vapC5 Family assigned · medium auto-curated

H37Rv Rv0627 · MTBC0 mtbc0_000651 · 28 aa · 715088–715171 (+) · RefSeq NP_215141.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ribonuclease VapC5
MTBC0 PGAP re-annotationgalactose-1-phosphate uridylyltransferase
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 P96917 SwissProt · reviewed · Evidence at protein level
UniProt nameRibonuclease VapC5
EC (curated) EC 3.1.-.-
Curated functionProbable toxic component of a type II toxin-antitoxin (TA) system. The cognate antitoxin is VapB5. Has limited RNase activity on substrates; activity is seen with a VapC5-VapB5 complex.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred namegalT
eggNOG descriptiongalactose-1-phosphate uridylyltransferase
Orthologous groupCOG1085
EC number EC 2.7.7.12
KEGG orthology K00965
KEGG pathways map00052, map00520, map01100, map04917
KEGG modules M00362, M00554, M00632

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 0.0 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 0 missense, 0 nonsense, 2 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 0.79% of strains (1147) · clonal

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 1.1e-179–125 PIN domain

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

Closest characterised functional partner: vapB5 (antitoxin VapB5), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0626 vapB5 antitoxin VapB5 999 1000 ctx neighborhood:882 cooccurence:769 experimental:999 textmining:818
Rv0596c vapB4 antitoxin VapB4 805 797 experimental:784
Rv3384c vapC46 ribonuclease VapC46 590 580 ctx cooccurence:510
Rv0625c transmembrane protein 581 580 ctx neighborhood:579
Rv3408 vapC47 ribonuclease VapC47 622 548 ctx cooccurence:540
Rv1871c hyp hypothetical protein 500 500 ctx cooccurence:496
Rv3385c vapB46 antitoxin VapB46 498 498
Rv3407 vapB47 antitoxin VapB47 481 481
Rv0300 vapB2 antitoxin VapB2 925 449 experimental:412 textmining:870
Rv1560 vapB11 antitoxin VapB11 438 438
Rv1952 vapB14 antitoxin VapB14 437 415
Rv2601A vapB41 antitoxin VapB41 432 410
Rv0065 vapC1 ribonuclease VapC1 666 321 textmining:529
Rv0549c vapC3 ribonuclease VapC3 637 266 textmining:526
Rv0582 vapC26 ribonuclease VapC26 646 252 textmining:546

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 VapC5
  • MTBC0 PGAP product: type II toxin-antitoxin system VapC family toxin
  • Pfam (hmmscan --cut_ga): PIN PF01850.28 (E=1e-17)
  • (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_215141.1)
  • 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 COG1085
  • Curated reference: UniProt P96917 (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 vapB5
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000651|Rv0627|vapC5
MSATPPPGGLDASVFIANERGRQLDEAL