vapC32 Family assigned · medium auto-curated

H37Rv Rv1114 · MTBC0 mtbc0_001196 · 124 aa · 1248050–1248424 (+) · RefSeq NP_215630.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ribonuclease VapC32
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 P9WF73 SwissProt · reviewed · Evidence at protein level
UniProt nameRibonuclease VapC32
EC (curated) EC 3.1.-.-
Curated functionToxic component of a type II toxin-antitoxin (TA) system. An RNase (By similarity). Upon expression in M.smegmatis inhibits colony formation. Its toxic effect is neutralized by coexpression with cognate antitoxin VapB32.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred namevapC
eggNOG descriptionToxic component of a toxin-antitoxin (TA) module. An RNase
Orthologous groupCOG1487
Gene Ontology (6) GO:0008150, GO:0040008, GO:0045926, GO:0048519, 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 0.379 · purifying
Polymorphic sites (≥ 0.1% of strains) 2 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
PINPF01850.28 7.6e-112–111 PIN domain

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

Closest characterised functional partner: vapB32 (antitoxin VapB32), high confidence from genomic context alone (score 977 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1113 vapB32 antitoxin VapB32 976 977 ctx neighborhood:882 cooccurence:774
Rv1112 ychF GTP-binding protein 595 595 ctx neighborhood:594
Rv1115 hyp hypothetical protein 478 477 ctx neighborhood:472
Rv1111c hyp hypothetical protein 438 438 ctx neighborhood:434
Rv0300 vapB2 antitoxin VapB2 433 434 experimental:412
Rv2494 vapC38 ribonuclease VapC38 655 430 ctx cooccurence:424 textmining:420
Rv2530c vapC39 ribonuclease VapC39 808 428 ctx cooccurence:417 textmining:679
Rv3320c vapC44 ribonuclease VapC44 416 417 ctx cooccurence:411
Rv0617 vapC29 ribonuclease VapC29 878 409 ctx cooccurence:403 textmining:803
Rv0549c vapC3 ribonuclease VapC3 580 408 ctx cooccurence:403
Rv2601A vapB41 antitoxin VapB41 429 407
Rv1952 vapB14 antitoxin VapB14 429 407
Rv0366c hyp hypothetical protein 403 403
Rv2103c vapC37 ribonuclease VapC37 770 371 textmining:650
Rv0277c vapC25 ribonuclease VapC25 868 343 textmining:808

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 VapC32
  • MTBC0 PGAP product: type II toxin-antitoxin system VapC family toxin
  • Pfam (hmmscan --cut_ga): PIN PF01850.28 (E=8e-11)
  • (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_215630.1)
  • 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 COG1487
  • Curated reference: UniProt P9WF73 (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 — 41 functional partner(s); context anchor vapB32
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001196|Rv1114|vapC32
MILVDTSVWIEHLRAADARLVELLGDDEAGCHPLVIEELALGSIKQRDVVLDLLANLYQFPVVTHDEVLRLVGRRRLWGRGLGAVDANLLGSVALVGGARLWTRDKRLKAACAESGVALAEEVS