{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P37573","uniProtkbId":"DISA_BACSU","entryAudit":{"firstPublicDate":"1994-10-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"1994-10-01","entryVersion":157,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Bacillus subtilis (strain 168)","taxonId":224308,"lineage":["Bacteria","Bacillati","Bacillota","Bacilli","Caryophanales","Bacillaceae","Bacillus"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000255","source":"HAMAP-Rule","id":"MF_01438"}],"value":"DNA integrity scanning protein DisA"}},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000255","source":"HAMAP-Rule","id":"MF_01438"}],"value":"Cyclic di-AMP synthase"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000255","source":"HAMAP-Rule","id":"MF_01438"}],"value":"c-di-AMP synthase"}]},{"fullName":{"value":"DNA integrity scanning protein A"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000255","source":"HAMAP-Rule","id":"MF_01438"}],"value":"Diadenylate cyclase"},"shortNames":[{"value":"DAC"}],"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000255","source":"HAMAP-Rule","id":"MF_01438"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18439896"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34073022"}],"value":"2.7.7.85"}]}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000255","source":"HAMAP-Rule","id":"MF_01438"}],"value":"disA"},"synonyms":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"9141693"}],"value":"comY"},{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"9141693"}],"value":"orf6"},{"value":"yacK"}],"orderedLocusNames":[{"value":"BSU00880"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16713562"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21566650"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22211522"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26240071"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34073022"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9141693"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"34073022"}],"value":"Participates in a DNA-damage check-point that is active prior to asymmetric division when DNA is damaged (PubMed:16713562, PubMed:9141693). Forms globular foci that rapidly scan along the chromosomes during sporulation, searching for lesions. Its ability to scan through the chromosome rapidly is due to its non-specific DNA-binding. When a lesion is present, DisA pauses at the lesion site (PubMed:21566650). This triggers a cellular response that culminates in a temporary block in sporulation initiation. It is required, at least partially, to inhibit the activity of the transcription factor spo0A, which controls, among others, early sporulation genes. In B.subtilis c-di-AMP is a second messenger that mediates growth, DNA repair and cell wall homeostasis (PubMed:22211522); it is toxic when present in excess (PubMed:26240071). Limits the replication fork reggression activity of RecG; DisA inhibits the ATPase activity of RecG (PubMed:34073022). By limiting RecG-mediated fork regression, DisA provides time for removal of potentially lethal DNA lesions (Probable) (PubMed:34073022)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18439896"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23192352"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25616256"}],"value":"One of 3 paralogous diadenylate cyclases (DAC) in this bacteria (PubMed:23192352). Has diadenylate cyclase activity, catalyzing the condensation of 2 ATP molecules into cyclic di-AMP (c-di-AMP) (PubMed:18439896, PubMed:25616256). c-di-AMP acts as a signaling molecule that couples DNA integrity with progression of sporulation. The rise in c-di-AMP level generated by DisA while scanning the chromosome operates as a positive signal that advances sporulation; upon encountering a lesion, the DisA focus arrests at the damaged site and halts c-di-AMP synthesis. Does not convert GTP to c-di-GMP (PubMed:18439896)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"2 ATP = 3',3'-c-di-AMP + 2 diphosphate","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:35655"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:33019"},{"database":"ChEBI","id":"CHEBI:71500"}],"ecNumber":"2.7.7.85","evidences":[{"evidenceCode":"ECO:0000255","source":"HAMAP-Rule","id":"MF_01438"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18439896"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34073022"}]}},{"commentType":"COFACTOR","cofactors":[{"name":"Mg(2+)","evidences":[{"evidenceCode":"ECO:0000255","source":"HAMAP-Rule","id":"MF_01438"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18439896"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:18420"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"A0R564"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18439896"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34073022"}],"value":"Diadenylate cyclase (DAC) activity is inhibited 2-fold by Holliday junction (HJ) DNA, further addition of RecG inhibits DAC activity 11-fold; RecG may relocate DisA from the HJ (PubMed:34073022). DAC is inhibited by the interaction with RadA (By similarity). Diadenylate cyclase activity is not affected by ssDNA or dsDNA, but three- and four-way junctions strongly inhibit the activity of DisA, suggesting the enzyme is regulated by branched nucleic acids (PubMed:18439896)"}],"commentType":"ACTIVITY REGULATION"},{"commentType":"BIOPHYSICOCHEMICAL PROPERTIES","kineticParameters":{"michaelisConstants":[{"constant":151.0,"unit":"uM","substrate":"ATP","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34073022"}]}],"note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34073022"}],"value":"kcat is 0.84 sec(-1) (PubMed:34073022)."}]}}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18439896"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23760274"}],"value":"Homooligomer (PubMed:18439896). Interacts with RadA (PubMed:23760274)"}],"commentType":"SUBUNIT"},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21566650"}],"value":"Present in a puncate pattern at 1.5 hours after sporulation onset, does not co-localize with c-di-AMP phosphodiesterase GdpP"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21566650"}],"value":"Cytoplasm","id":"SL-0086"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16713562"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17434969"}],"value":"Expression increases during late exponential phase and at the onset of sporulation (PubMed:16713562). Transcribed under partial control of SigM ECF sigma factor (PubMed:17434969)"}],"commentType":"INDUCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34073022"}],"value":"The C-terminal domain (residues 290-360) is required for DNA binding and to inhibit the ATPase activity of RecG (PubMed:34073022)"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21566650"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23192352"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25616256"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9141693"}],"value":"Decreases c-di-AMP levels in mid-exponential phase from about 3.8 uM to about 2.8 uM in strain BG214 (PubMed:25616256). No change in sensitivity to methyl methanesulfonate (MMS), decreased survival after UV irradiation in transition and stationary phase, strong decrease in competence (PubMed:9141693). Cells lacking this gene show a reduced c-di-AMP level compared to wild-type and cannot properly trigger the DNA damage response (PubMed:21566650). No effect on antibiotic sensitivity to the beta-lactam antibiotic cefuroxime (CEF), upon overexpression of the c-di-AMP phosphodiesterase GdpP increased sensitivity to CEF (PubMed:22211522). Double disA-cdaA mutants cannot be made, suggesting they are lethal, while double disA-cdaS and cdaA-cdaS mutants are viable (PubMed:22211522, PubMed:23192352). Depletion of cdaA in double disA-cdaA deletion cells leads to cell lysis (PubMed:22211522). Exponentially growing cells are 100-fold more sensitive to MMS, no change in response to H(2)O(2) or nalidixic acid; a double disA-radA deletion suppresses H(2)O(2) sensitivity of the radA mutant, but has no effect on MMS sensitivity, suggesting radA and disA might work in the same DNA repair pathway (PubMed:25616256)"}],"commentType":"DISRUPTION PHENOTYPE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000255","source":"HAMAP-Rule","id":"MF_01438"}],"value":"Belongs to the DisA family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":360,"modifier":"EXACT"}},"description":"DNA integrity scanning protein DisA","featureId":"PRO_0000049450"},{"type":"Domain","location":{"start":{"value":11,"modifier":"EXACT"},"end":{"value":149,"modifier":"EXACT"}},"description":"DAC","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU01130"}]},{"type":"Binding site","location":{"start":{"value":78,"modifier":"EXACT"},"end":{"value":78,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:30616"}],"evidences":[{"evidenceCode":"ECO:0000255","source":"HAMAP-Rule","id":"MF_01438"}],"ligand":{"name":"ATP","id":"ChEBI:CHEBI:30616"}},{"type":"Binding site","location":{"start":{"value":96,"modifier":"EXACT"},"end":{"value":96,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:30616"}],"evidences":[{"evidenceCode":"ECO:0000255","source":"HAMAP-Rule","id":"MF_01438"}],"ligand":{"name":"ATP","id":"ChEBI:CHEBI:30616"}},{"type":"Binding site","location":{"start":{"value":109,"modifier":"EXACT"},"end":{"value":113,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:30616"}],"evidences":[{"evidenceCode":"ECO:0000255","source":"HAMAP-Rule","id":"MF_01438"}],"ligand":{"name":"ATP","id":"ChEBI:CHEBI:30616"}},{"type":"Mutagenesis","location":{"start":{"value":77,"modifier":"EXACT"},"end":{"value":77,"modifier":"EXACT"}},"description":"Loss of enzymatic activity. 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