disA [2017-05-21 19:49:07]

DNA integrity scanning protein, diadenylate cyclase, delays [SW|sporulation] in the case of chromosome damage, the DisA-dependent checkpoint arrests [SW|DNA replication] during B. subtilis spore outgrowth until the germinating spores genome is free of damage

locus: BSU00880

pI: 5.57

mw: 40.58 kDa

protein length: 360 aa

gene length: 1080 bp

function: control of [SW|sporulation] initiation

product: DNA integrity scanning protein, has diadenylate cyclase activity

essential: no

ec: 2.7.7.85

synonyms: yacK

Genomic Context

categories

• [category|SW 1|Cellular processes] → [category|SW 1.1|Cell envelope and cell division] → [category|SW 1.1.8|Cell division] → [category|SW 1.1.8.2|Other genes]
• [category|SW 2|Metabolism] → [category|SW 2.5|Nucleotide metabolism] → [category|SW 2.5.3|Metabolism of signalling nucleotides]
• [category|SW 4|Lifestyles] → [category|SW 4.2|Sporulation] → [category|SW 4.2.3|Sporulation/ other]
• [category|SW 4|Lifestyles] → [category|SW 4.3|Coping with stress] → [category|SW 4.3.1|General stress proteins (controlled by SigB)]
• [category|SW 4|Lifestyles] → [category|SW 4.3|Coping with stress] → [category|SW 4.3.2|Cell envelope stress proteins (controlled by SigM, V, W, X, Y)]
• [category|SW 4|Lifestyles] → [category|SW 4.3|Coping with stress] → [category|SW 4.3.4|Heat shock proteins]

Gene

Coordinates: 107,476 → 108,558

Phenotypes of a mutant

• a [gene|AFE2A9998219162FE32E95628B3CA9071099B61A|cdaA] [gene|2B091CCEE9E34D659771E39B1FC9050A145048AB|disA] double mutant or [gene|AFE2A9998219162FE32E95628B3CA9071099B61A|cdaA] [gene|92EF98B872C1AD729B0BFAD46D3FA572E9C2AA32|cdaS] [gene|2B091CCEE9E34D659771E39B1FC9050A145048AB|disA] triple mutant is not viable on complex medium; however, the mutant grows at low potassium concentration (0.1 mM) [pubmed|28420751]

The protein

Catalyzed reaction/ biological activity

• synthesis of c-di-AMP from two molecules of ATP [Pubmed|23192352,21566650]

Protein family

• disA family (according to Swiss-Prot)

[SW|Domains]

• contains a [SW|DAC domain] for the synthesis of c-di-AMP [Pubmed|18439896]

Effectors of protein activity

• [protein|151F226370D225776F3FE7EA4901485095F1AC45|RadA] is an inhibitor of [protein|2B091CCEE9E34D659771E39B1FC9050A145048AB|DisA] activity [Pubmed|23760274]
• the presence of potassium results in enhanced activity [pubmed|28420751]

Structure

• [PDB|3C23] [Pubmed|18439896]

[SW|Localization]

• see a [http://download.cell.com/mmcs/journals/0092-8674/PIIS0092867406005034.mmc12.avi video] showing the movement of DisA in the cell (in real time) [Pubmed|16713562]
• forms discrete globular foci in germinating spres that colocalize with the nucleoid [Pubmed|24244006]

additional information

• subject to Clp-dependent proteolysis upon glucose starvation [pubmed|17981983]

Expression and Regulation

Operons

• genes: [gene|908DB17A39D518E84977250C55825E77FA02E391|ctsR]-[gene|CA0939064E70A97434FA450A69E779FD89880613|mcsA]-[gene|7B1B664A1AE1F641E8E7D9E2894D5C8FFFA92948|mcsB]-[gene|86A2F2F65290F4471D6FD03B694821C66C180D8A|clpC]-[gene|151F226370D225776F3FE7EA4901485095F1AC45|radA]-[gene|2B091CCEE9E34D659771E39B1FC9050A145048AB|disA]
  description: [Pubmed|8793870]

  sigma factors

  • [protein|081DF3EE9FA56209D648C7677188C61CE3AA8E41|SigM]: sigma factor, [Pubmed|17434969], in [regulon|081DF3EE9FA56209D648C7677188C61CE3AA8E41|SigM regulon]
  • [protein|360F48D576DE950DF79C1A2677B7A35A8D8CC30C|SigA]: sigma factor, [Pubmed|8793870], in [regulon|360F48D576DE950DF79C1A2677B7A35A8D8CC30C|SigA regulon]
  • [protein|580011DE5DC40EC9E7E0512791D328FAA010DCB8|SigB]: sigma factor, [pubmed|8793870] [pubmed|11544224], in [regulon|580011DE5DC40EC9E7E0512791D328FAA010DCB8|SigB regulon]
  • [protein|CFF318EE6CACDEE763FBF96A2ABB46E944679AAA|SigF]: sigma factor, [Pubmed|16497325], in [regulon|CFF318EE6CACDEE763FBF96A2ABB46E944679AAA|SigF regulon]

  regulatory mechanism

  • [protein|908DB17A39D518E84977250C55825E77FA02E391|CtsR]: repression, [pubmed|9987115,11179229,16163393,17380125], in [regulon|908DB17A39D518E84977250C55825E77FA02E391|CtsR regulon]
  • [protein|2C6386E9A63F410558D168798D077DF91590F454|Spx]: activation, [pubmed|30962353], in [regulon|2C6386E9A63F410558D168798D077DF91590F454|Spx regulon]

  regulation

  • expressed during germination and spore outgrowth [Pubmed|24244006]
  • induction during diamide stress ([protein|2C6386E9A63F410558D168798D077DF91590F454|Spx]) [pubmed|30962353]

• genes: [gene|2B091CCEE9E34D659771E39B1FC9050A145048AB|disA]
  description: [Pubmed|17434969]

  regulation

  • expressed during germination and spore outgrowth [Pubmed|24244006]

Biological materials

Mutant

• MGNA-B932 (yacK::erm), available at the [https://shigen.nig.ac.jp/bsub/resource/strainGeneDisrupted/detail/1931 NBRP B. subtilis, Japan]
• GP2142 (''[gene|2B091CCEE9E34D659771E39B1FC9050A145048AB|disA]''::''tet''), available in [SW|Jörg Stülke]'s lab
• BKG2 (''[gene|151F226370D225776F3FE7EA4901485095F1AC45|radA]-[gene|2B091CCEE9E34D659771E39B1FC9050A145048AB|disA]::spc''), available in [SW|Jörg Stülke]'s lab
• 1A939 ( ''disA''::''tet''), [Pubmed|16713562], available at [http://pasture.asc.ohio-state.edu/BGSC/getdetail.cfm?bgscid=1A939&Search=1A939 BGSC]

Expression vector

• IPTG inducible expression of His-''disA'' in ''E. coli'': pGP2563 (in [http://biochem.web.utah.edu/hill/links/pET19b.pdf pET19b]), available in [SW|Jörg Stülke]'s lab

two-hybrid system

• B. pertussis adenylate cyclase-based bacterial two hybrid system ([SW|BACTH]), available in [SW|Fabian Commichau]'s lab

References

Reviews

• 22933559,18714086,25869574,23812326

Original publications

• 24244006,8793870,9987115,16713562,23760274,11544224,17434969,18439896,16713555,12493822,21566650,23192352,23608499,25616256,26014055,27150552,28420751,28511132