fadE26 Resolved · high auto-curated
H37Rv Rv3504 · MTBC0 mtbc0_003719 ·
400 aa · 3947053–3948255 (+) ·
RefSeq NP_218021.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | acyl-CoA dehydrogenase FadE26 |
|---|---|
| MTBC0 PGAP re-annotation | acyl-CoA dehydrogenase |
| Revised (this work) | Acyl-CoA dehydrogenase. Pfam: Acyl-CoA_dh_N (PF02771.22), Acyl-CoA_dh_M (PF02770.25), Acyl-CoA_dh_1 (PF00441.30). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6YCA3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Acyl-CoA dehydrogenase FadE26 |
| EC (curated) |
EC 1.3.99.-
|
| Curated function | Involved in the first cycle of side chain dehydrogenation in the beta-oxidation of cholesterol catabolism. It contributes partly to the virulence by increasing the efficiency of beta-oxidation. Catalyzes the dehydrogenation of acyl-CoA ester side chains of (25S)-3-oxo-cholest-4-en-26-oyl-CoA (3-OCS-CoA) to yield (24E)-3-oxo-cholest-4,24-dien-26-oyl-CoA. Also able to dehydrogenate steroyl-CoA such as 3-oxo-chol-4-en-24-oyl-CoA (3-OCO-CoA) as well as 3-oxo-4-pregnene-20-carboxyl-CoA (3-OPC-CoA). It dehydrogenates only (25S)-OCS-CoA diastereomer (Probable). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
|---|---|
| Preferred name | fadE26 |
| eggNOG description | acyl-CoA dehydrogenase |
| Orthologous group | COG1960 |
| EC number |
EC 1.3.8.7
|
| KEGG orthology |
K00249
|
| KEGG pathways |
map00071, map00280, map00410, map00640, map01100, map01110, map01130, map01200, map01212, map03320
|
| KEGG modules |
M00013, M00036, M00087
|
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 | 0.227 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 2 missense, 0 nonsense, 0 frameshift |
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 | 4.0e-20 | 6–122 | Acyl-CoA dehydrogenase, N-terminal domain |
Acyl-CoA_dh_M | PF02770.25 | 9.4e-19 | 127–215 | Acyl-CoA dehydrogenase, middle domain |
Acyl-CoA_dh_1 | PF00441.30 | 2.1e-32 | 234–391 | Acyl-CoA dehydrogenase, C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: fadE27 (acyl-CoA dehydrogenase FadE27), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3505 fadE27 |
acyl-CoA dehydrogenase FadE27 | 999 | 1000 ctx | neighborhood:846 cooccurence:773 coexpression:458 experimental:999 database:900 textmining:946 |
Rv3502c |
3-oxoacyl-ACP reductase | 938 | 872 ctx | neighborhood:736 textmining:541 |
Rv3541c chsH1 hyp |
hypothetical protein | 876 | 872 ctx | cooccurence:755 |
Rv3516 echA19 |
enoyl-CoA hydratase EchA19 | 894 | 850 | database:643 |
Rv3522 ltp4 |
lipid transfer protein | 894 | 843 ctx | cooccurence:733 |
Rv3506 fadD17 |
long-chain-fatty-acid--CoA ligase FadD17 | 965 | 823 ctx | neighborhood:768 textmining:810 |
Rv3544c fadE28 |
acyl-CoA dehydrogenase FadE28 | 915 | 823 ctx | cooccurence:773 textmining:542 |
Rv3550 echA20 |
enoyl-CoA hydratase EchA20 | 895 | 818 ctx | cooccurence:591 textmining:452 |
Rv3515c fadD19 |
acyl-CoA synthetase | 936 | 816 ctx | cooccurence:538 database:500 textmining:669 |
Rv0860 fadB |
fatty oxidation protein FadB | 803 | 788 | coexpression:648 |
Rv3523 ltp3 |
lipid carrier protein | 879 | 787 ctx | cooccurence:636 textmining:459 |
Rv3564 fadE33 |
acyl-CoA dehydrogenase FadE33 | 915 | 781 ctx | cooccurence:764 textmining:629 |
Rv3540c ltp2 |
lipid transfer protein | 825 | 780 ctx | cooccurence:622 |
Rv3563 fadE32 |
acyl-CoA dehydrogenase FadE32 | 888 | 774 ctx | cooccurence:772 textmining:525 |
Rv3521 hyp |
hypothetical protein | 754 | 754 ctx | cooccurence:745 |
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 FadE26
- MTBC0 PGAP product: acyl-CoA dehydrogenase
- Pfam (hmmscan --cut_ga): Acyl-CoA_dh_N PF02771.22 (E=4e-20), Acyl-CoA_dh_M PF02770.25 (E=9e-19), Acyl-CoA_dh_1 PF00441.30 (E=2e-32)
- (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_218021.1)
- 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)
- 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 I6YCA3 (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 —
139 functional partner(s); context anchor
fadE27 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003719|Rv3504|fadE26 MRISYTPQQEELRRELRSYFATLMTPERREALSSVQGEYGVGNVYRETIAQMGRDGWLALGWPKEYGGQGRSAMDQLIFTDEAAIAGAPVPFLTINSVAPTIMAYGTDEQKRFFLPRIAAGDLHFSIGYSEPGAGTDLANLRTTAVRDGDDYVVNGQKMWTSLIQYADYVWLAVRTNPESSGAKKHRGISVLIVPTTAEGFSWTPVHTMAGPDTSATYYSDVRVPVANRVGEENAGWKLVTNQLNHERVALVSPAPIFGCLREVREWAQNTKDAGGTRLIDSEWVQLNLARVHAKAEVLKLINWELASSQSGPKDAGPSPADASAAKVFGTELATEAYRLLMEVLGTAATLRQNSPGALLRGRVERMHRACLILTFGGGTNEVQRDIIGMVALGLPRANR