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Gene Review

Pheo  -  pheomelanin

Mus musculus

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Disease relevance of Pheo


High impact information on Pheo


Biological context of Pheo

  • These results demonstrate that up-regulation of ITF2 during the pheomelanin switch is functionally significant and reveal that differential expression of a ubiquitous basic helix-loop-helix transcription factor can modulate expression of melanogenic genes and the differentiation of melanocytes [9].
  • Lack of the specific degradation products aminohydroxyphenylalanine and aminohydroxyphenylethylamine in Lacc+ strains upon hydriodic acid hydrolysis showed that pheomelanin was also not produced by the fungus in vivo [10].
  • Increased pheomelanin photosensitizes DNA damage in lightly pigmented cells [11].
  • Pheomelanin as a binding site for drugs and chemicals [12].
  • The hairs were excised with scissors into the gray and the white bands of the PCH subspecies and into the black and the yellow bands of the PCA subspecies, and were analyzed for total melanin, eumelanin, and pheomelanin by spectrophotometric and chemical methods [13].

Anatomical context of Pheo

  • Chemical analysis of the eumelanin: pheomelanin ratio in melanosomes and elemental analysis of isolated melanin showed that B16 and HP melanins are primarily eumelanic, with a higher ratio of pheomelanic component in HP melanin [14].
  • The effect of 5-S-cysteinyl-L-3,4-dihydroxyphenylalanine (cys-dopa), an intermediate in the pathway from L-3,4-dihydroxyphenylalanine (L-dopa) to pheomelanin, on the growth of eight human tumor cell lines in culture was compared to that of L-dopa [15].
  • Mammalian melanocytes can produce two basic types of melanin, eumelanin and pheomelanin, within discrete organelles termed melanosomes [16].
  • These results suggest that A/A epidermal melanoblasts are influenced by the A gene from the dermis of neonatal mice, and are capable of synthesizing pheomelanin in the culture [17].
  • Thiol concentrations may control the conversion of dopaquinone to pheomelanin in hair follicle melanocytes [18].

Associations of Pheo with chemical compounds


Regulatory relationships of Pheo

  • Pheomelanin production in the epidermis from 3.5- and 5.5-d-old A/A mice may be induced by the expression of the agouti gene in the dermis [17].

Other interactions of Pheo


Analytical, diagnostic and therapeutic context of Pheo

  • On the basis of a chemical analysis, the sootiness in KK-A(y)/a was the result of increased eumelanin (PTCA) and decreased pheomelanin (AHP) [27].
  • In the mouse, ligation of MSHR by agouti signaling protein (ASP) results in the production of pheomelanin [28].
  • It is suggested that higher dopa requirement in our melanoma cell culture system reflects the co-existence of eu- and pheomelanin synthesis taking place according to their genetically predetermined proportions [29].
  • Using HPLC, cysteine and GSH were measured in 1) hair follicles, liver and serum of Ay/a, AwJ/AwJ, and a/a (black) mice, and 2) adipose and spleen tissues of Ay/a and a/a mice on day 9 of regenerating hair growth (late pheomelanin phase) [18].
  • Since the same treatment resulted in pheomelanin formation as evidenced by electron microscopy, it is suggested that the GR increase correlates at least in part with changes in melanocyte metabolism [30].


  1. Melanin acts as a potent UVB photosensitizer to cause an atypical mode of cell death in murine skin. Takeuchi, S., Zhang, W., Wakamatsu, K., Ito, S., Hearing, V.J., Kraemer, K.H., Brash, D.E. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  2. Effects of ultraviolet-visible irradiation in the presence of melanin isolated from human black or red hair upon Ehrlich ascites carcinoma cells. Menon, I.A., Persad, S., Ranadive, N.S., Haberman, H.F. Cancer Res. (1983) [Pubmed]
  3. Quantitative analysis of eumelanin and pheomelanin in hair and melanomas. Ito, S., Jimbow, K. J. Invest. Dermatol. (1983) [Pubmed]
  4. Stimulation of pheomelanogenesis in cultured B16 melanoma cells by 4-tertiary butylcatechol. Kawashima, T., Halldin, M.M., Fukuyama, K., Castagnoli, N., Gellin, G.A., Epstein, W.L. Biochem. Pharmacol. (1985) [Pubmed]
  5. Noise-induced hearing loss: the effect of melanin in the stria vascularis. Bartels, S., Ito, S., Trune, D.R., Nuttall, A.L. Hear. Res. (2001) [Pubmed]
  6. Modulation of murine melanocyte function in vitro by agouti signal protein. Sakai, C., Ollmann, M., Kobayashi, T., Abdel-Malek, Z., Muller, J., Vieira, W.D., Imokawa, G., Barsh, G.S., Hearing, V.J. EMBO J. (1997) [Pubmed]
  7. Slc7a11 gene controls production of pheomelanin pigment and proliferation of cultured cells. Chintala, S., Li, W., Lamoreux, M.L., Ito, S., Wakamatsu, K., Sviderskaya, E.V., Bennett, D.C., Park, Y.M., Gahl, W.A., Huizing, M., Spritz, R.A., Ben, S., Novak, E.K., Tan, J., Swank, R.T. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  8. Characterization of genes modulated during pheomelanogenesis using differential display. Furumura, M., Sakai, C., Potterf, S.B., Vieira, W.D., Barsh, G.S., Hearing, V.J. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  9. Involvement of ITF2 in the transcriptional regulation of melanogenic genes. Furumura, M., Potterf, S.B., Toyofuku, K., Matsunaga, J., Muller, J., Hearing, V.J. J. Biol. Chem. (2001) [Pubmed]
  10. Catecholamine oxidative products, but not melanin, are produced by Cryptococcus neoformans during neuropathogenesis in mice. Liu, L., Wakamatsu, K., Ito, S., Williamson, P.R. Infect. Immun. (1999) [Pubmed]
  11. UVA, pheomelanin and the carcinogenesis of melanoma. Hill, H.Z., Hill, G.J. Pigment Cell Res. (2000) [Pubmed]
  12. Pheomelanin as a binding site for drugs and chemicals. Mårs, U., Larsson, B.S. Pigment Cell Res. (1999) [Pubmed]
  13. Cyclic oscillations in melanin composition within hairs of baboons. Ito, S., Wakamatsu, K., Matsunaga, N., Hearing, V.J., Carey, K.D., Anderson, S., Dooley, T.P. Pigment Cell Res. (2001) [Pubmed]
  14. Characterization of melanogenesis and morphogenesis of melanosomes by physicochemical properties of melanin and melanosomes in malignant melanoma. Jimbow, K., Miyake, Y., Homma, K., Yasuda, K., Izumi, Y., Tsutsumi, A., Ito, S. Cancer Res. (1984) [Pubmed]
  15. Selective toxicity of 5-S-cysteinyldopa, a melanin precursor, to tumor cells in vitro and in vivo. Fujita, K., Ito, S., Inoue, S., Yamamoto, Y., Takeuchi, J., Shamoto, M., Nagatsu, T. Cancer Res. (1980) [Pubmed]
  16. Modulation of melanogenic protein expression during the switch from eu- to pheomelanogenesis. Kobayashi, T., Vieira, W.D., Potterf, B., Sakai, C., Imokawa, G., Hearing, V.J. J. Cell. Sci. (1995) [Pubmed]
  17. Pheomelanin production in the epidermis from newborn agouti mice is induced by the expression of the agouti gene in the dermis. Hirobe, T., Takeuchi, S., Hotta, E., Wakamatsu, K., Ito, S. Pigment Cell Res. (2004) [Pubmed]
  18. Agouti alleles influence thiol concentrations in hair follicles and extrafollicular tissues of mice (Ay/a, AwJ/AwJ, a/a). Granholm, D.E., Reese, R.N., Granholm, N.H. Pigment Cell Res. (1995) [Pubmed]
  19. Enhancement of pheomelanogenesis by L-dopa in the mouse melanocyte cell line, TM10, in vitro. Sato, C., Ito, S., Takeuchi, T. J. Cell. Sci. (1987) [Pubmed]
  20. Stimulation of the proliferation and differentiation of mouse pink-eyed dilution epidermal melanocytes by excess tyrosine in serum-free primary culture. Hirobe, T., Wakamatsu, K., Ito, S., Abe, H., Kawa, Y., Mizoguchi, M. J. Cell. Physiol. (2002) [Pubmed]
  21. Glutathione plays a key role in the depigmenting and melanocytotoxic action of N-acetyl-4-S-cysteaminylphenol in black and yellow hair follicles. Alena, F., Dixon, W., Thomas, P., Jimbow, K. J. Invest. Dermatol. (1995) [Pubmed]
  22. Induction of melanization within hair bulb melanocytes in chinchilla mutant by melanogenic stimulants. Imokawa, G., Yada, Y., Hori, Y. J. Invest. Dermatol. (1988) [Pubmed]
  23. 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]
  24. Interaction of major coat color gene functions in mice as studied by chemical analysis of eumelanin and pheomelanin. Lamoreux, M.L., Wakamatsu, K., Ito, S. Pigment Cell Res. (2001) [Pubmed]
  25. The pinkeyed-dilution protein and the eumelanin/pheomelanin switch: in support of a unifying hypothesis. Lamoreux, M.L., Zhou, B.K., Rosemblat, S., Orlow, S.J. Pigment Cell Res. (1995) [Pubmed]
  26. Melanin content of cultured human melanocytes and UV-induced cytotoxicity. De Leeuw, S.M., Smit, N.P., Van Veldhoven, M., Pennings, E.M., Pavel, S., Simons, J.W., Schothorst, A.A. J. Photochem. Photobiol. B, Biol. (2001) [Pubmed]
  27. Quantitative trait loci that modify the sootiness of yellow pigmentation in KK-A(y)/a mice. Suto, J., Wakamatsu, K., Yamanaka, H., Ito, S., Sekikawa, K. Mamm. Genome (2000) [Pubmed]
  28. A polymorphism in the agouti signaling protein gene is associated with human pigmentation. Kanetsky, P.A., Swoyer, J., Panossian, S., Holmes, R., Guerry, D., Rebbeck, T.R. Am. J. Hum. Genet. (2002) [Pubmed]
  29. Effect of DOPA-loading on glutathione-dependent 5-S-cysteinyldopa genesis in melanoma cells in vitro. Mojamdar, M., Ichihashi, M., Mishima, Y. J. Invest. Dermatol. (1982) [Pubmed]
  30. Glutathione reductase activity in skin exposed to 4-tertiary butyl catechol. Yonemoto, K., Gellin, G.A., Epstein, W.L., Fukuyama, K. International archives of occupational and environmental health. (1983) [Pubmed]
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