vapC31 Family assigned · medium auto-curated

H37Rv Rv0749 · MTBC0 mtbc0_000795 · 142 aa · 845653–846081 (+) · RefSeq NP_215263.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ribonuclease VapC31
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 P9WF75 SwissProt · reviewed · Evidence at protein level
UniProt nameRibonuclease VapC31
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 VapB31 (By similarity).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionToxic 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
Orthologous groupCOG1848
KEGG orthology K07064
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) pseudogene candidate

pN/pS 0.265 · purifying
Polymorphic sites (≥ 0.1% of strains) 8 synonymous, 6 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 4.82% of strains (6996) · clonal

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 1.6e-163–133 PIN domain

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

Closest characterised functional partner: vapB31 (antitoxin VapB31), high confidence from genomic context alone (score 879 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0748 vapB31 antitoxin VapB31 928 879 ctx neighborhood:753 experimental:508 textmining:434
Rv0277c vapC25 ribonuclease VapC25 806 805 coexpression:804
Rv3697c vapC48 ribonuclease VapC48 775 775 ctx cooccurence:774
Rv0595c vapC4 ribonuclease VapC4 807 558 ctx cooccurence:550 textmining:581
Rv2871 vapB43 antitoxin VapB43 526 527 experimental:508
Rv0626 vapB5 antitoxin VapB5 520 521 ctx cooccurence:509
Rv1720c vapC12 ribonuclease VapC12 543 509 ctx cooccurence:506
Rv2548 vapC19 ribonuclease VapC19 693 490 ctx cooccurence:485 textmining:423
Rv0747 PE_PGRS10 PE-PGRS family protein PE_PGRS10 490 490 ctx neighborhood:490
Rv0743c hyp hypothetical protein 487 487
Rv0960 vapC9 ribonuclease VapC9 474 475 ctx cooccurence:472
Rv1397c vapC10 ribonuclease VapC10 765 441 ctx cooccurence:435 textmining:598
Rv3384c vapC46 ribonuclease VapC46 478 372
Rv0065 vapC1 ribonuclease VapC1 478 369
Rv0659c mazF2 toxin MazF2 406 332

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 VapC31
  • MTBC0 PGAP product: type II toxin-antitoxin system VapC family toxin
  • Pfam (hmmscan --cut_ga): PIN PF01850.28 (E=2e-16)
  • (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_215263.1)
  • 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 COG1848
  • Curated reference: UniProt P9WF75 (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 — 27 functional partner(s); context anchor vapB31
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000795|Rv0749|vapC31
MFLLDANVLLAAHRGDHPNHRTVRPWFDRLLAADDPFTVPNLVWASFLRLATNRRIFEIPSPRAEAFAFVEAVTAQPHHLPTNPGPRHLMLLRKLCDEADASGDLIPDAVLAAIAVGHHCAVVSLDRDFARFASVRHIRPPL