A 2ND TYROSINASE-RELATED PROTEIN, TRP-2, MAPS TO AND IS MUTATED AT THE MOUSE SLATY LOCUS
A 2ND TYROSINASE-RELATED PROTEIN, TRP-2, MAPS TO AND IS MUTATED AT THE MOUSE SLATY LOCUS
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DOI：
10.1002/j.1460-2075.1992.tb05083.x
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发表时间：
1992-02-01
期刊：
影响因子：
11.4
通讯作者：
HEARING, V
中科院分区：
文献类型：
--
作者：
JACKSON, IJ;CHAMBERS, DM;HEARING, V
我们已经克隆并测序了与黑素细胞特异性mRNAs家族的第三个成员相对应的小鼠cDNA，该家族编码酪氨酸酶和相关蛋白。这个新成员是酪氨酸酶相关蛋白-2(TRP-2)，它与家族中的另外两个蛋白有大约40%的氨基酸同源性，并具有相同的结构特征，包括两个铜结合部位、两个半胱氨酸富集区、一个信号肽和一个跨膜区。我们现在发现，该蛋白家族中富含半胱氨酸的区域之一是在许多细胞外和细胞表面蛋白中发现的类似EGF的重复序列。编码Trp-2的基因被映射到小鼠14号染色体上，位于毛色突变Slaty的区域。我们发现Slaty小鼠的Trp-2与野生型Trp-2有一个氨基酸差异；第一个铜结合位点上的精氨酸被谷氨酰胺取代。色氨酸-2(Trp-2)是一种被广泛研究的黑素合成酶，它催化多巴色素转化为5，6，2-二羟基吲哚-2-羧酸。纯合突变小鼠的DT活性下降了3倍或更多，这表明Trp-2/DT是在Slate基因座编码的，错义突变降低了酶的活性，但不会取消酶的活性。
We have cloned and sequenced mouse cDNAs corresponding to a third member of a family of melanocyte-specific mRNAs, which encode tyrosinase and related proteins. This new member, tyrosinase-related protein-2 (TRP-2), has approximately 40% amino acid identity with the two other proteins in the family and has the same structural features including two copper binding sites, two cysteine-rich regions, a signal peptide and a transmembrane domain. We now show that one of the cysteine-rich regions in this protein family is an 'EGF-like' repeat found in many extracellular and cell surface proteins. The gene encoding TRP-2 maps to mouse chromosome 14, in the region of the coat colour mutation slaty. We show that the TRP-2 of slaty mice has a single amino acid difference from wild-type TRP-2; a substitution of glutamine for arginine in the first copper binding site. TRP-2 is the much sought melanogenic enzyme DOPAchrome tautomerase (DT), which catalyses the conversion of DOPAchrome to 5,6,dihydroxyindole-2-carboxylic acid. Extracts from mice homozygous for the slaty mutation have a 3-fold or more reduction in DT activity, indicating that TRP-2/DT is encoded at the slaty locus, and the missense mutation reduces but does not abolish the enzyme activity.