vapC26 Resolved · high auto-curated

H37Rv Rv0582 · MTBC0 mtbc0_000612 · 135 aa · 681473–681880 (+) · RefSeq NP_215096.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ribonuclease VapC26
MTBC0 PGAP re-annotationtype II toxin-antitoxin system toxin ribonuclease C26
Revised (this work)Type II toxin-antitoxin system toxin ribonuclease C26. 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 O53779 SwissProt · reviewed · Evidence at protein level
UniProt nameRibonuclease VapC26
EC (curated) EC 3.1.-.-
Curated functionToxic 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 VapB26.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionToxic component of a toxin-antitoxin (TA) module. An RNase
Orthologous groupCOG2402
KEGG orthology K07065
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 n/a
Polymorphic sites (≥ 0.1% of strains) 0 synonymous, 1 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 6.3e-121–121 PIN domain

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

Closest characterised functional partner: vapB26 (antitoxin VapB26), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0581 vapB26 antitoxin VapB26 999 1000 ctx neighborhood:882 experimental:999 textmining:437
Rv0580c hyp hypothetical protein 601 602 ctx neighborhood:599
Rv1034c Probable transposase (fragment); Rv1034c, (MTCY10G2.15), len: 129 aa. Probable IS1560 transposase fragment, similar to part of Rv3387|E12023 587 587 ctx cooccurence:587
Rv3387 transposase 577 577 ctx cooccurence:577
Rv2961 transposase 576 576 ctx cooccurence:576
Rv2546 vapC18 ribonuclease VapC18 568 568 ctx cooccurence:561
Rv2549c vapC20 ribonuclease VapC20 910 565 ctx cooccurence:562 textmining:803
Rv3098A PemK-like protein 564 564 ctx cooccurence:564
Rv2757c vapC21 ribonuclease VapC21 595 547 ctx cooccurence:538
Rv2018 vapB45 hyp hypothetical protein 546 547 ctx cooccurence:545
Rv2735c hyp hypothetical protein 538 538 ctx cooccurence:538
Rv3386 transposase 515 515 ctx cooccurence:515
Rv0229c vapC51 hyp hypothetical protein 483 483 ctx cooccurence:474
Rv0659c mazF2 toxin MazF2 461 461 ctx cooccurence:456
Rv0595c vapC4 ribonuclease VapC4 887 439 ctx cooccurence:429 textmining:807

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 VapC26
  • MTBC0 PGAP product: type II toxin-antitoxin system toxin ribonuclease C26
  • Pfam (hmmscan --cut_ga): PIN PF01850.28 (E=6e-12)
  • (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_215096.1)
  • 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 COG2402
  • Curated reference: UniProt O53779 (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 — 44 functional partner(s); context anchor vapB26
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000612|Rv0582|vapC26
MIIDTSALLAYFDAAEPDHAAVSECIDSSADALVVSPYVVAELDYLVATRVGVDAELAVLRELAGGAWELANCGAAEIEQAARIVTKYQDQRIGIADAANVVLADRYRTRTILTLDRRHFSALRPIGGGRFTVIP