Homologous Superfamily

DNA integrity scanning protein, DisA, N-terminal domain superfamily (IPR036888)

Short name: DNA_integrity_DisA_N_sf

Overlapping entries


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) [PMID: 18439896, PMID: 25605729, PMID: 26441857, PMID: 26014055, PMID: 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 [PMID: 18439896, PMID: 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, IPR018906 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, IPR000445 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.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.