ift Resolved · high auto-curated
H37Rv Rv3902c · MTBC0 mtbc0_004136 ·
176 aa · 4411617–4412147 (-) ·
RefSeq NP_218419.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | necrotizing toxin immunity factor IFT |
| Revised (this work) | Necrotizing toxin immunity factor IFT. Pfam: Imm61 (PF15598.12). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O05443
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Immunity factor for TNT |
| Curated function | Antitoxin for tuberculosis necrotizing toxin (TNT). Acts by binding directly to TNT, which inhibits NAD(+) glycohydrolase activity of TNT and protects M.tuberculosis from self-poisoning. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Immunity protein 61 |
| Orthologous group | 2DEW1 |
Orthology-based transfer (eggNOG 5.0.2, diamond). EC/KO/GO/CAZy are computed annotations, not manual curation; cross-check against the primary literature before treating a specific reaction as established.
Conservation & selection (intra-MTBC, 145 209 strains)
| pN/pS | 0.205 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 2 missense, 0 nonsense, 0 frameshift |
pN/pS from segregating SNPs (singletons removed) normalised by possible sites. Low pN/pS = purifying selection (a strong signal that a "hypothetical" is a real, constrained gene). A high pN/pS is ambiguous: relaxed constraint or positive selection (drug resistance, antigenic variation) inflate it; e.g. rpoB/katG/pncA score high here for resistance, not loss of function. A clonal disruption (one allele over a clade) suggests lineage pseudogenisation; a convergent one (many independent alleles) is typical of resistance loss-of-function.
Domains (Pfam, hmmscan --cut_ga)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
Imm61 | PF15598.12 | 3.1e-65 | 14–167 | Immunity protein 61 |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: esxE (ESAT-6 like protein EsxE), high confidence from genomic context alone (score 883 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3903c cpnT hyp |
hypothetical protein | 996 | 978 ctx | neighborhood:882 experimental:817 textmining:870 |
Rv3904c esxE |
ESAT-6 like protein EsxE | 941 | 883 ctx | neighborhood:882 textmining:522 |
Rv3905c esxF |
ESAT-6 like protein EsxF | 953 | 881 ctx | neighborhood:880 textmining:630 |
Rv3899c hyp |
hypothetical protein | 662 | 663 | experimental:652 |
Rv2082 hyp |
hypothetical protein | 662 | 663 | experimental:652 |
Rv3906c hyp |
hypothetical protein | 970 | 634 ctx | neighborhood:629 textmining:922 |
Rv3907c pcnA |
poly(A) polymerase PcnA | 583 | 583 ctx | neighborhood:582 |
Rv3884c eccA2 |
ESX-2 secretion system protein EccA | 523 | 51 | textmining:518 |
Rv3896c hyp |
hypothetical protein | 804 | 47 | textmining:803 |
Rv0152c PE2 |
PE family protein PE2 | 433 | 41 | textmining:433 |
STRING combines evidence channels (neighborhood, fusion, cooccurrence, coexpression, experimental, database, text-mining) into a 0–1000 score. The ctx badge marks edges carried by the genomic-context channels (conserved neighborhood, fusion, phylogenetic co-occurrence), which are independent of orthology and structure and the strongest signal for an unknown gene. The no text-mining column recomputes the score from data alone, so a link that does not depend on the literature is visible. Association is a function hypothesis, not proof: corroborate with the operon context and the primary literature before assigning a function.
Evidence
- Legacy H37Rv annotation: hypothetical protein
- MTBC0 PGAP product: necrotizing toxin immunity factor IFT
- Pfam (hmmscan --cut_ga): Imm61 PF15598.12 (E=3e-65)
- (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)
Sources
- Ancestral sequence & coordinates: Harrison LB et al. (2024), An imputed ancestral reference genome for the MTBC, doi:10.1101/2023.09.07.556366
- Product annotation: NCBI PGAP on MTBC0; legacy from H37Rv NC_000962.3 (RefSeq NP_218419.1)
- Domains: Pfam-A via hmmscan --cut_ga — Imm61 (PF15598.12)
- Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
- Controlled vocabulary: eggNOG-mapper 2.1.12 (Cantalapiedra et al. 2021,
doi:10.1093/molbev/msab293), eggNOG 5.0 DB
(Huerta-Cepas et al. 2019) — OG
2DEW1 - Curated reference: UniProt O05443 (SwissProt, reviewed; Evidence at protein level)
- Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
10 functional partner(s); context anchor
esxE - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_004136|Rv3902c|ift MTIGVDLSTDLQDWIRLSGMNMIQGSETNDGRTILWNKGGEVRYFIDRLAGWYVITSSDRMSREGYEFAAASMSVIEKYLYGYFGGSVRSERELPAIRAPFQPEELMPEYSIGTMTFAGRQRDTLIDSSGTVVAITAADRLVELSHYLDVSVNVIKDSFLDSEGKPLFTLWKDYKG