Isolation, characterization, and mapping of the mouse and human Fgd2 genes, faciogenital dysplasia (FGD1; Aarskog syndrome) gene homologues.
Isolation, characterization, and mapping of the mouse and human Fgd2 genes, faciogenital dysplasia (FGD1; Aarskog syndrome) gene homologues.
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DOI：
10.1006/geno.1999.5903
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发表时间：
1999-08
期刊：
影响因子：
4.4
通讯作者：
N. Pasteris;J. Gorski
中科院分区：
文献类型：
--
作者：
N. Pasteris;J. Gorski
FGD1编码一种鸟嘌呤核苷酸交换因子，它能特异性地激活Rho GTP酶CDc42。FGD1基因突变导致面部生殖器发育不良(FGDY，Aarskog综合征)，这是一种X连锁发育障碍，对多种骨骼结构的形成产生不利影响。数据库搜索显示，秀丽线虫基因组包含FGD1同源物。由于线虫基因通常有多个脊椎动物同源物，我们假设存在多个哺乳动物FGD1相关序列。在这里，我们报告了使用简并PCR来分离和鉴定FGD1基因家族中的新成员--鼠和人的FGD2基因。FGD2基因编码一个727个氨基酸的蛋白质，预测质量为82 kDa。FGD2和FGD1具有跨越>；560个相邻氨基酸残基的高度序列同源性。FGD2和FGD1一样，含有相邻的Rhogef和PH结构域，第二个羧基末端PH结构域和一个独特的FYVE结构域。基因组聚合酶链式反应研究表明，FGd2和FGd1之间存在一定程度的保守基因结构。FGD2转录本存在于几个不同的组织中，并在小鼠胚胎发育过程中，表明在胚胎发育中发挥作用。遗传连锁和辐射杂交定位数据表明，FGD2和人FGD2分别定位于小鼠17号染色体和人6p21.2号染色体的同线区域。所有FGD1基因家族成员都含有相同的信号域和保守的结构组织，这有力地表明这些信号域形成了Rhogef蛋白FGD1家族成员的规范核心结构。
FGD1 encodes a guanine nucleotide exchange factor (GEF) that specifically activates the Rho GTPase Cdc42. FGD1 gene mutations result in faciogenital dysplasia (FGDY, Aarskog syndrome), an X-linked developmental disorder that adversely affects the formation of multiple skeletal structures. Database searches show that the Caenorhabditis elegans genome contains an FGD1 homologue. Since C. elegans genes often have multiple vertebrate homologues, we hypothesized the existence of multiple mammalian FGD1-related sequences. Here we report the use of degenerate PCR to isolate and characterize the mouse and human Fgd2 genes, new members of the FGD1 gene family. Fgd2 cDNA encodes a 727-amino-acid protein with a predicted mass of 82 kDa. Fgd2 and FGD1 share a high degree of sequence identity that spans >560 contiguous amino acid residues. Fgd2, like FGD1, contains adjacent RhoGEF and PH domains, a second carboxy-terminal PH domain, and a distinctive FYVE domain. Genomic PCR studies indicate some degree of conserved gene structure between Fgd2 and FGD1. Fgd2 transcripts are present in several diverse tissues and during mouse embryogenesis, suggesting a role in embryonic development. Genetic linkage and radiation hybrid mapping data show that Fgd2 and the human FGD2 ortholog map to syntenic regions of murine chromosome 17 and human chromosome 6p21.2, respectively. The observation that all FGD1 gene family members contain equivalent signaling domains and a conserved structural organization strongly suggests that these signaling domains form a canonical core structure for members of the FGD1 family of RhoGEF proteins.