mtrB Resolved · high auto-curated
H37Rv Rv3245c · MTBC0 mtbc0_003453 ·
567 aa · 3647053–3648756 (-) ·
RefSeq NP_217762.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | two component sensory histidine kinase MtrB |
|---|---|
| MTBC0 PGAP re-annotation | two-component system sensor histidine kinase MtrB |
| Revised (this work) | Two-component system sensor histidine kinase MtrB. Pfam: HAMP (PF00672.31), HisKA (PF00512.32), HATPase_c_2 (PF13581.13), 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 |
P9WGK9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Sensor histidine kinase MtrB |
| EC (curated) |
EC 2.7.13.3
|
| Curated function | Member of the two-component regulatory system MtrA/MtrB. Probably functions as a membrane-associated protein kinase that phosphorylates MtrA in response to environmental signals. Autophosphorylates and transfers phosphate to MtrA in vitro. Overexpression of MtrA alone decreases bacterial virulence in mouse infection; co-expression of MtrA and MtrB restores normal bacterial growth, suggesting that bacterial growth in macrophages requires an optimal ratio of MtrB to MtrA. Probably plays a role in cell division. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
T Signal transduction mechanisms
|
|---|---|
| Preferred name | mtrB |
| eggNOG description | Histidine kinase |
| Orthologous group | COG5000 |
| EC number |
EC 2.7.13.3
|
| KEGG orthology |
K07636, K07654
|
| KEGG pathways |
map02020
|
| KEGG modules |
M00434, M00461
|
| Gene Ontology (10) |
GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0008150, GO:0040007, GO:0044424, GO:0044444, GO:0044464
|
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 | 0.247 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 2 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 |
|---|---|---|---|---|
HAMP | PF00672.31 | 5.8e-12 | 232–283 | HAMP domain |
HisKA | PF00512.32 | 9.3e-17 | 296–362 | His Kinase A (phospho-acceptor) domain |
HATPase_c_2 | PF13581.13 | 2.6e-06 | 401–485 | Histidine kinase-like ATPase domain |
HATPase_c | PF02518.32 | 8.8e-24 | 409–518 | Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mtrA (two component DNA-binding response regulator MtrA), high confidence from genomic context alone (score 995 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3246c mtrA |
two component DNA-binding response regulator MtrA | 999 | 995 ctx | neighborhood:693 cooccurence:724 database:900 textmining:965 |
Rv3244c lpqB |
lipoprotein LpqB | 979 | 949 ctx | neighborhood:816 coexpression:651 textmining:621 |
Rv0491 regX3 |
two component sensory transduction protein RegX | 845 | 789 ctx | cooccurence:627 |
Rv0903c prrA |
two component transcriptional regulator PrrA | 863 | 783 ctx | cooccurence:617 |
Rv0981 mprA |
two-component response regulator MrpA | 829 | 767 ctx | cooccurence:580 |
Rv1033c trcR |
two component transcriptional regulator TrcR | 800 | 746 ctx | cooccurence:558 |
Rv3765c tcrX |
two component transcriptional regulator TcrX | 795 | 741 ctx | cooccurence:549 |
Rv0757 phoP |
two component system response transcriptional positive regulator PhoP | 809 | 733 ctx | cooccurence:531 |
Rv3242c hyp |
hypothetical protein | 711 | 712 ctx | neighborhood:595 |
Rv0602c tcrA |
two component DNA binding transcriptional regulator TcrA | 779 | 711 ctx | cooccurence:496 |
Rv1027c kdpE |
transcriptional regulator KdpE | 767 | 662 ctx | cooccurence:411 |
Rv0818 |
transcriptional regulator | 653 | 607 | |
Rv3243c hyp |
hypothetical protein | 597 | 598 ctx | neighborhood:591 |
Rv2884 |
transcriptional regulator | 644 | 597 | |
Rv3247c tmk |
thymidylate kinase | 574 | 574 ctx | neighborhood:573 |
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 sensory histidine kinase MtrB
- MTBC0 PGAP product: two-component system sensor histidine kinase MtrB
- Pfam (hmmscan --cut_ga): HAMP PF00672.31 (E=6e-12), HisKA PF00512.32 (E=9e-17), HATPase_c_2 PF13581.13 (E=3e-06), HATPase_c PF02518.32 (E=9e-24)
- (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_217762.1)
- Domains: Pfam-A via hmmscan --cut_ga — HAMP (PF00672.31), HisKA (PF00512.32), HATPase_c_2 (PF13581.13), 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
COG5000 - Curated reference: UniProt P9WGK9 (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 —
30 functional partner(s); context anchor
mtrA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003453|Rv3245c|mtrB MIFGSRRRIRGRRGRSGPMTRGLSALSRAVAVAWRRSLQLRVVALTLGLSLAVILALGFVLTSQVTNRVLDIKVRAAIDQIERARTTVSGIVNGEETRSLDSSLQLARNTLTSKTDPASGAGLAGAFDAVLMVPGDGPRAASTAGPVDQVPNALRGFVKAGQAAYQYATVQTEGFSGPALIIGTPTLSRVANLELYLIFPLASEQATITLVRGTMATGGLVLLVLLAGIALLVSRQVVVPVRSASRIAERFAEGHLSERMPVRGEDDMARLAVSFNDMAESLSRQIAQLEEFGNLQRRFTSDVSHELRTPLTTVRMAADLIYDHSADLDPTLRRSTELMVSELDRFETLLNDLLEISRHDAGVAELSVEAVDLRTTVNNALGNVGHLAEEAGIELLVDLPAEQVIAEVDARRVERILRNLIANAIDHAEHKPVRIRMAADEDTVAVTVRDYGVGLRPGEEKLVFSRFWRSDPSRVRRSGGTGLGLAISVEDARLHQGRLEAWGEPGEGACFRLTLPLVRGHKVTTSPLPMKPIPQPVLQPVAQPNPQPMPPEYKERQRPREHAEWSG