fadB4 Family assigned · medium auto-curated
H37Rv Rv3141 · MTBC0 mtbc0_003339 ·
323 aa · 3530797–3531768 (+) ·
RefSeq NP_217657.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | NADPH quinone oxidoreductase FadB |
|---|---|
| MTBC0 PGAP re-annotation | NADPH:quinone oxidoreductase family protein |
| Revised (this work) | NADPH:quinone oxidoreductase family protein. Pfam: ADH_N (PF08240.18), ADH_zinc_N (PF00107.33), ADH_zinc_N_2 (PF13602.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P95185
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable NADPH quinone oxidoreductase FadB4 |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | fadB4 |
| eggNOG description | NADPH quinone |
| Orthologous group | COG0604 |
| EC number |
EC 1.6.5.5
|
| KEGG orthology |
K00344
|
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 | 0.192 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 1 missense, 0 nonsense, 0 frameshift |
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 |
|---|---|---|---|---|
ADH_N | PF08240.18 | 1.1e-11 | 27–108 | Alcohol dehydrogenase GroES-like domain |
ADH_zinc_N | PF00107.33 | 2.9e-26 | 149–265 | Zinc-binding dehydrogenase |
ADH_zinc_N_2 | PF13602.13 | 3.0e-19 | 183–319 | Zinc-binding dehydrogenase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: pks15 (polyketide synthase), high confidence from genomic context alone (score 915 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2947c pks15 |
polyketide synthase | 916 | 915 ctx | fusion:899 |
Rv2382c mbtC |
polyketide synthetase | 915 | 915 ctx | fusion:899 |
Rv1180 pks3 |
polyketide beta-ketoacyl synthase | 915 | 914 ctx | fusion:898 |
Rv0130 htdZ |
3-hydroxyl-thioester dehydratase | 815 | 811 ctx | fusion:741 |
Rv1664 pks9 |
polyketide synthase | 752 | 751 ctx | fusion:702 |
Rv3140 fadE23 |
acyl-CoA dehydrogenase FadE23 | 814 | 664 ctx | neighborhood:615 textmining:469 |
Rv3139 fadE24 |
acyl-CoA dehydrogenase | 793 | 606 ctx | neighborhood:548 textmining:498 |
Rv3761c fadE36 |
acyl-CoA dehydrogenase FadE36 | 478 | 479 | |
Rv0154c fadE2 |
acyl-CoA dehydrogenase FadE2 | 459 | 460 | |
Rv0405 pks6 |
membrane bound polyketide synthase | 449 | 422 | |
Rv2932 ppsB |
phthiocerol synthesis polyketide synthase type I PpsB | 433 | 396 | |
Rv3138 pflA |
pyruvate formate lyase activating protein PflA | 873 | 385 | textmining:803 |
Rv3137 hisN |
histidinol-phosphatase | 780 | 368 | textmining:666 |
Rv2524c fas |
fatty acid synthase | 404 | 304 | |
Rv1912c fadB5 |
oxidoreductase FadB | 497 | 298 |
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 quinone oxidoreductase FadB
- MTBC0 PGAP product: NADPH:quinone oxidoreductase family protein
- Pfam (hmmscan --cut_ga): ADH_N PF08240.18 (E=1e-11), ADH_zinc_N PF00107.33 (E=3e-26), ADH_zinc_N_2 PF13602.13 (E=3e-19)
- (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_217657.1)
- Domains: Pfam-A via hmmscan --cut_ga — ADH_N (PF08240.18), ADH_zinc_N (PF00107.33), ADH_zinc_N_2 (PF13602.13)
- 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
COG0604 - Curated reference: UniProt P95185 (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 —
21 functional partner(s); context anchor
pks15 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003339|Rv3141|fadB4 MRAVRVTRLEGPDAVEVAEVEEPTSAGVVIEVHAAGVAFPDALLTRGRYQYRPEPPFVLGAEIAGVVRSAPDNSQVRSGDRVVGLTMLTGGMAEVAVLSPERVFKLPDNMTFEAGAGVLFNDLTVYFALAVRGRLQAGETVLVHGAAGGIGTSTLRLAPALGASRTVAVVSTQEKAELATVAGATDVVLAEGFKDAVQELTNGRGVDIVVDPVGGDRFTDSLRSLAAGGRLLVIGFTGGEIPTVKVNRLLLNNIDVVGVGWGAWSLTHPDALAQQWSQLERLLRSGKLPPPEPVVYPLDQAAAAIASLENRTAKGKVVLRVRD