senX3 Resolved · high auto-curated
H37Rv Rv0490 · MTBC0 mtbc0_000515 ·
410 aa · 582714–583946 (+) ·
RefSeq NP_215004.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | two component sensor histidine kinase SenX3 |
|---|---|
| MTBC0 PGAP re-annotation | two-component system sensor histidine kinase SenX3 |
| Revised (this work) | Two-component system sensor histidine kinase SenX3. Pfam: HisKA (PF00512.32), HATPase_c (PF02518.32). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WGK5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Sensor-like histidine kinase SenX3 |
| EC (curated) |
EC 2.7.13.3
|
| Curated function | Member of the two-component regulatory system SenX3/RegX3 involved in stress response. Autophosphorylates, and then transfers the phosphate group to RegX3 (By similarity). 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. SenX3 is a key regulator of mycobacterial replication in response to oxygen, nitric oxide (NO) and carbon monoxide (CO), and acts as an O(2) sensor that plays an important role in the reactivation of growth in response to the restoration of aer. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
T Signal transduction mechanisms
|
|---|---|
| Preferred name | senX3 |
| eggNOG description | Histidine kinase |
| Orthologous group | COG5002 |
| EC number |
EC 2.7.13.3
|
| KEGG orthology |
K07768
|
| KEGG pathways |
map02020
|
| KEGG modules |
M00443
|
| Gene Ontology (33) |
GO:0005575, GO:0005576, GO:0005623, GO:0005886, GO:0006464, GO:0006468, GO:0006793, GO:0006796, GO:0006807, GO:0008150, GO:0008152, GO:0009405 +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 | 0.243 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 3 missense, 1 nonsense, 0 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 1.00% of strains (1448) · 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 |
|---|---|---|---|---|
HisKA | PF00512.32 | 5.0e-15 | 157–221 | His Kinase A (phospho-acceptor) domain |
HATPase_c | PF02518.32 | 1.0e-28 | 268–378 | Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: regX3 (two component sensory transduction protein RegX), high confidence from genomic context alone (score 996 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0491 regX3 |
two component sensory transduction protein RegX | 999 | 996 ctx | neighborhood:729 cooccurence:763 database:900 textmining:978 |
Rv3246c mtrA |
two component DNA-binding response regulator MtrA | 948 | 871 ctx | cooccurence:764 textmining:620 |
Rv0903c prrA |
two component transcriptional regulator PrrA | 921 | 868 ctx | cooccurence:760 textmining:431 |
Rv0981 mprA |
two-component response regulator MrpA | 904 | 865 ctx | cooccurence:745 |
Rv1033c trcR |
two component transcriptional regulator TrcR | 887 | 855 ctx | cooccurence:744 |
Rv0757 phoP |
two component system response transcriptional positive regulator PhoP | 918 | 853 ctx | cooccurence:731 textmining:467 |
Rv3765c tcrX |
two component transcriptional regulator TcrX | 895 | 853 ctx | cooccurence:736 |
Rv0602c tcrA |
two component DNA binding transcriptional regulator TcrA | 889 | 850 ctx | cooccurence:737 |
Rv1027c kdpE |
transcriptional regulator KdpE | 856 | 824 ctx | cooccurence:690 |
Rv2884 |
transcriptional regulator | 865 | 781 ctx | cooccurence:617 textmining:410 |
Rv1332 |
transcriptional regulator | 766 | 767 | coexpression:732 |
Rv0489 gpm1 |
2,3-bisphosphoglycerate-dependent phosphoglycerate mutase | 773 | 747 ctx | neighborhood:743 |
Rv0818 |
transcriptional regulator | 841 | 742 ctx | cooccurence:537 textmining:410 |
Rv0486 mshA |
D-inositol 3-phosphate glycosyltransferase | 706 | 696 ctx | neighborhood:622 |
Rv0487 hyp |
hypothetical protein | 633 | 634 ctx | neighborhood:622 |
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: two component sensor histidine kinase SenX3
- MTBC0 PGAP product: two-component system sensor histidine kinase SenX3
- Pfam (hmmscan --cut_ga): HisKA PF00512.32 (E=5e-15), HATPase_c PF02518.32 (E=1e-28)
- (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_215004.1)
- Domains: Pfam-A via hmmscan --cut_ga — HisKA (PF00512.32), HATPase_c (PF02518.32)
- 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
COG5002 - Curated reference: UniProt P9WGK5 (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 —
44 functional partner(s); context anchor
regX3 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000515|Rv0490|senX3 MTVFSALLLAGVLSALALAVGGAVGMRLTSRVVEQRQRVATEWSGITVSQMLQCIVTLMPLGAAVVDTHRDVVYLNERAKELGLVRDRQLDDQAWRAARQALGGEDVEFDLSPRKRSATGRSGLSVHGHARLLSEEDRRFAVVFVHDQSDYARMEAARRDFVANVSHELKTPVGAMALLAEALLASADDSETVRRFAEKVLIEANRLGDMVAELIELSRLQGAERLPNMTDVDVDTIVSEAISRHKVAADNADIEVRTDAPSNLRVLGDQTLLVTALANLVSNAIAYSPRGSLVSISRRRRGANIEIAVTDRGIGIAPEDQERVFERFFRGDKARSRATGGSGLGLAIVKHVAANHDGTIRVWSKPGTGSTFTLALPALIEAYHDDERPEQAREPELRSNRSQREEELSR