Domain-Based and Family-Specific Sequence Identity Thresholds Increase the Levels of Reliable Protein Function Transfer
Domain-Based and Family-Specific Sequence Identity Thresholds Increase the Levels of Reliable Protein Function Transfer
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DOI：
10.1016/j.jmb.2008.12.045
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发表时间：
2009-03-27
影响因子：
5.6
通讯作者：
Orengo, Christine A.
中科院分区：
文献类型：
--
作者：
Addou, Sarah;Rentzsch, Robert;Orengo, Christine A.
同源蛋白质的功能差异是基于序列和结构的变化。据报道，酶的整体功能（50%的序列同一性）比整体结构（35%）更早出现分歧。我们在此研究的酶和非酶序列的功能保守使用的蛋白质结构域家族在CATH-Gene 3D。尽管自Tian和Skolnick上次综合研究以来，序列数据迅速增加，但我们的研究结果表明，40%和60%比对序列同一性的通用阈值仍然足以分别安全地继承三级和完整的酶委员会编号。除非多域架构匹配，否则在域级别上这将增加到50%和70%。来自京都基因和基因组百科全书和慕尼黑蛋白质序列功能目录信息中心的结构域似乎不太保守，可能是由于更以路径为中心的观点：安全功能转移需要80%的结构域序列同一性。比较域（更多的成对关系）和使用家族特异性阈值（不同的进化速度）在将功能转移到模型蛋白质组时产生最高的覆盖率。在Gene 3D中的523个蛋白质组中，酶注释平均增加了两倍。作为简单的“经验法则”，序列同一性阈值不需要生物信息学背景。我们将在未来发布的CATH-Gene 3D中提供并更新此信息。(C)2008爱思唯尔有限公司保留所有权利。
Divergence in function of homologous proteins is based on both sequence and structural changes. Overall enzyme function has been reported to diverge earlier (50% sequence identity) than overall structure (35%). We herein study the functional conservation of enzymes and non-enzyme sequences using the protein domain families in CATH-Gene3D. Despite the rapid increase in sequence data since the last comprehensive study by Tian and Skolnick, our findings suggest that generic thresholds of 40% and 60% aligned sequence identity are still sufficient to safely inherit third-level and full Enzyme Commission numbers, respectively. This increases to 50% and 70% on the domain level, unless the multi-domain architecture matches. Assignments from the Kyoto Encyclopedia of Genes and Genomes and the Munich Information Center for Protein Sequences Functional Catalogue seem to be less conserved with sequence, probably due to a more pathway-centric view: 80% domain sequence identity is required for safe function transfer. Comparing domains (more pairwise relationships) and the use of family-specific thresholds (varying evolutionary speeds) yields the highest coverage rates when transferring functions to model proteomes. An average twofold increase in enzyme annotations is seen for 523 proteomes in Gene3D. As simple 'rules of thumb', sequence identity thresholds do not require a bioinformatics background. We will provide and update this information with future releases of CATH-Gene3D. (C) 2008 Elsevier Ltd. All rights reserved.