ID   PCTIR_PSEAI             Reviewed;         308 AA.
AC   P0DV41;
DT   25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT   25-MAY-2022, sequence version 1.
DT   03-AUG-2022, entry version 2.
DE   RecName: Full=Pycsar effector protein PaPycTIR;
DE            Short=PaPycTIR {ECO:0000303|PubMed:34644530};
DE            EC=3.2.2.5 {ECO:0000250|UniProtKB:A0A0J5WTU0, ECO:0000305|PubMed:34644530};
GN   Name=pycTIR {ECO:0000303|PubMed:34644530}; ORFNames=Ga0130373_10434;
OS   Pseudomonas aeruginosa.
OC   Bacteria; Proteobacteria; Gammaproteobacteria; Pseudomonadales;
OC   Pseudomonadaceae; Pseudomonas.
OX   NCBI_TaxID=287;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=RW93;
RA   Weiser R.;
RL   Submitted (MAR-2015) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   PROBABLE FUNCTION, AND CLASSIFICATION.
RC   STRAIN=RW93;
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 A Pycsar system. {ECO:0000305|PubMed:34644530}.
CC   -!- FUNCTION: The effector gene of a two-gene Pycsar system. Expression of
CC       this and adjacent uridylate cyclase PaPycC (AC P0DV40) probably confers
CC       resistance to bacteriophage. The genes are probably only expressed in
CC       response to bacteriophage infection. Probably only responds to cUMP
CC       (produced by its cognate NTP cyclase), acts by depleting cellular
CC       NAD(+) levels. {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:0000250|UniProtKB:A0A0J5WTU0,
CC         ECO:0000305|PubMed:34644530};
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
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|PubMed:34644530}.
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DR   EMBL; CUYG01000043; -; NOT_ANNOTATED_CDS; Genomic_DNA.
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   4: Predicted;
KW   Antiviral defense; Cytoplasm; Hydrolase; Nucleotide-binding.
FT   CHAIN           1..308
FT                   /note="Pycsar effector protein PaPycTIR"
FT                   /id="PRO_0000455237"
FT   REGION          160..278
FT                   /note="TIR-like"
FT                   /evidence="ECO:0000305|PubMed:34644530"
FT   BINDING         54..143
FT                   /ligand="a nucleoside 3',5'-cyclic phosphate"
FT                   /ligand_id="ChEBI:CHEBI:58464"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00060"
SQ   SEQUENCE   308 AA;  34233 MW;  39BD9D50D1B8341D CRC64;
     MTTGKLIDRF EGPSGRAVLE EVLLEQKLVL GNQDLARRLA EVGTLEEIAK DAVLITEDAE
     DSEVYFIITG HFQVKVHDRE VATRGGGDHV GEMAALVPTA KRSATVLATE PSIVLKVSAA
     DFKSIADAYP SVWRQVTRQL VDRLHQRNDM VLPAHQSSHV FIICSVEALP IARAIENNLE
     HDKFFVKTWT QGVFRASQYA LESLEEQLDE CDFAIAIAQP DDSVTMREET KNTPRDNVIF
     ELGLFVGRLG RARTFLLEPR GDEVHLPSDL KGLTTIGYRL TKSEDQLPSS LSPACNQLRT
     IFNKLGPK