The gene encoding DRAP (BACE2), a glycosylated transmembrane protein of the aspartic protease family, maps to the Down critical region
The gene encoding DRAP (BACE2), a glycosylated transmembrane protein of the aspartic protease family, maps to the Down critical region
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DOI：
10.1016/s0014-5793(00)01192-3
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发表时间：
2000-02-18
期刊：
影响因子：
3.5
通讯作者：
Taramelli, R
中科院分区：
文献类型：
--
作者：
Acquati, F;Accarino, M;Taramelli, R
我们应用cDNA筛选方法从21号染色体21q22.3的Down critical region中克隆了一个基因组克隆（YAC 761 B5）。这些克隆中的一个（Down区域天冬氨酸蛋白酶（DRAP），根据基因命名法也被命名为BACE 2）揭示了与天冬氨酸蛋白酶家族成员中存在的几个基序的显著核苷酸和氨基酸序列同一性。特别地，包含在所有哺乳动物天冬氨酸蛋白酶中发现的两个催化位点的氨基酸序列是完全保守的。有趣的是，预测的蛋白质显示了一个典型的跨膜区，这是在与大多数其他已知的天冬氨酸蛋白酶，这是可溶性分子的差异。我们目前的初步证据，在体外翻译研究和细胞转染的基础上，该基因编码的糖基化蛋白，主要定位在细胞内，但在一定程度上也质膜。此外，DRAP/BACE 2与一种新发现的跨膜天冬氨酸蛋白酶β-分泌酶（BACE-1）具有高度同源性，并讨论了这一发现对唐氏综合征的意义。(C)2000年欧洲生物化学学会联合会。
We applied cDNA selection methods to a genomic clone (YAC 761B5) from chromosome 21 located in the so-called 'Down critical region' in 21q22.3, Starting from human fetal heart and brain mRNAs we obtained and sequenced several cDWA clones. One of these clones (Down region aspartic protease (DRAP), named also BACE2 according to the gene nomenclature) revealed a striking nucleotide and amino acid sequence identity with several motifs present in members of the aspartic protease family, In particular the amino acid sequences comprising the two catalytic sites found in all mammalian aspartic proteases are perfectly conserved. Interestingly, the predicted protein shows a typical membrane spanning region; this is at variance with most other known aspartic proteases, which are soluble molecules. We present preliminary evidence, on the basis of in vitro translation studies and cell transfection, that this gene encodes a glycosylated protein which localizes mainly intracellularly but to some extent also to the plasma membrane. Furthermore DRAP/BACE2 shares a high homology with a newly described beta-secretase enzyme (BACE-1) which is a transmembrane aspartic protease, The implications of this finding for Down syndrome are discussed. (C) 2000 Federation of European Biochemical Societies.