Rv3049c Resolved · high auto-curated

H37Rv Rv3049c · MTBC0 mtbc0_003241 · 524 aa · 3430819–3432393 (-) · RefSeq NP_217565.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)monooxygenase
MTBC0 PGAP re-annotationNAD(P)/FAD-dependent oxidoreductase
Revised (this work)NAD(P)/FAD-dependent oxidoreductase. Pfam: FMO-like (PF00743.26), Pyr_redox_3 (PF13738.13), NAD_binding_8 (PF13450.13), Lys_Orn_oxgnase (PF13434.13).

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

Curated reference (UniProt)

UniProt I6Y2E2 TrEMBL · unreviewed · Evidence at protein level
UniProt nameBaeyer-Villiger monooxygenase
Curated functionCatalyzes a Baeyer-Villiger oxidation reaction, i.e. the insertion of an oxygen atom into a carbon-carbon bond adjacent to a carbonyl, which converts ketones to esters or lactones using NADPH and/or NADH as an electron donor. Thus, can convert bicyclo[3.2.0]hept-2-en-6-one into the oxidative lactone products 2-oxabicyclo[3.3.0]oct-6-en-3-one and 3-oxabicyclo[3.3.0]oct-6-en-2-one. Is also able to catalyze the sulfoxidation of methyl phenyl sulfide (thioanisole).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category P Inorganic ion transport and metabolism
eggNOG descriptionFlavoprotein involved in K transport
Orthologous groupCOG2072

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 0.403 · purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 5 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.15% of strains (219) · 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
FMO-likePF00743.26 3.7e-1524–229 Flavin-binding monooxygenase-like
Pyr_redox_3PF13738.13 1.7e-1426–228 Pyridine nucleotide-disulphide oxidoreductase
NAD_binding_8PF13450.13 7.3e-1427–94 NAD(P)-binding Rossmann-like domain
Lys_Orn_oxgnasePF13434.13 1.7e-04111–215 L-lysine 6-monooxygenase/L-ornithine 5-monooxygenase

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

Closest characterised functional partner: Rv3050c (AsnC family transcriptional regulator), high confidence from genomic context alone (score 761 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3050c AsnC family transcriptional regulator 760 761 ctx neighborhood:757
Rv3048c nrdF2 ribonucleoside-diphosphate reductase subunit beta NrdF2 722 723 ctx neighborhood:719
Rv3052c nrdI NrdI protein 621 621 ctx neighborhood:619
Rv1245c short-chain type dehydrogenase/reductase 503 504 ctx cooccurence:445
Rv3085 sadH oxidoreductase SadH 459 459 ctx cooccurence:400
Rv3741c oxidoreductase 449 449 ctx cooccurence:441
Rv0860 fadB fatty oxidation protein FadB 567 444
Rv3742c oxidoreductase 441 441 ctx cooccurence:434
Rv1308 atpA ATP synthase subunit alpha 437 437 experimental:427
Rv1507c hyp hypothetical protein 414 415
Rv3097c lipY triacylglycerol lipase Lip 416 413
Rv1834 lipZ hydrolase 413 413
Rv3456c rplQ 50S ribosomal protein L17 412 413
Rv1309 atpG ATP synthase subunit gamma 412 413
Rv1310 atpD ATP synthase subunit beta 407 407

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: monooxygenase
  • MTBC0 PGAP product: NAD(P)/FAD-dependent oxidoreductase
  • Pfam (hmmscan --cut_ga): FMO-like PF00743.26 (E=4e-15), Pyr_redox_3 PF13738.13 (E=2e-14), NAD_binding_8 PF13450.13 (E=7e-14), Lys_Orn_oxgnase PF13434.13 (E=2e-04)
  • (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_217565.1)
  • Domains: Pfam-A via hmmscan --cut_ga — FMO-like (PF00743.26), Pyr_redox_3 (PF13738.13), NAD_binding_8 (PF13450.13), Lys_Orn_oxgnase (PF13434.13)
  • 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 COG2072
  • Curated reference: UniProt I6Y2E2 (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 — 27 functional partner(s); context anchor Rv3050c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003241|Rv3049c|
MSIADTAAKPSTPSPANQPPVRTRAVIIGTGFSGLGMAIALQKQGVDFVILEKADDVGGTWRDNTYPGCACDIPSHLYSFSFEPKADWKHLFSYWDEILGYLKGVTDKYGLRRYIEFNSLVDRGYWDDDECRWHVFTADGREYVAQFLISGAGALHIPSFPEIAGRDEFAGPAFHSAQWDHSIDLTGKRVAIVGTGASAIQIVPEIVGQVAELQLYQRTPPWVVPRTNEELPVSLRRALRTVPGLRALLRLGIYWAQEALAYGMTKRPNTLKIIEAYAKYNIRRSVKDRELRRKLTPRYRIGCKRILNSSTYYPAVADPKTELITDRIDRITHDGIVTADGTGREVFREADVIVYATGFHVTDSYTYVQIKGRHGEDLVDRWNREGIGAHRGITVANMPNLFFLLGPNTGLGHNSVVFMIESQIHYVADAIAKCDRMGVQALAPTREAQDRFNQELQRRLAGSVWNSGGCRSWYLDEHGKNTVLWCGYTWQYWLTTRSVNPAEYRFFGIGNGLSSDRATVAAAN