Rv3083 Resolved · high auto-curated

H37Rv Rv3083 · MTBC0 mtbc0_003277 · 495 aa · 3469868–3471355 (+) · RefSeq NP_217599.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)FAD-containing monooxygenase MymA
MTBC0 PGAP re-annotationNAD(P)/FAD-dependent oxidoreductase
Revised (this work)NAD(P)/FAD-dependent oxidoreductase. Pfam: Pyr_redox_2 (PF07992.21), NAD_binding_8 (PF13450.13), FMO-like (PF00743.26), 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 P9WNF7 SwissProt · reviewed · Evidence at protein level
UniProt namePutative FAD-containing monooxygenase MymA
EC (curated) EC 1.14.13.-
Curated functionRequired for maintaining the appropriate mycolic acid composition and permeability of the envelope on its exposure to acidic pH.

UniProt still lists this protein as Putative FAD-containing monooxygenase MymA; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred nameethA
eggNOG descriptionL-lysine 6-monooxygenase (NADPH-requiring)
Orthologous groupCOG2072
KEGG orthology K10215
KEGG pathways map00627, map01120
Gene Ontology (19) GO:0005575, GO:0005618, GO:0005623, GO:0008150, GO:0009268, GO:0009628, GO:0010447, GO:0030312, GO:0040007, GO:0044110, GO:0044116, GO:0044117 +7 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 0.535 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 9 synonymous, 15 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
Pyr_redox_2PF07992.21 9.9e-085–216 Pyridine nucleotide-disulphide oxidoreductase
NAD_binding_8PF13450.13 3.3e-079–62 NAD(P)-binding Rossmann-like domain
FMO-likePF00743.26 1.9e-1376–349 Flavin-binding monooxygenase-like
Lys_Orn_oxgnasePF13434.13 4.0e-0594–216 L-lysine 6-monooxygenase/L-ornithine 5-monooxygenase

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

Closest characterised functional partner: sadH (oxidoreductase SadH), high confidence from genomic context alone (score 989 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3085 sadH oxidoreductase SadH 997 989 ctx neighborhood:882 coexpression:860 textmining:803
Rv3084 lipR acetyl-hydrolase LipR 994 984 ctx neighborhood:882 coexpression:869 textmining:660
Rv3086 adhD alcohol dehydrogenase D 982 962 ctx neighborhood:721 coexpression:869 textmining:561
Rv3088 tgs4 diacyglycerol O-acyltransferase 990 951 ctx neighborhood:616 coexpression:860 textmining:803
Rv3089 fadD13 long chain-fatty-acid--CoA ligase FadD13 989 945 ctx neighborhood:616 coexpression:862 textmining:809
Rv3087 diacyglycerol O-acyltransferase 987 940 ctx neighborhood:590 coexpression:860 textmining:803
Rv3854c ethA monooxygenase EthA 906 905 database:900
Rv0233 nrdB ribonucleoside-diphosphate reductase subunit beta NrdB 733 733 coexpression:733
Rv3082c virS HTH-type transcriptional regulator VirS 931 659 ctx neighborhood:602 textmining:807
Rv0943c monooxygenase 608 608 ctx cooccurence:608
Rv1308 atpA ATP synthase subunit alpha 437 437 experimental:427
Rv1507c hyp hypothetical protein 412 413
Rv1309 atpG ATP synthase subunit gamma 411 412
Rv3456c rplQ 50S ribosomal protein L17 408 409
Rv1310 atpD ATP synthase subunit beta 403 404

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: FAD-containing monooxygenase MymA
  • MTBC0 PGAP product: NAD(P)/FAD-dependent oxidoreductase
  • Pfam (hmmscan --cut_ga): Pyr_redox_2 PF07992.21 (E=1e-07), NAD_binding_8 PF13450.13 (E=3e-07), FMO-like PF00743.26 (E=2e-13), Lys_Orn_oxgnase PF13434.13 (E=4e-05)
  • (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_217599.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Pyr_redox_2 (PF07992.21), NAD_binding_8 (PF13450.13), FMO-like (PF00743.26), 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 P9WNF7 (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 sadH
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003277|Rv3083|
MNQHFDVLIIGAGLSGIGTACHVTAEFPDKTIALLERRERLGGTWDLFRYPGVRSDSDMFTFGYKFRPWRDVKVLADGASIRQYIADTATEFGVDEKIHYGLKVNTAEWSSRQCRWTVAGVHEATGETRTYTCDYLISCTGYYNYDAGYLPDFPGVHRFGGRCVHPQHWPEDLDYSGKKVVVIGSGATAVTLVPAMAGSNPGSAAHVTMLQRSPSYIFSLPAVDKISEVLGRFLPDRWVYEFGRRRNIAIQRKLYQACRRWPKLMRRLLLWEVRRRLGRSVDMSNFTPNYLPWDERLCAVPNGDLFKTLASGAASVVTDQIETFTEKGILCKSGREIEADIIVTATGLNIQMLGGMRLIVDGAEYQLPEKMTYKGVLLENAPNLAWIIGYTNASWTLKSDIAGAYLCRLLRHMADNGYTVATPRDAQDCALDVGMFDQLNSGYVKRGQDIMPRQGSKHPWRVLMHYEKDAKILLEDPIDDGVLHFAAAAQDHAAA