vapC14 Resolved · medium auto-curated

H37Rv Rv1953 · MTBC0 - · 103 aa · 2200938–2201249 (+) · RefSeq NP_216469.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ribonuclease VapC14
MTBC0 PGAP re-annotation
Revised (this work)Ribonuclease VapC14.

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt P9WF99 SwissProt · reviewed · Inferred from homology
UniProt nameRibonuclease VapC14
EC (curated) EC 3.1.-.-
Curated functionToxic component of a type II toxin-antitoxin (TA) system. An RNase. The cognate antitoxin is VapB14 (By similarity).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred namevapC
eggNOG descriptionnuclease activity
Orthologous groupCOG1487
KEGG orthology K07062

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 0.168 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 1 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)

No Pfam-A domain above the gathering threshold (or not yet scanned).

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

Closest characterised functional partner: vapB14 (antitoxin VapB14), high confidence from genomic context alone (score 926 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1952 vapB14 antitoxin VapB14 928 926 ctx neighborhood:882
Rv0596c vapB4 antitoxin VapB4 529 529 experimental:513
Rv0626 vapB5 antitoxin VapB5 529 529 experimental:513
Rv1949c Rv1949c, (MTCY09F9.15), len: 319 aa. Conserved hypothetical protein, partial ORF. Rv1949c and Rv1950c|MTCY09F9.14 are similar but frameshift 472 473 ctx neighborhood:466
Rv1950c hyp hypothetical protein 471 471 ctx neighborhood:463
Rv1951c hyp hypothetical protein 465 465 ctx neighborhood:463
Rv1948c hyp hypothetical protein 464 465 ctx neighborhood:463
Rv2063A mazF7 mRNA interferase MazF7 462 461 ctx cooccurence:458
Rv0300 vapB2 antitoxin VapB2 433 433 experimental:412
Rv2601A vapB41 antitoxin VapB41 429 407

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): ribonuclease VapC14
  • (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_216469.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • 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 COG1487
  • Curated reference: UniProt P9WF99 (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 — 10 functional partner(s); context anchor vapB14
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv1953|vapC14
MTYVLDTNVVSALRVPGRHPAVAAWADSVQVAEQFVVAITLAEIERGVIAKERTDPTQSEHLRRWFDDKVLRIFVFARRGTNLIMQPLAGHIGYSLYSGISWF