CPNT_MYCBP
ID CPNT_MYCBP Reviewed; 846 AA.
AC A0A0H3MAA9;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 16-SEP-2015, sequence version 1.
DT 03-AUG-2022, entry version 29.
DE RecName: Full=Outer membrane channel protein CpnT {ECO:0000303|PubMed:25645841};
DE Contains:
DE RecName: Full=N-terminal channel domain {ECO:0000305};
DE Contains:
DE RecName: Full=Tuberculosis necrotizing toxin homolog {ECO:0000305};
DE Short=TNT homolog {ECO:0000305};
DE AltName: Full=NAD(+) glycohydrolase {ECO:0000250|UniProtKB:O05442};
DE EC=3.2.2.5 {ECO:0000250|UniProtKB:O05442};
GN Name=cpnT {ECO:0000303|PubMed:25645841};
GN OrderedLocusNames=BCG_3960c {ECO:0000312|EMBL:CAL73950.1};
OS Mycobacterium bovis (strain BCG / Pasteur 1173P2).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=410289;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=BCG / Pasteur 1173P2;
RX PubMed=17372194; DOI=10.1073/pnas.0700869104;
RA Brosch R., Gordon S.V., Garnier T., Eiglmeier K., Frigui W., Valenti P.,
RA Dos Santos S., Duthoy S., Lacroix C., Garcia-Pelayo C., Inwald J.K.,
RA Golby P., Garcia J.N., Hewinson R.G., Behr M.A., Quail M.A., Churcher C.,
RA Barrell B.G., Parkhill J., Cole S.T.;
RT "Genome plasticity of BCG and impact on vaccine efficacy.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:5596-5601(2007).
RN [2]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=BCG / Pasteur;
RX PubMed=25645841; DOI=10.1128/aac.04222-14;
RA Danilchanka O., Pires D., Anes E., Niederweis M.;
RT "The Mycobacterium tuberculosis outer membrane channel protein CpnT confers
RT susceptibility to toxic molecules.";
RL Antimicrob. Agents Chemother. 59:2328-2336(2015).
CC -!- FUNCTION: The N-terminal domain (NTD) forms an outer membrane channel
CC and is used for uptake of nutrients across the outer membrane. Also
CC confers susceptibility to structurally different antibiotics and
CC antituberculosis drugs, and to toxic immune factors such as nitric
CC oxide (NO). The C-terminal domain (TNT) is dispensable for normal
CC growth in macrophages. {ECO:0000269|PubMed:25645841}.
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:O05442};
CC -!- ACTIVITY REGULATION: Glycohydrolase activity is completely inhibited by
CC interaction with the immunity factor for TNT (IFT) homolog. This
CC inhibition protects M.bovis from self-poisoning.
CC {ECO:0000250|UniProtKB:O05442}.
CC -!- SUBUNIT: Interacts with the immunity factor for TNT (IFT) homolog.
CC {ECO:0000250|UniProtKB:O05442}.
CC -!- SUBCELLULAR LOCATION: [N-terminal channel domain]: Cell outer membrane
CC {ECO:0000250|UniProtKB:O05442}.
CC -!- SUBCELLULAR LOCATION: [Tuberculosis necrotizing toxin homolog]:
CC Secreted {ECO:0000250|UniProtKB:O05442}. Cell surface
CC {ECO:0000250|UniProtKB:O05442}. Note=M.bovis does not permeabilize
CC phagosomes and does not escape from phagosomes. Thus, the C-terminal
CC TNT domain is likely trapped in phagosomes during M.bovis BCG
CC infection, where it is incapable of inducing necrosis of macrophages.
CC {ECO:0000305|PubMed:25645841}.
CC -!- PTM: The C-terminal domain (TNT) is probably cleaved.
CC {ECO:0000250|UniProtKB:O05442}.
CC -!- DISRUPTION PHENOTYPE: Deletion of the gene confers high-level drug
CC resistance to a wide range of antibiotics and antituberculosis drugs,
CC and protects M.bovis from killing in macrophages that prevent
CC intracellular mycobacterial replication. Increases resistance to small,
CC hydrophilic antibiotics, to antituberculosis drugs, to large,
CC hydrophobic or hydrophilic antibiotics such as erythromycin, rifampicin
CC and streptomycin, and to nitric oxide. Under in vivo conditions, such
CC as in human THP-1 macrophages, absence of the gene drastically reduces
CC intracellular growth of M.bovis. {ECO:0000269|PubMed:25645841}.
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DR EMBL; AM408590; CAL73950.1; -; Genomic_DNA.
DR RefSeq; WP_003899759.1; NC_008769.1.
DR AlphaFoldDB; A0A0H3MAA9; -.
DR SMR; A0A0H3MAA9; -.
DR KEGG; mbb:BCG_3960c; -.
DR HOGENOM; CLU_013587_0_0_11; -.
DR OMA; RNGLCSI; -.
DR Proteomes; UP000001472; Chromosome.
DR GO; GO:0009279; C:cell outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0046930; C:pore complex; IEA:UniProtKB-KW.
DR GO; GO:0061810; F:NAD glycohydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0015288; F:porin activity; IEA:UniProtKB-KW.
DR GO; GO:0006811; P:ion transport; IEA:UniProtKB-KW.
DR InterPro; IPR025331; TNT.
DR Pfam; PF14021; TNT; 1.
PE 3: Inferred from homology;
KW Cell outer membrane; Hydrolase; Ion transport; Membrane; NAD; Porin;
KW Secreted; Transmembrane; Transmembrane beta strand; Transport.
FT CHAIN 1..846
FT /note="Outer membrane channel protein CpnT"
FT /id="PRO_0000437785"
FT CHAIN 1..?
FT /note="N-terminal channel domain"
FT /evidence="ECO:0000305"
FT /id="PRO_0000437786"
FT CHAIN ?..846
FT /note="Tuberculosis necrotizing toxin homolog"
FT /evidence="ECO:0000305"
FT /id="PRO_0000437787"
FT DOMAIN 751..846
FT /note="TNT"
FT /evidence="ECO:0000255"
FT REGION 1..443
FT /note="NTD"
FT /evidence="ECO:0000250|UniProtKB:O05442"
FT REGION 442..630
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 651..846
FT /note="TNT"
FT /evidence="ECO:0000250|UniProtKB:O05442"
FT COMPBIAS 449..508
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 757
FT /evidence="ECO:0000250|UniProtKB:Q4WL81"
FT ACT_SITE 822
FT /evidence="ECO:0000250|UniProtKB:Q4WL81"
FT BINDING 780
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q4WL81"
SQ SEQUENCE 846 AA; 88335 MW; CB7DF1D77C7C9A25 CRC64;
MAPLAVDPAA LDSAGGAVVA AGAGLGAVIS SLTAALAGCA GMAGDDPAGA VFGRSYDGSA
AALVQAMSVA RNGLCNLGDG VRMSAHNYSL AEAMSDVAGR AAPLPAPPPS GCVGVGAPPS
AVGGGGGAPK GWGWVAPYIG MIWPNGDSTK LRAAAVAWRS AGTQFALTEI QSTAGPMGVI
RAQQLPEAGL IESAFADAYA STTAVVGQCH QLAAQLDAYA ARIDAVHAAV LDLLARICDP
LTGIKEVWEF LTDQDEDEIQ RIAHDIAVVV DQFSGEVDAL AAEITAVVSH AEAVITAMAD
HAGKQWDRFL HSNPVGVVID GTGQQLKGFG EEAFGMAKDS WDLGPLRASI DPFGWYRSWE
EMLTGMAPLA GLGGENAPGV VESWKQFGKS LIHWDEWTTN PNEALGKTVF DAATLALPGG
PLSKLGSKGR DILAGVRGLK ERLEPTTPHL EPPATPPRPG PQPPRIEPPE SGHPAPAPAA
KPAPVPANGP LPHSPTESKP PPVDRPAEPV APSSASAGQP RVSAATTPGT HVPHGLPQPG
EHVPAQAPPA TTLLGGPPVE SAPATAHQPQ WATTPAAPAA APHSTPGGVH STESGPHGRS
LSAHGSEPTH DGASHGSGHG SGSEPPGLHA PHREQQLAMH SNEPAGEGWH RLSDEAVDPQ
YGEPLSRHWD FTDNPADRSR INPVVAQLME DPNAPFGRDP QGQPYTQERY QERFNSVGPW
GQQYSNFPPN NGAVPGTRIA YTNLEKFLSD YGPQLDRIGG DQGKYLAIME HGRPASWEQR
ALHVTSLRDP YHAYTIDWLP EGWFIEVSEV APGCGQPGGS IQVRIFDHQN EMRKVEELIR
RGVLRQ
