A novel SH3-containing human gene family preferentially expressed in the central nervous system

A novel SH3-containing human gene family preferentially expressed in the central nervous system
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DOI:
10.1006/geno.1997.4645
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发表时间:
1997-05-01
期刊:
影响因子:
4.4
通讯作者:
Migone, N
Migone, N
中科院分区:
生物学3区
文献类型:
--
作者:
Giachino, C;Lantelme, E;Migone, N

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Src-homology-3结构域(SH3)是一个进化上保守的,由细胞内蛋白携带的50- 60个氨基酸模块,参与细胞极化、运动、酶激活和转录调控的信号转导。SH3通过与富含脯氨酸的配体结合来驱动蛋白-蛋白相互作用,这种功能依赖于保守的二级结构,而SH3一级结构是高度多样化的。利用少数保守氨基酸聚集在N端和c端附近的事实,我们设计了跨越这两个区域的简并寡核苷酸,并通过PCR筛选了多种正常和肿瘤组织中含有sh3的转录本的表达。使用这种策略,我们已经确定了一个新的含有sh3的人类基因家族,该家族有6个相关转录本,映射到4个不同的染色体。SH3结构域位于c端,与Sem-5/Drk/GRB2的c端SH3具有56-50%的氨基酸同源性。这种新型SH3GL(来自含sr3的grb2 - like)基因家族的n端片段与任何已知的蛋白质都不相似。其中三个转录本在框架内,并表现出特殊的组织分布:SH3GL2优先表达于大脑,SH3GL3优先表达于大脑和睾丸,而SH3GL1普遍存在。(C) 1997学术出版社。
The Src-homology-3 domain (SH3) is an evolutionarily conserved, 50- to 60-amino-acid module carried by intracellular proteins involved in the transduction of signals for cell polarization, motility, enzymatic activation, and transcriptional regulation. The SH3 drives protein-protein interactions through binding to proline-rich ligands, This function relies on the conserved secondary structure, whereas the SH3 primary structure is highly diverse. Taking advantage of the fact that the few conserved amino acids are clustered near the N- and C-terminal ends, we designed degenerate oligonucleotides spanning these two regions and screened by PCR a variety of normal and tumor tissues for the expression of SH3-containing transcripts. Using this strategy, we have identified a novel SH3-containing human gene family of six related transcripts that map to four different chromosomes. The SH3 domain lies at the C-terminal end and shows 56-50% amino acid homology to the C-terminal SH3 of Sem-5/Drk/GRB2. The N-terminal segment of this novel SH3GL (from SR3-containing Grb2-Iike) gene family does not resemble any known protein. Three of these transcripts are in-frame and show a peculiar tissue distribution: SH3GL2 is preferentially expressed in the brain, SH3GL3 in brain and testis, and SH3GL1 is ubiquitous. (C) 1997 Academic Press.