vapC12 Family assigned · medium auto-curated

H37Rv Rv1720c · MTBC0 mtbc0_001832 · 129 aa · 1959045–1959434 (-) · RefSeq NP_216236.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ribonuclease VapC12
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 P9WFA3 SwissProt · reviewed · Inferred from homology
UniProt nameRibonuclease VapC12
EC (curated) EC 3.1.-.-
Curated functionToxic component of a type II toxin-antitoxin (TA) system. An RNase. The cognate antitoxin is VapB12 (By similarity).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionToxic component of a toxin-antitoxin (TA) module. An RNase
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 1.455 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 4 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 5.8e-072–116 PIN domain

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

Closest characterised functional partner: vapB12 (antitoxin VapB12), high confidence from genomic context alone (score 884 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1721c vapB12 antitoxin VapB12 944 884 ctx neighborhood:882 textmining:540
Rv3098A PemK-like protein 753 745 ctx cooccurence:744
Rv3384c vapC46 ribonuclease VapC46 757 674 ctx cooccurence:673
Rv1962c vapC35 ribonuclease VapC35 592 593 ctx cooccurence:592
Rv3407 vapB47 antitoxin VapB47 538 539 ctx cooccurence:524
Rv2801A mazE9 antitoxin MazE9 538 539 ctx cooccurence:538
Rv3408 vapC47 ribonuclease VapC47 811 537 ctx cooccurence:536 textmining:610
Rv0749 vapC31 ribonuclease VapC31 543 509 ctx cooccurence:506
Rv2103c vapC37 ribonuclease VapC37 660 501 ctx cooccurence:498
Rv1723 hydrolase 501 501 ctx neighborhood:498
Rv1722 carboxylase 499 500 ctx neighborhood:498
Rv2872 vapC43 ribonuclease VapC43 495 496 ctx cooccurence:491
Rv0277c vapC25 ribonuclease VapC25 568 489 ctx cooccurence:486
Rv0456A mazF1 toxin MazF1 487 468 ctx cooccurence:462
Rv3180c vapC49 ribonuclease VapC45 550 467 ctx cooccurence:464

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 VapC12
  • MTBC0 PGAP product: type II toxin-antitoxin system VapC family toxin
  • Pfam (hmmscan --cut_ga): PIN PF01850.28 (E=6e-07)
  • (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_216236.1)
  • 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 P9WFA3 (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 — 37 functional partner(s); context anchor vapB12
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001832|Rv1720c|vapC12
MIVLDASAAVELMLTTPAGAAVARRLRGETVHAPAHFDVEVIGAIRQAVVRQLISDHEGLVVVVNFLSLPVRRWPLKPFTQRAYQLRSTHTVADGAYVALAEGLGVPLITCDGRLAQSHGHNAEIELVA