Summary: CRISPR associated protein Cas1
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|CRISPR-associated protein 1|
CRISPR-associated protein 1 (cas1) is one of the two universally conserved proteins found in the CRISPR prokaryotic immune defense system. Cas1 is a metal-dependent DNA-specific endonuclease that produces double-stranded DNA fragments. Cas1 forms a stable complex with the other universally conserved CRISPR-associated protein, cas2, which is essential to spacer acquisition for CRISPR systems.
In July 2017, researchers led by Jennifer Doudna from the University of California at Berkeley, in Berkeley, California, using electron microscopy and X-ray crystallography, at the Advanced Light Source at Lawrence Berkeley National Laboratory, the Stanford Linear Accelerator Center, and the HHMI electron microscope facility at UC Berkeley, discovered how Cas1-Cas2, the proteins responsible for the ability of the CRISPR immune system (CRISPR means: clustered regularly interspaced short palindromic repeats) in bacteria to adapt to new viral infections, identify the site in the genome where they insert viral DNA so they can recognize it later and mount an attack. A protein called IHF plays a crucial role in this process. Scientists also discovered that Cas-1 inhibits Cas-2/3 enzymatic activity as a nuclease and in the same discussion postulated that Cas1-Cas2 had an evolutionary origin as a toxin-antitoxin complex. This could result in a change in the evolutionary model of the Cas1-Cas2 complex.
- Wiedenheft B, Zhou K, Jinek M, Coyle SM, Ma W, Doudna JA (2009). "Structural basis for DNase activity of a conserved protein implicated in CRISPR-mediated genome defense". Structure. 17 (6): 904â€“12. doi:10.1016/j.str.2009.03.019. PMIDÂ 19523907.
- NuÃ±ez JK, Kranzusch PJ, Noeske J, Wright AV, Davies CW, Doudna JA (2014). "Cas1-Cas2 complex formation mediates spacer acquisition during CRISPR-Cas adaptive immunity". Nat. Struct. Mol. Biol. 21 (6): 528â€“34. doi:10.1038/nsmb.2820. PMCÂ 4075942. PMIDÂ 24793649.
- "Researchers discover how CRISPR proteins find their target". 20 July 2017.
- Rollins, MaryClare F.; Chowdhury, Saikat; Carter, Joshua; Golden, Sarah M.; Wilkinson, Royce A.; Bondy-Denomy, Joseph; Lander, Gabriel C.; Wiedenheft, Blake (24 April 2017). "Cas1 and the Csy complex are opposing regulators of Cas2/3 nuclease activity". Proceedings of the National Academy of Sciences. 114 (26): E5113â€“E5121. doi:10.1073/pnas.1616395114. PMCÂ 5495223. PMIDÂ 28438998.
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 Cas1 Provide feedback
Clustered regularly interspaced short palindromic repeats (CRISPRs) are a family of DNA direct repeats found in many prokaryotic genomes. This family of proteins corresponds to Cas1, a CRISPR-associated protein. Cas1 may be involved in linking DNA segments to CRISPR .
Haft DH, Selengut J, Mongodin EF, Nelson KE; , PLoS Comput Biol. 2005;1:e60.: A guild of 45 CRISPR-associated (Cas) protein families and multiple CRISPR/Cas subtypes exist in prokaryotic genomes. PUBMED:16292354 EPMC:16292354
Bolotin A, Quinquis B, Sorokin A, Ehrlich SD; , Microbiology. 2005;151:2551-2561.: Clustered regularly interspaced short palindrome repeats (CRISPRs) have spacers of extrachromosomal origin. PUBMED:16079334 EPMC:16079334
This tab holds annotation information from the InterPro database.
InterPro entry IPR002729
The CRISPR-Cas system is a prokaryotic defense mechanism against foreign genetic elements. The key elements of this defense system are the Cas proteins and the CRISPR RNA.
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 mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain sequences complementary to antecedent mobile elements and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA).
The defense reaction is divided into three stages. In the adaptation stage, the invader DNA is cleaved, and a piece of it is selected to be integrated as a new spacer into the CRISPR locus, where it is stored as an identity tag for future attacks by this invader. During the second stage (the expression stage), the CRISPR RNA (pre-crRNA) is transcribed and subsequently processed into the mature crRNAs. In the third stage (the interference stage), Cas proteins, together with crRNAs, identify and degrade the invader [ PUBMED:17379808 , PUBMED:16545108 , PUBMED:21699496 ].
The CRISPR-Cas systems have been sorted into three major classes. In CRISPR-Cas types I and III, the mature crRNA is generally generated by a member of the Cas6 protein family. Whereas in system III the Cas6 protein acts alone, in some class I systems it is part of a complex of Cas proteins known as Cascade (CRISPR-associated complex for antiviral defense). The Cas6 protein is an endoribonuclease necessary for crRNA production whereas the additional Cas proteins that form the Cascade complex are needed for crRNA stability [ PUBMED:24459147 ].
This entry represents Cas1, which is a metal-dependent DNA-specific endonuclease [ PUBMED:19523907 ]. Cas1 may play a role in the recognition, cleavage, and/or integration of foreign nucleic acids into CRISPRs.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||metal ion binding (GO:0046872)|
|endonuclease activity (GO:0004519)|
|nucleic acid binding (GO:0003676)|
|Biological process||maintenance of CRISPR repeat elements (GO:0043571)|
|defense response to virus (GO:0051607)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
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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.
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|Seed source:||Enright A|
|Author:||Enright A , Ouzounis C , Bateman A|
|Number in seed:||339|
|Number in full:||4827|
|Average length of the domain:||234.00 aa|
|Average identity of full alignment:||21 %|
|Average coverage of the sequence by the domain:||73.78 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||19|
|Download:||download the raw HMM for this family|
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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:
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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.
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The tree shows the occurrence of this domain across different species. More...
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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.
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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 Cas_Cas1 domain has been found. There are 209 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 sequence.
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AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.