fgd1 Resolved · high auto-curated

H37Rv Rv0407 · MTBC0 mtbc0_000427 · 336 aa · 494148–495158 (+) · RefSeq NP_214921.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)F420-dependent glucose-6-phosphate dehydrogenase
MTBC0 PGAP re-annotationglucose-6-phosphate dehydrogenase (coenzyme-F420)
Revised (this work)Glucose-6-phosphate dehydrogenase (coenzyme-F420). Pfam: Bac_luciferase (PF00296.27).

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

Curated reference (UniProt)

UniProt P9WNE1 SwissProt · reviewed · Evidence at protein level
UniProt nameF420-dependent glucose-6-phosphate dehydrogenase
EC (curated) EC 1.1.98.2
Curated functionCatalyzes the coenzyme F420-dependent oxidation of glucose 6-phosphate to 6-phosphogluconolactone. Appears to have a role in resistance to oxidative stress, via its consumption of G6P that serves as a source of reducing power to combat oxidative stress in mycobacteria. More precisely, is likely involved in a F420-dependent anti-oxidant mechanism that protects M.tuberculosis against oxidative stress and bactericidal agents..; FUNCTION: Is essential for the bioreductive activation of the bicyclic 4-nitroimidazole prodrug PA-824 (a nitroimidazo-oxazine) developed for anti-tuberculosis therapy aga.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred namefgd
eggNOG descriptionCatalyzes the coenzyme F420-dependent oxidation of glucose 6-phosphate (G6P) to 6-phosphogluconolactone. Appears to have a role in resistance to oxidative stress, via its consumption of G6P that serves as a source of reducing power to combat oxidative stress in mycobacteria
Orthologous groupCOG2141
EC number EC 1.1.98.2
KEGG orthology K15510
Gene Ontology (44) GO:0003674, GO:0003824, GO:0005488, GO:0005515, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0008150 +32 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 0.656 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 6 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
Bac_luciferasePF00296.27 4.6e-6711–306 Luciferase-like monooxygenase

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

Closest characterised functional partner: pta (phosphate acetyltransferase), high confidence from genomic context alone (score 889 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0408 pta phosphate acetyltransferase 903 889 ctx neighborhood:882
Rv0409 ackA acetate kinase 889 889 ctx neighborhood:882
Rv0406c beta lactamase-like protein 787 787 ctx neighborhood:784
Rv0044c oxidoreductase 804 777 ctx cooccurence:771
Rv3261 fbiA 2-phospho-L-lactate transferase 990 747 ctx cooccurence:728 textmining:965
Rv3547 ddn deazaflavin-dependent nitroreductase 983 745 ctx cooccurence:745 textmining:936
Rv3178 nitroreductase 953 745 ctx cooccurence:745 textmining:824
Rv1558 hyp hypothetical protein 949 745 ctx cooccurence:745 textmining:812
Rv1261c hyp hypothetical protein 845 741 ctx cooccurence:739 textmining:430
Rv2983 cofC 2-phospho-L-lactate guanylyltransferase 970 689 ctx cooccurence:677 textmining:909
Rv3262 fbiB coenzyme F420:L-glutamate ligase 988 685 ctx cooccurence:641 textmining:965
Rv2161c hyp hypothetical protein 645 645 ctx cooccurence:641
Rv3093c oxidoreductase 604 604 ctx cooccurence:602
Rv3079c hyp hypothetical protein 594 595 ctx cooccurence:585
Rv3072c hyp hypothetical protein 591 568 ctx cooccurence:567

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: F420-dependent glucose-6-phosphate dehydrogenase
  • MTBC0 PGAP product: glucose-6-phosphate dehydrogenase (coenzyme-F420)
  • Pfam (hmmscan --cut_ga): Bac_luciferase PF00296.27 (E=5e-67)
  • (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_214921.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Bac_luciferase (PF00296.27)
  • 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 COG2141
  • Curated reference: UniProt P9WNE1 (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 pta
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000427|Rv0407|fgd1
MAELKLGYKASAEQFAPRELVELAVAAEAHGMDSATVSDHFQPWRHQGGHAPFSLSWMTAVGERTNRLLLGTSVLTPTFRYNPAVIAQAFATMGCLYPNRVFLGVGTGEALNEIATGYEGAWPEFKERFARLRESVGLMRQLWSGDRVDFDGDYYRLKGASIYDVPDGGVPVYIAAGGPAVAKYAGRAGDGFICTSGKGEELYTEKLMPAVREGAAAADRSVDGIDKMIEIKISYDPDPELALNNTRFWAPLSLTAEQKHSIDDPIEMEKAADALPIEQIAKRWIVASDPDEAVEKVGQYVTWGLNHLVFHAPGHDQRRFLELFQSDLAPRLRRLG