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      The PhosphoGRID Saccharomyces cerevisiae protein phosphorylation site database: version 2.0 update

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          Abstract

          PhosphoGRID is an online database that curates and houses experimentally verified in vivo phosphorylation sites in the Saccharomyces cerevisiae proteome (www.phosphogrid.org). Phosphosites are annotated with specific protein kinases and/or phosphatases, along with the condition(s) under which the phosphorylation occurs and/or the effects on protein function. We report here an updated data set, including nine additional high-throughput (HTP) mass spectrometry studies. The version 2.0 data set contains information on 20 177 unique phosphorylated residues, representing a 4-fold increase from version 1.0, and includes 1614 unique phosphosites derived from focused low-throughput (LTP) studies. The overlap between HTP and LTP studies represents only ∼3% of the total unique sites, but importantly 45% of sites from LTP studies with defined function were discovered in at least two independent HTP studies. The majority of new phosphosites in this update occur on previously documented proteins, suggesting that coverage of phosphoproteins in the yeast proteome is approaching saturation. We will continue to update the PhosphoGRID data set, with the expectation that the integration of information from LTP and HTP studies will enable the development of predictive models of phosphorylation-based signaling networks.

          Database URL: http://www.phosphogrid.org/

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          Most cited references45

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          Global analysis of Cdk1 substrate phosphorylation sites provides insights into evolution.

          To explore the mechanisms and evolution of cell-cycle control, we analyzed the position and conservation of large numbers of phosphorylation sites for the cyclin-dependent kinase Cdk1 in the budding yeast Saccharomyces cerevisiae. We combined specific chemical inhibition of Cdk1 with quantitative mass spectrometry to identify the positions of 547 phosphorylation sites on 308 Cdk1 substrates in vivo. Comparisons of these substrates with orthologs throughout the ascomycete lineage revealed that the position of most phosphorylation sites is not conserved in evolution; instead, clusters of sites shift position in rapidly evolving disordered regions. We propose that the regulation of protein function by phosphorylation often depends on simple nonspecific mechanisms that disrupt or enhance protein-protein interactions. The gain or loss of phosphorylation sites in rapidly evolving regions could facilitate the evolution of kinase-signaling circuits.
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            The BioGRID Interaction Database: 2011 update

            The Biological General Repository for Interaction Datasets (BioGRID) is a public database that archives and disseminates genetic and protein interaction data from model organisms and humans (http://www.thebiogrid.org). BioGRID currently holds 347 966 interactions (170 162 genetic, 177 804 protein) curated from both high-throughput data sets and individual focused studies, as derived from over 23 000 publications in the primary literature. Complete coverage of the entire literature is maintained for budding yeast (Saccharomyces cerevisiae), fission yeast (Schizosaccharomyces pombe) and thale cress (Arabidopsis thaliana), and efforts to expand curation across multiple metazoan species are underway. The BioGRID houses 48 831 human protein interactions that have been curated from 10 247 publications. Current curation drives are focused on particular areas of biology to enable insights into conserved networks and pathways that are relevant to human health. The BioGRID 3.0 web interface contains new search and display features that enable rapid queries across multiple data types and sources. An automated Interaction Management System (IMS) is used to prioritize, coordinate and track curation across international sites and projects. BioGRID provides interaction data to several model organism databases, resources such as Entrez-Gene and other interaction meta-databases. The entire BioGRID 3.0 data collection may be downloaded in multiple file formats, including PSI MI XML. Source code for BioGRID 3.0 is freely available without any restrictions.
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              Self-perpetuating states in signal transduction: positive feedback, double-negative feedback and bistability.

              Cell signaling systems that contain positive-feedback loops or double-negative feedback loops can, in principle, convert graded inputs into switch-like, irreversible responses. Systems of this sort are termed "bistable". Recently, several groups have engineered artificial bistable systems into Escherichia coli and Saccharomyces cerevisiae, and have shown that the systems exhibit interesting and potentially useful properties. In addition, two naturally occurring signaling systems, the p42 mitogen-activated protein kinase and c-Jun amino-terminal kinase pathways in Xenopus oocytes, have been shown to exhibit bistable responses. Here we review the basic properties of bistable circuits, the requirements for construction of a satisfactory bistable switch, and the recent progress towards constructing and analysing bistable signaling systems.
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                Author and article information

                Journal
                Database (Oxford)
                Database (Oxford)
                database
                databa
                Database: The Journal of Biological Databases and Curation
                Oxford University Press
                1758-0463
                2013
                11 May 2013
                11 May 2013
                : 2013
                : bat026
                Affiliations
                1Department of Biochemistry and Molecular Biology, Molecular Epigenetics, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3, 2Samuel Lunenfeld Research Institute, 600 University Avenue, Toronto, Ontario M5G 1X5 Canada, 3Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA and 4Institute for Research in Immunology and Cancer, Université de Montréal, Pavillon Marcelle-Coutu, 2950, chemin de Polytechnique, Montréal, Québec H3T 1J4, Canada
                Author notes
                *Corresponding author: Tel: +1 514 343 6668; Email: md.tyers@ 123456umontreal.ca
                Correspondence may also be addressed to Ivan Sadowski. Tel: +1 604 822 4524; Fax: +1 604 822 5227; Email: ijs.ubc@ 123456gmail.com

                Citation details: Sadowski,I., Breitkreutz,B.-J., Stark, C., et al. The PhosphoGRID Saccharomyces cerevisiae protein phosphorylation site database: version 2.0 update. Database (2013) Vol. 2013: article ID bat026; doi: 10.1093/database/bat026

                Article
                bat026
                10.1093/database/bat026
                3653121
                23674503
                0f1f8a72-62cd-4e96-8cbc-7c28bce61ba2
                © The Author(s) 2013. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 December 2012
                : 21 March 2013
                : 21 March 2013
                Page count
                Pages: 10
                Categories
                Original Article

                Bioinformatics & Computational biology
                Bioinformatics & Computational biology

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