fadE35 Resolved · high auto-curated
H37Rv Rv3797 · MTBC0 mtbc0_004025 ·
593 aa · 4275206–4276987 (+) ·
RefSeq NP_218314.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | acyl-CoA dehydrogenase FadE35 |
|---|---|
| MTBC0 PGAP re-annotation | DNA alkylation response protein |
| Revised (this work) | DNA alkylation response protein. Pfam: AidB_N (PF18158.7), 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 |
O53577
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable acyl-CoA dehydrogenase FadE35 |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
|---|---|
| Preferred name | fadE35 |
| 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 | 0.45 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 7 synonymous, 9 missense, 0 nonsense, 3 frameshift |
| Disruption | 3 distinct premature-stop/frameshift site(s); most common in 0.72% of strains (1045) · 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 |
|---|---|---|---|---|
AidB_N | PF18158.7 | 2.9e-07 | 33–187 | Adaptive response protein AidB N-terminal domain |
Acyl-CoA_dh_M | PF02770.25 | 2.1e-16 | 192–290 | Acyl-CoA dehydrogenase, middle domain |
Acyl-CoA_dh_1 | PF00441.30 | 2.1e-41 | 309–461 | Acyl-CoA dehydrogenase, C-terminal domain |
Acyl-CoA_dh_2 | PF08028.17 | 1.4e-13 | 325–446 | Acyl-CoA dehydrogenase, C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: fadE18 (acyl-CoA dehydrogenase FadE18), high confidence from genomic context alone (score 721 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0860 fadB |
fatty oxidation protein FadB | 805 | 789 | coexpression:650 |
Rv3028c fixB |
electron transfer flavoprotein subunit alpha | 787 | 779 | coexpression:408 experimental:419 |
Rv3029c fixA |
electron transfer flavoprotein subunit beta | 769 | 760 | coexpression:404 experimental:418 |
Rv1933c fadE18 |
acyl-CoA dehydrogenase FadE18 | 721 | 721 ctx | cooccurence:720 |
Rv1934c fadE17 |
acyl-CoA dehydrogenase FadE17 | 676 | 676 ctx | cooccurence:675 |
Rv2679 echA15 |
enoyl-CoA hydratase EchA15 | 664 | 652 | |
Rv0632c echA3 |
enoyl-CoA hydratase EchA3 | 648 | 635 | |
Rv3153 nuoI |
NADH-quinone oxidoreductase subunit I | 649 | 634 | |
Rv0456c echA2 |
enoyl-CoA hydratase EchA2 | 639 | 626 | |
Rv0673 echA4 |
enoyl-CoA hydratase EchA4 | 639 | 625 | |
Rv0675 echA5 |
enoyl-CoA hydratase EchA5 | 637 | 624 | |
Rv1346 mbtN |
acyl-[acyl-carrier-protein | 591 | 592 ctx | cooccurence:589 |
Rv2048c pks12 |
polyketide synthase | 616 | 585 | database:459 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 616 | 585 | database:459 |
Rv1527c pks5 |
polyketide synthase | 615 | 585 | 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 FadE35
- MTBC0 PGAP product: DNA alkylation response protein
- Pfam (hmmscan --cut_ga): AidB_N PF18158.7 (E=3e-07), Acyl-CoA_dh_M PF02770.25 (E=2e-16), Acyl-CoA_dh_1 PF00441.30 (E=2e-41), Acyl-CoA_dh_2 PF08028.17 (E=1e-13)
- (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_218314.1)
- Domains: Pfam-A via hmmscan --cut_ga — AidB_N (PF18158.7), 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 O53577 (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 —
117 functional partner(s); context anchor
fadE18 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_004025|Rv3797|fadE35 MPEYDLEAVDKLPFSTPEKAQRYQTENYRGAMGLNWYLTDPTLQFIMAYYLRPDELAFAEPHLTRIGELTGGPVTRWAEETDRNPPRLERYDRWGHDISRVVLPESFIQSKRAVIEARQAVRDDAARAGVKPSLALFAADYLLNQADIGMACALATGGNMVRSLVTAYAPPDVREFVLGKLNSGEWDGEAAQLLTERAGGSDLGALETTATRSGDVWLLNGFKWFASNCAGEAFVVLAKPEGAPDSTRGVATFLVLRTRRDGSRNGVRIRRLKDKLGTRSVASGEIEFVDAEAFLLSGEPSADAGPSDGKGLTRMMELTNRLRLGTASFALGNARRALVESLCYAGQRRAFGGALIDKPLMRRKLAEMVVDVEAALAMVFDGFGAANHRQPRCLPQRIAVPVTKLKTCRLGITVASDAIEIHGGNGYIETWPVARLLRDAQVNTIWEGPDNILCLDVRRGIEQTRAHETLLARLRDAVSVSDDDDTTRLVSRRIEDLDAAITAWTKLDRQLAEARLFPLAQFMGDVYAGALLTEQAAWERATRGTDRKALVARLYARRYLADQGPLRGIDADCDEALQRFDELVAGAFTAEQT