fadE25 Resolved · high auto-curated

H37Rv Rv3274c · MTBC0 mtbc0_003482 · 389 aa · 3679063–3680232 (-) · RefSeq NP_217791.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)acyl-CoA dehydrogenase
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), ACOX_C_alpha1 (PF22924.2).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt P9WQG1 SwissProt · reviewed · Evidence at protein level
UniProt nameProbable acyl-CoA dehydrogenase FadE25
EC (curated) EC 1.3.99.-

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Preferred namefadE25
eggNOG descriptionacyl-CoA dehydrogenase
Orthologous groupCOG1960
EC number EC 1.3.8.1
KEGG orthology K00248
KEGG pathways map00071, map00280, map00650, map01100, map01110, map01120, map01200, map01212
Gene Ontology (13) GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0016020, GO:0030312, GO:0044424, GO:0044444, GO:0044464 +1 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 0.324 · purifying
Polymorphic sites (≥ 0.1% of strains) 4 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)

PfamAccessioni-EvalueResiduesDescription
Acyl-CoA_dh_NPF02771.22 6.3e-3117–125 Acyl-CoA dehydrogenase, N-terminal domain
Acyl-CoA_dh_MPF02770.25 1.5e-28132–226 Acyl-CoA dehydrogenase, middle domain
Acyl-CoA_dh_1PF00441.30 8.6e-50238–388 Acyl-CoA dehydrogenase, C-terminal domain
Acyl-CoA_dh_2PF08028.17 1.7e-27254–376 Acyl-CoA dehydrogenase, C-terminal domain
ACOX_C_alpha1PF22924.2 2.1e-06271–388 Acyl-CoA oxidase, C-alpha1 domain

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

Closest characterised functional partner: fixB (electron transfer flavoprotein subunit alpha), high confidence from genomic context alone (score 941 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3028c fixB electron transfer flavoprotein subunit alpha 943 941 ctx cooccurence:694 coexpression:559 experimental:419
Rv3029c fixA electron transfer flavoprotein subunit beta 897 893 ctx cooccurence:694 coexpression:432 experimental:418
Rv3276c purK 5-(carboxyamino)imidazole ribonucleotide synthase 855 855 ctx neighborhood:849
Rv3275c purE 5-(carboxyamino)imidazole ribonucleotide mutase 853 854 ctx neighborhood:849
Rv0860 fadB fatty oxidation protein FadB 804 789 coexpression:649
Rv3224 iron-regulated short-chain dehydrogenase/reductase 747 747 coexpression:624
Rv1078 pra hyp hypothetical protein 746 746 coexpression:746
Rv3442c rpsI 30S ribosomal protein S9 703 703 coexpression:703
Rv3153 nuoI NADH-quinone oxidoreductase subunit I 654 640
Rv0632c echA3 enoyl-CoA hydratase EchA3 652 640 coexpression:425
Rv0636 hadB (3R)-hydroxyacyl-ACP dehydratase subunit HadB 629 612
Rv0951 sucC succinyl-CoA ligase subunit beta 624 609 coexpression:554
Rv0468 fadB2 3-hydroxybutyryl-CoA dehydrogenase 714 602 coexpression:427
Rv3774 echA21 enoyl-CoA hydratase EchA21 621 598
Rv0637 hadC (3R)-hydroxyacyl-ACP dehydratase subunit HadC 616 598

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
  • MTBC0 PGAP product: acyl-CoA dehydrogenase
  • Pfam (hmmscan --cut_ga): Acyl-CoA_dh_N PF02771.22 (E=6e-31), Acyl-CoA_dh_M PF02770.25 (E=2e-28), Acyl-CoA_dh_1 PF00441.30 (E=9e-50), Acyl-CoA_dh_2 PF08028.17 (E=2e-27), ACOX_C_alpha1 PF22924.2 (E=2e-06)
  • (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_217791.1)
  • 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), ACOX_C_alpha1 (PF22924.2)
  • 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 P9WQG1 (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 — 127 functional partner(s); context anchor fixB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003482|Rv3274c|fadE25
MVGWAGNPSFDLFKLPEEHDEMRSAIRALAEKEIAPHAAEVDEKARFPEEALVALNSSGFNAVHIPEEYGGQGADSVATCIVIEEVARVDASASLIPAVNKLGTMGLILRGSEELKKQVLPALAAEGAMASYALSEREAGSDAASMRTRAKADGDHWILNGAKCWITNGGKSTWYTVMAVTDPDRGANGISAFMVHKDDEGFTVGPKERKLGIKGSPTTELYFENCRIPGDRIIGEPGTGFKTALATLDHTRPTIGAQAVGIAQGALDAAIAYTKDRKQFGESISTFQAVQFMLADMAMKVEAARLMVYSAAARAERGEPDLGFISAASKCFASDVAMEVTTDAVQLFGGAGYTTDFPVERFMRDAKITQIYEGTNQIQRVVMSRALLR