fadE27 Family assigned · medium auto-curated

H37Rv Rv3505 · MTBC0 mtbc0_003720 · 373 aa · 3948280–3949401 (+) · RefSeq NP_218022.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)acyl-CoA dehydrogenase FadE27
MTBC0 PGAP re-annotationacyl-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 I6Y3Q0 SwissProt · reviewed · Evidence at protein level
UniProt nameAcyl-CoA dehydrogenase FadE27
EC (curated) EC 1.3.99.-
Curated functionInvolved 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.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Preferred namefadE27
eggNOG descriptionacyl-CoA dehydrogenase
Orthologous groupCOG1960
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 0.295 · purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 4 missense, 0 nonsense, 2 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 0.54% of strains (780) · 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)

PfamAccessioni-EvalueResiduesDescription
Acyl-CoA_dh_NPF02771.22 2.5e-127–117 Acyl-CoA dehydrogenase, N-terminal domain
Acyl-CoA_dh_1PF00441.30 1.8e-23223–368 Acyl-CoA dehydrogenase, C-terminal domain
Acyl-CoA_dh_2PF08028.17 2.6e-10231–344 Acyl-CoA dehydrogenase, C-terminal domain

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: fadE26 (acyl-CoA dehydrogenase FadE26), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3504 fadE26 acyl-CoA dehydrogenase FadE26 999 1000 ctx neighborhood:846 cooccurence:773 coexpression:458 experimental:999 database:900 textmining:946
Rv3502c 3-oxoacyl-ACP reductase 860 843 ctx neighborhood:717
Rv3516 echA19 enoyl-CoA hydratase EchA19 876 819 database:643
Rv3028c fixB electron transfer flavoprotein subunit alpha 816 809 ctx cooccurence:472 coexpression:410 experimental:419
Rv3506 fadD17 long-chain-fatty-acid--CoA ligase FadD17 917 808 ctx neighborhood:792 textmining:586
Rv3543c fadE29 acyl-CoA dehydrogenase FadE29 857 799 ctx cooccurence:772
Rv3029c fixA electron transfer flavoprotein subunit beta 806 798 ctx cooccurence:450 coexpression:404 experimental:418
Rv0860 fadB fatty oxidation protein FadB 803 788 coexpression:647
Rv3562 fadE31 acyl-CoA dehydrogenase FadE31 906 760 ctx cooccurence:759 textmining:627
Rv3560c fadE30 acyl-CoA dehydrogenase FadE30 795 751 ctx cooccurence:751
Rv1934c fadE17 acyl-CoA dehydrogenase FadE17 808 739 ctx cooccurence:738
Rv3541c chsH1 hyp hypothetical protein 747 738 ctx cooccurence:502
Rv1679 fadE16 acyl-CoA dehydrogenase FadE16 737 737 ctx cooccurence:737
Rv0752c fadE9 acyl-CoA dehydrogenase FadE9 737 737 ctx cooccurence:735
Rv3550 echA20 enoyl-CoA hydratase EchA20 810 701

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 FadE27
  • MTBC0 PGAP product: acyl-CoA dehydrogenase family protein
  • Pfam (hmmscan --cut_ga): Acyl-CoA_dh_N PF02771.22 (E=2e-12), Acyl-CoA_dh_1 PF00441.30 (E=2e-23), Acyl-CoA_dh_2 PF08028.17 (E=3e-10)
  • (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_218022.1)
  • 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 I6Y3Q0 (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 — 138 functional partner(s); context anchor fadE26
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003720|Rv3505|fadE27
MDFTTTEAAQDLGGLVDTIVDAVCTPEHQRELDKLEQRFDRELWRKLIDAGILSSAAPESLGGDGFGVLEQVAVLVALGHQLAAVPYLESVVLAAGALARFGSPELQQGWGVSAVSGDRILTVALDGEMGEGPVQAAGTGHGYRLTGTRTQVGYGPVADAFLVPAETDSGAAVFLVAAGDPGVAVTALATTGLGSVGHLELNGAKVDAARRVGGTDVAVWLGTLSTLSRTAFQLGVLERGLQMTAEYARTREQFDRPIGSFQAVGQRLADGYIDVKGLRLTLTQAAWRVAEDSLASRECPQPADIDVATAGFWAAEAGHRVAHTIVHVHGGVGVDTDHPVHRYFLAAKQTEFALGGATGQLRRIGRELAETPA