ddn Resolved · high auto-curated
H37Rv Rv3547 · MTBC0 mtbc0_003764 ·
151 aa · 4010521–4010976 (+) ·
RefSeq NP_218064.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | deazaflavin-dependent nitroreductase |
|---|---|
| MTBC0 PGAP re-annotation | deazaflavin-dependent nitroreductase Ddn |
| Revised (this work) | Deazaflavin-dependent nitroreductase Ddn. Pfam: F420H2_quin_red (PF04075.21). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WP15
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Deazaflavin-dependent nitroreductase |
| EC (curated) |
EC 1.-.-.-, EC 1.1.98.-
|
| Curated function | Involved in a F420-dependent anti-oxidant mechanism that protects M.tuberculosis against oxidative stress and bactericidal agents. Catalyzes the F420H(2)-dependent two-electron reduction of quinones to dihydroquinones, thereby preventing the formation of cytotoxic semiquinones obtained by the one-electron reduction pathway. In vitro, catalyzes the reduction of both benzoquinone and naphthoquinone analogs; since menaquinone is the sole quinone electron carrier in the respiratory chain in M.tuberculosis, the physiological electron acceptor for Fqr-mediated F420H(2) oxidation is therefore likely . |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
P Inorganic ion transport and metabolism
|
|---|---|
| Preferred name | ddn |
| eggNOG description | F420H(2)-dependent quinone reductase |
| Orthologous group | COG0748 |
| Gene Ontology (24) |
GO:0003674, GO:0005488, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0008150, GO:0008152, GO:0016020, GO:0030312, GO:0031406, GO:0036094 +12 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 | 0.203 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
F420H2_quin_red | PF04075.21 | 5.1e-58 | 22–151 | F420H(2)-dependent quinone reductase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: fadA5 (acetyl-CoA acetyltransferase FadA), high confidence from genomic context alone (score 778 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3546 fadA5 |
acetyl-CoA acetyltransferase FadA | 802 | 778 ctx | neighborhood:766 |
Rv3261 fbiA |
2-phospho-L-lactate transferase | 976 | 768 ctx | cooccurence:762 textmining:903 |
Rv3520c |
coenzyme F420-dependent oxidoreductase | 781 | 768 ctx | cooccurence:768 |
Rv0044c |
oxidoreductase | 775 | 761 ctx | cooccurence:761 |
Rv0407 fgd1 |
F420-dependent glucose-6-phosphate dehydrogenase | 983 | 745 ctx | cooccurence:745 textmining:936 |
Rv3262 fbiB |
coenzyme F420:L-glutamate ligase | 974 | 745 ctx | cooccurence:737 textmining:903 |
Rv2983 cofC |
2-phospho-L-lactate guanylyltransferase | 902 | 731 ctx | cooccurence:723 textmining:651 |
Rv0132c fgd2 |
F420-dependent glucose-6-phosphate dehydrogenase | 889 | 731 ctx | cooccurence:731 textmining:605 |
Rv1855c |
oxidoreductase | 730 | 713 ctx | cooccurence:713 |
Rv3093c |
oxidoreductase | 730 | 713 ctx | cooccurence:713 |
Rv2951c |
phthiodiolone/phenolphthiodiolone dimycocerosates ketoreductase | 720 | 703 ctx | cooccurence:702 |
Rv1360 |
oxidoreductase | 710 | 692 ctx | cooccurence:692 |
Rv0791c hyp |
hypothetical protein | 660 | 639 ctx | cooccurence:637 |
Rv0331 |
dehydrogenase/reductase | 651 | 636 | database:583 |
Rv3072c hyp |
hypothetical protein | 636 | 613 ctx | cooccurence:613 |
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: deazaflavin-dependent nitroreductase
- MTBC0 PGAP product: deazaflavin-dependent nitroreductase Ddn
- Pfam (hmmscan --cut_ga): F420H2_quin_red PF04075.21 (E=5e-58)
- (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_218064.1)
- Domains: Pfam-A via hmmscan --cut_ga — F420H2_quin_red (PF04075.21)
- 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
COG0748 - Curated reference: UniProt P9WP15 (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 —
46 functional partner(s); context anchor
fadA5 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003764|Rv3547|ddn MPKSPPRFLNSPLSDFFIKWMSRINTWMYRRNDGEGLGGTFQKIPVALLTTTGRKTGQPRVNPLYFLRDGGRVIVAASKGGAEKNPMWYLNLKANPKVQVQIKKEVLDLTARDATDEERAEYWPQLVTMYPSYQDYQSWTDRTIPIVVCEP