ID   DISA_MYCS2              Reviewed;         372 AA.
AC   A0R564;
DT   16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT   09-JAN-2007, sequence version 1.
DT   03-AUG-2022, entry version 97.
DE   RecName: Full=DNA integrity scanning protein DisA {ECO:0000255|HAMAP-Rule:MF_01438};
DE   AltName: Full=Cyclic-di-AMP synthase;
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};
GN   OrderedLocusNames=MSMEG_6080, MSMEI_5920;
OS   Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) (Mycobacterium
OS   smegmatis).
OC   Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC   Mycolicibacterium.
OX   NCBI_TaxID=246196;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 700084 / mc(2)155;
RA   Fleischmann R.D., Dodson R.J., Haft D.H., Merkel J.S., Nelson W.C.,
RA   Fraser C.M.;
RL   Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 700084 / mc(2)155;
RX   PubMed=17295914; DOI=10.1186/gb-2007-8-2-r20;
RA   Deshayes C., Perrodou E., Gallien S., Euphrasie D., Schaeffer C.,
RA   Van-Dorsselaer A., Poch O., Lecompte O., Reyrat J.-M.;
RT   "Interrupted coding sequences in Mycobacterium smegmatis: authentic
RT   mutations or sequencing errors?";
RL   Genome Biol. 8:R20.1-R20.9(2007).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 700084 / mc(2)155;
RX   PubMed=18955433; DOI=10.1101/gr.081901.108;
RA   Gallien S., Perrodou E., Carapito C., Deshayes C., Reyrat J.-M.,
RA   Van Dorsselaer A., Poch O., Schaeffer C., Lecompte O.;
RT   "Ortho-proteogenomics: multiple proteomes investigation through orthology
RT   and a new MS-based protocol.";
RL   Genome Res. 19:128-135(2009).
RN   [4]
RP   FUNCTION, CATALYTIC ACTIVITY, OPERON STRUCTURE, ACTIVITY REGULATION,
RP   INTERACTION WITH RADA, AND MUTAGENESIS OF ASP-84 AND HIS-137.
RC   STRAIN=ATCC 700084 / mc(2)155;
RX   PubMed=23760274; DOI=10.1074/jbc.m113.464883;
RA   Zhang L., He Z.G.;
RT   "Radiation-sensitive gene A (RadA) targets DisA, DNA integrity scanning
RT   protein A, to negatively affect cyclic di-AMP synthesis activity in
RT   Mycobacterium smegmatis.";
RL   J. Biol. Chem. 288:22426-22436(2013).
CC   -!- FUNCTION: Participates in a DNA-damage check-point. DisA forms globular
CC       foci that rapidly scan along the chromosomes searching for lesions.
CC       {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). c-di-AMP
CC       likely acts as a signaling molecule that may couple DNA integrity with
CC       a cellular process. {ECO:0000255|HAMAP-Rule:MF_01438,
CC       ECO:0000269|PubMed:23760274}.
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         ECO:0000269|PubMed:23760274};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000255|HAMAP-Rule:MF_01438};
CC   -!- ACTIVITY REGULATION: Diadenylate cyclase activity is inhibited by the
CC       interaction with RadA. {ECO:0000269|PubMed:23760274}.
CC   -!- SUBUNIT: Homooctamer (By similarity). Interacts with RadA; this
CC       interaction leads to the inhibition of the diadenylate cyclase activity
CC       of DisA. {ECO:0000255|HAMAP-Rule:MF_01438,
CC       ECO:0000269|PubMed:23760274}.
CC   -!- INDUCTION: Forms part of an operon with radA.
CC   -!- MISCELLANEOUS: Overexpression of DisA leads to cell expansion, induces
CC       cell aggregation, and inhibits bacterial growth and motility;
CC       coexpression of RadA rescues these abnormal phenotypes.
CC       {ECO:0000305|PubMed:23760274}.
CC   -!- SIMILARITY: Belongs to the DisA family. {ECO:0000255|HAMAP-
CC       Rule:MF_01438}.
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DR   EMBL; CP000480; ABK75799.1; -; Genomic_DNA.
DR   EMBL; CP001663; AFP42353.1; -; Genomic_DNA.
DR   RefSeq; WP_011731023.1; NZ_SIJM01000046.1.
DR   RefSeq; YP_890302.1; NC_008596.1.
DR   AlphaFoldDB; A0R564; -.
DR   SMR; A0R564; -.
DR   STRING; 246196.MSMEI_5920; -.
DR   PRIDE; A0R564; -.
DR   EnsemblBacteria; ABK75799; ABK75799; MSMEG_6080.
DR   EnsemblBacteria; AFP42353; AFP42353; MSMEI_5920.
DR   GeneID; 66737364; -.
DR   KEGG; msg:MSMEI_5920; -.
DR   KEGG; msm:MSMEG_6080; -.
DR   PATRIC; fig|246196.19.peg.5918; -.
DR   eggNOG; COG1623; Bacteria.
DR   OMA; VVRDYVP; -.
DR   OrthoDB; 1139866at2; -.
DR   Proteomes; UP000000757; Chromosome.
DR   Proteomes; UP000006158; 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; IPR041663; DisA/LigA_HHH.
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   Pfam; PF12826; HHH_2; 1.
DR   SUPFAM; SSF143597; SSF143597; 1.
DR   SUPFAM; SSF47781; SSF47781; 1.
DR   PROSITE; PS51794; DAC; 1.
PE   1: Evidence at protein level;
KW   ATP-binding; DNA damage; DNA repair; DNA-binding; Magnesium; Manganese;
KW   Nucleotide-binding; Nucleotidyltransferase; Reference proteome;
KW   Transferase.
FT   CHAIN           1..372
FT                   /note="DNA integrity scanning protein DisA"
FT                   /id="PRO_0000424181"
FT   DOMAIN          18..156
FT                   /note="DAC"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01130"
FT   BINDING         85
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01438"
FT   BINDING         103
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01438"
FT   BINDING         116..120
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01438"
FT   MUTAGEN         84
FT                   /note="D->A: Loss of enzymatic activity."
FT                   /evidence="ECO:0000269|PubMed:23760274"
FT   MUTAGEN         137
FT                   /note="H->A: Loss of enzymatic activity."
FT                   /evidence="ECO:0000269|PubMed:23760274"
SQ   SEQUENCE   372 AA;  40512 MW;  2D5CAD97E0596627 CRC64;
     MAVKSGARSG RNVVHLARPT LRETLGRLAP GTPLRDGLER ILRGRTGALI VLGYDDSVEA
     ICDGGFVLDV RYAPTRLREL SKMDGAVVLS SDGSRILRAN VQLVPDPSIP TDESGTRHRS
     AERTAIQTGY PVISVSHSMS IVTVYVAGER HVVPDSATIL SRANQTIATL ERYKGRLDEV
     SRQLSTAEIE DFVTLRDVMT VVQRLEMVRR ISLEIDADVV ELGTDGRQLK LQLDELVGDN
     ETARELIVRD YHANPDPPTA AQVAATLEEL DSLSDSELLD FTVLARVFGY PSTAEAQDSA
     MSSRGYRAMA AIPRLQFAHV DLLVRSFGSL QNLLAASADD LQSVDGIGSM WARHIREGLS
     LLAESTIADR LA