fadE5 Resolved · high auto-curated
H37Rv Rv0244c · MTBC0 mtbc0_000260 ·
611 aa · 294180–296015 (-) ·
RefSeq NP_214758.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | acyl-CoA dehydrogenase FadE5 |
|---|---|
| MTBC0 PGAP re-annotation | acyl-CoA dehydrogenase |
| Revised (this work) | Acyl-CoA dehydrogenase. Pfam: Acyl-CoA_dh_M (PF02770.25), Acyl-CoA_dh_1 (PF00441.30), Acyl-CoA_dh_C (PF12806.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53666
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Broad-specificity linear acyl-CoA dehydrogenase FadE5 |
| EC (curated) |
EC 1.3.8.1, EC 1.3.8.7, EC 1.3.8.8
|
| Curated function | Acyl-CoA dehydrogenase that exhibits broad specificity for linear acyl-CoA substrates, with a preference for long-chain substrates. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
|---|---|
| Preferred name | fadE5 |
| eggNOG description | acyl-CoA dehydrogenase |
| Orthologous group | COG1960 |
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 | 0.448 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 10 synonymous, 14 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.73% of strains (1060) · 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
Acyl-CoA_dh_M | PF02770.25 | 4.1e-14 | 162–271 | Acyl-CoA dehydrogenase, middle domain |
Acyl-CoA_dh_1 | PF00441.30 | 1.0e-12 | 288–454 | Acyl-CoA dehydrogenase, C-terminal domain |
Acyl-CoA_dh_C | PF12806.13 | 5.2e-30 | 475–607 | Acetyl-CoA dehydrogenase C-terminal like |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv3679 (anion transporter ATPase), medium confidence from genomic context alone (score 685 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0860 fadB |
fatty oxidation protein FadB | 909 | 793 | coexpression:656 textmining:581 |
Rv3028c fixB |
electron transfer flavoprotein subunit alpha | 783 | 774 | coexpression:410 experimental:419 |
Rv0487 hyp |
hypothetical protein | 746 | 747 ctx | cooccurence:745 |
Rv3029c fixA |
electron transfer flavoprotein subunit beta | 743 | 732 | coexpression:408 experimental:418 |
Rv3679 |
anion transporter ATPase | 684 | 685 ctx | cooccurence:682 |
Rv3680 |
anion transporter ATPase | 638 | 638 ctx | cooccurence:635 |
Rv3153 nuoI |
NADH-quinone oxidoreductase subunit I | 649 | 634 | |
Rv0632c echA3 |
enoyl-CoA hydratase EchA3 | 646 | 633 | |
Rv0971c echA7 |
enoyl-CoA hydratase EchA7 | 640 | 627 | |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 634 | 588 | database:459 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 619 | 588 | database:459 |
Rv2048c pks12 |
polyketide synthase | 617 | 587 | database:459 |
Rv1527c pks5 |
polyketide synthase | 615 | 585 | database:459 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 714 | 584 | database:459 |
Rv0905 echA6 |
enoyl-CoA hydratase EchA6 | 646 | 578 |
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 FadE5
- MTBC0 PGAP product: acyl-CoA dehydrogenase
- Pfam (hmmscan --cut_ga): Acyl-CoA_dh_M PF02770.25 (E=4e-14), Acyl-CoA_dh_1 PF00441.30 (E=1e-12), Acyl-CoA_dh_C PF12806.13 (E=5e-30)
- (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_214758.1)
- Domains: Pfam-A via hmmscan --cut_ga — Acyl-CoA_dh_M (PF02770.25), Acyl-CoA_dh_1 (PF00441.30), Acyl-CoA_dh_C (PF12806.13)
- 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 O53666 (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 —
126 functional partner(s); context anchor
Rv3679 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000260|Rv0244c|fadE5 MSHYRSNVRDQVFNLFEVLGVDKALGHGEFSDVDVDTARDMLAEVSRLAEGPVAESFVEGDRNPPVFDPKTHSVMLPESFKKSVNAMLEAGWDKVGIDEALGGMPMPKAVVWALHEHILGANPAVWMYAGGAGFAQILYHLGTEEQKKWAVLAAERGWGSTMVLTEPDAGSDVGAARTKAVQQADGSWHIDGVKRFITSGDSGDLFENIFHLVLARPEGAGPGTKGLSLYFVPKFLFDVETGEPGERNGVFVTNVEHKMGLKVSATCELAFGQHGVPAKGWLVGEVHNGIAQMFEVIEQARMMVGTKAIATLSTGYLNALQYAKSRVQGADLTQMTDKTAPRVTITHHPDVRRSLMTQKAYAEGLRALYLYTATFQDAAVAEVVHGVDAKLAVKVNDLMLPVVKGVGSEQAYAKLTESLQTLGGSGFLQDYPIEQYIRDAKIDSLYEGTTAIQAQDFFFRKIVRDKGVALAHVSGQIQEFVDSGAGNGRLKTERALLAKALTDVQGMAAALTGYLMAAQQDVTSLYKVGLGSVRFLMSVGDLIIGWLLQRQAAVAVAALDAGATGDERSFYEGKVAVASFFAKNFLPLLTSTREVIETLDNDIMELDEAAF