fadE23 Family assigned · medium auto-curated

H37Rv Rv3140 · MTBC0 mtbc0_003338 · 401 aa · 3529492–3530697 (+) · RefSeq NP_217656.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)acyl-CoA dehydrogenase FadE23
MTBC0 PGAP re-annotationacyl-CoA dehydrogenase family protein
Revised (this work)Acyl-CoA dehydrogenase family protein. Pfam: 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 P95186 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable acyl-CoA dehydrogenase FadE23

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Preferred namefadE23
eggNOG descriptionacyl-CoA dehydrogenase
Orthologous groupCOG1960
EC number EC 1.3.8.7
KEGG orthology K00249
KEGG pathways map00071, map00280, map00410, map00640, map01100, map01110, map01130, map01200, map01212, map03320
KEGG modules M00013, M00036, M00087

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 0.804 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 10 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_MPF02770.25 1.1e-24130–224 Acyl-CoA dehydrogenase, middle domain
Acyl-CoA_dh_1PF00441.30 8.1e-28241–393 Acyl-CoA dehydrogenase, C-terminal domain
Acyl-CoA_dh_2PF08028.17 7.8e-11258–381 Acyl-CoA dehydrogenase, C-terminal domain

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

Closest characterised functional partner: fadE24 (acyl-CoA dehydrogenase), high confidence from genomic context alone (score 985 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3139 fadE24 acyl-CoA dehydrogenase 994 985 ctx neighborhood:853 coexpression:860 textmining:637
Rv2790c ltp1 lipid-transfer protein 945 942 database:900
Rv0860 fadB fatty oxidation protein FadB 966 937 coexpression:647 database:750 textmining:488
Rv2502c accD1 acetyl-/propionyl-CoA carboxylase subunit beta 924 921 database:900
Rv0400c fadE7 acyl-CoA dehydrogenase FadE7 916 917 database:900
Rv0905 echA6 enoyl-CoA hydratase EchA6 851 846 database:750
Rv0243 fadA2 acetyl-CoA acetyltransferase FadA 865 845 coexpression:402 database:650
Rv1070c echA8 enoyl-CoA hydratase EchA8 860 845 database:750
Rv0673 echA4 enoyl-CoA hydratase EchA4 859 845 database:750
Rv1071c echA9 enoyl-CoA hydratase EchA9 853 845 database:750
Rv3774 echA21 enoyl-CoA hydratase EchA21 853 845 database:750
Rv3550 echA20 enoyl-CoA hydratase EchA20 851 845 database:750
Rv1141c echA11 enoyl-CoA hydratase EchA11 850 845 database:750
Rv2486 echA14 enoyl-CoA hydratase EchA14 850 845 database:750
Rv0632c echA3 enoyl-CoA hydratase EchA3 850 845 database:750

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 FadE23
  • MTBC0 PGAP product: acyl-CoA dehydrogenase family protein
  • Pfam (hmmscan --cut_ga): Acyl-CoA_dh_M PF02770.25 (E=1e-24), Acyl-CoA_dh_1 PF00441.30 (E=8e-28), Acyl-CoA_dh_2 PF08028.17 (E=8e-11)
  • (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_217656.1)
  • Domains: Pfam-A via hmmscan --cut_ga — 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 P95186 (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 — 128 functional partner(s); context anchor fadE24
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003338|Rv3140|fadE23
MAINLELPRKLQAIIVKTHQGAAEMMRPIARKYDLKEHAYPVELDTLINLFEGAAESFNFAGAHSLRDEDEGKDENHNGANMAAVVQTMEASWGDVAMMLSLPYQGLGNAAISAVATDEQLERLGKVWAAMAITEPEFGSDSAAVSTTATLDGDEYVINGEKIFVTAGSRATHIVVWATLDKSLGRPAIKSFIVPREHPGVTVERLEHKLGIKGSDTAVIRFDNARIPKGNLLGNPEIEVGKGFAGVMETFDNTRPIVAAMAVGIGRAALEEIRSVLTGAGVEISYDKPSHTQSAAAAEFLRMEADWEASYLLSLRAAWQADNNIPNSKEASMSKAKAGRMASDVTCKTVELAGTTGYSEQSLLEKWARDSKILDIFEGTQQIQQLVVARRLLGLSSSELK