Human FRAG1 encodes a novel membrane-spanning protein that localizes to chromosome 11p15.5, a region of frequent loss of heterozygosity in cancer
Human FRAG1 encodes a novel membrane-spanning protein that localizes to chromosome 11p15.5, a region of frequent loss of heterozygosity in cancer
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DOI：
10.1006/geno.1999.5980
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发表时间：
1999-11-15
期刊：
影响因子：
4.4
通讯作者：
Miki, T
中科院分区：
文献类型：
--
作者：
Lorenzi, MV;Castagnino, P;Miki, T
我们以前已经确定了成纤维细胞生长因子受体2（FGFR 2）和一个新的基因，FRAGI，在啮齿动物模型的骨肉瘤染色体重排。为了进一步评估FRAGI在疾病中的潜在作用，我们分离了人FRAGI的cDNA和基因组克隆。cDNA的序列分析揭示了原始FRAG 1序列中不包含的插入的存在。在人FRAGI中的这种插入编码了一个与蛋白质的前55个氨基酸高度同源并紧接其后的区域，表明在FRAG 1;1内存在重复结构域，称为FRAG 1同源性（FH）结构域。FRAG 1基因结构分析显示FH结构域由串联重复的外显子编码。数据库检索鉴定了几种与FRAG 1的FH结构域具有同源性的跨膜蛋白。此外，亲水性分析预测FRAGI编码一个完整的膜蛋白与多个跨膜节段。FRAGI mRNA以不同的丰度水平在人成人组织和几种肿瘤细胞系中广泛表达。通过荧光原位杂交和放射杂交分析，将人FRAGI定位于11号染色体p15.5带，该区域与Beckwith-Wiedemann综合征有关，也是多种肿瘤类型中杂合性丢失频繁的区域。这些结果表明，FRAGI可能是一个有用的候选基因与11p15.5的改变相关的遗传性疾病。(C)北京：科学出版社.
We have previously identified a chromosomal rearrangement between fibroblast growth factor receptor 2 (FGFR2) and a novel gene, FRAGI, in a rodent model of osteosarcoma. To assess the potential role of FRAGI in disease further, we have isolated cDNA and genomic clones of human FRAGI. Sequence analysis of the cDNA revealed the presence of an insertion not contained in the original FRAG1 sequence. This insertion in human FRAGI encoded a region highly homologous to and immediately following the first 55 amino acids of the protein, indicating the presence of a repetitive domain within FRAG1;1, designated the FRAG1 homology (FH) domain. Analysis of FRAG1 gene structure revealed that the FH domains were encoded by tandem duplicated exons. Database searches identified several transmembrane proteins displaying homology to the FH domain of FRAG1. In addition, hydropathy analysis predicted FRAGI to encode an integral membrane protein with multiple membrane-spanning segments. FRAGI mRNA was ubiquitously expressed in human adult tissues and several tumor cell lines at varying levels of abundance. Human FRAGI was mapped by fluorescence in situ hybridization and radiation hybrid analysis to chromosome 11 at band p15.5, a region implicated in Beckwith-Wiedemann syndrome and a region of frequent loss of heterozygosity in multiple tumor types. These results suggest that FRAGI may be a useful candidate gene for genetic disorders associated with alterations at 11p15.5. (C) 1999 Academic Press.