vapC38 Family assigned · medium auto-curated

H37Rv Rv2494 · MTBC0 mtbc0_002656 · 141 aa · 2831200–2831625 (+) · RefSeq NP_217010.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ribonuclease VapC38
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 O53219 SwissProt · reviewed · Evidence at protein level
UniProt nameRibonuclease VapC38
EC (curated) EC 3.1.-.-
Curated functionToxic component of a type II toxin-antitoxin (TA) system. An RNase. Its cognate antitoxin is VapB38 (By similarity).

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
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 1.532 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 4 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-093–122 PIN domain

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

Closest characterised functional partner: vapB38 (antitoxin VapB38), high confidence from genomic context alone (score 884 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2493 vapB38 antitoxin VapB38 931 884 ctx neighborhood:881 textmining:432
Rv2492 hyp hypothetical protein 619 619 ctx neighborhood:619
Rv2491 hyp hypothetical protein 619 619 ctx neighborhood:619
Rv2018 vapB45 hyp hypothetical protein 510 497 ctx cooccurence:492
Rv1114 vapC32 ribonuclease VapC32 655 430 ctx cooccurence:424 textmining:420
Rv1838c vapC13 ribonuclease VapC13 703 418 ctx cooccurence:415 textmining:511
Rv2528c mrr restriction system protein 410 410 ctx cooccurence:410
Rv2954c hyp hypothetical protein 408 408 ctx cooccurence:401
Rv0748 vapB31 antitoxin VapB31 424 407
Rv2871 vapB43 antitoxin VapB43 404 405
Rv1113 vapB32 antitoxin VapB32 401 402 ctx cooccurence:401
Rv2829c vapC22 ribonuclease VapC22 485 313
Rv0549c vapC3 ribonuclease VapC3 583 261 textmining:460
Rv0624 vapC30 ribonuclease VapC30 539 229 textmining:428
Rv2103c vapC37 ribonuclease VapC37 838 212 textmining:803

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 VapC38
  • MTBC0 PGAP product: type II toxin-antitoxin system VapC family toxin
  • Pfam (hmmscan --cut_ga): PIN PF01850.28 (E=7e-09)
  • (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_217010.1)
  • 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 O53219 (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 — 33 functional partner(s); context anchor vapB38
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002656|Rv2494|vapC38
MALLDVNALVALAWDSHIHHARIREWFTANATLGWATCPLTEAGFVRVSTNPKVLPSAIGIADARRVLVALRAVGGHRFLADDVSLVDDDVPLIVGYRQVTDAHLLTLARRRGVRLVTFDAGVFTLAQQRPKTPVELLTIL