Rv0565c Resolved · high auto-curated
H37Rv Rv0565c · MTBC0 mtbc0_000594 ·
486 aa · 659561–661021 (-) ·
RefSeq NP_215079.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | monooxygenase |
|---|---|
| MTBC0 PGAP re-annotation | NAD(P)/FAD-dependent oxidoreductase |
| Revised (this work) | NAD(P)/FAD-dependent oxidoreductase. Pfam: Thi4 (PF01946.24), Pyr_redox_2 (PF07992.21), FMO-like (PF00743.26), Pyr_redox_3 (PF13738.13), NAD_binding_8 (PF13450.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53762
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable monooxygenase |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
P Inorganic ion transport and metabolism
|
|---|---|
| Preferred name | ethA |
| eggNOG description | Flavoprotein involved in K transport |
| Orthologous group | COG2072 |
| KEGG orthology |
K10215
|
| KEGG pathways |
map00627, map01120
|
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) pseudogene candidate
| pN/pS | 0.473 · purifying |
|---|---|
| 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 1.38% of strains (1999) · 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
Thi4 | PF01946.24 | 3.6e-07 | 10–50 | Thi4 family |
Pyr_redox_2 | PF07992.21 | 2.7e-06 | 11–219 | Pyridine nucleotide-disulphide oxidoreductase |
FMO-like | PF00743.26 | 8.1e-16 | 12–225 | Flavin-binding monooxygenase-like |
Pyr_redox_3 | PF13738.13 | 2.8e-10 | 13–223 | Pyridine nucleotide-disulphide oxidoreductase |
NAD_binding_8 | PF13450.13 | 1.0e-08 | 14–67 | NAD(P)-binding Rossmann-like domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: gpdA1 (glycerol-3-phosphate dehydrogenase), high confidence from genomic context alone (score 807 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0566c hyp |
hypothetical protein | 934 | 934 ctx | neighborhood:788 coexpression:703 |
Rv0564c gpdA1 |
glycerol-3-phosphate dehydrogenase | 812 | 807 ctx | neighborhood:802 |
Rv0943c |
monooxygenase | 582 | 582 ctx | cooccurence:580 |
Rv1308 atpA |
ATP synthase subunit alpha | 437 | 438 | experimental:427 |
Rv1507c hyp |
hypothetical protein | 412 | 413 | |
Rv1309 atpG |
ATP synthase subunit gamma | 412 | 413 | |
Rv3456c rplQ |
50S ribosomal protein L17 | 407 | 407 | |
Rv1310 atpD |
ATP synthase subunit beta | 404 | 404 | |
Rv3846 sodA |
superoxide dismutase | 411 | 402 | |
Rv0363c fba |
fructose-bisphosphate aldolase | 414 | 392 | |
Rv0682 rpsL |
30S ribosomal protein S12 | 493 | 349 | |
Rv1393c |
monoxygenase | 436 | 309 | |
Rv3855 ethR |
HTH-type transcriptional repressor EthR | 438 | 249 | |
Rv1483 fabG1 |
3-oxoacyl-ACP reductase FabG | 490 | 127 | textmining:440 |
Rv2043c pncA |
pyrazinamidase/nicotinamidase PncA | 428 | 126 |
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): Thi4 PF01946.24 (E=4e-07), Pyr_redox_2 PF07992.21 (E=3e-06), FMO-like PF00743.26 (E=8e-16), Pyr_redox_3 PF13738.13 (E=3e-10), NAD_binding_8 PF13450.13 (E=1e-08)
- (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_215079.1)
- Domains: Pfam-A via hmmscan --cut_ga — Thi4 (PF01946.24), Pyr_redox_2 (PF07992.21), FMO-like (PF00743.26), Pyr_redox_3 (PF13738.13), NAD_binding_8 (PF13450.13)
- 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 O53762 (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 —
24 functional partner(s); context anchor
gpdA1 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000594|Rv0565c| MSVTPNAGCVDVVIVGAGISGLGAAYRIIERNPQLTYTILERRARIGGTWDLFRYPGVRSDSSIFTLSFPYEPWTREEGIADGAHIREYLTDMAHKYGIDRHIEFNSYVRAADWDSSTDTWTVTFEQNGVHKHYRSRFVFFGSGYYNYDEGYTPDFGGIEKFGGAVVHPQHWPEDLDYTGKKIVVIGSGATAVTLIPSLTDRAEKVTMLQRSPTYLISASKYSTFAAVVRKALPPKTSHLIVRMYNALLEAVFWFLSRKTPVFVKWLLRRTAIKNLPEGYDIETHFTPRYNPWDQRLCLIPDADLYNAITSGRAEVVTDHIDHFDATGIALKSGGHLDADIIVTATGLQLQALGGAAISLDGVEIDPRDRFVYKAHMLEDVPNLFWCVGYTNASWTLRADMTARATAKLLAHMAAHGHTRAAPHLGDEPMDEKPSWDIQAGYVKRAPYALPKSGTKRPWNVRQNYLADAIDYRFDRIEEAMVFGAA