Rv0268c Family assigned · medium auto-curated

H37Rv Rv0268c · MTBC0 - · 169 aa · 322764–323273 (-) · RefSeq NP_214782.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)Contains PhdYeFM_antitox (PF02604.27) domain(s); putative function inferred from the domain architecture.

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 P95225 SwissProt · reviewed · Inferred from homology
UniProt namePutative antitoxin Rv0268c
Curated functionPutative antitoxin component of a type II toxin-antitoxin (TA) system; however the expected toxin coding sequence is not found adjacent to this gene.

UniProt still lists this protein as Putative antitoxin Rv0268c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category D Cell cycle control, cell division, chromosome partitioning
eggNOG descriptiontoxin-antitoxin pair type II binding
Orthologous groupCOG2161
KEGG orthology K19159

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 n/a
Polymorphic sites (≥ 0.1% of strains) 0 synonymous, 2 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.12% of strains (167) · 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
PhdYeFM_antitoxPF02604.27 7.8e-1390–140 Antitoxin Phd_YefM, type II toxin-antitoxin system

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

Closest characterised functional partner: fadD2 (fatty-acid--CoA ligase FadD2), medium confidence from genomic context alone (score 448 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3358 relK toxin RelK 793 756 experimental:748
Rv0269c hyp hypothetical protein 941 597 ctx neighborhood:596 textmining:860
Rv0270 fadD2 fatty-acid--CoA ligase FadD2 448 448 ctx neighborhood:441
Rv0366c hyp hypothetical protein 672 78 textmining:659
Rv1103c mazE3 antitoxin MazE3 810 76 textmining:803
Rv2017 transcriptional regulator 664 72 textmining:653
Rv0229c vapC51 hyp hypothetical protein 470 69 textmining:454
Rv2515c hyp hypothetical protein 817 67 textmining:812
Rv2514c hyp hypothetical protein 868 63 textmining:865
Rv2022c higB2 hyp hypothetical protein 541 59 textmining:533
Rv0207c hyp hypothetical protein 732 58 textmining:728
Rv0208c trmB tRNA (guanine-N(7)-)-methyltransferase 761 51 textmining:759
Rv3641c fic cell filamentation protein Fic 438 49 textmining:434
Rv0367c hyp hypothetical protein 804 47 textmining:803
Rv0078A hyp hypothetical protein 804 47 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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): hypothetical protein
  • Pfam (hmmscan --cut_ga): PhdYeFM_antitox PF02604.27 (E=8e-13)
  • (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_214782.1)
  • Domains: Pfam-A via hmmscan --cut_ga — PhdYeFM_antitox (PF02604.27)
  • 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 COG2161
  • Curated reference: UniProt P95225 (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 — 17 functional partner(s); context anchor fadD2
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0268c|
MGTRSKSRTRQLKQSNGCTATTSGASDRRRRARRRTAPAWLREDEWLRHHLPHPPRQLSRCLHRRRRSACHHRYSRRTPKGGLPMTSSLVPISEARAHLSRLVRESADDDVVLMNHGRPAAILISAERYESLMEELEDLRDRLSVHEREHVTMPLDKLGAELGVDIGRV