phoR Resolved · high auto-curated
H37Rv Rv0758 · MTBC0 mtbc0_000807 ·
485 aa · 856821–858278 (+) ·
RefSeq NP_215272.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | two component system response sensor kinase PhoR |
|---|---|
| MTBC0 PGAP re-annotation | sensory box histidine kinase PhoR |
| Revised (this work) | Sensory box histidine kinase PhoR. Pfam: HAMP (PF00672.31), 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 |
P71815
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | histidine kinase |
| EC (curated) |
EC 2.7.13.3
|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
T Signal transduction mechanisms
|
|---|---|
| Preferred name | phoR |
| eggNOG description | Histidine kinase |
| Orthologous group | COG5002 |
| EC number |
EC 2.7.13.3
|
| KEGG orthology |
K02484
|
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 | 0.508 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 8 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 |
|---|---|---|---|---|
HAMP | PF00672.31 | 5.3e-11 | 179–230 | HAMP domain |
HisKA | PF00512.32 | 5.3e-18 | 250–312 | His Kinase A (phospho-acceptor) domain |
HATPase_c | PF02518.32 | 1.7e-31 | 358–468 | Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: phoP (two component system response transcriptional positive regulator PhoP), high confidence from genomic context alone (score 975 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0757 phoP |
two component system response transcriptional positive regulator PhoP | 999 | 975 ctx | neighborhood:817 cooccurence:772 textmining:978 |
Rv3765c tcrX |
two component transcriptional regulator TcrX | 880 | 859 ctx | cooccurence:748 |
Rv3246c mtrA |
two component DNA-binding response regulator MtrA | 866 | 855 ctx | cooccurence:746 |
Rv1033c trcR |
two component transcriptional regulator TrcR | 896 | 853 ctx | cooccurence:743 |
Rv0903c prrA |
two component transcriptional regulator PrrA | 860 | 853 ctx | cooccurence:740 |
Rv0602c tcrA |
two component DNA binding transcriptional regulator TcrA | 877 | 852 ctx | cooccurence:742 |
Rv0491 regX3 |
two component sensory transduction protein RegX | 915 | 849 ctx | cooccurence:727 textmining:462 |
Rv3454 |
Rv3454, (MTCY13E12.07), len: 422 aa. Probable conserved integral membrane protein, showing some similarity to various proteins (generally tr | 836 | 836 ctx | fusion:836 |
Rv0981 mprA |
two-component response regulator MrpA | 833 | 825 ctx | cooccurence:665 |
Rv1027c kdpE |
transcriptional regulator KdpE | 784 | 756 ctx | cooccurence:575 |
Rv0756c hyp |
hypothetical protein | 747 | 736 ctx | neighborhood:733 |
Rv2884 |
transcriptional regulator | 800 | 716 ctx | cooccurence:500 |
Rv0818 |
transcriptional regulator | 758 | 658 | |
Rv0983 pepD |
serine protease PepD | 589 | 572 | coexpression:410 |
Rv1223 htrA |
serine protease HtrA | 516 | 495 |
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 system response sensor kinase PhoR
- MTBC0 PGAP product: sensory box histidine kinase PhoR
- Pfam (hmmscan --cut_ga): HAMP PF00672.31 (E=5e-11), HisKA PF00512.32 (E=5e-18), HATPase_c PF02518.32 (E=2e-31)
- (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_215272.1)
- Domains: Pfam-A via hmmscan --cut_ga — HAMP (PF00672.31), 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
COG5002 - Curated reference: UniProt P71815 (TrEMBL, unreviewed; 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 —
34 functional partner(s); context anchor
phoP - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000807|Rv0758|phoR MARHLRGRLPLRVRLVAATLILVATGLVASGIAVTSMLQHRLTSRIDRVLLEEAQIWAQITLPLAPDPYPGHNPDRPPSRFYVRVISPDGQSYTALNDNTAIPAVPANNDVGRHPTTLPSIGGSKTLWRAVSVRASDGYLTTVAIDLADVRSTVRSLVLLQVGIGSAVLVVLGVAGYAVVRRSLRPLAEFEQTAAAIGAGQLDRRVPQWHPRTEVGRLSLALNGMLAQIQRAVASAESSAEKARDSEDRMRQFITDASHELRTPLTTIRGFAELYRQGAARDVGMLLSRIESEASRMGLLVDDLLLLARLDAHRPLELCRVDLLALASDAAHDARAMDPKRRITLEVLDGPGTPEVLGDESRLRQVLRNLVANAIQHTPESADVTVRVGTEGDDAILEVADDGPGMSQEDALRVFERFYRADSSRARASGGTGLGLSIVDSLVAAHGGAVTVTTALGEGCCFRVSLPRVSDVDQLSLTPVVPGPP