mftD Resolved · high auto-curated
H37Rv Rv0694 · MTBC0 mtbc0_000735 ·
396 aa · 797421–798611 (+) ·
RefSeq NP_215208.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | mycofactocin system heme/flavin oxidoreductase MftD |
|---|---|
| MTBC0 PGAP re-annotation | pre-mycofactocin synthase MftD |
| Revised (this work) | Pre-mycofactocin synthase MftD. Pfam: FMN_dh (PF01070.25), IMPDH (PF00478.32), Glu_synthase (PF01645.24). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WND7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Pre-mycofactocin synthase |
| EC (curated) |
EC 1.4.3.26
|
| Curated function | Involved in the biosynthesis of the enzyme cofactor mycofactocin (MFT). Catalyzes the oxidative deamination of AHDP (3-amino-5-[(4-hydroxyphenyl)methyl]-4,4-dimethyl-2-pyrrolidin-2-one), forming an alpha-keto amide moiety on the resulting molecule, which is called pre-mycofactocin (PMFT). This reaction occurs via a 5-[(4-hydroxyphenyl)methyl]-3-imino-4,4-dimethylpyrrolidin-2-one intermediate, which converts to PMFT. The alpha-keto amide moiety is the redox-active center for the redox activity of mycofactocin. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | lldD1 |
| eggNOG description | Dehydrogenase |
| Orthologous group | COG1304 |
| EC number |
EC 1.1.2.3, EC 1.1.3.15
|
| KEGG orthology |
K00101, K00104
|
| KEGG pathways |
map00620, map00630, map01100, map01110, map01120, map01130
|
| Gene Ontology (6) |
GO:0005575, GO:0005623, GO:0005886, GO:0016020, GO:0044464, GO:0071944
|
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 | 0.412 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 7 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 1.18% of strains (1708) · 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 |
|---|---|---|---|---|
FMN_dh | PF01070.25 | 1.9e-110 | 16–376 | FMN-dependent dehydrogenase |
IMPDH | PF00478.32 | 1.8e-06 | 295–334 | IMP dehydrogenase / GMP reductase domain |
Glu_synthase | PF01645.24 | 5.1e-06 | 298–336 | Conserved region in glutamate synthase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mftC (mycofactocin radical SAM maturase MftC), high confidence from genomic context alone (score 994 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0693 mftC |
mycofactocin radical SAM maturase MftC | 999 | 994 ctx | neighborhood:882 cooccurence:665 coexpression:860 textmining:875 |
Rv0692 mftB |
mycofactocin system protein MftB | 999 | 990 ctx | neighborhood:882 cooccurence:699 coexpression:734 textmining:907 |
Rv1617 pykA |
pyruvate kinase | 938 | 932 | database:900 |
Rv1872c lldD2 |
L-lactate dehydrogenase | 936 | 920 | database:900 |
Rv2967c pca |
pyruvate carboxylase | 912 | 906 | database:900 |
Rv2455c korA |
2-oxoglutarate oxidoreductase subunit KorA | 929 | 904 | database:900 |
Rv2332 mez |
malate oxidoreductase | 912 | 903 | database:900 |
Rv2497c bkdA |
3-methyl-2-oxobutanoate dehydrogenase subunit alpha | 906 | 903 | database:900 |
Rv2454c korB |
2-oxoglutarate oxidoreductase subunit KorB | 910 | 902 | database:900 |
Rv2241 aceE |
pyruvate dehydrogenase E1 component | 910 | 901 | database:900 |
Rv1127c ppdK |
pyruvate, phosphate dikinase PpdK | 906 | 901 | database:900 |
Rv2496c bkdB |
3-methyl-2-oxobutanoate dehydrogenase subunit beta | 904 | 901 | database:900 |
Rv3470c ilvB2 |
acetolactate synthase large subunit | 911 | 899 | database:893 |
Rv3003c ilvB1 |
acetolactate synthase large subunit IlvB | 904 | 899 | database:893 |
Rv3509c ilvX |
acetohydroxyacid synthase large subunit | 904 | 899 | database:893 |
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: mycofactocin system heme/flavin oxidoreductase MftD
- MTBC0 PGAP product: pre-mycofactocin synthase MftD
- Pfam (hmmscan --cut_ga): FMN_dh PF01070.25 (E=2e-110), IMPDH PF00478.32 (E=2e-06), Glu_synthase PF01645.24 (E=5e-06)
- (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_215208.1)
- Domains: Pfam-A via hmmscan --cut_ga — FMN_dh (PF01070.25), IMPDH (PF00478.32), Glu_synthase (PF01645.24)
- 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
COG1304 - Curated reference: UniProt P9WND7 (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
mftC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000735|Rv0694|mftD MAEAWFETVAIAQQRAKRRLPKSVYSSLIAASEKGITVADNVAAFSELGFAPHVIGATDKRDLSTTVMGQEVSLPVIISPTGVQAVDPGGEVAVARAAAARGTVMGLSSFASKPIEEVIAANPKTFFQVYWQGGRDALAERVERARQAGAVGLVVTTDWTFSHGRDWGSPKIPEEMNLKTILRLSPEAITRPRWLWKFAKTLRPPDLRVPNQGRRGEPGPPFFAAYGEWMATPPPTWEDIGWLRELWGGPFMLKGVMRVDDAKRAVDAGVSAISVSNHGGNNLDGTPASIRALPAVSAAVGDQVEVLLDGGIRRGSDVVKAVALGARAVMIGRAYLWGLAANGQAGVENVLDILRGGIDSALMGLGHASVHDLSPADILVPTGFIRDLGVPSRRDV