mprA Resolved · high auto-curated
H37Rv Rv0981 · MTBC0 mtbc0_001052 ·
228 aa · 1104158–1104844 (+) ·
RefSeq NP_215496.2
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | two-component response regulator MrpA |
|---|---|
| MTBC0 PGAP re-annotation | two-component system response regulator MprA |
| Revised (this work) | Two-component system response regulator MprA. 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 |
P9WGM9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Response regulator MprA |
| 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. Functions as a transcriptional regulator that recognizes a 19-bp nucleotide motif comprizing two loosely conserved 8-bp direct DNA-binding motif repeats separated by a 3-bp spacer region. MprB/MprA is involved in regulation of numerous stress-responsive genes, including up-regulation of two sigma factors, sigE and sigB as well as pepD and mprA, and repression . |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|---|
| Preferred name | mprA |
| 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. Functions as a transcriptional regulator that recognizes a 19-bp nucleotide motif comprizing two loosely conserved 8-bp direct DNA-binding motif repeats separated by a 3-bp spacer region |
| Orthologous group | COG0745 |
| KEGG orthology |
K07669, K07672
|
| KEGG pathways |
map02020
|
| KEGG modules |
M00460, M00463
|
| Gene Ontology (79) |
GO:0000160, GO:0003674, GO:0003676, GO:0003677, GO:0005488, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0006355, GO:0007154, GO:0007165 +67 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 | 0.278 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 3 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 | 1.1e-32 | 3–112 | Response regulator receiver domain |
Trans_reg_C | PF00486.35 | 1.5e-26 | 149–223 | Transcriptional regulatory protein, C terminal |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mprB (two component histidine-protein kinase/phosphatase MprB), high confidence from genomic context alone (score 999 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0982 mprB |
two component histidine-protein kinase/phosphatase MprB | 999 | 999 ctx | neighborhood:781 cooccurence:771 coexpression:861 database:900 textmining:893 |
Rv0600c |
two component sensor kinase HK1 | 896 | 892 ctx | cooccurence:756 |
Rv0902c prrB |
two component sensor histidine kinase PrrB | 901 | 877 ctx | cooccurence:719 |
Rv1032c trcS |
two component sensor histidine kinase TrcS | 883 | 867 ctx | cooccurence:694 |
Rv0490 senX3 |
two component sensor histidine kinase SenX3 | 904 | 865 ctx | cooccurence:745 |
Rv3764c tcrY |
two component sensor kinase TcrY | 859 | 851 ctx | cooccurence:654 |
Rv0758 phoR |
two component system response sensor kinase PhoR | 833 | 825 ctx | cooccurence:665 |
Rv0983 pepD |
serine protease PepD | 790 | 776 ctx | neighborhood:683 |
Rv3245c mtrB |
two component sensory histidine kinase MtrB | 829 | 767 ctx | cooccurence:580 |
Rv0601c |
two component sensor kinase HK2 | 746 | 737 ctx | cooccurence:404 |
Rv0984 moaB2 |
pterin-4-alpha-carbinolamine dehydratase | 840 | 693 ctx | neighborhood:678 textmining:502 |
Rv2998A |
Rv2998A, len: 67 aa. Probable conserved hypothetical protein, (possibly gene fragment), highly similar to central part of two-component sens | 666 | 654 | |
Rv3365c hyp |
hypothetical protein | 594 | 579 | |
Rv0979A rpmF |
50S ribosomal protein L32 | 556 | 557 ctx | neighborhood:544 |
Rv0976c hyp |
hypothetical protein | 548 | 548 ctx | neighborhood:544 |
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 response regulator MrpA
- MTBC0 PGAP product: two-component system response regulator MprA
- Pfam (hmmscan --cut_ga): Response_reg PF00072.31 (E=1e-32), Trans_reg_C PF00486.35 (E=2e-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_215496.2)
- 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 P9WGM9 (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
mprB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001052|Rv0981|mprA MRILVVDDDRAVRESLRRSLSFNGYSVELAHDGVEALDMIASDRPDALVLDVMMPRLDGLEVCRQLRSTGDDLPILVLTARDSVSERVAGLDAGADDYLPKPFALEELLARMRALLRRTKPEDAAESMAMRFSDLTLDPVTREVNRGQRRISLTRTEFALLEMLIANPRRVLTRSRILEEVWGFDFPTSGNALEVYVGYLRRKTEADGEPRLIHTVRGVGYVLRETPP