Protein phosphorylation is the most frequent post-translational modification by which the properties of eukaryotic proteins can be reversibly modified. In humans, over 500 protein kinases generate a huge phosphoproteome including more than 200,000 individual phosphosites, a figure which is still continuously increasing. The in vivo selectivity of protein kinases is the outcome of a multifaceted and finely tuned process where numerous factors play an integrated role. To gain information about the actual contribution to this process of local features that reflect the interaction of the protein targets with the catalytic site of the kinases, the prevalence of the commonest motifs determining the consensus sequence of Ser/Thr-specific kinases has been examined in the whole human phosphoproteome and in the phosphoproteomes generated by a panel of the 47 most pleiotropic protein kinases. Our analysis shows that: (1) most phosphosites do conform to at least one of the motifs considered, with a substantial proportion conforming to two or more of them; (2) some motifs, with special reference to the one recognized by protein kinase CK2 (pS/pT-x-x-E/D) are very promiscuous, being abundantly represented also at the phosphosites of all the other protein kinases considered; (3) by contrast, other phosphorylated motifs, notably pS/pT-P, pS/pT-Q and pS-x-E, are more discriminatory and selective, being nearly absent in the phosphosites that are not attributable to certain categories of kinases. The information provided will prove helpful to make reliable inferences based on the manual inspection of individual phosphosites.

蛋白质磷酸化是最常见的翻译后修饰，通过它可以可逆地修饰真核蛋白质的特性。在人类中，超过500种蛋白激酶产生巨大的磷酸化蛋白质组，其中包括200,000多个单独的磷酸位点，这个数字还在不断增加。蛋白质激酶的体内选择性是多方面的，经过微调的过程的结果，其中许多因素起着综合作用。要获得有关局部特征对这一过程的实际贡献的信息，以反映蛋白质靶标与激酶催化位点之间的相互作用，在整个人类磷酸化蛋白质组和一组47种最多效性蛋白激酶产生的磷酸化蛋白质组中，已经检查了确定Ser / Thr特异性激酶共有序列的最常见基序的普遍性。我们的分析表明：（1）大多数磷酸酯确实符合所考虑的至少一个基序，其中很大一部分符合其中两个或多个基序；（2）一些基序，特别是被蛋白激酶CK2（pS / pT-xxE / D）识别的基序非常混杂，在所有其他所考虑的蛋白激酶的磷酸位点也大量存在；（3）相比之下，其他磷酸化基序，特别是pS / pT-P，pS / pT-Q和pS-xE，则更具区分性和选择性，几乎不属于某些类别的激酶的磷酸位点。