dosT Resolved · high auto-curated
H37Rv Rv2027c · MTBC0 mtbc0_002160 ·
573 aa · 2301400–2303121 (-) ·
RefSeq NP_216543.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | two component sensor histidine kinase DosT |
|---|---|
| MTBC0 PGAP re-annotation | two-component system sensor histidine kinase DosT |
| Revised (this work) | Two-component system sensor histidine kinase DosT. Pfam: GAF (PF01590.33), GAF_2 (PF13185.13), GAF_3 (PF13492.13), HisKA_3 (PF07730.20), 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 |
P9WGK1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Oxygen sensor histidine kinase response regulator DosT |
| EC (curated) |
EC 2.7.13.3
|
| Curated function | Interacts with the two-component regulatory system DevR/DevS (DosR/DosS) involved in onset of the dormancy response. Required for full induction of the DevR (DosR) regulon; required during early adaptation to anaerobiosis, to start induction of the DevR regulon. May act as a direct hypoxia/oxygen sensor. O(2) acts as a switch, with the Fe(2+)-O(2)-bound protein inactive in autophosphorylation. Autophosphorylates under anaerobic but not aerobic conditions, binding of NO or CO has no effect on autophosphorylation. Binds a number of gases; O(2), NO, CO. May be a secondary sensor for CO. Donates a. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
F Nucleotide transport and metabolism
|
|---|---|
| eggNOG description | the two-component regulatory system DevR DevS (DosR DosS) involved in onset of the dormancy response. May act as a |
| Orthologous group | COG2203 |
| EC number |
EC 2.7.13.3
|
| KEGG orthology |
K07682
|
| KEGG pathways |
map02020
|
| KEGG modules |
M00482
|
| Gene Ontology (73) |
GO:0000166, GO:0000287, GO:0001666, GO:0003032, GO:0003674, GO:0003824, GO:0004672, GO:0004673, GO:0005488, GO:0005509, GO:0005524, GO:0006464 +61 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) pseudogene candidate
| pN/pS | 0.178 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 3 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 25.72% of strains (37352) · 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 |
|---|---|---|---|---|
GAF | PF01590.33 | 3.2e-16 | 62–198 | GAF domain |
GAF_2 | PF13185.13 | 4.3e-18 | 62–199 | GAF domain |
GAF_3 | PF13492.13 | 2.5e-08 | 317–365 | GAF domain |
HisKA_3 | PF07730.20 | 1.0e-10 | 384–445 | Histidine kinase |
HATPase_c | PF02518.32 | 3.8e-09 | 489–572 | Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2026c (universal stress protein), high confidence from genomic context alone (score 928 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2026c |
universal stress protein | 944 | 928 ctx | neighborhood:659 coexpression:731 |
Rv3133c devR |
two component transcriptional regulator DevR | 993 | 883 ctx | cooccurence:767 textmining:946 |
Rv0844c narL |
nitrate/nitrite response transcriptional regulator NarL | 912 | 770 ctx | cooccurence:573 textmining:635 |
Rv2032 acg |
NAD(P)H nitroreductase | 781 | 756 ctx | neighborhood:437 cooccurence:580 |
Rv2028c |
universal stress protein | 788 | 719 ctx | neighborhood:607 |
Rv0195 |
two component transcriptional regulator | 749 | 650 | |
Rv1747 |
ABC transporter ATP-binding protein/permease | 730 | 639 ctx | neighborhood:497 |
Rv2029c pfkB |
6-phosphofructokinase PfkB | 620 | 613 ctx | neighborhood:607 |
Rv2030c hyp |
hypothetical protein | 586 | 587 ctx | neighborhood:582 |
Rv2031c hspX |
alpha-crystallin | 848 | 578 ctx | neighborhood:574 textmining:655 |
Rv1364c |
sigma factor regulatory protein | 691 | 564 ctx | neighborhood:541 |
Rv3127 hyp |
hypothetical protein | 564 | 564 ctx | cooccurence:551 |
Rv0890c |
HTH-type transcriptional regulator | 593 | 551 | |
Rv2847c cysG |
multifunctional uroporphyrin-III C-methyltransferase/precorrin-2 oxidase/ferrochelatase | 546 | 547 ctx | neighborhood:544 |
Rv3131 |
NAD(P)H nitroreductase | 583 | 534 ctx | cooccurence:502 |
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 DosT
- MTBC0 PGAP product: two-component system sensor histidine kinase DosT
- Pfam (hmmscan --cut_ga): GAF PF01590.33 (E=3e-16), GAF_2 PF13185.13 (E=4e-18), GAF_3 PF13492.13 (E=2e-08), HisKA_3 PF07730.20 (E=1e-10), HATPase_c PF02518.32 (E=4e-09)
- (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_216543.1)
- Domains: Pfam-A via hmmscan --cut_ga — GAF (PF01590.33), GAF_2 (PF13185.13), GAF_3 (PF13492.13), HisKA_3 (PF07730.20), 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
COG2203 - Curated reference: UniProt P9WGK1 (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 —
47 functional partner(s); context anchor
Rv2026c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002160|Rv2027c|dosT MTHPDRANVNPGSPPLRETLSQLRLRELLLEVQDRIEQIVEGRDRLDGLIDAILAITSGLKLDATLRAIVHTAAELVDARYGALGVRGYDHRLVEFVYEGIDEETRHLIGSLPEGRGVLGALIEEPKPIRLDDISRHPASVGFPLHHPPMRTFLGVPVRIRDEVFGNLYLTEKADGQPFSDDDEVLVQALAAAAGIAVDNARLFEESRTREAWIEATRDIGTQMLAGADPAMVFRLIAEEALTLMAGAATLVAVPLDDEAPACEVDDLVIVEVAGEISPAVKQMTVAVSGTSIGGVFHDRTPRRFDRLDLAVDGPVEPGPALVLPLRAADTVAGVLVALRSADEQPFSDKQLDMMAAFADQAALAWRLATAQRQMREVEILTDRDRIARDLHDHVIQRLFAVGLTLQGAAPRARVPAVRESIYSSIDDLQEIIQEIRSAIFDLHAGPSRATGLRHRLDKVIDQLAIPALHTTVQYTGPLSVVDTVLANHAEAVLREAVSNAVRHANATSLAINVSVEDDVRVEVVDDGVGISGDITESGLRNLRQRADDAGGEFTVENMPTGGTLLRWSAPLR