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However, the vast majority of kinase-specific phosphorylation data remain undiscovered and existing experimental methods and computational phosphorylation site (P-site) prediction tools have various limitations with respect to addressing this problem.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>To address this issue, a novel protein kinase identification web server, PKIS, is here presented for the identification of the protein kinases responsible for experimentally verified P-sites at high specificity, which incorporates the composition of monomer spectrum (CMS) encoding strategy and support vector machines (SVMs). Compared to widely used P-site prediction tools including KinasePhos 2.0, Musite, and GPS2.1, PKIS largely outperformed these tools in identifying protein kinases associated with known P-sites. In addition, PKIS was used on all the P-sites in Phospho.ELM that currently lack kinase information. It successfully identified 14 potential SYK substrates with 36 known P-sites. Further literature search showed that 5 of them were indeed phosphorylated by SYK. Finally, an enrichment analysis was performed and 6 significant SYK-related signal pathways were identified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In general, PKIS can identify protein kinases for experimental phosphorylation sites efficiently. It is a valuable bioinformatics tool suitable for the study of protein phosphorylation. The PKIS web server is freely available at<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/bioinformatics.ustc.edu.cn\/pkis\" ext-link-type=\"uri\">http:\/\/bioinformatics.ustc.edu.cn\/pkis<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1471-2105-14-247","type":"journal-article","created":{"date-parts":[[2013,8,13]],"date-time":"2013-08-13T14:14:31Z","timestamp":1376403271000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["PKIS: computational identification of protein kinases for experimentally discovered protein phosphorylation sites"],"prefix":"10.1186","volume":"14","author":[{"given":"Liang","family":"Zou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Liao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ao","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minghui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2013,8,13]]},"reference":[{"issue":"6","key":"6022_CR1","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1016\/j.cmet.2011.03.024","volume":"13","author":"R Acin-Perez","year":"2011","unstructured":"Acin-Perez R, Gatti DL, Bai Y, Manfredi G: Protein phosphorylation and prevention of cytochrome oxidase inhibition by ATP: coupled mechanisms of energy metabolism regulation. 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