Pfam entry page organisation¶
In each Pfam entry page, different tabs with relevant information are available, as shown in the figure below.
Example of a Pfam entry page (PF02171). All the tabs explained below can be found on the left-hand side menu. The Overview tab is displayed by default.¶
Overview¶
The entry overview tab is the default display, where the type of Pfam entry, the short name and the clan (if the entry belongs to any) are shown at the top, more information about how clans are defined can be found in Summary. Usually, a curated description of the entry is displayed below, with the relevant literature references.
If there is a Wikipedia page for the entry, the first paragraph and the box with an image of a tridimensional structure and some cross-links are displayed. The full Wikipedia article can be open in a new tab by clicking on the title.
Proteins¶
The list of proteins matching this entry is displayed in this tab. This view can be customised to show:
All proteins (from the whole UniProtKB database).
Only Reviewed proteins (from SwissProt - manually curated).
Only Unreviewed proteins (from TrEMBL - derived from public databases automatically integrated into UniProt).
For each protein, the corresponding protein page in InterPro can be accessed by clicking on the protein accession or name; the InterPro taxonomy page can be accessed by clicking on the species name; and a small-size protein viewer displays the location of the Pfam entry in the protein. The coordinates of the match can be shown by hovering the mouse over it. You can also export this data in different formats, by clicking on the Export button, and customise the page settings, by clicking on the wheel icon.
Domain architectures¶
This tab shows the various domain arrangements of the proteins matched by the entry, ordered in descending order by the number of times that this architecture is seen. Identifying the different domains present in proteins is crucial to understand how they function.
The protein viewer displays a representative sequence for each domain architecture, where the domain size is based on the real length of the domain in the protein. When hovering over a domain, more details are shown in a tooltip, including the domain’s position.
From this page, all related Pfam entry pages can also be accessed by clicking on a Pfam accession at the top of the viewer or on a short name on the right-hand side of the viewer. The list of proteins with this architecture is available by clicking on the protein number.
Taxonomy¶
This tab shows by default a sunburst chart of all the species that the proteins matched by the Pfam entry belong to.
By default, eight individual nodes that are derived from the taxonomic lineage of each protein sequence, ranging from superkingdoms down to species, are displayed. For each node in the taxonomy tree there is a separate ring - and each ring is arranged radially, with the superkingdoms at the centre and the species around the outermost ring. The length of each ring is proportional to the number of proteins found within each taxon. You can choose how many rings you want to see from the options on the right-hand side of the page.
Segments of the sunburst chart are coloured according to their superkingdom, as explained in the Legends section. Mousing over any part of the sunburst chart shows the taxonomic name and level, with both the number of sequences and the number of species found at that level shown on the right-hand side.
These data can also be seen as a table and as a tree. In addition, it is possible to choose to see only data from key species instead. These visualisation options can be chosen from the icon panel above the sunburst. All this information can be downloaded in different formats.
Proteomes¶
A list of the reference proteomes matched by the entry is displayed in this tab. Each item in this list shows the Proteome ID (which is a link to the Proteome page in InterPro), the name of the species carrying this proteome and the number of proteins in this proteome that match the entry. From the Actions column, users can also see a list of these proteins by clicking the first icon (View matching proteins), download the data in different formats or View proteome information.
Structures¶
This tab displays a list of all the PDB structures linked to the proteins matching the Pfam entry. For each structure, you can see the PDB accession, the name of the structure in PDB, and a small-sized protein sequence viewer displaying the location of the Pfam entry in the protein structure chain.
Viewing the structures of domains and proteins helps to understand what their function might be, and how individual residues are arranged in the three-dimensional space. Often, two residues which seem distant along the linear protein sequence can be very close in the folded protein.
By clicking on a PDB accession, name or small image of the structure, a view of the corresponding InterPro structure page that summarises all of the entries of Pfam and other databases and resources for each chain of the structure will be displayed in a protein sequence viewer.
The position of each entry within the overall 3D structure can be visualised by choosing the Pfam entry of interest in the drop-down list Highlight Entry in the 3D structure or by clicking on the bar corresponding to the entry match in the protein sequence viewer. Additionally, links to similar PDB viewers and cross-references to other structural databases are provided in the External links section.
Signature¶
This tab shows the HMM logo of the Pfam model, visualised using Skylign. HMM logos are one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form.
The visualisation displays the amino acid conservation for each residue in the model. The rendered area can be dragged to a desired position to navigate large logos. Alternatively, a specific residue number can be written in the Model column text box. When selecting a particular residue in the logo, the probabilities of each amino acid are displayed in the bottom part.
AlphaFold¶
Many of the proteins found in the Pfam entry may have a predicted structure generated by AlphaFoldDB. A list of all the predicted structures available in AlphaFoldDB for the proteins belonging to this entry is displayed in this tab. For each protein in the list, its Uniprot accession, name, the species it belongs to, its length, and a button that allows you to show the predicted structure of this protein in the structure viewer are displayed.
It is also possible to click on the Uniprot accession to go to the InterPro protein page and go to the Alphafold tab, where the position of the different entries in the 3D structure viewer are displayed by clicking on the bar corresponding to the entry match in the protein sequence viewer.
Alignment¶
Three different alignments can be chosen and visualised in this tab:
The seed alignment shows the multiple sequence alignment used to create the HMM model in Pfam. This is a representative set of sequences of the family and it normally has a relatively short number of protein sequences (from the Uniprot Reference proteomes).
The full alignment shows all the protein sequences from the Uniprot Reference proteomes that match this model.
The uniprot alignment includes all the protein sequences matched by this Pfam model in the whole Uniprot database.
The colour coding of the alignment can be customised through the options available in the Colors section.
All the alignments can be downloaded by clicking on the Download button.
Curation¶
This tab is divided into two subsections:
In the first section, you can see details about Pfam curators and Sequence ontology.
The second section displays the HMM building command used to generate the HMM profile defining the Pfam entry and offers the possibility to download it.
Pfam entries creation and annotation¶
For each Pfam entry, the HMM model is run against the protein sequences belonging to the UniProt Reference Proteomes. Subsequently, Pfam curators set a statistical cut-off, known as a gathering threshold (GA) for an entry. Sequences failing to make a statistical match above this threshold are not reported as hits. The threshold is quite conservative, to minimise false positives (although they are unavoidable sometimes). The Pfam model is then run against the whole UniProtKB database before every InterPro release and these are the matches shown in the Proteins tab on the Pfam entry page.
Different Pfam entries have annotations providing diverse amounts of information. Many of them have a description created by Pfam curators. Anyone can contribute to this annotation by contacting directly the curators through the Add your annotation toolbox located on the right-hand side of the Overview tab.
If you know of a domain that is not present in Pfam, you can submit it to the Pfam helpdesk and we will endeavour to build a Pfam entry for it. Please note that our interest does not currently extend to small, species-specific protein families of unknown function, unless they are supported by a publication or other significant functional predictions. We kindly ask you to follow the How can I submit a new domain? section of the FAQ before submitting information for the creation of a new Pfam entry.
Select Add your annotation to give feedback to curators.¶
In addition, Pfam encourages the annotation of Pfam families via Wikipedia. Below the traditional description of the Pfam entry, you may find the text from a Wikipedia article that we feel provides a good description of the Pfam family.
If a family does not yet have a Wikipedia article assigned to it, there are several ways for you to help us add one. You can find more information about the process in the Wikipedia section.