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29  structures 3940  species 0  interactions 5306  sequences 28  architectures

Family: DAC (PF02457)

Summary: DisA bacterial checkpoint controller nucleotide-binding

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DisA bacterial checkpoint controller nucleotide-binding Provide feedback

The DisA protein is a bacterial checkpoint protein that dimerises into an octameric complex. The protein consists of three distinct domains. This domain is the first and is a globular, nucleotide-binding region; the next 146-289 residues constitute the DisA-linker family, PF10635 that consists of an elongated bundle of three alpha helices (alpha-6, alpha-10, and alpha-11), one side of which carries an additional three helices (alpha7-9), which thus forms a spine like-linker between domains 1 and 3. The C-terminal residues, of domain 3, are represented by family HHH, PF00633 the specific DNA-binding domain. The octameric complex thus has structurally linked nucleotide-binding and DNA-binding HhH domains and the nucleotide-binding domains are bound to a cyclic di-adenosine phosphate such that DisA is a specific di-adenylate cyclase. This N-terminal domain has been identified as a diadenylate cyclase (DAC) responsible for producing c-di-AMP from two molecules of ATP [1]. The di-adenylate cyclase activity is strongly suppressed by binding to branched DNA, but not to duplex or single-stranded DNA, suggesting a role for DisA as a monitor of the presence of stalled replication forks or recombination intermediates via DNA structure-modulated c-di-AMP synthesis [2].

Literature references

  1. He J, Yin W, Galperin MY, Chou SH;, Nucleic Acids Res. 2020 Feb 25. pii: 5755; [Epub ahead of print]: Cyclic di-AMP, a second messenger of primary importance: tertiary structures and binding mechanisms. PUBMED:32095817 EPMC:32095817

  2. Witte G, Hartung S, Buttner K, Hopfner KP; , Mol Cell. 2008;30:167-178.: Structural biochemistry of a bacterial checkpoint protein reveals diadenylate cyclase activity regulated by DNA recombination intermediates. PUBMED:18439896 EPMC:18439896


This tab holds annotation information from the InterPro database.

InterPro entry IPR003390

Cyclic di-AMP (c-di-AMP) is a bacterial secondary messenger molecule, which is associated with various physiological functions. It is involved in several important cellular processes, such as cell wall metabolism, maintenance of DNA integrity, ion transport, transcription regulation, and allosteric regulation of enzyme function. The 120-amino acid-long diadenylate cyclase (DAC) domain converts two ATP or ADP molecules into one c-di-AMP molecule. The majority of DAC domain-containing proteins are found in bacterial species, but a small number are also present in archaea of the phylum Euryarchaeota. In bacteria, DAC domain proteins are most frequently found in Gram-positive bacteria belonging to the phyla Firmicutes and Actinobacteria, including pathogenic bacteria such as Listeria monocytogenes or Staphylococcus aureus . Compared with the majority of bacterial species which encode only one DAC enzyme, members of the genus Bacillus generally encode three DAC domain-containing proteins: DisA, CdaA (previously named YbbP in the genus Bacillus or DacA in other genera) and CdaS (previously named YojJ in the genus Bacillus or DacB in others) [ PUBMED:18439896 , PUBMED:25605729 , PUBMED:26441857 , PUBMED:26014055 , PUBMED:23812326 ].

The DAC domain exhibits an overall globular alpha/beta fold with the long N-terminally located helix (alpha1) flanking the core. A slightly twisted central beta-sheet, made up of seven mixed-parallel and antiparallel beta-strands, forms the core globular part. Both sides of the beta-sheets are flanked by a total of five alpha-helices (alpha1-alpha5), resulting in the observed globular shape [ PUBMED:18439896 , PUBMED:25605729 ].

The DisA protein is a bacterial checkpoint protein that dimerises into an octameric complex. The protein consists of three distinct domains. The DAC domain is the first and is a globular, nucleotide-binding region; the next 146-289 residues constitute the DisA-linker family, INTERPRO that consists of an elongated bundle of three alpha helices (alpha-6, alpha-10, and alpha-11), one side of which carries an additional three helices (alpha7-9), which thus forms a spine like-linker between domains 1 and 3. The C-terminal residues, of domain 3, are represented by family HHH, INTERPRO the specific DNA-binding domain. The octameric complex thus has structurally linked nucleotide-binding and DNA-binding HhH domains and the nucleotide-binding domains are bound to a cyclic di-adenosine phosphate such that DisA is a specific di-adenylate cyclase. The di-adenylate cyclase activity is strongly suppressed by binding to branched DNA, but not to duplex or single-stranded DNA, suggesting a role for DisA as a monitor of the presence of stalled replication forks or recombination intermediates via DNA structure-modulated c-di-AMP synthesis.

Domain organisation

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Alignments

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(502)
Full
(5306)
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(22476)
RP15
(827)
RP35
(2900)
RP55
(5435)
RP75
(8625)
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  Seed
(502)
Full
(5306)
Representative proteomes UniProt
(22476)
RP15
(827)
RP35
(2900)
RP55
(5435)
RP75
(8625)
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  Seed
(502)
Full
(5306)
Representative proteomes UniProt
(22476)
RP15
(827)
RP35
(2900)
RP55
(5435)
RP75
(8625)
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.

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Curation and family details

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Curation View help on the curation process

Seed source: Pfam-B_1846 (release 5.4)
Previous IDs: DUF147; DisA_N;
Type: Family
Sequence Ontology: SO:0100021
Author: Bateman A , Coggill P
Number in seed: 502
Number in full: 5306
Average length of the domain: 118.50 aa
Average identity of full alignment: 35 %
Average coverage of the sequence by the domain: 38.28 %

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 20.6 20.6
Trusted cut-off 20.6 20.6
Noise cut-off 20.5 20.5
Model length: 119
Family (HMM) version: 18
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
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 DAC domain has been found. There are 29 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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