fadE33 Family assigned · medium auto-curated
H37Rv Rv3564 · MTBC0 mtbc0_003781 ·
318 aa · 4028924–4029880 (+) ·
RefSeq NP_218081.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | acyl-CoA dehydrogenase FadE33 |
|---|---|
| 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_1 (PF00441.30), Acyl-CoA_dh_2 (PF08028.17). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6YCF5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Acyl-CoA dehydrogenase IpdE2 |
| EC (curated) |
EC 1.3.99.-
|
| Curated function | Involved in cholesterol degradation. Catalyzes the dehydrogenation of 5OH-HIP-CoA to 5OH-HIPE-CoA. Can also use octanoyl-CoA and dihydroferuloyl-CoA, with lower efficiency. Cannot use 3-oxo-4-pregnene-20-carboxyl-CoA (3-OPC-CoA). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
|---|---|
| Preferred name | fadE33 |
| 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 | 0.732 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 4 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 | 2.7e-12 | 5–100 | Acyl-CoA dehydrogenase, N-terminal domain |
Acyl-CoA_dh_1 | PF00441.30 | 2.4e-22 | 186–294 | Acyl-CoA dehydrogenase, C-terminal domain |
Acyl-CoA_dh_2 | PF08028.17 | 1.0e-08 | 187–285 | Acyl-CoA dehydrogenase, C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: fadE31 (acyl-CoA dehydrogenase FadE31), high confidence from genomic context alone (score 996 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3562 fadE31 |
acyl-CoA dehydrogenase FadE31 | 999 | 996 ctx | neighborhood:881 cooccurence:768 coexpression:800 textmining:825 |
Rv3563 fadE32 |
acyl-CoA dehydrogenase FadE32 | 990 | 986 ctx | neighborhood:881 coexpression:852 |
Rv3560c fadE30 |
acyl-CoA dehydrogenase FadE30 | 997 | 978 ctx | neighborhood:770 cooccurence:770 coexpression:441 textmining:881 |
Rv3565 aspB |
aspartate aminotransferase AspB | 976 | 976 ctx | neighborhood:882 coexpression:804 |
Rv3561 fadD3 |
fatty-acid--CoA ligase FadD3 | 969 | 955 ctx | neighborhood:801 coexpression:783 |
Rv3559c |
oxidoreductase | 954 | 953 ctx | neighborhood:770 coexpression:710 |
Rv1934c fadE17 |
acyl-CoA dehydrogenase FadE17 | 925 | 834 ctx | cooccurence:773 textmining:571 |
Rv0860 fadB |
fatty oxidation protein FadB | 802 | 787 | coexpression:646 |
Rv3028c fixB |
electron transfer flavoprotein subunit alpha | 795 | 786 ctx | cooccurence:411 coexpression:409 experimental:419 |
Rv3029c fixA |
electron transfer flavoprotein subunit beta | 792 | 784 ctx | cooccurence:410 coexpression:404 experimental:418 |
Rv3504 fadE26 |
acyl-CoA dehydrogenase FadE26 | 915 | 781 ctx | cooccurence:764 textmining:629 |
Rv3543c fadE29 |
acyl-CoA dehydrogenase FadE29 | 922 | 779 ctx | cooccurence:760 textmining:662 |
Rv2724c fadE20 |
acyl-CoA dehydrogenase FadE20 | 731 | 731 ctx | cooccurence:731 |
Rv3556c fadA6 |
acetyl-CoA acetyltransferase FadA | 823 | 721 ctx | neighborhood:523 |
Rv0752c fadE9 |
acyl-CoA dehydrogenase FadE9 | 717 | 718 ctx | cooccurence:716 |
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 FadE33
- MTBC0 PGAP product: acyl-CoA dehydrogenase family protein
- Pfam (hmmscan --cut_ga): Acyl-CoA_dh_N PF02771.22 (E=3e-12), Acyl-CoA_dh_1 PF00441.30 (E=2e-22), Acyl-CoA_dh_2 PF08028.17 (E=1e-08)
- (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_218081.1)
- Domains: Pfam-A via hmmscan --cut_ga — Acyl-CoA_dh_N (PF02771.22), Acyl-CoA_dh_1 (PF00441.30), Acyl-CoA_dh_2 (PF08028.17)
- 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 I6YCF5 (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 —
148 functional partner(s); context anchor
fadE31 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003781|Rv3564|fadE33 MTPPEERQMLRETVASLVAKHAGPAAVRAAMASDRGYDESLWRLLCEQVGAAALVIPEELGGAGGELADAAIVVQELGRALVPSPLLGTTLAELALLAAAKPDAQALTELAQGSAIGALVLDPDYVVNGDIADIVVAATSGQLTRWTRFSAQPVATMDPTRRLARLQSEETEPLCPDPGIADTAAILLAAEQIGAAERCLQLTVEYAKSRVQFGRPIGSFQALKHRMADLYVTIAAARAVVADACHAPTPTNAATARLAASEALSTAAAEGIQLHGGIAITWEHDMHLYFKRAHGSAQLLESPREVLRRLESEVWESP