fadE29 Resolved · high auto-curated

H37Rv Rv3543c · MTBC0 mtbc0_003760 · 387 aa · 4005654–4006817 (-) · RefSeq NP_218060.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)acyl-CoA dehydrogenase FadE29
MTBC0 PGAP re-annotationacyl-CoA dehydrogenase FadE29
Revised (this work)Acyl-CoA dehydrogenase FadE29. 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 P71858 SwissProt · reviewed · Evidence at protein level
UniProt nameAcyl-CoA dehydrogenase FadE29
EC (curated) EC 1.3.99.-
Curated functionInvolved in the third cycle of side chain dehydrogenation in the beta-oxidation of cholesterol catabolism. 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-CoA)-3a-alpha-H- 7a-beta-methylhexahydro-4-indanone (indanone-CoA ester), hexahydroindanone and pregenenone.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Preferred namefadE29
eggNOG descriptionacyl-CoA dehydrogenase
Orthologous groupCOG1960
Gene Ontology (63) GO:0000166, GO:0003674, GO:0005488, GO:0006066, GO:0006082, GO:0006629, GO:0006631, GO:0006635, GO:0006706, GO:0006707, GO:0008150, GO:0008152 +51 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 0.54 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 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)

PfamAccessioni-EvalueResiduesDescription
Acyl-CoA_dh_NPF02771.22 4.5e-216–118 Acyl-CoA dehydrogenase, N-terminal domain
Acyl-CoA_dh_MPF02770.25 4.6e-20122–207 Acyl-CoA dehydrogenase, middle domain
Acyl-CoA_dh_1PF00441.30 2.1e-25228–378 Acyl-CoA dehydrogenase, C-terminal domain

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

Closest characterised functional partner: fadE28 (acyl-CoA dehydrogenase FadE28), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3544c fadE28 acyl-CoA dehydrogenase FadE28 999 1000 ctx neighborhood:882 fusion:480 cooccurence:773 coexpression:730 database:900 textmining:979
Rv3541c chsH1 hyp hypothetical protein 999 994 ctx neighborhood:881 cooccurence:757 database:639 textmining:857
Rv3542c chsH2 hyp hypothetical protein 994 990 ctx neighborhood:881 cooccurence:747 coexpression:421 database:500 textmining:478
Rv3540c ltp2 lipid transfer protein 998 980 ctx neighborhood:881 cooccurence:602 coexpression:577 textmining:907
Rv3546 fadA5 acetyl-CoA acetyltransferase FadA 995 944 ctx neighborhood:778 database:500 textmining:919
Rv3545c cyp125 steroid C26-monooxygenase 983 916 ctx neighborhood:882 textmining:816
Rv3522 ltp4 lipid transfer protein 968 838 ctx cooccurence:721 textmining:815
Rv3505 fadE27 acyl-CoA dehydrogenase FadE27 857 799 ctx cooccurence:772
Rv3550 echA20 enoyl-CoA hydratase EchA20 931 796 ctx cooccurence:537 textmining:680
Rv0860 fadB fatty oxidation protein FadB 828 788 coexpression:647
Rv3523 ltp3 lipid carrier protein 963 781 ctx cooccurence:624 textmining:840
Rv3564 fadE33 acyl-CoA dehydrogenase FadE33 922 779 ctx cooccurence:760 textmining:662
Rv3563 fadE32 acyl-CoA dehydrogenase FadE32 929 774 ctx cooccurence:771 textmining:702
Rv1933c fadE18 acyl-CoA dehydrogenase FadE18 769 770 ctx cooccurence:727
Rv3521 hyp hypothetical protein 793 753 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 FadE29
  • MTBC0 PGAP product: acyl-CoA dehydrogenase FadE29
  • Pfam (hmmscan --cut_ga): Acyl-CoA_dh_N PF02771.22 (E=4e-21), Acyl-CoA_dh_M PF02770.25 (E=5e-20), Acyl-CoA_dh_1 PF00441.30 (E=2e-25)
  • (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_218060.1)
  • 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 P71858 (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 — 144 functional partner(s); context anchor fadE28
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003760|Rv3543c|fadE29
MFIDLTPEQRQLQAEIRQYFSNLISPDERTEMEKDRHGPAYRAVIRRMGRDGRLGVGWPKEFGGLGFGPIEQQIFVNEAHRADVPLPAVTLQTVGPTLQAHGSELQKKKFLPAILAGEAHFAIGYTEPEAGTDLASLRTTAVRDGDHYIVNGQKVFTTGAHDADYIWLACRTDPNAAKHKGISILIVDTKDPGYSWTPIILADGAHHTNATYYNDVRVPVDMLVGKENDGWRLITTQLNNERVMLGPAGRFASIYDRVHAWASVPGGNGVTPIDHDDVKRALGEIRAIWRINELLNWQVASAGEDINMADAAATKVFGTERVQRAGRLAEEIVGKYGNPAEPDTAELLRWLDAQTKRNLVITFGGGVNEVMREMIAASGLKVPRVPR