ethA Resolved · high auto-curated
H37Rv Rv3854c · MTBC0 mtbc0_004087 ·
489 aa · 4350114–4351583 (-) ·
RefSeq NP_218371.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | monooxygenase EthA |
|---|---|
| MTBC0 PGAP re-annotation | FAD-containing monooxygenase EthA |
| Revised (this work) | FAD-containing monooxygenase EthA. Pfam: Pyr_redox_2 (PF07992.21), Pyr_redox_3 (PF13738.13), NAD_binding_8 (PF13450.13), FMO-like (PF00743.26). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WNF9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | FAD-containing monooxygenase EthA |
| EC (curated) |
EC 1.14.13.-
|
| Curated function | Monooxygenase able to convert a wide range of ketones to the corresponding esters or lactones via a Baeyer-Villiger oxidation reaction. Can act on long-chain aliphatic ketones (2-hexanone to 2-dodecanone) and on aromatic ketones (phenylacetone and benzylacetone). Is also able to catalyze enantioselective sulfoxidation of methyl-p-tolylsulfide. In vivo, likely functions as a BVMO, but the exact nature of the physiological substrate(s) remains to be established..; FUNCTION: Is responsible for the activation of several thiocarbamide-containing pro-drugs into cytotoxic species. Thus, catalyzes the. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
P Inorganic ion transport and metabolism
|
|---|---|
| Preferred name | ethA |
| eggNOG description | monooxygenase EthA |
| Orthologous group | COG2072 |
| KEGG orthology |
K10215
|
| KEGG pathways |
map00627, map01120
|
| Gene Ontology (42) |
GO:0000166, GO:0003674, GO:0003824, GO:0004497, GO:0004499, GO:0005488, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829 +30 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 | 0.73 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 14 missense, 0 nonsense, 7 frameshift |
| Disruption | 7 distinct premature-stop/frameshift site(s); most common in 0.58% of strains (841) · convergent |
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 |
|---|---|---|---|---|
Pyr_redox_2 | PF07992.21 | 3.1e-06 | 6–212 | Pyridine nucleotide-disulphide oxidoreductase |
Pyr_redox_3 | PF13738.13 | 1.2e-07 | 8–211 | Pyridine nucleotide-disulphide oxidoreductase |
NAD_binding_8 | PF13450.13 | 3.1e-08 | 9–57 | NAD(P)-binding Rossmann-like domain |
FMO-like | PF00743.26 | 1.3e-11 | 80–346 | Flavin-binding monooxygenase-like |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ethR (HTH-type transcriptional repressor EthR), high confidence from genomic context alone (score 709 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3083 mymA |
FAD-containing monooxygenase MymA | 906 | 905 | database:900 |
Rv3855 ethR |
HTH-type transcriptional repressor EthR | 935 | 709 ctx | neighborhood:604 textmining:786 |
Rv0943c |
monooxygenase | 558 | 558 ctx | cooccurence:558 |
Rv1308 atpA |
ATP synthase subunit alpha | 435 | 436 | experimental:427 |
Rv1507c hyp |
hypothetical protein | 412 | 413 | |
Rv1309 atpG |
ATP synthase subunit gamma | 409 | 409 | |
Rv3456c rplQ |
50S ribosomal protein L17 | 407 | 408 | |
Rv1310 atpD |
ATP synthase subunit beta | 401 | 402 | |
Rv3461c rpmJ |
50S ribosomal protein L36 | 401 | 401 | |
Rv3846 sodA |
superoxide dismutase | 405 | 396 | |
Rv0363c fba |
fructose-bisphosphate aldolase | 414 | 391 | |
Rv2373c dnaJ2 |
chaperone protein DnaJ | 406 | 384 | |
Rv0352 dnaJ1 |
chaperone protein DnaJ | 401 | 379 | |
Rv0701 rplC |
50S ribosomal protein L3 | 518 | 351 | |
Rv0682 rpsL |
30S ribosomal protein S12 | 420 | 351 |
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 EthA
- MTBC0 PGAP product: FAD-containing monooxygenase EthA
- Pfam (hmmscan --cut_ga): Pyr_redox_2 PF07992.21 (E=3e-06), Pyr_redox_3 PF13738.13 (E=1e-07), NAD_binding_8 PF13450.13 (E=3e-08), FMO-like PF00743.26 (E=1e-11)
- (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_218371.1)
- Domains: Pfam-A via hmmscan --cut_ga — Pyr_redox_2 (PF07992.21), Pyr_redox_3 (PF13738.13), NAD_binding_8 (PF13450.13), FMO-like (PF00743.26)
- 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 P9WNF9 (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
ethR - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_004087|Rv3854c|ethA MTEHLDVVIVGAGISGVSAAWHLQDRCPTKSYAILEKRESMGGTWDLFRYPGIRSDSDMYTLGFRFRPWTGRQAIADGKPILEYVKSTAAMYGIDRHIRFHHKVISADWSTAENRWTVHIQSHGTLSALTCEFLFLCSGYYNYDEGYSPRFAGSEDFVGPIIHPQHWPEDLDYDAKNIVVIGSGATAVTLVPALADSGAKHVTMLQRSPTYIVSQPDRDGIAEKLNRWLPETMAYTAVRWKNVLRQAAVYSACQKWPRRMRKMFLSLIQRQLPEGYDVRKHFGPHYNPWDQRLCLVPNGDLFRAIRHGKVEVVTDTIERFTATGIRLNSGRELPADIIITATGLNLQLFGGATATIDGQQVDITTTMAYKGMMLSGIPNMAYTVGYTNASWTLKADLVSEFVCRLLNYMDDNGFDTVVVERPGSDVEERPFMEFTPGYVLRSLDELPKQGSRTPWRLNQNYLRDIRLIRRGKIDDEGLRFAKRPAPVGV