TCPF_ENTFA
ID TCPF_ENTFA Reviewed; 274 AA.
AC Q833J1;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 86.
DE RecName: Full=NAD(+) hydrolase TcpF {ECO:0000305};
DE EC=3.2.2.6 {ECO:0000269|PubMed:29395922};
DE AltName: Full=TIR domain-containing protein in E.faecalis {ECO:0000303|PubMed:25369374, ECO:0000303|PubMed:29395922};
DE Short=tcpF {ECO:0000303|PubMed:25369374, ECO:0000303|PubMed:29395922};
GN Name=tcpF {ECO:0000303|PubMed:25369374, ECO:0000303|PubMed:29395922};
GN OrderedLocusNames=EF_1959 {ECO:0000312|EMBL:AAO81706.1};
OS Enterococcus faecalis (strain ATCC 700802 / V583).
OC Bacteria; Firmicutes; Bacilli; Lactobacillales; Enterococcaceae;
OC Enterococcus.
OX NCBI_TaxID=226185;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700802 / V583;
RX PubMed=12663927; DOI=10.1126/science.1080613;
RA Paulsen I.T., Banerjei L., Myers G.S.A., Nelson K.E., Seshadri R.,
RA Read T.D., Fouts D.E., Eisen J.A., Gill S.R., Heidelberg J.F., Tettelin H.,
RA Dodson R.J., Umayam L.A., Brinkac L.M., Beanan M.J., Daugherty S.C.,
RA DeBoy R.T., Durkin S.A., Kolonay J.F., Madupu R., Nelson W.C.,
RA Vamathevan J.J., Tran B., Upton J., Hansen T., Shetty J., Khouri H.M.,
RA Utterback T.R., Radune D., Ketchum K.A., Dougherty B.A., Fraser C.M.;
RT "Role of mobile DNA in the evolution of vancomycin-resistant Enterococcus
RT faecalis.";
RL Science 299:2071-2074(2003).
RN [2]
RP FUNCTION.
RX PubMed=25147569; DOI=10.1155/2014/918143;
RA Kraemer T.D., Quintanar Haro O.D., Domann E., Chakraborty T.,
RA Tchatalbachev S.;
RT "The TIR domain containing locus of Enterococcus faecalis is predominant
RT among urinary tract infection isolates and downregulates host inflammatory
RT response.";
RL Int. J. Microbiol. 2014:918143-918143(2014).
RN [3]
RP FUNCTION, AND INTERACTION WITH HOST MYD88.
RX PubMed=25369374; DOI=10.1371/journal.pone.0112010;
RA Zou J., Baghdayan A.S., Payne S.J., Shankar N.;
RT "A TIR domain protein from E. faecalis attenuates MyD88-mediated signaling
RT and NF-kappaB activation.";
RL PLoS ONE 9:E112010-E112010(2014).
RN [4]
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: Virulence factor that suppresses host Toll-like receptor
CC (TLR)-mediated cytokine production upon infection (PubMed:25147569,
CC PubMed:25369374). Acts as a NAD(+) hydrolase (NADase) by catalyzing
CC cleavage of NAD(+) into ADP-D-ribose (ADPR) and nicotinamide
CC (PubMed:29395922). Interacts with various phosphatidylinositol
CC phosphates, such as phosphatidylinositol 3-phosphate (PtdIns(3)P),
CC phosphatidylinositol 4-phosphate (PtdIns(4)P), phosphatidylinositol
CC 3,4-bisphosphate (PtdIns(3,4)P), phosphatidylinositol 3,5-bisphosphate
CC (PtdIns(3,5)P), phosphatidylinositol 4,5- bisphosphate (PtdIns(4,5)P),
CC and phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P)
CC (PubMed:25147569). {ECO:0000269|PubMed:25147569,
CC ECO:0000269|PubMed:25369374, 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 -!- SUBUNIT: Interacts with host MYD88. {ECO:0000269|PubMed:25369374}.
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; AE016830; AAO81706.1; -; Genomic_DNA.
DR RefSeq; NP_815636.1; NC_004668.1.
DR RefSeq; WP_002357099.1; NZ_KE136528.1.
DR AlphaFoldDB; Q833J1; -.
DR STRING; 226185.EF_1959; -.
DR EnsemblBacteria; AAO81706; AAO81706; EF_1959.
DR GeneID; 60894195; -.
DR KEGG; efa:EF1959; -.
DR PATRIC; fig|226185.45.peg.1565; -.
DR eggNOG; ENOG50332G0; Bacteria.
DR HOGENOM; CLU_094901_0_0_9; -.
DR PHI-base; PHI:3441; -.
DR Proteomes; UP000001415; Chromosome.
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:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; IDA:UniProtKB.
DR GO; GO:0043325; F:phosphatidylinositol-3,4-bisphosphate binding; IDA:UniProtKB.
DR GO; GO:0080025; F:phosphatidylinositol-3,5-bisphosphate binding; IDA:UniProtKB.
DR GO; GO:0032266; F:phosphatidylinositol-3-phosphate binding; IDA:UniProtKB.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:UniProtKB.
DR GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; IDA:UniProtKB.
DR GO; GO:0019677; P:NAD catabolic process; IDA:UniProtKB.
DR GO; GO:0034125; P:negative regulation of MyD88-dependent toll-like receptor signaling pathway; 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 SUPFAM; SSF52200; SSF52200; 1.
PE 1: Evidence at protein level;
KW Hydrolase; NAD; Reference proteome; Virulence.
FT CHAIN 1..274
FT /note="NAD(+) hydrolase TcpF"
FT /id="PRO_0000449144"
FT DOMAIN 3..140
FT /note="TIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT ACT_SITE 83
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT BINDING 12..13
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT BINDING 47
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
SQ SEQUENCE 274 AA; 31799 MW; D10115B1C15B1A7B CRC64;
MSNGKKIFIS HSSKDQEYVD AFIQLLKKFG FRTQDIFYSS TIETGVQPGE LIFDTIKREL
TNQPVMLYFL SDHYYQSIPC LNEMGASWML SDKHYPIALN NFSMKDMKGV ISSERLAIAF
NDKTSTNEIN CLLKKLSHDT DVQAEPDFEL NVEKNIQPFQ NKLTQLIRQA SYLKPDEKGY
FETILSTHRP VYGTAKGVYD CFKLPSLIEP KSLGLDTLSE DESHWLFFFL TWGTFQEGEK
VRFKLKKDKA YNNREFSDIG KCKNIYVSYL EKVE
