parE1 Family assigned · medium auto-curated

H37Rv Rv1959c · MTBC0 mtbc0_002074 · 98 aa · 2222797–2223093 (-) · RefSeq NP_216475.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)toxin ParE1
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 P9WHG7 SwissProt · reviewed · Evidence at protein level
UniProt nameToxin ParE1
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 ParD1.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred nameparE1
eggNOG descriptionBelongs to the RelE toxin family
Orthologous groupCOG3668
KEGG orthology K19092
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 0.648 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 1 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.18% of strains (265) · 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-245–93 ParE toxin of type II toxin-antitoxin system, parDE

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

Closest characterised functional partner: parD1 (antitoxin ParD1), high confidence from genomic context alone (score 995 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1960c parD1 antitoxin ParD1 999 995 ctx neighborhood:882 cooccurence:774 experimental:756 textmining:815
Rv2472 hyp hypothetical protein 775 766 experimental:756
Rv2801A mazE9 antitoxin MazE9 774 764 experimental:756
Rv1103c mazE3 antitoxin MazE3 774 764 experimental:756
Rv1958c hyp hypothetical protein 655 656 ctx neighborhood:647
Rv1961 hyp hypothetical protein 589 589 ctx neighborhood:585
Rv2515c hyp hypothetical protein 416 417
Rv2142c parE2 toxin ParE2 876 87 textmining:870
Rv1603 hisA 1-(5-phosphoribosyl)-5-((5-phosphoribosylamino)methylideneamino)imidazole-4-carboxamide isomerase 517 55 textmining:510
Rv2142A parD2 antitoxin ParD2 841 41 textmining:841

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 ParE1
  • MTBC0 PGAP product: type II toxin-antitoxin system RelE/ParE family toxin
  • Pfam (hmmscan --cut_ga): ParE_toxin PF05016.22 (E=5e-24)
  • (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_216475.1)
  • 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 P9WHG7 (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 — 10 functional partner(s); context anchor parD1
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002074|Rv1959c|parE1
MSSRYLLSPAAQAHLEEIWDCTYDRWGVDQAEQYLRELQHAIDRAAANPRIGRACDEIRPGYRKLSAGSHTLFYRVTGEGTIDVVRVLHQRMDVDRNL