All families / PF14021
PF14021: TNT
Tuberculosis necrotizing toxin
- Curation status
- SEEDED
- Seed status
- EX DUF
- Characterization
- UNSCORED
Grounding
PF14021: Tuberculosis necrotizing toxin
IPR025331: integrated entry for Tuberculosis necrotizing toxin
Source 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 [InterPro reference 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 [InterPro reference 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 [InterPro reference PUB00082601].
Evidence and references
- InterPro entry and its literature references. PUB identifiers are internal InterPro references, not PubMed identifiers. Unresolved citations link to the originating entry.
- Frozen description source: InterPro/Pfam API
Source descriptions and links are provenance, not independent functional validation.
Evidence counts: not scored.
Curated functional assertions
No curated functional assertions supplied.
Protein sequence examples
No sibling protein candidate in the scanned commits.
Pfam membership is not functional evidence. Whole-protein sequences do not establish domain boundaries. A coverage gap here is not absence from UniProt.
Sequences and metadata: UniProt Consortium, CC BY 4.0.
Domain matches
No residue-level domain match evidence is available in this build. Structure and AlphaFold counters do not supply coordinates or establish function.
Snapshot counters
- proteins
- 2,673
- matches
- 2,676
- proteomes
- 1,695
- taxa
- 2,848
- structures
- 8
- alphafold models
- 1,685
- domain architectures
- 109
Classification basis
pfam previous unknown name
No scoring reasons supplied.
Related Mech records
This family joined the worklist after the frozen cross-Mech scan, so other Mechs were not searched for it. Missing links here are not evidence that other Mechs lack it; rows shown come from mentions of a former DUF/UPF name.
No cross-Mech examples are present in the supplied snapshot.
Curation history and reviews
No retained curation events supplied.
No retained review supplied.
Record source
Status and evidence
- Seed status
- A name-based classification of frozen InterPro/Pfam metadata. UNKNOWN CANDIDATE means the metadata explicitly says the function is unknown. KNOWN HISTORICAL DUF means a DUF name matched without that wording; this heuristic is not proof of a known function and does not establish experimental characterization. EX DUF means Pfam renamed the family away from a DUF/UPF name, as recorded in Pfam's previous identifiers; a rename usually follows published work on some members but is naming history, not proof of function for every member. Some EX DUF families' current names or descriptions still say the function is unknown; their classification basis lists this, and scoring does not treat them as characterized. FALSE POSITIVE TEXT HIT means the naming rules did not match.
- Characterization
- A separate evidence-scoring result. UNSCORED means no score has been calculated; it is not evidence that the family lacks a known function. Missing scores are not negative evidence. PARTIALLY CHARACTERIZED has partial support; KNOWN HISTORICAL DUF can inherit the seed label or reflect a known-function signal. Neither label implies experimental validation.
- Evidence counts
- Source-specific signals, not unique proteins, publications, or confidence scores. Known counts Rhea reactions and experimentally supported GO molecular-function annotations. Partial counts functional/domain assignments. Context counts structural, environmental, orthology, interaction and neighborhood signals; context alone does not assign function. Repeated annotations may not be independent.
- Curation status
- Reported separately from seed classification and characterization. SNAPSHOT ONLY means no curated metadata was supplied for this build. SEEDED denotes a source-derived record, not an expert-reviewed functional claim.
- Missing counts
- Not available means the source did not supply that counter. A zero is a reported count. Not scored means evidence counts are unavailable.