Bioinformatics and Genomics Laboratory, World Premier International Immunology Frontier Research Center, Osaka University, Osaka, Japan.
Mol Biol Evol. 2013 May;30(5):1172-87. doi: 10.1093/molbev/mst022. Epub 2013 Feb 7.
Reversible protein ubiquitination regulates virtually all known cellular activities. Here, we present a quantitatively evaluated and broadly applicable method to predict eukaryotic ubiquitinating enzymes (UBE) and deubiquitinating enzymes (DUB) and its application to 50 distinct genomes belonging to four of the five major phylogenetic supergroups of eukaryotes: unikonts (including metazoans, fungi, choanozoa, and amoebozoa), excavates, chromalveolates, and plants. Our method relies on a collection of profile hidden Markov models, and we demonstrate its superior performance (coverage and classification accuracy >99%) by identifying approximately 25% and approximately 35% additional UBE and DUB genes in yeast and human, which had not been reported before. In yeast, we predict 85 UBE and 24 DUB genes, for 814 UBE and 107 DUB genes in the human genome. Most UBE and DUB families are present in all eukaryotic lineages, with plants and animals harboring massively enlarged repertoires of ubiquitin ligases. Unicellular organisms, on the other hand, typically harbor less than 300 UBEs and less than 40 DUBs per genome. Ninety-one UBE/DUB genes are orthologous across all four eukaryotic supergroups, and these likely represent a primordial core of enzymes of the ubiquitination system probably dating back to the first eukaryotes approximately 2 billion years ago. Our genome-wide predictions are available through the Database of Ubiquitinating and Deubiquitinating Enzymes (www.DUDE-db.org), where users can also perform advanced sequence and phylogenetic analyses and submit their own predictions.
蛋白质可逆泛素化调节着几乎所有已知的细胞活动。在这里，我们提出了一种定量评估和广泛适用的方法，用于预测真核生物的泛素化酶（UBE）和去泛素化酶（DUB），并将其应用于属于真核生物五个主要系统发育超群中的四个的 50 个不同基因组：单系生物（包括后生动物、真菌、原生动物和肉足动物）、挖掘生物、叶绿体生物和植物。我们的方法依赖于一组轮廓隐藏马尔可夫模型，通过在酵母和人类中分别鉴定出约 25%和约 35%的额外 UBE 和 DUB 基因，证明了其卓越的性能（覆盖率和分类准确性>99%），这些基因以前没有被报道过。在酵母中，我们预测了 85 个 UBE 和 24 个 DUB 基因，而在人类基因组中则预测了 814 个 UBE 和 107 个 DUB 基因。大多数 UBE 和 DUB 家族存在于所有真核生物谱系中，而植物和动物则拥有大量的泛素连接酶。另一方面，单细胞生物通常每个基因组中含有不到 300 个 UBE 和不到 40 个 DUB。91 个 UBE/DUB 基因在所有四个真核超群中是同源的，这些基因可能代表了泛素化系统的原始核心酶，其起源可能可以追溯到大约 20 亿年前的第一个真核生物。我们的全基因组预测可通过泛素化和去泛素化酶数据库（www.DUDE-db.org）获得，用户可以在该数据库中执行高级序列和系统发育分析，并提交他们自己的预测。
