prrB Resolved · high auto-curated
H37Rv Rv0902c · MTBC0 mtbc0_000956 ·
446 aa · 1007715–1009055 (-) ·
RefSeq NP_215417.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | two component sensor histidine kinase PrrB |
|---|---|
| MTBC0 PGAP re-annotation | two-component system sensor histidine kinase PrrB |
| Revised (this work) | Two-component system sensor histidine kinase PrrB. 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 |
P9WGK7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Sensor-type histidine kinase PrrB |
| EC (curated) |
EC 2.7.13.3
|
| Curated function | Member of the two-component regulatory system PrrB/PrrA that is involved specifically in early intracellular multiplication of Mycobacterium and is essential for its viability. Functions as a sensor protein kinase which is autophosphorylated at a histidine residue and transfers its phosphate group to the conserved aspartic acid residue in the regulatory domain of PrrA. In turn, PrrA binds to the upstream promoter regions of target genes including itself to positively regulate their expression. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
T Signal transduction mechanisms
|
|---|---|
| Preferred name | prrB |
| eggNOG description | Histidine kinase |
| Orthologous group | COG0642 |
| EC number |
EC 2.7.13.3
|
| KEGG orthology |
K07655
|
| KEGG pathways |
map02020
|
| KEGG modules |
M00462
|
| Gene Ontology (66) |
GO:0000166, GO:0003674, GO:0003824, GO:0004672, GO:0005488, GO:0005515, GO:0005524, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0005887 +54 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 | n/a |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 0 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 | 5.0e-07 | 168–217 | HAMP domain |
HisKA | PF00512.32 | 3.0e-11 | 232–293 | His Kinase A (phospho-acceptor) domain |
HATPase_c | PF02518.32 | 3.9e-21 | 340–443 | Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: prrA (two component transcriptional regulator PrrA), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0903c prrA |
two component transcriptional regulator PrrA | 999 | 1000 ctx | neighborhood:879 cooccurence:767 coexpression:815 experimental:669 database:900 textmining:963 |
Rv1033c trcR |
two component transcriptional regulator TrcR | 948 | 888 ctx | cooccurence:736 textmining:561 |
Rv0757 phoP |
two component system response transcriptional positive regulator PhoP | 963 | 878 ctx | cooccurence:718 textmining:711 |
Rv3765c tcrX |
two component transcriptional regulator TcrX | 922 | 877 ctx | cooccurence:721 |
Rv0981 mprA |
two-component response regulator MrpA | 901 | 877 ctx | cooccurence:719 |
Rv0491 regX3 |
two component sensory transduction protein RegX | 886 | 874 ctx | cooccurence:700 |
Rv0602c tcrA |
two component DNA binding transcriptional regulator TcrA | 944 | 870 ctx | cooccurence:700 textmining:594 |
Rv3246c mtrA |
two component DNA-binding response regulator MtrA | 953 | 866 ctx | cooccurence:694 textmining:666 |
Rv1027c kdpE |
transcriptional regulator KdpE | 936 | 861 ctx | cooccurence:677 textmining:559 |
Rv2096c pafB |
proteasome accessory factor B | 770 | 770 | coexpression:770 |
Rv0875c hyp |
hypothetical protein | 740 | 740 | coexpression:740 |
Rv1248c kgd |
multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase | 759 | 731 | experimental:422 database:538 |
Rv2496c bkdB |
3-methyl-2-oxobutanoate dehydrogenase subunit beta | 745 | 731 | database:590 |
Rv2495c bkdC |
branched-chain keto acid dehydrogenase E2 component | 730 | 720 | experimental:401 database:538 |
Rv2884 |
transcriptional regulator | 730 | 719 |
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 PrrB
- MTBC0 PGAP product: two-component system sensor histidine kinase PrrB
- Pfam (hmmscan --cut_ga): HAMP PF00672.31 (E=5e-07), HisKA PF00512.32 (E=3e-11), HATPase_c PF02518.32 (E=4e-21)
- (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_215417.1)
- 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 P9WGK7 (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 —
93 functional partner(s); context anchor
prrA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000956|Rv0902c|prrB MNILSRIFARTPSLRTRVVVATAIGAAIPVLIVGTVVWVGITNDRKERLDRRLDEAAGFAIPFVPRGLDEIPRSPNDQDALITVRRGNVIKSNSDITLPKLQDDYADTYVRGVRYRVRTVEIPGPEPTSVAVGATYDATVAETNNLHRRVLLICTFAIGAAAVFAWLLAAFAVRPFKQLAEQTRSIDAGDEAPRVEVHGASEAIEIAEAMRGMLQRIWNEQNRTKEALASARDFAAVSSHELRTPLTAMRTNLEVLSTLDLPDDQRKEVLNDVIRTQSRIEATLSALERLAQGELSTSDDHVPVDITDLLDRAAHDAARIYPDLDVSLVPSPTCIIVGLPAGLRLAVDNAIANAVKHGGATLVQLSAVSSRAGVEIAIDDNGSGVPEGERQVVFERFSRGSTASHSGSGLGLALVAQQAQLHGGTASLENSPLGGARLVLRLPGPS