vapC41 Family assigned · medium auto-curated

H37Rv Rv2602 · MTBC0 mtbc0_002770 · 146 aa · 2953897–2954337 (+) · RefSeq NP_217118.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ribonuclease VapC41
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 P9WF59 SwissProt · reviewed · Evidence at protein level
UniProt nameRibonuclease VapC41
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 VapB41.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionToxic component of a toxin-antitoxin (TA) module. An RNase
Orthologous groupCOG1848
KEGG orthology K07064
Gene Ontology (8) GO:0005575, GO:0005576, 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 1.034 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 3 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 2.0e-143–137 PIN domain

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

Closest characterised functional partner: vapB41 (antitoxin VapB41), high confidence from genomic context alone (score 930 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2601A vapB41 antitoxin VapB41 930 930 ctx neighborhood:882 coexpression:431
Rv2600 integral membrane protein 554 553 ctx neighborhood:551
Rv2601 speE spermidine synthase 531 531 ctx neighborhood:528
Rv0748 vapB31 antitoxin VapB31 407 408
Rv2871 vapB43 antitoxin VapB43 403 404
Rv2829c vapC22 ribonuclease VapC22 470 71 textmining:453
Rv2494 vapC38 ribonuclease VapC38 473 70 textmining:458
Rv2103c vapC37 ribonuclease VapC37 544 63 textmining:534
Rv2530c vapC39 ribonuclease VapC39 629 55 textmining:624
Rv2548 vapC19 ribonuclease VapC19 571 51 textmining:567
Rv0598c vapC27 ribonuclease VapC27 532 51 textmining:528
Rv0656c vapC6 ribonuclease VapC6 656 48 textmining:654
Rv2757c vapC21 ribonuclease VapC21 418 48 textmining:414
Rv1838c vapC13 ribonuclease VapC13 610 47 textmining:608
Rv3320c vapC44 ribonuclease VapC44 519 47 textmining:516

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 VapC41
  • MTBC0 PGAP product: type II toxin-antitoxin system VapC family toxin
  • Pfam (hmmscan --cut_ga): PIN PF01850.28 (E=2e-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_217118.1)
  • 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 P9WF59 (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 — 17 functional partner(s); context anchor vapB41
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002770|Rv2602|vapC41
MLLCDTNIWLALALSGHVHHRASRAWLDTINAPGVIHFCRATQQSLLRLLTNRTVLGAYGSPPLTNREAWAAYAAFLDDDRIVLAGAEPDGLEAQWRAFAVRQSPAPKVWMDAYLAAFALTGGFELVTTDTAFTQYGGIELRLLAK