MURINE AND HUMAN B-LOCUS PIGMENTATION GENES ENCODE A GLYCOPROTEIN (GP75) WITH CATALASE ACTIVITY
MURINE AND HUMAN B-LOCUS PIGMENTATION GENES ENCODE A GLYCOPROTEIN (GP75) WITH CATALASE ACTIVITY
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DOI：
10.1073/pnas.87.12.4809
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发表时间：
1990-06-01
影响因子：
11.1
通讯作者：
MOELLMANN, G
中科院分区：
文献类型：
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作者：
HALABAN, R;MOELLMANN, G
黑素合成在很大程度上由酪氨酸酶(单酚单加氧酶；单苯酚，L-多巴：氧氧化还原酶，EC 1.14.18.1)调节，而酪氨酸酶缺陷会导致白化。其他色素沉着决定因素(例如，在酪氨酸酶阳性白化病和小鼠毛色突变中起作用的那些)的机制尚不清楚。小鼠的一种色素沉着基因，棕色(B)基因，当突变时会导致棕色(b/b)或色素减少(BLT/BLT)，而不是野生型黑色(B/B)。我们发现，b基因座编码具有过氧化氢酶(H_2O_2：H_2O_2氧化还原酶，EC 1.11.1.6)(过氧化氢酶B)活性的糖蛋白。只有c位点蛋白是酪氨酸酶。由于过氧化氢可能是黑素生成活动的副产物，尤其是过氧化氢已知可以破坏黑色素前体和黑色素，我们得出结论，色素沉着不仅受酪氨酸酶控制，还受氢过氧化物酶控制。我们的研究表明，过氧化氢酶B与已知的人类黑素体糖蛋白gp75相同；b突变位于血红素相关区域；BLT突变使蛋白质容易快速蛋白质降解。
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.