vapC23 Family assigned · medium auto-curated

H37Rv Rv2863 · MTBC0 mtbc0_003045 · 126 aa · 3195658–3196038 (+) · RefSeq NP_217379.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ribonuclease VapC23
MTBC0 PGAP re-annotationtype 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 P9WF89 SwissProt · reviewed · Inferred from homology
UniProt nameRibonuclease VapC23
EC (curated) EC 3.1.-.-
Curated functionToxic component of a type II toxin-antitoxin (TA) system. An RNase. The cognate antitoxin is VapB23 (By similarity).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category G Carbohydrate transport and metabolism
eggNOG descriptionToxic component of a toxin-antitoxin (TA) module. An RNase
Orthologous groupCOG1848
KEGG orthology K07064

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 0.34 · purifying
Polymorphic sites (≥ 0.1% of strains) 2 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 1.3e-212–121 PIN domain

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

Closest characterised functional partner: vapB23 (antitoxin VapB23), high confidence from genomic context alone (score 833 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2862A vapB23 antitoxin VapB23 833 833 ctx neighborhood:833
Rv2862c hyp hypothetical protein 543 543 ctx neighborhood:543
Rv2861c mapB methionine aminopeptidase 460 460 ctx neighborhood:459
Rv0748 vapB31 antitoxin VapB31 404 405
Rv2871 vapB43 antitoxin VapB43 752 403 textmining:602
Rv0616A vapB29 antitoxin VapB29 664 62 textmining:657
Rv3181c vapB49 antitoxin VapB45 658 59 textmining:652
Rv0596c vapB4 antitoxin VapB4 631 58 textmining:625
Rv2548 vapC19 ribonuclease VapC19 425 51 textmining:419
Rv2757c vapC21 ribonuclease VapC21 444 48 textmining:440
Rv0624 vapC30 ribonuclease VapC30 522 47 textmining:519
Rv0661c vapC7 ribonuclease VapC7 544 46 textmining:542
Rv0595c vapC4 ribonuclease VapC4 531 45 textmining:530
Rv0229c vapC51 hyp hypothetical protein 433 45 textmining:431
Rv0582 vapC26 ribonuclease VapC26 652 44 textmining:651

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 VapC23
  • MTBC0 PGAP product: type II toxin-antitoxin system VapC family toxin
  • Pfam (hmmscan --cut_ga): PIN PF01850.28 (E=1e-21)
  • (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_217379.1)
  • 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 P9WF89 (SwissProt, reviewed; Inferred from homology)
  • 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 — 26 functional partner(s); context anchor vapB23
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003045|Rv2863|vapC23
MIFVDTNVFMYAVGRDHPLRMPAREFLEHSLEHQDRLVTSAEAMQELLNAYVPVGRNSTLDSALTLVRALTEIWPVEAADVAHARTLHHRHPGLGARDLLHLACCQRRGVTRIKTFDHTLASAFRS