Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | MerR family transcriptional regulator |
|---|
| MTBC0 PGAP re-annotation | hypoxia response transcriptional regulator |
|---|
| Revised (this work) | Hypoxia response transcriptional regulator. Pfam: MerR_1 (PF13411.13), MerR (PF00376.30), MerR-DNA-bind (PF09278.18). |
|---|
Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53384
TrEMBL · unreviewed
· Predicted
|
|---|
| UniProt name | Probable transcriptional regulatory protein |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|
| eggNOG description | transcriptional regulator, MerR |
|---|
| Orthologous group | COG0789 |
|---|
| KEGG orthology |
K19591
|
|---|
| KEGG modules |
M00769
|
|---|
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, 2 missense, 0 nonsense, 1 frameshift
|
|---|
| Disruption |
1 distinct premature-stop/frameshift site(s); most common in
0.26% of strains
(376) · 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|
MerR_1 | PF13411.13 |
1.4e-18 | 1–67 |
MerR HTH family regulatory protein |
MerR | PF00376.30 |
3.3e-16 | 2–39 |
MerR family regulatory protein |
MerR-DNA-bind | PF09278.18 |
1.4e-18 | 44–108 |
MerR, DNA binding |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv0792c |
transcriptional regulator |
755 |
740 |
coexpression:740 |
Rv2017 |
transcriptional regulator |
638 |
620 |
coexpression:539 |
Rv2373c dnaJ2 |
chaperone protein DnaJ |
623 |
600 |
experimental:469 |
Rv0352 dnaJ1 |
chaperone protein DnaJ |
611 |
586 |
experimental:469 |
Rv2220 glnA1 |
glutamine synthetase |
539 |
516 |
|
Rv2222c glnA2 |
glutamine synthetase |
538 |
514 |
|
Rv1878 glnA3 |
glutamine synthetase GlnA |
537 |
513 |
|
Rv2860c glnA4 |
glutamine synthetase |
535 |
512 |
|
Rv2710 sigB |
RNA polymerase sigma factor SigB |
516 |
486 |
experimental:436 |
Rv3457c rpoA |
DNA-directed RNA polymerase subunit alpha |
509 |
485 |
experimental:463 |
Rv2703 sigA |
RNA polymerase sigma factor SigA |
515 |
484 |
experimental:436 |
Rv1390 rpoZ |
DNA-directed RNA polymerase subunit omega |
500 |
481 |
experimental:463 |
Rv0667 rpoB |
DNA-directed RNA polymerase subunit beta |
509 |
478 |
experimental:475 |
Rv0668 rpoC |
DNA-directed RNA polymerase subunit beta' |
485 |
466 |
experimental:463 |
Rv0904c accD3 |
acetyl-CoAcarboxylase carboxyl transferase subunit beta |
445 |
445 |
experimental:416 |
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: MerR family transcriptional regulator
- MTBC0 PGAP product: hypoxia response transcriptional regulator
- Pfam (hmmscan --cut_ga): MerR_1 PF13411.13 (E=1e-18), MerR PF00376.30 (E=3e-16), MerR-DNA-bind PF09278.18 (E=1e-18)
- (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_217851.1)
- Domains: Pfam-A via hmmscan --cut_ga — MerR_1 (PF13411.13), MerR (PF00376.30), MerR-DNA-bind (PF09278.18)
- 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
COG0789
- Curated reference: UniProt
O53384
(TrEMBL, unreviewed; Predicted)
- 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)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003547|Rv3334|
MKISEVAALTNTSTKTLRFYENSGLLPPPARTASGYRNYGPEIVDRLRFIHRGQAAGLALQEVRQILAIHDRGEAPCAHVRQLLSTRIDEVRAQIAELIALEGHLQTLLDHASYGPPTEHDHSTVCWILESDLDEPTAIEVSDIHA
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