fadE6 Family assigned · medium auto-curated

H37Rv Rv0271c · MTBC0 mtbc0_000288 · 731 aa · 326648–328843 (-) · RefSeq NP_214785.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)acyl-CoA dehydrogenase FadE6
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_1 (PF00441.30), Acyl-CoA_dh_2 (PF08028.17), Acyl-CoA_dh_M (PF02770.25).

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

Curated reference (UniProt)

UniProt P95228 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable acyl-CoA dehydrogenase FadE6

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Preferred namefadE6
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 0.294 · purifying
Polymorphic sites (≥ 0.1% of strains) 12 synonymous, 10 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.94% of strains (1362) · clonal

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-106–112 Acyl-CoA dehydrogenase, N-terminal domain
Acyl-CoA_dh_1PF00441.30 8.9e-25217–340 Acyl-CoA dehydrogenase, C-terminal domain
Acyl-CoA_dh_2PF08028.17 1.6e-08218–321 Acyl-CoA dehydrogenase, C-terminal domain
Acyl-CoA_dh_MPF02770.25 5.8e-18469–561 Acyl-CoA dehydrogenase, middle domain

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

Closest characterised functional partner: Rv0273c (transcriptional regulator), high confidence from genomic context alone (score 785 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0272c hyp hypothetical protein 802 802 ctx neighborhood:757
Rv0860 fadB fatty oxidation protein FadB 804 789 coexpression:650
Rv0273c transcriptional regulator 785 785 ctx neighborhood:715
Rv3541c chsH1 hyp hypothetical protein 770 762 ctx cooccurence:549
Rv3029c fixA electron transfer flavoprotein subunit beta 733 716 coexpression:408 experimental:418
Rv3028c fixB electron transfer flavoprotein subunit alpha 722 711 coexpression:412 experimental:419
Rv3522 ltp4 lipid transfer protein 712 702 ctx cooccurence:498
Rv0274 hyp hypothetical protein 685 673 ctx neighborhood:544
Rv3550 echA20 enoyl-CoA hydratase EchA20 682 670
Rv3540c ltp2 lipid transfer protein 678 667 ctx cooccurence:431
Rv3523 ltp3 lipid carrier protein 677 666 ctx cooccurence:433
Rv3153 nuoI NADH-quinone oxidoreductase subunit I 651 637
Rv3538 dehydrogenase 628 628
Rv3548c short-chain type dehydrogenase/reductase 614 601
Rv3509c ilvX acetohydroxyacid synthase large subunit 607 601 database:407

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 FadE6
  • MTBC0 PGAP product: acyl-CoA dehydrogenase family protein
  • Pfam (hmmscan --cut_ga): Acyl-CoA_dh_N PF02771.22 (E=4e-10), Acyl-CoA_dh_1 PF00441.30 (E=9e-25), Acyl-CoA_dh_2 PF08028.17 (E=2e-08), Acyl-CoA_dh_M PF02770.25 (E=6e-18)
  • (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_214785.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Acyl-CoA_dh_N (PF02771.22), Acyl-CoA_dh_1 (PF00441.30), Acyl-CoA_dh_2 (PF08028.17), Acyl-CoA_dh_M (PF02770.25)
  • 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 P95228 (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 — 127 functional partner(s); context anchor Rv0273c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000288|Rv0271c|fadE6
MSIAITPEHYELADSVRSLVARVAPSEVLHAALESPVENPPPYWQAAAEQGLQGVHLAESVGGQGFGILELAVVLAEFGYGAVPGPFVPSAIASALIAAHDPQAKVLAELATGAAIAAYALDSGLTATRHGDVLVIRGEVRAVPAAAQASVLVLPVAIESRDEWVVLRNDQLEIEAVKSLDPLRPIAHVRANAVDVSDDALLSNLTMTTAHALMSTLLSAEAVGVARWATDTASAYAKIREQFGRPIGQFQAIKHKCAEMIADTERATAAVWDAARALDDAGESSSDVEFAAAVAATLAPATAQRCTQDCIQVHGGIGFTWEHDTNVYYRRALMLAACFGRGSEYPQRVVDTATTAGMRPVDIDLDPSTEKLRAQIRAEVAALKAMPREPRTVAIAEGGWVLPYLPKPWGRAASPVEQIIIAQEFTAGRVKRPQIAIATWIVPSIVAFGTDNQKQRLLPPTFRGDIFWCQLFSEPGAGSDLASLATKATRVDGGWRITGQKIWTTGAQYSQWGALLARTDPSAPKHNGITYFLLDMKSEGVQVKPLRELTGKEFFNTVYLDDVFVPDELVLGEVNRGWEVSRNTLTAERVSIGGSDSTFLPTLGEFVDFVRDYRFEGQFDQVARHRAGQLIAEGHATKLLNLRSTLLTLAGGDPMAPAAISKLLSMRTGQGYAEFAVSSFGTDAVIGDTERLPGKWGEYLLASRATTIYGGTSEVQLNIIAERLLGLPRDP