fadE34 Resolved · high auto-curated
H37Rv Rv3573c · MTBC0 mtbc0_003792 ·
711 aa · 4037754–4039889 (-) ·
RefSeq NP_218090.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | acyl-CoA dehydrogenase FadE34 |
|---|---|
| MTBC0 PGAP re-annotation | acyl-CoA dehydrogenase |
| Revised (this work) | Acyl-CoA dehydrogenase. Pfam: Acyl-CoA_dh_N (PF02771.22), Acyl-CoA_dh_1 (PF00441.30), Acyl-CoA_dh_M (PF02770.25). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P96855
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Acyl-CoA dehydrogenase FadE34 |
| EC (curated) |
EC 1.3.99.-
|
| Curated function | Involved in the second 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 the five-carbon steroid side chain of 3-oxo-chol-4-en-24-oyl-CoA (3-OCO-CoA) to yield 3-oxochol-4,22-dien-24-oyl-CoA. Can also use 3beta-hydroxy-chol-5-ene-24-oyl-CoA, and shows weak activity with cholyl-CoA and deoxycholyl-CoA. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
|---|---|
| Preferred name | fadE34 |
| eggNOG description | acyl-CoA dehydrogenase |
| Orthologous group | COG1960 |
| Gene Ontology (6) |
GO:0005575, GO:0005623, GO:0005886, GO:0016020, GO:0044464, GO:0071944
|
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 | 0.309 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 5 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 | 6.8e-09 | 6–103 | Acyl-CoA dehydrogenase, N-terminal domain |
Acyl-CoA_dh_1 | PF00441.30 | 1.8e-19 | 212–328 | Acyl-CoA dehydrogenase, C-terminal domain |
Acyl-CoA_dh_M | PF02770.25 | 7.4e-19 | 462–555 | Acyl-CoA dehydrogenase, middle domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: kstR (HTH-type transcriptional regulator KstR), high confidence from genomic context alone (score 862 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3541c chsH1 hyp |
hypothetical protein | 868 | 864 ctx | cooccurence:741 |
Rv3574 kstR |
HTH-type transcriptional regulator KstR | 901 | 862 ctx | neighborhood:730 cooccurence:503 |
Rv3522 ltp4 |
lipid transfer protein | 901 | 826 ctx | cooccurence:704 textmining:456 |
Rv0860 fadB |
fatty oxidation protein FadB | 803 | 788 | coexpression:647 |
Rv3540c ltp2 |
lipid transfer protein | 924 | 783 ctx | cooccurence:628 textmining:668 |
Rv3523 ltp3 |
lipid carrier protein | 862 | 782 ctx | cooccurence:628 |
Rv3550 echA20 |
enoyl-CoA hydratase EchA20 | 822 | 763 ctx | cooccurence:470 |
Rv3546 fadA5 |
acetyl-CoA acetyltransferase FadA | 951 | 756 | database:500 textmining:810 |
Rv3538 |
dehydrogenase | 737 | 737 ctx | cooccurence:488 |
Rv3542c chsH2 hyp |
hypothetical protein | 734 | 733 ctx | cooccurence:723 |
Rv3521 hyp |
hypothetical protein | 732 | 732 ctx | cooccurence:723 |
Rv3029c fixA |
electron transfer flavoprotein subunit beta | 719 | 707 | coexpression:404 experimental:418 |
Rv3028c fixB |
electron transfer flavoprotein subunit alpha | 714 | 702 | coexpression:408 experimental:419 |
Rv3516 echA19 |
enoyl-CoA hydratase EchA19 | 783 | 677 | |
Rv3548c |
short-chain type dehydrogenase/reductase | 724 | 656 ctx | cooccurence:475 |
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 FadE34
- MTBC0 PGAP product: acyl-CoA dehydrogenase
- Pfam (hmmscan --cut_ga): Acyl-CoA_dh_N PF02771.22 (E=7e-09), Acyl-CoA_dh_1 PF00441.30 (E=2e-19), Acyl-CoA_dh_M PF02770.25 (E=7e-19)
- (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_218090.1)
- Domains: Pfam-A via hmmscan --cut_ga — Acyl-CoA_dh_N (PF02771.22), Acyl-CoA_dh_1 (PF00441.30), Acyl-CoA_dh_M (PF02770.25)
- 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 P96855 (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 —
137 functional partner(s); context anchor
kstR - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003792|Rv3573c|fadE34 MVATVTDEQSAARELVRGWARTAASGAAATAAVRDMEYGFEEGNADAWRPVFAGLAGLGLFGVAVPEDCGGAGGSIEDLCAMVDEAARALVPGPVATTAVATLVVSDPKLRSALASGERFAGVAIDGGVQVDPKTSTASGTVGRVLGGAPGGVVLLPADGNWLLVDTACDEVVVEPLRATDFSLPLARMVLTSAPVTVLEVSGERVEDLAATVLAAEAAGVARWTLDTAVAYAKVREQFGKPIGSFQAVKHLCAQMLCRAEQADVAAADAARAAADSDGTQLSIAAAVAASIGIDAAKANAKDCIQVLGGIGCTWEHDAHLYLRRAHGIGGFLGGSGRWLRRVTALTQAGVRRRLGVDLAEVAGLRPEIAAAVAEVAALPEEKRQVALADTGLLAPHWPAPYGRGASPAEQLLIDQELAAAKVERPDLVIGWWAAPTILEHGTPEQIERFVPATMRGEFLWCQLFSEPGAGSDLASLRTKAVRADGGWLLTGQKVWTSAAHKARWGVCLARTDPDAPKHKGITYFLVDMTTPGIEIRPLREITGDSLFNEVFLDNVFVPDEMVVGAVNDGWRLARTTLANERVAMATGTALGNPMEELLKVLGDMELDVAQQDRLGRLILLAQAGALLDRRIAELAVGGQDPGAQSSVRKLIGVRYRQALAEYLMEVSDGGGLVENRAVYDFLNTRCLTIAGGTEQILLTVAAERLLGLPR