Summary: CRISPR-associated protein Cse1 (CRISPR_cse1)
This is the Wikipedia entry entitled "CRISPR". More...
The Wikipedia text that you see displayed here is a download from Wikipedia. This means that the information we display is a copy of the information from the Wikipedia database. The button next to the article title ("Edit Wikipedia article") takes you to the edit page for the article directly within Wikipedia. You should be aware you are not editing our local copy of this information. Any changes that you make to the Wikipedia article will not be displayed here until we next download the article from Wikipedia. We currently download new content on a nightly basis.
Does Pfam agree with the content of the Wikipedia entry ?
Pfam has chosen to link families to Wikipedia articles. In some case we have created or edited these articles but in many other cases we have not made any direct contribution to the content of the article. The Wikipedia community does monitor edits to try to ensure that (a) the quality of article annotation increases, and (b) vandalism is very quickly dealt with. However, we would like to emphasise that Pfam does not curate the Wikipedia entries and we cannot guarantee the accuracy of the information on the Wikipedia page.
Editing Wikipedia articles
Before you edit for the first time
Wikipedia is a free, online encyclopedia. Although anyone can edit or contribute to an article, Wikipedia has some strong editing guidelines and policies, which promote the Wikipedia standard of style and etiquette. Your edits and contributions are more likely to be accepted (and remain) if they are in accordance with this policy.
You should take a few minutes to view the following pages:
How your contribution will be recorded
Anyone can edit a Wikipedia entry. You can do this either as a new user or you can register with Wikipedia and log on. When you click on the "Edit Wikipedia article" button, your browser will direct you to the edit page for this entry in Wikipedia. If you are a registered user and currently logged in, your changes will be recorded under your Wikipedia user name. However, if you are not a registered user or are not logged on, your changes will be logged under your computer's IP address. This has two main implications. Firstly, as a registered Wikipedia user your edits are more likely seen as valuable contribution (although all edits are open to community scrutiny regardless). Secondly, if you edit under an IP address you may be sharing this IP address with other users. If your IP address has previously been blocked (due to being flagged as a source of 'vandalism') your edits will also be blocked. You can find more information on this and creating a user account at Wikipedia.
If you have problems editing a particular page, contact us at firstname.lastname@example.org and we will try to help.
The community annotation is a new facility of the Pfam web site. If you have problems editing or experience problems with these pages please contact us.
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
CRISPR-associated protein Cse1 (CRISPR_cse1) Provide feedback
Clusters of short DNA repeats with non-homologous spacers, which are found at regular intervals in the genomes of phylogenetically distinct prokaryotic species, comprise a family with recognisable features. This family is known as CRISPR (short for Clustered, Regularly Interspaced Short Palindromic Repeats). A number of protein families appear only in association with these repeats and are designated Cas (CRISPR-Associated) proteins. This entry, represented by CT1972 from Chlorobaculum tepidum, is found in the CRISPR/Cas subtype Ecoli regions of many bacteria (most of which are mesophiles), and not in Archaea. It is designated Cse1.
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR013381
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 Cse1 family of Cas proteins, which includes CT1972 from Chlorobium tepidum [PUBMED:16292354]. These proteins are found in the CRISPR/Cas subtype Escherichia coli regions of many bacteria (most of which are mesophiles), and not in Archaea.
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
- the UniProt description of the protein sequence
- the number of residues in the sequence
- the Pfam graphic itself.
Loading domain graphics...
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- 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:
- Pfam viewer
- an HTML-based viewer that uses DAS to retrieve alignment fragments on request
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
If you find these logos useful in your own work, please consider citing the following article:
Note: You can also download the data file for the tree.
Curation and family details
|Author:||TIGRFAMs, Coggill P|
|Number in seed:||55|
|Number in full:||645|
|Average length of the domain:||456.40 aa|
|Average identity of full alignment:||33 %|
|Average coverage of the sequence by the domain:||89.10 %|
|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:||5|
|Download:||download the raw HMM for this family|
Weight segments by...
Change the size of the sunburst
selected sequences to HMM
a FASTA-format file
- 0 sequences
- 0 species
How the sunburst is generated
Colouring and labels
Anomalies in the taxonomy tree
Missing taxonomic levels
Unmapped species names
Too many species/sequences
The tree shows the occurrence of this domain across different species. More...
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
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_Cse1 domain has been found. There are 4 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...