pknL Resolved · high auto-curated

H37Rv Rv2176 · MTBC0 mtbc0_002310 · 399 aa · 2463948–2465147 (+) · RefSeq NP_216692.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)serine/threonine-protein kinase PknL
MTBC0 PGAP re-annotationprotein kinase
Revised (this work)Protein kinase. Pfam: Pkinase (PF00069.32), PK_Tyr_Ser-Thr (PF07714.24).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt P9WI63 SwissProt · reviewed · Evidence at protein level
UniProt nameSerine/threonine-protein kinase PknL
EC (curated) EC 2.7.11.1
Curated functionPhosphorylates the DNA-binding protein Rv2175c. May be involved in the regulation of cell division and cell envelope biosynthesis.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
L Replication, recombination and repair
T Signal transduction mechanisms
Preferred namepknL
eggNOG descriptionserine threonine protein kinase
Orthologous groupCOG0515
EC number EC 2.7.11.1
KEGG orthology K08884, K12132
Gene Ontology (63) GO:0003674, GO:0003824, GO:0004672, GO:0004674, GO:0005575, GO:0005623, GO:0005886, GO:0006464, GO:0006468, GO:0006793, GO:0006796, GO:0006807 +51 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 1.102 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 8 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.26% of strains (377) · 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)

PfamAccessioni-EvalueResiduesDescription
PkinasePF00069.32 1.4e-4621–265 Protein kinase domain
PK_Tyr_Ser-ThrPF07714.24 1.2e-2922–264 Protein tyrosine and serine/threonine kinase

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: pstP (phosphoserine/threonine phosphatase PstP), high confidence from genomic context alone (score 862 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0018c pstP phosphoserine/threonine phosphatase PstP 950 862 ctx cooccurence:769 textmining:659
Rv2175c DNA-binding protein 957 788 ctx neighborhood:787 textmining:808
Rv1827 garA glycogen accumulation regulator GarA 791 667 ctx cooccurence:415 experimental:443
Rv0019c fhaB FHA domain-containing protein FhaB 748 564 textmining:447
Rv0020c fhaA FHA domain-containing protein FhaA 659 487
Rv1747 ABC transporter ATP-binding protein/permease 459 387
Rv0014c pknB serine/threonine-protein kinase PknB 497 339
Rv2914c pknI serine/threonine-protein kinase PknI 513 331
Rv1746 pknF serine/threonine-protein kinase PknF 685 307 textmining:564
Rv2088 pknJ transmembrane serine/threonine-protein kinase PknJ 495 296
Rv3080c pknK serine/threonine-protein kinase PknK 489 296
Rv0931c pknD serine/threonine-protein kinase PknD 452 270
Rv1266c pknH serine/threonine-protein kinase PknH 462 267
Rv2145c wag31 cell wall synthesis protein Wag31 446 265
Rv0410c pknG serine/threonine-protein kinase PknG 762 263 textmining:690

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 PknL
  • MTBC0 PGAP product: protein kinase
  • Pfam (hmmscan --cut_ga): Pkinase PF00069.32 (E=1e-46), PK_Tyr_Ser-Thr PF07714.24 (E=1e-29)
  • (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_216692.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Pkinase (PF00069.32), PK_Tyr_Ser-Thr (PF07714.24)
  • 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 P9WI63 (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 — 21 functional partner(s); context anchor pstP
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002310|Rv2176|pknL
MVEAGTRDPLESALLDSRYLVQAKIASGGTSTVYRGLDVRLDRPVALKVMDSRYAGDEQFLTRFRLEARAVARLNNRALVAVYDQGKDGRHPFLVMELIEGGTLRELLIERGPMPPHAVVAVLRPVLGGLAAAHRAGLVHRDVKPENILISDDGDVKLADFGLVRAVAAASITSTGVILGTAAYLSPEQVRDGNADPRSDVYSVGVLVYELLTGHTPFTGDSALSIAYQRLDADVPRASAVIDGVPPQFDELVACATARNPADRYADAIAMGADLEAIAEELALPEFRVPAPRNSAQHRSAALYRSRITQQGQLGAKPVHHPTRQLTRQPGDCSEPASGSEPEHEPITGQFAGIAIEEFIWARQHARRMVLVWVSVVLAITGLVASAAWTIGSNLSGLL