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9  structures 348  species 0  interactions 464  sequences 3  architectures

Family: Cas_Cas6 (PF01881)

Summary: CRISPR associated protein Cas6

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CRISPR associated protein Cas6 Provide feedback

This group of families is one of several protein families that are always found associated with prokaryotic CRISPRs, themselves a family of clustered regularly interspaced short palindromic repeats, DNA repeats found in nearly half of all bacterial and archaeal genomes. These DNA repeat regions have a remarkably regular structure: unique sequences of constant size, called spacers, sit between each pair of repeats [1]. It has been shown that the CRISPRs are virus-derived sequences acquired by the host to enable them to resist viral infection. The Cas proteins from the host use the CRISPRs to mediate an antiviral response. After transcription of the CRISPR, a complex of Cas proteins termed Cascade cleaves a CRISPR RNA precursor in each repeat and retains the cleavage products containing the virus-derived sequence. Assisted by the helicase Cas3, these mature CRISPR RNAs then serve as small guide RNAs that enable Cascade to interfere with virus proliferation [2]. Cas5 contains an endonuclease motif, whose inactivation leads to loss of resistance, even in the presence of phage-derived spacers [3].

Literature references

  1. 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

  2. Brouns SJ, Jore MM, Lundgren M, Westra ER, Slijkhuis RJ, Snijders AP, Dickman MJ, Makarova KS, Koonin EV, van der Oost J;, Science. 2008;321:960-964.: Small CRISPR RNAs guide antiviral defense in prokaryotes. PUBMED:18703739 EPMC:18703739

  3. Sorek R, Kunin V, Hugenholtz P;, Nat Rev Microbiol. 2008;6:181-186.: CRISPR--a widespread system that provides acquired resistance against phages in bacteria and archaea. PUBMED:18157154 EPMC:18157154


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR010156

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 a broadly distributed, highly divergent Cas family, as represented by TM1814 from Thermotoga maritima. TM1814 contains a C-terminal motif GXGXXXXXGXG, where the each X between two Gly is hydrophobic and the spacer XXXXX contains (usually) one Arg or Lys. Members of this protein family are found associated with several different CRISPR/cas system subtypes, and consequently it has been designated Cas6. Cas6 is found within a cluster of three cas genes associated with CRISPR structures in many bacterial species, named cas1B, cas5 and cas6 [PUBMED:16079334].

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan RAMPS-Cas5-like (CL0362), which has the following description:

This group of families is one of several protein families that are always found associated with prokaryotic CRISPRs, themselves a family of clustered regularly interspaced short palindromic repeats, DNA repeats found in nearly half of all bacterial and archaeal genomes. These DNA repeat regions have a remarkably regular structure: unique sequences of constant size, called spacers, sit between each pair of repeats [1]. It has been shown that the CRISPRs are virus-derived sequences acquired by the host to enable them to resist viral infection. The Cas proteins from the host use the CRISPRs to mediate an antiviral response. After transcription of the CRISPR, a complex of Cas proteins termed Cascade cleaves a CRISPR RNA precursor in each repeat and retains the cleavage products containing the virus-derived sequence. Assisted by the helicase Cas3, these mature CRISPR RNAs then serve as small guide RNAs that enable Cascade to interfere with virus proliferation [2]. Cas5 contains an endonuclease motif, whose inactivation leads to loss of resistance, even in the presence of phage-derived spacers [3].

The clan contains the following 7 members:

Cas6 Cas_Cas5d Cas_Cas6 Cas_Cmr3 CRISPR_assoc DUF2276 RAMPs

Alignments

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...

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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
(46)
Full
(464)
Representative proteomes NCBI
(474)
Meta
(12)
RP15
(73)
RP35
(128)
RP55
(169)
RP75
(200)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(46)
Full
(464)
Representative proteomes NCBI
(474)
Meta
(12)
RP15
(73)
RP35
(128)
RP55
(169)
RP75
(200)
Alignment:
Format:
Order:
Sequence:
Gaps:
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Download options

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
(46)
Full
(464)
Representative proteomes NCBI
(474)
Meta
(12)
RP15
(73)
RP35
(128)
RP55
(169)
RP75
(200)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   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.

External links

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.

Pfam alignments:

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: Enright A
Previous IDs: DUF57;
Type: Family
Author: Enright A, Ouzounis C, Bateman A
Number in seed: 46
Number in full: 464
Average length of the domain: 148.10 aa
Average identity of full alignment: 20 %
Average coverage of the sequence by the domain: 61.04 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 23.6 23.6
Trusted cut-off 23.7 23.7
Noise cut-off 23.4 23.5
Model length: 155
Family (HMM) version: 11
Download: download the raw HMM for this family

Species distribution

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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 Cas_Cas6 domain has been found. There are 9 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.

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