vapC47 Family assigned · medium auto-curated

H37Rv Rv3408 · MTBC0 mtbc0_003622 · 136 aa · 3851987–3852397 (+) · RefSeq NP_217925.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ribonuclease VapC47
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 P9WF49 SwissProt · reviewed · Evidence at protein level
UniProt nameRibonuclease VapC47
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 translation and colony formation. Its toxic effect on colony formation is neutralized by coexpression with cognate antitoxin VapB47; the effect on translation has not been tested but is probably neutralized also.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionToxic component of a toxin-antitoxin (TA) module. An RNase
Orthologous groupCOG1848
KEGG orthology K07064, K07065
Gene Ontology (36) GO:0006417, GO:0008150, GO:0009889, GO:0009890, GO:0009892, GO:0010468, GO:0010556, GO:0010558, GO:0010605, GO:0010608, GO:0010629, GO:0017148 +24 more

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 0.743 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 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 2.2e-122–118 PIN domain

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

Closest characterised functional partner: vapB47 (antitoxin VapB47), high confidence from genomic context alone (score 992 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3407 vapB47 antitoxin VapB47 991 992 ctx neighborhood:882 cooccurence:672 coexpression:800
Rv3385c vapB46 antitoxin VapB46 786 786 ctx cooccurence:763
Rv0626 vapB5 antitoxin VapB5 710 710 ctx cooccurence:702
Rv3406 dioxygenase 668 669 ctx neighborhood:669
Rv0665 vapC8 ribonuclease VapC8 596 597 ctx cooccurence:594
Rv0627 vapC5 ribonuclease VapC5 622 548 ctx cooccurence:540
Rv1720c vapC12 ribonuclease VapC12 811 537 ctx cooccurence:536 textmining:610
Rv3405c HTH-type transcriptional regulator 488 489 ctx neighborhood:486
Rv1102c mazF3 mRNA interferase MazF3 639 488 ctx cooccurence:472
Rv0960 vapC9 ribonuclease VapC9 646 478 ctx cooccurence:473
Rv0595c vapC4 ribonuclease VapC4 698 465 ctx cooccurence:457 textmining:459
Rv3098A PemK-like protein 465 465 ctx cooccurence:463
Rv0065 vapC1 ribonuclease VapC1 488 442 ctx cooccurence:438
Rv0549c vapC3 ribonuclease VapC3 885 441 ctx cooccurence:439 textmining:803
Rv0748 vapB31 antitoxin VapB31 485 412

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 VapC47
  • MTBC0 PGAP product: type II toxin-antitoxin system VapC family toxin
  • Pfam (hmmscan --cut_ga): PIN PF01850.28 (E=2e-12)
  • (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_217925.1)
  • 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 P9WF49 (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 — 42 functional partner(s); context anchor vapB47
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003622|Rv3408|vapC47
MIYMDTSALTKLLISEPETTELRTWLTAQSGQGEDAATSTLGRVELMRVVARYGQPGQTERARYLLDGLDILPLTEPVIGLAETIGPATLRSLDAIHLAAAAQIKRELTAFVTYDHRLLSGCREVGFVTASPGAVR