Focus on Molecules: RPGR.
Focus on Molecules: RPGR.
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DOI：
10.1016/j.exer.2006.03.006
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发表时间：
2007-07
影响因子：
3.4
通讯作者：
A. Wright;X. Shu
中科院分区：
文献类型：
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作者：
A. Wright;X. Shu
视网膜色素变性GTPase Regulator （RPGR）基因位于染色体Xp21区。1和跨越172千碱基（Vervoort et al., 2000）。有多个选择性剪接转录本，它们都编码一个氨基(N)端RCC1样结构域（RLD），其结构与RCC1蛋白相似，RCC1蛋白是小gtp结合蛋白Ran的鸟嘌呤核苷酸交换因子。RCC1的x射线晶体结构由七叶螺旋桨组成，每个叶片由内部重复的51e68残基组成。RPGR的RLD与RPGRIP1和一个17 kDa的烯丙基结合蛋白相互作用。最初鉴定的转录本广泛表达，包含19个外显子（RPGRex1e19），编码预测的90 kDa蛋白（Meindl等，1996）。外显子1e11编码RLD，而外显子12e19编码富含酸性残基的羧基(C)末端结构域，并以异戊二烯酰化锚定信号结束（图1）。随后，人们发现了其他转录本，其中最重要的是RPGRORF15，它在光感受器中表达最高，是已知的唯一与视网膜疾病有关的转录本。人类rpgref15包含RPGRex1e19的外显子1e14和一个大的可选拼接的c端外显子ORF15，编码567个氨基酸。人rpgorf15全长异构体编码1152个氨基酸的蛋白。ORF15外显子编码一个功能未知的重复的富含甘氨酸和谷氨酸的结构域和一个进化保守的基本c端结构域（ORF15C2），该结构域与有丝分裂纺锤体极点的多功能伴侣蛋白核磷蛋白（NPM）结合。
The Retinitis Pigmentosa GTPase Regulator (RPGR) gene is located in chromosomal region Xp21. 1 and spans 172 kilobases (Vervoort et al., 2000). There are multiple alternatively spliced transcripts, all of which encode an amino (N)-terminal RCC1-like domain (RLD) that is structurally similar to the RCC1 protein, a guanine nucleotide exchange factor for the small GTP-binding protein, Ran. The X-ray crystallographic structure of RCC1 consists of a sevenbladed propeller formed from internal repeats of 51e68 residues per blade. The RLD of RPGR interacts with RPGRIP1 and a 17 kDa Prenyl Binding Protein.The transcript that was initially identified is widely expressed and contains nineteen exons (RPGRex1e19), encoding a predicted 90 kDa protein (Meindl et al., 1996). Exons 1e11 encode the RLD, while exons 12e19 encode a carboxyl (C)-terminal domain rich in acidic residues and ending in an isoprenylation anchorage signal (Fig. 1). Subsequently, alternative transcripts have been found, the most important of which is RPGRORF15, which shows highest expression in photoreceptors, and is the only transcript known to be involved in retinal disease. Human RPGRORF15 contains exons 1e14 of RPGRex1e19 plus a large alternatively spliced C-terminal exon, ORF15, encoding 567 amino acids. The full length human RPGRORF15 isoform encodes a 1152-amino-acid protein. Exon ORF15 encodes a repetitive glycine and glutamic acid-rich domain of unknown function and a basic C-terminal domain (ORF15C2), which is evolutionarily conserved and binds the multifunctional chaperone nucleophosmin (NPM) at mitotic spindle poles.