This family is a member of clan (CL00017), which contains the following 2 members:IRES_HCV IRES_Pesti
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There are various ways to view or download the seed alignments that we store. You can use a sequence viewer to look at them, or you can look at a plain text version of the sequence in a variety of different formats. More...
You can choose from two different sequence viewers:
- a Java applet developed at the University of Dundee. You will need Java installed before running jalview
- an HTML page showing the seed alignment in blocks. We do not store separate alignments with species or "name/start-end" labels, but you can switch between these different labels within the block viewer
You can download (or view in your browser) a text representation of an Rfam seed alignment in various formats:
- Gapped FASTA
- Ungapped FASTA
You can view Rfam seed alignments in your browser in various ways. Choose the viewer that you want to use and click the "View" button to show the alignment in a pop-up window.
You can view or download Rfam seed alignments in several formats. Check either the "download" button, to save the formatted alignment, or "view", to see it in your browser window, and click "Generate".
Submit a new alignment
We're happy receive updated seed alignments for new or existing families. Submit your new alignment and we'll take a look.
This section shows a variety of different secondary structure representations for this family. More...
In this page you can view static images showing the secondary structure of this family using a variety of colouring schemes:
Conservation (cons): this plot colours each character by how well conserved it is. A site with 100% sequence conservation is coloured red, 0% is violet.
Covariation (cov): this plot colours each base-pair according to how much the corresponding nucleotides are co-varying. A base-pair position at which every pair of nucleotides is co-variant with respect to every other pair in the alignment gets a score of 2 and is coloured red. Conversely, a base-pair position at every pair is anti-co-variant with respect to every other pair (e.g. lots of mutations to non-canonical pairs) gets a score of -2 and is coloured violet. Further information on this metric can be found in this document.
Sequence entropy (ent): this plot colours each character by how under- or over-represented the residues at the site are. Sites where one or more nucleotides are over-represented while the other nucleotides are either non-existent or near the background frequencies, receive positive scores; sites where all the nucleotides are under-represented receive negative scores. Further information on this metric can be found in this document.
Fraction of canonical basepairs (fcbp): this plot colours each base-pair by the percentage of canonical basepairs (A:U, C:G, G:U) which are found in the corresponding position in the alignment. A pair of sites with 100% canonical pairs is coloured red, a site with 0% is violet.
Maximum parse of the covariance model (maxcm): this plot takes the covariance model for the family and generates the sequence with the maximum possible score for that model. Each character is coloured by how many bits it contributes to the total score.
Sequence: for most of the above cases, the representative sequence used for the backbone is the most informative sequence (MIS). Any residue that has a higher frequency than than the background frequency is projected into the IUPAC redundancy codes.
Normal: this plot simply colours each stem loop
R-chie (rchie): arc diagrams showing secondary structure, calculated using the R-chie package. The consensus secondary structure is visualized as arc diagrams on top of each diagram, where a basepair in an arc, connect two columns of the block of sequences below. The block of sequences below represent the multiple sequence alignment of the Rfam seed, where each sequence is a horizontal strip. Sequences in the alignments are ordered so sequences that best fit the structure are on top, and those that do not fit as well are towards the bottom. For seed alignments for over 500 sequences, 500 random sequences were chosen. Rfam entries without sturcture have a blank plot. Colour information can be found on the R-chie FAQ.
You can also view the secondary structure in the VARNA applet. The applet is shown in a separate pop-up window.
The bulk of the code for generating these graphics was kindly supplied by Andreas Gruber and Ivo Hofacker. The statistics were implemented by Rfam.
The R-chie arc diagrams were calculated using R-chie:
You can view the secondary structure of the family using the here.applet. You can see more information about VARNA iself
Current Rfam structure
R-scape optimised structure
- Statistically significant basepair with covariation
- 97% conserved nucleotide
- 90% conserved nucleotide
- 75% conserved nucleotide
- 50% conserved nucleotide
- R: A or G
- Y: C or U
Tip: The diagrams are interactive:
you can pan and zoom to see more details
or hover over nucleotides and basepairs.
R-scape is a method for testing whether covariation analysis supports the presence of a conserved RNA secondary structure. This page shows R-scape analysis of the secondary structure from the Rfam seed alignment and a new structure with covariation support that is compatible with the same alignment.
Move your mouse over the image to show details and click to show full image.
- Arc colours
- 100% canonical basepair
- Nucleotide colours
- Valid basepairing
- Two-sided covariation
- One-sided covariation
Weight segments by...
Change the size of the sunburst
Click on a node to select that node and its sub-tree.
- 0 sequences
- 0 species
This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the More....
This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.
How the sunburst is generated
The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:
Colouring and labels
Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.
As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.
Anomalies in the taxonomy tree
There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.
Missing taxonomic levels
Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.
Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
Too many species/sequences
For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.
The tree shows the occurrence of this RNA across different species. More...
For the majority of our families we provide an interactive tree representation, which allows you to select specific nodes in the tree and view the selected sequences as an alignment.
Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.
If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.
For all of the sequence regions (RNA annotations) in a full alignment, we count the total number that are found in the alignment. This total is shown in the purple box.
We also count the number of unique sequences on which each RNA is found, which is shown in green. Note that an RNA annotation may appear multiple times on the same sequence, leading to the difference between these two numbers (think of repeats like tRNA where the same RNA is found in tandem along a single sequence).
Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the RNA is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree. In these few cases if you do really need to see a representation of the tree for this entry, please contact us and we will be happy to discuss ways to generate it for you.
You can use the tree controls to manipulate how the interactive tree is displayed:
- show/hide the summary boxes
- highlight species that are represented in the seed alignment
- expand/collapse the tree or expand it to a given depth
- select a sub-tree or a set of species within the tree and view them graphically or as an alignment
- save a plain text representation of the tree
Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.
This page displays the predicted phylogenetic tree for the alignment. More...
These trees were generated using either a maximum likelihood approach or neighbour-joining. If the number of sequences in the alignment was less than or equal to 64 then the maximum likelihood approach of Rivas and Eddy was used . For families with more than 64 sequences in the alignment the neighbour-joining approach with F84 distances as implemented in phylip was used .
Note: You can also download the data file for the seed tree.
We do not have tree information for this family. This is most likely due to the size of the family and the number of species covered. For very large families it is too computationally expensive to calculate trees and the resulting tree images would be too large to display in a browser.
There are 1 motifs which match this family.
This section shows the Rfam motifs that match sequences within the seed alignment of this family. Users should be aware that the motifs are structural constructs and do not necessarily conform to taxonomic boundaries in the way that Rfam families do. More...
Motifs in this context are defined as recurring RNA sequences and/or secondary structures found within larger structures that can be modeled by either a covariance model (CM) or a profile HMM. The motifs models come from release 0.3 of the RMfam database available at github.
To annotate the family with a motif model, the seed sequence was first filtered using a 0.9 fraction identity cut-off. The filtered seed was then scanned using Infernal cmscan (v1.1) with a concatenated CM file containing each of the motifs. Significance of hits between a seed sequence and the CM was based on a gathering threshold that was individually set for each motif. Only motifs where more than two and at least 10% of seed sequences scored higher than the gathering threshold were included for the next stage of processing. These subsets of motifs were then rescanned against the entire (non-filtered) seed to generate matches.
Number of Hits: the number of sequences in the family seed that score above the gathering threshold from motif.
Fraction of Hits: the fraction of sequences in the family seed that score above the gathering threshold from motif.
Sum of Bits: the sum of the bit scores of matches between the motif and the family seed sequence.
Image: plot illustrating where on the consensus secondary structure matches occur between seed sequences and the motif model.
|Original order||Motif Accession||Motif Description||Number of Hits||Fraction of Hits||Sum of Bits||Image|
This section shows the database cross-references that we have for this Rfam family.
Gallego J, Varani G Biochem Soc Trans 2002;30:140-145. The hepatitis C virus internal ribosome-entry site: a new target for antiviral research. PUBMED:12023841
Pirakitikulr N, Kohlway A, Lindenbach BD, Pyle AM Mol Cell. 2016;62:111-120. The Coding Region of the HCV Genome Contains a Network of Regulatory RNA Structures. PUBMED:26924328
Lytle JR, Wu L, Robertson HD RNA 2002;8:1045-1055. Domains on the hepatitis C virus internal ribosome entry site for 40s subunit binding. PUBMED:12212848
Romero-Lopez C, Berzal-Herranz A Int J Mol Sci. 2020; [Epub ahead of print] The Role of the RNA-RNA Interactome in the Hepatitis C Virus Life Cycle. PUBMED:32098260
Beales LP, Rowlands DJ, Holzenburg A RNA 2001;7:661-670. The internal ribosome entry site (IRES) of hepatitis C virus visualized by electron microscopy. PUBMED:11350030
Fricke M, Dunnes N, Zayas M, Bartenschlager R, Niepmann M, Marz M RNA. 2015;21:1219-1232. Conserved RNA secondary structures and long-range interactions in hepatitis C viruses. PUBMED:25964384
External database links
|Gene Ontology:||GO:0043022 (ribosome binding);|
|Sequence Ontology:||SO:0000243 (internal_ribosome_entry_site);|
Curation and family details
This section shows the detailed information about the Rfam family. We're happy to receive updated or improved alignments for new or existing families. Submit your new alignment and we'll take a look.
|Seed source||Kevin Lamkiewicz, Sandra Triebel, Manja Marz|
|Structure source||Predicted; BM VeGETA v.0.4, LocARNA 2.0.0RC8, RNAfold ViennaRNA v.2.4.18|
|Author||Lamkiewicz K, Triebel S, Marz M|
cmbuild -F CM SEED
cmcalibrate --mpi CM
cmsearch --cpu 4 --verbose --nohmmonly -T 30.00 -Z 742849.287494 CM SEQDB