whiB3 Family assigned · medium auto-curated
H37Rv Rv3416 · MTBC0 mtbc0_003630 ·
102 aa · 3860331–3860639 (+) ·
RefSeq NP_217933.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | redox-responsive transcriptional regulator WhiB3 |
|---|---|
| MTBC0 PGAP re-annotation | redox-responsive transcriptional regulator WhiB3 |
| Revised (this work) | Redox-responsive transcriptional regulator WhiB3. Pfam: Whib (PF02467.22). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WF41
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Redox- and pH-responsive transcriptional regulator WhiB3 |
| Curated function | A redox-sensitive transcriptional regulator. Maintains intracellular redox homeostasis by regulating catabolic metabolism and polyketide biosynthesis. Regulates expression of the redox buffer ergothioneine (ERG) in a carbon-source-dependent manner; loss of ERG or mycothiol (MSH, the other major redox buffer in this bacteria) leads to respiratory alterations and bioenergetic deficiencies that negatively impact virulence. In response to low external pH (like that found in host macrophage phagosomes) alters endogenous gene expression leading to acid resistance; MSH and WhiB3 are probably part of . |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|---|
| Preferred name | whiB3 |
| eggNOG description | Acts as a transcriptional regulator. Probably redox- responsive. The apo- but not holo-form probably binds DNA |
| Orthologous group | 2CC1Y |
| KEGG orthology |
K18955
|
| Gene Ontology (55) |
GO:0003674, GO:0003676, GO:0003677, GO:0003824, GO:0005488, GO:0005575, GO:0005618, GO:0005623, GO:0008150, GO:0008152, GO:0009273, GO:0009405 +43 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 | n/a |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 0 synonymous, 1 missense, 1 nonsense, 0 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.46% of strains (664) · 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 |
|---|---|---|---|---|
Whib | PF02467.22 | 1.2e-26 | 17–85 | Transcription factor WhiB |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv1830 (HTH-type transcriptional regulator), medium confidence from genomic context alone (score 558 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2901c hyp |
hypothetical protein | 670 | 671 ctx | cooccurence:669 |
Rv2703 sigA |
RNA polymerase sigma factor SigA | 863 | 631 | experimental:627 textmining:646 |
Rv1830 |
HTH-type transcriptional regulator | 575 | 558 ctx | cooccurence:553 |
Rv2119 hyp |
hypothetical protein | 551 | 551 ctx | cooccurence:550 |
Rv3415c hyp |
hypothetical protein | 499 | 499 ctx | neighborhood:499 |
Rv3220c pdtaS |
two component sensor kinase | 484 | 484 ctx | cooccurence:477 |
Rv1440 secG |
protein-export membrane protein SecG | 476 | 476 ctx | cooccurence:469 |
Rv1390 rpoZ |
DNA-directed RNA polymerase subunit omega | 474 | 474 ctx | cooccurence:471 |
Rv0807 hyp |
hypothetical protein | 472 | 473 ctx | cooccurence:465 |
Rv2738c hyp |
hypothetical protein | 465 | 465 ctx | cooccurence:465 |
Rv3414c sigD |
ECF RNA polymerase sigma factor SigD | 470 | 453 ctx | neighborhood:450 |
Rv3413c rsdA |
anti-sigma-D factor RsdA | 450 | 450 ctx | neighborhood:450 |
Rv1025 hyp |
hypothetical protein | 444 | 444 ctx | cooccurence:441 |
Rv0525 hyp |
hypothetical protein | 438 | 439 ctx | cooccurence:438 |
Rv1331 clpS |
ATP-dependent Clp protease adapter protein ClpS | 425 | 426 ctx | cooccurence:424 |
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: redox-responsive transcriptional regulator WhiB3
- MTBC0 PGAP product: redox-responsive transcriptional regulator WhiB3
- Pfam (hmmscan --cut_ga): Whib PF02467.22 (E=1e-26)
- (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_217933.1)
- Domains: Pfam-A via hmmscan --cut_ga — Whib (PF02467.22)
- 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
2CC1Y - Curated reference: UniProt P9WF41 (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 —
32 functional partner(s); context anchor
Rv1830 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003630|Rv3416|whiB3 MPQPEQLPGPNADIWNWQLQGLCRGMDSSMFFHPDGERGRARTQREQRAKEMCRRCPVIEACRSHALEVGEPYGVWGGLSESERDLLLKGTMGRTRGIRRTA