Rv3359 Resolved · high auto-curated

H37Rv Rv3359 · MTBC0 mtbc0_003574 · 396 aa · 3798052–3799242 (+) · RefSeq NP_217876.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)oxidoreductase
MTBC0 PGAP re-annotationNADH:flavin oxidoreductase
Revised (this work)NADH:flavin oxidoreductase. Pfam: Oxidored_FMN (PF00724.27).

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

Curated reference (UniProt)

UniProt O50388 TrEMBL · unreviewed · Evidence at protein level
UniProt namePossible oxidoreductase

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
eggNOG descriptionNADH flavin oxidoreductase
Orthologous groupCOG1902
EC number EC 1.8.1.20
KEGG orthology K22347

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 0.351 · purifying
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 3 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
Oxidored_FMNPF00724.27 1.0e-4211–248 NADH:flavin oxidoreductase / NADH oxidase family

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

Closest characterised functional partner: folD (bifunctional methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase), high confidence from genomic context alone (score 739 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3356c folD bifunctional methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase 754 739 ctx neighborhood:738
Rv3355c integral membrane protein 739 739 ctx neighborhood:738
Rv3358 relK toxin RelK 666 666 ctx neighborhood:661
Rv3357 relJ antitoxin RelJ 665 664 ctx neighborhood:661
Rv0310c hyp hypothetical protein 596 575 ctx cooccurence:512
Rv3169 hyp hypothetical protein 564 565 ctx cooccurence:561
Rv1747 ABC transporter ATP-binding protein/permease 558 536 ctx neighborhood:536
Rv3029c fixA electron transfer flavoprotein subunit beta 545 517 experimental:484
Rv3360 hyp hypothetical protein 509 509 ctx neighborhood:506
Rv0770 oxidoreductase 491 492
Rv3552 CoA-transferase subunit beta 483 481 ctx cooccurence:470
Rv3168 aminoglycoside phosphotransferase 457 457 ctx cooccurence:415
Rv0771 4-carboxymuconolactone decarboxylase 475 454 ctx cooccurence:438
Rv3028c fixB electron transfer flavoprotein subunit alpha 496 452 experimental:431
Rv1162 narH nitrate reductase subunit beta 451 452 experimental:449

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: oxidoreductase
  • MTBC0 PGAP product: NADH:flavin oxidoreductase
  • Pfam (hmmscan --cut_ga): Oxidored_FMN PF00724.27 (E=1e-42)
  • (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_217876.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Oxidored_FMN (PF00724.27)
  • 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 COG1902
  • Curated reference: UniProt O50388 (TrEMBL, unreviewed; 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 — 19 functional partner(s); context anchor folD
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003574|Rv3359|
MAPGSCEAPDVFNPAKLGPLTLRNRVIKAATFEARTPDALVTDDLIEYHRLPAAGGVAMTTVAYCAVSPGGRTGGNQIWMRPHAVPGLRRLTEAIHAEGAAISAQIGHAGPVADARSNQATALAPVRFFNPIAMRFAQKATREDIDDVLAAHAHAARLAVDAGFDAVEIHLGHNYLASAFLSPLLNRRDDEFGGSLQNRAKVARGLVMAVRRAVRQQVAVTAKLNMTDGIRGGITVDEALTTARWLQDDGGLDAIELTAGSSLVNPMYLFRGDAPVKEFAAAFKPPLRWGIRMTGHRFFREYPYRDAYLLREARLFRAELTIPLILLGGITNRTTMDLAMAEGFEFVAMARALLAEPDLVNRIAAEGSQVRSACTHCNQCMATIYRRTHCVVTGAP