ID   PCTIR_BURCE             Reviewed;         303 AA.
AC   A0A0J5WTU0;
DT   25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT   14-OCT-2015, sequence version 1.
DT   03-AUG-2022, entry version 12.
DE   RecName: Full=Pycsar effector protein BcPycTIR;
DE            Short=BcPycTIR {ECO:0000303|PubMed:34644530};
DE            EC=3.2.2.5 {ECO:0000269|PubMed:34644530};
GN   Name=pycTIR {ECO:0000303|PubMed:34644530};
GN   ORFNames=VL15_12780 {ECO:0000303|Ref.1};
OS   Burkholderia cepacia (Pseudomonas cepacia).
OC   Bacteria; Proteobacteria; Betaproteobacteria; Burkholderiales;
OC   Burkholderiaceae; Burkholderia; Burkholderia cepacia complex.
OX   NCBI_TaxID=292;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=LK29;
RA   Chan X.Y.;
RT   "Draft genome of Burkholderia cepacia LK29.";
RL   Submitted (MAY-2015) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   FUNCTION AS AN NAD HYDROLASE, CATALYTIC ACTIVITY, ACTIVITY REGULATION,
RP   SUBUNIT, SUBCELLULAR LOCATION, AND CLASSIFICATION.
RC   STRAIN=LK29;
RX   PubMed=34644530; DOI=10.1016/j.cell.2021.09.031;
RA   Tal N., Morehouse B.R., Millman A., Stokar-Avihail A., Avraham C.,
RA   Fedorenko T., Yirmiya E., Herbst E., Brandis A., Mehlman T.,
RA   Oppenheimer-Shaanan Y., Keszei A.F.A., Shao S., Amitai G., Kranzusch P.J.,
RA   Sorek R.;
RT   "Cyclic CMP and cyclic UMP mediate bacterial immunity against phages.";
RL   Cell 0:0-0(2021).
CC   -!- FUNCTION: Pycsar (pyrimidine cyclase system for antiphage resistance)
CC       provides immunity against bacteriophage. The pyrimidine cyclase (PycC)
CC       synthesizes cyclic nucleotides in response to infection; these serve as
CC       specific second messenger signals. The signals activate the adjacent
CC       effector, leading to bacterial cell death and abortive phage infection.
CC       A clade B Pycsar system. {ECO:0000305|PubMed:34644530}.
CC   -!- FUNCTION: The effector protein of a two-gene Pycsar system. Upon
CC       activation by cyclic UMP (cUMP) degrades cellular NAD(+). Expression of
CC       this and adjacent uridylate cyclase BcPycC (AC A0A0J5ZXG5) probably
CC       confers resistance to bacteriophage. The genes are probably only
CC       expressed in response to bacteriophage infection. This protein probably
CC       only responds to cUMP (produced by its cognate NTP cyclase).
CC       {ECO:0000305|PubMed:34644530}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + NAD(+) = ADP-D-ribose + H(+) + nicotinamide;
CC         Xref=Rhea:RHEA:16301, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:17154, ChEBI:CHEBI:57540, ChEBI:CHEBI:57967; EC=3.2.2.5;
CC         Evidence={ECO:0000269|PubMed:34644530};
CC   -!- ACTIVITY REGULATION: Activated by cyclic UMP (cUMP) and to a lesser
CC       extent by cCMP. {ECO:0000269|PubMed:34644530}.
CC   -!- SUBUNIT: Purified protein forms large 2-dimensional sheets when
CC       incubated with cUMP and shorter filaments in the presence of cCMP.
CC       {ECO:0000269|PubMed:34644530}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305|PubMed:34644530}.
CC   -!- DOMAIN: Has an N-terminal cyclic nucleotide-binding domain and a C-
CC       terminal Toll/interleukin-1 receptor-like domain (TIR) that probably
CC       has the NAD(+) hydrolase activity. {ECO:0000305}.
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DR   EMBL; LDWR01000021; KML58094.1; -; Genomic_DNA.
DR   RefSeq; WP_048245918.1; NZ_LDWR01000021.1.
DR   EnsemblBacteria; KML58094; KML58094; VL15_12780.
DR   PATRIC; fig|292.27.peg.2411; -.
DR   Proteomes; UP000036338; Unassembled WGS sequence.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR   GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR   GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR   CDD; cd00038; CAP_ED; 1.
DR   Gene3D; 2.60.120.10; -; 1.
DR   InterPro; IPR018490; cNMP-bd-like.
DR   InterPro; IPR000595; cNMP-bd_dom.
DR   InterPro; IPR014710; RmlC-like_jellyroll.
DR   InterPro; IPR019302; TIR-like_dom.
DR   Pfam; PF00027; cNMP_binding; 1.
DR   Pfam; PF10137; TIR-like; 1.
DR   SMART; SM00100; cNMP; 1.
DR   SUPFAM; SSF51206; SSF51206; 1.
DR   PROSITE; PS50042; CNMP_BINDING_3; 1.
PE   1: Evidence at protein level;
KW   Antiviral defense; Cytoplasm; Hydrolase; Nucleotide-binding.
FT   CHAIN           1..303
FT                   /note="Pycsar effector protein BcPycTIR"
FT                   /id="PRO_0000455233"
FT   REGION          154..273
FT                   /note="TIR-like"
FT                   /evidence="ECO:0000305|PubMed:34644530"
FT   BINDING         22..138
FT                   /ligand="a nucleoside 3',5'-cyclic phosphate"
FT                   /ligand_id="ChEBI:CHEBI:58464"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00060"
SQ   SEQUENCE   303 AA;  33324 MW;  6E36AF544F59E98A CRC64;
     MIERFSGEAG KRLRVEALTG QKLVGGDKGL AAELADMAEL ISVKAGDVII QQDGTDNDLY
     FIITGAFDIV VNATPIRRRF PGDSVGEMAA VEPVQKRSAT VSAAADSLVA KITEQQLSEL
     GSRYPDIWRR MAKELSKRLI ERNQFVNAKR EKIRVFVISS AEALGVAHLL QSMFAHDKFL
     TVPWNQGVFK VANYTLDDIE RELDQCDFAV AIAHGDDVTN ARGTEWPAPR DNVVFELGLF
     MGRLGRKRAI LMEPRGEGVK LPSDMAGVTT IPYVYDEKND TEAKFGPAAT ALRKHIMSLG
     TIS