Rv0299 Resolved · high auto-curated

H37Rv Rv0299 · MTBC0 mtbc0_000318 · 100 aa · 366815–367117 (+) · RefSeq NP_214813.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)toxin
MTBC0 PGAP re-annotationtoxin-antitoxin system toxin
Revised (this work)Toxin-antitoxin system toxin. Pfam: Rv0299_toxin (PF27466.1).

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

Curated reference (UniProt)

UniProt O07226 SwissProt · reviewed · Evidence at protein level
UniProt nameToxin Rv0299
Curated functionToxic component of a type II toxin-antitoxin (TA) system. Upon expression in M.smegmatis inhibits colony formation. Its toxic effect is neutralized by coexpression with cognate antitoxin Rv0298/MT0312.

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group2BJJP
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 1.132 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 3 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
Rv0299_toxinPF27466.1 2.5e-415–98 Type II toxin-antitoxin system toxin Rv0299

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

Closest characterised functional partner: Rv0298 (antitoxin), high confidence from genomic context alone (score 887 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0298 antitoxin 989 887 ctx neighborhood:882 textmining:912
Rv0300 vapB2 antitoxin VapB2 781 781 ctx neighborhood:667
Rv0301 vapC2 ribonuclease VapC2 683 683 ctx neighborhood:667
Rv0297 PE_PGRS5 PE-PGRS family protein PE_PGRS5 499 498 ctx neighborhood:498
Rv0302 transcriptional regulator 430 430 ctx neighborhood:423
Rv0303 dehydrogenase/reductase 421 421 ctx neighborhood:421
Rv3697c vapC48 ribonuclease VapC48 550 54 textmining:544
Rv0910 toxin 551 53 textmining:546
Rv3749c vapC50 hyp hypothetical protein 810 50 textmining:809
Rv3750c vapB50 excisionase 804 50 textmining:803
Rv0461 transmembrane protein 653 47 textmining:651
Rv0909 antitoxin 549 47 textmining:547
Rv0624 vapC30 ribonuclease VapC30 437 47 textmining:434
Rv0424c hyp hypothetical protein 652 46 textmining:651
Rv2021c higA2 transcriptional regulator 552 46 textmining:550

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: toxin
  • MTBC0 PGAP product: toxin-antitoxin system toxin
  • Pfam (hmmscan --cut_ga): Rv0299_toxin PF27466.1 (E=2e-41)
  • (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_214813.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Rv0299_toxin (PF27466.1)
  • 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 2BJJP
  • Curated reference: UniProt O07226 (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 — 27 functional partner(s); context anchor Rv0298
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000318|Rv0299|
MIAPGDIAPRRDSEHELYVAVLSNALHRAADTGRVITCPFIPGRVPEDLLAMVVAVEQPNGTLLPELVQWLHVAALGAPLGNAGVAALREAASVVTALLC