Rv2654c Resolved · medium auto-curated

H37Rv Rv2654c · MTBC0 mtbc0_002828 · 81 aa · 2999192–2999437 (-) · RefSeq NP_217170.1

Annotation: from legacy to revised

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

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

Curated reference (UniProt)

UniProt P9WJ11 SwissProt · reviewed · Evidence at protein level
UniProt nameAntitoxin Rv2654c
Curated functionAntitoxin component of a type II toxin-antitoxin (TA) system. Upon expression in M.smegmatis neutralizes the effect of cognate toxin Rv2653c.

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

pN/pS 0.414 · 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)

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

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

Closest characterised functional partner: Rv2656c (prophage protein), high confidence from genomic context alone (score 784 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2656c prophage protein 921 784 ctx neighborhood:781 textmining:652
Rv2655c prophage protein 784 784 ctx neighborhood:781
Rv2657c prophage protein 896 782 ctx neighborhood:781 textmining:542
Rv2658c prophage protein 852 747 ctx neighborhood:746 textmining:441
Rv2659c prophage integrase 815 738 ctx neighborhood:737
Rv2653c toxin 934 571 ctx neighborhood:567 textmining:853
Rv2652c prophage protein 497 496 ctx neighborhood:493
Rv2660c hyp hypothetical protein 476 476 ctx neighborhood:461
Rv2661c hyp hypothetical protein 462 462 ctx neighborhood:461
Rv0909 antitoxin 655 46 textmining:654
Rv0298 antitoxin 434 44 textmining:433
Rv0910 toxin 653 42 textmining:653
Rv1545 hyp hypothetical protein 510 42 textmining:510
Rv3622c PE32 PE family protein PE32 511 41 textmining:511
Rv2355 Probable transposase; Rv2355, (MTCY98.24), len: 328 aa. Probable IS6110 transposase. Identical to many other M. tuberculosis IS6110 transpos 433 41 textmining:433

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: antitoxin
  • MTBC0 PGAP product: type II toxin-antitoxin system antitoxin
  • (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_217170.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
  • Curated reference: UniProt P9WJ11 (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 — 16 functional partner(s); context anchor Rv2656c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002828|Rv2654c|
MSGHALAARTLLAAADELVGGPPVEASAAALAGDAAGAWRTAAVELARALVRAVAESHGVAAVLFAATAAAAAAVDRGDPP