Comprehensive Data Resource And Analysis For Protein Post-translational Modifications

Post-translational modifications (PTMs) of proteins play essential roles in almost all cellular processes, and are closely related to physiological activity and disease development of living organisms. For example, phosphorylation involved in almost all physiological and pathological processes, such as cell signal transduction, enzyme activity regulation, metabolism, celluar growth, proliferation and differentiation; Glycosylation plays an important role in protein stability and solubility, antigenicity, protein targeting, cell-cell interactions and other biological function; ubiquitination is important for cell differentiation and apoptosis, DNA repair and protein degradation; Methylation and acetylation can affect transcriptional regulation. The development of tandem mass spectrometry (MS/MS) has resulted in a rapid increase of PTMs identified on proteins from different species. The collection and systematic ordering of PTM data should provide invaluable information for understanding cellular processes and signaling pathways regulated by PTMs. For this original purpose we developed SysPTM, a systematic resource installed with comprehensive PTM data and a suite of web tools (PTMBlast, PTMPathway, PTMPhylog, PTMCluster) for annotation of PTMs. The first version of SysPTM was released in2009and has been well used since.However, during these years, there has been a significant advance with the generation of PTM-data and, consequently, more sophisticated analysis requirements have to be met. Here we submit an updated version of SysPTM2.0(http://lifecenter.sgst.cn/SysPTM/), The new version of the SysPTM2.0results in more than doubled data content, i.e.471109PTM sites on53235proteins, covering over100modification types across2031species, detailed with widened functional annotation derived from MS/MS experiments and various public data resources. The utilities of four analysis tools (PTMBlast, PTMPathway, PTMPhylog, PTMCluster) have been greatly improved to support batch query and on-line calculation analysis processes of relevant biological functions of PTMs. In addition, a new session, SysPTM-H, is developed to graphically represent the combinatorial histone PTMs and dynamic regulations of histone modifying enzymes. A fifth tool, PTMGO, is implemented to facilitate a better understanding of PTM events in complex biological processes. Other improvements also include unified protein identifier, redesigned web interfaces, new data browsing tools and more in-depth proteogenomics annotation, etc. Now SysPTM2.0not only facilitates resourceful annotation of PTM sites but allows systematic investigation of PTM functions by the user.Further analyses on large-scale level of PTM dataset included in SysPTM2.0were taken in this study. Statistical analysis revealed the distribution of PTM sites on the different regions of the protein sequences and there is a complex regulatory mechanism between acetylation, ubiquitination and phosphorylation. This study used the early developed analysis tools for deeper data mining. For example, Combined with PTMCluster we found that the center of identified PTM clusters can be used as a feature for PTM co-regulation analysis between PTM sites. Based on the protein structures, some sequence motifs for S-nitrosylation cysteines had been identified. We also found that different PTM sites have different preferences for protein secondary structure and tend to be located on the surface of the protein tertiary structure. These conclusions will be useful for detailed investigation of PTM functions.