Rv1558 Resolved · high auto-curated
H37Rv Rv1558 · MTBC0 mtbc0_001666 ·
148 aa · 1774911–1775357 (+) ·
RefSeq NP_216074.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | F420H(2)-dependent quinone reductase |
| Revised (this work) | F420H(2)-dependent quinone reductase. 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 |
P9WP11
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | F420H(2)-dependent quinone reductase Rv1558 |
| EC (curated) |
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 menadione to menadiol; 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 to be the endogenous me. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|---|
| eggNOG description | nitroreductase |
| Orthologous group | COG1846 |
| 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 | 0.107 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 1 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.19% of strains (270) · 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 |
|---|---|---|---|---|
F420H2_quin_red | PF04075.21 | 5.9e-58 | 14–143 | F420H(2)-dependent quinone reductase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mmpL6 (transmembrane transport protein MmpL6), high confidence from genomic context alone (score 868 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1557 mmpL6 |
transmembrane transport protein MmpL6 | 868 | 868 ctx | neighborhood:867 |
Rv1559 ilvA |
threonine dehydratase IlvA | 841 | 835 ctx | neighborhood:830 |
Rv0044c |
oxidoreductase | 768 | 759 ctx | cooccurence:758 |
Rv3261 fbiA |
2-phospho-L-lactate transferase | 835 | 751 ctx | cooccurence:747 |
Rv0407 fgd1 |
F420-dependent glucose-6-phosphate dehydrogenase | 949 | 745 ctx | cooccurence:745 textmining:812 |
Rv3520c |
coenzyme F420-dependent oxidoreductase | 750 | 741 ctx | cooccurence:738 |
Rv3262 fbiB |
coenzyme F420:L-glutamate ligase | 812 | 717 ctx | cooccurence:707 |
Rv2983 cofC |
2-phospho-L-lactate guanylyltransferase | 773 | 702 ctx | cooccurence:694 |
Rv0132c fgd2 |
F420-dependent glucose-6-phosphate dehydrogenase | 704 | 693 ctx | cooccurence:693 |
Rv1855c |
oxidoreductase | 696 | 685 ctx | cooccurence:682 |
Rv2951c |
phthiodiolone/phenolphthiodiolone dimycocerosates ketoreductase | 744 | 665 ctx | cooccurence:662 |
Rv3204 |
DNA-methyltransferase | 656 | 656 ctx | fusion:656 |
Rv0331 |
dehydrogenase/reductase | 651 | 636 | database:583 |
Rv3093c |
oxidoreductase | 633 | 619 ctx | cooccurence:619 |
Rv1561 vapC11 |
ribonuclease VapC11 | 566 | 566 ctx | neighborhood:563 |
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: hypothetical protein
- MTBC0 PGAP product: F420H(2)-dependent quinone reductase
- Pfam (hmmscan --cut_ga): F420H2_quin_red PF04075.21 (E=6e-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_216074.1)
- 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
COG1846 - Curated reference: UniProt P9WP11 (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 —
35 functional partner(s); context anchor
mmpL6 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001666|Rv1558| MPLSGEYAPSPLDWSREQADTYMKSGGTEGTQLQGKPVILLTTVGAKTGKLRKTPLMRVEHDGQYAIVASLGGAPKNPVWYHNVVKNPRVELQDGTVTGDYDAREVFGDEKAIWWQRAVAVWPDYASYQTKTDRQIPVFVLTPVRAGG