pknK Resolved · high auto-curated
H37Rv Rv3080c · MTBC0 mtbc0_003274 ·
1110 aa · 3464020–3467352 (-) ·
RefSeq NP_217596.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | serine/threonine-protein kinase PknK |
|---|---|
| MTBC0 PGAP re-annotation | serine/threonine protein kinase PknK |
| Revised (this work) | Serine/threonine protein kinase PknK. Pfam: Pkinase (PF00069.32), PK_Tyr_Ser-Thr (PF07714.24), NPHP3_N (PF24883.3), AAA_16 (PF13191.13), WHD_MalT (PF25873.1). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WI65
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Serine/threonine-protein kinase PknK |
| EC (curated) |
EC 2.7.11.1
|
| Curated function | Key microbial factor involved in regulation of early and late events in tuberculosis infection, and in host-pathogen interactions. Modulates host immunity during early infection. Slows mycobacterial growth during chronic infection in host and during a variety of stress conditions in vitro. Regulates the expression of a large subset of tRNA genes as a means to facilitate adaptation to changing growth environments. In vitro, directs the inhibition of transcription and translation processes in a phosphorylation-dependent manner. Phosphorylates the transcriptional regulator VirS, thereby increasin. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K TranscriptionL Replication, recombination and repairT Signal transduction mechanisms
|
|---|---|
| Preferred name | pknK |
| eggNOG description | PFAM Protein kinase |
| Orthologous group | COG0515 |
| EC number |
EC 2.7.11.1
|
| KEGG orthology |
K12132, K13419
|
| Gene Ontology (65) |
GO:0003674, GO:0003824, GO:0004672, GO:0004674, GO:0005488, GO:0005515, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829 +53 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 | 0.634 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 7 synonymous, 12 missense, 0 nonsense, 3 frameshift |
| Disruption | 3 distinct premature-stop/frameshift site(s); most common in 0.46% of strains (672) · clonal |
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 | 3.1e-41 | 27–272 | Protein kinase domain |
PK_Tyr_Ser-Thr | PF07714.24 | 2.3e-31 | 29–273 | Protein tyrosine and serine/threonine kinase |
NPHP3_N | PF24883.3 | 1.2e-06 | 347–492 | Nephrocystin 3, N-terminal |
AAA_16 | PF13191.13 | 3.1e-10 | 349–484 | AAA ATPase domain |
WHD_MalT | PF25873.1 | 1.3e-25 | 588–668 | MalT winged helix domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: pstP (phosphoserine/threonine phosphatase PstP), high confidence from genomic context alone (score 757 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3079c hyp |
hypothetical protein | 902 | 902 ctx | neighborhood:647 coexpression:735 |
Rv0018c pstP |
phosphoserine/threonine phosphatase PstP | 794 | 757 ctx | cooccurence:633 |
Rv3081 hyp |
hypothetical protein | 683 | 683 ctx | neighborhood:610 |
Rv3091 hyp |
hypothetical protein | 477 | 477 ctx | cooccurence:457 |
Rv2305 hyp |
hypothetical protein | 453 | 454 ctx | cooccurence:440 |
Rv1827 garA |
glycogen accumulation regulator GarA | 727 | 443 | textmining:531 |
Rv2031c hspX |
alpha-crystallin | 460 | 435 | experimental:415 |
Rv1541c lprI |
lipoprotein LprI | 434 | 435 ctx | cooccurence:408 |
Rv0251c hsp |
heat shock protein | 459 | 433 | experimental:415 |
Rv2490c PE_PGRS43 |
PE-PGRS family protein PE_PGRS43 | 430 | 431 | |
Rv0014c pknB |
serine/threonine-protein kinase PknB | 621 | 429 | |
Rv0019c fhaB |
FHA domain-containing protein FhaB | 449 | 426 | |
Rv1747 |
ABC transporter ATP-binding protein/permease | 562 | 420 | |
Rv1920 |
membrane protein | 416 | 417 | |
Rv2487c PE_PGRS42 |
PE-PGRS family protein PE_PGRS42 | 402 | 403 |
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 PknK
- MTBC0 PGAP product: serine/threonine protein kinase PknK
- Pfam (hmmscan --cut_ga): Pkinase PF00069.32 (E=3e-41), PK_Tyr_Ser-Thr PF07714.24 (E=2e-31), NPHP3_N PF24883.3 (E=1e-06), AAA_16 PF13191.13 (E=3e-10), WHD_MalT PF25873.1 (E=1e-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_217596.1)
- Domains: Pfam-A via hmmscan --cut_ga — Pkinase (PF00069.32), PK_Tyr_Ser-Thr (PF07714.24), NPHP3_N (PF24883.3), AAA_16 (PF13191.13), WHD_MalT (PF25873.1)
- 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 P9WI65 (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 —
36 functional partner(s); context anchor
pstP - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003274|Rv3080c|pknK MTDVDPHATRRDLVPNIPAELLEAGFDNVEEIGRGGFGVVYRCVQPSLDRAVAVKVLSTDLDRDNLERFLREQRAMGRLSGHPHIVTVLQVGVLAGGRPFIVMPYHAKNSLETLIRRHGPLDWRETLSIGVKLAGALEAAHRVGTLHRDVKPGNILLTDYGEPQLTDFGIARIAGGFETATGVIAGSPAFTAPEVLEGASPTPASDVYSLGATLFCALTGHAAYERRSGERVIAQFLRITSQPIPDLRKQGLPADVAAAIERAMARHPADRPATAADVGEELRDVQRRNGVSVDEMPLPVELGVERRRSPEAHAAHRHTGGGTPTVPTPPTPATKYRPSVPTGSLVTRSRLTDILRAGGRRRLILIHAPSGFGKSTLAAQWREELSRDGAAVAWLTIDNDDNNEVWFLSHLLESIRRVRPTLAESLGHVLEEHGDDAGRYVLTSLIDEIHENDDRIAVVIDDWHRVSDSRTQAALGFLLDNGCHHLQLIVTSWSRAGLPVGRLRIGDELAEIDSAALRFDTDEAAALLNDAGGLRLPRADVQALTTSTDGWAAALRLAALSLRGGGDATQLLRGLSGASDVIHEFLSENVLDTLEPELREFLLVASVTERTCGGLASALAGITNGRAMLEEAEHRGLFLQRTEDDPNWFRFHQMFADFLHRRLERGGSHRVAELHRRASAWFAENGYLHEAVDHALAAGDPARAVDLVEQDETNLPEQSKMTTLLAIVQKLPTSMVVSRARLQLAIAWANILLQRPAPATGALNRFETALGRAELPEATQADLRAEADVLRAVAEVFADRVERVDDLLAEAMSRPDTLPPRVPGTAGNTAALAAICRFEFAEVYPLLDWAAPYQEMMGPFGTVYAQCLRGMAARNRLDIVAALQNFRTAFEVGTAVGAHSHAARLAGSLLAELLYETGDLAGAGRLMDESYLLGSEGGAVDYLAARYVIGARVKAAQGDHEGAADRLSTGGDTAVQLGLPRLAARINNERIRLGIALPAAVAADLLAPRTIPRDNGIATMTAELDEDSAVRLLSAGDSADRDQACQRAGALAAAIDGTRRPLAALQAQILHIETLAATGRESDARNELAPVATKCAELGLSRLLVDAGLA