TCPA_THEAD
ID TCPA_THEAD Reviewed; 329 AA.
AC A0A151EH88;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 08-JUN-2016, sequence version 1.
DT 03-AUG-2022, entry version 16.
DE RecName: Full=NAD(+) hydrolase TcpA {ECO:0000305};
DE EC=3.2.2.6 {ECO:0000269|PubMed:29395922};
DE AltName: Full=TIR domain-containing protein in T.archaeon {ECO:0000303|PubMed:29395922};
DE Short=tcpA {ECO:0000303|PubMed:29395922};
GN Name=tcpA {ECO:0000303|PubMed:29395922};
GN ORFNames=AYK19_21110 {ECO:0000312|EMBL:KYK27962.1};
OS Theionarchaea archaeon (strain DG-70-1).
OC Archaea; Euryarchaeota; Theionarchaea.
OX NCBI_TaxID=1803814;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Baker B.J., Lazar C.S., Teske A.P., Dick G.J.;
RL Submitted (FEB-2016) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF GLU-267, AND ACTIVE SITE.
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.
CC {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; LSSC01000186; KYK27962.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A151EH88; -.
DR SMR; A0A151EH88; -.
DR STRING; 1803814.AYK19_21110; -.
DR EnsemblBacteria; KYK27962; KYK27962; AYK19_21110.
DR Proteomes; UP000075539; Unassembled WGS sequence.
DR GO; GO:0070122; F:isopeptidase activity; IEA:InterPro.
DR GO; GO:0140492; F:metal-dependent deubiquitinase activity; IEA:InterPro.
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; IPR000555; JAMM/MPN+_dom.
DR InterPro; IPR037518; MPN.
DR InterPro; IPR000157; TIR_dom.
DR InterPro; IPR035897; Toll_tir_struct_dom_sf.
DR Pfam; PF01398; JAB; 1.
DR Pfam; PF13676; TIR_2; 1.
DR SMART; SM00232; JAB_MPN; 1.
DR SMART; SM00255; TIR; 1.
DR SUPFAM; SSF52200; SSF52200; 1.
DR PROSITE; PS50249; MPN; 1.
DR PROSITE; PS50104; TIR; 1.
PE 1: Evidence at protein level;
KW Hydrolase; NAD.
FT CHAIN 1..329
FT /note="NAD(+) hydrolase TcpA"
FT /id="PRO_0000449142"
FT DOMAIN 5..134
FT /note="MPN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01182"
FT DOMAIN 192..324
FT /note="TIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT ACT_SITE 267
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204,
FT ECO:0000305|PubMed:29395922"
FT BINDING 201..202
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT BINDING 231
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT MUTAGEN 267
FT /note="E->A: Loss of NAD(+) hydrolase activity."
FT /evidence="ECO:0000269|PubMed:29395922"
SQ SEQUENCE 329 AA; 37443 MW; 5D02AD9AD04D3DD2 CRC64;
MAKSVSISYL ALEQIFNDTI GAGEIKVAGL LVGHPVNGGV HIARTIPTSR GTVTYVRISA
EEISRAVEEL NPGEKIVGWY HSRPGQGVFF SQDDIETHEK CLDFNPYFQA LVIDPHQAKY
GTPMADCVRF YTVRNHKEVP IHGYKLTGSS MQSYYDPKEF VFDKYGFPHH YTLTHAGKTK
ISHRKSNMDA SFEYDVFICH AHEDKEFFVR ELAEKLHSKG LRVWYDEFTL SLGDNLRRSI
ENGLAKSRYG IVVLSKRFFE KEWPQKELDG LVAKEVEGKK VILPVWHGIT REEVQSFSSI
LANRLAASSE KGIDYVVNEI LRVLRKKSV
