vapC21 Resolved · high auto-curated
H37Rv Rv2757c · MTBC0 mtbc0_002934 ·
138 aa · 3092585–3093001 (-) ·
RefSeq NP_217273.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | ribonuclease VapC21 |
|---|---|
| MTBC0 PGAP re-annotation | type II toxin-antitoxin system toxin ribonuclease C21 |
| Revised (this work) | Type II toxin-antitoxin system toxin ribonuclease C21. 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 |
P9WF91
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Ribonuclease VapC21 |
| 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 VapB21. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | vapC |
| eggNOG description | Toxic component of a toxin-antitoxin (TA) module. An RNase |
| Orthologous group | COG1487 |
| 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 | 0.976 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 1 missense, 2 nonsense, 0 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 0.32% of strains (460) · 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 | 2.7e-14 | 5–122 | PIN domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: vapB21 (antitoxin VapB21), high confidence from genomic context alone (score 980 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2758c vapB21 |
antitoxin VapB21 | 979 | 980 ctx | neighborhood:882 coexpression:804 |
Rv2756c hsdM |
type I restriction/modification system DNA methylase HsdM | 890 | 888 ctx | neighborhood:598 coexpression:733 |
Rv2759c vapC42 |
ribonuclease VapC42 | 828 | 764 ctx | neighborhood:753 |
Rv2760c vapB42 |
antitoxin VapB42 | 760 | 760 ctx | neighborhood:753 |
Rv2761c hsdS |
type I restriction/modification system specificity determinant HsdS | 741 | 741 ctx | neighborhood:731 |
Rv2762c hyp |
hypothetical protein | 960 | 711 ctx | neighborhood:707 textmining:870 |
Rv2755c hsdS.1 |
Rv2755c, (MTV002.20c), len: 91 aa. Possible hsdS.1,fragment of type I restriction/modification system specificity determinant (S protein), s | 593 | 594 ctx | neighborhood:572 |
Rv0582 vapC26 |
ribonuclease VapC26 | 595 | 547 ctx | cooccurence:538 |
Rv2763c dfrA |
dihydrofolate reductase | 612 | 528 ctx | neighborhood:523 |
Rv1607 chaA |
ionic transporter integral membrane protein ChaA | 502 | 502 ctx | cooccurence:499 |
Rv3407 vapB47 |
antitoxin VapB47 | 442 | 443 | |
Rv0300 vapB2 |
antitoxin VapB2 | 433 | 434 | experimental:412 |
Rv2601A vapB41 |
antitoxin VapB41 | 432 | 410 | |
Rv1952 vapB14 |
antitoxin VapB14 | 429 | 407 | |
Rv2764c thyA |
thymidylate synthase ThyA | 506 | 403 ctx | neighborhood:400 |
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 VapC21
- MTBC0 PGAP product: type II toxin-antitoxin system toxin ribonuclease C21
- Pfam (hmmscan --cut_ga): PIN PF01850.28 (E=3e-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_217273.1)
- 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 P9WF91 (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 —
32 functional partner(s); context anchor
vapB21 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002934|Rv2757c|vapC21 MTTRYLLDKSAAYRAHLPAVRHRLEPLMERGLLARCGITDLEFGVSARSREDHRTLGTYRRDALEYVNTPDTVWVRAWEIQEALTDKGFHRSVKIPDLIIAAVAEHHGIPVMHYDQDFERIAAITRQPVEWVVAPGTA