Tutorial: The system component entry page
About:
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This tutorial explains the organization and functionality of the web pages that present all the information available in TCDB for each individual component (entry) within a transport system. You can get to these system entries from multiple pages where queries can be submitted to TCDB (e.g., via the TCDB search box, blast/psiblast forms, or the substrate search tool, etc.).
We will use as a case study the page describing the multi-component uptake system 3.A.1.1.1, a member of the ABC Superfamily (TC# 3.A.1). Because this is a multi-component system, the corresponding system page simply lists all 4 subunits (components) necessary for the system to perform its function (Figure 1). The sections below describe the web page that appears when you click on the individual membrane component P68183 (Figure 1A).
Figure 1. Multi-component system 3.A.1.1.1. A. Individual component of the system that will be used in this tutorial.The links of all 4 components in Figure 1, lead to very similar pages describing each individual protein component (entry). In the case of single-component systems, the system page directly describes the only component of the system (see for example the page for the MFS system 2.A.1.1.1).
The pages describing system entries are organized in 3 sections to facilitate their description: (1) the header, system description and primary tools, (2) external database links and references, and (3) other tools and access to sequence data.
Section 1: The header, system description and primary tools
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Figure 2 describes the location of the first four parts of the page describing any component (in this case P68183) of a transport system in TCDB.
The header consists of two general parts unrelated to the system analyzed in this tutorial: (1) the search box (Figure 2A) is used to submit keyword queries to TCDB, and it is explained with step-by-step examples in its own tutorial and (2) the top menu bar (Figure 2B) gives access to global information about TCDB including help. The top menu bar is explained with detail in the TCDB homepage tutorial.
Figure 2. Section 1 of the system component page. A. TCDB Search Box. B. Top menu bar. C. Quick access to tools operating on the component. D. Detailed system description.Above the system description, there are 3 shortcut buttons linking to tools that operate directly on the sequence of the system component under analysis (Figure 1C). The system description contains curated information detailing everything that is known about the function and evolution of the system. When available, the text includes references to the scientific literature (Figure 1D). The 3 shortcut buttons in Figure 2C are described below:
Plot Hydropathy
This button runs our program WHAT on the proteins sequence of component P68183. This program plots the Hydropathy/amphipathicity curves of the protein sequences and the TMSs as predicted by the program HMMTOP (see Figure 3).
Figure 3. Hydropathy/Amphipathicity and TMS topology.Loop Finder
This button runs our program Re-entrant Loop Finder Tool designed to identify moderately hydrophobic re-entrant loops in Pore-Loop (P-loop) channels. P-loops are not known to occur in the ABC family, so the program would only return a hydropathy curve for system component P68183 as in Figure 3. However, if you run this program in families that contain P-loops (e.g., members of the VIC superfamily), you will see the P-loops shaded in blue in the hydropathy plots. As an example, go to the system 1.A.1.13.2 and click on the Loop Finder button.BLAST against TCDB
This button is a shortcut to run TC-BLAST on the sequence of system component P68183. For a description of the TC-BLAST output and step-by-step examples, follow our TC-BLAST tutorial.
The description of the system (Figure 2D) is common to all components of the same transport system. However, the rows immediately below the description describe attributes of each individual component: (1) Accession Number (UniProt or RefSeq), (2) Protein Name, (3) Length, (4) Molecular Weight, (5) Species name (including the accession to the NCBI Taxonomy database), (6) Number of TMSs predicted by HMMTOP, (7) Location/Topology/Orientation, and (8) transported substrates.
NOTE: Substrates are shared between all components within the same multi-component system regardless of whether or not individual components make direct contact with the substrate. The rationale is that all components are needed for transporting the substrate(s) across the membrane.
Section 2: External database links and references.
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This section (Figure 4) consists of links to external resources falling in two categories: links to other related biological databases that complement the information on the system (Figure 4A and 4C), and links to the relevant literature in PubMed (Figure 4B).
Figure 4. Section 2 of the system component page. A. External references to biological databases. B. References to the literature relevant for the system. C. Accessions to the corresponding 3D structures in PDB.TCDB provides links to multiple external databases (Figure 4A and 4C) including the NCBI Protein database, the NCBI Gene database, the Protein Family (PFAM) database, the EcoCyc database, the Gene Ontology database, the Protein DataBank (PDB), the Database of Interacting Proteins (DIP) and more. Every scientific paper cited in the system description includes a link to PubMed (Figure 4B).
Section 3: Other tools and access to sequence data.
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This section (Figure 5) provides links to additional external tools (Figure 5A) and local tools (Figure 5B), as well as to the actual protein sequence of the corresponding system component (Figure 5C).
Figure 5. External Section 2 of the system component page. A. External tools for further analysis. B. Local links to the inference of TMSs (equivalent to the link in Figure 2C). C. The protein sequence.The links to EXTERNAL SEARCHES (Figure 5A) allow the direct submission of the sequence of component P68183 to the NCBI BlastP service, the NCBI Conserved Domains and Protein Classification (CDD) database, and more.
The links in the ANALYZE region (Figure 5B) infer TMS and plot hydropathy/amphipathicity curves. Just like the button Hydropathy in Figure 2C. You can plot the hydropathy of your own query protein via our BioTools server, by clicking on the link to our WHAT program.
The sequence of the protein is available at the bottom of the page (Figure 5C). By default, the sequence is presented in GenBank format, however, it can also be extracted in FASTA format by clicking on the link "FASTA formatted sequence".