ID   THSB_BACCS              Reviewed;         192 AA.
AC   J8G8J6;
DT   03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT   31-OCT-2012, sequence version 1.
DT   03-AUG-2022, entry version 26.
DE   RecName: Full=Thoeris protein ThsB {ECO:0000303|PubMed:29371424};
GN   Name=thsB {ECO:0000303|PubMed:29371424};
GN   ORFNames=II9_05449 {ECO:0000312|EMBL:EJR09241.1};
OS   Bacillus cereus (strain MSX-D12).
OC   Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae; Bacillus;
OC   Bacillus cereus group.
OX   NCBI_TaxID=1053222;
RN   [1] {ECO:0000312|EMBL:EJR09241.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=MSX-D12;
RG   The Broad Institute Genome Sequencing Platform;
RG   The Broad Institute Genome Sequencing Center for Infectious Disease;
RA   Feldgarden M., Van der Auwera G.A., Mahillon J., Duprez V., Timmery S.,
RA   Mattelet C., Dierick K., Sun M., Yu Z., Zhu L., Hu X., Shank E.B.,
RA   Swiecicka I., Hansen B.M., Andrup L., Young S.K., Zeng Q., Gargeya S.,
RA   Fitzgerald M., Haas B., Abouelleil A., Alvarado L., Arachchi H.M.,
RA   Berlin A., Chapman S.B., Goldberg J., Griggs A., Gujja S., Hansen M.,
RA   Howarth C., Imamovic A., Larimer J., McCowen C., Montmayeur A., Murphy C.,
RA   Neiman D., Pearson M., Priest M., Roberts A., Saif S., Shea T., Sisk P.,
RA   Sykes S., Wortman J., Nusbaum C., Birren B.;
RT   "The Genome Sequence of Bacillus cereus MSX-D12.";
RL   Submitted (APR-2012) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   FUNCTION IN ANTIVIRAL DEFENSE, DISRUPTION PHENOTYPE, AND EXPRESSION IN
RP   B.SUBTILIS.
RC   STRAIN=MSX-D12;
RX   PubMed=29371424; DOI=10.1126/science.aar4120;
RA   Doron S., Melamed S., Ofir G., Leavitt A., Lopatina A., Keren M.,
RA   Amitai G., Sorek R.;
RT   "Systematic discovery of antiphage defense systems in the microbial
RT   pangenome.";
RL   Science 359:0-0(2018).
RN   [3]
RP   FUNCTION IN ANTIVIRAL DEFENSE, FUNCTION, ACTIVITY REGULATION, AND
RP   MUTAGENESIS OF GLU-85.
RC   STRAIN=MSX-D12;
RX   PubMed=34853457; DOI=10.1038/s41586-021-04098-7;
RA   Ofir G., Herbst E., Baroz M., Cohen D., Millman A., Doron S., Tal N.,
RA   Malheiro D.B.A., Malitsky S., Amitai G., Sorek R.;
RT   "Antiviral activity of bacterial TIR domains via immune signalling
RT   molecules.";
RL   Nature 600:116-120(2021).
RN   [4] {ECO:0007744|PDB:6LHY}
RP   X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS), SUBUNIT, AND DOMAIN.
RC   STRAIN=MSX-D12;
RX   PubMed=32499527; DOI=10.1038/s41467-020-16703-w;
RA   Ka D., Oh H., Park E., Kim J.H., Bae E.;
RT   "Structural and functional evidence of bacterial antiphage protection by
RT   Thoeris defense system via NAD+ degradation.";
RL   Nat. Commun. 11:2816-2816(2020).
CC   -!- FUNCTION: TIR-like domain-containing component of antiviral defense
CC       system Thoeris, composed of ThsA and ThsB. Expression of ThsA and ThsB
CC       in B.subtilis (strain BEST7003) confers resistance to phages SBSphiC,
CC       SBSphiJ and SPO1 (PubMed:29371424, PubMed:34853457). Phage infection
CC       activates this protein so that 30 to 45 minutes post-infection with
CC       phage SPO1 it generates a signal molecule that in turn activates the
CC       NAD(+) hydrolase activity of ThsA. The signal is similar to cyclic ADP-
CC       D-ribose, but how it differs is unknown (PubMed:34853457). In vitro
CC       purified (but unactivated) ThsB had no NAD(+) hydrolyzing activity, no
CC       activity on AMP, CMP, GMP or UMP, does not alter the activity of ThsA,
CC       does not bind DNA (PubMed:32499527). {ECO:0000269|PubMed:29371424,
CC       ECO:0000269|PubMed:32499527, ECO:0000269|PubMed:34853457}.
CC   -!- ACTIVITY REGULATION: Activated upon phage infection.
CC       {ECO:0000305|PubMed:34853457}.
CC   -!- SUBUNIT: Monomer; not seen to interact with ThsA.
CC       {ECO:0000269|PubMed:32499527}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC   -!- DOMAIN: Has an N-terminal TIR domain and an C-terminal antiparallel
CC       beta-sheet. {ECO:0000269|PubMed:32499527}.
CC   -!- DISRUPTION PHENOTYPE: When this gene is missing the Thoeris system does
CC       not confer phage resistance in B.subtilis.
CC       {ECO:0000269|PubMed:29371424}.
CC   -!- SIMILARITY: Belongs to the Thoeris B TIR-like family. {ECO:0000305}.
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DR   EMBL; AHEQ01000050; EJR09241.1; -; Genomic_DNA.
DR   RefSeq; WP_001129548.1; NZ_JH792019.1.
DR   PDB; 6LHY; X-ray; 1.80 A; A/B=1-192.
DR   PDBsum; 6LHY; -.
DR   SMR; J8G8J6; -.
DR   EnsemblBacteria; EJR09241; EJR09241; II9_05449.
DR   PATRIC; fig|1053222.3.peg.5516; -.
DR   HOGENOM; CLU_098991_0_0_9; -.
DR   Proteomes; UP000006971; Unassembled WGS sequence.
DR   InterPro; IPR036490; MTH538_sf.
DR   InterPro; IPR015032; MTH538_TIR-like_domain.
DR   Pfam; PF08937; DUF1863; 1.
DR   SUPFAM; SSF52206; SSF52206; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Antiviral defense; Cytoplasm.
FT   CHAIN           1..192
FT                   /note="Thoeris protein ThsB"
FT                   /id="PRO_0000456260"
FT   MUTAGEN         85
FT                   /note="E->Q: No longer confers resistance to phage SPO1, no
FT                   change in NAD(+) levels during SPO1 infection. Does not
FT                   generate the signal molecule."
FT                   /evidence="ECO:0000269|PubMed:34853457"
SQ   SEQUENCE   192 AA;  22321 MW;  838C7C8E81B9D26C CRC64;
     MAKRVFFSFH YQDVIDFRVN VVRNHWVTKL NQSAAGVFDA SLWEDAKKTS DIALKRLING
     GLNNTSVTCV LIGSQTFNRR WVRYEIMKSI EKGNKIIGIH INAFKDKYGN IKSKGPNPFD
     YLGYQYSSDG KQLHLYEWTG GKWEEYKDLA PYRVNQIAPE SLRGKFYSLS SVYRVYDWVA
     DDGYNKFSSW VN