TopFIND 2.0--linking protein termini with proteolytic processing and modifications altering protein function

Abstract

Protein termini provide critical insights into the functional state of individual proteins. With recent advances in specific proteomics approaches to enrich for N- and C-terminomes, the global analysis of whole terminomes at a proteome-wide scale is now possible. Information on the actual N- and C-termini of proteins in vivo and any post-translational modifications, including their generation by proteolytic processing, is rapidly accumulating. To access this information we present version 2.0 of TopFIND (http://clipserve.clip.ubc.ca/topfind), a knowledgebase for protein termini, terminus modifications and underlying proteolytic processing. Built on a protein-centric framework TopFIND covers five species: Homo sapiens, Mus musculus, Arabidopsis thaliana, Saccharomyces cerevisiae and Escherichia coli and incorporates information from curated community submissions, publications, UniProtKB and MEROPS. Emphasis is placed on the detailed description and classification of evidence supporting the reported identification of each cleavage site, terminus and modification. A suite of filters can be applied to select supporting evidence. A dynamic network representation of the relationship between proteases, their substrates and inhibitors as well as visualization of protease cleavage site specificities complements the information displayed. Hence, TopFIND supports in depth investigation of protein termini information to spark new hypotheses on protein function by correlating cleavage events and termini with protein domains and mutations.