trcS Family assigned · medium auto-curated
H37Rv Rv1032c · MTBC0 mtbc0_001111 ·
509 aa · 1163763–1165292 (-) ·
RefSeq NP_215548.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | two component sensor histidine kinase TrcS |
|---|---|
| MTBC0 PGAP re-annotation | HAMP domain-containing sensor histidine kinase |
| Revised (this work) | HAMP domain-containing sensor histidine kinase. Pfam: 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 |
P96368
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Sensor histidine kinase TrcS |
| EC (curated) |
EC 2.7.13.3
|
| Curated function | Member of the two-component regulatory system TrcS/TrcR. Phosphorylates TrcR. The TrcR-TrcS regulatory system may act as a transition regulatory system involved in adapting to an intracellular environment and transitioning from latency to reactivation. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
T Signal transduction mechanisms
|
|---|---|
| Preferred name | trcS |
| eggNOG description | Histidine kinase |
| Orthologous group | COG0642 |
| EC number |
EC 2.7.13.3
|
| KEGG orthology |
K02484, K07656
|
| KEGG pathways |
map02020
|
| KEGG modules |
M00463
|
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 | 1.625 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 9 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 |
|---|---|---|---|---|
HisKA | PF00512.32 | 2.2e-19 | 278–344 | His Kinase A (phospho-acceptor) domain |
HATPase_c | PF02518.32 | 2.6e-26 | 387–500 | Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: trcR (two component transcriptional regulator TrcR), high confidence from genomic context alone (score 999 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1033c trcR |
two component transcriptional regulator TrcR | 999 | 999 ctx | neighborhood:881 cooccurence:769 database:900 textmining:830 |
Rv1027c kdpE |
transcriptional regulator KdpE | 925 | 913 ctx | neighborhood:544 cooccurence:591 |
Rv3765c tcrX |
two component transcriptional regulator TcrX | 922 | 900 ctx | cooccurence:771 |
Rv0903c prrA |
two component transcriptional regulator PrrA | 903 | 879 ctx | cooccurence:724 |
Rv0491 regX3 |
two component sensory transduction protein RegX | 886 | 879 ctx | cooccurence:723 |
Rv0757 phoP |
two component system response transcriptional positive regulator PhoP | 896 | 878 ctx | cooccurence:720 |
Rv3246c mtrA |
two component DNA-binding response regulator MtrA | 892 | 877 ctx | cooccurence:719 |
Rv0602c tcrA |
two component DNA binding transcriptional regulator TcrA | 899 | 872 ctx | cooccurence:706 |
Rv0981 mprA |
two-component response regulator MrpA | 883 | 867 ctx | cooccurence:694 |
Rv2884 |
transcriptional regulator | 806 | 795 ctx | cooccurence:526 |
Rv0818 |
transcriptional regulator | 758 | 743 ctx | cooccurence:412 |
Rv1248c kgd |
multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase | 757 | 728 | experimental:422 database:538 |
Rv2496c bkdB |
3-methyl-2-oxobutanoate dehydrogenase subunit beta | 741 | 727 | database:590 |
Rv2215 dlaT |
pyruvate dehydrogenase E2 component dihydrolipoamide acyltransferase | 722 | 711 | experimental:401 database:538 |
Rv1734c hyp |
hypothetical protein | 722 | 711 | 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 sensor histidine kinase TrcS
- MTBC0 PGAP product: HAMP domain-containing sensor histidine kinase
- Pfam (hmmscan --cut_ga): HisKA PF00512.32 (E=2e-19), HATPase_c PF02518.32 (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_215548.1)
- Domains: Pfam-A via hmmscan --cut_ga — 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 P96368 (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 —
62 functional partner(s); context anchor
trcR - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001111|Rv1032c|trcS MIPDRNTRSRKAPCWRPRSLRQQLLLGVLAVVTVVLVAVGVVSVLSLSGYVTAMNDAELVESLHALNHSYTRYRDSAQTSTPTGNLPMSQAVLEFTGQTPGNLIAVLHDGVVIGSAVFSEDGARPAPPDVIRAIEAQVWDGGPPRVESLGSLGAYQVDSSAAGADRLFVGVSLSLANQIIARKKVTTVALVGAALVVTAALTVWVVGYALRPLRRVAATAAEVATMPLTDDDHQISVRVRPGDTDPDNEVGIVGHTLNRLLDNVDGALAHRVDSDLRMRQFITDASHELRTPLAAIQGYAELTRQDSSDLPPTTEYALARIESEARRMTLLVDELLLLSRLSEGEDLETEDLDLTDLVINAVNDAAVAAPTHRWVKNLPDEPVWVNGDHARLHQLVSNLLTNAWVHTQPGVTVTIGITCHRTGPNAPCVELSVTDDGPDIDPEILPHLFDRFVRASKSRSNGSGHGLGLAIVSSIVKAHRGSVTAESGNGQTVFRVRLPMIEQQIATTA