CTL epitope from tyrosinase containing two cysteine residues: implications for tumor vaccine development. Kittlesen, D.J., Thompson, L.W., Gulden, P.H., Skipper, J.C., Colella, T.A., Shabanowitz, J., Hunt, D.F., Engelhard, V.H., Slingluff, C.L., Shabanowitz, J.A. J. Immunol. (1998) [Pubmed]
  15. Transcriptional regulation of differentiation, selective toxicity and ATGCAAAT binding of bisbenzimidazole derivatives in human melanoma cells. Wong, S.S., Sturm, R.A., Michel, J., Zhang, X.M., Danoy, P.A., McGregor, K., Jacobs, J.J., Kaushal, A., Dong, Y., Dunn, I.S. Biochem. Pharmacol. (1994) [Pubmed]
  16. Alteration of tyrosinase activity in human melanocytes and melanoma cells by histamine H2 and H3 ligands. Le Gros, G., Zhang, X.M., Parsons, P.G. Melanoma Res. (1994) [Pubmed]
  17. TYRP2-mediated resistance to cis-diamminedichloroplatinum (II) in human melanoma cells is independent of tyrosinase and TYRP1 expression and melanin content. Pak, B.J., Li, Q., Kerbel, R.S., Ben-David, Y. Melanoma Res. (2000) [Pubmed]
  18. Abnormal acidification of melanoma cells induces tyrosinase retention in the early secretory pathway. Halaban, R., Patton, R.S., Cheng, E., Svedine, S., Trombetta, E.S., Wahl, M.L., Ariyan, S., Hebert, D.N. J. Biol. Chem. (2002) [Pubmed]
  19. Tyrosinase-related proteins suppress tyrosinase-mediated cell death of melanocytes and melanoma cells. Rad, H.H., Yamashita, T., Jin, H.Y., Hirosaki, K., Wakamatsu, K., Ito, S., Jimbow, K. Exp. Cell Res. (2004) [Pubmed]
  20. Skin pigmentation, biogeographical ancestry and admixture mapping. Shriver, M.D., Parra, E.J., Dios, S., Bonilla, C., Norton, H., Jovel, C., Pfaff, C., Jones, C., Massac, A., Cameron, N., Baron, A., Jackson, T., Argyropoulos, G., Jin, L., Hoggart, C.J., McKeigue, P.M., Kittles, R.A. Hum. Genet. (2003) [Pubmed]
  21. Chromosomal structure of the human TYRP1 and TYRP2 loci and comparison of the tyrosinase-related protein gene family. Sturm, R.A., O'Sullivan, B.J., Box, N.F., Smith, A.G., Smit, S.E., Puttick, E.R., Parsons, P.G., Dunn, I.S. Genomics (1995) [Pubmed]
  22. Differential regulation of melanosomal proteins after hinokitiol treatment. Choi, Y.G., Bae, E.J., Kim, D.S., Park, S.H., Kwon, S.B., Na, J.I., Park, K.C. J. Dermatol. Sci. (2006) [Pubmed]
  23. Mitogenic and melanogenic stimulation of normal human melanocytes by melanotropic peptides. Abdel-Malek, Z., Swope, V.B., Suzuki, I., Akcali, C., Harriger, M.D., Boyce, S.T., Urabe, K., Hearing, V.J. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  24. Heterogeneous expression of immunotherapy candidate proteins gp100, MART-1, and tyrosinase in human melanoma cell lines and in human melanocytic lesions. de Vries, T.J., Fourkour, A., Wobbes, T., Verkroost, G., Ruiter, D.J., van Muijen, G.N. Cancer Res. (1997) [Pubmed]
  25. Epitope mapping of the melanosomal matrix protein gp100 (PMEL17): rapid processing in the endoplasmic reticulum and glycosylation in the early Golgi compartment. Yasumoto, K., Watabe, H., Valencia, J.C., Kushimoto, T., Kobayashi, T., Appella, E., Hearing, V.J. J. Biol. Chem. (2004) [Pubmed]
  26. AP-3 mediates tyrosinase but not TRP-1 trafficking in human melanocytes. Huizing, M., Sarangarajan, R., Strovel, E., Zhao, Y., Gahl, W.A., Boissy, R.E. Mol. Biol. Cell (2001) [Pubmed]
  27. Human melanocytes and melanomas express novel mRNA isoforms of the tyrosinase-related protein-2/DOPAchrome tautomerase gene: molecular and functional characterization. Pisarra, P., Lupetti, R., Palumbo, A., Napolitano, A., Prota, G., Parmiani, G., Anichini, A., Sensi, M. J. Invest. Dermatol. (2000) [Pubmed]
  28. Mutations of the human tyrosinase gene associated with tyrosinase related oculocutaneous albinism (OCA1). Mutations in brief no. 204. Online. Oetting, W.S., Fryer, J.P., King, R.A. Hum. Mutat. (1998) [Pubmed]
  29. Nonlinkage of bipolar illness to tyrosine hydroxylase, tyrosinase, and D2 and D4 dopamine receptor genes on chromosome 11. De bruyn, A., Mendelbaum, K., Sandkuijl, L.A., Delvenne, V., Hirsch, D., Staner, L., Mendlewicz, J., Van Broeckhoven, C. The American journal of psychiatry. (1994) [Pubmed]
  30. Contribution of melanogenic proteins to the heterogeneous pigmentation of human melanocytes. Abdel-Malek, Z., Swope, V., Collins, C., Boissy, R., Zhao, H., Nordlund, J. J. Cell. Sci. (1993) [Pubmed]
  31. In situ and in vitro evidence for DCoH/HNF-1 alpha transcription of tyrosinase in human skin melanocytes. Schallreuter, K.U., Kothari, S., Hasse, S., Kauser, S., Lindsey, N.J., Gibbons, N.C., Hibberts, N., Wood, J.M. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  32. Selective down-regulation of tyrosinase family gene TYRP1 by inhibition of the activity of melanocyte transcription factor, MITF. Fang, D., Tsuji, Y., Setaluri, V. Nucleic Acids Res. (2002) [Pubmed]
  33. Cotransfection of genes encoding human tyrosinase and tyrosinase-related protein-1 prevents melanocyte death and enhances melanin pigmentation and gene expression of Lamp-1. Luo, D., Chen, H., Jimbow, K. Exp. Cell Res. (1994) [Pubmed]
  34. Heat shock protein 70: role in antigen presentation and immune stimulation. Milani, V., Noessner, E., Ghose, S., Kuppner, M., Ahrens, B., Scharner, A., Gastpar, R., Issels, R.D. International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group. (2002) [Pubmed]
  35. The use of computer-assisted video image analysis for the quantification of CD8+ T lymphocytes producing tumor necrosis factor alpha spots in response to peptide antigens. Herr, W., Linn, B., Leister, N., Wandel, E., Meyer zum Büschenfelde, K.H., Wölfel, T. J. Immunol. Methods (1997) [Pubmed]
  36. The receptor for activated C-kinase-I (RACK-I) anchors activated PKC-beta on melanosomes. Park, H.Y., Wu, H., Killoran, C.E., Gilchrest, B.A. J. Cell. Sci. (2004) [Pubmed]
  37. Bioelectrochemical analysis of neuropathy target esterase activity in blood. Sigolaeva, L.V., Makower, A., Eremenko, A.V., Makhaeva, G.F., Malygin, V.V., Kurochkin, I.N., Scheller, F.W. Anal. Biochem. (2001) [Pubmed]
  38. MITF mediates cAMP-induced protein kinase C-beta expression in human melanocytes. Park, H.Y., Wu, C., Yonemoto, L., Murphy-Smith, M., Wu, H., Stachur, C.M., Gilchrest, B.A. Biochem. J. (2006) [Pubmed]
  39. Modulation of microphthalmia-associated transcription factor gene expression alters skin pigmentation. Lin, C.B., Babiarz, L., Liebel, F., Roydon Price, E., Kizoulis, M., Gendimenico, G.J., Fisher, D.E., Seiberg, M. J. Invest. Dermatol. (2002) [Pubmed]
  40. Molecular and prognostic classification of advanced melanoma: a multi-marker microcontamination assay of peripheral blood stem cells. Schrader, A.J., Probst-Kepper, M., Grosse, J., Kunter, U., Schenk, F., Franzke, A., Atzpodien, J., Buer, J. Melanoma Res. (2000) [Pubmed]
  41. Current update and trends in melanin pigmentation and melanin biology. Jimbow, K. The Keio journal of medicine. (1995) [Pubmed]
  42. Rufous oculocutaneous albinism in southern African Blacks is caused by mutations in the TYRP1 gene. Manga, P., Kromberg, J.G., Box, N.F., Sturm, R.A., Jenkins, T., Ramsay, M. Am. J. Hum. Genet. (1997) [Pubmed]
  43. Functional analysis of microphthalmia-associated transcription factor in pigment cell-specific transcription of the human tyrosinase family genes. Yasumoto, K., Yokoyama, K., Takahashi, K., Tomita, Y., Shibahara, S. J. Biol. Chem. (1997) [Pubmed]
  44. Cloning of the human DOPAchrome tautomerase/tyrosinase-related protein 2 gene and identification of two regulatory regions required for its pigment cell-specific expression. Yokoyama, K., Yasumoto, K., Suzuki, H., Shibahara, S. J. Biol. Chem. (1994) [Pubmed]
  45. Diverse expansion potential and heterogeneous avidity in tumor-associated antigen-specific T lymphocytes from primary melanoma patients. Palermo, B., Campanelli, R., Mantovani, S., Lantelme, E., Manganoni, A.M., Carella, G., Da Prada, G., della Cuna, G.R., Romagne, F., Gauthier, L., Necker, A., Giachino, C. Eur. J. Immunol. (2001) [Pubmed]
  46. Detection of tyrosinase and tyrosinase-related protein 1 sequences from peripheral blood of melanoma patients using reverse transcription-polymerase chain reaction. Jin, H.Y., Yamashita, T., Minamitsuji, Y., Omori, F., Jimbow, K. J. Dermatol. Sci. (2003) [Pubmed]
  47. Generation of cytotoxic T-cell responses with synthetic melanoma-associated peptides in vivo: implications for tumor vaccines with melanoma-associated antigens. Jäeger, E., Bernhard, H., Romero, P., Ringhoffer, M., Arand, M., Karbach, J., Ilsemann, C., Hagedorn, M., Knuth, A. Int. J. Cancer (1996) [Pubmed]
  48. Retroviral infection with human tyrosinase-related protein-1 (TRP-1) cDNA upregulates tyrosinase activity and melanin synthesis in a TRP-1-deficient melanoma cell line. Zhao, H., Eling, D.J., Medrano, E.E., Boissy, R.E. J. Invest. Dermatol. (1996) [Pubmed]
WikiGenes - Universities