Summary: CRISPR associated protein
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CRISPR Edit Wikipedia article
CRISPRs (Clustered Regularly Interspaced Short Palindromic Repeats) are loci containing multiple short direct repeats that are found in the genomes of approximately 40% of sequenced bacteria and 90% of sequenced archaea. CRISPR functions as a prokaryotic immune system, in that it confers resistance to exogenous genetic elements such as plasmids and phages. The CRISPR system provides a form of acquired immunity. Short segments of foreign DNA, called spacers, are incorporated into the genome between CRISPR repeats, and serve as a 'memory' of past exposures. CRISPR spacers are then used to recognize and silence exogenous genetic elements in a manner analogous to RNAi in eukaryotic organisms.
Discovery of CRISPR 
The clustered genomic repeats that are today known as CRISPR were first described in 1987 for the bacterium Escherichia coli. In 2000, similar clustered repeats were identified in the genomes of additional bacteria and archaea, and were termed Short Regularly Spaced Repeats (SRSR). SRSR were renamed CRISPR in 2002. A set of genes, some encoding putative nuclease or helicase proteins, were found to be associated with CRISPR repeats (the cas, or CRISPR-associated, genes).
CRISPR locus structure 
CRISPR repeats and spacers 
CRISPR repeats range in size from 24 to 48 base pairs. They usually show some dyad symmetry, implying the formation of a secondary structure such as a hairpin, but are not truly palindromic. CRISPR repeats are separated by spacers of similar length. Some CRISPR spacer sequences have identity to sequences from plasmids and phage, although some spacers have identity to the prokaryote's own genome (self-targeting spacers). New spacers can be added rapidly in response to phage infection.
cas genes and CRISPR subtypes 
The CRISPR-associated (cas) genes are often associated with CRISPR repeat-spacer arrays. More than forty different Cas protein families have been described. Of these protein families, Cas1 appears to be ubiquitous among different CRISPR/Cas systems. Particular combinations of cas genes and repeat structures have been used to define 8 CRISPR subtypes (Ecoli, Ypest, Nmeni, Dvulg, Tneap, Hmari, Apern, and Mtube), some of which are associated with an additional gene module encoding repeat-associated mysterious proteins (RAMPs). More than one CRISPR subtype may occur in a single genome. The sporadic distribution of the CRISPR/Cas subtypes suggests that the system is subject to horizontal gene transfer during microbial evolution.
|CRISPR associated protein|
crystal structure of a crispr-associated protein from thermus thermophilus
|CRISPR associated protein Cas2|
crystal structure of a hypothetical protein tt1823 from thermus thermophilus
|CRISPR-associated protein Cse1|
|CRISPR-associated protein Cse2|
CRISPR mechanism 
Exogenous DNA is apparently processed by proteins encoded by some of the CRISPR-associated (cas) genes into small elements (of ~30bp in length), which are then somehow inserted into the CRISPR locus near the leader sequence. RNAs from the CRISPR loci are constitutively expressed and are processed by Cas proteins to small RNAs composed of individual exogenously derived sequence elements with some flanking repeat sequence. The RNAs guide other Cas proteins to silence exogenous genetic elements at the RNA or DNA level. There is evidence for functional diversity among the different CRISPR subtypes. The Cse (Cas subtype Ecoli) proteins (called CasA-E in E. coli) form a functional complex, Cascade, that processes CRISPR RNA transcripts into spacer-repeat units that are retained by Cascade. In other prokaryotes, Cas6 processes the CRISPR transcripts. Interestingly, CRISPR-based phage inactivation in E. coli requires Cascade and Cas3, but not Cas1 and Cas2. The Cmr (Cas RAMP module) proteins found in Pyrococcus furiosus and other prokaryotes form a functional complex with small CRISPR RNAs that recognizes and cleaves complementary target RNAs.
Evolutionary significance and possible applications 
Through the CRISPR-Cas mechanism bacteria can acquire immunity against certain phages and thus halt further transmission of targeted phages. For this reason, some researchers have proposed that the CRISPR-Cas system is a Lamarckian inheritance mechanism. Others investigated the coevolution of host and viral genomes by analysis of CRISPR sequences.
The proof-of-principle demonstration of selective engineered redirection of the CRISPR-Cas system in 2012 provided a first step toward realization of some of the several proposals for CRISPR-derived biotechnology:
- Artificial immunization against phage by introduction of engineered CRISPR loci in industrially important bacteria, including those used in food production and large-scale fermentations.
- Genome engineering at cellular or organismic level by reprogramming of a CRISPR-Cas system to achieve RNA-guided genome engineering, proof of concept studies has demonstrated examples on this front both in vitro and in vivo.
- Knockdown of endogenous genes by transformation with a plasmid which contains a CRISPR area with a spacer, which inhibits a target gene.
- Discrimination of different bacterial strains by comparison of CRISPR spacer sequences (spoligotyping).
- Horvath P, Barrangou R (January 2010). "CRISPR/Cas, the immune system of bacteria and archaea". Science 327 (5962): 167â70. doi:10.1126/science.1179555. PMID 20056882.
- 71/79 Archaea, 463/1008 Bacteria CRISPRdb, Date: 19.6.2010
- Grissa I, Vergnaud G, Pourcel C (2007). "The CRISPRdb database and tools to display CRISPRs and to generate dictionaries of spacers and repeats". BMC Bioinformatics 8: 172. doi:10.1186/1471-2105-8-172. PMC 1892036. PMID 17521438.
- Barrangou R, Fremaux C, Deveau H, et al. (March 2007). "CRISPR provides acquired resistance against viruses in prokaryotes". Science 315 (5819): 1709â12. doi:10.1126/science.1138140. PMID 17379808.
- Marraffini LA, Sontheimer EJ (December 2008). "CRISPR Interference Limits Horizontal Gene Transfer in Staphylococci by Targeting DNA". Science 322 (5909): 1843â5. doi:10.1126/science.1165771. PMC 2695655. PMID 19095942.
- Marraffini LA, Sontheimer EJ (February 2010). "CRISPR interference: RNA-directed adaptive immunity in bacteria and archaea". Nat Rev Genet 11 (3): 181â190. doi:10.1038/nrg2749. PMC 2928866. PMID 20125085.
- Ishino Y, Shinagawa H, Makino K, Amemura M, Nakata A (1987). "Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product". J Bacteriol 169 (12): 5429â33. PMC 213968. PMID 3316184.
- Mojica FJM, DÃez-VillaseÃ±or C, Soria E, Juez G (2000). "Biological significance of a family of regularly spaced repeats in the genomes of Archaea, Bacteria and mitochondria". Mol Microbiol 36 (1): 244â6. doi:10.1046/j.1365-2958.2000.01838.x. PMID 10760181.
- Jansen R, Embden JD, Gaastra W, Schouls LM (2002). "Identification of genes that are associated with DNA repeats in prokaryotes". Mol Microbiol 43 (6): 1565â75. doi:10.1046/j.1365-2958.2002.02839.x. PMID 11952905.
- Haft DH, Selengut J, Mongodin EF, Nelson KE (2005). "A Guild of 45 CRISPR-Associated (Cas) Protein Families and Multiple CRISPR/Cas Subtypes Exist in Prokaryotic Genomes". PLoS Comput Biol. 1 (6): e60. doi:10.1371/journal.pcbi.0010060. PMC 1282333. PMID 16292354.
- Kunin V, Sorek R, Hugenholtz P (2007). "Evolutionary conservation of sequence and secondary structures in CRISPR repeats". Genome Biol 8 (4): R61. doi:10.1186/gb-2007-8-4-r61. PMC 1896005. PMID 17442114.
- Mojica FJ, DÃez-VillaseÃ±or C, GarcÃa-MartÃnez J, Soria E (February 2005). "Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements". J. Mol. Evol. 60 (2): 174â82. doi:10.1007/s00239-004-0046-3. PMID 15791728.
- Bolotin A, Quinquis B, Sorokin A, Ehrlich SD (August 2005). "Clustered regularly interspaced short palindrome repeats (CRISPRs) have spacers of extrachromosomal origin". Microbiology (Reading, Engl.) 151 (Pt 8): 2551â61. doi:10.1099/mic.0.28048-0. PMID 16079334.
- Pourcel C, Salvignol G, Vergnaud G (2005). "CRISPR elements in Yersinia pestis acquire new repeats by preferential uptake of bacteriophage DNA, and provide additional tools for evolutionary studies". Microbiology 151 (Pt 3): 653â63. doi:10.1099/mic.0.27437-0. PMID 15758212.
- Stern A, Keren L, Wurtzel O, Amitai G, Sorek R (August 2010). "Self-targeting by CRISPR: gene regulation or autoimmunity?". Trends Genet. 26 (8): 335â40. doi:10.1016/j.tig.2010.05.008. PMC 2910793. PMID 20598393.
- Tyson GW, Banfield JF (January 2008). "Rapidly evolving CRISPRs implicated in acquired resistance of microorganisms to viruses". Environ. Microbiol. 10 (1): 200â7. doi:10.1111/j.1462-2920.2007.01444.x. PMID 17894817.
- Makarova KS, Grishin NV, Shabalina SA, Wolf YI, Koonin EV (2006). "A putative RNA-interference-based immune system in prokaryotes: computational analysis of the predicted enzymatic machinery, functional analogies with eukaryotic RNAi, and hypothetical mechanisms of action". Biol Direct 1: 7. doi:10.1186/1745-6150-1-7. PMC 1462988. PMID 16545108.
- Brouns SJ, Jore MM, Lundgren M, et al. (August 2008). "Small CRISPR RNAs guide antiviral defense in prokaryotes". Science 321 (5891): 960â4. doi:10.1126/science.1159689. PMID 18703739.
- Koonin EV, Wolf YI (2009). "Is evolution Darwinian or/and Lamarckian?". Biol Direct 4: 42. doi:10.1186/1745-6150-4-42. PMC 2781790. PMID 19906303.
- Heidelberg JF, Nelson WC, Schoenfeld T, Bhaya D (2009). "Germ Warfare in a Microbial Mat Community: CRISPRs Provide Insights into the Co-Evolution of Host and Viral Genomes". In Ahmed, Niyaz. PLoS ONE 4 (1): e4169. doi:10.1371/journal.pone.0004169. PMC 2612747. PMID 19132092.
- Hale, Caryn R.; Majumdar, Sonali; Elmore, Joshua; Pfister, Neil; Compton, Mark; Olson, Sara; Resch, Alissa M.; Glover, Claiborne V.C.; Graveley, Brenton R.; Terns, Rebecca M.; Terns, Michael P. (5 Jan 2012), "Essential Features and Rational Design of CRISPR RNAs that Function with the Cas RAMP Module Complex to Cleave RNAs", Molecular Cell, New Articles (preprints), doi:10.1016/j.molcel.2011.10.023, retrieved 6 Jan 2012
- Sorek R, Kunin V, Hugenholtz P (2008). "CRISPR--a widespread system that provides acquired resistance against phages in bacteria and archaea". Nat Rev Microbiol 6 (3): 181â6. doi:10.1038/nrmicro1793. PMID 18157154.
- Jinek, M; Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. (2012). "A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity". Science. PMID 22745249.
- Cong, Le; Ran FA, Cox D, Lin S, Barretto R, Habib N, Hsu PD, Wu X, Jiang W, Marraffini LA, Zhang F. (2013). "Multiplex genome engineering using CRISPR/Cas systems.". Science. PMID 23287718.
- Mali, P; Yang L, Esvelt KM, Aach J, Guell M, DiCarlo JE, Norville JE, Church GM. (2013). "RNA-guided human genome engineering via Cas9.". Science. PMID 23287722.
- Cong, Le; Wang H, Yang H, Shivalila CS, Dawlaty MM, Cheng AW, Zhang F, Jaenisch R. (2013). "One-Step Generation of Mice Carrying Mutations in Multiple Genes by CRISPR/Cas-Mediated Genome Engineering.". Cell. PMID 23643243.
Further reading 
- Horvath P, Romero DA, CoÃ»tÃ©-Monvoisin AC, et al. (February 2008). "Diversity, Activity, and Evolution of CRISPR Loci in Streptococcus thermophilus". J. Bacteriol. 190 (4): 1401â12. doi:10.1128/JB.01415-07. PMC 2238196. PMID 18065539.
- Deveau H, Barrangou R, Garneau JE, et al. (February 2008). "Phage Response to CRISPR-Encoded Resistance in Streptococcus thermophilus". J. Bacteriol. 190 (4): 1390â400. doi:10.1128/JB.01412-07. PMC 2238228. PMID 18065545.
- Andersson AF, Banfield JF (2008). "Virus population dynamics and acquired virus resistance in natural microbial communities". Science 320 (5879): 1047â50. doi:10.1126/science.1157358. PMID 18497291.
- Hale C, Kleppe K, Terns RM, Terns MP (December 2008). "Prokaryotic silencing (psi)RNAs in Pyrococcus furiosus". RNA 14 (12): 2572â9. doi:10.1261/rna.1246808. PMC 2590957. PMID 18971321.
- Carte J, Wang R, Li H, Terns RM, Terns MP (December 2008). "Cas6 is an endoribonuclease that generates guide RNAs for invader defense in prokaryotes". Genes Dev. 22 (24): 3489â96. doi:10.1101/gad.1742908. PMC 2607076. PMID 19141480.
- Shah SA, Hansen NR, Garrett RA (February 2009). "Distribution of CRISPR spacer matches in viruses and plasmids of crenarchaeal acidothermophiles and implications for their inhibitory mechanism". Biochem. Soc. Trans. 37 (Pt 1): 23â8. doi:10.1042/BST0370023. PMID 19143596.
- LillestÃ¸l RK, Shah SA, BrÃ¼gger K, et al. (April 2009). "CRISPR families of the crenarchaeal genus Sulfolobus: bidirectional transcription and dynamic properties". Molecular Microbiology 72 (1): 259â72. doi:10.1111/j.1365-2958.2009.06641.x. PMID 19239620.
- Mojica FJ, DÃez-VillaseÃ±or C, GarcÃa-MartÃnez J, Almendros C (March 2009). "Short motif sequences determine the targets of the prokaryotic CRISPR defence system". Microbiology (Reading, Engl.) 155 (Pt 3): 733â40. doi:10.1099/mic.0.023960-0. PMID 19246744.
- van der Ploeg JR (June 2009). "Analysis of CRISPR in Streptococcus mutans suggests frequent occurrence of acquired immunity against infection by M102-like bacteriophages". Microbiology (Reading, Engl.) 155 (Pt 6): 1966â76. doi:10.1099/mic.0.027508-0. PMID 19383692.
- Hale CR, Zhao P, Olson S, et al. (November 2009). "RNA-Guided RNA Cleavage by a CRISPR RNA-Cas Protein Complex". Cell 139 (5): 945â56. doi:10.1016/j.cell.2009.07.040. PMC 2951265. PMID 19945378.
- van der Oost J, Brouns SJ (November 2009). "RNAi: prokaryotes get in on the act". Cell 139 (5): 863â5. doi:10.1016/j.cell.2009.11.018. PMID 19945373.
- Marraffini LA, Sontheimer EJ (January 2010). "Self vs. non-self discrimination during CRISPR RNA-directed immunity". Nature 463 (7280): 568â71. doi:10.1038/nature08703. PMC 2813891. PMID 20072129.
- Karginov FV, Hannon GJ (January 2010). "The CRISPR system: small RNA-guided defense in bacteria and archaea". Mol. Cell 37 (1): 7â19. doi:10.1016/j.molcel.2009.12.033. PMC 2819186. PMID 20129051.
- Pul U, Wurm R, Arslan Z, Geissen R, Hofmann N, Wagner R (March 2010). "Identification and characterization of E. coli CRISPR-cas promoters and their silencing by H-NS". Molecular Microbiology 75 (6): 1495â512. doi:10.1111/j.1365-2958.2010.07073.x. PMID 20132443.
- DÃez-VillaseÃ±or C, Almendros C, GarcÃa-MartÃnez J, Mojica FJ (May 2010). "Diversity of CRISPR loci in Escherichia coli". Microbiology (Reading, Engl.) 156 (Pt 5): 1351â61. doi:10.1099/mic.0.036046-0. PMID 20133361.
- Deveau H, Garneau JE, Moineau S (June 2010). "CRISPR/Cas System and Its Role in Phage-Bacteria Interactions". Annu Rev Microbiol 64: 475â93. doi:10.1146/annurev.micro.112408.134123. PMID 20528693.
- Koonin EV, Makarova KS (December 2009). "CRISPR-Cas: an adaptive immunity system in prokaryotes". F1000 Biol Rep 1: 95. doi:10.3410/B1-95. PMC 2884157. PMID 20556198.
- Touchon M, Rocha EP (2010). "The Small, Slow and Specialized CRISPR and Anti-CRISPR of Escherichia and Salmonella". In Randau, Lennart. PLoS ONE 5 (6): e11126. doi:10.1371/journal.pone.0011126. PMC 2886076. PMID 20559554.
- Rfam page for the CRISPR entries
This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
CRISPR associated protein Provide feedback
This domain forms an anti-parallel beta strand structure with flanking alpha helical regions.
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR010179
Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are a family of DNA direct repeats separated by regularly sized non-repetitive spacer sequences that are found in most bacterial and archaeal genomes [PUBMED:17442114]. CRISPRs appear to provide acquired resistance against bacteriophages, possibly acting with an RNA interference-like mechanism to inhibit gene functions of invasive DNA elements [PUBMED:17379808, PUBMED:16545108]. Differences in the number and type of spacers between CRISPR repeats correlate with phage sensitivity. It is thought that following phage infection, bacteria integrate new spacers derived from phage genomic sequences, and that the removal or addition of particular spacers modifies the phage-resistance phenotype of the cell. Therefore, the specificity of CRISPRs may be determined by spacer-phage sequence similarity.
In addition, there are many protein families known as CRISPR-associated sequences (Cas), which are encoded in the vicinity of CRISPR loci [PUBMED:16292354]. CRISPR/cas gene regions can be quite large, with up to 20 different, tandem-arranged cas genes next to a CRISPR cluster or filling the region between two repeat clusters. Cas genes and CRISPRs are found on mobile genetic elements such as plasmids, and have undergone extensive horizontal transfer. Cas proteins are thought to be involved in the propagation and functioning of CRISPRs. Some Cas proteins show similarity to helicases and repair proteins, although the functions of most are unknown. Cas families can be divided into subtypes according to operon organisation and phylogeny.
This entry represents the Cse3 (CRISPR/Cas Subtype Ecoli protein 3) family of Cas proteins. The Thermus thermophilus HB8 family member has been crystallised and found to have a structure consisting of two domains with opposing parallel beta-sheets, known as a beta-sheet platform [PUBMED:16672237]. This structure is similar to those found in the sex-lethal protein and poly(A)-binding protein and is consistent with an RNA-binding function.
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
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This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
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We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...
There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
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- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
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You can download (or view in your browser) a text representation of a Pfam alignment in various formats:
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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
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This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
|Number in seed:||50|
|Number in full:||667|
|Average length of the domain:||206.90 aa|
|Average identity of full alignment:||36 %|
|Average coverage of the sequence by the domain:||97.62 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||6|
|Download:||download the raw HMM for this family|
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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 domain across different species. More...
We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.
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 domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.
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 domain 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, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
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.
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the CRISPR_assoc domain has been found. There are 14 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
Loading structure mapping...