whiB4 Family assigned · medium auto-curated
H37Rv Rv3681c · MTBC0 mtbc0_003901 ·
118 aa · 4145146–4145502 (-) ·
RefSeq NP_218198.2
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | transcriptional regulator WhiB4 |
|---|---|
| MTBC0 PGAP re-annotation | transcriptional regulator WhiB4 |
| Revised (this work) | Transcriptional regulator WhiB4. 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 |
P9WF39
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Transcriptional regulator WhiB4 |
| Curated function | Redox-responsive transcriptional regulator that regulates a set of genes involved in protection against environmental stresses encountered during infection. The loss of the O(2) and NO-responsive 4Fe-4S cluster and subsequent redox modifications of Cys residue thiols (possibly by disulfide bond formation) may activate its role in gene regulation. The thiol-oxidized apo-form binds in a sequence non-specific manner to GC-rich DNA, probably in the minor groove. Represses transcription of a number of genes including itself. The reduced apo-form and holo-form do not bind DNA. The apo-form can act a. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|---|
| Preferred name | whiB4 |
| 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 (33) |
GO:0003674, GO:0003676, GO:0003677, GO:0003824, GO:0005488, GO:0005575, GO:0005618, GO:0005623, GO:0008150, GO:0008152, GO:0015036, GO:0016491 +21 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 | 0.498 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 3 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.13% of strains (189) · 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 | 2.7e-23 | 31–93 | Transcription factor WhiB |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: secG (protein-export membrane protein SecG), high confidence from genomic context alone (score 711 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2584c apt |
adenine phosphoribosyltransferase | 777 | 768 | coexpression:768 |
Rv1440 secG |
protein-export membrane protein SecG | 711 | 711 ctx | cooccurence:700 |
Rv2901c hyp |
hypothetical protein | 710 | 711 ctx | cooccurence:709 |
Rv1830 |
HTH-type transcriptional regulator | 719 | 708 ctx | cooccurence:705 |
Rv1390 rpoZ |
DNA-directed RNA polymerase subunit omega | 707 | 691 ctx | cooccurence:477 experimental:431 |
Rv0525 hyp |
hypothetical protein | 598 | 598 ctx | cooccurence:596 |
Rv3221A rshA |
anti-sigma factor RshA | 608 | 590 | |
Rv1321 nucS |
endonuclease NucS | 585 | 569 ctx | cooccurence:549 |
Rv1331 clpS |
ATP-dependent Clp protease adapter protein ClpS | 545 | 545 ctx | cooccurence:545 |
Rv2478c hyp |
hypothetical protein | 538 | 538 ctx | cooccurence:527 |
Rv3683 hyp |
hypothetical protein | 518 | 518 ctx | neighborhood:416 |
Rv0736 rslA |
anti-sigma-L factor RslA | 509 | 486 | |
Rv1222 rseA |
anti-sigma E factor RseA | 496 | 475 | |
Rv2256c hyp |
hypothetical protein | 474 | 474 ctx | cooccurence:471 |
Rv0668 rpoC |
DNA-directed RNA polymerase subunit beta' | 486 | 458 | experimental:456 |
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 WhiB4
- MTBC0 PGAP product: transcriptional regulator WhiB4
- Pfam (hmmscan --cut_ga): Whib PF02467.22 (E=3e-23)
- (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_218198.2)
- 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 P9WF39 (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 —
45 functional partner(s); context anchor
secG - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003901|Rv3681c|whiB4 MSGTRPAARRTNLTAAQNVVRSVDAEERIAWVSKALCRTTDPDELFVRGAAQRKAAVICRHCPVMQECAADALDNKVEFGVWGGMTERQRRALLKQHPEVVSWSDYLEKRKRRTGTAG