DISA_CLOD6
ID DISA_CLOD6 Reviewed; 356 AA.
AC Q18CB2;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 25-JUL-2006, sequence version 1.
DT 03-AUG-2022, entry version 93.
DE RecName: Full=DNA integrity scanning protein DisA {ECO:0000255|HAMAP-Rule:MF_01438};
DE AltName: Full=Cyclic di-AMP synthase {ECO:0000255|HAMAP-Rule:MF_01438};
DE Short=c-di-AMP synthase {ECO:0000255|HAMAP-Rule:MF_01438};
DE AltName: Full=Diadenylate cyclase {ECO:0000255|HAMAP-Rule:MF_01438};
DE EC=2.7.7.85 {ECO:0000255|HAMAP-Rule:MF_01438};
GN Name=disA {ECO:0000255|HAMAP-Rule:MF_01438}; OrderedLocusNames=CD630_00280;
OS Clostridioides difficile (strain 630) (Peptoclostridium difficile).
OC Bacteria; Firmicutes; Clostridia; Eubacteriales; Peptostreptococcaceae;
OC Clostridioides.
OX NCBI_TaxID=272563;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=630;
RX PubMed=16804543; DOI=10.1038/ng1830;
RA Sebaihia M., Wren B.W., Mullany P., Fairweather N.F., Minton N.,
RA Stabler R., Thomson N.R., Roberts A.P., Cerdeno-Tarraga A.M., Wang H.,
RA Holden M.T.G., Wright A., Churcher C., Quail M.A., Baker S., Bason N.,
RA Brooks K., Chillingworth T., Cronin A., Davis P., Dowd L., Fraser A.,
RA Feltwell T., Hance Z., Holroyd S., Jagels K., Moule S., Mungall K.,
RA Price C., Rabbinowitsch E., Sharp S., Simmonds M., Stevens K., Unwin L.,
RA Whithead S., Dupuy B., Dougan G., Barrell B., Parkhill J.;
RT "The multidrug-resistant human pathogen Clostridium difficile has a highly
RT mobile, mosaic genome.";
RL Nat. Genet. 38:779-786(2006).
RN [2]
RP FUNCTION.
RX PubMed=25965978; DOI=10.1021/jacs.5b00275;
RA Kellenberger C.A., Chen C., Whiteley A.T., Portnoy D.A., Hammond M.C.;
RT "RNA-based fluorescent biosensors for live cell imaging of second messenger
RT cyclic di-AMP.";
RL J. Am. Chem. Soc. 137:6432-6435(2015).
CC -!- FUNCTION: Participates in a DNA-damage check-point that is active prior
CC to asymmetric division when DNA is damaged. DisA forms globular foci
CC that rapidly scan along the chromosomes during sporulation, searching
CC for lesions. When a lesion is present, DisA pauses at the lesion site.
CC This triggers a cellular response that culminates in a temporary block
CC in sporulation initiation. {ECO:0000255|HAMAP-Rule:MF_01438}.
CC -!- FUNCTION: Has also diadenylate cyclase activity, catalyzing the
CC condensation of 2 ATP molecules into cyclic di-AMP (c-di-AMP)
CC (PubMed:25965978). c-di-AMP acts as a signaling molecule that couples
CC DNA integrity with progression of sporulation. The rise in c-di-AMP
CC level generated by DisA while scanning the chromosome, operates as a
CC positive signal that advances sporulation; upon encountering a lesion,
CC the DisA focus arrests at the damaged site and halts c-di-AMP
CC synthesis. {ECO:0000255|HAMAP-Rule:MF_01438,
CC ECO:0000269|PubMed:25965978}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 ATP = 3',3'-c-di-AMP + 2 diphosphate; Xref=Rhea:RHEA:35655,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:71500; EC=2.7.7.85;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01438};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01438};
CC -!- SUBUNIT: Homooctamer. {ECO:0000255|HAMAP-Rule:MF_01438}.
CC -!- SIMILARITY: Belongs to the DisA family. {ECO:0000255|HAMAP-
CC Rule:MF_01438}.
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DR EMBL; AM180355; CAJ66842.1; -; Genomic_DNA.
DR RefSeq; WP_004453975.1; NZ_CP010905.2.
DR RefSeq; YP_001086491.1; NC_009089.1.
DR AlphaFoldDB; Q18CB2; -.
DR SMR; Q18CB2; -.
DR STRING; 272563.CD630_00280; -.
DR EnsemblBacteria; CAJ66842; CAJ66842; CD630_00280.
DR GeneID; 66352524; -.
DR KEGG; cdf:CD630_00280; -.
DR KEGG; pdc:CDIF630_00090; -.
DR PATRIC; fig|272563.120.peg.32; -.
DR eggNOG; COG1623; Bacteria.
DR OMA; VVRDYVP; -.
DR PhylomeDB; Q18CB2; -.
DR BioCyc; PDIF272563:G12WB-80-MON; -.
DR Proteomes; UP000001978; Chromosome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0106408; F:diadenylate cyclase activity; IEA:UniProtKB-EC.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-UniRule.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-UniRule.
DR GO; GO:0019932; P:second-messenger-mediated signaling; IEA:UniProtKB-UniRule.
DR Gene3D; 1.20.1260.110; -; 1.
DR Gene3D; 3.40.1700.10; -; 1.
DR HAMAP; MF_01438; DisA; 1.
DR InterPro; IPR038331; DisA_sf.
DR InterPro; IPR036888; DNA_integrity_DisA_N_sf.
DR InterPro; IPR018906; DNA_integrity_scan_DisA_link.
DR InterPro; IPR003390; DNA_integrity_scan_DisA_N.
DR InterPro; IPR023763; DNA_integrity_scanning_protein.
DR InterPro; IPR010994; RuvA_2-like.
DR Pfam; PF02457; DAC; 1.
DR Pfam; PF10635; DisA-linker; 1.
DR SUPFAM; SSF143597; SSF143597; 1.
DR SUPFAM; SSF47781; SSF47781; 1.
DR PROSITE; PS51794; DAC; 1.
PE 3: Inferred from homology;
KW ATP-binding; DNA damage; DNA repair; DNA-binding; Magnesium;
KW Nucleotide-binding; Nucleotidyltransferase; Reference proteome;
KW Transferase.
FT CHAIN 1..356
FT /note="DNA integrity scanning protein DisA"
FT /id="PRO_1000017367"
FT DOMAIN 7..147
FT /note="DAC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01130"
FT BINDING 74
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01438"
FT BINDING 92
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01438"
FT BINDING 105..109
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01438"
SQ SEQUENCE 356 AA; 40369 MW; F2DBAF4E4DE386AA CRC64;
MENFLDNKNM LYALKMISPG TPLRLGLNNV LRAKTGGLIV IATNEDVMKI VDGGFAINAE
YSPSYLYELA KMDGAIVLSG DVKKILFANA QLIPDYFIET SETGTRHRTA ERVAKQTGAI
VIGISQRRNV ITVYRGNEKY VVEDISKIFT KANQAIQTLE KYKTVLDQAV TNLNALEFND
LVTIYDVALV MQKMEMVMRV TSIIEKYVIE LGDEGTLVSM QLEELMGTTR IDQKLIFKDY
NKENTEIKEL MKKVKNLNSE ELIELVNMAK LLGYSGFSES MDMPIKTRGY RILSKIHRLP
TAIIENLVNY FENFQQILDA SIEELDEVEG IGEIRATYIK NGLIKMKQLV LLDRHI
