mtrA Resolved · high auto-curated
H37Rv Rv3246c · MTBC0 mtbc0_003454 ·
228 aa · 3648806–3649492 (-) ·
RefSeq NP_217763.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | two component DNA-binding response regulator MtrA |
|---|---|
| MTBC0 PGAP re-annotation | two-component system response regulator MtrA |
| Revised (this work) | Two-component system response regulator MtrA. 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 |
P9WGM7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | DNA-binding response regulator MtrA |
| Curated function | Member of the two-component regulatory system MtrA/MtrB. Binds direct repeat motifs of sequence 5'-GTCACAGCG-3', phosphorylation confers higher affinity. Overexpression decreases bacteria viability upon infection of human THP-1 macrophage cell line, due at least in part to impaired blockage of phagosome-lysosome fusion (upon infection bacteria usually remain in phagosomes). Infecting C57BL/6 mice with an overexpressing strain leads to an attentuated infection in both spleen and lungs. The level of dnaA mRNA increases dramatically. Binds the promoter of dnaA, fbpD, ripA and itself, as well as o. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|---|
| Preferred name | mtrA |
| eggNOG description | response regulator |
| Orthologous group | COG0745 |
| KEGG orthology |
K07670
|
| KEGG pathways |
map02020
|
| KEGG modules |
M00461
|
| Gene Ontology (65) |
GO:0005575, GO:0005623, GO:0005886, GO:0006355, GO:0006464, GO:0006468, GO:0006793, GO:0006796, GO:0006807, GO:0008150, GO:0008152, GO:0009889 +53 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 | 0.0 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 0 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 | 2.8e-30 | 8–117 | Response regulator receiver domain |
Trans_reg_C | PF00486.35 | 1.2e-26 | 149–224 | Transcriptional regulatory protein, C terminal |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mtrB (two component sensory histidine kinase MtrB), high confidence from genomic context alone (score 995 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3245c mtrB |
two component sensory histidine kinase MtrB | 999 | 995 ctx | neighborhood:693 cooccurence:724 database:900 textmining:965 |
Rv0600c |
two component sensor kinase HK1 | 912 | 897 ctx | cooccurence:767 |
Rv1032c trcS |
two component sensor histidine kinase TrcS | 892 | 877 ctx | cooccurence:719 |
Rv0490 senX3 |
two component sensor histidine kinase SenX3 | 948 | 871 ctx | cooccurence:764 textmining:620 |
Rv3764c tcrY |
two component sensor kinase TcrY | 885 | 870 ctx | cooccurence:703 |
Rv0902c prrB |
two component sensor histidine kinase PrrB | 953 | 866 ctx | cooccurence:694 textmining:666 |
Rv0758 phoR |
two component system response sensor kinase PhoR | 866 | 855 ctx | cooccurence:746 |
Rv0982 mprB |
two component histidine-protein kinase/phosphatase MprB | 866 | 843 ctx | cooccurence:639 |
Rv3244c lpqB |
lipoprotein LpqB | 936 | 820 ctx | neighborhood:814 textmining:661 |
Rv3247c tmk |
thymidylate kinase | 794 | 794 ctx | neighborhood:794 |
Rv3243c hyp |
hypothetical protein | 730 | 731 ctx | neighborhood:729 |
Rv3248c sahH |
adenosylhomocysteinase | 731 | 721 ctx | neighborhood:719 |
Rv0601c |
two component sensor kinase HK2 | 687 | 637 | |
Rv3242c hyp |
hypothetical protein | 593 | 578 ctx | neighborhood:556 |
Rv2998A |
Rv2998A, len: 67 aa. Probable conserved hypothetical protein, (possibly gene fragment), highly similar to central part of two-component sens | 591 | 576 |
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 DNA-binding response regulator MtrA
- MTBC0 PGAP product: two-component system response regulator MtrA
- Pfam (hmmscan --cut_ga): Response_reg PF00072.31 (E=3e-30), Trans_reg_C PF00486.35 (E=1e-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_217763.1)
- 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 P9WGM7 (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 —
52 functional partner(s); context anchor
mtrB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003454|Rv3246c|mtrA MDTMRQRILVVDDDASLAEMLTIVLRGEGFDTAVIGDGTQALTAVRELRPDLVLLDLMLPGMNGIDVCRVLRADSGVPIVMLTAKTDTVDVVLGLESGADDYIMKPFKPKELVARVRARLRRNDDEPAEMLSIADVEIDVPAHKVTRNGEQISLTPLEFDLLVALARKPRQVFTRDVLLEQVWGYRHPADTRLVNVHVQRLRAKVEKDPENPTVVLTVRGVGYKAGPP