PMAP: databases for analyzing proteolytic events and pathways

The Proteolysis MAP (PMAP, http://www.proteolysis.org) 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.

[1]  R. Carrell,et al.  Plakalbumin, α1-antitrypsin, antithrombin and the mechanism of inflammatory thrombosis , 1985, Nature.

[2]  Neil D. Rawlings,et al.  MEROPS: the peptidase database , 2009, Nucleic Acids Res..

[3]  L. Loew,et al.  Quantitative cell biology with the Virtual Cell. , 2003, Trends in cell biology.

[4]  Elliot L. Elson,et al.  Interstitial Collagenase Is a Brownian Ratchet Driven by Proteolysis of Collagen , 2004, Science.

[5]  A. Lupas.  Prediction and analysis of coiled-coil structures. , 1996, Methods in enzymology.

[6]  Cathy H. Wu,et al.  UniProt: the Universal Protein knowledgebase , 2004, Nucleic Acids Res..

[7]  G J Barton,et al.  Application of multiple sequence alignment profiles to improve protein secondary structure prediction , 2000, Proteins.

[8]  Sue Povey,et al.  The HUGO Gene Nomenclature Database, 2006 updates , 2005, Nucleic Acids Res..

[9]  T. Blundell,et al.  Comparative protein modelling by satisfaction of spatial restraints. , 1993, Journal of molecular biology.

[10]  J. Nunemacher.  REVIEW , 2001, Brain and Language.

[11]  S. Brunak,et al.  Improved prediction of signal peptides: SignalP 3.0. , 2004, Journal of molecular biology.

[12]  B. Strooper,et al.  The presenilins in Alzheimer's disease--proteolysis holds the key. , 1999, Science.

[13]  R. Carrell,et al.  Plakalbumin, alpha 1-antitrypsin, antithrombin and the mechanism of inflammatory thrombosis. , 1985, Nature.

[14]  Sean R. Eddy,et al.  Profile hidden Markov models , 1998, Bioinform..

[15]  Marc W. Kirschner,et al.  How Proteolysis Drives the Cell Cycle , 1996, Science.

[16]  J. Ward,et al.  MT1-MMP-Deficient Mice Develop Dwarfism, Osteopenia, Arthritis, and Connective Tissue Disease due to Inadequate Collagen Turnover , 1999, Cell.

[17]  G. Salvesen,et al.  Caspases: Intracellular Signaling by Proteolysis , 1997, Cell.

[18]  J. Ellenberg,et al.  Resolution of Chiasmata in Oocytes Requires Separase-Mediated Proteolysis , 2006, Cell.

[19]  J. Wootton,et al.  Analysis of compositionally biased regions in sequence databases. , 1996, Methods in enzymology.

[20]  Peter B. McGarvey,et al.  UniRef: comprehensive and non-redundant UniProt reference clusters , 2007, Bioinform..

[21]  Allan Kuchinsky,et al.  An architecture for biological information extraction and representation , 2004, SAC '04.

[22]  James C. Whisstock,et al.  PoPS: a computational tool for modeling and predicting protease specificity , 2004, Proceedings. 2004 IEEE Computational Systems Bioinformatics Conference, 2004. CSB 2004..

[23]  Hanno Steen,et al.  Development of human protein reference database as an initial platform for approaching systems biology in humans. , 2003, Genome research.

[24]  P. Shannon,et al.  Cytoscape: a software environment for integrated models of biomolecular interaction networks. , 2003, Genome research.

[25]  A. Krogh,et al.  Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. , 2001, Journal of molecular biology.

[26]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[27]  William S. Hlavacek,et al.  BioNetGen: software for rule-based modeling of signal transduction based on the interactions of molecular domains , 2004, Bioinform..

[28]  Rodrigo Lopez,et al.  Web Services at the European Bioinformatics Institute , 2007, Nucleic Acids Res..

[29]  Jeffrey W. Smith,et al.  CutDB: a proteolytic event database , 2006, Nucleic Acids Res..