prrA Resolved · high auto-curated
H37Rv Rv0903c · MTBC0 mtbc0_000957 ·
236 aa · 1009066–1009776 (-) ·
RefSeq NP_215418.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | two component transcriptional regulator PrrA |
|---|---|
| MTBC0 PGAP re-annotation | two-component system response regulator PrrA |
| Revised (this work) | Two-component system response regulator PrrA. Pfam: Response_reg (PF00072.31), Trans_reg_C (PF00486.35). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WGM1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Transcriptional regulatory protein PrrA |
| 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. Upon phosphorylation by PrrB, functions as a transcription regulator by direct binding to promoter regions of target genes to positively regulate their expression. Autoregulates its own expression. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|---|
| Preferred name | prrA |
| eggNOG description | transcriptional |
| Orthologous group | COG0745 |
| KEGG orthology |
K07671
|
| KEGG pathways |
map02020
|
| KEGG modules |
M00462
|
| Gene Ontology (24) |
GO:0000287, GO:0003674, GO:0005488, GO:0005509, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0008150, GO:0016020 +12 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 | 0.38 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 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 |
|---|---|---|---|---|
Response_reg | PF00072.31 | 3.8e-30 | 13–123 | Response regulator receiver domain |
Trans_reg_C | PF00486.35 | 3.2e-26 | 160–233 | Transcriptional regulatory protein, C terminal |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: prrB (two component sensor histidine kinase PrrB), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0902c prrB |
two component sensor histidine kinase PrrB | 999 | 1000 ctx | neighborhood:879 cooccurence:767 coexpression:815 experimental:669 database:900 textmining:963 |
Rv0600c |
two component sensor kinase HK1 | 914 | 897 ctx | cooccurence:766 |
Rv0982 mprB |
two component histidine-protein kinase/phosphatase MprB | 897 | 893 ctx | cooccurence:747 |
Rv1032c trcS |
two component sensor histidine kinase TrcS | 903 | 879 ctx | cooccurence:724 |
Rv3764c tcrY |
two component sensor kinase TcrY | 901 | 874 ctx | cooccurence:710 |
Rv0490 senX3 |
two component sensor histidine kinase SenX3 | 921 | 868 ctx | cooccurence:760 textmining:431 |
Rv0758 phoR |
two component system response sensor kinase PhoR | 860 | 853 ctx | cooccurence:740 |
Rv3245c mtrB |
two component sensory histidine kinase MtrB | 863 | 783 ctx | cooccurence:617 |
Rv1019 |
transcriptional regulator | 784 | 783 | coexpression:783 |
Rv2096c pafB |
proteasome accessory factor B | 757 | 757 | coexpression:757 |
Rv0038 hyp |
hypothetical protein | 744 | 744 | coexpression:744 |
Rv1100 hyp |
hypothetical protein | 734 | 734 | coexpression:734 |
Rv1488 hyp |
hypothetical protein | 733 | 734 | coexpression:734 |
Rv1152 |
transcriptional regulator | 743 | 733 | coexpression:733 |
Rv0601c |
two component sensor kinase HK2 | 739 | 689 |
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 transcriptional regulator PrrA
- MTBC0 PGAP product: two-component system response regulator PrrA
- Pfam (hmmscan --cut_ga): Response_reg PF00072.31 (E=4e-30), Trans_reg_C PF00486.35 (E=3e-26)
- (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_215418.1)
- Domains: Pfam-A via hmmscan --cut_ga — Response_reg (PF00072.31), Trans_reg_C (PF00486.35)
- 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
COG0745 - Curated reference: UniProt P9WGM1 (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
prrB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000957|Rv0903c|prrA MGGMDTGVTSPRVLVVDDDSDVLASLERGLRLSGFEVATAVDGAEALRSATENRPDAIVLDINMPVLDGVSVVTALRAMDNDVPVCVLSARSSVDDRVAGLEAGADDYLVKPFVLAELVARVKALLRRRGSTATSSSETITVGPLEVDIPGRRARVNGVDVDLTKREFDLLAVLAEHKTAVLSRAQLLELVWGYDFAADTNVVDVFIGYLRRKLEAGGGPRLLHTVRGVGFVLRMQ