Vignal A, Rahuel C, London J, Cherif Zahar B, Schaff S, Hattab C, Okubo Y, Cartron J P
Institut National de la Santé et de la Recherche Médicale, Unité 76, Paris, France.
Eur J Biochem. 1990 Aug 17;191(3):619-25. doi: 10.1111/j.1432-1033.1990.tb19166.x.
A new gene closely related to the glycophorin A (GPA) and glycophorin B (GPB) genes has been identified in the normal human genome as well as in that of persons with known alterations of GPA and/or GPB expression. This gene, called glycophorin E (GPE), is transcribed into a 0.6-kb message which encodes a 78-amino-acid protein with a putative leader peptide of 19 residues. The first 26 amino acids of the mature protein are identical to those of M-type glycophorin A (GPA), but the C-terminal domain (residues 27-59) differs significantly from those of glycophorins A and B (GPA and GPB). The GPE gene consists of four exons distributed over 30 kb of DNA, and its nucleotide sequence is homologous to those of the GPA and GPB genes in the 5' region, up to exon 3. Because of branch and splice site mutations, the GPE gene contains a large intron sequence partially used as exons in GPA and GPB genes. Compared to its counterpart in the GPB gene, exon 3 of the GPE gene contains several point mutations, an insertion of 24 bp, and a stop codon which shortens the reading frame. Downstream from exon 3, the GPE and the GPB sequences are virtually identical and include the same Alu repeats. Thus, it is likely that the GPE and GPB genes have evolved by a similar mechanism. From the analysis of the GPA, GPB and GPE genes in glycophorin variants [En(a-), S-s-U- and Mk], it is proposed that the three genes are organized in tandem on chromosome 4. Deletion events within this region may remove one or two structural gene(s) and may generate new hybrid structures in which the promoter region of one gene is positioned upstream from the body of another gene of the same family. This model of gene organization provides a basis with which to explain the diversity of the glycophorin gene family.
在正常人类基因组以及已知糖蛋白A（GPA）和/或糖蛋白B（GPB）表达改变的人群基因组中，已鉴定出一个与GPA和GPB基因密切相关的新基因。这个基因被称为糖蛋白E（GPE），转录成一条0.6 kb的信使核糖核酸，编码一种含78个氨基酸的蛋白质，带有一个19个残基的推定前导肽。成熟蛋白的前26个氨基酸与M型糖蛋白A（GPA）的相同，但C末端结构域（第27 - 59位残基）与糖蛋白A和B（GPA和GPB）的显著不同。GPE基因由分布在30 kb DNA上的四个外显子组成，其核苷酸序列在5'区域直至外显子3与GPA和GPB基因的同源。由于分支和剪接位点突变，GPE基因包含一个大的内含子序列，在GPA和GPB基因中部分用作外显子。与GPB基因中的对应外显子相比，GPE基因的外显子3包含几个点突变、一个24 bp的插入以及一个缩短阅读框的终止密码子。在外显子3下游，GPE和GPB序列实际上是相同的，并且包含相同的Alu重复序列。因此，GPE和GPB基因很可能通过类似的机制进化。通过对糖蛋白变体[En(a-)、S-s-U-和Mk]中的GPA、GPB和GPE基因分析，提出这三个基因在4号染色体上串联排列。该区域内的缺失事件可能会去除一个或两个结构基因，并可能产生新的杂交结构，其中一个基因的启动子区域位于同一家族另一个基因的主体上游。这种基因组织模型为解释糖蛋白基因家族的多样性提供了一个基础。
