fadH Resolved · high auto-curated
H37Rv Rv1175c · MTBC0 mtbc0_001264 ·
674 aa · 1314643–1316667 (-) ·
RefSeq NP_215691.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | NADPH dependent 2,4-dienoyl-CoA reductase FadH |
|---|---|
| MTBC0 PGAP re-annotation | NADPH-dependent 2%2C4-dienoyl-CoA reductase |
| Revised (this work) | NADPH-dependent 2%2C4-dienoyl-CoA reductase. Pfam: Oxidored_FMN (PF00724.27), Pyr_redox_2 (PF07992.21), Pyr_redox (PF00070.34), FAD_oxidored (PF12831.14), DAO (PF01266.31), FAD_binding_2 (PF00890.31), NAD_binding_8 (PF13450.13), Amino_oxidase (PF01593.31). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O50431
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable NADPH dependent 2,4-dienoyl-CoA reductase FadH |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | fadH |
| eggNOG description | COG1902 NADH flavin oxidoreductases, Old Yellow Enzyme family |
| Orthologous group | COG0446 |
| EC number |
EC 1.3.1.34
|
| KEGG orthology |
K00219
|
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 | 0.466 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 10 synonymous, 13 missense, 0 nonsense, 4 frameshift |
| Disruption | 4 distinct premature-stop/frameshift site(s); most common in 0.23% of strains (331) · convergent |
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 |
|---|---|---|---|---|
Oxidored_FMN | PF00724.27 | 1.2e-80 | 8–332 | NADH:flavin oxidoreductase / NADH oxidase family |
Pyr_redox_2 | PF07992.21 | 1.1e-24 | 378–636 | Pyridine nucleotide-disulphide oxidoreductase |
Pyr_redox | PF00070.34 | 5.5e-06 | 378–458 | Pyridine nucleotide-disulphide oxidoreductase |
FAD_oxidored | PF12831.14 | 3.7e-08 | 379–415 | FAD dependent oxidoreductase |
DAO | PF01266.31 | 8.0e-08 | 379–413 | FAD dependent oxidoreductase |
FAD_binding_2 | PF00890.31 | 7.4e-06 | 379–418 | FAD binding domain |
NAD_binding_8 | PF13450.13 | 8.1e-10 | 381–435 | NAD(P)-binding Rossmann-like domain |
Amino_oxidase | PF01593.31 | 5.3e-04 | 387–413 | Flavin containing amine oxidoreductase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: gltB (glutamate synthase large subunit), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3859c gltB |
glutamate synthase large subunit | 999 | 1000 ctx | neighborhood:544 coexpression:999 experimental:999 textmining:670 |
Rv3029c fixA |
electron transfer flavoprotein subunit beta | 996 | 995 | experimental:994 |
Rv1937 |
oxygenase | 996 | 992 | experimental:973 database:568 textmining:647 |
Rv3028c fixB |
electron transfer flavoprotein subunit alpha | 950 | 933 | experimental:922 |
Rv1176c hyp |
hypothetical protein | 910 | 910 ctx | neighborhood:882 |
Rv1162 narH |
nitrate reductase subunit beta | 908 | 899 | experimental:899 |
Rv3230c |
stearoyl-CoA 9-desaturase electron transfer protein | 862 | 812 | experimental:430 database:568 |
Rv3554 fdxB |
electron transfer protein FdxB | 901 | 786 | experimental:430 database:568 textmining:558 |
Rv3571 kshB |
3-ketosteroid-9-alpha-hydroxylase reductase subunit | 837 | 777 | experimental:430 database:568 |
Rv2776c |
oxidoreductase | 836 | 776 | experimental:430 database:568 |
Rv0766c cyp123 |
cytochrome P450 Cyp123 | 759 | 745 ctx | neighborhood:522 database:485 |
Rv1177 fdxC |
ferredoxin FdxC | 793 | 681 ctx | neighborhood:522 |
Rv0860 fadB |
fatty oxidation protein FadB | 736 | 571 | textmining:411 |
Rv0761c adhB |
alcohol dehydrogenase B | 590 | 565 ctx | neighborhood:544 |
Rv0385 |
monooxygenase | 677 | 556 | experimental:471 |
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: NADPH dependent 2,4-dienoyl-CoA reductase FadH
- MTBC0 PGAP product: NADPH-dependent 2%2C4-dienoyl-CoA reductase
- Pfam (hmmscan --cut_ga): Oxidored_FMN PF00724.27 (E=1e-80), Pyr_redox_2 PF07992.21 (E=1e-24), Pyr_redox PF00070.34 (E=5e-06), FAD_oxidored PF12831.14 (E=4e-08), DAO PF01266.31 (E=8e-08), FAD_binding_2 PF00890.31 (E=7e-06), NAD_binding_8 PF13450.13 (E=8e-10), Amino_oxidase PF01593.31 (E=5e-04)
- (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_215691.1)
- Domains: Pfam-A via hmmscan --cut_ga — Oxidored_FMN (PF00724.27), Pyr_redox_2 (PF07992.21), Pyr_redox (PF00070.34), FAD_oxidored (PF12831.14), DAO (PF01266.31), FAD_binding_2 (PF00890.31), NAD_binding_8 (PF13450.13), Amino_oxidase (PF01593.31)
- 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
COG0446 - Curated reference: UniProt O50431 (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 —
87 functional partner(s); context anchor
gltB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001264|Rv1175c|fadH MTNPYPNLLSPLDLGFTTLRNRVVMGSMHTGLEDRARHIDRLADYFAERARGGVGLIITGGYAPNRTGWLLPFASELVTSAQARRHRRITRAVHDSGAKILLQILHAGRYAYHPLAVSASPIKAPITPFRPRALSARGVEATIADFARCAQLARDAGYDGVEIMGSEGYLLNQFLAPRTNKRTDSWGGTPANRRRFPVEIIRRSRAAVGSDFIICYRLSMADYVAEGQSWDEIVALATEVEGAGATIINSGFGWHEARVPTIVTSVPGGAFVDISSAVAEHVTIPVVASNRINMPQAAERILAETQVRLISMARPMLSDPDWVLKAQSNRVDEINTCISCNQACLDHAFARKTVSCLLNPRAGRETQLVLSPTRRARSVAVVGAGPAGLATAANAAQRGHRVTLFEANDFIGGQFDMARRIPGKEEFSETIRYFSTILAKHGVEVRLGTRVAAQELTGYDEVVLATGVAPRIPAIPGIDHPMVLTYAEAITGVRPVGRTVAVVGAGGIGFDVTELLVTDSSPTLNLKEWKAEWGVADPREARGALTTPLPAPPAREVYLLQRTKGPQGKRLGKTTGWVHRASLKAKGVHQLSGVNYEQINDDGLHISFGPKRRRPQLLAVDNVVVCAGQEPVRDLESELRRHGINPHIIGGAAVAAELDAKRAIKQGTELAARL