vapC15 Family assigned · medium auto-curated

H37Rv Rv2010 · MTBC0 mtbc0_002138 · 132 aa · 2281886–2282284 (+) · RefSeq NP_216526.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ribonuclease VapC15
MTBC0 PGAP re-annotationPIN domain nuclease
Revised (this work)PIN domain nuclease. 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 P9WF97 SwissProt · reviewed · Evidence at protein level
UniProt nameRibonuclease VapC15
EC (curated) EC 3.1.-.-
Curated functionToxic component of a type II toxin-antitoxin (TA) system. Degrades total E.coli RNA, which is partially inhibited by cognate antitoxin VapB15. Upon expression in M.smegmatis inhibits colony formation, which is neutralized by coexpression with VapB15.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred namevapC
eggNOG descriptionnuclease activity
Orthologous groupCOG1487
Gene Ontology (12) GO:0001666, GO:0006950, GO:0008150, GO:0009628, GO:0036293, GO:0040008, GO:0045926, GO:0048519, GO:0050789, GO:0050896, GO:0065007, GO:0070482

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 0.351 · purifying
Polymorphic sites (≥ 0.1% of strains) 1 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)

PfamAccessioni-EvalueResiduesDescription
PINPF01850.28 1.2e-161–120 PIN domain

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

Closest characterised functional partner: vapB15 (antitoxin VapB15), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2009 vapB15 antitoxin VapB15 999 1000 ctx neighborhood:882 experimental:999 textmining:888
Rv1560 vapB11 antitoxin VapB11 961 961 ctx cooccurence:706 experimental:853
Rv2008c hyp hypothetical protein 723 724 ctx neighborhood:600
Rv0623 vapB30 antitoxin VapB30 752 480 ctx cooccurence:454 textmining:544
Rv0624 vapC30 ribonuclease VapC30 893 478 textmining:804
Rv0300 vapB2 antitoxin VapB2 814 454 experimental:412 textmining:674
Rv2601A vapB41 antitoxin VapB41 434 412
Rv1952 vapB14 antitoxin VapB14 429 407
Rv2549c vapC20 ribonuclease VapC20 784 395 textmining:658
Rv0960 vapC9 ribonuclease VapC9 401 387
Rv0609 vapC28 ribonuclease VapC28 840 383 textmining:753
Rv1561 vapC11 ribonuclease VapC11 473 375
Rv0626 vapB5 antitoxin VapB5 767 356 textmining:654
Rv0582 vapC26 ribonuclease VapC26 757 316 textmining:659
Rv2829c vapC22 ribonuclease VapC22 482 301

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 VapC15
  • MTBC0 PGAP product: PIN domain nuclease
  • Pfam (hmmscan --cut_ga): PIN PF01850.28 (E=1e-16)
  • (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_216526.1)
  • 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 COG1487
  • Curated reference: UniProt P9WF97 (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 — 35 functional partner(s); context anchor vapB15
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002138|Rv2010|vapC15
MIVDTSVWIAYLSTSESLASRWLADRIAADSTVIVPEVVMMELLIGKTDEDTAALRRRLLQRFAIEPLAPVRDAEDAAAIHRRCRRGGDTVRSLIDCQVAAMALRIGVAVAHRDRDYEAIRTHCGLRTEPLF