vapC1 Resolved · high auto-curated

H37Rv Rv0065 · MTBC0 mtbc0_000072 · 133 aa · 71966–72367 (+) · RefSeq NP_214579.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ribonuclease VapC1
MTBC0 PGAP re-annotationtype II toxin-antitoxin system ribonuclease VapC1
Revised (this work)Type II toxin-antitoxin system ribonuclease VapC1. 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 P9WFC1 SwissProt · reviewed · Inferred from homology
UniProt nameRibonuclease VapC1
EC (curated) EC 3.1.-.-
Curated functionToxic component of a type II toxin-antitoxin (TA) system. The cognate antitoxin is VapB1 (By similarity). Has ribonuclease activity.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category F Nucleotide transport and metabolism
eggNOG descriptiontoxic component of a
Orthologous groupCOG4113

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 0.352 · purifying
Polymorphic sites (≥ 0.1% of strains) 3 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 3.2e-065–123 PIN domain

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

Closest characterised functional partner: vapB1 (antitoxin VapB1), high confidence from genomic context alone (score 882 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0064A vapB1 antitoxin VapB1 906 882 ctx neighborhood:882
Rv3098A PemK-like protein 748 740 ctx cooccurence:739
Rv0064 transmembrane protein 711 711 ctx neighborhood:682
Rv3407 vapB47 antitoxin VapB47 625 625 ctx cooccurence:613
Rv3384c vapC46 ribonuclease VapC46 848 575 ctx cooccurence:571 textmining:657
Rv1962c vapC35 ribonuclease VapC35 505 506 ctx cooccurence:504
Rv3180c vapC49 ribonuclease VapC45 549 496 ctx cooccurence:493
Rv2801A mazE9 antitoxin MazE9 508 494 ctx cooccurence:493
Rv1495 mazF4 mRNA interferase MazF4 504 452 ctx cooccurence:451
Rv3408 vapC47 ribonuclease VapC47 488 442 ctx cooccurence:438
Rv0595c vapC4 ribonuclease VapC4 604 423 ctx cooccurence:416
Rv0456A mazF1 toxin MazF1 500 421 ctx cooccurence:409
Rv2018 vapB45 hyp hypothetical protein 462 407 ctx cooccurence:406
Rv0582 vapC26 ribonuclease VapC26 637 381 textmining:438
Rv2103c vapC37 ribonuclease VapC37 634 375 textmining:439

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 VapC1
  • MTBC0 PGAP product: type II toxin-antitoxin system ribonuclease VapC1
  • Pfam (hmmscan --cut_ga): PIN PF01850.28 (E=3e-06)
  • (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_214579.1)
  • 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 COG4113
  • Curated reference: UniProt P9WFC1 (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 — 39 functional partner(s); context anchor vapB1
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000072|Rv0065|vapC1
MDECVVDAAAVVDALAGKGASAIVLRGLLKESISNAPHLLDAEVGHALRRAVLSDEISEEQARAALDALPYLIDNRYPHSPRLIEYTWQLRHNVTFYDALYVALATALDVPLLTGDSRLAAAPGLPCEIKLVR