Dataset Information

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.

SUBMITTER: Lange PF

PROVIDER: S-EPMC3244998 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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

Lange Philipp F PF Huesgen Pitter F PF Overall Christopher M CM

Nucleic acids research 20111118 Database issue

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 ...[more]

PMID: 22102574

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Project description:Most receptor-like protein tyrosine phosphatases (PTPases) display a high degree of homology with cell adhesion molecules in their extracellular domains. We studied the functional significance of processing for the receptor-like PTPases LAR and PTPsigma. PTPsigma biosynthesis and intracellular processing resembled that of the related PTPase LAR and was expressed on the cell surface as a two-subunit complex. Both LAR and PTPsigma underwent further proteolytical processing upon treatment of cells with either calcium ionophore A23187 or phorbol ester TPA. Induction of LAR processing by TPA in 293 cells did require overexpression of PKCalpha. Induced proteolysis resulted in shedding of the extracellular domains of both PTPases. This was in agreement with the identification of a specific PTPsigma cleavage site between amino acids Pro821 and Ile822. Confocal microscopy studies identified adherens junctions and desmosomes as the preferential subcellular localization for both PTPases matching that of plakoglobin. Consistent with this observation, we found direct association of plakoglobin and beta-catenin with the intracellular domain of LAR in vitro. Taken together, these data suggested an involvement of LAR and PTPsigma in the regulation of cell contacts in concert with cell adhesion molecules of the cadherin/catenin family. After processing and shedding of the extracellular domain, the catalytically active intracellular portions of both PTPases were internalized and redistributed away from the sites of cell-cell contact, suggesting a mechanism that regulates the activity and target specificity of these PTPases. Calcium withdrawal, which led to cell contact disruption, also resulted in internalization but was not associated with prior proteolytic cleavage and shedding of the extracellular domain. We conclude that the subcellular localization of LAR and PTPsigma is regulated by at least two independent mechanisms, one of which requires the presence of their extracellular domains and one of which involves the presence of intact cell-cell contacts.

Dataset Information

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

Publications

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

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