title: PTMcode v2: a resource for functional associations of post-translational modifications within and between proteins.
abstract: The post-translational regulation of proteins is mainly driven by two molecular events, their modification by several types of moieties and their interaction with other proteins. These two processes are interdependent and together are responsible for the function of the protein in a particular cell state. Several databases focus on the prediction and compilation of protein-protein interactions (PPIs) and no less on the collection and analysis of protein post-translational modifications (PTMs), however, there are no resources that concentrate on describing the regulatory role of PTMs in PPIs. We developed several methods based on residue co-evolution and proximity to predict the functional associations of pairs of PTMs that we apply to modifications in the same protein and between two interacting proteins. In order to make data available for understudied organisms, PTMcode v2 (http://ptmcode.embl.de) includes a new strategy to propagate PTMs from validated modified sites through orthologous proteins. The second release of PTMcode covers 19 eukaryotic species from which we collected more than 300,000 experimentally verified PTMs (>1,300,000 propagated) of 69 types extracting the post-translational regulation of >100,000 proteins and >100,000 interactions. In total, we report 8 million associations of PTMs regulating single proteins and over 9.4 million interplays tuning PPIs.
authors.affiliation: European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Pablo
authors.initials: P
authors.lastname: Minguez
authors.affiliation: Biobyte solutions GmbH, Bothestr 142, 69117 Heidelberg, Germany.
authors.forename: Ivica
authors.identifier: http://orcid.org/0000-0003-3560-4288
authors.initials: I
authors.lastname: Letunic
authors.affiliation: European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Luca
authors.initials: L
authors.lastname: Parca
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.
authors.forename: Luz
authors.initials: L
authors.lastname: Garcia-Alonso
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Dopazo
authors.affiliation: European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Jaime
authors.initials: J
authors.lastname: Huerta-Cepas
authors.affiliation: European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany Max-Delbruck-Centre for Molecular Medicine, Berlin-Buch, Germany bork@embl.de.
authors.forename: Peer
authors.initials: P
authors.lastname: Bork
mesh_terms: D030562:Databases, Protein; D020407:Internet; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational