Rv2653c Resolved · medium auto-curated

H37Rv Rv2653c · MTBC0 mtbc0_002827 · 107 aa · 2998789–2999112 (-) · RefSeq NP_217169.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)toxin
MTBC0 PGAP re-annotationtype II toxin-antitoxin system toxin
Revised (this work)Type II toxin-antitoxin system toxin.

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

Curated reference (UniProt)

UniProt P9WJ13 SwissProt · reviewed · Evidence at protein level
UniProt nameToxin Rv2653c
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 Rv2654c.

Conservation & selection (intra-MTBC, 145 209 strains)

pN/pS 0.719 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 7 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.21% of strains (299) · 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)

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

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

Closest characterised functional partner: Rv2652c (prophage protein), medium confidence from genomic context alone (score 693 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2652c prophage protein 693 693 ctx neighborhood:685
Rv2655c prophage protein 585 586 ctx neighborhood:567
Rv2656c prophage protein 724 578 ctx neighborhood:573
Rv2654c antitoxin 934 571 ctx neighborhood:567 textmining:853
Rv2657c prophage protein 679 568 ctx neighborhood:567
Rv2658c prophage protein 770 543 ctx neighborhood:541 textmining:516
Rv2659c prophage integrase 695 536 ctx neighborhood:533
Rv2650c prophage protein 431 431 ctx neighborhood:424
Rv2651c prophage protease 429 429 ctx neighborhood:426
Rv1397c vapC10 ribonuclease VapC10 446 47 textmining:443
Rv0837c hyp hypothetical protein 435 47 textmining:432
Rv2526 vapB17 antitoxin VapB17 437 45 textmining:435
Rv0909 antitoxin 680 44 textmining:679
Rv0656c vapC6 ribonuclease VapC6 517 43 textmining:516
Rv1102c mazF3 mRNA interferase MazF3 432 42 textmining:432

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: type II toxin-antitoxin system toxin
  • (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_217169.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
  • Curated reference: UniProt P9WJ13 (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 — 23 functional partner(s); context anchor Rv2652c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002827|Rv2653c|
MTHKRTKRQPAIAAGLNAPRRNRVGRQHGWPADVPSAEQRRAQRQRDLEAIRRAYAEMVATSHEIDDDTAELALLSMHLDDEQRRLEAGMKLGWHPYQFPDEPDSKQ