Paffenholz R, Franke W W
Division of Cell Biology, German Cancer Research Center, Heidelberg, Germany.
Differentiation. 1997 Aug;61(5):293-304. doi: 10.1046/j.1432-0436.1997.6150293.x.
The plakoglobin/armadillo multigene family comprises many proteins widely differing in sizes and functions which have in common a variable number of tandemly repeated arm sequences of about 42 amino acids (aa). In a search for proteins with sequence homology to the desmosomal-plaque-associated arm-repeat-containing protein, plakophilin 1, we have identified a novel plakoglobin/armadillo protein. This new member of the multigene family is predominantly, if not exclusively, expressed in neural and neuroendocrine tissues, hence the name neural plakophilin-related arm-repeat protein (NPRAP). The murine cDNA codes for a protein of 1247 aa, with a predicted molecular weight of 135 kDa and a pI of 7.57. The orthologous human protein differs only in a few aa, indicative of the evolutionary stability of NPRAP. In human and murine cDNAs, we have found different transcripts of the NPRAP gene, suggesting that in each species the protein exists in at least two isoforms. The NPRA protein contains three different regions: a 528-aa amino-terminal "head" domain, including a potential coiled-coil-forming alpha-helix segment, a central domain with 10 imperfect arm-repeat units, and a 212-aa carboxy-terminal "tail" domain. By aa sequence, NPRAP is highly homologous to three proteins: p120cas, p0071 and ARVCP, which represent a distinct subgroup within the plakoglobin/armadillo family. By in situ hybridization and immunofluorescence microscopy using NPRAP-specific antibodies, we have demonstrated NPRAP and its mRNA in the perikarya of various kinds of CNS neurons in embryonic and adult mice, but minimal amounts have also been detected by immunoblot analysis in some other tissues containing neural or neuroendocrine elements. We have not seen significant enrichment of NPRAP at cell junctions or in nuclei. Possible NPRAP functions are discussed and the correlation of NPRAP synthesis with neuronal differentiation processes is emphasized.
桥粒斑珠蛋白/犰狳多基因家族包含许多大小和功能差异很大的蛋白质，它们的共同特点是具有数量可变的约42个氨基酸（aa）的串联重复臂序列。在寻找与桥粒斑相关的含臂重复蛋白桥粒芯蛋白1具有序列同源性的蛋白质时，我们鉴定出一种新型的桥粒斑珠蛋白/犰狳蛋白。这个多基因家族的新成员主要（如果不是唯一的话）在神经和神经内分泌组织中表达，因此命名为神经桥粒芯蛋白相关臂重复蛋白（NPRAP）。小鼠cDNA编码一个1247个氨基酸的蛋白质，预测分子量为135 kDa，等电点为7.57。直系同源的人类蛋白质仅在少数氨基酸上有所不同，这表明NPRAP在进化上具有稳定性。在人类和小鼠cDNA中我们发现了NPRAP基因的不同转录本，这表明在每个物种中该蛋白质至少以两种异构体形式存在。NPRAP蛋白包含三个不同区域：一个528个氨基酸的氨基末端“头部”结构域，包括一个潜在的形成卷曲螺旋的α螺旋片段；一个具有10个不完全臂重复单元的中央结构域；以及一个212个氨基酸的羧基末端“尾部”结构域。通过氨基酸序列分析，NPRAP与三种蛋白质高度同源：p120cas、p0071和ARVCP，它们代表桥粒斑珠蛋白/犰狳家族中的一个独特亚组。通过原位杂交和使用NPRAP特异性抗体的免疫荧光显微镜检查，我们在胚胎和成年小鼠的各种中枢神经系统神经元的胞体中证实了NPRAP及其mRNA，但在一些其他含有神经或神经内分泌成分的组织中通过免疫印迹分析也检测到了少量。我们没有在细胞连接处或细胞核中发现NPRAP的显著富集。文中讨论了NPRAP可能的功能，并强调了NPRAP合成与神经元分化过程的相关性。
