vapC2 Family assigned · medium auto-curated
H37Rv Rv0301 · MTBC0 mtbc0_000320 ·
141 aa · 367383–367808 (+) ·
RefSeq NP_214815.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | ribonuclease VapC2 |
|---|---|
| MTBC0 PGAP re-annotation | PIN domain nuclease |
| Revised (this work) | PIN domain nuclease. 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 |
P9WFB9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Ribonuclease VapC2 |
| EC (curated) |
EC 3.1.-.-
|
| Curated function | Toxic component of a type II toxin-antitoxin (TA) system. Acts as an RNase. Upon expression in M.smegmatis inhibits translation, growth and colony formation. All its toxic effects are neutralized by coexpression with cognate antitoxin VapB2. |
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 | COG1487 |
| Gene Ontology (57) |
GO:0003674, GO:0003824, GO:0004518, GO:0004540, GO:0006139, GO:0006417, GO:0006725, GO:0006807, GO:0008150, GO:0008152, GO:0009889, GO:0009890 +45 more
|
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 | 0.352 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 1 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.65% of strains (945) · 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 | 4.4e-14 | 7–125 | PIN domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: vapB2 (antitoxin VapB2), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0300 vapB2 |
antitoxin VapB2 | 999 | 1000 ctx | neighborhood:882 experimental:999 textmining:870 |
Rv0299 |
toxin | 683 | 683 ctx | neighborhood:667 |
Rv0298 |
antitoxin | 675 | 675 ctx | neighborhood:667 |
Rv0302 |
transcriptional regulator | 593 | 593 ctx | neighborhood:520 |
Rv0303 |
dehydrogenase/reductase | 504 | 504 ctx | neighborhood:504 |
Rv0297 PE_PGRS5 |
PE-PGRS family protein PE_PGRS5 | 417 | 417 ctx | neighborhood:417 |
Rv2601A vapB41 |
antitoxin VapB41 | 434 | 412 | |
Rv3407 vapB47 |
antitoxin VapB47 | 411 | 411 | |
Rv1952 vapB14 |
antitoxin VapB14 | 431 | 408 | |
Rv2010 vapC15 |
ribonuclease VapC15 | 636 | 281 | textmining:515 |
Rv0626 vapB5 |
antitoxin VapB5 | 847 | 260 | textmining:803 |
Rv2009 vapB15 |
antitoxin VapB15 | 643 | 240 | textmining:550 |
Rv2545 vapB18 |
antitoxin VapB18 | 718 | 217 | textmining:655 |
Rv0960 vapC9 |
ribonuclease VapC9 | 400 | 214 | |
Rv1114 vapC32 |
ribonuclease VapC32 | 600 | 204 | textmining:519 |
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 VapC2
- MTBC0 PGAP product: PIN domain nuclease
- Pfam (hmmscan --cut_ga): PIN PF01850.28 (E=4e-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_214815.1)
- 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
COG1487 - Curated reference: UniProt P9WFB9 (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 —
36 functional partner(s); context anchor
vapB2 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000320|Rv0301|vapC2 MTDQRWLIDKSALVRLTDSPDMEIWSNRIERGLVHITGVTRLEVGFSAECGEIARREFREPPLSAMPVEYLTPRIEDRALEVQTLLADRGHHRGPSIPDLLIAATAELSGLTVLHVDKDFDAIAALTGQKTERLTHRPPSA