In silico-initiated cloning and molecular characterization of a novel human member of the L1 gene family of neural cell adhesion molecules
In silico-initiated cloning and molecular characterization of a novel human member of the L1 gene family of neural cell adhesion molecules
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DOI：
10.1007/s004390050829
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发表时间：
1998-09-01
期刊：
影响因子：
5.3
通讯作者：
Lerman, MI
中科院分区：
文献类型：
--
作者：
Wei, MH;Karavanova, I;Lerman, MI
为了发现导致3 p（-）综合征患者精神发育迟缓的基因，我们在NCBI数据库（dbEST和Uni-Gene）中使用计算机模拟搜索神经基因。一个EST与大鼠CAM L1基因具有很强的同源性，随后定位到3 p26，用于分离全长cDNA。对该cDNA的分子分析表明，它由染色体3 p26位点编码，是神经细胞粘附分子L1基因家族的新成员，称为CALL（细胞粘附L1样）。多条证据表明CALL可能是小鼠基因CHL 1的人类直系同源物：它在蛋白质水平上具有84%的相同性，具有相同的结构域结构，相同的膜拓扑结构和相似的表达模式。系统发育分析证实了CALL和CHL 1的同源性。通过原位杂交，CALL显示在大鼠发育过程中在中枢神经系统、脊髓和周围神经系统中以及时的方式区域性表达。北方分析和EST表示表明，它在大脑中表达，在一些成人组织和肿瘤细胞系中也在神经系统外表达。CALL的胞质结构域在L1亚家族的其他成员中是保守的，并且具有可能在信号转导途径中涉及CALL的序列基序。
To discover genes contributing to mental retardation in 3p(-) syndrome patients we have used in silico searches for neural genes in NCBI databases (dbEST and Uni-Gene). An EST with strong homology to the rat CAM L1 gene subsequently mapped to 3p26 was used to isolate a full-length cDNA. Molecular analysis of this cDNA, referred to as CALL (cell adhesion L1-like), showed that it is encoded by a chromosome 3p26 locus and is a novel member of the L1 gene family of neural cell adhesion molecules. Multiple lines of evidence suggest CALL is likely the human ortholog of the murine gene CHL1: it is 84% identical on the protein level, has the same domain structure, same membrane topology, and a similar expression pattern. The orthology of CALL and CHL1 was confirmed by phylogenetic analysis. By in situ hybridization, CALL is shown to be expressed regionally in a timely fashion in the central nervous system, spinal cord, and peripheral nervous system during rat development. Northern analysis and EST representation reveal that it is expressed in the brain and also outside the nervous system in some adult human tissues and tumor cell lines. The cytoplasmic domain of CALL is conserved among other members of the L1 subfamily and features sequence motifs that may involve CALL in signal transduction pathways.