parE2 Family assigned · medium auto-curated

H37Rv Rv2142c · MTBC0 mtbc0_002277 · 105 aa · 2429572–2429889 (-) · RefSeq NP_216658.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)toxin ParE2
MTBC0 PGAP re-annotationtype II toxin-antitoxin system RelE/ParE family toxin
Revised (this work)Type II toxin-antitoxin system RelE/ParE family toxin. Pfam: ParE_toxin (PF05016.22).

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

Curated reference (UniProt)

UniProt P9WHG5 SwissProt · reviewed · Evidence at protein level
UniProt nameToxin ParE2
Curated functionToxic component of a type II toxin-antitoxin (TA) system. Upon expression in E.coli inhibits cell growth and colony formation. Its toxic effect is neutralized by coexpression with cognate antitoxin ParD2.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category D Cell cycle control, cell division, chromosome partitioning
eggNOG descriptionPlasmid stabilization system
Orthologous groupCOG3668
KEGG orthology K19093
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 0.0 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 0 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.21% of strains (302) · 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
ParE_toxinPF05016.22 4.9e-076–91 ParE toxin of type II toxin-antitoxin system, parDE

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

Closest characterised functional partner: parD2 (antitoxin ParD2), high confidence from genomic context alone (score 882 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2142A parD2 antitoxin ParD2 976 882 ctx neighborhood:882 textmining:806
Rv2143 hyp hypothetical protein 470 470 ctx neighborhood:467
Rv1959c parE1 toxin ParE1 876 87 textmining:870
Rv1960c parD1 antitoxin ParD1 804 50 textmining:803
Rv1603 hisA 1-(5-phosphoribosyl)-5-((5-phosphoribosylamino)methylideneamino)imidazole-4-carboxamide isomerase 654 47 textmining:652

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 ParE2
  • MTBC0 PGAP product: type II toxin-antitoxin system RelE/ParE family toxin
  • Pfam (hmmscan --cut_ga): ParE_toxin PF05016.22 (E=5e-07)
  • (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_216658.1)
  • Domains: Pfam-A via hmmscan --cut_ga — ParE_toxin (PF05016.22)
  • 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 COG3668
  • Curated reference: UniProt P9WHG5 (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 — 5 functional partner(s); context anchor parD2
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002277|Rv2142c|parE2
MTRRLRVHNGVEDDLFEAFSYYADAAPDQIDRLYNLFVDAVTKRIPQAPNAFAPLFKHYRHIYLRPFRYYVAYRTTDEAIDILAVRHGMENPNAVEAEISGRTFE