Rv3220c Family assigned · medium auto-curated
H37Rv Rv3220c · MTBC0 mtbc0_003426 ·
501 aa · 3618171–3619676 (-) ·
RefSeq NP_217736.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | two component sensor kinase |
|---|---|
| MTBC0 PGAP re-annotation | histidine kinase N-terminal domain-containing protein |
| Revised (this work) | Histidine kinase N-terminal domain-containing protein. Pfam: GAF_PdtaS (PF12282.16), HisKA_2 (PF07568.19), HWE_HK (PF07536.21), HATPase_c_2 (PF13581.13), 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 |
P9WGL5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Sensor histidine kinase PdtaS |
| EC (curated) |
EC 2.7.13.3
|
| Curated function | Member of the two-component regulatory system PdtaR/PdtaS. This two-component system plays an essential role in mycobacterial adaptation to poor nutrient conditions. Nutrient deprivation results in increasing intracellular concentrations of cyclic diguanosine monophosphate (c-di-GMP), which binds to the PdtaS sensor and promotes its autophosphorylation, leading to the activation of the signaling cascade. The phosphate group is then transferred to PdtaR..; FUNCTION: In addition, the PdtaR/PdtaS two-component system controls copper and nitric oxide (NO) resistance downstream of the intramembrane. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
T Signal transduction mechanisms
|
|---|---|
| Preferred name | pdtaS |
| eggNOG description | Histidine kinase |
| Orthologous group | COG3920 |
| EC number |
EC 2.7.13.3
|
| KEGG orthology |
K00936
|
| KEGG modules |
M00839
|
| Gene Ontology (62) |
GO:0000155, GO:0000160, GO:0000166, GO:0003674, GO:0003824, GO:0004672, GO:0004673, GO:0005488, GO:0005524, GO:0006464, GO:0006468, GO:0006793 +50 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 | 0.543 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 6 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 |
|---|---|---|---|---|
GAF_PdtaS | PF12282.16 | 2.4e-44 | 4–150 | Histidine kinase PdtaS, GAF domain |
HisKA_2 | PF07568.19 | 9.0e-22 | 300–367 | Histidine kinase |
HWE_HK | PF07536.21 | 3.7e-08 | 300–371 | HWE histidine kinase |
HATPase_c_2 | PF13581.13 | 6.5e-07 | 391–468 | Histidine kinase-like ATPase domain |
HATPase_c | PF02518.32 | 9.0e-12 | 397–493 | Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: TB7.3 (acetyl-CoA carboxylase biotin carboxyl carrier protein subunit), high confidence from genomic context alone (score 869 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3221c TB7.3 |
acetyl-CoA carboxylase biotin carboxyl carrier protein subunit | 869 | 869 ctx | neighborhood:865 |
Rv1626 pdtaR |
two-component system transcriptional regulator | 984 | 786 ctx | cooccurence:756 textmining:928 |
Rv0513 |
transmembrane protein | 730 | 730 | coexpression:730 |
Rv3219 whiB1 |
transcriptional regulator WhiB1 | 731 | 616 ctx | cooccurence:612 |
Rv3223c sigH |
ECF RNA polymerase sigma factor SigH | 599 | 578 ctx | neighborhood:508 |
Rv3260c whiB2 |
transcriptional regulator WhiB2 | 595 | 566 ctx | cooccurence:561 |
Rv0510 hemC |
porphobilinogen deaminase | 535 | 536 | coexpression:474 |
Rv3221A rshA |
anti-sigma factor RshA | 533 | 515 ctx | neighborhood:508 |
Rv1830 |
HTH-type transcriptional regulator | 511 | 491 ctx | cooccurence:486 |
Rv3416 whiB3 |
redox-responsive transcriptional regulator WhiB3 | 484 | 484 ctx | cooccurence:477 |
Rv2901c hyp |
hypothetical protein | 459 | 460 ctx | cooccurence:425 |
Rv3224 |
iron-regulated short-chain dehydrogenase/reductase | 453 | 453 ctx | neighborhood:447 |
Rv3195 hyp |
hypothetical protein | 444 | 445 ctx | cooccurence:442 |
Rv3222c hyp |
hypothetical protein | 425 | 425 ctx | neighborhood:415 |
Rv0015c pknA |
serine/threonine-protein kinase PknA | 416 | 415 | coexpression:415 |
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 kinase
- MTBC0 PGAP product: histidine kinase N-terminal domain-containing protein
- Pfam (hmmscan --cut_ga): GAF_PdtaS PF12282.16 (E=2e-44), HisKA_2 PF07568.19 (E=9e-22), HWE_HK PF07536.21 (E=4e-08), HATPase_c_2 PF13581.13 (E=7e-07), HATPase_c PF02518.32 (E=9e-12)
- (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_217736.1)
- Domains: Pfam-A via hmmscan --cut_ga — GAF_PdtaS (PF12282.16), HisKA_2 (PF07568.19), HWE_HK (PF07536.21), HATPase_c_2 (PF13581.13), 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
COG3920 - Curated reference: UniProt P9WGL5 (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 —
25 functional partner(s); context anchor
TB7.3 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003426|Rv3220c| MSTLGDLLAEHTVLPGSAVDHLHAVVGEWQLLADLSFADYLMWVRRDDGVLVCVAQCRPNTGPTVVHTDAVGTVVAANSMPLVAATFSGGVPGREGAVGQQNSCQHDGHSVEVSPVRFGDQVVAVLTRHQPELAARRRSGHLETAYRLCATDLLRMLAEGTFPDAGDVAMSRSSPRAGDGFIRLDVDGVVSYASPNALSAYHRMGLTTELEGVNLIDATRPLISDPFEAHEVDEHVQDLLAGDGKGMRMEVDAGGATVLLRTLPLVVAGRNVGAAILIRDVTEVKRRDRALISKDATIREIHHRVKNNLQTVAALLRLQARRTSNAEGREALIESVRRVSSIALVHDALSMSVDEQVNLDEVIDRILPIMNDVASVDRPIRINRVGDLGVLDSDRATALIMVITELVQNAIEHAFDPAAAEGSVTIRAERSARWLDVVVHDDGLGLPQGFSLEKSDSLGLQIVRTLVSAELDGSLGMRDARERGTDVVLRVPVGRRGRLML