mprB Resolved · high auto-curated
H37Rv Rv0982 · MTBC0 mtbc0_001053 ·
504 aa · 1104844–1106358 (+) ·
RefSeq NP_215497.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | two component histidine-protein kinase/phosphatase MprB |
|---|---|
| MTBC0 PGAP re-annotation | two-component system sensor histidine kinase MprB |
| Revised (this work) | Two-component system sensor histidine kinase MprB. Pfam: HAMP (PF00672.31), 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 |
P9WGL1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Signal transduction histidine-protein kinase/phosphatase MprB |
| EC (curated) |
EC 2.7.13.3, EC 3.1.3.-
|
| Curated function | Member of the two-component regulatory system MprB/MprA which contributes to maintaining a balance among several systems involved in stress resistance and is required for establishment and maintenance of persistent infection in the host. In response to environmental signals MprB acts both as a membrane-associated protein kinase that undergoes autophosphorylation and subsequently transfers the phosphate to MprA, and as a protein phosphatase that dephosphorylates phospho-MprA. MprB/MprA is involved in regulation of numerous stress-responsive genes, including up-regulation of two sigma factors, s. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
T Signal transduction mechanisms
|
|---|---|
| Preferred name | mprB |
| eggNOG description | Member of the two-component regulatory system MprB MprA which contributes to maintaining a balance among several systems involved in stress resistance and is required for establishment and maintenance of persistent infection in the host. In response to environmental signals MprB acts as both a membrane-associated protein kinase that undergoes autophosphorylation and subsequently transfers the phosphate to MprA, and a protein phosphatase that dephosphorylates phospho-MprA |
| Orthologous group | COG0642 |
| EC number |
EC 2.7.13.3
|
| KEGG orthology |
K07653
|
| KEGG pathways |
map02020
|
| KEGG modules |
M00460
|
| Gene Ontology (53) |
GO:0000160, GO:0003674, GO:0003824, GO:0004721, GO:0005575, GO:0005576, GO:0005623, GO:0005886, GO:0006464, GO:0006468, GO:0006470, GO:0006793 +41 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 | 0.513 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 7 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 | 1.9e-11 | 184–234 | HAMP domain |
HisKA | PF00512.32 | 9.8e-12 | 240–311 | His Kinase A (phospho-acceptor) domain |
HATPase_c | PF02518.32 | 2.7e-23 | 351–463 | Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mprA (two-component response regulator MrpA), high confidence from genomic context alone (score 999 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0981 mprA |
two-component response regulator MrpA | 999 | 999 ctx | neighborhood:781 cooccurence:771 coexpression:861 database:900 textmining:893 |
Rv0983 pepD |
serine protease PepD | 941 | 939 ctx | neighborhood:702 coexpression:805 |
Rv0903c prrA |
two component transcriptional regulator PrrA | 897 | 893 ctx | cooccurence:747 |
Rv0602c tcrA |
two component DNA binding transcriptional regulator TcrA | 872 | 867 ctx | cooccurence:696 |
Rv1033c trcR |
two component transcriptional regulator TrcR | 870 | 866 ctx | cooccurence:691 |
Rv3765c tcrX |
two component transcriptional regulator TcrX | 864 | 859 ctx | cooccurence:674 |
Rv0491 regX3 |
two component sensory transduction protein RegX | 859 | 854 ctx | cooccurence:655 |
Rv3246c mtrA |
two component DNA-binding response regulator MtrA | 866 | 843 ctx | cooccurence:639 |
Rv0757 phoP |
two component system response transcriptional positive regulator PhoP | 843 | 837 ctx | cooccurence:620 |
Rv1027c kdpE |
transcriptional regulator KdpE | 830 | 824 ctx | cooccurence:596 |
Rv0984 moaB2 |
pterin-4-alpha-carbinolamine dehydratase | 817 | 790 ctx | neighborhood:693 |
Rv2496c bkdB |
3-methyl-2-oxobutanoate dehydrogenase subunit beta | 747 | 733 | database:590 |
Rv1248c kgd |
multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase | 759 | 730 | experimental:422 database:538 |
Rv2884 |
transcriptional regulator | 738 | 729 | |
Rv2495c bkdC |
branched-chain keto acid dehydrogenase E2 component | 735 | 725 | experimental:401 database:538 |
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 histidine-protein kinase/phosphatase MprB
- MTBC0 PGAP product: two-component system sensor histidine kinase MprB
- Pfam (hmmscan --cut_ga): HAMP PF00672.31 (E=2e-11), HisKA PF00512.32 (E=1e-11), HATPase_c PF02518.32 (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_215497.1)
- Domains: Pfam-A via hmmscan --cut_ga — HAMP (PF00672.31), 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
COG0642 - Curated reference: UniProt P9WGL1 (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 —
77 functional partner(s); context anchor
mprA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001053|Rv0982|mprB MWWFRRRDRAPLRATSSLSLRWRVMLLAMSMVAMVVVLMSFAVYAVISAALYSDIDNQLQSRAQLLIASGSLAADPGKAIEGTAYSDVNAMLVNPGQSIYTAQQPGQTLPVGAAEKAVIRGELFMSRRTTADQRVLAIRLTNGSSLLISKSLKPTEAVMNKLRWVLLIVGGIGVAVAAVAGGMVTRAGLRPVGRLTEAAERVARTDDLRPIPVFGSDELARLTEAFNLMLRALAESRERQARLVTDAGHELRTPLTSLRTNVELLMASMAPGAPRLPKQEMVDLRADVLAQIEELSTLVGDLVDLSRGDAGEVVHEPVDMADVVDRSLERVRRRRNDIHFDVEVIGWQVYGDTAGLSRMALNLMDNAAKWSPPGGHVGVRLSQLDASHAELVVSDRGPGIPVQERRLVFERFYRSASARALPGSGLGLAIVKQVVLNHGGLLRIEDTDPGGQPPGTSIYVLLPGRRMPIPQLPGATAGARSTDIENSRGSANVISVESQSTRAT