Rv1176c Family assigned · medium auto-curated
H37Rv Rv1176c · MTBC0 mtbc0_001265 ·
189 aa · 1316664–1317233 (-) ·
RefSeq NP_215692.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | PadR family transcriptional regulator |
| Revised (this work) | PadR family transcriptional regulator. Pfam: PadR (PF03551.21), Vir_act_alpha_C (PF10400.16). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O50432
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable transcriptional regulator Rv1176c |
| Curated function | Probable transcriptional regulator that may help mitigate the effect of oxidative stress and help mycobacteria survive inside macrophages. Binds to its own promoter region. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|---|
| Preferred name | padR |
| eggNOG description | Virulence activator alpha C-term |
| Orthologous group | COG1695 |
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 | 0.672 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 2 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.79% of strains (1149) · 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 |
|---|---|---|---|---|
PadR | PF03551.21 | 1.2e-12 | 7–80 | Transcriptional regulator PadR-like family |
Vir_act_alpha_C | PF10400.16 | 5.4e-20 | 105–185 | Virulence activator alpha C-term |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: fadH (NADPH dependent 2,4-dienoyl-CoA reductase FadH), high confidence from genomic context alone (score 910 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1175c fadH |
NADPH dependent 2,4-dienoyl-CoA reductase FadH | 910 | 910 ctx | neighborhood:882 |
Rv3488 hyp |
hypothetical protein | 810 | 810 | coexpression:810 |
Rv1960c parD1 |
antitoxin ParD1 | 740 | 740 | coexpression:740 |
Rv0158 |
transcriptional regulator | 737 | 732 | coexpression:732 |
Rv1177 fdxC |
ferredoxin FdxC | 731 | 732 ctx | neighborhood:731 |
Rv1178 dapC |
aminotransferase | 730 | 731 ctx | neighborhood:727 |
Rv0744c |
transcriptional regulator | 730 | 730 | coexpression:730 |
Rv3830c |
TetR family transcriptional regulator | 692 | 687 | coexpression:687 |
Rv1174c TB8.4 |
low molecular weight T-cell antigen | 517 | 517 ctx | neighborhood:515 |
Rv1151c cobB |
NAD-dependent protein deacylase | 527 | 472 | coexpression:454 |
Rv2912c |
TetR family HTH-type transcriptional regulator | 459 | 449 | coexpression:449 |
Rv3405c |
HTH-type transcriptional regulator | 451 | 441 | coexpression:441 |
Rv2282c |
LysR family HTH-type transcriptional regulator | 431 | 431 | coexpression:431 |
Rv1218c |
tetronasin ABC transporter ATP-binding protein | 425 | 426 | |
Rv3167c |
TetR family transcriptional regulator | 431 | 420 |
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: hypothetical protein
- MTBC0 PGAP product: PadR family transcriptional regulator
- Pfam (hmmscan --cut_ga): PadR PF03551.21 (E=1e-12), Vir_act_alpha_C PF10400.16 (E=5e-20)
- (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_215692.1)
- Domains: Pfam-A via hmmscan --cut_ga — PadR (PF03551.21), Vir_act_alpha_C (PF10400.16)
- 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
COG1695 - Curated reference: UniProt O50432 (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 —
20 functional partner(s); context anchor
fadH - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001265|Rv1176c| MALPHAILVSLCEQASSGYELARRFDRSIGYFWTATHQQIYRTLRVMENNNWVRATTVLQHGRPDKKVYAISDSGRAELARWIAEPLSPTRPGRGSALTDSSTRDIAVKLRGAGYGDVAALYTQVTALRAERVKSLDTYRGIEKRTFADPSALDGAALHQYLVLRGGIRAEESAIDWLDEVAEALQEKR