Rv1474c Family assigned · medium auto-curated
H37Rv Rv1474c · MTBC0 mtbc0_001577 ·
187 aa · 1672446–1673009 (-) ·
RefSeq NP_215990.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | transcriptional regulator |
|---|---|
| MTBC0 PGAP re-annotation | helix-turn-helix domain-containing protein |
| Revised (this work) | Helix-turn-helix domain-containing protein. Pfam: TetR_N (PF00440.30). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53165
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | HTH-type transcriptional repressor Rv1474c |
| Curated function | Represses the expression of the aconitase gene acn and its own expression, in an iron-responsive manner. Binds to the inverted repeat element present in the upstream region of acn (Rv1475c)-Rv1474c operon. Preferentially binds to major groove of the DNA. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|---|
| Preferred name | acnR |
| eggNOG description | Transcriptional regulator |
| Orthologous group | COG1309 |
| KEGG orthology |
K21962
|
| Gene Ontology (29) |
GO:0000287, GO:0003674, GO:0003676, GO:0003677, GO:0005488, GO:0006355, GO:0008150, GO:0009889, GO:0010468, GO:0010556, GO:0019219, GO:0019222 +17 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 | 0.114 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 1 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 | 3.6e-17 | 16–62 | Bacterial regulatory proteins, tetR family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: acn (iron-regulated aconitate hydratase), high confidence from genomic context alone (score 906 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1475c acn |
iron-regulated aconitate hydratase | 905 | 906 ctx | neighborhood:879 |
Rv0674 hyp |
hypothetical protein | 732 | 732 | coexpression:732 |
Rv2744c 35kd_ag hyp |
hypothetical protein | 683 | 683 ctx | cooccurence:675 |
Rv2179c |
3'-5' exoribonuclease | 658 | 658 ctx | cooccurence:658 |
Rv0948c |
chorismate mutase | 645 | 646 ctx | cooccurence:633 |
Rv1343c lprD |
lipoprotein LprD | 629 | 629 ctx | cooccurence:629 |
Rv1638A hyp |
hypothetical protein | 625 | 625 ctx | cooccurence:620 |
Rv1476 |
membrane protein | 616 | 616 ctx | neighborhood:608 |
Rv2446c |
integral membrane protein | 501 | 501 ctx | cooccurence:495 |
Rv0863 hyp |
hypothetical protein | 500 | 501 ctx | cooccurence:498 |
Rv2468c hyp |
hypothetical protein | 497 | 498 ctx | cooccurence:493 |
Rv3205c hyp |
hypothetical protein | 491 | 491 ctx | cooccurence:478 |
Rv2698 |
transmembrane protein | 483 | 483 ctx | cooccurence:483 |
Rv2474c hyp |
hypothetical protein | 482 | 483 ctx | cooccurence:475 |
Rv0556 |
transmembrane protein | 478 | 478 ctx | cooccurence:475 |
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: transcriptional regulator
- MTBC0 PGAP product: helix-turn-helix domain-containing protein
- Pfam (hmmscan --cut_ga): TetR_N PF00440.30 (E=4e-17)
- (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_215990.1)
- Domains: Pfam-A via hmmscan --cut_ga — TetR_N (PF00440.30)
- 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 O53165 (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 —
30 functional partner(s); context anchor
acn - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001577|Rv1474c| MPKVSEDHLAARRRQILDGARRCFAEYGYDKATVRRLEQAIGMSRGAIFHHFRDKDALFFALAREDTERMAAVASREGLIGVMRDMLAAPDQFDWLATRLEIARKLRNDPDFSRGWAERSAELAAATTDRLRRQKQANRVRDDVPSDVLRCYLDLVLDGLLARLASGEDPQRLAAVLDLVENSVRRS