id: Pfam:PF14021
pfam_id: PF14021
name: Tuberculosis necrotizing toxin
short_name: TNT
seed_status: EX_DUF
characterization_status: UNSCORED
curation_status: SEEDED
source_url: https://www.ebi.ac.uk/interpro/api/entry/pfam/PF14021
counters:
  proteins: 2673
  matches: 2676
  proteomes: 1695
  taxa: 2848
  structures: 8
  alphafold_models: 1685
  domain_architectures: 109
provenance:
  snapshot_id: interpro-pfam-duf-2026-10-10
  path: data/worklists/interpro-pfam-duf-2026-10-10.json
  sha256: 17fb625876c9326ed284263a47bcd84e0d7844a31c040dc06cd2260c36f1c383
  generated_at: '2026-10-10T07:44:21.614711Z'
  source_url: https://www.ebi.ac.uk/interpro/api/entry/pfam/
interpro_id: InterPro:IPR025331
description: This is the C-terminal domain secreted by Mycobacterium tuberculosis (Mtb). It induces necrosis
  of infected cells to evade immune responses. Mtb utilizes the protein CpnT to kill human macrophages
  by secreting its C-terminal domain (CTD), named tuberculosis necrotizing toxin (TNT) that induces necrosis.
  It acts as a NAD+ glycohydrolase which hydrolyzes the essential cellular coenzyme NAD+ in the cytosol
  of infected macrophages resulting in necrotic cell death [[cite:PUB00082601]]. CpnT transports its toxic
  CTD from the cell surface of M. tuberculosis by proteolytic cleavage, where the toxin is cleaved to
  induce host cell death [[cite:PUB00082600]]. Structural analysis determined that the TNT core contains
  only six beta-strands as opposed to seven found in all known NAD+-utilizing toxins, and is significantly
  smaller, with only two short alpha-helices and two 3/10 helices. Furthermore, the putative NAD+ binding
  pocket identified Q822, Y765 and R757 as residues possibly involved in NAD+-binding and hydrolysis based
  on similar positions of catalytic amino acids of ADP-ribosylating toxins. While glutamine 822 residue
  was detected to be highly conserved among TNT homologs [[cite:PUB00082601]].