vapC34 Family assigned · medium auto-curated

H37Rv Rv1741 · MTBC0 mtbc0_001854 · 82 aa · 1979989–1980237 (+) · RefSeq NP_216257.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ribonuclease VapC34
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 P9WF71 SwissProt · reviewed · Inferred from homology
UniProt namePutative ribonuclease VapC34
EC (curated) EC 3.1.-.-
Curated functionToxic component of a possible type II toxin-antitoxin (TA) system. A putative RNase. Its cognate antitoxin is VapB34 (By similarity).

UniProt still lists this protein as Putative ribonuclease VapC34; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
Preferred namevapC
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 n/a
Polymorphic sites (≥ 0.1% of strains) 0 synonymous, 3 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 7.0e-061–52 PIN domain

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

Closest characterised functional partner: vapB34 (antitoxin VapB34), high confidence from genomic context alone (score 970 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1740 vapB34 antitoxin VapB34 972 970 ctx neighborhood:801 experimental:853
Rv0623 vapB30 antitoxin VapB30 876 864 experimental:853
Rv1742 hyp hypothetical protein 792 792 ctx neighborhood:785
Rv1739c sulfate ABC transporter permease 572 572 ctx neighborhood:568
Rv1743 pknE serine/threonine-protein kinase PknE 536 536 ctx neighborhood:533
Rv0608 vapB28 antitoxin VapB28 455 433
Rv1982A vapB36 antitoxin VapB36 464 430
Rv2760c vapB42 antitoxin VapB42 452 430

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 VapC34
  • MTBC0 PGAP product: type II toxin-antitoxin system VapC family toxin
  • Pfam (hmmscan --cut_ga): PIN PF01850.28 (E=7e-06)
  • (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_216257.1)
  • 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 P9WF71 (SwissProt, reviewed; Inferred from homology)
  • 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 — 8 functional partner(s); context anchor vapB34
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001854|Rv1741|vapC34
MVIDTSALVAMLNDEPEAQRFEIAVAADHVWLMSTASYPEMATVIETRFGEPGGREPKVSGQPLLYKGDDFACIDIRAVLAG