vapC19 Family assigned · medium auto-curated
H37Rv Rv2548 · MTBC0 mtbc0_002715 ·
125 aa · 2892405–2892782 (+) ·
RefSeq NP_217064.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | ribonuclease VapC19 |
|---|---|
| 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 |
P9WF93
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Ribonuclease VapC19 |
| 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 VapB19. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | PIN domain |
| Orthologous group | COG1487 |
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 | 0.239 · 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 |
|---|---|---|---|---|
PIN | PF01850.28 | 9.9e-12 | 3–111 | PIN domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: vapB19 (antitoxin VapB19), high confidence from genomic context alone (score 884 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2547 vapB19 |
antitoxin VapB19 | 941 | 884 ctx | neighborhood:882 textmining:518 |
Rv2546 vapC18 |
ribonuclease VapC18 | 740 | 740 ctx | neighborhood:739 |
Rv2545 vapB18 |
antitoxin VapB18 | 588 | 589 ctx | neighborhood:508 |
Rv0277c vapC25 |
ribonuclease VapC25 | 736 | 493 ctx | cooccurence:489 textmining:502 |
Rv0749 vapC31 |
ribonuclease VapC31 | 693 | 490 ctx | cooccurence:485 textmining:423 |
Rv3098A |
PemK-like protein | 480 | 479 ctx | cooccurence:476 |
Rv2544 lppB |
lipoprotein LppB | 475 | 476 ctx | neighborhood:473 |
Rv2543 lppA |
lipoprotein LppA | 464 | 464 ctx | neighborhood:458 |
Rv2063A mazF7 |
mRNA interferase MazF7 | 452 | 451 ctx | cooccurence:448 |
Rv2103c vapC37 |
ribonuclease VapC37 | 747 | 449 ctx | cooccurence:438 textmining:561 |
Rv2872 vapC43 |
ribonuclease VapC43 | 653 | 432 ctx | cooccurence:430 textmining:414 |
Rv0626 vapB5 |
antitoxin VapB5 | 432 | 432 | |
Rv0300 vapB2 |
antitoxin VapB2 | 430 | 430 | experimental:412 |
Rv2807 hyp |
hypothetical protein | 424 | 425 ctx | cooccurence:423 |
Rv2549c vapC20 |
ribonuclease VapC20 | 718 | 420 ctx | cooccurence:408 textmining:534 |
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 VapC19
- MTBC0 PGAP product: type II toxin-antitoxin system VapC family toxin
- Pfam (hmmscan --cut_ga): PIN PF01850.28 (E=1e-11)
- (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_217064.1)
- 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 P9WF93 (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 —
49 functional partner(s); context anchor
vapB19 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002715|Rv2548|vapC19 MKLIDTTIAVDHLRGEPAAAVLLAELINNGEEIAASELVRFELLAGVRESELAALEAFFSAVVWTLVTEDIARIGGRLARRYRSSHRGIDDVDYLIAATAIVVDADLLTTNVRHFPMFPDLQPPY