vapC27 Family assigned · medium auto-curated

H37Rv Rv0598c · MTBC0 mtbc0_000628 · 137 aa · 700706–701119 (-) · RefSeq NP_215112.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ribonuclease VapC27
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 P9WF83 SwissProt · reviewed · Evidence at protein level
UniProt nameRibonuclease VapC27
EC (curated) EC 3.1.-.-
Curated functionProbably the toxic component of a type II toxin-antitoxin (TA) system. An RNase (By similarity). Its cognate antitoxin is VapB27.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionPIN domain
Orthologous groupCOG1848
Gene Ontology (2) GO:0005575, GO:0005576

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 0.582 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 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 1.9e-147–127 PIN domain

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

Closest characterised functional partner: vapB27 (antitoxin VapB27), high confidence from genomic context alone (score 909 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0599c vapB27 antitoxin VapB27 957 909 ctx neighborhood:882 textmining:546
Rv0600c two component sensor kinase HK1 526 526 ctx neighborhood:523
Rv0597c hyp hypothetical protein 450 449 ctx neighborhood:424
Rv0596c vapB4 antitoxin VapB4 514 306
Rv0595c vapC4 ribonuclease VapC4 696 291 textmining:590
Rv0609 vapC28 ribonuclease VapC28 672 164 textmining:624
Rv3181c vapB49 antitoxin VapB45 446 74 textmining:427
Rv0301 vapC2 ribonuclease VapC2 631 73 textmining:618
Rv2010 vapC15 ribonuclease VapC15 400 73
Rv3320c vapC44 ribonuclease VapC44 662 68 textmining:653
Rv0617 vapC29 ribonuclease VapC29 525 67 textmining:512
Rv2530c vapC39 ribonuclease VapC39 635 55 textmining:630
Rv0627 vapC5 ribonuclease VapC5 469 55 textmining:461
Rv2103c vapC37 ribonuclease VapC37 660 53 textmining:656
Rv2494 vapC38 ribonuclease VapC38 656 53 textmining:652

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 VapC27
  • MTBC0 PGAP product: type II toxin-antitoxin system VapC family toxin
  • Pfam (hmmscan --cut_ga): PIN PF01850.28 (E=2e-14)
  • (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_215112.1)
  • 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 P9WF83 (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 — 31 functional partner(s); context anchor vapB27
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000628|Rv0598c|vapC27
MKPPLAVDTSVAIPLLVRTHTAHAAVVAWWAHREAALCGHALAETYSVLTRLPRDLRLAPMDAARLLTERFAAPLLLSSRTTEHLPRVLAQFEITGGAVYDALVALAAAEHRAELATRDARAKDTYEKIGVHVVVAA