Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | TetR family transcriptional regulator |
|---|
| MTBC0 PGAP re-annotation | TetR/AcrR family transcriptional regulator |
|---|
| Revised (this work) | TetR/AcrR family transcriptional regulator. Pfam: TetR_N (PF00440.30), TetR_C_46 (PF21943.2). |
|---|
Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O05858
SwissProt · reviewed
· Evidence at protein level
|
|---|
| UniProt name | HTH-type transcriptional activator FasR |
|---|
| Curated function | Transcriptional activator that plays a central role in sensing mycobacterial long-chain fatty acids and regulating lipid biosynthesis. Activates the expression of the genes encoding the fatty acid synthase (fas) and the 4-phosphopantetheinyl transferase (acpS), whose products are involved in the fatty acid and mycolic acid biosynthesis. Specifically binds to three conserved operator sequences present in the fas-acpS promoter region. Not essential for M.tuberculosis viability, although it is required for the optimal growth in vitro and for virulence in macrophages and in a mouse model of infect. |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|
| eggNOG description | tetR family |
|---|
| Orthologous group | COG1309 |
|---|
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, 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 |
7.9e-17 | 44–90 |
Bacterial regulatory proteins, tetR family |
TetR_C_46 | PF21943.2 |
3.6e-08 | 113–218 |
Tetracyclin repressor-like, C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv0844c narL |
nitrate/nitrite response transcriptional regulator NarL |
751 |
751 |
coexpression:751 |
Rv2788 sirR |
transcriptional repressor SirR |
738 |
733 |
coexpression:732 |
Rv1960c parD1 |
antitoxin ParD1 |
732 |
732 |
coexpression:732 |
Rv1167c |
transcriptional regulator |
731 |
731 |
coexpression:731 |
Rv0273c |
transcriptional regulator |
663 |
651 |
coexpression:651 |
Rv1474c |
transcriptional regulator |
457 |
458 |
|
Rv0238 |
transcriptional regulator |
421 |
422 |
|
Rv2506 |
TetR family transcriptional regulator |
408 |
407 |
|
Rv1014c pth |
peptidyl-tRNA hydrolase |
400 |
401 |
|
Rv2794c pptT |
4'-phosphopantetheinyl transferase |
477 |
64 |
textmining:465 |
Rv3597c lsr2 |
iron-regulated H-NS-like protein |
595 |
47 |
textmining:593 |
Rv3221c TB7.3 |
acetyl-CoA carboxylase biotin carboxyl carrier protein subunit |
631 |
46 |
textmining:630 |
Rv2395A aprA |
acid and phagosome regulated protein AprA |
511 |
41 |
textmining:511 |
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: TetR family transcriptional regulator
- MTBC0 PGAP product: TetR/AcrR family transcriptional regulator
- Pfam (hmmscan --cut_ga): TetR_N PF00440.30 (E=8e-17), TetR_C_46 PF21943.2 (E=4e-08)
- (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_217724.1)
- Domains: Pfam-A via hmmscan --cut_ga — TetR_N (PF00440.30), TetR_C_46 (PF21943.2)
- 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
O05858
(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 —
13 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003413|Rv3208|
MSDLAKTAQRRALRSSGSARPDEDVPAPNRRGNRLPRDERRGQLLVVASDVFVDRGYHAAGMDEIADRAGVSKPVLYQHFSSKLELYLAVLHRHVENLVSGVHQALSTTTDNRQRLHVAVQAFFDFIEHDSQGYRLIFENDFVTEPEVAAQVRVATESCIDAVFALISADSGLDPHRARMIAVGLVGMSVDCARYWLDADKPISKSDAVEGTVQFAWGGLSHVPLTRS
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