kdpD Resolved · high auto-curated
H37Rv Rv1028c · MTBC0 mtbc0_001105 ·
860 aa · 1156441–1159023 (-) ·
RefSeq NP_215544.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | sensor protein KdpD |
|---|---|
| MTBC0 PGAP re-annotation | sensor histidine kinase KdpD |
| Revised (this work) | Sensor histidine kinase KdpD. Pfam: KdpD (PF02702.24), Usp (PF00582.33), DUF4118 (PF13493.12), 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 |
P9WGL3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Sensor protein KdpD |
| EC (curated) |
EC 2.7.13.3
|
| Curated function | Member of the two-component regulatory system KdpD/KdpE involved in the regulation of the kdp operon. 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 KdpE in response to environmental signals such as low levels of potassium ion, osmotic imbalance, acid and nutrient stresses. In turn, KdpE binds to the upstream promoter regions of target genes to positively regulate their expression. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
T Signal transduction mechanisms
|
|---|---|
| Preferred name | kdpD |
| eggNOG description | Histidine kinase |
| Orthologous group | COG0642 |
| EC number |
EC 2.7.13.3
|
| KEGG orthology |
K07646
|
| KEGG pathways |
map02020
|
| KEGG modules |
M00454
|
| Gene Ontology (9) |
GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005886, GO:0016020, GO:0044424, GO:0044464, GO:0071944
|
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 | 0.695 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 10 synonymous, 18 missense, 1 nonsense, 7 frameshift |
| Disruption | 8 distinct premature-stop/frameshift site(s); most common in 17.64% of strains (25616) · convergent |
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 |
|---|---|---|---|---|
KdpD | PF02702.24 | 2.4e-98 | 25–234 | Osmosensitive K+ channel His kinase sensor domain |
Usp | PF00582.33 | 4.6e-11 | 255–358 | Universal stress protein family |
DUF4118 | PF13493.12 | 2.3e-23 | 400–507 | Domain of unknown function (DUF4118) |
HisKA | PF00512.32 | 1.7e-14 | 633–700 | His Kinase A (phospho-acceptor) domain |
HATPase_c | PF02518.32 | 1.7e-22 | 749–854 | Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: kdpE (transcriptional regulator KdpE), high confidence from genomic context alone (score 999 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1027c kdpE |
transcriptional regulator KdpE | 999 | 999 ctx | neighborhood:881 cooccurence:689 experimental:635 database:900 textmining:907 |
Rv1031 kdpC |
potassium-transporting ATPase subunit C | 994 | 986 ctx | neighborhood:747 cooccurence:771 coexpression:780 textmining:641 |
Rv1030 kdpB |
potassium-transporting ATPase subunit B | 992 | 983 ctx | neighborhood:747 cooccurence:771 coexpression:724 textmining:568 |
Rv1029 kdpA |
potassium-transporting ATPase subunit A | 989 | 978 ctx | neighborhood:747 cooccurence:772 coexpression:653 textmining:522 |
Rv1033c trcR |
two component transcriptional regulator TrcR | 833 | 592 | experimental:417 textmining:609 |
Rv1650 pheT |
phenylalanine--tRNA ligase subunit beta | 544 | 544 ctx | neighborhood:544 |
Rv0903c prrA |
two component transcriptional regulator PrrA | 746 | 512 | experimental:417 textmining:502 |
Rv0602c tcrA |
two component DNA binding transcriptional regulator TcrA | 683 | 512 | experimental:417 |
Rv0981 mprA |
two-component response regulator MrpA | 611 | 512 | experimental:417 |
Rv2884 |
transcriptional regulator | 564 | 512 | experimental:417 |
Rv3246c mtrA |
two component DNA-binding response regulator MtrA | 810 | 511 | experimental:417 textmining:629 |
Rv3765c tcrX |
two component transcriptional regulator TcrX | 594 | 511 | experimental:417 |
Rv0818 |
transcriptional regulator | 563 | 511 | experimental:417 |
Rv0757 phoP |
two component system response transcriptional positive regulator PhoP | 563 | 511 | experimental:417 |
Rv0491 regX3 |
two component sensory transduction protein RegX | 563 | 511 | experimental:417 |
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: sensor protein KdpD
- MTBC0 PGAP product: sensor histidine kinase KdpD
- Pfam (hmmscan --cut_ga): KdpD PF02702.24 (E=2e-98), Usp PF00582.33 (E=5e-11), DUF4118 PF13493.12 (E=2e-23), HisKA PF00512.32 (E=2e-14), HATPase_c PF02518.32 (E=2e-22)
- (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_215544.1)
- Domains: Pfam-A via hmmscan --cut_ga — KdpD (PF02702.24), Usp (PF00582.33), DUF4118 (PF13493.12), 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 P9WGL3 (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 —
23 functional partner(s); context anchor
kdpE - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001105|Rv1028c|kdpD MTLLFADLCAIFTPYRWMIEHVTTKRGQLRIYLGAAPGVGKTYAMLGEAHRRLERGTDVVAAVVETHGRNKTAKLLEGIEMIPPRYVEYRGARFPELDVEAVLRRHPQVVLVDELAHTNTPGSKNPKRWQDVQEILDAGITVISTVNIQHLEGLNDVVEQITGIEQKEKIPDEIVRAADQVELVDITPEALRRRLAHGNVYAAERVDAALSNYFRTGNLTALREIALLWLADQVDAALEKYRADKKITATWEARERVVVAVTGGPESETLVRRASRIASKSSAELMVVHVIRGDGLAGVSAPQLGRVRELATSLGATMHTVVGDDVPTALLDFAREMNATQLVVGTSRRSRWARLFDEGIGARTVQESGGIDVHMVTHPAASRASGWSRVSPRERHIASWLAALVVPSVICAITVAWLDRFMGIGGESALFFIGVLIVALLGGVAPAALSALLSGMLLNYFLTEPRYTWTIAEPDAAVTEFVLLAMAVAVAVLVDGAASRTREARRASQEAELLALFAGSVLRGADLATLLQRVRETYSQRAVTMLRVRQGASTGETVACVGTNPCRDVDSADTAIEVGDDEFWMLMAGRKLAARDRRVLTAVATQAAGLVKQRELAEEAGQAEAIARADELRRSLLSAVSHDLRTPLAAAKVAVSSLRTEDVAFSPEDTAELLATIEESIDQLTALVANLLDSSRLAAGVIRPQLRRAYLEEAVQRALVSIGKGATGFYRSGIDRVKVDVGDAVAMADAGLLERVLANLIDNALRYAPDCVVRVNAGRVRERVLINVIDEGPGVPRGTEEQLFAPFQRPGDHDNTTGVGLGMSVARGFVEAMGGTISATDTPGGGLTVVIDLAAPEDRP