Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | AraC family transcriptional regulator |
|---|
| MTBC0 PGAP re-annotation | helix-turn-helix transcriptional regulator |
|---|
| Revised (this work) | Helix-turn-helix transcriptional regulator. Pfam: Cupin_2 (PF07883.18), AraC_binding (PF02311.26), HTH_AraC (PF00165.30), HTH_18 (PF12833.14). |
|---|
Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P96245
TrEMBL · unreviewed
· Evidence at protein level
|
|---|
| UniProt name | HTH-type transcriptional regulator RipA |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|
| eggNOG description | araC family |
|---|
| Orthologous group | COG1917 |
|---|
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 |
0.342 · purifying
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
7 synonymous, 7 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 |
|---|
Cupin_2 | PF07883.18 |
3.0e-07 | 14–74 |
Cupin domain |
AraC_binding | PF02311.26 |
5.4e-06 | 18–96 |
AraC-like ligand binding domain |
HTH_AraC | PF00165.30 |
5.9e-07 | 156–197 |
Bacterial regulatory helix-turn-helix proteins, AraC family |
HTH_18 | PF12833.14 |
8.0e-22 | 172–244 |
Helix-turn-helix domain |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv0792c |
transcriptional regulator |
842 |
826 |
coexpression:820 |
Rv2912c |
TetR family HTH-type transcriptional regulator |
829 |
821 |
coexpression:817 |
Rv1395 |
HTH-type transcriptional regulator |
823 |
816 |
coexpression:743 |
Rv1167c |
transcriptional regulator |
817 |
808 |
coexpression:770 |
Rv3830c |
TetR family transcriptional regulator |
813 |
803 |
coexpression:799 |
Rv1985c lysG |
HTH-type transcriptional regulator |
822 |
792 |
coexpression:733 |
Rv1674c |
transcriptional regulator |
793 |
777 |
coexpression:751 |
Rv3082c virS |
HTH-type transcriptional regulator VirS |
786 |
777 |
coexpression:739 |
Rv1151c cobB |
NAD-dependent protein deacylase |
781 |
767 |
coexpression:738 |
Rv3736 |
AraC/XylS family transcriptional regulator |
751 |
741 |
coexpression:697 |
Rv3167c |
TetR family transcriptional regulator |
825 |
740 |
coexpression:734 |
Rv1963c mce3R |
transcriptional repressor Mce3R |
792 |
737 |
coexpression:731 |
Rv2703 sigA |
RNA polymerase sigma factor SigA |
766 |
732 |
experimental:722 |
Rv2710 sigB |
RNA polymerase sigma factor SigB |
766 |
732 |
experimental:722 |
Rv3840 |
transcriptional regulator |
730 |
730 |
coexpression:730 |
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: AraC family transcriptional regulator
- MTBC0 PGAP product: helix-turn-helix transcriptional regulator
- Pfam (hmmscan --cut_ga): Cupin_2 PF07883.18 (E=3e-07), AraC_binding PF02311.26 (E=5e-06), HTH_AraC PF00165.30 (E=6e-07), HTH_18 PF12833.14 (E=8e-22)
- (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_218350.1)
- Domains: Pfam-A via hmmscan --cut_ga — Cupin_2 (PF07883.18), AraC_binding (PF02311.26), HTH_AraC (PF00165.30), HTH_18 (PF12833.14)
- 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
COG1917
- Curated reference: UniProt
P96245
(TrEMBL, unreviewed; 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 —
89 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_004062|Rv3833|
MSENSHHRLATTSLTLPPGARIERHRHPSHQIVYPSAGAVSVTTHAGTWITPVNRAIWIPAGCWHQHKFHGHTQFHGVALDPQRYRGGPATPTVLAVNPLMRELIIACSQADRTDTDEHHRMLAVLQDQLPTTSIREPLWVPSPTDRRLRHACALIADNLTQPLTLQQIGGRIGVSQRTLSRLFSDELGMTFPQWRTQLRLQHALVLLAERHDVTSVASECGWATPSAFIDTYRQAFGHTPGQAAKPMAATRLTRLRRARDRR
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