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Gene Review

DCT  -  dopachrome tautomerase

Homo sapiens

Synonyms: DT, L-dopachrome Delta-isomerase, L-dopachrome tautomerase, TRP-2, TRP2, ...
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Disease relevance of DCT

  • Quantitative reverse transcription PCR analysis carried out on total and/or cytoplasmic mRNA demonstrated that, in contrast to the fully spliced TRP-2 mRNA expressed in melanomas, normal skin melanocytes, and retina, the TRP-2-INT2 mRNA could be detected at significant levels in melanomas but not in normal cells of the melanocytic lineage [1].
  • A series of 5' deletion studies of the human DT gene promoter revealed that the 32-bp element, located between -447 and -415, is sufficient to confer pigment cell-specific expression of a reporter gene on a homologous promoter, but not on a heterologous simian virus 40 promoter [2].
  • The present study shows unexpected features of TRP-2 and may enhance our understanding of the pathophysiology of retinoblastoma [3].
  • Moreover, we found a single case of a glioblastoma multiforme that expresses TRP-2 mRNA but not tyrosinase mRNA, suggesting that TRP-2 may function in human neural tissues under certain conditions [4].
  • Here, we demonstrate that this correlation between constitutive TYRP2 expression and CDDP resistance applies to a panel of distinct human melanoma cell lines obtained from patients with melanoma at various stages of disease progression [5].

Psychiatry related information on DCT

  • Two flash-fusion threshold (2FFT), simple reaction time (SRT), digital copying (DCT), symbol-digit modalities (SDMT), and Gibson's spiral maze tests (GSMT) and mood rating scales for tension, alertness, depression, detachment, and anxiety were used [6].
  • The usefulness, inter-rater reliability, and validity of six mental tests, the MMS, the GMS, the MSQ, the VRT, the OLT, and the DCT were studied in 81 patients over the age of 75 years [7].

High impact information on DCT

  • Because the terminal nephron segments, including the DCT and collecting tubule, reabsorb only a small portion of the filtered Mg (approximately 5%), the loop of Henle plays a major role in the determination of Mg reabsorption, and it is in this segment that the major regulatory factors act to maintain Mg balance [8].
  • Immunization against TRP-2 induced autoantibodies and autoreactive cytotoxic T cells [9].
  • Absence of endogenous TRP-2-INT2 expression in melanocytes was also confirmed by lack of recognition of HLA-A*68011-transduced, TRP-2(+) melanocyte lines by CTL 128 [1].
  • The sequence coding for the antigenic epitope is located at the 5' end of intron 2 and is available for translation in the same open reading frame of the fully spliced TRP-2 mRNA [1].
  • Identification of tyrosinase-related protein 2 as a tumor rejection antigen for the B16 melanoma [10].

Chemical compound and disease context of DCT


Biological context of DCT

  • DCT may contribute to the homeostasis of RPE by detoxifying DOPA-derived metabolites [15].
  • Internal deletion studies using a homologous or a heterologous promoter revealed that the pigment cell-specific expression of a reporter gene mediated by the 32-bp element is dependent on the presence of another region of the DT gene spanning from -268 to -56, which was termed the proximal region [2].
  • We have cloned and sequenced the human genomic DNA segments encoding the 5'-flanking region and the first two exons of the DOPAchrome tautomerase (DT)/tyrosinase-related protein 2 (TRP-2) gene [2].
  • These results indicate that the presence of two regulatory regions, the 32-bp element and the proximal region, is required for pigment cell-specific expression of the DT gene [2].
  • Screening of a melanoma-derived cDNA library with a tyrosinase-related protein-2 probe allowed identification of two novel isoforms [11].

Anatomical context of DCT


Associations of DCT with chemical compounds


Physical interactions of DCT


Regulatory relationships of DCT


Other interactions of DCT

  • These biological activities of TYRP1 and DCT may work through the interaction with TYR in melanosomal compartment [21].
  • This novel 3'-untranslated region contains an alternatively spliced, tyrosinase-related protein-2 last exon in the second isoform (tyrosinase-related protein-2-8b) [11].
  • Therefore, OTX2 may regulate RPE-specific target genes, such as DCT, thereby maintaining the homeostasis of RPE [15].
  • Studies using inhibitors for protein kinases involved in cell signaling pathways suggested that stress-activated kinase p38 and mitogen-activated protein kinase kinase MEK are involved in TPA-independent regulation of TYRP2 expression in melanocytes [17].
  • Interestingly, gp100 and TRP-2 gene transcripts were detected in patients having recurrent and/or metastatic disease at the time of testing [22].

Analytical, diagnostic and therapeutic context of DCT


  1. Translation of a retained intron in tyrosinase-related protein (TRP) 2 mRNA generates a new cytotoxic T lymphocyte (CTL)-defined and shared human melanoma antigen not expressed in normal cells of the melanocytic lineage. Lupetti, R., Pisarra, P., Verrecchia, A., Farina, C., Nicolini, G., Anichini, A., Bordignon, C., Sensi, M., Parmiani, G., Traversari, C. J. Exp. Med. (1998) [Pubmed]
  2. 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]
  3. Expression of tyrosinase-related protein 2/DOPAchrome tautomerase in the retinoblastoma. Udono, T., Takahashi, K., Yasumoto , K., Yoshizawa, M., Takeda, K., Abe, T., Tamai, M., Shibahara, S. Exp. Eye Res. (2001) [Pubmed]
  4. Role of neurofibromin in modulation of expression of the tyrosinase-related protein 2 gene. Suzuki, H., Takahashi, K., Yasumoto, K., Amae, S., Yoshizawa, M., Fuse, N., Shibahara, S. J. Biochem. (1998) [Pubmed]
  5. 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]
  6. Central effects of beta-adrenoceptor antagonists. Salem, S.A., McDevitt, D.G. Clin. Pharmacol. Ther. (1983) [Pubmed]
  7. Efficacy of short mental tests in the detection of mental impairment in old age. Engedal, K., Haugen, P., Gilje, K., Laake, P. Comprehensive gerontology. Section A, Clinical and laboratory sciences. (1988) [Pubmed]
  8. Renal magnesium handling and its hormonal control. de Rouffignac, C., Quamme, G. Physiol. Rev. (1994) [Pubmed]
  9. Coupling and uncoupling of tumor immunity and autoimmunity. Bowne, W.B., Srinivasan, R., Wolchok, J.D., Hawkins, W.G., Blachere, N.E., Dyall, R., Lewis, J.J., Houghton, A.N. J. Exp. Med. (1999) [Pubmed]
  10. Identification of tyrosinase-related protein 2 as a tumor rejection antigen for the B16 melanoma. Bloom, M.B., Perry-Lalley, D., Robbins, P.F., Li, Y., el-Gamil, M., Rosenberg, S.A., Yang, J.C. J. Exp. Med. (1997) [Pubmed]
  11. 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]
  12. Sulfur-containing amino acids decrease cisplatin cytotoxicity and uptake in renal tubule epithelial cell lines. Kröning, R., Lichtenstein, A.K., Nagami, G.T. Cancer Chemother. Pharmacol. (2000) [Pubmed]
  13. A phase II study of dose-dense docetaxel and mitoxantrone in the treatment of patients with high-risk metastatic breast cancer. König, E., Kurbacher, C., Schwonzen, M., Breidenbach, M., Mallmann, P. Anticancer Drugs (2002) [Pubmed]
  14. Tyrosinase-related protein 2 as a mediator of melanoma specific resistance to cis-diamminedichloroplatinum(II): therapeutic implications. Chu, W., Pak, B.J., Bani, M.R., Kapoor, M., Lu, S.J., Tamir, A., Kerbel, R.S., Ben-David, Y. Oncogene (2000) [Pubmed]
  15. OTX2 regulates expression of DOPAchrome tautomerase in human retinal pigment epithelium. Takeda, K., Yokoyama, S., Yasumoto, K., Saito, H., Udono, T., Takahashi, K., Shibahara, S. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  16. Comparison of the melanogenesis in human black and light brown melanocytes. Maeda, K., Yokokawa, Y., Hatao, M., Naganuma, M., Tomita, Y. J. Dermatol. Sci. (1997) [Pubmed]
  17. Regulation of tyrosinase-related protein-2 (TYRP2) in human melanocytes: relationship to growth and morphology. Fang, D., Kute, T., Setaluri, V. Pigment Cell Res. (2001) [Pubmed]
  18. 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]
  19. Effect of arbutin on melanogenic proteins in human melanocytes. Chakraborty, A.K., Funasaka, Y., Komoto, M., Ichihashi, M. Pigment Cell Res. (1998) [Pubmed]
  20. Enhanced survival associated with vitiligo expression during maintenance biotherapy for metastatic melanoma. Boasberg, P.D., Hoon, D.S., Piro, L.D., Martin, M.A., Fujimoto, A., Kristedja, T.S., Bhachu, S., Ye, X., Deck, R.R., O'Day, S.J. J. Invest. Dermatol. (2006) [Pubmed]
  21. 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]
  22. RT-PCR detection of tyrosinase, gp100, MART1/Melan-A, and TRP-2 gene transcripts in peripheral blood of melanoma patients. Samija, M., Juretić, A., Solarić, M., Samija, I., Bingulac-Popović, J., Grahovac, B., Stanec, M., Oresić, V. Croat. Med. J. (2001) [Pubmed]
  23. 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. Khong, H.T., Rosenberg, S.A. J. Immunol. (2002) [Pubmed]
  24. Levels of dopachrome tautomerase in human melanocytes cultured in vitro. Bernd, A., Ramirez-Bosca, A., Kippenberger, S., Martinez-Liarte, J.H., Holzmann, H., Solano, F. Melanoma Res. (1994) [Pubmed]
  25. Cytotoxic T cell targeting of TRP-2 sensitizes human malignant glioma to chemotherapy. Liu, G., Akasaki, Y., Khong, H.T., Wheeler, C.J., Das, A., Black, K.L., Yu, J.S. Oncogene (2005) [Pubmed]
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