Rv0600c Resolved · high auto-curated
H37Rv Rv0600c · MTBC0 - ·
168 aa · 697904–698410 (-) ·
RefSeq NP_215114.2
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | two component sensor kinase HK1 |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Two component sensor kinase HK1. 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 |
O07778
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Sensor histidine kinase component HK1 |
| EC (curated) |
EC 2.7.13.3
|
| Curated function | Member of the three-protein two-component system HK1/HK2/TcrA. Kinase that binds ATP and catalyzes the transfer of a phosphoryl group from ATP to HK2. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
T Signal transduction mechanisms
|
|---|---|
| eggNOG description | Histidine kinase |
| Orthologous group | COG0642 |
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 | 0.36 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 1 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 | 6.7e-25 | 34–140 | Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: tcrA (two component DNA binding transcriptional regulator TcrA), high confidence from genomic context alone (score 938 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0602c tcrA |
two component DNA binding transcriptional regulator TcrA | 970 | 938 ctx | neighborhood:441 cooccurence:762 textmining:541 |
Rv0903c prrA |
two component transcriptional regulator PrrA | 914 | 897 ctx | cooccurence:766 |
Rv3246c mtrA |
two component DNA-binding response regulator MtrA | 912 | 897 ctx | cooccurence:767 |
Rv0491 regX3 |
two component sensory transduction protein RegX | 900 | 896 ctx | cooccurence:765 |
Rv0981 mprA |
two-component response regulator MrpA | 896 | 892 ctx | cooccurence:756 |
Rv1033c trcR |
two component transcriptional regulator TrcR | 913 | 891 ctx | cooccurence:755 |
Rv0757 phoP |
two component system response transcriptional positive regulator PhoP | 895 | 891 ctx | cooccurence:753 |
Rv3765c tcrX |
two component transcriptional regulator TcrX | 911 | 887 ctx | cooccurence:746 |
Rv2884 |
transcriptional regulator | 877 | 872 ctx | cooccurence:710 |
Rv1027c kdpE |
transcriptional regulator KdpE | 892 | 871 ctx | cooccurence:707 |
Rv0601c |
two component sensor kinase HK2 | 947 | 864 ctx | neighborhood:511 experimental:500 textmining:630 |
Rv0818 |
transcriptional regulator | 809 | 801 ctx | cooccurence:548 |
Rv1248c kgd |
multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase | 758 | 728 | experimental:422 database:538 |
Rv2496c bkdB |
3-methyl-2-oxobutanoate dehydrogenase subunit beta | 742 | 728 | database:590 |
Rv1734c hyp |
hypothetical protein | 727 | 716 | 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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): two component sensor kinase HK1
- Pfam (hmmscan --cut_ga): HATPase_c PF02518.32 (E=7e-25)
- (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_215114.2)
- 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
COG0642 - Curated reference: UniProt O07778 (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 —
61 functional partner(s); context anchor
tcrA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0600c| MPITPLLHESVARFAATGADITTRAEPDLFVSIDPDHLRRILTAVLDNAITHGDGEIAVTAHARDGAVDIGVRDHGPGFADHFLPVAFDRFTRADTARGGRGSGLGLAIVAALTTTHGGHANATNHPDGGAELRITLPTPRPPFHEELPRITSSDTKDPNREHDTSDQ