Proteins on genomes.jbrowse.org
2 videos in this tutorial
The tutorials target the JBrowse v5 beta, and the v4.3.0 release
on the download page lacks some of what they show. To install the
beta of JBrowse Web, run npm install -g @jbrowse/cli@next, then
jbrowse create jbrowse2 --branch v5.0.0-beta.17. Desktop beta builds are coming soon.
A missense variant changes one codon, and what it does depends on where that residue sits in the folded protein and how conserved it is across related proteins. The protein browser on genomes.jbrowse.org takes a gene symbol and opens the gene, its 3D structure and an alignment of related proteins as one JBrowse session, linked so that a residue picked in one view lights up in the other two. We'll:
- open TP53 in the protein browser on R248, a cancer hotspot, and read the session it launches
- change what the session opens on: a domain, a structure, a coloring
- launch the same views from a gene's right-click menu, where you choose the structure and the species to align, on NLRP1, whose domains differ between mammals
Prerequisites
- for the right-click route in your own JBrowse, the protein3d and msaview plugins from the plugin store (Adding the plugins to your own instance); genomes.jbrowse.org already loads them
The data
Nothing to download: the protein browser and the two plugins fetch from these services, per gene, when you open a session. Adding the plugins to your own instance covers your own JBrowse.
The files
| What it is | File |
|---|---|
| AlphaFold DB, the predicted structures | alphafold.ebi.ac.uk |
| PDBe, the experimental structures | pdbe/ |
| UniProt, the protein each gene encodes and the projected Domains, Chains, Mutations and AA Modifications tracks | www.uniprot.org |
| InterPro, the protein browser's domain map and the Pfam seed alignments | interpro/ |
| PDBe-KB, the protein browser's partner and ligand lists | pdbe-kb/ |
| UniRef, the cluster a protein with no NCBI orthologs is aligned with | uniref |
| NCBI's ortholog report, the rows of an ortholog alignment | rest-api/ |
| NCBI's Conserved Domain Database, the alignment's domain overlay | cdd.shtml |
Opening TP53 in the protein browser
We'll start on TP53's R248, one of the residues most often mutated in human cancer, where the protein contacts DNA. Open the protein browser and click the TP53 chip, which focuses the page on that residue:
- The page draws the protein end to end with its InterPro domains, marks R248 on the ruler, and shows the focus beside the launch button as Opens at Cancer hotspot R248.
- Tick Advanced. The Structure box shows the entry the chip picked, 3KMD, the DNA-binding core of p53 bound to DNA.
- Set Color to AlphaMissense pathogenicity, which paints each residue by how damaging AlphaMissense predicts a substitution there to be.
- Click Open in JBrowse ↗.
Typing a gene into the search box and pressing Search opens the same card with no focus. Advanced also adds a species box, which takes any species name or NCBI taxon ID whose genome genomes.jbrowse.org hosts with NCBI gene annotation, and the chips after TP53 open other organisms on a residue each, such as rifampicin resistance in M. tuberculosis rpoB.
Reading the TP53 session
Open in JBrowse opens a new tab with one session and three views of the same transcript:
- The gene, its coding exons back to back with the introns cut out, read 5′ to 3′, above ClinVar's variants and AlphaMissense's scores
- The alignment, the seed alignment of the Pfam family R248 falls in, P53, opened on the columns around R248 with TP53's own row, linked to the gene, in the middle. The launch button's tooltip names the alignment before you click.
- The structure, 3KMD in Mol*, with R248 selected
Hover a codon in the gene view and its residue lights up on the structure and its column in the alignment; hover the structure or the alignment and the codon lights up in turn. g2p_mapper maps each position through the transcript's coding sequence, so introns, UTRs and residues the structure does not cover highlight nothing.
Changing what the TP53 session opens on
The page picks the session's alignment and structure from the focus beside the launch button. Click Clear to drop it, and choose another:
- A domain: click a block on the map's Domains row. The session opens on the domain, with the seed alignment of its Pfam family.
- A residue: type a position into the Residue box, which Advanced shows while nothing is focused. The alignment becomes the Pfam seed of the domain the residue falls in, and the structure the PDB entry in which that residue was seen touching DNA, a small molecule or another protein, else the AlphaFold model.
- A partner or a ligand: under Advanced, click Partners… or Ligands… on the map to list the proteins and small molecules PDB entries show touching this one. Clicking one opens the complex they were seen in.
- A truncation: under a focused residue, More about residue offers to open on the residues a stop codon there, or skipping its exon, would remove.
- Nothing: the session opens on the whole gene, the AlphaFold model and an alignment of the gene's orthologs from NCBI, one per species, built in the browser when the session opens. NCBI lists orthologs for vertebrates and insects; any other protein gets its UniRef50 cluster instead.
Structure under Advanced overrides the pick with any AlphaFold or PDB entry, and Color also offers ClinVar pathogenic variants and, on an AlphaFold model, AlphaFold confidence (pLDDT). The page URL holds the gene, the focus and the structure, so ?gene=TP53&ref=9606&residue=248&structure=3kmd reopens this launch.
Launching from the gene's right-click menu
The protein browser picks the structure and the alignment for you. A gene's right-click menu, in any JBrowse with the protein3d and msaview plugins, lets you pick both, and starts from a gene already on screen.
Open hg38 on genomes.jbrowse.org, type TP53
into the location box, and right-click the gene. The menu has Launch protein
view from protein3d and Launch MSA view from msaview. Choose Launch
protein view.
The dialog opens on its AlphaFoldDB search tab:
- Look up from the feature's identifiers (selected) maps the transcript's accession to UniProt entries and picks the reviewed one.
- Choose transcript isoform opens on the isoform you right-clicked, picks which transcript becomes the query, and tags the isoforms whose translation matches the structure's residues.
- Launch renders the structure.
The structure opens under the genome view, linked the same way as the protein browser's. Where its sequence differs from the transcript's translation, the Pairwise alignment panel shows each residue the structure lacks as a gap, and Import manual alignment... in the view menu takes a pairwise alignment of your own in Clustal format instead. The lookup needs a gene feature with a recognizable protein or transcript ID, which the RefSeq gene tracks on the hosted configs have.
The protein view also has per-residue tracks for pLDDT, domains, helices and hydrophobicity. Open side by side, at the foot of the list the arrow beside the dialog's Launch button opens, puts the protein view beside the genome view. Click the nuclear export signal on the alignment panel's Motif row to select its residues and band their codons on the gene.
Other structure sources and views in the Launch dialog
The dialog's other tabs take a structure from elsewhere:
- PDB search lists the experimental structures PDBe maps to the protein's UniProt entry
- Foldseek search finds structures similar to the protein's
- File or URL takes a PDB or mmCIF file of yours
Click the arrow beside Launch to list everything the dialog can build. Launch 1D protein annotation view opens a linear genome view whose genome is the protein. The plugin registers the UniProt accession as a temporary assembly with the amino-acid sequence as its reference, so coordinates are residues. The view opens with these tracks on:
- UniProt features, a section per feature type
- Antigen
- AlphaFold confidence (pLDDT) and AlphaMissense scores
- ClinVar, the transcript's missense variants
Launch an alignment from the same right-click menu too, and each panel's menu has Arrange all views → Side by side, which puts the genome, alignment and structure in three columns.
Choosing the species to align for NLRP1
Launch MSA view builds an alignment from the orthologs NCBI publishes for
most annotated genes, one per species, with the rows and the aligner yours to
choose. We'll use NLRP1, an inflammasome sensor whose domain architecture
varies between mammals. Type NLRP1 into the location box, right-click the gene
and choose Launch MSA view. The dialog opens on its Orthologs tab:
- Query species is the species the gene came from, free text resolved against NCBI's taxonomy: a scientific name, a common name or a taxon id
- Rows to align is how many species to build. NCBI orders its ortholog report from the reference organisms outward, so this takes the closest N
- Choose isoform picks which transcript becomes the query row, the one the genome view stays linked to
- MSA Algorithm sets which aligner EBI runs, Clustal Omega by default
- BLAST query, a separate tab, takes a gene with no resolvable symbol
Press Submit. The alignment opens below the genome view, with a tree on the left and NCBI's conserved domains drawn over the residues once NCBI returns them. It opens at residue zoom on the N terminus; View → Zoom → Fit width (View is the eye icon in the alignment's toolbar) puts the whole alignment on screen, which is the zoom the domain blocks read at.
Reading NLRP1's conserved-domain overlay on the MSA
Each colored block is an NCBI conserved domain, drawn in alignment columns. The pyrin (PYD) domain sits at the N terminus of human NLRP1 and is absent from mouse Nlrp1a. NACHT, the winged helix, HD2, FIIND and CARD run across nearly every row and are the control; the whale rows have only the C-terminal end.
The domain calls come from NCBI's protein records. For a protein NCBI has no calls for:
react-msaview-cli interproscanscans the sequences into a domain file.- File → Open annotation file... reads that file in. The dialog's How to
make one link opens a
walkthrough that also
covers
interpro, the instant path when the rows are UniProt accessions.
UniProt domains in genome coordinates for NLRP1
UCSC projects UniProt's annotations onto the genome, so the hosted config holds them as tracks. Turn on UniProt - Domains (under Genes and Gene Predictions) in the linear view you launched from, then narrow it to one record:
- Filter by... in the track menu applies the row
uniProtIdisQ9C000, the gene's reviewed UniProt entry. Without it, the track draws a domain once per isoform, and isoforms sharing exons overlap. - UniProt - Chains, Mutations and AA Modifications project the rest of the record.
More protein browser sessions
A protein browser session takes any other JBrowse track beside the codon, and a second protein view beside the first. Each figure's live link opens its session.1
Open a figure's live link and hover the highlighted codon in the genome view; each protein view then lights the residue it codes for.
Adding the plugins to your own instance
The plugin store lists the two plugins as Protein3d and MSAView, and Installing plugins covers each way to install them.
The protein3d and msaview plugins add view types launched from a gene's
right-click menu in JBrowse Web and Desktop. The single-view embedded components
host only a linear genome view, so neither view type appears there.
JBrowseR's JBrowseRApp takes both runtime plugins and a views
list, while anywidget's JBrowseApp has no plugin
loading yet.2
The approach is described in Proteins in the Genome Browser (Journal of Molecular Biology, 2026).
See also
- Tutorial: Basic usage of genomes.jbrowse.org
- Tutorial: Synteny on genomes.jbrowse.org
- Tutorial: TP53 from prediction to crystal
- Tutorial: Variants on protein structures part 1: sickle cell from GWAS hit to haemoglobin S
- Tutorial: Protein domains on gene models
External links
- Protein browser
- JBrowseMSA user guide
- jbrowse-plugin-protein3d
- jbrowse-plugin-msaview
- g2p_mapper
- AlphaFold DB
- UniProt
- InterPro
- NCBI Datasets gene orthologs
- NCBI Conserved Domain Database
- Proteins in the Genome Browser
Citations
- Broz and Dixit (2016). Inflammasomes: mechanism of assembly, regulation and signalling
Notes
-
Some of these crystals carry engineered mutations. In the TP53 figure, 2J1X and 9S9O carry the stabilizing M133L, V203A, N239Y and N268D, none of them in the pocket. In the KRAS figure, 6OIM carries C51S, C80L and C118S, which remove the construct's other cysteines a covalent drug could react with. ↩
-
A
ProteinViewentry in a session-spec URL opens a connected view for demo links and embedded apps. The short form takesuniprotId,transcriptIdand aconnectedViewwith theassembly,locandtracksto look the transcript up in; the plugin derives the AlphaFold structure and translates the transcript's CDS. The explicit form takes a structureurl, feature and protein sequence, for a transcript no loaded track serves. AProteinViewwith only aurlopens as a standalone structure. The protein3d launching guide has both forms. ↩
Feedback on this tutorial is welcome: contact us.