Systematic characterization and prediction of post-translational modification cross-talk between proteins

Abstract

Motivation Protein post-translational modifications (PTMs) regulate a wide range of cellular protein functions. Many PTM sites from the same (intra) or different (inter) proteins often cooperate with each other to perform a function, which is defined as PTM cross-talk. PTM cross-talk within proteins attracted great attentions in the past a few years. However, the inter-protein PTM cross-talk is largely under studied due to its large protein pair space and lack of a gold standard dataset, even though the PTM interplay between proteins is a key element in cell signaling and regulatory networks. Results In this study, 199 inter-protein PTM cross-talk pairs in 82 pairs of human proteins were collected from literature, which to our knowledge is the first effort in compiling such dataset. By comparing with background PTM pairs from the same protein pairs, we found that inter-protein cross-talk PTM pairs have higher sequence co-evolution at both PTM residue and motif levels. Also, we found that cross-talk PTMs have higher co-modification across multiple species and 88 human tissues or conditions. Furthermore, we showed that these features are predictive for PTM cross-talk between proteins, and applied a random forest model to integrate these features with achieving an area under the receiver operating characteristic curve of 0.81 in 10-fold cross-validation, prevailing over using any single feature alone. Therefore, this method would be a valuable tool to identify inter-protein PTM cross-talk at proteome-wide scale. Availability and implementation A web server for prioritization of both intra- and inter-protein PTM cross-talk candidates is at http://bioinfo.bjmu.edu.cn/ptm-x/. Python code for local computer is also freely available at https://github.com/huangyh09/PTM-X. Supplementary information Supplementary data are available at Bioinformatics online.

qPTMplants: an integrative database of quantitative post-translational modifications in plants

“…Different PTM types can occur on the same residue or multiple residues of the same protein, and these modifications may collectively modulate various biological processes in a manner named PTM crosstalk ( 6 , 50–53 ). From the collected PTM data of Arabidopsis in qPTMplants, 49 types of PTM crosstalk at the same residue from 6134 PTM events in 2972 sites were identified, including 25 types of crosstalk between two different PTMs and 24 types of crosstalk among multiple PTMs (Figure 6 and Supplementary Table S4 ).…”

Decoding Post-Translational Modification Crosstalk With Proteomics

“…Another resource, the PTM-X web server ( http://bioinfo.bjmu.edu.cn/ptm-x/ ), aims at predicting intra- and inter-PTM crosstalk ( 85 ). PTM-X was trained on different features extracted from literature curated data for 193 PTM crosstalk pairs in 77 human proteins to predict intra-protein PTM crosstalk and on 199 PTM crosstalk pairs in 82 pair of human proteins to predict inter-protein PTM crosstalk ( 85 ). On the PTM-X web server, PTM sites can be queried and predictive scores for crosstalk obtained.…”

Cracking chromatin with proteomics: From chromatome to histone modifications

“…In the last years, MS-based proteomics has contributed to the identification of a very large number of PTMs, which has prompted the development of innovative software tools for the analysis and visualization of hPTM data to facilitate data interpretation [117,[139][140][141][142]. Moreover, information on post-translational modifications have been more recently integrated with structural data in interactive database that allow to study functional associations between PTMs and to predict their crosstalk [143][144][145]. In particular, histone-specific datasets from middle-down proteomic experiments have been recently established where hPTMs dynamics as well as known positive and negative crosstalk can be explored [117,146].…”