vapB46 Resolved · high auto-curated

H37Rv Rv3385c · MTBC0 - · 102 aa · 3799635–3799943 (-) · RefSeq NP_217902.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)antitoxin VapB46
MTBC0 PGAP re-annotation
Revised (this work)Antitoxin VapB46. Pfam: PhdYeFM_antitox (PF02604.27).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt P9WF13 SwissProt · reviewed · Evidence at protein level
UniProt nameAntitoxin VapB46
Curated functionAntitoxin component of a type II toxin-antitoxin (TA) system. Upon expression in M.smegmatis neutralizes the effect of cognate toxin VapC46.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category D Cell cycle control, cell division, chromosome partitioning
eggNOG descriptionantitoxin component of a
Orthologous groupCOG4118
Gene Ontology (6) GO:0008150, GO:0040008, GO:0045927, GO:0048518, 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 0.131 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 3 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
PhdYeFM_antitoxPF02604.27 7.2e-0912–51 Antitoxin Phd_YefM, type II toxin-antitoxin system

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

Closest characterised functional partner: vapC46 (ribonuclease VapC46), high confidence from genomic context alone (score 959 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3384c vapC46 ribonuclease VapC46 959 959 ctx neighborhood:780 cooccurence:766
Rv3408 vapC47 ribonuclease VapC47 786 786 ctx cooccurence:763
Rv1962c vapC35 ribonuclease VapC35 766 766 ctx cooccurence:741
Rv3407 vapB47 antitoxin VapB47 612 612 ctx cooccurence:610
Rv0626 vapB5 antitoxin VapB5 545 545 ctx cooccurence:537
Rv3386 transposase 544 544 ctx neighborhood:542
Rv3387 transposase 542 542 ctx neighborhood:542
Rv0665 vapC8 ribonuclease VapC8 502 502
Rv0627 vapC5 ribonuclease VapC5 498 498
Rv0595c vapC4 ribonuclease VapC4 443 443
Rv2548 vapC19 ribonuclease VapC19 407 407
Rv1720c vapC12 ribonuclease VapC12 405 406

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): antitoxin VapB46
  • Pfam (hmmscan --cut_ga): PhdYeFM_antitox PF02604.27 (E=7e-09)
  • (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_217902.1)
  • Domains: Pfam-A via hmmscan --cut_ga — PhdYeFM_antitox (PF02604.27)
  • 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 COG4118
  • Curated reference: UniProt P9WF13 (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 — 12 functional partner(s); context anchor vapC46
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3385c|vapB46
MTPTACATVSTMTSVGVRALRQRASELLRRVEAGETIEITDRGRPVALLSPLPQGGPYEQLLASGEIERATLDVVDLPEPLDLDAGVELPSVTLARLREHER