pknG Resolved · high auto-curated

H37Rv Rv0410c · MTBC0 mtbc0_000430 · 750 aa · 498427–500679 (-) · RefSeq NP_214924.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)serine/threonine-protein kinase PknG
MTBC0 PGAP re-annotationserine/threonine protein kinase PknG
Revised (this work)Serine/threonine protein kinase PknG. Pfam: PknG_rubred (PF16919.12), Pkinase (PF00069.32), PK_Tyr_Ser-Thr (PF07714.24), PknG_TPR (PF16918.12).

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

Curated reference (UniProt)

UniProt P9WI73 SwissProt · reviewed · Evidence at protein level
UniProt nameSerine/threonine-protein kinase PknG
EC (curated) EC 2.7.11.1
Curated functionPhosphorylates GarA. May play a role in metabolic regulation via control of the phosphorylation status of GarA. Plays a crucial role in the survival of mycobacteria within host macrophages, by blocking the intracellular degradation of mycobacteria in lysosomes. Required for intrinsic antibiotic resistance.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
L Replication, recombination and repair
T Signal transduction mechanisms
Preferred namepknG
eggNOG descriptionserine threonine protein kinase
Orthologous groupCOG0515
EC number EC 2.7.11.1
KEGG orthology K14949
KEGG pathways map05152
Gene Ontology (143) GO:0001898, GO:0001899, GO:0002682, GO:0002684, GO:0003674, GO:0003824, GO:0004672, GO:0004674, GO:0005488, GO:0005515, GO:0005575, GO:0005622 +131 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 0.72 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 10 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
PknG_rubredPF16919.12 2.1e-4169–141 Protein kinase G rubredoxin domain
PkinasePF00069.32 4.4e-31151–345 Protein kinase domain
PK_Tyr_Ser-ThrPF07714.24 1.7e-12157–305 Protein tyrosine and serine/threonine kinase
PknG_TPRPF16918.12 7.0e-159409–748 Protein kinase G tetratricopeptide repeat

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

Closest characterised functional partner: glnX (membrane protein), high confidence from genomic context alone (score 994 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0412c glnX membrane protein 994 994 ctx neighborhood:881 cooccurence:746 coexpression:815
Rv0411c glnH glutamine-binding lipoprotein GlnH 996 986 ctx neighborhood:882 coexpression:854 textmining:776
Rv1827 garA glycogen accumulation regulator GarA 995 902 experimental:899 textmining:959
Rv0413 mutT3 8-oxo-dGTP diphosphatase 738 640 ctx neighborhood:635
Rv0018c pstP phosphoserine/threonine phosphatase PstP 897 594 textmining:757
Rv1746 pknF serine/threonine-protein kinase PknF 957 584 ctx cooccurence:583 textmining:903
Rv1277 hyp hypothetical protein 421 398
Rv1747 ABC transporter ATP-binding protein/permease 498 391
Rv0014c pknB serine/threonine-protein kinase PknB 857 365 textmining:785
Rv3800c pks13 polyketide synthase 405 350
Rv0020c fhaA FHA domain-containing protein FhaA 695 331 textmining:563
Rv0019c fhaB FHA domain-containing protein FhaB 725 327 textmining:609
Rv3360 hyp hypothetical protein 463 325
Rv1821 secA2 accessory Sec system translocase SecA2 560 280 textmining:414
Rv2145c wag31 cell wall synthesis protein Wag31 477 273

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 PknG
  • MTBC0 PGAP product: serine/threonine protein kinase PknG
  • Pfam (hmmscan --cut_ga): PknG_rubred PF16919.12 (E=2e-41), Pkinase PF00069.32 (E=4e-31), PK_Tyr_Ser-Thr PF07714.24 (E=2e-12), PknG_TPR PF16918.12 (E=7e-159)
  • (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_214924.1)
  • Domains: Pfam-A via hmmscan --cut_ga — PknG_rubred (PF16919.12), Pkinase (PF00069.32), PK_Tyr_Ser-Thr (PF07714.24), PknG_TPR (PF16918.12)
  • 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 P9WI73 (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 — 37 functional partner(s); context anchor glnX
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000430|Rv0410c|pknG
MAKASETERSGPGTQPADAQTATSATVRPLSTQAVFRPDFGDEDNFPHPTLGPDTEPQDRMATTSRVRPPVRRLGGGLVEIPRAPDIDPLEALMTNPVVPESKRFCWNCGRPVGRSDSETKGASEGWCPYCGSPYSFLPQLNPGDIVAGQYEVKGCIAHGGLGWIYLALDRNVNGRPVVLKGLVHSGDAEAQAMAMAERQFLAEVVHPSIVQIFNFVEHTDRHGDPVGYIVMEYVGGQSLKRSKGQKLPVAEAIAYLLEILPALSYLHSIGLVYNDLKPENIMLTEEQLKLIDLGAVSRINSFGYLYGTPGFQAPEIVRTGPTVATDIYTVGRTLAALTLDLPTRNGRYVDGLPEDDPVLKTYDSYGRLLRRAIDPDPRQRFTTAEEMSAQLTGVLREVVAQDTGVPRPGLSTIFSPSRSTFGVDLLVAHTDVYLDGQVHAEKLTANEIVTALSVPLVDPTDVAASVLQATVLSQPVQTLDSLRAARHGALDADGVDFSESVELPLMEVRALLDLGDVAKATRKLDDLAERVGWRWRLVWYRAVAELLTGDYDSATKHFTEVLDTFPGELAPKLALAATAELAGNTDEHKFYQTVWSTNDGVISAAFGLARARSAEGDRVGAVRTLDEVPPTSRHFTTARLTSAVTLLSGRSTSEVTEEQIRDAARRVEALPPTEPRVLQIRALVLGGALDWLKDNKASTNHILGFPFTSHGLRLGVEASLRSLARVAPTQRHRYTLVDMANKVRPTSTF