Rv3727 Resolved · high auto-curated
H37Rv Rv3727 · MTBC0 mtbc0_003952 ·
602 aa · 4197076–4198884 (+) ·
RefSeq NP_218244.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | oxidoreductase |
|---|---|
| MTBC0 PGAP re-annotation | FAD-dependent oxidoreductase |
| Revised (this work) | FAD-dependent oxidoreductase. Pfam: FAD_binding_3 (PF01494.26), DAO (PF01266.31), FAD_binding_2 (PF00890.31), NAD_binding_8 (PF13450.13), Amino_oxidase (PF01593.31). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O69694
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | Possible oxidoreductase |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| eggNOG description | Flavin containing amine oxidoreductase |
| Orthologous group | COG1233 |
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 | 0.397 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 7 synonymous, 8 missense, 0 nonsense, 3 frameshift |
| Disruption | 3 distinct premature-stop/frameshift site(s); most common in 0.46% of strains (662) · 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 |
|---|---|---|---|---|
FAD_binding_3 | PF01494.26 | 1.4e-05 | 7–48 | FAD binding domain |
DAO | PF01266.31 | 5.5e-07 | 9–44 | FAD dependent oxidoreductase |
FAD_binding_2 | PF00890.31 | 2.7e-04 | 9–45 | FAD binding domain |
NAD_binding_8 | PF13450.13 | 6.2e-10 | 12–76 | NAD(P)-binding Rossmann-like domain |
Amino_oxidase | PF01593.31 | 8.6e-16 | 17–322 | Flavin containing amine oxidoreductase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: PPE8 (PPE family protein PPE8), high confidence from genomic context alone (score 768 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0355c PPE8 |
PPE family protein PPE8 | 767 | 768 ctx | cooccurence:765 |
Rv1004c |
membrane protein | 763 | 764 ctx | cooccurence:760 |
Rv3347c PPE55 |
PPE family protein PPE55 | 763 | 763 ctx | cooccurence:762 |
Rv0304c PPE5 |
PPE family protein PPE5 | 763 | 763 ctx | cooccurence:760 |
Rv0341 iniB |
isoniazid inducible protein IniB | 808 | 762 ctx | cooccurence:761 |
Rv2209 |
integral membrane protein | 762 | 762 ctx | cooccurence:761 |
Rv3350c PPE56 |
PPE family protein PPE56 | 762 | 762 ctx | cooccurence:761 |
Rv1452c PE_PGRS28 |
PE-PGRS family protein PE_PGRS28 | 760 | 760 ctx | cooccurence:760 |
Rv1917c PPE34 |
PPE family protein PPE34 | 759 | 759 ctx | cooccurence:747 |
Rv2490c PE_PGRS43 |
PE-PGRS family protein PE_PGRS43 | 758 | 758 ctx | cooccurence:758 |
Rv3879c espK |
ESX-1 secretion-associated protein EspK | 758 | 758 ctx | cooccurence:758 |
Rv2954c hyp |
hypothetical protein | 753 | 753 ctx | cooccurence:750 |
Rv1651c PE_PGRS30 |
PE-PGRS family protein PE_PGRS30 | 751 | 751 ctx | cooccurence:751 |
Rv3343c PPE54 |
PPE family protein PPE54 | 749 | 749 ctx | cooccurence:746 |
Rv0894 |
transcriptional regulator | 746 | 746 | coexpression:746 |
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: FAD-dependent oxidoreductase
- Pfam (hmmscan --cut_ga): FAD_binding_3 PF01494.26 (E=1e-05), DAO PF01266.31 (E=6e-07), FAD_binding_2 PF00890.31 (E=3e-04), NAD_binding_8 PF13450.13 (E=6e-10), Amino_oxidase PF01593.31 (E=9e-16)
- (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_218244.1)
- Domains: Pfam-A via hmmscan --cut_ga — FAD_binding_3 (PF01494.26), DAO (PF01266.31), FAD_binding_2 (PF00890.31), NAD_binding_8 (PF13450.13), Amino_oxidase (PF01593.31)
- 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
COG1233 - Curated reference: UniProt O69694 (TrEMBL, unreviewed; Predicted)
- 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 —
111 functional partner(s); context anchor
PPE8 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003952|Rv3727| MKPSPADTHVVIAGAGIAGLAAAMILAEAGVRVTLCEAASEAGGKAKSLRLADGHPTEHSLRVYTDTYQTLLTLFSRIPTEHDRTVLDNLVGVSMVSATAQGVIGRIAAPVALQRRRPTFARIIGKVVEPPRQLVRILLRGPMVIVGLAQRGVPATDVLHYLYAHLRLLWMCRERLLAELGDISYADYLQLGCKSAQAQEFFSAVPRIYVAARTSAEAAAIAPIVLKGLFRLKSNCPSALNDAKLPAIMMMDGPTSERMVDPWIRHLTRLGVDIHFNTRVGDLEFDDGRVTALISSDGRRFACDYALLAVPYLTLRELAKSAHVKRYLPQLTQQHALALEASNGIQCFLRDLPATWPPFIRPGVVTTHLQSQWSLVCVLQGEGFWKNVRLPEGTRYVLSITWSDVETPGPVFDRPLSECTPDEILTECLTQCGLDKSNVLGWRIDHELKHLDEAEYEKVASELPPHLVSAPARGQRMVNFSPLTVLMPGARHRSPGICTSVPNLLLAGEVIYSPDLTLFVPTMEKAACSGYLAARQIMNMVASHAAPLRIDFRDPAPFAVLRRVDRWFWSRRRRPPDRSTFATPPTAMPAPSHLTDVDRSAS