fadE12 Resolved · high auto-curated

H37Rv Rv0972c · MTBC0 mtbc0_001038 · 388 aa · 1089799–1090965 (-) · RefSeq NP_215487.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)acyl-CoA dehydrogenase fadE12
MTBC0 PGAP re-annotationacyl-CoA dehydrogenase
Revised (this work)Acyl-CoA dehydrogenase. Pfam: Acyl-CoA_dh_N (PF02771.22), Acyl-CoA_dh_M (PF02770.25), 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 P9WQG3 SwissProt · reviewed · Evidence at protein level
UniProt nameAcyl-CoA dehydrogenase FadE12
EC (curated) EC 1.3.99.-
Curated functionHas acyl-CoA dehydrogenase activity on a number of substrates. N-octanoyl-CoA is the best tested, but n-lauroyl-CoA, n-palmitoyl-CoA and isovaleryl-CoA were also used.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Preferred namefadE12
eggNOG descriptionacyl-CoA dehydrogenase
Orthologous groupCOG1960
KEGG orthology K00257
Gene Ontology (14) GO:0003674, GO:0003824, GO:0003995, GO:0005575, GO:0005623, GO:0005886, GO:0008150, GO:0008152, GO:0016020, GO:0016491, GO:0016627, GO:0044464 +2 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 0.48 · purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 6 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 3.6e-289–119 Acyl-CoA dehydrogenase, N-terminal domain
Acyl-CoA_dh_MPF02770.25 1.5e-16124–204 Acyl-CoA dehydrogenase, middle domain
Acyl-CoA_dh_1PF00441.30 2.4e-30239–380 Acyl-CoA dehydrogenase, C-terminal domain
Acyl-CoA_dh_2PF08028.17 1.4e-07247–351 Acyl-CoA dehydrogenase, C-terminal domain

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

Closest characterised functional partner: accA2 (acetyl/propionyl-CoA carboxylase subuit alpha), high confidence from genomic context alone (score 986 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0973c accA2 acetyl/propionyl-CoA carboxylase subuit alpha 993 986 ctx neighborhood:882 coexpression:874 textmining:584
Rv0974c accD2 acetyl-/propionyl-CoA carboxylase subunit beta 992 986 ctx neighborhood:881 coexpression:876 textmining:491
Rv0975c fadE13 acyl-CoA dehydrogenase FadE13 982 982 ctx neighborhood:882 coexpression:800
Rv0976c hyp hypothetical protein 961 960 ctx neighborhood:881 cooccurence:487
Rv0971c echA7 enoyl-CoA hydratase EchA7 982 950 ctx neighborhood:882 textmining:652
Rv3029c fixA electron transfer flavoprotein subunit beta 815 808 ctx cooccurence:470 coexpression:410 experimental:418
Rv0860 fadB fatty oxidation protein FadB 819 794 coexpression:657
Rv3028c fixB electron transfer flavoprotein subunit alpha 797 789 ctx cooccurence:412 coexpression:412 experimental:419
Rv3505 fadE27 acyl-CoA dehydrogenase FadE27 687 688 ctx cooccurence:685
Rv3153 nuoI NADH-quinone oxidoreductase subunit I 651 637
Rv3825c pks2 phthioceranic/hydroxyphthioceranic acid synthase 619 588 database:459
Rv2933 ppsC phthiocerol synthesis polyketide synthase type I PpsC 616 585 database:459
Rv1527c pks5 polyketide synthase 616 585 database:459
Rv2048c pks12 polyketide synthase 615 584 database:459
Rv2940c mas multifunctional mycocerosic acid synthase 615 584 database:459

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 fadE12
  • MTBC0 PGAP product: acyl-CoA dehydrogenase
  • Pfam (hmmscan --cut_ga): Acyl-CoA_dh_N PF02771.22 (E=4e-28), Acyl-CoA_dh_M PF02770.25 (E=1e-16), Acyl-CoA_dh_1 PF00441.30 (E=2e-30), Acyl-CoA_dh_2 PF08028.17 (E=1e-07)
  • (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_215487.1)
  • 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), 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 P9WQG3 (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 — 121 functional partner(s); context anchor accA2
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001038|Rv0972c|fadE12
MTDTSFIESEERQALRKAVASWVANYGHEYYLDKARKHEHTSELWAEAGKLGFLGVNLPEEYGGGGAGMYELSLVMEEMAAAGSALLLMVVSPAINGTIIAKFGTDDQKKRWLPGIADGSLTMAFAITEPDAGSNSHKITTTARRDGSDWIIKGQKVFISGIDQAQAVLVVGRSEEAKTGKLRPALFVVPTDAPGFSYTPIEMELVSPERQFQVFLDDVRLPADALVGAEDAAIAQLFAGLNPERIMGAASAVGMGRFALGRAVDYVKTRKVWSTPIGAHQGLAHPLAQCHIEVELAKLMTQKAATLYDHGDDFGAAEAANMAKYAAAEASSRAVDQAVQSMGGNGLTKEYGVAAMMTSARLARIAPISREMVLNFVAQTSLGLPRSY