regX3 Resolved · high auto-curated
H37Rv Rv0491 · MTBC0 - ·
227 aa · 580809–581492 (+) ·
RefSeq NP_215005.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | two component sensory transduction protein RegX |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Two component sensory transduction protein RegX. Pfam: Response_reg (PF00072.31), Trans_reg_C (PF00486.35). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
P9WGL9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Sensory transduction protein RegX3 |
| Curated function | Member of the two-component regulatory system SenX3/RegX3 involved in stress response. The system is involved in phosphate starvation response. Plays a role in modulating expression of aerobic response and in the regulation of response to hypoxia. Involved in virulence. Regulates dozens of genes, directly or indirectly. Is directly involved in the regulation of the expression of gltA, cydAB and ald. Binds to the upstream regions of the hypoxia-associated genes Rv3334, whiB7, Rv0195, Rv0196 and Rv1960c. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|---|
| Preferred name | regX3 |
| eggNOG description | COG0745 Response regulators consisting of a CheY-like receiver domain and a winged-helix DNA-binding domain |
| Orthologous group | COG0745 |
| KEGG orthology |
K07776
|
| KEGG pathways |
map02020
|
| KEGG modules |
M00443
|
| Gene Ontology (37) |
GO:0003674, GO:0003676, GO:0003677, GO:0005488, GO:0006355, GO:0008150, GO:0009405, GO:0009889, GO:0010468, GO:0010556, GO:0010565, GO:0019216 +25 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 | 0.345 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 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 |
|---|---|---|---|---|
Response_reg | PF00072.31 | 7.0e-29 | 4–113 | Response regulator receiver domain |
Trans_reg_C | PF00486.35 | 4.4e-29 | 150–225 | Transcriptional regulatory protein, C terminal |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: senX3 (two component sensor histidine kinase SenX3), high confidence from genomic context alone (score 996 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0490 senX3 |
two component sensor histidine kinase SenX3 | 999 | 996 ctx | neighborhood:729 cooccurence:763 database:900 textmining:978 |
Rv0600c |
two component sensor kinase HK1 | 900 | 896 ctx | cooccurence:765 |
Rv1032c trcS |
two component sensor histidine kinase TrcS | 886 | 879 ctx | cooccurence:723 |
Rv3764c tcrY |
two component sensor kinase TcrY | 883 | 877 ctx | cooccurence:715 |
Rv0902c prrB |
two component sensor histidine kinase PrrB | 886 | 874 ctx | cooccurence:700 |
Rv0982 mprB |
two component histidine-protein kinase/phosphatase MprB | 859 | 854 ctx | cooccurence:655 |
Rv0758 phoR |
two component system response sensor kinase PhoR | 915 | 849 ctx | cooccurence:727 textmining:462 |
Rv3245c mtrB |
two component sensory histidine kinase MtrB | 845 | 789 ctx | cooccurence:627 |
Rv0486 mshA |
D-inositol 3-phosphate glycosyltransferase | 689 | 678 ctx | neighborhood:604 |
Rv0489 gpm1 |
2,3-bisphosphoglycerate-dependent phosphoglycerate mutase | 696 | 673 ctx | neighborhood:660 |
Rv0601c |
two component sensor kinase HK2 | 661 | 649 | |
Rv0487 hyp |
hypothetical protein | 609 | 610 ctx | neighborhood:604 |
Rv0485 |
transcriptional regulator | 607 | 591 ctx | neighborhood:579 |
Rv2998A |
Rv2998A, len: 67 aa. Probable conserved hypothetical protein, (possibly gene fragment), highly similar to central part of two-component sens | 592 | 577 | |
Rv3365c hyp |
hypothetical protein | 592 | 577 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): two component sensory transduction protein RegX
- Pfam (hmmscan --cut_ga): Response_reg PF00072.31 (E=7e-29), Trans_reg_C PF00486.35 (E=4e-29)
- (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_215005.1)
- Domains: Pfam-A via hmmscan --cut_ga — Response_reg (PF00072.31), Trans_reg_C (PF00486.35)
- 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
COG0745 - Curated reference: UniProt P9WGL9 (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 —
49 functional partner(s); context anchor
senX3 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0491|regX3 MTSVLIVEDEESLADPLAFLLRKEGFEATVVTDGPAALAEFDRAGADIVLLDLMLPGMSGTDVCKQLRARSSVPVIMVTARDSEIDKVVGLELGADDYVTKPYSARELIARIRAVLRRGGDDDSEMSDGVLESGPVRMDVERHVVSVNGDTITLPLKEFDLLEYLMRNSGRVLTRGQLIDRVWGADYVGDTKTLDVHVKRLRSKIEADPANPVHLVTVRGLGYKLEG