About KiNECTOR...

KiNECTOR is an open-access, knowledgebase developed by Kinexus Bioinformatics Corporation to track the linkages of extracellular mediators to kinase-based cell signalling pathways in human cells. The CytoNET module of KiNECTOR documents human cell receptor interactions (RIs) directly with extracellular mediators and intracellular proteins. The KiNET module of KiNECTOR further tracks over 24,000 human kinase-substrate relationships (KSRs). All of these interactions are displayed in a unique graphic format, that permits retrieval of key information and serves as a portal to other reputable websites that also contain additional detailed information on these signalling proteins or small molecule mediators. These maps also provide direct links to antibody products available from Kinexus that facilitate further studies of these regulatory proteins and aid in interpretation of the findings from the antibody microarray services provided by Kinexus. Over 80% of the 21,300 proteins encoded by the human genome appear to be subject to phosphorylation that may be altered in response to over 600 extracellular mediators that include small molecules and proteins such as hormones and cytokines. While at least 250,000 and possibly a million phosphosites exist in the human phosphoproteome, only a small fraction of these are likely to be consequential. Future studies are needed to define the most important RIs and KSRs for a comprehensive understanding of the most critical regulatory networks that govern cellular communications and control. The information provided on KiNECTOR were retrieved from several sources, including UniProt, STRING, PhosphoNET, and PhosphoSitePlus, and other websites and the scientific literature. The protein-protein interactions displayed on KiNECTOR correspond to only those that have been experimentally verified in multiple studies. Consequently, not all known or possible protein-protein interactions are shown.

Instructions...

KiNECTOR is designed to be intuitive and simple to navigate. You can use the UniProt ID or common short names for the signalling proteins of interest in order to find direct receptor interactions and kinase interactions. Lists of possible options for proteins are generated by typing at least three letters of their names or identification numbers, and waiting for a few moments for a complete list of options to appear. Follow the steps outlined on the query webpages when searching for connections. Eight possible types of queries are available in the KiNECTOR atlas. These include: 1) Extracellular mediator-based interaction query; 2) Receptor-based interaction query; 3) Intracellular protein-based receptor interaction query; 4) Extracellular mediators and receptors tissue and cell distribution query; 5) Covalent modifications of extracellular mediator proteins and receptors query; 6) Kinase-based phosphoprotein substrate query; 7) Phosphoprotein substrate-based kinase query; and 8) Kinase direct and indirect phosphoprotein target query. Except for the last type of query, only direct interactions are visualized on the maps. However, it is feasible to easily identify further protein interactions from these maps. Clicking on an interacting protein icon (node) connected with a line or arrow (edge) will generate a new map of direct protein interactions with this protein as the central hub. For some queries, the number of interactions may be too large and clear visual representation is not possible on a single map. By activating the available filters, simpler maps can be generated. Extra map pages can be shown by clicking "Previous" or "Next" buttons. Hovering the cursor above the icons (nodes) for proteins or post-translation modification sites generates a pop-up that provides functional information and links to websites with further information and available antibody products from Kinexus. The Kinase direct and indirect phosphoprotein target query permits the user to find direct and indirect connections between a starting protein kinase of interest and a phosphorylated target protein. For this query, clicking on the line (edge) will reveal the specific phosphosites that are modified by the upstream kinase on the target phosphoprotein.

Other Useful Online Resources From Kinexus...

KiNECTOR is one of several useful open-access, online resources in the SigNET Knowledge-Bank that are available from Kinexus to promote cell signalling research by academic and industrial scientists. SigNET features over 3 million webpages of information Direct links to several of our other knowledgebases in the SigNET Knowledge-Bank are provided just below the header at the top of each webpage in KiNECTOR. TranscriptoNET provides gene expression data on over 21,000 human genes in over 600 diverse human cell lines, organs and tissues. KinaseNET offers detailed information about 536 human protein kinases, whereas OncoNET provides expression and mutation data for 3000 cancer-related proteins in diverse human tissues and cell lines. PhosphoNET features data on nearly 1 million confirmed or predicted phosphorylation sites in over 21,000 human proteins, including known and predicted kinases and phosphatases that target these phosphosites, and the evolutionary conservation of these phosphosites in over 20 other species. KinATLAS reveals interactions between these proteins with each other in signalling systems as well as interactions with kinase inhibitory compounds. Our DrugKiNET knowledgebase features comprehensive information on over 800 compounds that have been experimentally determined to inhibit human protein kinases. This includes the retrieval of the lowest reported compound IC50, Ki and Kd values from several reputable sources for over 105,000 experimentally tested, non-redundant kinase-compound pairs. Using this information for training, we developed two kinase inhibitor prediction algorithms to further predict another 200,000 possible kinase-compound interactions. DrugProNET provides identification of the critical amino acids in drug targets for binding of over 800 drugs. For semi-quantitative data on actual protein expression in over 2,000 diverse biological specimens, please also visit our open-access KiNET-AM DataBank with over 2000 antibody microarray analyses with over 1700 diverse pan- and phosphosite-specific antibodies. Most of these antibodies are available from Kinexus for screening lysates from cells and tissues using our Kinex™ KAM antibody microarrays or as stand-alone products at our https://kinexus-ca.myshopify.com/ website.

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