aao Resolved · high auto-curated
H37Rv Rv1905c · MTBC0 mtbc0_002020 ·
320 aa · 2169543–2170505 (-) ·
RefSeq NP_216421.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | D-amino acid oxidase |
|---|---|
| MTBC0 PGAP re-annotation | FAD-dependent oxidoreductase |
| Revised (this work) | FAD-dependent oxidoreductase. Pfam: DAO (PF01266.31), FAD_binding_2 (PF00890.31). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WP27
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | D-amino-acid oxidase |
| EC (curated) |
EC 1.4.3.3
|
| Curated function | Catalyzes the oxidative deamination of D-amino acids with broad substrate specificity (By similarity). Enables the organism to utilize D-amino acids as a source of nutrients (By similarity). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | aao |
| eggNOG description | FAD dependent oxidoreductase |
| Orthologous group | COG0665 |
| EC number |
EC 1.4.3.3
|
| KEGG orthology |
K00273
|
| KEGG pathways |
map00260, map00311, map00330, map00472, map01100, map01130, map04146
|
| Gene Ontology (22) |
GO:0003674, GO:0003824, GO:0003884, GO:0006082, GO:0006520, GO:0006807, GO:0008150, GO:0008152, GO:0009987, GO:0016491, GO:0016638, GO:0016641 +10 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 | 1.624 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 8 missense, 1 nonsense, 0 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.10% of strains (152) · 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 |
|---|---|---|---|---|
DAO | PF01266.31 | 1.5e-38 | 8–315 | FAD dependent oxidoreductase |
FAD_binding_2 | PF00890.31 | 6.3e-06 | 8–57 | FAD binding domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0219 (transmembrane protein), medium confidence from genomic context alone (score 623 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1832 gcvB |
glycine dehydrogenase | 933 | 910 | database:900 |
Rv0070c glyA2 |
serine hydroxymethyltransferase | 913 | 905 | database:900 |
Rv1093 glyA1 |
serine hydroxymethyltransferase | 912 | 905 | database:900 |
Rv1059 hyp |
hypothetical protein | 900 | 900 | database:900 |
Rv0926c hyp |
hypothetical protein | 900 | 900 | database:900 |
Rv0331 |
dehydrogenase/reductase | 853 | 834 | experimental:821 |
Rv2211c gcvT |
aminomethyltransferase | 870 | 823 | experimental:773 |
Rv1837c glcB |
malate synthase | 830 | 813 | database:800 |
Rv1257c |
oxidoreductase | 809 | 803 | database:800 |
Rv2280 |
Rv2280, (MTCY339.30c), len: 459 aa. Probable dehydrogenase. Similar to D-lactate dehydrogenase (cytochrome) precursor e.g. G1061264 (587 aa) | 807 | 801 | database:800 |
Rv0467 icl1 |
isocitrate lyase | 807 | 800 | database:800 |
Rv1915 aceAa |
isocitrate lyase AceAa | 807 | 800 | database:800 |
Rv1916 aceAb |
isocitrate lyase AceAb | 807 | 800 | database:800 |
Rv1906c hyp |
hypothetical protein | 942 | 722 ctx | neighborhood:717 textmining:803 |
Rv0219 |
transmembrane protein | 623 | 623 ctx | cooccurence:623 |
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: D-amino acid oxidase
- MTBC0 PGAP product: FAD-dependent oxidoreductase
- Pfam (hmmscan --cut_ga): DAO PF01266.31 (E=1e-38), FAD_binding_2 PF00890.31 (E=6e-06)
- (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_216421.1)
- Domains: Pfam-A via hmmscan --cut_ga — DAO (PF01266.31), FAD_binding_2 (PF00890.31)
- 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
COG0665 - Curated reference: UniProt P9WP27 (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 —
133 functional partner(s); context anchor
Rv0219 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002020|Rv1905c|aao MAIGEQQVIVIGAGVSGLTSAICLAEAGWPVRVWAAALPQQTTSAVAGAVWGPRPKEPVAKVRGWIEQSLHVFRDLAKDPATGVRMTPALSVGDRIETGAMPPGLELIPDVRPADPADVPGGFRAGFHATLPMIDMPQYLDCLTQRLAATGCEIETRPLRSLAEAAEAAPIVINCAGLGARELAGDATVWPRFGQHVVLTNPGLEQLFIERTGGSEWICYFAHPQRVVCGGISIPGRWDTTPEPEITERILQRCRRIQPRLAEAAVIETITGLRPDRPSVRVEAEPIGRALCIHNYGHGGDGVTLSWGCAREVVNLVGGG