CPLM: a database of protein lysine modifications

Abstract

We reported an integrated database of Compendium of Protein Lysine Modifications (CPLM; http://cplm.biocuckoo.org) for protein lysine modifications (PLMs), which occur at active ε-amino groups of specific lysine residues in proteins and are critical for orchestrating various biological processes. The CPLM database was updated from our previously developed database of Compendium of Protein Lysine Acetylation (CPLA), which contained 7151 lysine acetylation sites in 3311 proteins. Here, we manually collected experimentally identified substrates and sites for 12 types of PLMs, including acetylation, ubiquitination, sumoylation, methylation, butyrylation, crotonylation, glycation, malonylation, phosphoglycerylation, propionylation, succinylation and pupylation. In total, the CPLM database contained 203,972 modification events on 189,919 modified lysines in 45,748 proteins for 122 species. With the dataset, we totally identified 76 types of co-occurrences of various PLMs on the same lysine residues, and the most abundant PLM crosstalk is between acetylation and ubiquitination. Up to 53.5% of acetylation and 33.1% of ubiquitination events co-occur at 10 746 lysine sites. Thus, the various PLM crosstalks suggested that a considerable proportion of lysines were competitively and dynamically regulated in a complicated manner. Taken together, the CPLM database can serve as a useful resource for further research of PLMs.

Figure 1.

The heatmaps for the protein number distribution of different PLM types and species. The species names in red, green, blue and purple are from animals, bacteria, fungi and plants, respectively. (A) The heatmap for the number of substrates; (B) the heatmap for the number of modified lysine residues.

Figure 2.

The browse options of CPLM. Two browse approaches including by PLM types and by species were provided to browse the database. (A) By PLM types; (B) the protein list for specified PLM and selected organism; (C) by species; (D) the detailed information of human dead box protein 39.

Figure 3.

The search options. (A) The database could be queried with simple keywords input; (B) the ‘Advance Search’ allows users to submit combination of up to three terms for searching; (C) the database could be queried with a protein sequence to find identical or homologous proteins.

Figure 4.

The summary for the number of concurrent sites among different types of PTMs. (A) The concurrences between two types of PLMs while the detailed numbers are provided in Supplementary Table S2; (B) the concurrences among multiple (>2) types of PLMs while the detailed number are shown in the top.