pknB Family assigned · medium auto-curated

H37Rv Rv0014c · MTBC0 mtbc0_000018 · 626 aa · 15590–17470 (-) · RefSeq NP_214528.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)serine/threonine-protein kinase PknB
MTBC0 PGAP re-annotationStk1 family PASTA domain-containing Ser/Thr kinase
Revised (this work)Stk1 family PASTA domain-containing Ser/Thr kinase. Pfam: Pkinase (PF00069.32), PK_Tyr_Ser-Thr (PF07714.24), ABC1 (PF03109.23), Pkinase_fungal (PF17667.8), PASTA (PF03793.25).

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

Curated reference (UniProt)

UniProt P9WI81 SwissProt · reviewed · Evidence at protein level
UniProt nameSerine/threonine-protein kinase PknB
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 GarA, GlmU, PapA5, FhaB (Rv0019c), FhaA (Rv0020c), MviN, PstP, EmbR, Rv1422, Rv1747, RseA and RmlA. Also catalyzes the phosphorylation of the core proteasome alpha-subunit (PrcA), and thereby regulates the proteolytic activity of the proteasome. Is a major regulator of the oxygen-dependent rep.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
L Replication, recombination and repair
T Signal transduction mechanisms
Preferred namepknB
eggNOG descriptionserine threonine protein kinase
Orthologous groupCOG0515
EC number EC 2.7.11.1
KEGG orthology K08884, K12132
Gene Ontology (128) GO:0000270, GO:0003674, GO:0003824, GO:0004672, GO:0004674, GO:0005488, GO:0005515, GO:0005575, GO:0005618, GO:0005623, GO:0006022, GO:0006023 +116 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 0.306 · purifying
Polymorphic sites (≥ 0.1% of strains) 9 synonymous, 8 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 9.1e-5011–265 Protein kinase domain
PK_Tyr_Ser-ThrPF07714.24 7.4e-3513–264 Protein tyrosine and serine/threonine kinase
ABC1PF03109.23 2.2e-0789–165 ABC1 atypical kinase-like domain
Pkinase_fungalPF17667.8 1.9e-05111–202 Fungal protein kinase
PASTAPF03793.25 1.9e-15360–422 PASTA 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 997 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0018c pstP phosphoserine/threonine phosphatase PstP 999 997 ctx neighborhood:881 cooccurence:770 coexpression:667 experimental:693 textmining:920
Rv0015c pknA serine/threonine-protein kinase PknA 990 985 ctx neighborhood:881 coexpression:829
Rv1827 garA glycogen accumulation regulator GarA 999 982 ctx cooccurence:471 experimental:964 textmining:949
Rv0020c fhaA FHA domain-containing protein FhaA 996 968 ctx neighborhood:700 experimental:870 textmining:882
Rv0019c fhaB FHA domain-containing protein FhaB 991 959 ctx neighborhood:780 experimental:711 textmining:798
Rv0017c rodA cell division protein RodA 993 940 ctx neighborhood:881 textmining:894
Rv0016c pbpA penicillin-binding protein PbpA 993 888 ctx neighborhood:881 textmining:945
Rv0178 Mce associated membrane protein 804 805 coexpression:798
Rv1747 ABC transporter ATP-binding protein/permease 945 801 experimental:711 textmining:736
Rv1614 lgt prolipoprotein diacylglyceryl transferase 770 762 coexpression:732
Rv3783 rfbD O-antigen/lipopolysaccharide ABC transporter permease RfbD 741 741 coexpression:733
Rv3360 hyp hypothetical protein 937 732 experimental:711 textmining:775
Rv1407 fmu 16S rRNA m5C967 methyltransferase 719 701 ctx neighborhood:544
Rv2927c sepIVA hyp hypothetical protein 712 624 coexpression:408
Rv1901 cinA competence damage-inducible protein CinA 592 578 ctx neighborhood:544

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 PknB
  • MTBC0 PGAP product: Stk1 family PASTA domain-containing Ser/Thr kinase
  • Pfam (hmmscan --cut_ga): Pkinase PF00069.32 (E=9e-50), PK_Tyr_Ser-Thr PF07714.24 (E=7e-35), ABC1 PF03109.23 (E=2e-07), Pkinase_fungal PF17667.8 (E=2e-05), PASTA PF03793.25 (E=2e-15)
  • (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_214528.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Pkinase (PF00069.32), PK_Tyr_Ser-Thr (PF07714.24), ABC1 (PF03109.23), Pkinase_fungal (PF17667.8), PASTA (PF03793.25)
  • 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 P9WI81 (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 — 78 functional partner(s); context anchor pstP
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000018|Rv0014c|pknB
MTTPSHLSDRYELGEILGFGGMSEVHLARDLRLHRDVAVKVLRADLARDPSFYLRFRREAQNAAALNHPAIVAVYDTGEAETPAGPLPYIVMEYVDGVTLRDIVHTEGPMTPKRAIEVIADACQALNFSHQNGIIHRDVKPANIMISATNAVKVMDFGIARAIADSGNSVTQTAAVIGTAQYLSPEQARGDSVDARSDVYSLGCVLYEVLTGEPPFTGDSPVSVAYQHVREDPIPPSARHEGLSADLDAVVLKALAKNPENRYQTAAEMRADLVRVHNGEPPEAPKVLTDAERTSLLSSAAGNLSGPRTDPLPRQDLDDTDRDRSIGSVGRWVAVVAVLAVLTVVVTIAINTFGGITRDVQVPDVRGQSSADAIATLQNRGFKIRTLQKPDSTIPPDHVIGTDPAANTSVSAGDEITVNVSTGPEQREIPDVSTLTYAEAVKKLTAAGFGRFKQANSPSTPELVGKVIGTNPPANQTSAITNVVIIIVGSGPATKDIPDVAGQTVDVAQKNLNVYGFTKFSQASVDSPRPAGEVTGTNPPAGTTVPVDSVIELQVSKGNQFVMPDLSGMFWVDAEPRLRALGWTGMLDKGADVDAGGSQHNRVVYQNPPAGTGVNRDGIITLRFGQ