Rv0845 Resolved · high auto-curated
H37Rv Rv0845 · MTBC0 - ·
425 aa · 941190–942467 (+) ·
RefSeq NP_215360.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | sensor histidine kinase NarS |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Sensor histidine kinase NarS. Pfam: HATPase_c (PF02518.32). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
O53857
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Sensor histidine kinase NarS |
| EC (curated) |
EC 2.7.13.3
|
| Curated function | Member of the two-component regulatory system NarS/NarL involved in gene expression during aerobic nitrate metabolism. Plays therefore a crucial role in anaerobic survival of mycobacteria in host. 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 NarL. In turn, NarL binds to the upstream promoter regions of target genes to regulate their expression during aerobic nitrate metabolism. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
T Signal transduction mechanisms
|
|---|---|
| eggNOG description | Histidine kinase |
| Orthologous group | COG4585 |
| EC number |
EC 2.7.13.3
|
| KEGG orthology |
K02480
|
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 | 1.322 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 7 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 |
|---|---|---|---|---|
HATPase_c | PF02518.32 | 2.3e-09 | 337–424 | Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: narL (nitrate/nitrite response transcriptional regulator NarL), high confidence from genomic context alone (score 970 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0844c narL |
nitrate/nitrite response transcriptional regulator NarL | 987 | 970 ctx | neighborhood:783 cooccurence:767 textmining:596 |
Rv3133c devR |
two component transcriptional regulator DevR | 884 | 853 ctx | cooccurence:726 |
Rv0195 |
two component transcriptional regulator | 839 | 818 ctx | cooccurence:662 |
Rv1006 hyp |
hypothetical protein | 617 | 617 ctx | cooccurence:615 |
Rv2047c hyp |
hypothetical protein | 625 | 602 ctx | cooccurence:597 |
Rv0890c |
HTH-type transcriptional regulator | 592 | 573 | |
Rv1358 |
transcriptional regulator | 574 | 554 | |
Rv2488c |
LuxR family transcriptional regulator | 572 | 553 | |
Rv0386 |
transcriptional regulator | 572 | 553 | |
Rv1868 hyp |
hypothetical protein | 526 | 527 ctx | cooccurence:526 |
Rv1435c hyp |
hypothetical protein | 522 | 522 ctx | cooccurence:518 |
Rv2862c hyp |
hypothetical protein | 520 | 500 | coexpression:483 |
Rv0966c hyp |
hypothetical protein | 519 | 499 | coexpression:482 |
Rv1118c hyp |
hypothetical protein | 490 | 467 | |
Rv0339c iniR |
transcriptional regulator | 490 | 466 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): sensor histidine kinase NarS
- Pfam (hmmscan --cut_ga): HATPase_c PF02518.32 (E=2e-09)
- (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_215360.1)
- Domains: Pfam-A via hmmscan --cut_ga — 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
COG4585 - Curated reference: UniProt O53857 (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 —
31 functional partner(s); context anchor
narL - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0845| MPSYGNLGRLGGRHEYGVLVAMTSSAELDRVRWAHQLRSYRIASVLRIGVVGLMVAAMVVGTSRSEWPQQIVLIGVYAVAALWALLLAYSASRRFFALRRFRSMGRLEPFAFTAVDVLILTGFQLLSTDGIYPLLIMILLPVLVGLDVSTRRAAVVLACTLVGFAVAVLGDPVMLRAIGWPETIFRFALYAFLCATALMVVRIEERHTRSVAGLSALRAELLAQTMTASEVLQRRIAEAIHDGPLQDVLAARQELIELDAVTPGDERVGRALAGLQSASERLRQATFELHPAVLEQVGLGPAVKQLAASTAQRSGIKISTDIDYPIRSGIDPIVFGVVRELLSNVVRHSGATTASVRLGITDEKCVLDVADDGVGVTGDTMARRLGEGHIGLASHRARVDAAGGVLVFLATPRGTHVCVELPLKR