pknD Resolved · high auto-curated
H37Rv Rv0931c · MTBC0 mtbc0_000989 ·
664 aa · 1041137–1043131 (-) ·
RefSeq NP_215446.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | serine/threonine-protein kinase PknD |
|---|---|
| MTBC0 PGAP re-annotation | serine/threonine protein kinase PknD |
| Revised (this work) | Serine/threonine protein kinase PknD. Pfam: Pkinase (PF00069.32), PK_Tyr_Ser-Thr (PF07714.24), NHL (PF01436.28). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WI79
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Serine/threonine-protein kinase PknD |
| EC (curated) |
EC 2.7.11.1
|
| Curated function | Part of a signaling pathway that enables adaptation to osmotic stress through cell wall remodeling and virulence factor production. Phosphorylates the osmosensory protein OprA, which inhibits binding of OprA to Rv2638, leading to the regulation of osmotically regulated genes, including the ESX-1-associated virulence factor espA. In addition, directly phosphorylates the alternative sigma factor SigF and its regulator, Rv1364c, which regulates the SigF-Rv1364c interaction. Can also phosphorylate the FHA domain of Rv1747..; FUNCTION: Key microbial factor required for central nervous system tuberc. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K TranscriptionL Replication, recombination and repairT Signal transduction mechanisms
|
|---|---|
| Preferred name | pknD |
| eggNOG description | serine threonine protein kinase |
| Orthologous group | COG0515 |
| EC number |
EC 2.7.11.1
|
| KEGG orthology |
K08884
|
| Gene Ontology (106) |
GO:0003674, GO:0003824, GO:0004672, GO:0004674, GO:0005488, GO:0005575, GO:0005576, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829 +94 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 | 6.061 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 16 missense, 1 nonsense, 3 frameshift |
| Disruption | 4 distinct premature-stop/frameshift site(s); most common in 9.97% of strains (14481) · 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 |
|---|---|---|---|---|
Pkinase | PF00069.32 | 2.2e-43 | 15–262 | Protein kinase domain |
PK_Tyr_Ser-Thr | PF07714.24 | 9.6e-28 | 17–261 | Protein tyrosine and serine/threonine kinase |
NHL | PF01436.28 | 5.3e-08 | 509–535 | NHL repeat |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: pstP (phosphoserine/threonine phosphatase PstP), high confidence from genomic context alone (score 877 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0018c pstP |
phosphoserine/threonine phosphatase PstP | 903 | 877 ctx | cooccurence:750 coexpression:440 |
Rv0932c pstS2 |
phosphate ABC transporter substrate-binding lipoprotein PstS | 878 | 869 ctx | neighborhood:716 coexpression:557 |
Rv2383c mbtB |
phenyloxazoline synthase | 694 | 682 | coexpression:671 |
Rv2194 qcrC |
ubiquinol-cytochrome C reductase cytochrome subunit C | 687 | 668 | experimental:622 |
Rv1747 |
ABC transporter ATP-binding protein/permease | 821 | 613 | textmining:559 |
Rv1827 garA |
glycogen accumulation regulator GarA | 799 | 611 ctx | cooccurence:430 textmining:505 |
Rv0019c fhaB |
FHA domain-containing protein FhaB | 588 | 563 | |
Rv3737 |
transmembrane protein | 549 | 550 ctx | neighborhood:544 |
Rv2031c hspX |
alpha-crystallin | 561 | 509 | experimental:500 |
Rv0440 groEL2 |
molecular chaperone GroEL | 531 | 507 | experimental:500 |
Rv2124c metH |
methionine synthase | 489 | 489 ctx | neighborhood:485 |
Rv3800c pks13 |
polyketide synthase | 513 | 488 | coexpression:444 |
Rv0020c fhaA |
FHA domain-containing protein FhaA | 763 | 475 | textmining:568 |
Rv0933 pstB |
phosphate ABC transporter ATP-binding protein PstB | 460 | 457 ctx | neighborhood:451 |
Rv1157c hyp |
hypothetical protein | 469 | 443 | coexpression:424 |
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: serine/threonine-protein kinase PknD
- MTBC0 PGAP product: serine/threonine protein kinase PknD
- Pfam (hmmscan --cut_ga): Pkinase PF00069.32 (E=2e-43), PK_Tyr_Ser-Thr PF07714.24 (E=1e-27), NHL PF01436.28 (E=5e-08)
- (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_215446.1)
- Domains: Pfam-A via hmmscan --cut_ga — Pkinase (PF00069.32), PK_Tyr_Ser-Thr (PF07714.24), NHL (PF01436.28)
- 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
COG0515 - Curated reference: UniProt P9WI79 (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 —
45 functional partner(s); context anchor
pstP - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000989|Rv0931c|pknD MSDAVPQVGSQFGPYQLLRLLGRGGMGEVYEAEDTRKHRVVALKLISPQYSDNAVFRARMQREADTAGRLTEPHIVPIHDYGEINGQFFVEMRMIDGTSLRALLKQYGPLTPARAVAIVRQIAAALDAAHANGVTHRDVKPENILVTASDFAYLVDFGIARAASDPGLTQTGTAVGTYNYMAPERFTGDEVTYRADIYALACVLGECLTGAPPYRADSVERLIAAHLMDPAPQPSQLRPGRVPPALDQVIAKGMAKNPAERFMSAGDLAIAAHDALTTSEQHQATTILRRGDNATLLATPADTGLSQSESGIAGAGTGPPTPGAARWSPGDSATVAGPLAADSRGGNWPSQTGHSPAVPNALQASLGHAVPPAGNKRKVWAVVGAAAIVLVAIVAAAGYLVLRPSWSPTQASGQTVLPFTGIDFRLSPSGVAVDSAGNVYVTSEGMYGRVVKLATGSTGTTVLPFNGLYQPQGLAVDGAGTVYVTDFNNRVVTLAAGSNNQTVLPFDGLNYPEGLAVDTQGAVYVADRGNNRVVKLAAGSKTQTVLPFTGLNDPDGVAVDNSGNVYVTDTDNNRVVKLEAESNNQVVLPFTDITAPWGIAVDEAGTVYVTEHNTNQVVKLLAGSTTSTVLPFTGLNTPLAVAVDSDRTVYVADRGNDRVVKLTS