Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | HTH-type transcriptional repressor EthR |
|---|
| MTBC0 PGAP re-annotation | HTH-type transcriptional regulator EthR |
|---|
| Revised (this work) | HTH-type transcriptional regulator EthR. Pfam: TetR_N (PF00440.30), EthR_C (PF21313.3). |
|---|
Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WMC1
SwissProt · reviewed
· Evidence at protein level
|
|---|
| UniProt name | HTH-type transcriptional regulator EthR |
|---|
| Curated function | Involved in the repression of the monooxygenase EthA which is responsible of the formation of the active metabolite of ethionamide (ETH). |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|
| Preferred name | ethR |
|---|
| eggNOG description | Transcriptional regulator |
|---|
| Orthologous group | COG1309 |
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| KEGG orthology |
K21961
|
|---|
| Gene Ontology (60) |
GO:0000976, GO:0001067, GO:0003674, GO:0003676, GO:0003677, GO:0003690, GO:0003700, GO:0005488, GO:0005575, GO:0005622, GO:0005623, GO:0005737 +48 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 |
0.526 · relaxed/neutral
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
2 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|
TetR_N | PF00440.30 |
5.8e-13 | 29–73 |
Bacterial regulatory proteins, tetR family |
EthR_C | PF21313.3 |
3.1e-52 | 103–213 |
Transcriptional regulator EthR, C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv0158 |
transcriptional regulator |
869 |
869 |
coexpression:802 |
Rv3060c |
GntR family transcriptional regulator |
842 |
837 |
coexpression:837 |
Rv1985c lysG |
HTH-type transcriptional regulator |
833 |
831 |
coexpression:810 |
Rv0624 vapC30 |
ribonuclease VapC30 |
799 |
799 |
coexpression:799 |
Rv1019 |
transcriptional regulator |
799 |
799 |
coexpression:799 |
Rv3183 higA3 |
transcriptional regulator |
797 |
797 |
coexpression:797 |
Rv3263 |
DNA methylase |
793 |
793 |
coexpression:793 |
Rv3557c kstR2 |
HTH-type transcriptional regulator KstR2 |
791 |
778 |
coexpression:748 |
Rv0691c mftR |
mycofactocin biosynthesis transcriptional regulator MftR |
782 |
776 |
coexpression:731 |
Rv3840 |
transcriptional regulator |
767 |
767 |
coexpression:767 |
Rv3736 |
AraC/XylS family transcriptional regulator |
768 |
765 |
coexpression:765 |
Rv1960c parD1 |
antitoxin ParD1 |
765 |
765 |
coexpression:765 |
Rv3167c |
TetR family transcriptional regulator |
779 |
753 |
coexpression:716 |
Rv0339c iniR |
transcriptional regulator |
734 |
734 |
coexpression:734 |
Rv1776c |
transcriptional regulator |
734 |
734 |
coexpression:734 |
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: HTH-type transcriptional repressor EthR
- MTBC0 PGAP product: HTH-type transcriptional regulator EthR
- Pfam (hmmscan --cut_ga): TetR_N PF00440.30 (E=6e-13), EthR_C PF21313.3 (E=3e-52)
- (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_218372.1)
- Domains: Pfam-A via hmmscan --cut_ga — TetR_N (PF00440.30), EthR_C (PF21313.3)
- 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
COG1309
- Curated reference: UniProt
P9WMC1
(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 —
57 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_004088|Rv3855|ethR
MTTSAASQASLPRGRRTARPSGDDRELAILATAENLLEDRPLADISVDDLAKGAGISRPTFYFYFPSKEAVLLTLLDRVVNQADMALQTLAENPADTDRENMWRTGINVFFETFGSHKAVTRAGQAARATSVEVAELWSTFMQKWIAYTAAVIDAERDRGAAPRTLPAHELATALNLMNERTLFASFAGEQPSVPEARVLDTLVHIWVTSIYGENR
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