fadE22 Resolved · high auto-curated
H37Rv Rv3061c · MTBC0 mtbc0_003253 ·
721 aa · 3444626–3446791 (-) ·
RefSeq NP_217577.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | acyl-CoA dehydrogenase FadE22 |
|---|---|
| MTBC0 PGAP re-annotation | acyl-CoA dehydrogenase |
| Revised (this work) | Acyl-CoA dehydrogenase. Pfam: Acyl-CoA_dh_N (PF02771.22), Acyl-CoA_dh_1 (PF00441.30), 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 |
I6X654
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable acyl-CoA dehydrogenase FadE22 |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
|---|---|
| Preferred name | fadE22 |
| 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) pseudogene candidate
| pN/pS | 1.146 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 13 missense, 0 nonsense, 3 frameshift |
| Disruption | 3 distinct premature-stop/frameshift site(s); most common in 7.31% of strains (10621) · 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_N | PF02771.22 | 5.7e-20 | 6–116 | Acyl-CoA dehydrogenase, N-terminal domain |
Acyl-CoA_dh_1 | PF00441.30 | 1.2e-23 | 204–329 | Acyl-CoA dehydrogenase, C-terminal domain |
Acyl-CoA_dh_M | PF02770.25 | 2.1e-17 | 461–555 | Acyl-CoA dehydrogenase, middle domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ligB (DNA ligase), high confidence from genomic context alone (score 771 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0860 fadB |
fatty oxidation protein FadB | 804 | 789 | coexpression:649 |
Rv3062 ligB |
DNA ligase | 771 | 771 ctx | neighborhood:770 |
Rv3060c |
GntR family transcriptional regulator | 728 | 718 ctx | neighborhood:651 |
Rv3029c fixA |
electron transfer flavoprotein subunit beta | 723 | 712 | coexpression:406 experimental:418 |
Rv3541c chsH1 hyp |
hypothetical protein | 721 | 711 ctx | cooccurence:447 |
Rv3028c fixB |
electron transfer flavoprotein subunit alpha | 717 | 706 | coexpression:408 experimental:419 |
Rv3550 echA20 |
enoyl-CoA hydratase EchA20 | 703 | 684 | |
Rv0310c hyp |
hypothetical protein | 660 | 649 ctx | cooccurence:416 |
Rv3523 ltp3 |
lipid carrier protein | 661 | 648 | |
Rv1935c echA13 |
enoyl-CoA hydratase EchA13 | 660 | 648 | |
Rv3522 ltp4 |
lipid transfer protein | 655 | 642 | |
Rv3153 nuoI |
NADH-quinone oxidoreductase subunit I | 649 | 634 | |
Rv2679 echA15 |
enoyl-CoA hydratase EchA15 | 647 | 633 | |
Rv3540c ltp2 |
lipid transfer protein | 634 | 621 | |
Rv3509c ilvX |
acetohydroxyacid synthase large subunit | 618 | 612 | 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 FadE22
- MTBC0 PGAP product: acyl-CoA dehydrogenase
- Pfam (hmmscan --cut_ga): Acyl-CoA_dh_N PF02771.22 (E=6e-20), Acyl-CoA_dh_1 PF00441.30 (E=1e-23), Acyl-CoA_dh_M PF02770.25 (E=2e-17)
- (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_217577.1)
- Domains: Pfam-A via hmmscan --cut_ga — Acyl-CoA_dh_N (PF02771.22), Acyl-CoA_dh_1 (PF00441.30), 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 I6X654 (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 —
129 functional partner(s); context anchor
ligB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003253|Rv3061c|fadE22 MGIALTDDHRELSGVARAFLTSQKVRWAARASLDAAGDARPPFWQNLAELGWLGLHIDERHGGSGYGLSELVVVIEELGRAVAPGLFVPTVIASAVVAKEGTDDQRARLLPALIDGTLTAGVGLDSQVQVTDGVADGEAGIVLGAGLAELLLVAAGDDVLVLERGRKGVSVDVPENFDPTRRSGRVRLDNVRVTTDDILLGAYESALARARTLLAAEAVGGAADCVDSAVAYAKVRQQFGRTIATFQAVKHHCANMLVAAESAIAAVWDAARAAAEDEEQFRLAAAVAAALAFPAYARNAELNIQVHGGIGFTWEHDAHLHLRRALVTVGLFGGDAPVRDVFERTAAGVTRAISLDLPAQAEELRARIRSDAAEIAALEKDAQRDKLIETGYVMPHWPRPWGRAAGAVEQLVIEEEFSAAGIERPDYSITGWVILTLIQHGTPWQIERFVEKALRQQEIWCQLFSEPDAGSDAASVKTRATRVEGGWKINGQKVWTSGAQYCARGLATVRTDPDAPKHAGITTVIIDMLAPGVEVRPLRQITGDSEFNEVFFNDVFVPDEDVVGAPNSGWTVARATLGNERVSIGGSGSYYEAMAAKLVQLVQRRSDAFAGAPIRVGAFLAEDHALRLLNLRRAARSVEGAGPGPEGNITKLKVAEHMIEGAAIAAALWGPEIALLDGPGRVIGRTVMGARGMAIAGGTSEVTRNQIAERILGMPRDPLIS