Abstract
Transmembrane (TM) proteins have crucial roles in various cellular processes. The location of post-translational modifications (PTMs) on TM proteins is associated with their functional roles in various cellular processes. Given the importance of PTMs in the functioning of TM proteins, this study developed topPTM (available online at http://topPTM.cse.yzu.edu.tw), a new dbPTM module that provides a public resource for identifying the functional PTM sites on TM proteins with structural topology. Experimentally verified TM topology data were integrated from TMPad, TOPDB, PDBTM and OPM. In addition to the PTMs obtained from dbPTM, experimentally verified PTM sites were manually extracted from research articles by text mining. In an attempt to provide a full investigation of PTM sites on TM proteins, all UniProtKB protein entries containing annotations related to membrane localization and TM topology were considered potential TM proteins. Two effective tools were then used to annotate the structural topology of the potential TM proteins. The TM topology of TM proteins is represented by graphical visualization, as well as by the PTM sites. To delineate the structural correlation between the PTM sites and TM topologies, the tertiary structure of PTM sites on TM proteins was visualized by Jmol program. Given the support of research articles by manual curation and the investigation of domain–domain interactions in Protein Data Bank, 1347 PTM substrate sites are associated with protein–protein interactions for 773 TM proteins. The database content is regularly updated on publication of new data by continuous surveys of research articles and available resources.
Highlights
Protein post-translational modification (PTM) involving addition of chemical groups is an extremely important biological mechanism that adjusts the physical and chemical properties, folding, conformation, stability and activity of proteins; posttranslational modifications (PTMs) alters protein function [1].High-throughput mass spectrometry (MS)-based proteomics has identified >200 different PTMs [2], including phosphorylation for signal transduction; acetylation and methylation of histone for gene regulation; attachment of hydrophobic groups for membrane localization; and glycosylation for changing protein half-life, targeting substrates and promotion of cell–cell and cell–matrix interactions [3]
In addition to the PTMs obtained from dbPTM, experimentally verified PTM sites were manually extracted from research articles by text mining
The case study of CCR5 in this work showed that topPTM is an informative system for providing structural distribution and functional investigation of PTMs for TM proteins
Summary
Protein post-translational modification (PTM) involving addition of chemical groups is an extremely important biological mechanism that adjusts the physical and chemical properties, folding, conformation, stability and activity of proteins; PTM alters protein function [1]. An updated version of dbPTM was proposed as an informative resource for investigating substrate specificity and functional association of PTMs [8]. A genome-wide study has reported that 20–30% of the proteins encoded by a Study to develop topPTM, a new dbPTM module for identifying functional PTMs and structural topology of TM proteins. To provide a full investigation of TM proteins, UniProtKB [22] protein entries containing information regarding membrane localization and membrane topology are used for a thorough study of TM proteins because they are considered potential TM proteins in topPTM. With the support of dbPTM, all the experimentally verified PTMs were mapped to TM proteins of topPTM. The functional analysis of PTMs on TM proteins was simplified by graphically visualizing all PTM sites and TM topologies on TM proteins
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