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ASXL2基因的电子鉴定与特征分析

Identification and characterization of ASXL2 gene in silico.

作者信息

Katoh Masuko, Katoh Masaru

机构信息

M&M Medical BioInformatics, Narashino 275-0022, Japan.

出版信息

Int J Oncol. 2003 Sep;23(3):845-50.

Abstract

Drosophila Asx is a Polycomb group gene. Because Drosophila Asx mutations exhibit anterior and posterior transformations, Drosophila Asx is one of the ETP (Enhancers of trithorax and Polycomb) genes with dual functions in transcriptional activation and silencing. ASXL1 is one of human homologs of Drosophila Asx. Here, we searched for ASXL1-related gene within the human genome by using bioinformatics, and identified the ASXL2 gene. Nucleotide sequence of human ASXL2 cDNA was determined by assembling the nucleotide sequences of human EST AI797346, and partial cDNAs MGC44431 (BC042999) and KIAA1685 (AB051472). Nucleotide sequence of mouse Asxl2 was derived from uncharacterized mouse cDNA 9930017F14 (AK036839). Human ASXL2 (1435 aa) showed 79.4% total-amino-acid identity with mouse Asxl2 (1370 aa), and 29.8% total-amino-acid identity with human ASXL1. ASXN domain (codon 1-86 of ASXL2), ASXM domain (codon 269-380 of ASXL2), and PHD domain (codon 1400-1431 of ASXL2) were conserved between human ASXL2 and ASXL1. Human ASXL2 gene, consisting of at least 13 exons, was mapped to human chromosome 2p23.3, one of recombination hot spots or fragile sites associated with carcinogenesis. The DNMT3A-ASXL2-KIF3C locus on human chromosome 2p23.3 and the DNMT3B-ASXL1-KIF3B locus on human chromosome 20q11.21 were paralogous regions within the human genome. Polycomb group and trithorax group proteins are implicated in embryogenesis and carcinogenesis due to transcriptional regulation of target genes through histone modification and chromatin remodeling. Based on functional conservation and human chromosomal localization, ASXL2 and ASXL1 genes were predicted cancer-associated genes.

摘要

果蝇Asx是一种多梳蛋白家族基因。由于果蝇Asx突变表现出前后体节转化,果蝇Asx是具有转录激活和沉默双重功能的ETP(三体胸节和多梳蛋白增强子)基因之一。ASXL1是果蝇Asx在人类中的同源物之一。在此,我们利用生物信息学在人类基因组中搜索与ASXL1相关的基因,并鉴定出了ASXL2基因。通过组装人类EST AI797346以及部分cDNA MGC44431(BC042999)和KIAA1685(AB051472)的核苷酸序列,确定了人类ASXL2 cDNA的核苷酸序列。小鼠Asxl2的核苷酸序列来自未鉴定的小鼠cDNA 9930017F14(AK036839)。人类ASXL2(1435个氨基酸)与小鼠Asxl2(1370个氨基酸)的总氨基酸同一性为79.4%,与人类ASXL1的总氨基酸同一性为29.8%。人类ASXL2和ASXL1之间,ASXN结构域(ASXL2的第1至86密码子)、ASXM结构域(ASXL2的第269至380密码子)和PHD结构域(ASXL2的第1400至1431密码子)是保守的。人类ASXL2基因由至少13个外显子组成,定位于人类染色体2p23.3,这是与致癌作用相关的重组热点或脆性位点之一。人类染色体2p23.3上的DNMT3A - ASXL2 - KIF3C基因座和人类染色体20q11.21上的DNMT3B - ASXL1 - KIF3B基因座是人类基因组中的旁系同源区域。多梳蛋白家族和三体胸节蛋白家族的蛋白质通过组蛋白修饰和染色质重塑对靶基因进行转录调控,从而参与胚胎发育和致癌过程。基于功能保守性和人类染色体定位,ASXL2和ASXL1基因被预测为癌症相关基因。

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