PhosphoPOINT: a comprehensive human kinase interactome and phospho-protein database
PhosphoPOINT: a comprehensive human kinase interactome and phospho-protein database
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DOI：
10.1093/bioinformatics/btn297
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发表时间：
2008-08-15
期刊：
影响因子：
5.8
通讯作者：
Huang, Chi-Ying F.
中科院分区：
文献类型：
--
作者：
Yang, Chia-Ying;Chang, Chao-Hui;Huang, Chi-Ying F.
动机：为了充分了解蛋白激酶如何调节生物过程，必须首先确定它的底物(S)和相互作用蛋白(S)。然而，在已知的518个人类丝氨酸/苏氨酸/酪氨酸激酶中，35个具有已知底物，而14个具有识别底物识别基序。相比之下，有85个蛋白有蛋白质相互作用(PPI)数据集，这增加了我们从这些PPI中揭示潜在的激酶-底物对的可能性。结果：PhosPhoPOINT是一个全面的人类激酶相互作用组和磷酸化蛋白数据库，由4195个磷酸化蛋白组成，总共有15 738个磷酸化位点。磷酸化的POINT注释了激酶之间的相互作用，与它们的下游底物以及与相互作用的(磷酸)蛋白质之间的相互作用，以调节激酶-底物对。Phosphy POINT实现了各种基因表达谱和基因本体论细胞成分信息，以评估每个激酶及其相互作用的(磷酸)蛋白质/底物。将导致氨基酸变化的单核苷酸多态与具有磷蛋白数据集的蛋白质整合在一起，表明磷酸化位点在改变时会导致疾病表型；连锁的表型包括精神分裂症和高血压。PhosPhoPOINT还提供了使用大约300个已知的激酶/磷酸酶底物/结合基序来搜索所有磷酸肽的功能。总而言之，PhosPhoPOINT为激酶、它们的下游底物和它们相互作用的(磷酸)蛋白提供了强大的注释，这应该会加速动粒中介信号的功能表征。
Motivation: To fully understand how a protein kinase regulates biological processes, it is imperative to first identify its substrate(s) and interacting protein(s). However, of the 518 known human serine/threonine/tyrosine kinases, 35 of these have known substrates, while 14 of the kinases have identified substrate recognition motifs. In contrast, 85 of the kinases have protein-protein interaction (PPI) datasets, raising the possibility that we might reveal potential kinase-substrate pairs from these PPIs.Results: PhosphoPOINT, a comprehensive human kinase interactome and phospho-protein database, is a collection of 4195 phospho-proteins with a total of 15 738 phosphorylation sites. PhosphoPOINT annotates the interactions among kinases, with their down-stream substrates and with interacting (phospho)-proteins to modulate the kinase-substrate pairs. PhosphoPOINT implements various gene expression profiles and Gene Ontology cellular component information to evaluate each kinase and their interacting (phospho)-proteins/substrates. Integration of cSNPs that cause amino acids change with the proteins with the phosphoprotein dataset reveals that 64 phosphorylation sites result in a disease phenotypes when changed; the linked phenotypes include schizophrenia and hypertension. PhosphoPOINT also provides a search function for all phospho-peptides using about 300 known kinase/phosphatase substrate/binding motifs. Altogether, PhosphoPOINT provides robust annotation for kinases, their downstream substrates and their interaction (phospho)-proteins and this should accelerate the functional characterization of kinomemediated signaling.