pkaPS: prediction of protein kinase A phosphorylation sites with the simplified kinase-substrate binding model.
pkaPS: prediction of protein kinase A phosphorylation sites with the simplified kinase-substrate binding model.
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DOI：
10.1186/1745-6150-2-1
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发表时间：
2007-01-12
期刊：
影响因子：
5.5
通讯作者：
Eisenhaber F
中科院分区：
文献类型：
--
作者：
Neuberger G;Schneider G;Eisenhaber F
蛋白激酶A（cAMP依赖性激酶，PKA）是一种丝氨酸/苏氨酸激酶，其Ca.已知有150种底物蛋白。基于使用现有的实验数据的识别基序的改进，我们希望应用简化的底物蛋白结合模型准确预测PKA磷酸化位点，这种方法是以前成功的预测脂质翻译后修饰和PTS 1过氧化物酶体易位信号。已经发现两侧磷酸化残基侧翼的大约20个序列位置在其序列变异性方面受到限制（区域-18. 23，位置为0）。保守的物理模式可以合理化的定性结合模型与蛋白激酶A的催化裂缝。位置-6...+ 4周围的磷酸化位点的影响，在不同程度上与激酶的直接相互作用。该序列延伸嵌入在优先由具有柔性主链和小侧链的亲水残基组成的固有无序区域中。这方面的知识已被纳入一个简化的分析模型的生产性结合底物蛋白与PKA。pkaPS预测因子的评分函数可以可靠地区分PKA磷酸化位点与具有非允许序列环境的丝氨酸/苏氨酸（灵敏度约为96%，特异性约为94%）。pkaPS工具已应用于整个人类蛋白质组。在新预测的PKA靶点中，有完全未表征的蛋白质组以及显然众所周知的家族，如核糖体蛋白L21 e、L22和L 6。补充数据以及作为WWW服务器的预测工具可在. Erik货车Nimwegen（瑞士巴塞尔大学生物中心）、Sandor Pongor（国际遗传工程和生物技术中心，意大利的里雅斯特）、Igor Zhulin（美国田纳西大学橡树岭国家实验室）。
Protein kinase A (cAMP-dependent kinase, PKA) is a serine/threonine kinase, for which ca. 150 substrate proteins are known. Based on a refinement of the recognition motif using the available experimental data, we wished to apply the simplified substrate protein binding model for accurate prediction of PKA phosphorylation sites, an approach that was previously successful for the prediction of lipid posttranslational modifications and of the PTS1 peroxisomal translocation signal. Approximately 20 sequence positions flanking the phosphorylated residue on both sides have been found to be restricted in their sequence variability (region -18...+23 with the site at position 0). The conserved physical pattern can be rationalized in terms of a qualitative binding model with the catalytic cleft of the protein kinase A. Positions -6...+4 surrounding the phosphorylation site are influenced by direct interaction with the kinase in a varying degree. This sequence stretch is embedded in an intrinsically disordered region composed preferentially of hydrophilic residues with flexible backbone and small side chain. This knowledge has been incorporated into a simplified analytical model of productive binding of substrate proteins with PKA. The scoring function of the pkaPS predictor can confidently discriminate PKA phosphorylation sites from serines/threonines with non-permissive sequence environments (sensitivity of ~96% at a specificity of ~94%). The tool "pkaPS" has been applied on the whole human proteome. Among new predicted PKA targets, there are entirely uncharacterized protein groups as well as apparently well-known families such as those of the ribosomal proteins L21e, L22 and L6. The supplementary data as well as the prediction tool as WWW server are available at . Erik van Nimwegen (Biozentrum, University of Basel, Switzerland), Sandor Pongor (International Centre for Genetic Engineering and Biotechnology, Trieste, Italy), Igor Zhulin (University of Tennessee, Oak Ridge National Laboratory, USA).
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影响因子：
5.6
作者：
Eisenhaber, B;Schneider, G;Eisenhaber, F
通讯作者：
Eisenhaber, F
影响因子：
5.6
作者：
Blom, N;Gammeltoft, S;Brunak, S
通讯作者：
Brunak, S
影响因子：
14.9
作者：
The UniProt Consortium
通讯作者：
The UniProt Consortium
影响因子：
3.4
作者：
Eisenhaber, B;Eisenhaber, F;Neuberger, G
通讯作者：
Neuberger, G
影响因子：
5.6
作者：
Eisenhaber, B;Bork, P;Eisenhaber, F
通讯作者：
Eisenhaber, F