vapC25 Family assigned · medium auto-curated
H37Rv Rv0277c · MTBC0 mtbc0_000294 ·
142 aa · 333090–333518 (-) ·
RefSeq NP_214791.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | ribonuclease VapC25 |
|---|---|
| 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 |
P9WF85
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Ribonuclease VapC25 |
| 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 VapB25. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | 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 |
| Orthologous group | COG1848 |
| KEGG orthology |
K07064
|
| Gene Ontology (6) |
GO:0008150, GO:0040008, GO:0045926, GO:0048519, GO:0050789, GO:0065007
|
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 | 0.21 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 10 synonymous, 6 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 |
|---|---|---|---|---|
PIN | PF01850.28 | 2.4e-14 | 3–133 | PIN domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: vapC48 (ribonuclease VapC48), high confidence from genomic context alone (score 775 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0749 vapC31 |
ribonuclease VapC31 | 806 | 805 | coexpression:804 |
Rv3697c vapC48 |
ribonuclease VapC48 | 775 | 775 ctx | cooccurence:774 |
Rv0277A vapB25 |
Rv0277A, len: 85 aa. Possible vapB25, antitoxin,part of toxin-antitoxin (TA) operon with Rv0277c, see Arcus et al. 2005. Has in-frame stop c | 873 | 705 ctx | neighborhood:705 textmining:587 |
Rv0278c PE_PGRS3 |
PE-PGRS family protein PE_PGRS3 | 660 | 660 ctx | neighborhood:660 |
Rv0748 vapB31 |
antitoxin VapB31 | 798 | 573 | experimental:508 textmining:547 |
Rv2871 vapB43 |
antitoxin VapB43 | 526 | 527 | experimental:508 |
Rv0595c vapC4 |
ribonuclease VapC4 | 879 | 518 ctx | cooccurence:509 textmining:761 |
Rv2548 vapC19 |
ribonuclease VapC19 | 736 | 493 ctx | cooccurence:489 textmining:502 |
Rv1720c vapC12 |
ribonuclease VapC12 | 568 | 489 ctx | cooccurence:486 |
Rv0960 vapC9 |
ribonuclease VapC9 | 460 | 460 ctx | cooccurence:452 |
Rv0626 vapB5 |
antitoxin VapB5 | 457 | 457 ctx | cooccurence:440 |
Rv1397c vapC10 |
ribonuclease VapC10 | 665 | 449 ctx | cooccurence:439 textmining:419 |
Rv3384c vapC46 |
ribonuclease VapC46 | 522 | 380 | |
Rv0549c vapC3 |
ribonuclease VapC3 | 419 | 364 | |
Rv0065 vapC1 |
ribonuclease VapC1 | 744 | 352 | textmining:622 |
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 VapC25
- MTBC0 PGAP product: type II toxin-antitoxin system VapC family toxin
- Pfam (hmmscan --cut_ga): PIN PF01850.28 (E=2e-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_214791.1)
- 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 P9WF85 (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 —
31 functional partner(s); context anchor
vapC48 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000294|Rv0277c|vapC25 MFLIDVNVLLAAHRGDHPNHRTVRPWFDRLLAADDPFTVPNLVWASFLRLTTNRRIFEIPSPRADAFAFVEAVNAQPHHLPTSPGPRHLVLLRKLCDEADASGDLIPDAVLGAIAVEHHCAVVSLDRDFARFASVRHIRPPI