dbPTM 3.0: an informative resource for investigating substrate site specificity and functional association of protein post-translational modifications

Abstract

Protein modification is an extremely important post-translational regulation that adjusts the physical and chemical properties, conformation, stability and activity of a protein; thus altering protein function. Due to the high throughput of mass spectrometry (MS)-based methods in identifying site-specific post-translational modifications (PTMs), dbPTM (http://dbPTM.mbc.nctu.edu.tw/) is updated to integrate experimental PTMs obtained from public resources as well as manually curated MS/MS peptides associated with PTMs from research articles. Version 3.0 of dbPTM aims to be an informative resource for investigating the substrate specificity of PTM sites and functional association of PTMs between substrates and their interacting proteins. In order to investigate the substrate specificity for modification sites, a newly developed statistical method has been applied to identify the significant substrate motifs for each type of PTMs containing sufficient experimental data. According to the data statistics in dbPTM, >60% of PTM sites are located in the functional domains of proteins. It is known that most PTMs can create binding sites for specific protein-interaction domains that work together for cellular function. Thus, this update integrates protein–protein interaction and domain–domain interaction to determine the functional association of PTM sites located in protein-interacting domains. Additionally, the information of structural topologies on transmembrane (TM) proteins is integrated in dbPTM in order to delineate the structural correlation between the reported PTM sites and TM topologies. To facilitate the investigation of PTMs on TM proteins, the PTM substrate sites and the structural topology are graphically represented. Also, literature information related to PTMs, orthologous conservations and substrate motifs of PTMs are also provided in the resource. Finally, this version features an improved web interface to facilitate convenient access to the resource.

Transformative Impact of Proteomics on Cardiovascular Health and Disease

“…89,90 An overview across all species in dbPTM 3.0 (accessed November 2014) revealed 221 020 experimentally validated PTMs compared with 14 589 and 36 466 experimentally validated PTMs in version 1.0 (2006) and version 2.0 (2009), respectively. 91 Given the lack of experimental data on the 3-dimensional structure of the vast majority of proteins, it is not surprising that many more putative PTM sites are anticipated from predicted protein structure. The most commonly detected PTMs to date are phosphorylation, ubiquitylation, acetylation, N-and O-linked glycosylation, and methylation.…”

Lysine Malonylation Is Elevated in Type 2 Diabetic Mouse Models and Enriched in Metabolic Associated Proteins

“…Post-translational modifications (PTMs) 1 have been recognized as a common feature of proteins (1)(2)(3). More than 300 types of PTMs have been identified according to the Swiss-Prot database (4,5). Most of them use small molecular compounds as group donors.…”

A Phosphotyrosine Switch for Cargo Sequestration at Clathrin-coated Buds

“…Instead, Tyr-888 projects out from strand ␤11 of the five-stranded antiparallel ␤-sheet that forms the base of the ␤2 platform subdomain (37,62,66) (Fig. 2B) and displays a computed 6.87% of the surface area as accessible (similar to the 4.95% surface accessibility for Tyr-737) (123). This suggests that conformational recognition as opposed to a linear peptide-based identification motif depending on specificity-determining flanking residues is necessary for the Tyr(P)-888 modification of this FIGURE 7.…”