whiB5 Family assigned · medium auto-curated
H37Rv Rv0022c · MTBC0 mtbc0_000027 ·
139 aa · 27005–27424 (-) ·
RefSeq NP_214536.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | transcriptional regulator WhiB5 |
|---|---|
| MTBC0 PGAP re-annotation | transcriptional regulator WhiB5 |
| Revised (this work) | Transcriptional regulator WhiB5. 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 |
P71592
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Transcriptional regulator WhiB5 |
| Curated function | A transcription factor that is probably redox-responsive. Probably plays a role in immunomodulation and reactivation after chronic infection. Its induction results in transcription of a number of genes including sigM, and the genes for 2 type VII secretion systems ESX-2 and ESX-4. Seems to negatively regulate its own expression. The apo-form has been shown to act as a protein disulfide reductase. The apo- but not holo-form probably binds DNA. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|---|
| Preferred name | whiB5 |
| eggNOG description | Acts as a transcriptional regulator. Probably redox- responsive. The apo- but not holo-form probably binds DNA |
| Orthologous group | 2AU18 |
| KEGG orthology |
K18956
|
| Gene Ontology (6) |
GO:0005575, GO:0005618, GO:0005623, GO:0030312, GO:0044464, GO:0071944
|
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) pseudogene candidate
| pN/pS | 2.086 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 5 missense, 1 nonsense, 1 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 5.95% of strains (8643) · 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 | 7.6e-11 | 7–82 | Transcription factor WhiB |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0023 (transcriptional regulator), high confidence from genomic context alone (score 773 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3449 mycP4 |
membrane-anchored mycosin | 801 | 801 | coexpression:801 |
Rv3448 eccD4 |
ESX-4 secretion system protein EccD4 | 799 | 799 | coexpression:799 |
Rv3446c hyp |
hypothetical protein | 788 | 788 | coexpression:788 |
Rv0023 |
transcriptional regulator | 773 | 773 ctx | neighborhood:771 |
Rv0025 hyp |
hypothetical protein | 737 | 738 ctx | neighborhood:737 |
Rv0027 hyp |
hypothetical protein | 642 | 642 ctx | neighborhood:638 |
Rv0028 hyp |
hypothetical protein | 641 | 641 ctx | neighborhood:638 |
Rv0024 |
NLP/P60 family protein | 630 | 617 ctx | neighborhood:615 |
Rv0021c hyp |
hypothetical protein | 521 | 521 ctx | neighborhood:516 |
Rv3447c eccC4 |
ESX-4 secretion system protein EccC4 | 408 | 409 | coexpression:409 |
Rv3903c cpnT hyp |
hypothetical protein | 404 | 404 | coexpression:404 |
Rv0026 hyp |
hypothetical protein | 418 | 382 | |
Rv1460 sufR |
transcriptional regulator | 401 | 89 | |
Rv3911 sigM |
ECF RNA polymerase sigma factor SigM | 532 | 84 | textmining:511 |
Rv3727 |
oxidoreductase | 660 | 70 | textmining:650 |
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 WhiB5
- MTBC0 PGAP product: transcriptional regulator WhiB5
- Pfam (hmmscan --cut_ga): Whib PF02467.22 (E=8e-11)
- (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_214536.1)
- 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
2AU18 - Curated reference: UniProt P71592 (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 —
19 functional partner(s); context anchor
Rv0023 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000027|Rv0022c|whiB5 MAHPCATDPELWFGYPDDDGSDGAAKARAYERSATQARIQCLRRCPLLQQRRCAQHAVEHRVEYGVWAGIKLPGGQYRKREQLAAAHDVLRRIAGGEINSRQLPDNAALLARNEGLEVTPVPGVVVHLPIAQVGPQPAA