ID   TCPO_METOL              Reviewed;         341 AA.
AC   A0A1I4KS07;
DT   26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT   12-APR-2017, sequence version 1.
DT   03-AUG-2022, entry version 13.
DE   RecName: Full=NAD(+) hydrolase TcpO {ECO:0000305};
DE            EC=3.2.2.6 {ECO:0000269|PubMed:29395922};
DE   AltName: Full=TIR domain-containing protein in M.olleyae {ECO:0000303|PubMed:29395922};
DE            Short=tcpO {ECO:0000303|PubMed:29395922};
GN   Name=tcpO {ECO:0000303|PubMed:29395922};
GN   ORFNames=SAMN02910297_01820 {ECO:0000312|EMBL:SFL81530.1};
OS   Methanobrevibacter olleyae.
OC   Archaea; Euryarchaeota; Methanomada group; Methanobacteria;
OC   Methanobacteriales; Methanobacteriaceae; Methanobrevibacter.
OX   NCBI_TaxID=294671;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=DSM 16632;
RA   Varghese N.;
RL   Submitted (OCT-2016) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=29395922; DOI=10.1016/j.cub.2017.12.024;
RA   Essuman K., Summers D.W., Sasaki Y., Mao X., Yim A.K.Y., DiAntonio A.,
RA   Milbrandt J.;
RT   "TIR domain proteins are an ancient family of NAD+-consuming enzymes.";
RL   Curr. Biol. 28:421-430(2018).
CC   -!- FUNCTION: NAD(+) hydrolase (NADase) that catalyzes cleavage of NAD(+)
CC       into ADP-D-ribose (ADPR) and nicotinamide (PubMed:29395922). In
CC       addition to ADPR, also generates a cyclization variant of cyclic ADPR
CC       (cADPR), termed v-cADPR, for which the cyclizing bond is unknown
CC       (PubMed:29395922). {ECO:0000269|PubMed:29395922}.
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=3.2.2.6;
CC         Evidence={ECO:0000269|PubMed:29395922};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16302;
CC         Evidence={ECO:0000269|PubMed:29395922};
CC   -!- DOMAIN: The TIR domain mediates NAD(+) hydrolase (NADase) activity.
CC       Self-association of TIR domains is required for NADase activity.
CC       {ECO:0000255|PROSITE-ProRule:PRU00204}.
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DR   EMBL; FOTL01000044; SFL81530.1; -; Genomic_DNA.
DR   RefSeq; WP_074798936.1; NZ_FOTL01000044.1.
DR   AlphaFoldDB; A0A1I4KS07; -.
DR   SMR; A0A1I4KS07; -.
DR   OrthoDB; 123591at2157; -.
DR   Proteomes; UP000183442; Unassembled WGS sequence.
DR   GO; GO:0050135; F:NAD(P)+ nucleosidase activity; IEA:UniProtKB-EC.
DR   GO; GO:0003953; F:NAD+ nucleosidase activity; IDA:UniProtKB.
DR   GO; GO:0061809; F:NAD+ nucleotidase, cyclic ADP-ribose generating; IEA:UniProtKB-EC.
DR   GO; GO:0019677; P:NAD catabolic process; IDA:UniProtKB.
DR   GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR   Gene3D; 3.40.50.10140; -; 1.
DR   InterPro; IPR000157; TIR_dom.
DR   InterPro; IPR035897; Toll_tir_struct_dom_sf.
DR   Pfam; PF13676; TIR_2; 1.
DR   SMART; SM00255; TIR; 1.
DR   SUPFAM; SSF52200; SSF52200; 1.
DR   PROSITE; PS50104; TIR; 1.
PE   1: Evidence at protein level;
KW   Hydrolase; NAD.
FT   CHAIN           1..341
FT                   /note="NAD(+) hydrolase TcpO"
FT                   /id="PRO_0000449145"
FT   DOMAIN          204..336
FT                   /note="TIR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT   ACT_SITE        279
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT   BINDING         213..214
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT   BINDING         243
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
SQ   SEQUENCE   341 AA;  41264 MW;  1D0BBEFCAEAE6C40 CRC64;
     MEDLEIFLKR FEDLLIDLAT YNENESNDYI IYRKKLLSYD YLKDFIPDFI IKNRKPQFFR
     AYMQEIGGYK ERRDLIYKGF ERLYDYETIK NFDSDNSYNV NQIENFLERF EDLLIDLATE
     NLKKDGFEEY SLFRKKFLTC NYFKDMPIFL KRNPKHFRYY MQSQGGYKER RKIISEEFNK
     LFSIIEGSNF NSDSNNKNKS INKKEYDIFV SHSSEDKEDF VKEFVNLLKQ KGLSVWYDDD
     IVKIGHNLRK RISKGIKSSN YAVVIFSEDF FKSKWTNYEY DNIFLDFYDE EKVLPILHDL
     TIEDLEKFDG SIPLIRALST KKFTVEEIIH EILERINEEK S