pknE Resolved · high auto-curated

H37Rv Rv1743 · MTBC0 mtbc0_001856 · 566 aa · 1981076–1982776 (+) · RefSeq NP_216259.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)serine/threonine-protein kinase PknE
MTBC0 PGAP re-annotationserine/threonine protein kinase PknE
Revised (this work)Serine/threonine protein kinase PknE. Pfam: Pkinase (PF00069.32), PK_Tyr_Ser-Thr (PF07714.24), Thioredoxin_4 (PF13462.13).

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

Curated reference (UniProt)

UniProt P9WI77 SwissProt · reviewed · Evidence at protein level
UniProt nameSerine/threonine-protein kinase PknE
EC (curated) EC 2.7.11.1
Curated functionImportant for survival of the bacterium in the host during infection. Promotes the survival of infected macrophages by activating multiple signaling responses and suppressing apoptosis of macrophages during nitrate stress. May contribute to the adaptation of M.tuberculosis during stress conditions by maintaining the cellular integrity. Can phosphorylate the FHA domain of Rv1747.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
L Replication, recombination and repair
T Signal transduction mechanisms
Preferred namepknE
eggNOG descriptionserine threonine protein kinase
Orthologous groupCOG0515
EC number EC 2.7.11.1
KEGG orthology K08884, K12132
Gene Ontology (65) GO:0003674, GO:0003824, GO:0004672, GO:0004674, GO:0005575, GO:0005576, GO:0006464, GO:0006468, GO:0006793, GO:0006796, GO:0006807, GO:0006950 +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 1.194 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 7 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)

PfamAccessioni-EvalueResiduesDescription
PkinasePF00069.32 1.1e-4216–229 Protein kinase domain
PK_Tyr_Ser-ThrPF07714.24 4.3e-2718–260 Protein tyrosine and serine/threonine kinase
Thioredoxin_4PF13462.13 1.2e-06389–544 Thioredoxin

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

Closest characterised functional partner: pstP (phosphoserine/threonine phosphatase PstP), high confidence from genomic context alone (score 855 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0018c pstP phosphoserine/threonine phosphatase PstP 902 855 ctx cooccurence:762
Rv1827 garA glycogen accumulation regulator GarA 833 637 ctx cooccurence:460 textmining:561
Rv0019c fhaB FHA domain-containing protein FhaB 601 557
Rv1740 vapB34 antitoxin VapB34 540 540 ctx neighborhood:533
Rv1742 hyp hypothetical protein 540 539 ctx neighborhood:535
Rv1741 vapC34 ribonuclease VapC34 536 536 ctx neighborhood:533
Rv1747 ABC transporter ATP-binding protein/permease 692 524
Rv2031c hspX alpha-crystallin 523 521 experimental:500
Rv0020c fhaA FHA domain-containing protein FhaA 777 510 textmining:564
Rv0440 groEL2 molecular chaperone GroEL 567 507 experimental:500
Rv1364c sigma factor regulatory protein 567 435
Rv1739c sulfate ABC transporter permease 419 419 ctx neighborhood:415
Rv0014c pknB serine/threonine-protein kinase PknB 641 416 textmining:411
Rv1712 cmk cytidylate kinase 416 416 coexpression:409
Rv2874 dipZ integral membrane C-type cytochrome biogenesis protein DipZ 457 346

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 PknE
  • MTBC0 PGAP product: serine/threonine protein kinase PknE
  • Pfam (hmmscan --cut_ga): Pkinase PF00069.32 (E=1e-42), PK_Tyr_Ser-Thr PF07714.24 (E=4e-27), Thioredoxin_4 PF13462.13 (E=1e-06)
  • (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_216259.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Pkinase (PF00069.32), PK_Tyr_Ser-Thr (PF07714.24), Thioredoxin_4 (PF13462.13)
  • 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 P9WI77 (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 — 34 functional partner(s); context anchor pstP
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001856|Rv1743|pknE
MDGTAESREGTQFGPYRLRRLVGRGGMGDVYEAEDTVRERIVALKLMSETLSSDPVFRTRMQREARTAGRLQEPHVVPIHDFGEIDGQLYVDMRLINGVDLAAMLRRQGPLAPPRAVAIVRQIGSALDAAHAAGATHRDVKPENILVSADDFAYLVDFGIASATTDEKLTQLGNTVGTLYYMAPERFSESHATYRADIYALTCVLYECLTGSPPYQGDQLSVMGAHINQAIPRPSTVRPGIPVAFDAVIARGMAKNPEDRYVTCGDLSAAAHAALATADQDRATDILRRSQVAKLPVPSTHPVSPGTRWPQPTPWAGGAPPWGPPSSPLPRSARQPWLWVGVAVAVVVALAGGLGIALAHPWRSSGPRTSAPPPPPPADAVELRVLNDGVFVGSSVAPTTIDIFNEPICPPCGSFIRSYASDIDTAVADKQLAVRYHLLNFLDDQSHSKNYSTRAVAASYCVAGQNDPKLYASFYSALFGSDFQPQENAASDRTDAELAHLAQTVGAEPTAISCIKSGADLGTAQTKATNASETLAGFNASGTPFVWDGSMVVNYQDPSWLARLIG