pknA Resolved · high auto-curated

H37Rv Rv0015c · MTBC0 mtbc0_000019 · 431 aa · 17467–18762 (-) · RefSeq NP_214529.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)serine/threonine-protein kinase PknA
MTBC0 PGAP re-annotationserine/threonine protein kinase PknA
Revised (this work)Serine/threonine protein kinase PknA. Pfam: Pkinase (PF00069.32), PK_Tyr_Ser-Thr (PF07714.24), Kdo (PF06293.21), ABC1 (PF03109.23).

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

Curated reference (UniProt)

UniProt P9WI83 SwissProt · reviewed · Evidence at protein level
UniProt nameSerine/threonine-protein kinase PknA
EC (curated) EC 2.7.11.1
Curated functionProtein kinase that regulates many aspects of mycobacterial physiology, and is critical for growth in vitro and survival of the pathogen in the host. Is a key component of a signal transduction pathway that regulates cell growth, cell shape and cell division via phosphorylation of target proteins such as FtsZ, Wag31, GlmU, PstP, EmbR and Rv1422. Also catalyzes the phosphorylation of the proteasome alpha-subunit (PrcA) and unprocessed proteasome beta-subunit (pre-PrcB), which results in the inhibition of processing of pre-PrcB and assembly of the proteasome complex, and thereby enhances the myc.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
L Replication, recombination and repair
T Signal transduction mechanisms
Preferred namepknA
eggNOG descriptionserine threonine protein kinase
Orthologous groupCOG0515
EC number EC 2.7.11.1
KEGG orthology K08884, K12132
Gene Ontology (83) GO:0003674, GO:0003824, GO:0004672, GO:0004674, GO:0005575, GO:0005576, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0006464 +71 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 0.148 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 2 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 4.1e-4613–261 Protein kinase domain
PK_Tyr_Ser-ThrPF07714.24 1.2e-3215–260 Protein tyrosine and serine/threonine kinase
KdoPF06293.21 2.7e-0557–153 Lipopolysaccharide kinase (Kdo/WaaP) family
ABC1PF03109.23 2.7e-0690–168 ABC1 atypical kinase-like domain

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

Closest characterised functional partner: pknB (serine/threonine-protein kinase PknB), high confidence from genomic context alone (score 985 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0014c pknB serine/threonine-protein kinase PknB 990 985 ctx neighborhood:881 coexpression:829
Rv0018c pstP phosphoserine/threonine phosphatase PstP 998 982 ctx neighborhood:882 cooccurence:769 textmining:930
Rv0017c rodA cell division protein RodA 987 914 ctx neighborhood:882 textmining:858
Rv0019c fhaB FHA domain-containing protein FhaB 979 901 ctx neighborhood:780 textmining:798
Rv0016c pbpA penicillin-binding protein PbpA 993 887 ctx neighborhood:882 textmining:941
Rv0020c fhaA FHA domain-containing protein FhaA 970 837 ctx neighborhood:700 textmining:828
Rv0513 transmembrane protein 733 733 coexpression:733
Rv1827 garA glycogen accumulation regulator GarA 960 701 ctx cooccurence:467 experimental:443 textmining:873
Rv2031c hspX alpha-crystallin 511 507 experimental:500
Rv0440 groEL2 molecular chaperone GroEL 554 505 experimental:500
Rv0511 hemD uroporphyrin-III C-methyltransferase 479 480 coexpression:463
Rv3220c pdtaS two component sensor kinase 416 415 coexpression:415
Rv1747 ABC transporter ATP-binding protein/permease 596 411
Rv2914c pknI serine/threonine-protein kinase PknI 517 329
Rv3360 hyp hypothetical protein 600 325 textmining:432

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 PknA
  • MTBC0 PGAP product: serine/threonine protein kinase PknA
  • Pfam (hmmscan --cut_ga): Pkinase PF00069.32 (E=4e-46), PK_Tyr_Ser-Thr PF07714.24 (E=1e-32), Kdo PF06293.21 (E=3e-05), ABC1 PF03109.23 (E=3e-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_214529.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Pkinase (PF00069.32), PK_Tyr_Ser-Thr (PF07714.24), Kdo (PF06293.21), ABC1 (PF03109.23)
  • 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 P9WI83 (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 — 42 functional partner(s); context anchor pknB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000019|Rv0015c|pknA
MSPRVGVTLSGRYRLQRLIATGGMGQVWEAVDNRLGRRVAVKVLKSEFSSDPEFIERFRAEARTTAMLNHPGIASVHDYGESQMNGEGRTAYLVMELVNGEPLNSVLKRTGRLSLRHALDMLEQTGRALQIAHAAGLVHRDVKPGNILITPTGQVKITDFGIAKAVDAAPVTQTGMVMGTAQYIAPEQALGHDASPASDVYSLGVVGYEAVSGKRPFAGDGALTVAMKHIKEPPPPLPPDLPPNVRELIEITLVKNPAMRYRSGGPFADAVAAVRAGRRPPRPSQTPPPGRAAPAAIPSGTTARVAANSAGRTAASRRSRPATGGHRPPRRTFSSGQRALLWAAGVLGALAIIIAVLLVIKAPGDNSPQQAPTPTVTTTGNPPASNTGGTDASPRLNWTERGETRHSGLQSWVVPPTPHSRASLARYEIAQ