Murine and human b locus pigmentation genes encode a glycoprotein (gp75) with catalase activity.
Melanogenesis is regulated in large part by tyrosinase (monophenol monooxygenase; monophenol, L-dopa:oxygen oxidoreductase, EC 1.14.18.1), and defective tyrosinase leads to albinism. The mechanisms for other pigmentation determinants (e.g., those operative in tyrosinase-positive albinism and in murine coat-color mutants) are not yet known. One murine pigmentation gene, the brown (b) locus, when mutated leads to a brown (b/b) or hypopigmented (Blt/Blt) coat versus the wild-type black (B/B). We show that the b locus codes for a glycoprotein with the activity of a catalase (hydrogen-peroxide:hydrogen-peroxide oxidoreductase, EC 1.11.1.6) (catalase B). Only the c locus protein is a tyrosinase. Because peroxides may be by-products of melanogenic activity and hydrogen peroxide in particular is known to destroy melanin precursors and melanin, we conclude that pigmentation is controlled not only by tyrosinase but also by a hydroperoxidase. Our studies indicate that catalase B is identical with gp75, a known human melanosomal glycoprotein; that the b mutation is in a heme-associated domain; and that the Blt mutation renders the protein susceptible to rapid proteolytic degradation.
Halaban
R
R
Department of Dermatology, Yale University School of Medicine, New Haven, CT 06510.
Moellmann
G
G
D000417:Albinism / Q000235:genetics; D000818:Animals; D002374:Catalase / Q000235:genetics* / Q000378:metabolism; D004156:Catechol Oxidase / Q000235:genetics*; D002460:Cell Line; D002478:Cells, Cultured; D000939:Epitopes / Q000032:analysis; D004912:Erythrocytes / Q000201:enzymology; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D007700:Kinetics; D008544:Melanocytes / Q000201:enzymology*; D008546:Melanoma, Experimental / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D014442:Monophenol Monooxygenase / Q000235:genetics* / Q000378:metabolism; D010858:Pigmentation / Q000235:genetics*
D000939:Epitopes; D006023:Glycoproteins; D004156:Catechol Oxidase; D002374:Catalase; D014442:Monophenol Monooxygenase