vapB21 Family assigned · medium auto-curated

H37Rv Rv2758c · MTBC0 mtbc0_002935 · 88 aa · 3092998–3093264 (-) · RefSeq NP_217274.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)antitoxin VapB21
MTBC0 PGAP re-annotationtype II toxin-antitoxin system VapB family antitoxin
Revised (this work)Type II toxin-antitoxin system VapB family antitoxin. Pfam: VapB_antitoxin (PF09957.16).

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

Curated reference (UniProt)

UniProt P9WJ43 SwissProt · reviewed · Evidence at protein level
UniProt nameAntitoxin VapB21
Curated functionAntitoxin component of a type II toxin-antitoxin (TA) system. Upon expression in M.smegmatis neutralizes the effect of cognate toxin VapC21.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
eggNOG descriptionpositive regulation of growth
Orthologous groupCOG5450
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 0.674 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 2 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
VapB_antitoxinPF09957.16 7.2e-0916–56 Bacterial antitoxin of type II TA system, VapB

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

Closest characterised functional partner: vapC21 (ribonuclease VapC21), high confidence from genomic context alone (score 980 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2757c vapC21 ribonuclease VapC21 979 980 ctx neighborhood:882 coexpression:804
Rv2759c vapC42 ribonuclease VapC42 756 756 ctx neighborhood:753
Rv2760c vapB42 antitoxin VapB42 755 755 ctx neighborhood:753
Rv2761c hsdS type I restriction/modification system specificity determinant HsdS 735 735 ctx neighborhood:731
Rv2762c hyp hypothetical protein 710 710 ctx neighborhood:707
Rv2756c hsdM type I restriction/modification system DNA methylase HsdM 618 618 ctx neighborhood:598
Rv2755c hsdS.1 Rv2755c, (MTV002.20c), len: 91 aa. Possible hsdS.1,fragment of type I restriction/modification system specificity determinant (S protein), s 586 587 ctx neighborhood:572
Rv2763c dfrA dihydrofolate reductase 530 530 ctx neighborhood:523
Rv2764c thyA thymidylate synthase ThyA 403 403 ctx neighborhood:400
Rv2494 vapC38 ribonuclease VapC38 683 47 textmining:682
Rv0960 vapC9 ribonuclease VapC9 521 47 textmining:518

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: antitoxin VapB21
  • MTBC0 PGAP product: type II toxin-antitoxin system VapB family antitoxin
  • Pfam (hmmscan --cut_ga): VapB_antitoxin PF09957.16 (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_217274.1)
  • Domains: Pfam-A via hmmscan --cut_ga — VapB_antitoxin (PF09957.16)
  • 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 COG5450
  • Curated reference: UniProt P9WJ43 (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 — 11 functional partner(s); context anchor vapC21
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002935|Rv2758c|vapB21
MHRGYALVVCSPGVTRTMIDIDDDLLARAAKELGTTTKKDTVHAALRAALRASAARSLMNRMAENATGTQDEALVNAMWRDGHPENTA