Classification of protein kinases on the basis of both kinase and non-kinase regions.
Classification of protein kinases on the basis of both kinase and non-kinase regions.
复制标题
DOI：
10.1371/journal.pone.0012460
复制
发表时间：
2010-09-15
期刊：
影响因子：
3.7
通讯作者：
Srinivasan N
中科院分区：
文献类型：
--
作者：
Martin J;Anamika K;Srinivasan N
蛋白质磷酸化是调节所有生命王国中的信号转导途径的通用方式。在许多生物体中，其通过Ser/Thr/Tyr蛋白激酶的大家族实现，所述大家族传统上基于其催化结构域的氨基酸序列被分类为组和亚家族。许多蛋白激酶在性质上是多结构域的，但是在将激酶分类成组或亚家族时通常不考虑附属结构域的多样性及其组织。在这里，我们提出了一种方法，认为完整的基因产物的氨基酸序列，以建议在预先分类的序列集的改进。该策略是基于无重复的相似性得分和迭代曲线下面积（AUC）计算。通过检测两个序列之间的共同模式并使用替换矩阵对其进行评分来计算相似性得分，并采用一致的归一化方案。这使我们能够处理全长序列，并隐含地考虑到结构域多样性和结构域改组。我们定量验证我们的方法对212个人类蛋白激酶的子集。然后，我们采用它对人类蛋白激酶的完整剧目，并建议在KinG数据库中存储的亚家族分配，这是基于催化结构域的一些定性的改进。基于我们的新措施，我们描绘了37例潜在的混合激酶：经典的分类完全基于催化结构域的序列是不一致的全长相似性得分计算在这里，这隐含地考虑多域的性质和催化激酶域以外的区域。我们还提供了原生动物寄生虫溶组织内阿米巴的一些杂交激酶的例子。多域体系结构的隐式考虑是对其他分类方案的补充。所提出的算法也可用于对具有多结构域结构的其他酶家族进行分类。
Protein phosphorylation is a generic way to regulate signal transduction pathways in all kingdoms of life. In many organisms, it is achieved by the large family of Ser/Thr/Tyr protein kinases which are traditionally classified into groups and subfamilies on the basis of the amino acid sequence of their catalytic domains. Many protein kinases are multi-domain in nature but the diversity of the accessory domains and their organization are usually not taken into account while classifying kinases into groups or subfamilies. Here, we present an approach which considers amino acid sequences of complete gene products, in order to suggest refinements in sets of pre-classified sequences. The strategy is based on alignment-free similarity scores and iterative Area Under the Curve (AUC) computation. Similarity scores are computed by detecting common patterns between two sequences and scoring them using a substitution matrix, with a consistent normalization scheme. This allows us to handle full-length sequences, and implicitly takes into account domain diversity and domain shuffling. We quantitatively validate our approach on a subset of 212 human protein kinases. We then employ it on the complete repertoire of human protein kinases and suggest few qualitative refinements in the subfamily assignment stored in the KinG database, which is based on catalytic domains only. Based on our new measure, we delineate 37 cases of potential hybrid kinases: sequences for which classical classification based entirely on catalytic domains is inconsistent with the full-length similarity scores computed here, which implicitly consider multi-domain nature and regions outside the catalytic kinase domain. We also provide some examples of hybrid kinases of the protozoan parasite Entamoeba histolytica. The implicit consideration of multi-domain architectures is a valuable inclusion to complement other classification schemes. The proposed algorithm may also be employed to classify other families of enzymes with multi-domain architecture.
登录
查看更多内容
影响因子：
4.5
作者：
Goldberg, Jonathan M.;Manning, Gerard;Liu, Allen;Fey, Petra;Pilcher, Karen E.;Xu, Yanji;Smith, Janet L.
通讯作者：
Smith, Janet L.
影响因子：
2.9
作者：
Anamika;Srinivasan, N;Krupa, A
通讯作者：
Krupa, A
影响因子：
5.8
作者：
Buzko, O;Shokat, KM
通讯作者：
Shokat, KM
影响因子：
2.9
作者：
Jacobs, Marc D.;Caron, Paul R.;Hare, Brian J.
通讯作者：
Hare, Brian J.
影响因子：
2.9
作者：
Gowri, V. S.;Tina, K. G.;Srinivasan, N.
通讯作者：
Srinivasan, N.