relG Family assigned · medium auto-curated
H37Rv Rv2866 · MTBC0 mtbc0_003048 ·
87 aa · 3198488–3198751 (+) ·
RefSeq NP_217382.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | toxin RelG |
|---|---|
| MTBC0 PGAP re-annotation | type 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 |
O33348
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Toxin RelG |
| EC (curated) |
EC 3.1.-.-
|
| Curated function | Toxic 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 cognate antitoxin RelB2 (shown only for M.smegmatis). Overexpression also increases the number of gentamicin-tolerant and levofloxacin-tolerant persister cells..; FUNCTION: In combination with cognate antitoxin RelF represses its own promoter. Has been seen. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|---|
| eggNOG description | ParE toxin of type II toxin-antitoxin system, parDE |
| Orthologous group | COG2026 |
| Gene Ontology (70) |
GO:0003674, GO:0003824, GO:0004518, GO:0004519, GO:0006139, GO:0006355, GO:0006401, GO:0006725, GO:0006807, GO:0008150, GO:0008152, GO:0009056 +58 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 | 0.0 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 0 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
ParE_toxin | PF05016.22 | 1.2e-12 | 5–85 | ParE toxin of type II toxin-antitoxin system, parDE |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: relF (antitoxin RelF), high confidence from genomic context alone (score 994 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2865 relF |
antitoxin RelF | 998 | 994 ctx | neighborhood:788 cooccurence:773 experimental:893 textmining:820 |
Rv1247c relB |
antitoxin RelB | 956 | 870 ctx | cooccurence:773 experimental:409 textmining:680 |
Rv0659c mazF2 |
toxin MazF2 | 639 | 576 ctx | cooccurence:564 |
Rv1942c mazF5 |
toxin MazF5 | 596 | 545 ctx | cooccurence:534 |
Rv2864c |
penicillin-binding lipoprotein | 437 | 438 ctx | neighborhood:436 |
Rv3357 relJ |
antitoxin RelJ | 764 | 295 | textmining:680 |
Rv2021c higA2 |
transcriptional regulator | 505 | 218 | |
Rv2022c higB2 hyp |
hypothetical protein | 454 | 169 | |
Rv3358 relK |
toxin RelK | 832 | 77 | textmining:826 |
Rv2034 |
ArsR family HTH-type transcriptional repressor | 518 | 51 | textmining:513 |
Rv3189 hyp |
hypothetical protein | 516 | 50 | textmining:512 |
Rv3188 hyp |
hypothetical protein | 514 | 47 | textmining:511 |
Rv2867c |
GCN5-like N-acetyltransferase | 658 | 46 | textmining:657 |
Rv0918 hyp |
hypothetical protein | 492 | 46 | textmining:490 |
Rv2451 hyp |
hypothetical protein | 657 | 41 | textmining:657 |
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 RelG
- MTBC0 PGAP product: type II toxin-antitoxin system RelE/ParE family toxin
- Pfam (hmmscan --cut_ga): ParE_toxin PF05016.22 (E=1e-12)
- (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_217382.1)
- 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 O33348 (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 —
15 functional partner(s); context anchor
relF - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003048|Rv2866|relG MPYTVRFTTTARRDLHKLPPRILAAVVEFAFGDLSREPLRVGKPLRRELAGTFSARRGTYRLLYRIDDEHTTVVILRVDHRADIYRR