relK Family assigned · medium auto-curated

H37Rv Rv3358 · MTBC0 mtbc0_003573 · 85 aa · 3797753–3798010 (+) · RefSeq NP_217875.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)toxin RelK
MTBC0 PGAP re-annotationTxe/YoeB family addiction module toxin
Revised (this work)Txe/YoeB family addiction module toxin. Pfam: YoeB_toxin (PF06769.21).

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

Curated reference (UniProt)

UniProt P9WF09 SwissProt · reviewed · Evidence at protein level
UniProt nameToxin RelK
EC (curated) EC 3.1.-.-
Curated functionToxic component of a type II toxin-antitoxin (TA) system. Has RNase activity and preferentially cleaves at the 3'-end of purine ribonucleotides (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 antitoxin RelJ (shown only for M.smegmatis). Overexpression also increases the number of rifampcin-tolerant persister cells..; FUNCTION: In combination with RelJ represses its own promoter. Several DNA-protein complexes are formed in vitro depending on the .

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred namerelK
eggNOG descriptionYoeB-like toxin of bacterial type II toxin-antitoxin system
Orthologous groupCOG4115
KEGG orthology K19158
Gene Ontology (68) GO:0003674, GO:0003824, GO:0004518, GO:0004519, GO:0006139, GO:0006355, GO:0006401, GO:0006725, GO:0006807, GO:0008150, GO:0008152, GO:0009056 +56 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 0.896 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 3 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)

PfamAccessioni-EvalueResiduesDescription
YoeB_toxinPF06769.21 9.1e-406–85 YoeB-like toxin of bacterial type II toxin-antitoxin system

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

Closest characterised functional partner: relJ (antitoxin RelJ), high confidence from genomic context alone (score 999 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3357 relJ antitoxin RelJ 999 999 ctx neighborhood:882 cooccurence:773 experimental:966 textmining:929
Rv1247c relB antitoxin RelB 956 765 experimental:748 textmining:824
Rv2865 relF antitoxin RelF 923 763 experimental:748 textmining:690
Rv0268c hyp hypothetical protein 793 756 experimental:748
Rv3359 oxidoreductase 666 666 ctx neighborhood:661
Rv3356c folD bifunctional methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase 588 589 ctx neighborhood:589
Rv3355c integral membrane protein 556 557 ctx neighborhood:557
Rv2788 sirR transcriptional repressor SirR 499 500 experimental:500
Rv3360 hyp hypothetical protein 426 426 ctx neighborhood:426
Rv2866 relG toxin RelG 832 77 textmining:826
Rv1246c relE toxin RelE 889 76 textmining:885
Rv1991c mazF6 mRNA interferase MazF6 579 55 textmining:573
Rv1955 higB toxin HigB 661 49 textmining:659
Rv2019 vapC45 hyp hypothetical protein 643 47 textmining:641
Rv1495 mazF4 mRNA interferase MazF4 542 47 textmining:540

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 RelK
  • MTBC0 PGAP product: Txe/YoeB family addiction module toxin
  • Pfam (hmmscan --cut_ga): YoeB_toxin PF06769.21 (E=9e-40)
  • (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_217875.1)
  • Domains: Pfam-A via hmmscan --cut_ga — YoeB_toxin (PF06769.21)
  • 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 COG4115
  • Curated reference: UniProt P9WF09 (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 — 29 functional partner(s); context anchor relJ
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003573|Rv3358|relK
MRSVNFDPDAWEDFLFWLAADRKTARRITRLIGEIQRDPFSGIGKPEPLQGELSGYWSRRIDDEHRLVYRAGDDEVTMLKARYHY