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Gene Review

Dct  -  dopachrome tautomerase

Mus musculus

Synonyms: DCT, DT, L-dopachrome Delta-isomerase, L-dopachrome tautomerase, SLATY locus protein, ...
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Disease relevance of Dct


Psychiatry related information on Dct


High impact information on Dct


Chemical compound and disease context of Dct


Biological context of Dct

  • At the Dct locus, three mutations are known that lead to pigmentation phenotype [13].
  • We have used deletion mutants of the Dct promoter, transfections with developmentally relevant transcription factors, and gel shift assays to define transcriptional determinants of Dct expression [14].
  • The gene encoding TRP-2 maps to mouse chromosome 14, in the region of the coat colour mutation slaty [15].
  • Based on apoDCT preparation with cyanide and reconstitution experiments, we propose that DCT have zinc instead of copper at the two metal-binding sites and that those sites actually correspond to the active site [16].
  • Other factors also may influence melanogenesis and a unique melanogenic inhibitor suppresses tyrosinase and DOPAchrome tautomerase activities, but does not affect the spontaneous rate of DOPAchrome decarboxylation to DHI [17].

Anatomical context of Dct


Associations of Dct with chemical compounds

  • DOPAchrome tautomerase is one such melanogenic enzyme that isomerizes the pigmented intermediate DOPAchrome to DHICA (5,6-dihydroxyindole-2-carboxylic acid) rather than to DHI (5,6-dihydroxyindole), which would be generated spontaneously [10].
  • Dopachrome tautomerase (DCT) catalyzes the conversion of L-dopachrome into 5,6-dihydroxyindole-2-carboxylic acid through the melanogenic biosynthetic pathway [16].
  • They are thought to be more immature because they were positive to KIT, TRP1, and TRP2, but not to ETR(B), tyrosinase, and DOPA reaction [19].
  • After some crest cells in the migration staging area have begun to migrate on a medial pathway, a subpopulation of crest-derived cells remaining in the migration staging area expresses mRNAs for the receptor tyrosine kinase, c-kit, and tyrosinase-related protein-2, both of which are characteristic of melanocyte precursors [20].
  • From the present data, the existence of additional ligands for metal ions other than zinc in the DCT molecule, such as the proposed cysteine iron-binding sites, cannot be completely ruled out [21].

Regulatory relationships of Dct

  • In addition, 5-MOP stimulated TRP-1 synthesis and induced a dose-dependent decrease of DCT activity without any modification in the expression of the protein [22].
  • TRP-1 and tyrosinase probes also detected melanoblasts but were both expressed later in development than TRP-2 [18].
  • We demonstrate that in Ods, the Dct promoter is capable of acting over a distance of 1 Mb to induce inappropriate expression of Sox9 in the retinal pigmented epithelium of the eye, causing the observed microphthalmia [23].
  • In the trunk region of wild-type embryos, Mitf-expressing cells that coexpressed the melanoblast marker Dct and the tyrosine kinase receptor Kit were found in the dorsolateral neural crest migration pathway [24].
  • 5. Pax6(-/-) cells in the retinal pigment epithelium could express Trp2, a component of the pigmentation pathway, at E14.5 and a small number went on to differentiate and produce pigment at E16 [25].

Other interactions of Dct

  • The pattern of steel and c-kit hybridisation in the developing brain differed from that of TRP-2 [18].
  • TRP-2/DT, a new early melanoblast marker, shows that steel growth factor (c-kit ligand) is a survival factor [18].
  • If N-glycosylation inhibitors prevent the association with calnexin, the TRP-2 nascent chain undergoes an accelerated degradation process [1].
  • Despite the increasing evidence of its efficiency as a melanoma antigen, little is known about the maturation and intracellular trafficking of TRP-2 [1].
  • The slaty mutation affects eumelanin and pheomelanin synthesis in mouse melanocytes [26].

Analytical, diagnostic and therapeutic context of Dct


  1. The inhibition of early N-glycan processing targets TRP-2 to degradation in B16 melanoma cells. Negroiu, G., Dwek, R.A., Petrescu, S.M. J. Biol. Chem. (2003) [Pubmed]
  2. Neural crest-directed gene transfer demonstrates Wnt1 role in melanocyte expansion and differentiation during mouse development. Dunn, K.J., Williams, B.O., Li, Y., Pavan, W.J. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  3. Dendritic cell-based genetic immunization in mice with a recombinant adenovirus encoding murine TRP2 induces effective anti-melanoma immunity. Tüting, T., Steitz, J., Brück, J., Gambotto, A., Steinbrink, K., DeLeo, A.B., Robbins, P., Knop, J., Enk, A.H. The journal of gene medicine. (1999) [Pubmed]
  4. Central nervous system tumor immunity generated by a recombinant listeria monocytogenes vaccine targeting tyrosinase related protein-2 and real-time imaging of intracranial tumor burden. Prins, R.M., Bruhn, K.W., Craft, N., Lin, J.W., Kim, C.H., Odesa, S.K., Miller, J.F., Liau, L.M. Neurosurgery (2006) [Pubmed]
  5. Loss of sex discrimination and male-male aggression in mice deficient for TRP2. Stowers, L., Holy, T.E., Meister, M., Dulac, C., Koentges, G. Science (2002) [Pubmed]
  6. Pheromones, vomeronasal function, and gender-specific behavior. Keverne, E.B. Cell (2002) [Pubmed]
  7. 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]
  8. Collecting duct-specific gene inactivation of alphaENaC in the mouse kidney does not impair sodium and potassium balance. Rubera, I., Loffing, J., Palmer, L.G., Frindt, G., Fowler-Jaeger, N., Sauter, D., Carroll, T., McMahon, A., Hummler, E., Rossier, B.C. J. Clin. Invest. (2003) [Pubmed]
  9. Tyrosinase related protein 1 (TRP1) functions as a DHICA oxidase in melanin biosynthesis. Kobayashi, T., Urabe, K., Winder, A., Jiménez-Cervantes, C., Imokawa, G., Brewington, T., Solano, F., García-Borrón, J.C., Hearing, V.J. EMBO J. (1994) [Pubmed]
  10. A second tyrosinase-related protein, TRP-2, is a melanogenic enzyme termed DOPAchrome tautomerase. Tsukamoto, K., Jackson, I.J., Urabe, K., Montague, P.M., Hearing, V.J. EMBO J. (1992) [Pubmed]
  11. Melatonin antagonizes alpha-melanocyte-stimulating hormone enhancement of melanogenesis in mouse melanoma cells by blocking the hormone-induced accumulation of the c locus tyrosinase. Valverde, P., Benedito, E., Solano, F., Oaknin, S., Lozano, J.A., García-Borrón, J.C. Eur. J. Biochem. (1995) [Pubmed]
  12. Cytotoxic T lymphocytes responding to low dose TRP2 antigen are induced against B16 melanoma by liposome-encapsulated TRP2 peptide and CpG DNA adjuvant. Jérôme, V., Graser, A., Müller, R., Kontermann, R.E., Konur, A. J. Immunother. (2006) [Pubmed]
  13. Melanocytes and pigmentation are affected in dopachrome tautomerase knockout mice. Guyonneau, L., Murisier, F., Rossier, A., Moulin, A., Beermann, F. Mol. Cell. Biol. (2004) [Pubmed]
  14. Direct interaction of Sox10 with the promoter of murine Dopachrome Tautomerase (Dct) and synergistic activation of Dct expression with Mitf. Jiao, Z., Mollaaghababa, R., Pavan, W.J., Antonellis, A., Green, E.D., Hornyak, T.J. Pigment Cell Res. (2004) [Pubmed]
  15. A second tyrosinase-related protein, TRP-2, maps to and is mutated at the mouse slaty locus. Jackson, I.J., Chambers, D.M., Tsukamoto, K., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., Hearing, V. EMBO J. (1992) [Pubmed]
  16. Dopachrome tautomerase is a zinc-containing enzyme. Solano, F., Martinez-Liarte, J.H., Jiménez-Cervantes, C., García-Borrón, J.C., Lozano, J.A. Biochem. Biophys. Res. Commun. (1994) [Pubmed]
  17. Functional properties of cloned melanogenic proteins. Hearing, V.J., Tsukamoto, K., Urabe, K., Kameyama, K., Montague, P.M., Jackson, I.J. Pigment Cell Res. (1992) [Pubmed]
  18. TRP-2/DT, a new early melanoblast marker, shows that steel growth factor (c-kit ligand) is a survival factor. Steel, K.P., Davidson, D.R., Jackson, I.J. Development (1992) [Pubmed]
  19. Stem cell factor and/or endothelin-3 dependent immortal melanoblast and melanocyte populations derived from mouse neural crest cells. Kawa, Y., Ito, M., Ono, H., Asano, M., Takano, N., Ooka, S., Watabe, H., Hosaka, E., Baba, T., Kubota, Y., Mizoguchi, M. Pigment Cell Res. (2000) [Pubmed]
  20. Soluble and cell-bound forms of steel factor activity play distinct roles in melanocyte precursor dispersal and survival on the lateral neural crest migration pathway. Wehrle-Haller, B., Weston, J.A. Development (1995) [Pubmed]
  21. Molecular mechanism for catalysis by a new zinc-enzyme, dopachrome tautomerase. Solano, F., Jiménez-Cervantes, C., Martínez-Liarte, J.H., García-Borrón, J.C., Jara, J.R., Lozano, J.A. Biochem. J. (1996) [Pubmed]
  22. Regulation of melanogenesis induced by 5-methoxypsoralen without ultraviolet light in murine melanoma cells. Mengeaud, V., Ortonne, J.P. Pigment Cell Res. (1994) [Pubmed]
  23. Long-range activation of Sox9 in Odd Sex (Ods) mice. Qin, Y., Kong, L.K., Poirier, C., Truong, C., Overbeek, P.A., Bishop, C.E. Hum. Mol. Genet. (2004) [Pubmed]
  24. Melanocyte development in vivo and in neural crest cell cultures: crucial dependence on the Mitf basic-helix-loop-helix-zipper transcription factor. Opdecamp, K., Nakayama, A., Nguyen, M.T., Hodgkinson, C.A., Pavan, W.J., Arnheiter, H. Development (1997) [Pubmed]
  25. The roles of Pax6 in the cornea, retina, and olfactory epithelium of the developing mouse embryo. Collinson, J.M., Quinn, J.C., Hill, R.E., West, J.D. Dev. Biol. (2003) [Pubmed]
  26. The slaty mutation affects eumelanin and pheomelanin synthesis in mouse melanocytes. Hirobe, T., Wakamatsu, K., Ito, S., Kawa, Y., Soma, Y., Mizoguchi, M. Eur. J. Cell Biol. (2006) [Pubmed]
  27. Dopachrome tautomerase (Dct) regulates neural progenitor cell proliferation. Jiao, Z., Zhang, Z.G., Hornyak, T.J., Hozeska, A., Zhang, R.L., Wang, Y., Wang, L., Roberts, C., Strickland, F.M., Chopp, M. Dev. Biol. (2006) [Pubmed]
  28. Stimulation of melanogenesis by tetradecanoylphorbol 13-acetate (TPA) in mouse melanocytes and neural crest cells. Prince, S., Wiggins, T., Hulley, P.A., Kidson, S.H. Pigment Cell Res. (2003) [Pubmed]
  29. Genetic vaccination with "self" tyrosinase-related protein 2 causes melanoma eradication but not vitiligo. Bronte, V., Apolloni, E., Ronca, R., Zamboni, P., Overwijk, W.W., Surman, D.R., Restifo, N.P., Zanovello, P. Cancer Res. (2000) [Pubmed]
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