Jain Shruti, Bhattacharyya Kausik, Bakshi Rachit, Narang Ankita, Brahmachari Vani
Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, 110007, India.
Proteins. 2017 Apr;85(4):682-693. doi: 10.1002/prot.25248. Epub 2017 Feb 6.
The genome annotation and identification of gene function depends on conserved biochemical activity. However, in the cell, proteins with the same biochemical function can participate in different cellular pathways and cannot complement one another. Similarly, two proteins of very different biochemical functions are put in the same class of cellular function; for example, the classification of a gene as an oncogene or a tumour suppressor gene is not related to its biochemical function, but is related to its cellular function. We have taken an approach to identify peptide signatures for cellular function in proteins with known biochemical function. ATPases as a test case, we classified ATPases (2360 proteins) and kinases (517 proteins) from the human genome into different cellular function categories such as transcriptional, replicative, and chromatin remodelling proteins. Using publicly available tool, MEME, we identify peptide signatures shared among the members of a given category but not between cellular functional categories; for example, no motif sharing is seen between chromatin remodelling and transporter ATPases, similarly between receptor Serine/Threonine Kinase and Receptor Tyrosine Kinase. There are motifs shared within each category with significant E value and high occurrence. This concept of signature for cellular function was applied to developmental regulators, the polycomb and trithorax proteins which led to the prediction of the role of INO80, a chromatin remodelling protein, in development. This has been experimentally validated earlier for its role in homeotic gene regulation and its interaction with regulatory complexes like the Polycomb and Trithorax complex. Proteins 2017; 85:682-693. © 2016 Wiley Periodicals, Inc.
基因组注释和基因功能的鉴定依赖于保守的生化活性。然而，在细胞中，具有相同生化功能的蛋白质可能参与不同的细胞途径，且不能相互补充。同样，两种生化功能差异很大的蛋白质却被归为同一类细胞功能；例如，一个基因被归类为癌基因或肿瘤抑制基因与其生化功能无关，而是与其细胞功能有关。我们采用了一种方法来鉴定具有已知生化功能的蛋白质中细胞功能的肽段特征。以ATP酶为例，我们将人类基因组中的ATP酶（2360种蛋白质）和激酶（517种蛋白质）分类到不同的细胞功能类别中，如转录、复制和染色质重塑蛋白。使用公开可用的工具MEME，我们鉴定了给定类别成员之间共享但细胞功能类别之间不共享的肽段特征；例如，在染色质重塑ATP酶和转运体ATP酶之间没有发现基序共享，同样在受体丝氨酸/苏氨酸激酶和受体酪氨酸激酶之间也没有。每个类别中都有具有显著E值和高出现频率的共享基序。这种细胞功能特征的概念被应用于发育调节因子——多梳蛋白和三胸蛋白，这导致了对染色质重塑蛋白INO80在发育中的作用的预测。此前已经通过实验验证了其在同源异型基因调控中的作用以及与多梳和三胸复合体等调控复合物的相互作用。《蛋白质》2017年；85:682 - 693。©2016威利期刊公司
