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). |
|---|
Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6X7F9
SwissProt · reviewed
· Evidence at protein level
|
|---|
| UniProt name | Transcriptional regulator Rv3488 |
|---|
| Curated function | May have transcription regulation and metal-detoxifying functions through which it may enhance intracellular survival of mycobacteria. Binds to its own promoter region and to the Rv1999c promoter region. It displays strong affinity for cadmium ions, but can also bind zinc, manganese and nickel. Expression increases the intracellular survival of recombinant M.smegmatis in murine macrophage cell line and increases its tolerance to cadmium ions. |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|
| eggNOG description | Members of the PadR-like family are transcriptional regulators that appear to be related to the pfam01047 family. this family includes PadR, a protein that is involved in negative regulation of phenolic acid metabolism |
|---|
| 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 |
n/a
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
0 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 |
|---|
PadR | PF03551.21 |
9.5e-22 | 13–83 |
Transcriptional regulator PadR-like family |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv3840 |
transcriptional regulator |
834 |
834 |
coexpression:834 |
Rv1151c cobB |
NAD-dependent protein deacylase |
822 |
822 |
coexpression:816 |
Rv1176c hyp |
hypothetical protein |
810 |
810 |
coexpression:810 |
Rv3183 higA3 |
transcriptional regulator |
806 |
806 |
coexpression:803 |
Rv0339c iniR |
transcriptional regulator |
811 |
805 |
coexpression:805 |
Rv0691c mftR |
mycofactocin biosynthesis transcriptional regulator MftR |
807 |
804 |
coexpression:804 |
Rv3263 |
DNA methylase |
803 |
804 |
coexpression:804 |
Rv1960c parD1 |
antitoxin ParD1 |
801 |
801 |
coexpression:801 |
Rv0273c |
transcriptional regulator |
803 |
800 |
coexpression:800 |
Rv2760c vapB42 |
antitoxin VapB42 |
798 |
798 |
coexpression:798 |
Rv3736 |
AraC/XylS family transcriptional regulator |
803 |
796 |
coexpression:796 |
Rv3830c |
TetR family transcriptional regulator |
791 |
788 |
coexpression:788 |
Rv1267c embR |
transcriptional regulator EmbR |
785 |
785 |
coexpression:785 |
Rv0158 |
transcriptional regulator |
782 |
778 |
coexpression:778 |
Rv1675c cmr |
HTH-type transcriptional regulator Cmr |
778 |
778 |
coexpression:778 |
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=9e-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_218005.1)
- Domains: Pfam-A via hmmscan --cut_ga — PadR (PF03551.21)
- 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
I6X7F9
(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 —
61 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003703|Rv3488|
MREFQRAAVRLHILHHAADNEVHGAWLTQELSRHGYRVSPGTLYPTLHRLEADGLLVSEQRVVDGRARRVYRATPAGRAALTEDRRALEELAREVLGGQSHTAGNGT
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