Rv3520c Resolved · high auto-curated

H37Rv Rv3520c · MTBC0 - · 347 aa · 3956325–3957368 (-) · RefSeq NP_218037.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)coenzyme F420-dependent oxidoreductase
MTBC0 PGAP re-annotation
Revised (this work)Coenzyme F420-dependent oxidoreductase. 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.

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt O53565 SwissProt · reviewed · Evidence at protein level
UniProt namePutative coenzyme F420-dependent oxidoreductase Rv3520c
EC (curated) EC 1.-.-.-

UniProt still lists this protein as Putative coenzyme F420-dependent oxidoreductase Rv3520c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
eggNOG descriptionF420-dependent oxidoreductase
Orthologous groupCOG2141
Gene Ontology (8) GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0016020, GO:0030312, 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 0.509 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 6 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.13% of strains (188) · 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)

PfamAccessioni-EvalueResiduesDescription
Bac_luciferasePF00296.27 6.1e-7217–328 Luciferase-like monooxygenase

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

Closest characterised functional partner: Rv0940c (oxidoreductase), high confidence from genomic context alone (score 870 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0940c oxidoreductase 870 870 ctx neighborhood:544 cooccurence:726
Rv3521 hyp hypothetical protein 986 822 ctx neighborhood:771 textmining:928
Rv3522 ltp4 lipid transfer protein 943 815 ctx neighborhood:760 textmining:705
Rv3523 ltp3 lipid carrier protein 953 790 ctx neighborhood:748 textmining:787
Rv3262 fbiB coenzyme F420:L-glutamate ligase 786 773 ctx cooccurence:742
Rv3547 ddn deazaflavin-dependent nitroreductase 781 768 ctx cooccurence:768
Rv3178 nitroreductase 773 760 ctx cooccurence:758
Rv1261c hyp hypothetical protein 759 760 ctx cooccurence:758
Rv3261 fbiA 2-phospho-L-lactate transferase 763 750 ctx cooccurence:741
Rv1558 hyp hypothetical protein 750 741 ctx cooccurence:738
Rv1855c oxidoreductase 728 729 ctx cooccurence:716
Rv0132c fgd2 F420-dependent glucose-6-phosphate dehydrogenase 727 727 ctx cooccurence:726
Rv2893 oxidoreductase 734 724 ctx cooccurence:724
Rv2161c hyp hypothetical protein 719 720 ctx cooccurence:709
Rv0953c oxidoreductase 633 633 ctx cooccurence:633

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): coenzyme F420-dependent oxidoreductase
  • Pfam (hmmscan --cut_ga): Bac_luciferase PF00296.27 (E=6e-72)
  • (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_218037.1)
  • 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 O53565 (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 — 27 functional partner(s); context anchor Rv0940c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3520c|
MEAGMKLGLQLGYWGAQPPQNHAELVAAAEDAGFDTVFTAEAWGSDAYTPLAWWGSSTQRVRLGTSVIQLSARTPTACAMAALTLDHLSGGRHILGLGVSGPQVVEGWYGQRFPKPLARTREYIDIVRQVWARESPVTSAGPHYRLPLTGEGTTGLGKALKPITHPLRADIPIMLGAEGPKNVALAAEICDGWLPIFYSPRMAGMYNEWLDEGFARPGARRSREDFEICATAQVVITDDRAAAFAGIKPFLALYMGGMGAEETNFHADVYRRMGYTQVVDEVTKLFRSGRKDEAAEIIPDELVDDAVIVGDIDHVRKQMAVWEAAGVTMMVVTAGSAEQVRDLAALV