BTPA_BRUMB
ID BTPA_BRUMB Reviewed; 275 AA.
AC C0RGW8;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 1.
DT 03-AUG-2022, entry version 64.
DE RecName: Full=NAD(+) hydrolase BtpA {ECO:0000305};
DE EC=3.2.2.6 {ECO:0000269|PubMed:29395922};
DE AltName: Full=Brucella TIR-containing protein 1 {ECO:0000303|PubMed:18266466};
DE Short=Btp1 {ECO:0000303|PubMed:18266466};
DE AltName: Full=TIR domain-containing protein in Brucella {ECO:0000303|PubMed:27311859};
DE Short=TcpB {ECO:0000303|PubMed:27311859};
GN Name=btpA {ECO:0000303|PubMed:24076024};
GN Synonyms=btp1 {ECO:0000303|PubMed:18266466},
GN tcpB {ECO:0000303|PubMed:27311859};
GN OrderedLocusNames=BMEA_A0279 {ECO:0000312|EMBL:ACO00076.1};
OS Brucella melitensis biotype 2 (strain ATCC 23457).
OC Bacteria; Proteobacteria; Alphaproteobacteria; Hyphomicrobiales;
OC Brucellaceae; Brucella/Ochrobactrum group; Brucella.
OX NCBI_TaxID=546272;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 23457;
RA Setubal J.C., Boyle S., Crasta O.R., Gillespie J.J., Kenyon R.W., Lu J.,
RA Mane S., Nagrani S., Shallom J.M., Shallom S., Shukla M., Snyder E.E.,
RA Sobral B.W., Wattam A.R., Will R., Williams K., Yoo H., Munk C., Tapia R.,
RA Han C., Detter J.C., Bruce D., Brettin T.S.;
RT "Brucella melitensis ATCC 23457 whole genome shotgun sequencing project.";
RL Submitted (MAR-2009) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION.
RX PubMed=18266466; DOI=10.1371/journal.ppat.0040021;
RA Salcedo S.P., Marchesini M.I., Lelouard H., Fugier E., Jolly G., Balor S.,
RA Muller A., Lapaque N., Demaria O., Alexopoulou L., Comerci D.J.,
RA Ugalde R.A., Pierre P., Gorvel J.P.;
RT "Brucella control of dendritic cell maturation is dependent on the TIR-
RT containing protein Btp1.";
RL PLoS Pathog. 4:E21-E21(2008).
RN [3]
RP POSSIBLE INTERACTION WITH HOST MYD88.
RX PubMed=22155231; DOI=10.1016/j.bbrc.2011.11.104;
RA Chaudhary A., Ganguly K., Cabantous S., Waldo G.S., Micheva-Viteva S.N.,
RA Nag K., Hlavacek W.S., Tung C.S.;
RT "The Brucella TIR-like protein TcpB interacts with the death domain of
RT MyD88.";
RL Biochem. Biophys. Res. Commun. 417:299-304(2012).
RN [4]
RP INTERACTION WITH HOST TIRAP.
RX PubMed=27311859; DOI=10.1016/j.bbrc.2016.06.064;
RA Li W., Ke Y., Wang Y., Yang M., Gao J., Zhan S., Xinying D., Huang L.,
RA Li W., Chen Z., Li J.;
RT "Brucella TIR-like protein TcpB/Btp1 specifically targets the host adaptor
RT protein MAL/TIRAP to promote infection.";
RL Biochem. Biophys. Res. Commun. 477:509-514(2016).
RN [5]
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).
RN [6] {ECO:0007744|PDB:4LZP}
RP X-RAY CRYSTALLOGRAPHY (3.15 ANGSTROMS) OF 100-275, SUBUNIT, AND MUTAGENESIS
RP OF ARG-167; ASP-176 AND SER-260.
RX PubMed=24076024; DOI=10.1016/j.febslet.2013.09.007;
RA Kaplan-Turkoz B., Koelblen T., Felix C., Candusso M.P., O'Callaghan D.,
RA Vergunst A.C., Terradot L.;
RT "Structure of the Toll/interleukin 1 receptor (TIR) domain of the
RT immunosuppressive Brucella effector BtpA/Btp1/TcpB.";
RL FEBS Lett. 587:3412-3416(2013).
CC -!- FUNCTION: Virulence factor that interferes with host Toll-like receptor
CC 2 (TLR2) and TLR4 signaling, resulting in the reduction of dendritic
CC cell maturation, inhibition of pro-inflammatory cytokine secretion and
CC impaired NF-kappa-B activation in macrophages (PubMed:18266466). Acts
CC as a NAD(+) hydrolase (NADase) by catalyzing cleavage of NAD(+) into
CC ADP-D-ribose (ADPR) and nicotinamide (PubMed:29395922). In addition to
CC ADPR, also generates a cyclization variant of cyclic ADPR (cADPR),
CC termed v-cADPR, for which the cyclizing bond is unknown
CC (PubMed:29395922). {ECO:0000269|PubMed:18266466,
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 -!- SUBUNIT: Homodimer (PubMed:24076024). Interacts with host TIRAP
CC (PubMed:27311859). May interact with host MYD88 (PubMed:22155231).
CC Interaction with host MYD88 however requires confirmation as it could
CC not be confirmed by another study (PubMed:27311859).
CC {ECO:0000269|PubMed:22155231, ECO:0000269|PubMed:24076024,
CC ECO:0000269|PubMed:27311859}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}. Note=Translocated into
CC the host cell via the type IV secretion system (T4SS). {ECO:0000305}.
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; CP001488; ACO00076.1; -; Genomic_DNA.
DR RefSeq; WP_004684737.1; NC_012441.1.
DR PDB; 4LZP; X-ray; 3.15 A; A/B/C/D=100-275.
DR PDBsum; 4LZP; -.
DR AlphaFoldDB; C0RGW8; -.
DR SMR; C0RGW8; -.
DR EnsemblBacteria; ACO00076; ACO00076; BMEA_A0279.
DR GeneID; 29594531; -.
DR KEGG; bmi:BMEA_A0279; -.
DR HOGENOM; CLU_086674_0_0_5; -.
DR OMA; FISHAWE; -.
DR Proteomes; UP000001748; Chromosome I.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
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 3D-structure; Hydrolase; NAD; Secreted.
FT CHAIN 1..275
FT /note="NAD(+) hydrolase BtpA"
FT /id="PRO_0000449140"
FT DOMAIN 142..275
FT /note="TIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT REGION 17..66
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 17..35
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 36..56
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 217
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT BINDING 151..152
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT BINDING 181
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT MUTAGEN 167
FT /note="R->E: Does not affect homodimerization."
FT /evidence="ECO:0000269|PubMed:24076024"
FT MUTAGEN 176
FT /note="D->R: Does not affect homodimerization."
FT /evidence="ECO:0000269|PubMed:24076024"
FT MUTAGEN 260
FT /note="S->A: Impaired homodimerization."
FT /evidence="ECO:0000269|PubMed:24076024"
FT HELIX 101..131
FT /evidence="ECO:0007829|PDB:4LZP"
FT STRAND 144..150
FT /evidence="ECO:0007829|PDB:4LZP"
FT STRAND 152..154
FT /evidence="ECO:0007829|PDB:4LZP"
FT TURN 155..158
FT /evidence="ECO:0007829|PDB:4LZP"
FT HELIX 159..168
FT /evidence="ECO:0007829|PDB:4LZP"
FT HELIX 176..178
FT /evidence="ECO:0007829|PDB:4LZP"
FT HELIX 186..196
FT /evidence="ECO:0007829|PDB:4LZP"
FT STRAND 197..204
FT /evidence="ECO:0007829|PDB:4LZP"
FT HELIX 206..210
FT /evidence="ECO:0007829|PDB:4LZP"
FT HELIX 215..218
FT /evidence="ECO:0007829|PDB:4LZP"
FT TURN 219..221
FT /evidence="ECO:0007829|PDB:4LZP"
FT STRAND 232..236
FT /evidence="ECO:0007829|PDB:4LZP"
FT HELIX 241..245
FT /evidence="ECO:0007829|PDB:4LZP"
FT HELIX 249..253
FT /evidence="ECO:0007829|PDB:4LZP"
FT TURN 259..261
FT /evidence="ECO:0007829|PDB:4LZP"
FT HELIX 264..272
FT /evidence="ECO:0007829|PDB:4LZP"
SQ SEQUENCE 275 AA; 30922 MW; 8AB300D6A6F76AE1 CRC64;
MSSYSSNIDR LQREIARLKA DDSREMSKEK QAQSKAHKAQ QAISSAKSLS TQKSKMSELE
RATRDGAAIG KKRADIAKKI ADKAKQLSSY QAKQFKADEQ AVKKVAQEQK RLSDERTKHE
AFIKQSLSSM RTTASATMEA EEEYDFFISH ASEDKEAFVQ DLVAALRDLG AKIFYDAYTL
KVGDSLRRKI DQGLANSKFG IVVLSEHFFS KQWPARELDG LTAMEIGGQT RILPIWHKVS
YDEVRRFSPS LADKVALNTS LKSVEEIAKE LHSLI
