fadE9 Family assigned · medium auto-curated
H37Rv Rv0752c · MTBC0 mtbc0_000799 ·
390 aa · 847667–848839 (-) ·
RefSeq NP_215266.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | acyl-CoA dehydrogenase FadE9 |
|---|---|
| MTBC0 PGAP re-annotation | acyl-CoA dehydrogenase family protein |
| Revised (this work) | Acyl-CoA dehydrogenase family protein. Pfam: Acyl-CoA_dh_N (PF02771.22), Acyl-CoA_dh_M (PF02770.25), Acyl-CoA_dh_1 (PF00441.30), Acyl-CoA_dh_2 (PF08028.17), ACOX_C_alpha1 (PF22924.2). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6Y4R2
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable acyl-CoA dehydrogenase FadE9 |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
|---|---|
| Preferred name | fadE9 |
| eggNOG description | acyl-CoA dehydrogenase |
| Orthologous group | COG1960 |
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 | 3.047 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 9 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.61% of strains (891) · 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 |
|---|---|---|---|---|
Acyl-CoA_dh_N | PF02771.22 | 9.1e-29 | 6–115 | Acyl-CoA dehydrogenase, N-terminal domain |
Acyl-CoA_dh_M | PF02770.25 | 2.7e-24 | 121–218 | Acyl-CoA dehydrogenase, middle domain |
Acyl-CoA_dh_1 | PF00441.30 | 2.8e-48 | 233–381 | Acyl-CoA dehydrogenase, C-terminal domain |
Acyl-CoA_dh_2 | PF08028.17 | 3.7e-18 | 250–368 | Acyl-CoA dehydrogenase, C-terminal domain |
ACOX_C_alpha1 | PF22924.2 | 2.2e-06 | 317–380 | Acyl-CoA oxidase, C-alpha1 domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mmsB (3-hydroxyisobutyrate dehydrogenase), high confidence from genomic context alone (score 989 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0751c mmsB |
3-hydroxyisobutyrate dehydrogenase | 988 | 989 ctx | neighborhood:879 cooccurence:516 coexpression:821 |
Rv0753c mmsA |
methylmalonate-semialdehyde dehydrogenase | 987 | 987 ctx | neighborhood:882 coexpression:875 |
Rv3028c fixB |
electron transfer flavoprotein subunit alpha | 851 | 845 ctx | cooccurence:466 coexpression:408 experimental:419 |
Rv0860 fadB |
fatty oxidation protein FadB | 804 | 789 | coexpression:649 |
Rv3029c fixA |
electron transfer flavoprotein subunit beta | 781 | 772 | coexpression:404 experimental:418 |
Rv1071c echA9 |
enoyl-CoA hydratase EchA9 | 760 | 752 ctx | cooccurence:425 |
Rv3505 fadE27 |
acyl-CoA dehydrogenase FadE27 | 737 | 737 ctx | cooccurence:735 |
Rv3564 fadE33 |
acyl-CoA dehydrogenase FadE33 | 717 | 718 ctx | cooccurence:716 |
Rv3153 nuoI |
NADH-quinone oxidoreductase subunit I | 649 | 634 | |
Rv3563 fadE32 |
acyl-CoA dehydrogenase FadE32 | 607 | 607 ctx | cooccurence:603 |
Rv3544c fadE28 |
acyl-CoA dehydrogenase FadE28 | 589 | 590 ctx | cooccurence:586 |
Rv1070c echA8 |
enoyl-CoA hydratase EchA8 | 601 | 586 | |
Rv1935c echA13 |
enoyl-CoA hydratase EchA13 | 600 | 585 | |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 613 | 583 | database:459 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 613 | 583 | database:459 |
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: acyl-CoA dehydrogenase FadE9
- MTBC0 PGAP product: acyl-CoA dehydrogenase family protein
- Pfam (hmmscan --cut_ga): Acyl-CoA_dh_N PF02771.22 (E=9e-29), Acyl-CoA_dh_M PF02770.25 (E=3e-24), Acyl-CoA_dh_1 PF00441.30 (E=3e-48), Acyl-CoA_dh_2 PF08028.17 (E=4e-18), ACOX_C_alpha1 PF22924.2 (E=2e-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_215266.1)
- Domains: Pfam-A via hmmscan --cut_ga — Acyl-CoA_dh_N (PF02771.22), Acyl-CoA_dh_M (PF02770.25), Acyl-CoA_dh_1 (PF00441.30), Acyl-CoA_dh_2 (PF08028.17), ACOX_C_alpha1 (PF22924.2)
- 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
COG1960 - Curated reference: UniProt I6Y4R2 (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 —
107 functional partner(s); context anchor
mmsB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000799|Rv0752c|fadE9 MFVLNDDERVIVETAAAFAGKRLAPHALEWDAAKHFPVDVLREAAELGMAAIYCRDDVGGSGLRRLDGVRIFEQLAIADPVTAAFLSIHNMCAWMIDSFGTDEQRKDWIPRLATMGVIASYCLTEPGAGSDAGALSTRAVRHGSGKGGDYVLDGVKQFISGAAASDVYVVMARTGAEGPRGVSAFIVEKGTPGLSFGAPEAKMGWHAQPTAQVVLDGVRVPAEAMLGGADGEGAGFGIAMSGLNGGRLNIAACSLGGAQAAFDKAGAYVRDRQAFGGSLLDEPTVRFTLADMATGLQTSRMLLWRAASALDDDDADKVELCAMAKRYVTDTCFEVADQALQLHGGYGYLREYGLEKIVRDLRVHRILEGTNEIMRLVIGRAEAARFRATV