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62  structures 2346  species 0  interactions 3504  sequences 5  architectures

Family: CRISPR_Cas2 (PF09827)

Summary: CRISPR associated protein Cas2

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This is the Wikipedia entry entitled "CRISPR". More...

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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 Cas2 Provide feedback

This entry represents members of the family of Cas2, one of the first four protein families found to be associated with prokaryotic genomes containing multiple CRISPR elements. CRISPR systems protect against invasive nucleic acid sequences, including phage. Cas2 proteins have been characterised as either endoribonuclease (for ssRNA) or endodeoxyribonuclease (for dsDNA), depending on the system to which the Cas2 belongs [1,2]. The cas genes usually are found near the palindromic repeats. The structural subunit of Cas2, belongs to the VapD family of interferases. The interferase catalytic site is intact in the majority of the Cas2 proteins but is disrupted in some, and is not required for spacer acquisition [3,4]. This entry also includes the endoribonuclease VapD [5].

Literature references

  1. Barrangou R, Fremaux C, Deveau H, Richards M, Boyaval P, Moineau S, Romero DA, Horvath P; , Science. 2007;315:1709-1712.: CRISPR provides acquired resistance against viruses in prokaryotes. PUBMED:17379808 EPMC:17379808

  2. Beloglazova N, Brown G, Zimmerman MD, Proudfoot M, Makarova KS, Kudritska M, Kochinyan S, Wang S, Chruszcz M, Minor W, Koonin EV, Edwards AM, Savchenko A, Yakunin AF;, J Biol Chem. 2008;283:20361-20371.: A novel family of sequence-specific endoribonucleases associated with the clustered regularly interspaced short palindromic repeats. PUBMED:18482976 EPMC:18482976

  3. Koonin EV, Makarova KS;, Philos Trans R Soc Lond B Biol Sci. 2019;374:20180087.: Origins and evolution of CRISPR-Cas systems. PUBMED:30905284 EPMC:30905284

  4. Nunez JK, Kranzusch PJ, Noeske J, Wright AV, Davies CW, Doudna JA;, Nat Struct Mol Biol. 2014;21:528-534.: Cas1-Cas2 complex formation mediates spacer acquisition during CRISPR-Cas adaptive immunity. PUBMED:24793649 EPMC:24793649

  5. Kwon AR, Kim JH, Park SJ, Lee KY, Min YH, Im H, Lee I, Lee KY, Lee BJ;, Nucleic Acids Res. 2012;40:4216-4228.: Structural and biochemical characterization of HP0315 from Helicobacter pylori as a VapD protein with an endoribonuclease activity. PUBMED:22241770 EPMC:22241770


This tab holds annotation information from the InterPro database.

InterPro entry IPR019199

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 also includes the endoribonuclease VapD [ PUBMED:22241770 ]. These proteins are defined by a conserved region found at the N terminus of the VapD protein [ PUBMED:1398971 ].

This entry represents members of the family of Cas2, one of the first four protein families found to be associated with prokaryotic genomes containing multiple CRISPR elements. CRISPR systems protect against invasive nucleic acid sequences, including phage. Cas2 proteins have been characterised as either endoribonuclease (for ssRNA) or endodeoxyribonuclease (for dsDNA), depending on the system to which the Cas2 belongs [ PUBMED:18482976 ]. The cas genes usually are found near the palindromic repeats. It's worth noting that there is a distinct branch of the Cas2 family INTERPRO showing a very low level of sequence identity [ PUBMED:16292354 , PUBMED:22942283 ].

The structural subunit of Cas2, belongs to the VapD family of interferases. The interferase catalytic site is intact in the majority of the Cas2 proteins but is disrupted in some, and is not required for spacer acquisition [ PUBMED:30905284 , PUBMED:24793649 ].

Domain organisation

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Alignments

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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.

  Seed
(350)
Full
(3504)
Representative proteomes UniProt
(13995)
RP15
(699)
RP35
(2119)
RP55
(3588)
RP75
(5523)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

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Format an alignment

  Seed
(350)
Full
(3504)
Representative proteomes UniProt
(13995)
RP15
(699)
RP35
(2119)
RP55
(3588)
RP75
(5523)
Alignment:
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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.

  Seed
(350)
Full
(3504)
Representative proteomes UniProt
(13995)
RP15
(699)
RP35
(2119)
RP55
(3588)
RP75
(5523)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

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...

Trees

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.

Curation View help on the curation process

Seed source: COGs (COG3512)
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: COGs, Finn RD , Sammut SJ
Number in seed: 350
Number in full: 3504
Average length of the domain: 76.20 aa
Average identity of full alignment: 26 %
Average coverage of the sequence by the domain: 77.81 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 23.8 23.8
Trusted cut-off 23.8 23.8
Noise cut-off 23.7 23.7
Model length: 74
Family (HMM) version: 11
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
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Viroids Viroids Unclassified sequence Unclassified sequence

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Structures

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_Cas2 domain has been found. There are 62 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.

Protein Predicted structure External Information
P9WPJ3 View 3D Structure Click here
Q57831 View 3D Structure Click here