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Gene Review

Tyrp1  -  tyrosinase-related protein 1

Mus musculus

Synonyms: 5,6-dihydroxyindole-2-carboxylic acid oxidase, Brown locus protein, Catalase B, DHICA oxidase, Oca3, ...
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Disease relevance of Tyrp1


High impact information on Tyrp1

  • How this "reverse" coupling works was unclear, but store IP(3)Rs were proposed to bind and regulate plasma membrane TRP cation channels [6].
  • The antibody reacted with mouse, rabbit, dog, sheep, monkey, Sprague-Dawley and Lewis/Brown Norway rat tubular basement membranes, but not with that of Lewis rat or guinea pig, or with human skin, thyroid, parotid, lung, liver or pancreas [7].
  • To identify mutations that induce immunity, here we have developed a systematic approach in which combinatorial DNA libraries encoding large numbers of random mutations in two syngeneic tyrosinase-related proteins are used to immunize black mice [8].
  • Obesity. Brown fat and yellow mice [9].
  • To understand this process better, we have examined the native state of viral DNA in cells acutely infected by murine leukemia virus (MLV), using both a physical assay for viral DNA and a functional assay for integration activity (Brown et al. 1987) [10].

Chemical compound and disease context of Tyrp1


Biological context of Tyrp1


Anatomical context of Tyrp1

  • This reduced stability of Tyr can be partly rescued by infection with the wild type Tyrp1 gene, and this is accompanied by phenotypic rescue of infected melanocytes [20].
  • In this study we have used two different techniques (expression of TRP1 in transfected fibroblasts and immunoaffinity purification of TRP1 from melanocytes) to examine the enzymatic function(s) of TRP1 [21].
  • There is a significant reduction in the level of TRP-1 in the RPE/choroid of the Mitfvit mouse [17].
  • For over 40 years germ-cell mutagenesis experiments have generated many new mutations at the brown (b or Tyrp1) locus on mouse Chromosome (Chr) 4 [19].
  • We present here results on N-glycan processing of TRP-1 and tyrosinase and compare the maturation process and activity of both glycoproteins in the presence of inhibitors of the endoplasmic reticulum stages of N-glycosylation [22].

Associations of Tyrp1 with chemical compounds

  • The data demonstrate that the specific melanogenic function of TRP1 is the oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) to a carboxylated indole-quinone at a down-stream point in the melanin biosynthetic pathway [21].
  • The DHICA oxidase activity of LEMT displayed a Km for DHICA of about 0.8 mM, as compared to 1.9 mM for L-DOPA and 0.23 nM for L-tyrosine [23].
  • The inhibition affected to similar extents the Dopa oxidase activity associated to tyrosinase-related protein-1 (TRP-1) and tyrosinase [1].
  • Based on the relationship between ascorbate added, enzyme activity, and lag period, it is very likely that the DHICA converting activity is indeed a DHICA oxidase activity [23].
  • Regarding protein levels of these enzymes, the amount of tyrosinase was decreased by linoleic acid and increased by palmitic acid, whereas the amounts of TRP1 and TRP2 did not change after incubation with fatty acids [24].

Physical interactions of Tyrp1

  • In sum, these results suggest that, in addition to its catalytic function in oxidizing DHICA, Tyrp1 may play an important role in stabilizing Tyr, a second potential role in the regulation of melanin formation [20].
  • During the normal folding pathway, TRP-1 interacts with calnexin [25].

Regulatory relationships of Tyrp1

  • 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 [26].
  • TRP-1 was induced simultaneously with tyrosinase, although its inducibility was lower than that of tyrosinase [27].
  • METHODS: Diabetes was induced in heterozygous PPARgamma(+/-) mice and Brown Norway rats with an intraperitoneal streptozotocin (STZ) injection [28].
  • These results suggest that the expressions of tyrosinase and TRP-1 genes are coordinately regulated by melanotropic reagents through cAMP-dependent protein kinase and protein kinase C in mouse B16-F1 cells, and that their coordinate expression causes eumelanin biosynthesis [27].

Other interactions of Tyrp1

  • Although the brown locus, encoding TRP1, was actually the first member of the tyrosinase gene family to be cloned, its catalytic function (which results in the production of black rather than brown melanin) has been in general dispute [21].
  • A second tyrosinase-related protein, TRP-2, is a melanogenic enzyme termed DOPAchrome tautomerase [29].
  • The data suggests that transcription of the gene encoding TRP-1 is extremely dependent upon functional Mitf [17].
  • TGF-beta1 mediated this effect by increasing the rate of degradation of tyrosinase and TRP-1 [1].
  • Therefore, the inhibitory effect of TNF-alpha on tyrosinase and TRP-1 results from combined effect on mRNA levels and enzymatic activity or protein stability [30].

Analytical, diagnostic and therapeutic context of Tyrp1


  1. Transforming growth factor-beta1 inhibits basal melanogenesis in B16/F10 mouse melanoma cells by increasing the rate of degradation of tyrosinase and tyrosinase-related protein-1. Martínez-Esparza, M., Jiménez-Cervantes, C., Beermann, F., Aparicio, P., Lozano, J.A., García-Borrón, J.C. J. Biol. Chem. (1997) [Pubmed]
  2. Genetic context determines susceptibility to intraocular pressure elevation in a mouse pigmentary glaucoma. Anderson, M.G., Libby, R.T., Mao, M., Cosma, I.M., Wilson, L.A., Smith, R.S., John, S.W. BMC Biol. (2006) [Pubmed]
  3. Oculocutaneous albinism types 1 and 3 are ER retention diseases: mutation of tyrosinase or Tyrp1 can affect the processing of both mutant and wild-type proteins. Toyofuku, K., Wada, I., Valencia, J.C., Kushimoto, T., Ferrans, V.J., Hearing, V.J. FASEB J. (2001) [Pubmed]
  4. Tyrosinase-related protein-2 and -1 are trafficked on distinct routes in B16 melanoma cells. Negroiu, G., Dwek, R.A., Petrescu, S.M. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  5. Redundant and alternative roles for activating Fc receptors and complement in an antibody-dependent model of autoimmune vitiligo. Trcka, J., Moroi, Y., Clynes, R.A., Goldberg, S.M., Bergtold, A., Perales, M.A., Ma, M., Ferrone, C.R., Carroll, M.C., Ravetch, J.V., Houghton, A.N. Immunity (2002) [Pubmed]
  6. Homer binds TRPC family channels and is required for gating of TRPC1 by IP3 receptors. Yuan, J.P., Kiselyov, K., Shin, D.M., Chen, J., Shcheynikov, N., Kang, S.H., Dehoff, M.H., Schwarz, M.K., Seeburg, P.H., Muallem, S., Worley, P.F. Cell (2003) [Pubmed]
  7. Interstitial nephritis with anti-tubular-basement-membrane antibody. Bergstein, J., Litman, N. N. Engl. J. Med. (1975) [Pubmed]
  8. Autoimmunity and tumor immunity induced by immune responses to mutations in self. Engelhorn, M.E., Guevara-Patiño, J.A., Noffz, G., Hooper, A.T., Lou, O., Gold, J.S., Kappel, B.J., Houghton, A.N. Nat. Med. (2006) [Pubmed]
  9. Obesity. Brown fat and yellow mice. Friedman, J.M. Nature (1993) [Pubmed]
  10. A nucleoprotein complex mediates the integration of retroviral DNA. Bowerman, B., Brown, P.O., Bishop, J.M., Varmus, H.E. Genes Dev. (1989) [Pubmed]
  11. 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]
  12. Prevention of mercuric chloride-induced nephritis in the brown Norway rat by treatment with antibodies against the alpha 4 integrin. Molina, A., Sánchez-Madrid, F., Bricio, T., Martín, A., Barat, A., Alvarez, V., Mampaso, F. J. Immunol. (1994) [Pubmed]
  13. Relocalization of apoptosis-inducing factor in photoreceptor apoptosis induced by retinal detachment in vivo. Hisatomi, T., Sakamoto, T., Murata, T., Yamanaka, I., Oshima, Y., Hata, Y., Ishibashi, T., Inomata, H., Susin, S.A., Kroemer, G. Am. J. Pathol. (2001) [Pubmed]
  14. Proteasome inhibition: A novel mechanism to combat asthma. Elliott, P.J., Pien, C.S., McCormack, T.A., Chapman, I.D., Adams, J. J. Allergy Clin. Immunol. (1999) [Pubmed]
  15. IL-6 deficiency causes enhanced pathology in Twitcher (globoid cell leukodystrophy) mice. Pedchenko, T.V., LeVine, S.M. Exp. Neurol. (1999) [Pubmed]
  16. Lincomycin abrogates dexamethasone-enhanced melanogenesis in B16 melanoma cells. Kim, D.G., Kim, H.Y., Kim, M.Y., Lee, M.Y., You, K.R. Pigment Cell Res. (1998) [Pubmed]
  17. Expression of tyrosinase and the tyrosinase related proteins in the Mitfvit (vitiligo) mouse eye: implications for the function of the microphthalmia transcription factor. Smith, S.B., Zhou, B.K., Orlow, S.J. Exp. Eye Res. (1998) [Pubmed]
  18. A comparative transcript map and candidates for mutant phenotypes in the Tyrp1 (brown) deletion complex homologous to human 9p21-23. Simpson, E.H., Suffolk, R., Bell, J.A., Jordan, S.A., Johnson, D.K., Hunsicker, P.R., Weber, J.S., Justice, M.J., Jackson, I.J. Mamm. Genome (2000) [Pubmed]
  19. A high-resolution map of the brown (b, Tyrp1) deletion complex of mouse chromosome 4. Bell, J.A., Rinchik, E.M., Raymond, S., Suffolk, R., Jackson, I.J. Mamm. Genome (1995) [Pubmed]
  20. Tyrosinase stabilization by Tyrp1 (the brown locus protein). Kobayashi, T., Imokawa, G., Bennett, D.C., Hearing, V.J. J. Biol. Chem. (1998) [Pubmed]
  21. 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]
  22. Protein specific N-glycosylation of tyrosinase and tyrosinase-related protein-1 in B16 mouse melanoma cells. Negroiu, G., Branza-Nichita, N., Petrescu, A.J., Dwek, R.A., Petrescu, S.M. Biochem. J. (1999) [Pubmed]
  23. A new enzymatic function in the melanogenic pathway. The 5,6-dihydroxyindole-2-carboxylic acid oxidase activity of tyrosinase-related protein-1 (TRP1). Jiménez-Cervantes, C., Solano, F., Kobayashi, T., Urabe, K., Hearing, V.J., Lozano, J.A., García-Borrón, J.C. J. Biol. Chem. (1994) [Pubmed]
  24. Possible involvement of proteolytic degradation of tyrosinase in the regulatory effect of fatty acids on melanogenesis. Ando, H., Funasaka, Y., Oka, M., Ohashi, A., Furumura, M., Matsunaga, J., Matsunaga, N., Hearing, V.J., Ichihashi, M. J. Lipid Res. (1999) [Pubmed]
  25. Folding and maturation of tyrosinase-related protein-1 are regulated by the post-translational formation of disulfide bonds and by N-glycan processing. Negroiu, G., Dwek, R.A., Petrescu, S.M. J. Biol. Chem. (2000) [Pubmed]
  26. Regulation of melanogenesis induced by 5-methoxypsoralen without ultraviolet light in murine melanoma cells. Mengeaud, V., Ortonne, J.P. Pigment Cell Res. (1994) [Pubmed]
  27. Eumelanin biosynthesis is regulated by coordinate expression of tyrosinase and tyrosinase-related protein-1 genes. Kuzumaki, T., Matsuda, A., Wakamatsu, K., Ito, S., Ishikawa, K. Exp. Cell Res. (1993) [Pubmed]
  28. Effects of Peroxisome Proliferator-Activated Receptor {gamma} and Its Ligand on Blood-Retinal Barrier in a Streptozotocin-Induced Diabetic Model. Muranaka, K., Yanagi, Y., Tamaki, Y., Usui, T., Kubota, N., Iriyama, A., Terauchi, Y., Kadowaki, T., Araie, M. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  29. 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]
  30. Mechanisms of melanogenesis inhibition by tumor necrosis factor-alpha in B16/F10 mouse melanoma cells. Martínez-Esparza, M., Jiménez-Cervantes, C., Solano, F., Lozano, J.A., García-Borrón, J.C. Eur. J. Biochem. (1998) [Pubmed]
  31. The DHICA oxidase activity of the melanosomal tyrosinases LEMT and HEMT. Jiménez-Cervantes, C., Solano, F., Lozano, J.A., García-Borrón, J.C. Pigment Cell Res. (1994) [Pubmed]
  32. The identification and partial cloning by PCR of the gene for tyrosinase-related protein-1 in the Mexican axolotl. Mason, K.A., Mason, S.K. Pigment Cell Res. (1995) [Pubmed]
  33. Regulation of melanogenesis in B16 mouse melanoma cells by protein kinase C. Mahalingam, H., Vaughn, J., Novotny, J., Gruber, J.R., Niles, R.M. J. Cell. Physiol. (1996) [Pubmed]
  34. Molecular interactions within the melanogenic complex: formation of heterodimers of tyrosinase and TRP1 from B16 mouse melanoma. Jiménez-Cervantes, C., Martínez-Esparza, M., Solano, F., Lozano, J.A., García-Borrón, J.C. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
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