Copley Richard R
Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK.
BMC Genomics. 2005 Nov 27;6:169. doi: 10.1186/1471-2164-6-169.
The Engrailed Homology 1 (EH1) motif is a small region, believed to have evolved convergently in homeobox and forkhead containing proteins, that interacts with the Drosophila protein groucho (C. elegans unc-37, Human Transducin-like Enhancers of Split). The small size of the motif makes its reliable identification by computational means difficult. I have systematically searched the predicted proteomes of Drosophila, C. elegans and human for further instances of the motif.
Using motif identification methods and database searching techniques, I delimit which homeobox and forkhead domain containing proteins also have likely EH1 motifs. I show that despite low database search scores, there is a significant association of the motif with transcription factor function. I further show that likely EH1 motifs are found in combination with T-Box, Zinc Finger and Doublesex domains as well as discussing other plausible candidate associations. I identify strong candidate EH1 motifs in basal metazoan phyla.
Candidate EH1 motifs exist in combination with a variety of transcription factor domains, suggesting that these proteins have repressor functions. The distribution of the EH1 motif is suggestive of convergent evolution, although in many cases, the motif has been conserved throughout bilaterian orthologs. Groucho mediated repression was established prior to the evolution of bilateria.
Engrailed同源结构域1（EH1）基序是一个小区域，据信在含同源异型框和叉头结构域的蛋白质中趋同进化，它与果蝇蛋白groucho（秀丽隐杆线虫unc-37，人类类转导素样分裂增强子）相互作用。该基序尺寸小，难以通过计算手段可靠识别。我系统地在果蝇、秀丽隐杆线虫和人类的预测蛋白质组中搜索该基序的更多实例。
使用基序识别方法和数据库搜索技术，我划定了哪些含同源异型框和叉头结构域的蛋白质可能也具有EH1基序。我表明，尽管数据库搜索得分较低，但该基序与转录因子功能存在显著关联。我进一步表明，可能的EH1基序与T盒、锌指和双性域结合存在，同时还讨论了其他可能的候选关联。我在基础后生动物门中鉴定出了强有力的候选EH1基序。
候选EH1基序与多种转录因子结构域结合存在，表明这些蛋白质具有阻遏功能。EH1基序的分布表明存在趋同进化，尽管在许多情况下，该基序在两侧对称动物的直系同源物中都得以保留。Groucho介导的阻遏作用在两侧对称动物进化之前就已确立。
