Recently, an interesting and important question has emerged from feedbacks of experimentalists. Frequently, experimental researchers prefer to study novel PTM sites to elucidate new functions. Thus, it's important to show whether there have been any sites experimentally verified as real PTM sites in given proteins. And such information will be greatly useful for researchers to avoid reduplicate work. Although we and other bioinformatists developed numerous tools for PTM sites prediction, these softwares could only regard prediction results as potentially real sites. Currently, several public databases, e.g., Phospho.ELM (Diella, et al., 2004; Diella, et al., 2008) and UniProt (Boutet, et al., 2007), have been developed to contain PTM information of proteins. However, these annotations are usually not integrated. Moreover, due to the diversity and heterogeneity of protein names, it's difficult to fully obtain the known PTM information for a given protein, by database searching.

In this work, we developed a novel software of PTMs Peptide Scanner (PPS), to reveal known or highly potential PTM sites in eukaryotic proteins. Five typical PTMs were considered, including phosphorylation, sumoylation, palmitoylation, methylation and acetylation. And the experimentally verified PTM sites were taken from Phospho.ELM 7.0 (Diella, et al., 2004; Diella, et al., 2008) and our previous studies (Chen, et al., 2006; Li, et al., 2006; Ren, et al., 2008; Xue, et al., 2006; Xue, et al., 2006; Zhou, et al., 2006), containing 18 179 known sites. Based on our previous hypothesis of similar peptides with potentially similar functions, we designed a straightforward approach of conserved peptide matching (CPM) algorithm. Given a protein sequence as input, PPS will compare it to the experimentally verified PTMs peptides to find the identical or highly conserved hits. The identical hits might be bona fide modified peptides in experimentally verified proteins or conserved in their highly similar homologs. Thus, PPS could be useful for annotation of covalent modifications information across eukaryotes. As an application, we computationally revealed 71 663 identical hits in six eukaryotic organisms, including H. sapiens, M. musculus, D. melanogaster, C. elegans, S. pombe, and S. cerevisiae. Obviously, most of these results could be highly potential PTM sites and greatly helpful for further experimental verification. Furthermore, highly conserved hits might also point to potentially conserved modifications. In our results, there were 7 911 highly potential PTM hits (with ≤3 conservative substitutions) found in the six eukaryotes. In addition, we carried out a proteome-wide study of creation or disruption of covalent modification sites by alternative splicing (AS) in H. sapiens. Taken together, we proposed PPS could be a multiple useful tool for PTM sites analyses. Finally, the online service and local packages of PPS 1.0 were implemented in JAVA 1.5.

The PPS 1.0 is freely available at: http://pps.biocuckoo.org


PPS 1.0 User Interface

For publication of results please cite the following article:

PPS 1.0: A computational software for revealing known or highly potential post-translational modification sites in eukaryotes.
Jian Ren, Xinjiao Gao, Changjiang Jin, Xuebiao Yao, Longping Wen and Yu Xue.