vapC11 Resolved · high auto-curated

H37Rv Rv1561 · MTBC0 mtbc0_001669 · 134 aa · 1776943–1777347 (+) · RefSeq NP_216077.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ribonuclease VapC11
MTBC0 PGAP re-annotationtype II toxin-antitoxin system toxin ribonuclease VapC11
Revised (this work)Type II toxin-antitoxin system toxin ribonuclease VapC11. 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 P9WFA5 SwissProt · reviewed · Evidence at protein level
UniProt nameRibonuclease VapC11
EC (curated) EC 3.1.-.-
Curated functionToxic component of a type II toxin-antitoxin (TA) system. Acts as an RNase. Upon expression in E.coli and M.smegmatis inhibits translation, cell growth and colony formation. Its toxic effects on cell growth and colony formation are neutralized by coexpression with cognate antitoxin VapB11; the effect on translation has not been tested but is probably also neutralized.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionToxic component of a toxin-antitoxin (TA) module. An RNase
Orthologous groupCOG1487
Gene Ontology (69) GO:0003674, GO:0003824, GO:0004518, GO:0004540, GO:0006139, GO:0006417, GO:0006725, GO:0006807, GO:0008150, GO:0008152, GO:0009605, GO:0009607 +57 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 0.688 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 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)

PfamAccessioni-EvalueResiduesDescription
PINPF01850.28 1.2e-182–124 PIN domain

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: vapB11 (antitoxin VapB11), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1560 vapB11 antitoxin VapB11 999 1000 ctx neighborhood:882 cooccurence:703 coexpression:817 experimental:999
Rv2009 vapB15 antitoxin VapB15 872 872 experimental:853
Rv3677c beta lactamase 765 765 coexpression:765
Rv2531c amino acid decarboxylase 687 687 coexpression:687
Rv1559 ilvA threonine dehydratase IlvA 668 668 ctx neighborhood:659
Rv0624 vapC30 ribonuclease VapC30 795 653 coexpression:514 textmining:434
Rv0158 transcriptional regulator 651 651 coexpression:651
Rv1558 hyp hypothetical protein 566 566 ctx neighborhood:563
Rv1557 mmpL6 transmembrane transport protein MmpL6 561 561 ctx neighborhood:556
Rv2759c vapC42 ribonuclease VapC42 460 458
Rv0300 vapB2 antitoxin VapB2 438 439 experimental:412
Rv3263 DNA methylase 432 432 coexpression:431
Rv2601A vapB41 antitoxin VapB41 430 408
Rv1952 vapB14 antitoxin VapB14 429 407
Rv2010 vapC15 ribonuclease VapC15 473 375

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 VapC11
  • MTBC0 PGAP product: type II toxin-antitoxin system toxin ribonuclease VapC11
  • Pfam (hmmscan --cut_ga): PIN PF01850.28 (E=1e-18)
  • (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_216077.1)
  • 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 P9WFA5 (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 vapB11
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001669|Rv1561|vapC11
MILIDTSAWVEYFRATGSIAAVEVRRLLSEEAARIAMCEPIAMEILSGALDDNTHTTLERLVNGLPSLNVDDAIDFRAAAGIYRAARRAGETVRSINDCLIAALAIRHGARIVHRDADFDVIARITNLQAASFR