fgd2 Resolved · high auto-curated
H37Rv Rv0132c · MTBC0 mtbc0_000143 ·
360 aa · 160046–161128 (-) ·
RefSeq NP_214646.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | F420-dependent glucose-6-phosphate dehydrogenase |
|---|---|
| MTBC0 PGAP re-annotation | F420-dependent hydroxymycolic acid dehydrogenase |
| Revised (this work) | F420-dependent hydroxymycolic acid dehydrogenase. 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 |
P96809
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | F420-dependent hydroxymycolic acid dehydrogenase |
| EC (curated) |
EC 1.1.98.-
|
| Curated function | Catalyzes the coenzyme F420-dependent oxidation of hydroxymycolic acids (H-MAs) to ketomycolic acids (K-MAs), a lipid class making up the mycobacterial pseudo-outer membrane and over one-third of the dry weight of M.tuberculosis. Does not exhibit F420-dependent glucose-6-phosphate dehydrogenase (FGD) activity. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | fgd2 |
| eggNOG description | Luciferase-like monooxygenase |
| Orthologous group | COG2141 |
| EC number |
EC 1.1.98.2
|
| KEGG orthology |
K15510
|
| Gene Ontology (6) |
GO:0005575, GO:0005623, GO:0005886, GO:0016020, GO:0044464, GO:0071944
|
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 | 0.697 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 6 missense, 2 nonsense, 1 frameshift |
| Disruption | 3 distinct premature-stop/frameshift site(s); most common in 0.26% of strains (382) · clonal |
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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
Bac_luciferase | PF00296.27 | 2.3e-54 | 48–281 | Luciferase-like monooxygenase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0044c (oxidoreductase), high confidence from genomic context alone (score 765 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0044c |
oxidoreductase | 765 | 765 ctx | cooccurence:763 |
Rv3261 fbiA |
2-phospho-L-lactate transferase | 878 | 758 ctx | cooccurence:750 textmining:520 |
Rv3262 fbiB |
coenzyme F420:L-glutamate ligase | 888 | 735 ctx | cooccurence:701 textmining:596 |
Rv3547 ddn |
deazaflavin-dependent nitroreductase | 889 | 731 ctx | cooccurence:731 textmining:605 |
Rv3520c |
coenzyme F420-dependent oxidoreductase | 727 | 727 ctx | cooccurence:726 |
Rv3178 |
nitroreductase | 731 | 715 ctx | cooccurence:712 |
Rv0131c fadE1 |
acyl-CoA dehydrogenase FadE1 | 713 | 713 ctx | neighborhood:687 |
Rv2983 cofC |
2-phospho-L-lactate guanylyltransferase | 795 | 712 ctx | cooccurence:700 |
Rv1261c hyp |
hypothetical protein | 709 | 710 ctx | cooccurence:708 |
Rv3093c |
oxidoreductase | 705 | 705 ctx | cooccurence:705 |
Rv1558 hyp |
hypothetical protein | 704 | 693 ctx | cooccurence:693 |
Rv3072c hyp |
hypothetical protein | 688 | 689 ctx | cooccurence:688 |
Rv1936 |
monooxygenase | 623 | 624 ctx | cooccurence:620 |
Rv0133 |
GCN5-like N-acetyltransferase | 571 | 571 ctx | neighborhood:557 |
Rv0134 ephF |
epoxide hydrolase EphF | 454 | 454 |
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: F420-dependent hydroxymycolic acid dehydrogenase
- Pfam (hmmscan --cut_ga): Bac_luciferase PF00296.27 (E=2e-54)
- (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_214646.1)
- 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 P96809 (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 —
23 functional partner(s); context anchor
Rv0044c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000143|Rv0132c|fgd2 MTGISRRTFGLAAGFGAIGAGGLGGGCSTRSGPTPTPEPASRGVGVVLSHEQFRTDRLVAHAQAAEQAGFRYVWASDHLQPWQDNEGHSMFPWLTLALVGNSTSSILFGTGVTCPIYRYHPATVAQAFASLAILNPGRVFLGLGTGERLNEQAATDTFGNYRERHDRLIEAIVLIRQLWSGERISFTGHYFRTDELKLYDTPAMPPPIFVAASGPQSATLAGRYGDGWIAQARDINDAKLLAAFAAGAQAAGRDPTTLGKRAELFAVVGDDKAAARAADLWRFTAGAVDQPNPVEIQRAAESNPIEKVLANWAVGTDPGVHIGAVQAVLDAGAVPFLHFPQDDPITAIDFYRTNVLPELR