vapC42 Family assigned · medium auto-curated

H37Rv Rv2759c · MTBC0 mtbc0_002936 · 131 aa · 3093290–3093685 (-) · RefSeq NP_217275.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ribonuclease VapC42
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 P9WF57 SwissProt · reviewed · Evidence at protein level
UniProt nameRibonuclease VapC42
EC (curated) EC 3.1.-.-
Curated functionToxic component of a type II toxin-antitoxin (TA) system. An RNase. Its cognate antitoxin is VapB42 (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 groupCOG3742
KEGG orthology K19686

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 0.0 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 0 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 1.1e-191–125 PIN domain

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

Closest characterised functional partner: vapB42 (antitoxin VapB42), high confidence from genomic context alone (score 987 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2760c vapB42 antitoxin VapB42 987 987 ctx neighborhood:882 coexpression:834
Rv0623 vapB30 antitoxin VapB30 959 944 ctx cooccurence:772 experimental:754
Rv2761c hsdS type I restriction/modification system specificity determinant HsdS 811 810 ctx neighborhood:801
Rv2762c hyp hypothetical protein 802 803 ctx neighborhood:800
Rv1740 vapB34 antitoxin VapB34 792 769 experimental:754
Rv2757c vapC21 ribonuclease VapC21 828 764 ctx neighborhood:753
Rv2758c vapB21 antitoxin VapB21 756 756 ctx neighborhood:753
Rv3439c hyp hypothetical protein 730 730 coexpression:730
Rv1560 vapB11 antitoxin VapB11 623 624 ctx cooccurence:529
Rv3164c moxR3 methanol dehydrogenase transcriptional regulator MoxR 615 615 coexpression:615
Rv2755c hsdS.1 Rv2755c, (MTV002.20c), len: 91 aa. Possible hsdS.1,fragment of type I restriction/modification system specificity determinant (S protein), s 600 600 ctx neighborhood:530
Rv2763c dfrA dihydrofolate reductase 595 596 ctx neighborhood:593
Rv0273c transcriptional regulator 580 580 coexpression:580
Rv2756c hsdM type I restriction/modification system DNA methylase HsdM 553 552 ctx neighborhood:532
Rv0919 GCN5-like N-acetyltransferase 475 475 ctx cooccurence:472

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 VapC42
  • MTBC0 PGAP product: type II toxin-antitoxin system VapC family toxin
  • Pfam (hmmscan --cut_ga): PIN PF01850.28 (E=1e-19)
  • (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_217275.1)
  • 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 COG3742
  • Curated reference: UniProt P9WF57 (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 — 25 functional partner(s); context anchor vapB42
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002936|Rv2759c|vapC42
MIVDTSAIVAIVSGESGAQVLKEALERSPNSRMSAPNYVELCAIMQRRDRPEISRLVDRLLDDYGIQVEAVDADQARVAAQAYRDYGRGSGHPARLNLGDTYSYALAQVTGEPLLFRGDDFTHTDIRPACT