mftC Resolved · high auto-curated
H37Rv Rv0693 · MTBC0 mtbc0_000734 ·
391 aa · 796243–797418 (+) ·
RefSeq NP_215207.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | mycofactocin radical SAM maturase MftC |
|---|---|
| MTBC0 PGAP re-annotation | mycofactocin radical SAM maturase |
| Revised (this work) | Mycofactocin radical SAM maturase. Pfam: Radical_SAM (PF04055.28), SPASM (PF13186.12). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WJ79
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Mycofactocin maturase MftC |
| EC (curated) |
EC 1.3.98.7, EC 4.1.99.26
|
| Curated function | Radical S-adenosylmethionine (SAM) enzyme responsible for the first step of the biosynthesis of the enzyme cofactor mycofactocin (MFT). Catalyzes two reactions at the C-terminus of the mycofactocin precursor (the MftA peptide). The first one is the oxidative decarboxylation of the C-terminal L-tyrosine of MftA, forming an unsaturated tyramine moiety. The second reaction is the cross-linking of the tyramine with the penultimate L-valine residue, forming a five-membered lactam ring. Its activity requires the presence of the MftB chaperone. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | pqqE |
| eggNOG description | Radical SAM |
| Orthologous group | COG0535 |
| 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)
| pN/pS | 0.226 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 4 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 |
|---|---|---|---|---|
Radical_SAM | PF04055.28 | 1.9e-28 | 25–180 | Radical SAM superfamily |
SPASM | PF13186.12 | 1.5e-06 | 251–313 | Iron-sulfur cluster-binding domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mftB (mycofactocin system protein MftB), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0692 mftB |
mycofactocin system protein MftB | 999 | 1000 ctx | neighborhood:882 cooccurence:774 coexpression:845 database:900 textmining:907 |
Rv0694 mftD |
mycofactocin system heme/flavin oxidoreductase MftD | 999 | 994 ctx | neighborhood:882 cooccurence:665 coexpression:860 textmining:875 |
Rv0695 mftE |
mycofactocin system creatinine amidohydrolase family protein MftE | 995 | 970 ctx | neighborhood:738 cooccurence:758 database:500 textmining:861 |
Rv0696 mftF |
mycofactocin biosynthesis glycosyltransferase MftF | 993 | 932 ctx | neighborhood:702 cooccurence:770 textmining:907 |
Rv0691c mftR |
mycofactocin biosynthesis transcriptional regulator MftR | 961 | 893 ctx | neighborhood:602 cooccurence:741 textmining:658 |
Rv0691A mftA |
mycofactocin precursor | 957 | 882 ctx | neighborhood:882 textmining:655 |
Rv0697 mftG |
dehydrogenase | 718 | 706 ctx | neighborhood:702 |
Rv1990A |
Rv1990A, len: 111 aa. Possible dehydrogenase (fragment), similar to N-terminal part of several dehydrogenases and hypothetical proteins, e.g | 682 | 670 ctx | cooccurence:667 |
Rv0690c hyp |
hypothetical protein | 621 | 621 ctx | neighborhood:596 |
Rv2425c hyp |
hypothetical protein | 553 | 554 ctx | cooccurence:536 |
Rv2750 |
dehydrogenase | 762 | 465 ctx | cooccurence:461 textmining:575 |
Rv0687 |
NAD-dependent oxidoreductase | 746 | 434 ctx | cooccurence:429 textmining:571 |
Rv0761c adhB |
alcohol dehydrogenase B | 749 | 277 | textmining:668 |
Rv1162 narH |
nitrate reductase subunit beta | 419 | 252 | |
Rv1163 narJ |
nitrate reductase subunit delta | 427 | 159 |
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 radical SAM maturase MftC
- MTBC0 PGAP product: mycofactocin radical SAM maturase
- Pfam (hmmscan --cut_ga): Radical_SAM PF04055.28 (E=2e-28), SPASM PF13186.12 (E=2e-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_215207.1)
- Domains: Pfam-A via hmmscan --cut_ga — Radical_SAM (PF04055.28), SPASM (PF13186.12)
- 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
COG0535 - Curated reference: UniProt P9WJ79 (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 —
22 functional partner(s); context anchor
mftB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000734|Rv0693|mftC MTSPVPRLIEQFERGLDAPICLTWELTYACNLACVHCLSSSGKRDPGELSTRQCKDIIDELERMQVFYVNIGGGEPTVRPDFWELVDYATAHHVGVKFSTNGVRITPEVATRLAATDYVDVQISLDGATAEVNDAIRGTGSFDMAVRALQNLAAAGFAGVKISVVITRRNVAQLDEFATLASRYGATLRITRLRPSGRGTDVWADLHPTADQQVQLYDWLVSKGERVLTGDSFFHLAPLGQSGALAGLNMCGAGRVVCLIDPVGDVYACPFAIHDHFLAGNVLSDGGFQNVWKNSSLFRELREPQSAGACGSCGHYDSCRGGCMAAKFFTGLPLDGPDPECVQGHSEPALARERHLPRPRADHSRGRRVSKPVPLTLSMRPPKRPCNESPV