PMAP: Databases for analyzing proteolytic events and pathways

The Center on Proteolytic Pathways, The Cancer Research Center and The Inflammatory and Infectious Disease Center, The Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Nucleic Acids Research (Impact Factor: 9.11). 11/2008; 37(Database issue):D611-8. DOI: 10.1093/nar/gkn683
Source: PubMed


The Proteolysis MAP (PMAP, is a user-friendly website intended to aid the scientific community in reasoning about proteolytic networks and pathways. PMAP is comprised of five databases, linked together in one environment. The foundation databases, ProteaseDB and SubstrateDB, are driven by an automated annotation pipeline that generates dynamic 'Molecule Pages', rich in molecular information. PMAP also contains two community annotated databases focused on function; CutDB has information on more than 5000 proteolytic events, and ProfileDB is dedicated to information of the substrate recognition specificity of proteases. Together, the content within these four databases will ultimately feed PathwayDB, which will be comprised of known pathways whose function can be dynamically modeled in a rule-based manner, and hypothetical pathways suggested by semi-automated culling of the literature. A Protease Toolkit is also available for the analysis of proteases and proteolysis. Here, we describe how the databases of PMAP can be used to foster understanding of proteolytic pathways, and equally as significant, to reason about proteolysis.

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Available from: Alexey M Eroshkin
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    • "PMAP-CutDB b Jeffrey Smith H, M, R, A, D, C Igarashi et al. 2009 MEROPS b Neil Rawlings & Alan Barret H, M, R, A, D, C Rawlings et al. 2012 are claimed to have for individual caspases in whole cell and in vivo assays where multiple caspases are present (Garcia-Calvo et al. 1998; Ekert et al. 1999), as well as in some in vitro assays (Berger et al. 2006b; McStay et al. 2008; Pereira and Song 2008; Benkova et al. 2009). "
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    ABSTRACT: Caspases are proteases that initiate and execute apoptotic cell death. These caspase-dependent events are caused by cleavage of specific substrates that propagate the proapoptotic signal. A number of techniques have been developed to follow caspase activity in vitro and from apoptotic cellular extracts. Many of these techniques use molecules that are based on optimal peptide motifs for each caspase and on our understanding of caspase cleavage events that occur during apoptosis. Although these approaches are useful, there are several drawbacks associated with them. The optimal peptide motifs are not unique recognition sites for each caspase, so techniques that use them may yield information about more than one caspase. Furthermore, caspase cleavage does not take into account the different caspase activation mechanisms. Recently, probes having greater specificity for individual caspases have been developed and are being used successfully. This introduction provides background on the various caspases and introduces a set of complementary techniques to examine the activity, substrate specificity, and activation status of caspases from in vitro or cell culture experiments.
    Full-text · Article · Aug 2014 · Cold Spring Harbor Protocols
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    • "For prediction of disordered/ordered structure, the sequences were applied to Consensus Disorder Prediction ( [34]. Secondary structure prediction of SE36 was performed by Consensus secondary structure prediction in NPS@ server [33]. "
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    ABSTRACT: The malaria vaccine candidate antigen, SE36, is based on the N-terminal 47 kDa domain of Plasmodium falciparum serine repeat antigen 5 (SERA5). In epidemiological studies, we have previously shown the inhibitory effects of SE36 specific antibodies on in vitro parasite growth and the negative correlation between antibody level and malaria symptoms. A phase 1 b trial of the BK-SE36 vaccine in Uganda elicited 72% protective efficacy against symptomatic malaria in children aged 6-20 years during the follow-up period 130-365 days post-second vaccination. Here, we performed epitope mapping with synthetic peptides covering the whole sequence of SE36 to identify and map dominant epitopes in Ugandan adult serum presumed to have clinical immunity to P. falciparum malaria. High titer sera from the Ugandan adults predominantly reacted with peptides corresponding to two successive N-terminal regions of SERA5 containing octamer repeats and serine rich sequences, regions of SERA5 that were previously reported to have limited polymorphism. Affinity purified antibodies specifically recognizing the octamer repeats and serine rich sequences exhibited a high antibody-dependent cellular inhibition (ADCI) activity that inhibited parasite growth. Furthermore, protein structure predictions and structural analysis of SE36 using spectroscopic methods indicated that N-terminal regions possessing inhibitory epitopes are intrinsically unstructured. Collectively, these results suggest that strict tertiary structure of SE36 epitopes is not required to elicit protective antibodies in naturally immune Ugandan adults.
    Full-text · Article · Jun 2014 · PLoS ONE
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    • "However, this database does not easily allow a user to perform specific meta-analyses such as a direct comparison among substrates. PMAP/CutDB on the other hand is a community-driven (Wikipedia style) database, implying that any scientist can add new substrates or substrate predictions (15,16). The intrinsic disadvantage is that the quality of the reported substrates cannot be guaranteed, especially because the original data leading to the discovery of a substrate can only be accessed by using the provided links to the original article. "
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    ABSTRACT: We here present The Online Protein Processing Resource (TOPPR;, an online database that contains thousands of published proteolytically processed sites in human and mouse proteins. These cleavage events were identified with COmbinded FRActional DIagonal Chromatography proteomics technologies, and the resulting database is provided with full data provenance. Indeed, TOPPR provides an interactive visual display of the actual fragmentation mass spectrum that led to each identification of a reported processed site, complete with fragment ion annotations and search engine scores. Apart from warehousing and disseminating these data in an intuitive manner, TOPPR also provides an online analysis platform, including methods to analyze protease specificity and substrate-centric analyses. Concretely, TOPPR supports three ways to retrieve data: (i) the retrieval of all substrates for one or more cellular stimuli or assays; (ii) a substrate search by UniProtKB/Swiss-Prot accession number, entry name or description; and (iii) a motif search that retrieves substrates matching a user-defined protease specificity profile. The analysis of the substrates is supported through the presence of a variety of annotations, including predicted secondary structure, known domains and experimentally obtained 3D structure where available. Across substrates, substrate orthologs and conserved sequence stretches can also be shown, with iceLogo visualization provided for the latter.
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