relE Resolved · high auto-curated

H37Rv Rv1246c · MTBC0 mtbc0_001335 · 97 aa · 1397129–1397422 (-) · RefSeq NP_215762.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)toxin RelE
MTBC0 PGAP re-annotationtype II toxin-antitoxin system mRNA interferase RelE
Revised (this work)Type II toxin-antitoxin system mRNA interferase RelE. 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 O50461 SwissProt · reviewed · Evidence at protein level
UniProt nameToxin RelE
EC (curated) EC 3.1.-.-
Curated functionToxic component of a type II toxin-antitoxin (TA) system. Has RNase activity (By similarity). Overexpression in M.tuberculosis or M.smegmatis inhibits colony formation in a bacteriostatic rather than bacteriocidal fashion. Its toxic effect is neutralized by coexpression with cognate antitoxin RelB (shown only for M.smegmatis)..; FUNCTION: In combination with RelB represses its own promoter. Has been seen to bind DNA in complex with cognate antitoxin RelB but not alone.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
Preferred namerelE
eggNOG descriptionParE toxin of type II toxin-antitoxin system, parDE
Orthologous groupCOG2026
Gene Ontology (39) GO:0003674, GO:0003824, GO:0004518, GO:0004519, GO:0006139, GO:0006401, GO:0006725, GO:0006807, GO:0008150, GO:0008152, GO:0009056, GO:0009057 +27 more

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, 1 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.26% of strains (380) · 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 1.8e-109–88 ParE toxin of type II toxin-antitoxin system, parDE

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

Closest characterised functional partner: relB (antitoxin RelB), high confidence from genomic context alone (score 983 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1247c relB antitoxin RelB 997 983 ctx neighborhood:882 cooccurence:774 textmining:878
Rv2865 relF antitoxin RelF 975 872 ctx cooccurence:774 textmining:815
Rv1245c short-chain type dehydrogenase/reductase 654 653 ctx neighborhood:651
Rv0659c mazF2 toxin MazF2 755 644 ctx cooccurence:633
Rv1942c mazF5 toxin MazF5 705 584 ctx cooccurence:572
Rv1248c kgd multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase 576 576 ctx neighborhood:564
Rv2017 transcriptional regulator 511 449 ctx cooccurence:413
Rv3387 transposase 439 440 ctx cooccurence:436
Rv2961 transposase 431 432 ctx cooccurence:428
Rv1034c Probable transposase (fragment); Rv1034c, (MTCY10G2.15), len: 129 aa. Probable IS1560 transposase fragment, similar to part of Rv3387|E12023 406 407 ctx cooccurence:405
Rv3749c vapC50 hyp hypothetical protein 492 314
Rv0595c vapC4 ribonuclease VapC4 600 297 textmining:455
Rv1102c mazF3 mRNA interferase MazF3 732 281 textmining:643
Rv3750c vapB50 excisionase 452 264
Rv1495 mazF4 mRNA interferase MazF4 582 228 textmining:482

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 RelE
  • MTBC0 PGAP product: type II toxin-antitoxin system mRNA interferase RelE
  • Pfam (hmmscan --cut_ga): ParE_toxin PF05016.22 (E=2e-10)
  • (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_215762.1)
  • 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 COG2026
  • Curated reference: UniProt O50461 (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 — 37 functional partner(s); context anchor relB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001335|Rv1246c|relE
MSDDHPYHVAITATAARDLQRLPEKIAAACVEFVFGPLLNNPHRLGKPLRNDLEGLHSARRGDYRVVYAIDDGHHRVEIIHIARRSASYRMNPCRPR