UniProt:O05442 cpnT

chain
  • chain:1-846
  • chain:1-
  • chain:-846
checksum CB7DF1D77C7C9A25
comment
  • FUNCTION Has a dual function in uptake of nutrients and induction of host cell death. The N-terminal domain (NTD) forms an outer membrane channel and is used for uptake of nutrients across the outer membrane. The secreted C-terminal toxic domain (TNT) acts as a glycohydrolase, which hydrolyzes the essential cellular coenzyme NAD(+) in the cytosol of infected macrophages, leading to necrotic host cell death. Both functions are required for survival, replication and cytotoxicity of M.tuberculosis in macrophages.CATALYTIC ACTIVITY H2O + NAD(+) = ADP-D-ribose + H(+) + nicotinamideACTIVITY REGULATION Glycohydrolase activity is completely inhibited by interaction with the immunity factor for TNT (IFT). This inhibition protects M.tuberculosis from self-poisoning.BIOPHYSICOCHEMICAL PROPERTIES kcat is 52 sec(-1).SUBUNIT Interacts with the immunity factor for TNT (IFT) (PubMed:26237511). Oligomer formation is required for channel activity (PubMed:24753609).INTERACTION Secreted into the cytosol of infected macrophages while the bacteria are still confined to the phagosome. Access to the macrophage cytosol depends on the ESX-1 / type VII secretion system (T7SS).PTM The C-terminal toxic domain is cleaved, probably after integration of CpnT into the outer membrane.DISRUPTION PHENOTYPE Deletion reduces growth on glycerol and glucose as sole carbon sources. Deletion mutant does not replicate in differentiated THP-1 macrophages and lacks cytotoxicity (PubMed:24753609). Lack of cpnT does not increase drug resistance in vitro (PubMed:25645841). Deletion mutant does not decrease NAD(+) levels in infected macrophages (PubMed:26237511).
created [InstanceEdit:9637696] Jassal, Bijay, 2019-02-19
crossReference
databaseName UniProt
dbId 9637681
description
  • recommendedName: fullName evidence="9"Outer membrane channel protein CpnT alternativeName: fullName evidence="7"Channel protein with necrosis-inducing toxin component recommendedName: fullName evidence="9"N-terminal channel domain /component component recommendedName: fullName evidence="8"Tuberculosis necrotizing toxin shortName evidence="8"TNT alternativeName: fullName evidence="8"NAD(+) glycohydrolase ecNumber evidence="6"3.2.2.5 /component
displayName UniProt:O05442 cpnT
geneName
  • cpnT
  • Rv3903c
identifier O05442
isSequenceChanged false
keyword
  • 3D-structure
  • Cell outer membrane
  • Host cytoplasm
  • Hydrolase
  • Ion transport
  • Membrane
  • NAD
  • Porin
  • Reference proteome
  • Secreted
  • Toxin
  • Transmembrane
  • Transmembrane beta strand
  • Transport
  • Virulence
modified [InstanceEdit:11642743] Wright, Adam, 2024-03-11
name
  • cpnT
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • CPNT_MYCTU
  • F2GDR4
  • I6Y4T3
  • Q7D4M4
sequenceLength 846
species [Species:176806] Mycobacterium tuberculosis
url https://purl.uniprot.org/uniprot/O05442
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