The MIntAct project—IntAct as a common curation platform for 11 molecular interaction databases

Abstract

IntAct (freely available at http://www.ebi.ac.uk/intact) is an open-source, open data molecular interaction database populated by data either curated from the literature or from direct data depositions. IntAct has developed a sophisticated web-based curation tool, capable of supporting both IMEx- and MIMIx-level curation. This tool is now utilized by multiple additional curation teams, all of whom annotate data directly into the IntAct database. Members of the IntAct team supply appropriate levels of training, perform quality control on entries and take responsibility for long-term data maintenance. Recently, the MINT and IntAct databases decided to merge their separate efforts to make optimal use of limited developer resources and maximize the curation output. All data manually curated by the MINT curators have been moved into the IntAct database at EMBL-EBI and are merged with the existing IntAct dataset. Both IntAct and MINT are active contributors to the IMEx consortium (http://www.imexconsortium.org).

Simultaneous identification of specifically interacting paralogs and interprotein contacts by direct coupling analysis

“…This results in 4,885 potential PPIs within the same operon, in comparison with more than 9 million protein pairs in total. IntAct (27), one of the most comprehensive database for the PPI network, reports 3,643 PPI for E. coli, of which more than one-third (1,341 pairs) are intraoperon PPI. A domainbased database of structurally known PPI, iPfam (38), reports 4,100 interacting family pairs (∼2,000 of which are homodimers).…”

“…However, the case of multiple paralogs with noncolocalized genes has remained out of reach for coevolutionary analysis, despite its enormous relevance: Out of the 4,499 Pfam-29 (26) protein families with more than 500 sequences, 3,221 have, on average, more than two paralogs per species, and 1,378 families even more than five paralogs. Another observation underlines the importance of addressing generally localized genes: Out of 3,643 protein−protein interactions reported for Escherichia coli in the IntAct Molecular Interaction database (27), only 1,341 (36.8%) concern intraoperon interactions.…”

Reconstructed Ancestral Enzymes Impose a Fitness Cost upon Modern Bacteria Despite Exhibiting Favourable Biochemical Properties

“…Therefore, the insertion of an ancestral LeuB into a modern leucine biosynthesis pathway has the potential to cause downstream effects, such as increased or decreased expression of the other enzymes, build-up of pathway intermediates and/or reduced pathway efficiency. Furthermore, the product of leucine biosynthesis is involved in the regulation of valine and isoleucine biosynthesis (Freundlich et al 1962), and LeuB is involved in a number of protein-protein interactions according to the IntAct database (Orchard et al 2014), including one with the large subunit of acetolactate synthase (ilvI) from the isoleucine biosynthesis pathway, so the consequences of a less than optimal leucine biosynthetic pathway could be far reaching for metabolism in general. This hypothesis is speculative, but warrants further research.…”

Intronic miRNA miR-3666 Modulates its Host Gene FOXP2 Functions in Neurodevelopment and May Contribute to Pathogenesis of Neurological Disorders Schizophrenia and Autism

“…These genes were selected based on their significance in neurodevelopment and potential in being directly or indirectly affected by FOXP2 and miR-3666. Protein-protein interaction studies were done using STRING (version 10.0) [36,37], BioGRID (version 3.4) [38] and IntAct [39] databases. STRING database was used to build a protein-protein interaction network model keeping all parameters in default.…”