vapC40 Family assigned · medium auto-curated
H37Rv Rv2596 · MTBC0 mtbc0_002763 ·
134 aa · 2949287–2949691 (+) ·
RefSeq NP_217112.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | ribonuclease VapC40 |
|---|---|
| MTBC0 PGAP re-annotation | type II toxin-antitoxin system VapC family toxin |
| Revised (this work) | Type II toxin-antitoxin system VapC family toxin. Pfam: PIN (PF01850.28). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WF61
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Ribonuclease VapC40 |
| EC (curated) |
EC 3.1.-.-
|
| Curated function | Toxic component of a type II toxin-antitoxin (TA) system. An RNase (By similarity). Its cognate antitoxin is VapB40. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Toxic component of a toxin-antitoxin (TA) module. An RNase |
| Orthologous group | COG1848 |
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 | n/a |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 0 synonymous, 3 missense, 1 nonsense, 0 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.20% of strains (290) · clonal |
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 |
|---|---|---|---|---|
PIN | PF01850.28 | 1.5e-14 | 4–121 | PIN domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: vapB40 (antitoxin VapB40), high confidence from genomic context alone (score 883 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2595 vapB40 |
antitoxin VapB40 | 883 | 883 ctx | neighborhood:882 |
Rv2597 |
membrane protein | 590 | 590 ctx | neighborhood:590 |
Rv2598 hyp |
hypothetical protein | 587 | 587 ctx | neighborhood:584 |
Rv2592c ruvB |
Holliday junction ATP-dependent DNA helicase RuvB | 572 | 572 ctx | neighborhood:567 |
Rv2593c ruvA |
Holliday junction ATP-dependent DNA helicase RuvA | 572 | 572 ctx | neighborhood:567 |
Rv2594c ruvC |
crossover junction endodeoxyribonuclease RuvC | 570 | 571 ctx | neighborhood:567 |
Rv2599 |
membrane protein | 545 | 545 ctx | neighborhood:544 |
Rv2601 speE |
spermidine synthase | 416 | 416 ctx | neighborhood:410 |
Rv2010 vapC15 |
ribonuclease VapC15 | 604 | 57 | textmining:598 |
Rv1561 vapC11 |
ribonuclease VapC11 | 569 | 57 | textmining:562 |
Rv0617 vapC29 |
ribonuclease VapC29 | 420 | 55 | textmining:412 |
Rv0960 vapC9 |
ribonuclease VapC9 | 400 | 53 | |
Rv3408 vapC47 |
ribonuclease VapC47 | 804 | 50 | textmining:803 |
Rv0240 vapC24 |
ribonuclease VapC24 | 761 | 47 | textmining:760 |
Rv2494 vapC38 |
ribonuclease VapC38 | 656 | 47 | textmining:654 |
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: ribonuclease VapC40
- MTBC0 PGAP product: type II toxin-antitoxin system VapC family toxin
- Pfam (hmmscan --cut_ga): PIN PF01850.28 (E=1e-14)
- (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_217112.1)
- Domains: Pfam-A via hmmscan --cut_ga — PIN (PF01850.28)
- 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
COG1848 - Curated reference: UniProt P9WF61 (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 —
22 functional partner(s); context anchor
vapB40 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002763|Rv2596|vapC40 MIAPDTSVLVAGFATWHEGHEAAVRALNRGVHLIAHAAVETYSVLTRLPPPHRIAPVAVHAYLADITSSNYLALDARSYRGLTDHLAEHDVTGGATYDALVGFTAKAAGAKLLTRDLRAVETYERLRVEVELVT