fadE24 Family assigned · medium auto-curated

H37Rv Rv3139 · MTBC0 mtbc0_003337 · 468 aa · 3528065–3529471 (+) · RefSeq NP_217655.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)acyl-CoA dehydrogenase
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_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 P95187 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable acyl-CoA dehydrogenase FadE24

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Preferred namefadE24
eggNOG descriptionacyl-CoA dehydrogenase
Orthologous groupCOG1960

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 3.247 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 9 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 2.1e-21111–220 Acyl-CoA dehydrogenase, N-terminal domain
Acyl-CoA_dh_MPF02770.25 4.1e-13228–314 Acyl-CoA dehydrogenase, middle domain
Acyl-CoA_dh_1PF00441.30 5.7e-29337–464 Acyl-CoA dehydrogenase, C-terminal domain
Acyl-CoA_dh_2PF08028.17 3.1e-12345–460 Acyl-CoA dehydrogenase, C-terminal domain

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

Closest characterised functional partner: fadE23 (acyl-CoA dehydrogenase FadE23), high confidence from genomic context alone (score 985 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3140 fadE23 acyl-CoA dehydrogenase FadE23 994 985 ctx neighborhood:853 coexpression:860 textmining:637
Rv3029c fixA electron transfer flavoprotein subunit beta 834 827 ctx cooccurence:523 coexpression:410 experimental:418
Rv3028c fixB electron transfer flavoprotein subunit alpha 828 822 ctx cooccurence:504 coexpression:414 experimental:419
Rv0860 fadB fatty oxidation protein FadB 849 821 coexpression:647
Rv3138 pflA pyruvate formate lyase activating protein PflA 829 788 ctx neighborhood:785
Rv1679 fadE16 acyl-CoA dehydrogenase FadE16 743 744 ctx cooccurence:737
Rv0243 fadA2 acetyl-CoA acetyltransferase FadA 706 668 coexpression:577
Rv0241c htdX 3-hydroxyacyl-thioester dehydratase HtdX 651 651
Rv1346 mbtN acyl-[acyl-carrier-protein 644 644 ctx cooccurence:637
Rv3153 nuoI NADH-quinone oxidoreductase subunit I 649 635
Rv3563 fadE32 acyl-CoA dehydrogenase FadE32 653 612 ctx cooccurence:602
Rv3141 fadB4 NADPH quinone oxidoreductase FadB 793 606 ctx neighborhood:548 textmining:498
Rv3137 hisN histidinol-phosphatase 662 606 ctx neighborhood:602
Rv2524c fas fatty acid synthase 648 600
Rv1527c pks5 polyketide synthase 619 588 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
  • MTBC0 PGAP product: acyl-CoA dehydrogenase family protein
  • Pfam (hmmscan --cut_ga): Acyl-CoA_dh_N PF02771.22 (E=2e-21), Acyl-CoA_dh_M PF02770.25 (E=4e-13), Acyl-CoA_dh_1 PF00441.30 (E=6e-29), Acyl-CoA_dh_2 PF08028.17 (E=3e-12)
  • (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_217655.1)
  • 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 P95187 (TrEMBL, unreviewed; 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 fadE23
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003337|Rv3139|fadE24
MTNTTSAANAAKPSGARTDRRGRTTGVGLAPHKRTGIDVALALLTPIVGQEFLDKYRLRDPLNRSLRYGVKTMFATAGAATRQFQRVQGLRGGPTRLKSSGRDYFDLTPDDDQKLIIETVDEFAEEVLRPAAHDADDAATYPSDLTAKAAELGITAINIPEDFDGIAEHRSSVTNVLVAEALAYGDMGLALPILAPGGVASALTHWGSADQQATYLKEFAGENVPQACVAITEPQPLFDPTRLKTTAVRTPSGYRLDGVKSLIPAAADAELFIVGAQLGGKPALFIVESAASGLTVKADPSMGIRGAALGQVELCGVSVPLNARLGEDEASDNDYSEALALARLGWAALAVGTSHAVLDYVVPYVKQRQAFGEPIAHRQAVAFMCANIAIELDGLRLITWRGASRAEQGLPFAREAALAKRLGSDKGMQIGLDGVQLLGGHGYTKEHPVERWYRDLRAIGVAEGVVVI