DISA_MYCTU
ID DISA_MYCTU Reviewed; 358 AA.
AC P9WNW5; F2GJT2; O53571; Q7D584;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 44.
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}; Synonyms=dacA;
GN OrderedLocusNames=Rv3586;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBSTRATE SPECIFICITY, SUBUNIT,
RP DOMAIN, PH DEPENDENCE, AND MUTAGENESIS OF GLY-73 AND 105-ARG--ARG-107.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=22529992; DOI=10.1371/journal.pone.0035206;
RA Bai Y., Yang J., Zhou X., Ding X., Eisele L.E., Bai G.;
RT "Mycobacterium tuberculosis Rv3586 (DacA) is a diadenylate cyclase that
RT converts ATP or ADP into c-di-AMP.";
RL PLoS ONE 7:E35206-E35206(2012).
RN [4]
RP INTERACTION WITH RADA.
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. To a lesser extent, can also use ADP as substrate
CC to produce c-di-AMP. Does not convert GTP to c-di-GMP. Also exhibits
CC residual ATPase and ADPase activities in vitro. {ECO:0000255|HAMAP-
CC Rule:MF_01438, ECO:0000269|PubMed:22529992}.
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:22529992};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01438,
CC ECO:0000269|PubMed:22529992};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01438,
CC ECO:0000269|PubMed:22529992};
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01438,
CC ECO:0000269|PubMed:22529992};
CC Note=Magnesium. Can also use Mn(2+), and, to a lesser extent, Co(2+).
CC Cannot use Ni(2+), Ca(2+) and Fe(2+). {ECO:0000255|HAMAP-Rule:MF_01438,
CC ECO:0000269|PubMed:22529992};
CC -!- ACTIVITY REGULATION: Diadenylate cyclase activity is inhibited by the
CC interaction with RadA. {ECO:0000250}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Is more active at pH 8.0 rather than at pH 7.0 or pH 6.0.
CC {ECO:0000269|PubMed:22529992};
CC -!- SUBUNIT: Homooctamer. Interacts with RadA. {ECO:0000255|HAMAP-
CC Rule:MF_01438, ECO:0000269|PubMed:22529992,
CC ECO:0000269|PubMed:23760274}.
CC -!- DOMAIN: The N-terminal catalytic domain contributes to tetramerization
CC and the C-terminal domain provides additional dimerization. Both
CC domains are required for full catalytic activity. The C-terminal domain
CC may play a role in stabilizing the active conformation.
CC {ECO:0000269|PubMed:22529992}.
CC -!- SIMILARITY: Belongs to the DisA family. {ECO:0000255|HAMAP-
CC Rule:MF_01438}.
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DR EMBL; AL123456; CCP46409.1; -; Genomic_DNA.
DR PIR; C70804; C70804.
DR RefSeq; NP_218103.1; NC_000962.3.
DR RefSeq; WP_003900111.1; NZ_NVQJ01000014.1.
DR AlphaFoldDB; P9WNW5; -.
DR SMR; P9WNW5; -.
DR STRING; 83332.Rv3586; -.
DR PaxDb; P9WNW5; -.
DR DNASU; 887485; -.
DR GeneID; 887485; -.
DR KEGG; mtu:Rv3586; -.
DR PATRIC; fig|83332.111.peg.3996; -.
DR TubercuList; Rv3586; -.
DR eggNOG; COG1623; Bacteria.
DR OMA; VVRDYVP; -.
DR PhylomeDB; P9WNW5; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0004016; F:adenylate cyclase activity; IBA:GO_Central.
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 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..358
FT /note="DNA integrity scanning protein DisA"
FT /id="PRO_0000424180"
FT DOMAIN 6..144
FT /note="DAC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01130"
FT BINDING 73
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01438"
FT BINDING 91
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01438"
FT BINDING 104..108
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01438"
FT MUTAGEN 73
FT /note="G->A: Retains diadenylate cyclase activity."
FT /evidence="ECO:0000269|PubMed:22529992"
FT MUTAGEN 105..107
FT /note="RHR->AAA: Abolishes ATP-binding and diadenylate
FT cyclase activity."
FT /evidence="ECO:0000269|PubMed:22529992"
SQ SEQUENCE 358 AA; 39031 MW; 2D7E56E7C82E5F82 CRC64;
MHAVTRPTLR EAVARLAPGT GLRDGLERIL RGRTGALIVL GHDENVEAIC DGGFSLDVRY
AATRLRELCK MDGAVVLSTD GSRIVRANVQ LVPDPSIPTD ESGTRHRSAE RAAIQTGYPV
ISVSHSMNIV TVYVRGERHV LTDSATILSR ANQAIATLER YKTRLDEVSR QLSRAEIEDF
VTLRDVMTVV QRLELVRRIG LVIDYDVVEL GTDGRQLRLQ LDELLGGNDT ARELIVRDYH
ANPEPPSTGQ INATLDELDA LSDGDLLDFT ALAKVFGYPT TTEAQDSTLS PRGYRAMAGI
PRLQFAHADL LVRAFGTLQG LLAASAGDLQ SVDGIGAMWA RHVREGLSQL AESTISDQ
