fadE28 Resolved · high auto-curated

H37Rv Rv3544c · MTBC0 mtbc0_003761 · 339 aa · 4006802–4007821 (-) · RefSeq NP_218061.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)acyl-CoA dehydrogenase FadE28
MTBC0 PGAP re-annotationacyl-CoA dehydrogenase FadE28
Revised (this work)Acyl-CoA dehydrogenase FadE28. Pfam: Acyl-CoA_dh_N (PF02771.22), 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 P71857 SwissProt · reviewed · Evidence at protein level
UniProt nameAcyl-CoA dehydrogenase FadE28
EC (curated) EC 1.3.99.-
Curated functionInvolved in the third cycle of side chain dehydrogenation in the beta-oxidation of cholesterol catabolism. May play an important role for the initial macrophage invasion, possibly in response to the acidification of phagosome. It contributes partly to the virulence by increasing the efficiency of beta-oxidation. Catalyzes the dehydrogenation of 2'-propanoyl-CoA ester side chains of 3-oxo-4-pregnene-20-carboxyl-CoA (3-OPC-CoA) to yield 3-oxo-4,17-pregnadiene-20-carboxyl-CoA (3-OPDC-CoA). Also able to dehydrogenate steroyl-CoA such as 3-oxo-chol-4-en-24-oyl-CoA (3-OCO-CoA), 1beta-(2'-propanoyl-C.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Preferred namefadE28
eggNOG descriptionacyl-CoA dehydrogenase
Orthologous groupCOG1960
Gene Ontology (67) GO:0000166, GO:0003674, GO:0005488, GO:0006066, GO:0006082, GO:0006629, GO:0006631, GO:0006635, GO:0006706, GO:0006707, GO:0008150, GO:0008152 +55 more

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 0.246 · 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)

PfamAccessioni-EvalueResiduesDescription
Acyl-CoA_dh_NPF02771.22 7.6e-0920–99 Acyl-CoA dehydrogenase, N-terminal domain
Acyl-CoA_dh_1PF00441.30 2.1e-15204–327 Acyl-CoA dehydrogenase, C-terminal domain

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

Closest characterised functional partner: fadE29 (acyl-CoA dehydrogenase FadE29), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3543c fadE29 acyl-CoA dehydrogenase FadE29 999 1000 ctx neighborhood:882 fusion:480 cooccurence:773 coexpression:730 database:900 textmining:979
Rv3541c chsH1 hyp hypothetical protein 997 989 ctx neighborhood:881 cooccurence:674 database:639 textmining:810
Rv3542c chsH2 hyp hypothetical protein 980 980 ctx neighborhood:881 cooccurence:674 database:500
Rv3540c ltp2 lipid transfer protein 995 962 ctx neighborhood:881 cooccurence:476 textmining:878
Rv3546 fadA5 acetyl-CoA acetyltransferase FadA 988 942 ctx neighborhood:778 database:500 textmining:815
Rv3545c cyp125 steroid C26-monooxygenase 987 929 ctx neighborhood:882 textmining:833
Rv3504 fadE26 acyl-CoA dehydrogenase FadE26 915 823 ctx cooccurence:773 textmining:542
Rv3522 ltp4 lipid transfer protein 897 789 ctx cooccurence:642 textmining:535
Rv0860 fadB fatty oxidation protein FadB 809 788 coexpression:647
Rv3563 fadE32 acyl-CoA dehydrogenase FadE32 920 769 ctx cooccurence:768 textmining:668
Rv3028c fixB electron transfer flavoprotein subunit alpha 776 767 coexpression:408 experimental:419
Rv3562 fadE31 acyl-CoA dehydrogenase FadE31 761 761 ctx cooccurence:760
Rv3029c fixA electron transfer flavoprotein subunit beta 769 760 coexpression:404 experimental:418
Rv3560c fadE30 acyl-CoA dehydrogenase FadE30 890 758 ctx cooccurence:757 textmining:566
Rv3550 echA20 enoyl-CoA hydratase EchA20 868 737 ctx cooccurence:408 textmining:520

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 FadE28
  • MTBC0 PGAP product: acyl-CoA dehydrogenase FadE28
  • Pfam (hmmscan --cut_ga): Acyl-CoA_dh_N PF02771.22 (E=8e-09), Acyl-CoA_dh_1 PF00441.30 (E=2e-15)
  • (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_218061.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Acyl-CoA_dh_N (PF02771.22), 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 P71857 (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 — 156 functional partner(s); context anchor fadE29
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003761|Rv3544c|fadE28
MDFDPTAEQQAVADVVTSVLERDISWEALVCGGVTALPVPERLGGDGVGLFEVGALLTEVGRHGAVTPALATLGLGVVPLLELASAEQQDRFLAGVAKGGVLTAALNEPGAALPDRPATSFVGGRLSGTKVGVGYAEQADWMLVTADNAVVVVSPTADGVRMVRTPTSNGSDEYVMTMDGVAVADCDILADVAAHRVNQLALAVMGAYADGLVAGALRLTADYVANRKQFGKPLSTFQTVAAQLAEVYIASRTIDLVAKSVIWRLAEDLDAGDDLGVLGYWVTSQAPPAMQICHHLHGGMGMDVTYPMHRYYSTIKDLTRLLGGPSHRLELLGARCSLT