vapC46 Family assigned · medium auto-curated
H37Rv Rv3384c · MTBC0 mtbc0_003597 ·
130 aa · 3824604–3824996 (-) ·
RefSeq NP_217901.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | ribonuclease VapC46 |
|---|---|
| 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 |
O50411
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Ribonuclease VapC46 |
| EC (curated) |
EC 3.1.-.-
|
| Curated function | Toxic component of a type II toxin-antitoxin (TA) system. An RNase (By similarity). Upon expression in M.smegmatis inhibits colony formation. Its toxic effect is neutralized by coexpression with cognate antitoxin VapB46. |
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 |
| KEGG orthology |
K07064
|
| Gene Ontology (12) |
GO:0005575, GO:0005623, GO:0005886, GO:0008150, GO:0016020, GO:0040008, GO:0044464, GO:0045926, GO:0048519, GO:0050789, GO:0065007, GO:0071944
|
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 | 0.128 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 9 synonymous, 3 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.12% of strains (175) · 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 | 4.6e-14 | 4–120 | PIN domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: vapB46 (antitoxin VapB46), high confidence from genomic context alone (score 959 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3385c vapB46 |
antitoxin VapB46 | 959 | 959 ctx | neighborhood:780 cooccurence:766 |
Rv3407 vapB47 |
antitoxin VapB47 | 699 | 699 ctx | cooccurence:688 |
Rv1720c vapC12 |
ribonuclease VapC12 | 757 | 674 ctx | cooccurence:673 |
Rv0626 vapB5 |
antitoxin VapB5 | 636 | 636 ctx | cooccurence:620 |
Rv0960 vapC9 |
ribonuclease VapC9 | 621 | 622 ctx | cooccurence:616 |
Rv0627 vapC5 |
ribonuclease VapC5 | 590 | 580 ctx | cooccurence:510 |
Rv0065 vapC1 |
ribonuclease VapC1 | 848 | 575 ctx | cooccurence:571 textmining:657 |
Rv0549c vapC3 |
ribonuclease VapC3 | 642 | 567 ctx | cooccurence:562 |
Rv3098A |
PemK-like protein | 562 | 546 ctx | cooccurence:545 |
Rv3387 |
transposase | 524 | 524 ctx | neighborhood:524 |
Rv3386 |
transposase | 524 | 524 ctx | neighborhood:524 |
Rv0456A mazF1 |
toxin MazF1 | 513 | 496 ctx | cooccurence:487 |
Rv0665 vapC8 |
ribonuclease VapC8 | 488 | 477 ctx | cooccurence:473 |
Rv2801A mazE9 |
antitoxin MazE9 | 463 | 463 ctx | cooccurence:462 |
Rv1102c mazF3 |
mRNA interferase MazF3 | 522 | 444 ctx | cooccurence:438 |
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 VapC46
- MTBC0 PGAP product: type II toxin-antitoxin system VapC family toxin
- Pfam (hmmscan --cut_ga): PIN PF01850.28 (E=5e-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_217901.1)
- 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 O50411 (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 —
27 functional partner(s); context anchor
vapB46 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003597|Rv3384c|vapC46 MAAIYLDSSAIVKLAVREPESDALRRYLRTRHPRVSSALARAEVMRALLDKGESARKAGRRALAHLDLLRVDKRVLDLAGGLLPFELRTLDAIHLATAQRLGVDLGRLCTYDDRMRDAAKTLGMAVIAPS