mftE Resolved · high auto-curated
H37Rv Rv0695 · MTBC0 mtbc0_000736 ·
251 aa · 798801–799556 (+) ·
RefSeq NP_215209.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | mycofactocin system creatinine amidohydrolase family protein MftE |
|---|---|
| MTBC0 PGAP re-annotation | mycofactocin biosynthesis peptidyl-dipeptidase MftE |
| Revised (this work) | Mycofactocin biosynthesis peptidyl-dipeptidase MftE. Pfam: Creatininase (PF02633.20). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WP59
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Mycofactocin precursor peptide peptidase |
| EC (curated) |
EC 3.4.14.14
|
| Curated function | Peptidase involved in the biosynthesis of the enzyme cofactor mycofactocin (MFT). Catalyzes cleavage of the MftC-modified MftA peptide to liberate its final two residues, which consist of a cross-linked valine-decarboxylated tyrosine dipeptide (named 3-amino-5-[(4-hydroxyphenyl)methyl]-4,4-dimethyl-2-pyrrolidin-2-one or ADHP). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | mftE |
| eggNOG description | creatinine amidohydrolase family protein |
| Orthologous group | COG1402 |
| EC number |
EC 3.5.2.10
|
| KEGG orthology |
K01470
|
| KEGG pathways |
map00330
|
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 | 0.249 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 2 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 |
|---|---|---|---|---|
Creatininase | PF02633.20 | 1.9e-61 | 25–238 | Creatinine amidohydrolase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mftF (mycofactocin biosynthesis glycosyltransferase MftF), high confidence from genomic context alone (score 991 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0696 mftF |
mycofactocin biosynthesis glycosyltransferase MftF | 999 | 991 ctx | neighborhood:813 cooccurence:695 coexpression:860 textmining:929 |
Rv0693 mftC |
mycofactocin radical SAM maturase MftC | 995 | 970 ctx | neighborhood:738 cooccurence:758 database:500 textmining:861 |
Rv0692 mftB |
mycofactocin system protein MftB | 998 | 967 ctx | neighborhood:738 cooccurence:757 database:500 textmining:943 |
Rv0694 mftD |
mycofactocin system heme/flavin oxidoreductase MftD | 988 | 879 ctx | neighborhood:738 cooccurence:447 textmining:907 |
Rv0697 mftG |
dehydrogenase | 845 | 845 ctx | neighborhood:813 |
Rv0691c mftR |
mycofactocin biosynthesis transcriptional regulator MftR | 845 | 815 ctx | cooccurence:707 |
Rv1639c hyp |
hypothetical protein | 731 | 731 | coexpression:731 |
Rv0690c hyp |
hypothetical protein | 545 | 545 ctx | neighborhood:529 |
Rv0691A mftA |
mycofactocin precursor | 934 | 514 ctx | neighborhood:514 textmining:870 |
Rv1990A |
Rv1990A, len: 111 aa. Possible dehydrogenase (fragment), similar to N-terminal part of several dehydrogenases and hypothetical proteins, e.g | 465 | 466 ctx | cooccurence:453 |
Rv1681 moeX |
molybdopterin biosynthesis protein MoeX | 428 | 345 | |
Rv0687 |
NAD-dependent oxidoreductase | 634 | 297 | textmining:501 |
Rv2750 |
dehydrogenase | 629 | 281 | textmining:505 |
Rv0761c adhB |
alcohol dehydrogenase B | 737 | 237 | textmining:670 |
Rv1872c lldD2 |
L-lactate dehydrogenase | 537 | 151 | textmining:477 |
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 creatinine amidohydrolase family protein MftE
- MTBC0 PGAP product: mycofactocin biosynthesis peptidyl-dipeptidase MftE
- Pfam (hmmscan --cut_ga): Creatininase PF02633.20 (E=2e-61)
- (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_215209.1)
- Domains: Pfam-A via hmmscan --cut_ga — Creatininase (PF02633.20)
- 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
COG1402 - Curated reference: UniProt P9WP59 (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 —
18 functional partner(s); context anchor
mftF - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000736|Rv0695|mftE MNSSYHRRVPVVGELGSATSSQLPSTSPSIVIPLGSTEQHGPHLPLDTDTRIATAVARTVTARLHAEDLPIAQEEWLMAPAIAYGASGEHQRFAGTISIGTEALTMLLVEYGRSAACWARRLVFVNGHGGNVGALTRAVGLLRAEGRDAGWCPCTCPGGDPHAGHTETSVLLHLSPADVRTERWRAGNRAPLPVLLPSMRRGGVAAVSETGVLGDPTTATAAEGRRIFAAMVDDCVRRVARWMPQPDGMLT