vapC28 Family assigned · medium auto-curated

H37Rv Rv0609 · MTBC0 mtbc0_000639 · 133 aa · 707038–707439 (+) · RefSeq NP_215123.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ribonuclease VapC28
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 P9WF81 SwissProt · reviewed · Evidence at protein level
UniProt nameRibonuclease VapC28
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 VapB28.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionToxic component of a toxin-antitoxin (TA) module. An RNase
Orthologous groupCOG3742
KEGG orthology K19686
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 0.114 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 6 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 1.9e-181–124 PIN domain

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

Closest characterised functional partner: vapB30 (antitoxin VapB30), high confidence from genomic context alone (score 945 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0623 vapB30 antitoxin VapB30 950 945 ctx cooccurence:772 experimental:754
Rv0608 vapB28 antitoxin VapB28 932 930 ctx neighborhood:882
Rv0609A hyp hypothetical protein 836 835 ctx neighborhood:801
Rv1740 vapB34 antitoxin VapB34 785 763 experimental:754
Rv0607 hyp hypothetical protein 679 679 ctx neighborhood:675
Rv0606 Possible transposase (fragment); Rv0606, (MTCY19H5.16c), len: 247 aa. Possible truncated transposase for IS_1536 element, highly similar to 569 569 ctx neighborhood:552
Rv0605 IS1536 family serine type transposase 568 568 ctx neighborhood:552
Rv1560 vapB11 antitoxin VapB11 544 544 ctx cooccurence:540
Rv0919 GCN5-like N-acetyltransferase 480 480 ctx cooccurence:477
Rv2760c vapB42 antitoxin VapB42 457 435
Rv1982A vapB36 antitoxin VapB36 464 430
Rv2010 vapC15 ribonuclease VapC15 840 383 textmining:753
Rv1561 vapC11 ribonuclease VapC11 758 317 textmining:660
Rv1114 vapC32 ribonuclease VapC32 846 236 textmining:807
Rv2530c vapC39 ribonuclease VapC39 738 232 textmining:673

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 VapC28
  • MTBC0 PGAP product: type II toxin-antitoxin system VapC family toxin
  • Pfam (hmmscan --cut_ga): PIN PF01850.28 (E=2e-18)
  • (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_215123.1)
  • 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 P9WF81 (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 — 29 functional partner(s); context anchor vapB30
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000639|Rv0609|vapC28
MIVDTSAIIAILRDEDDAAAYADALANADVRRLSAASYLECGIVLDSQRDPVISRALDELIEEAEFVVEPVTERQARLARAAYADFGRGSGHPAGLNFGDCLSYALAIDRREPLLWKGNDFGHTGVQRALDRR