menH Resolved · high auto-curated
H37Rv Rv0558 · MTBC0 - ·
234 aa · 649689–650393 (+) ·
RefSeq YP_177738.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | demethylmenaquinone methyltransferase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Demethylmenaquinone methyltransferase. Pfam: Ubie_methyltran (PF01209.25), Methyltransf_23 (PF13489.13), Methyltransf_31 (PF13847.13), Methyltransf_25 (PF13649.13), Methyltransf_11 (PF08241.19). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
P9WFR3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Demethylmenaquinone methyltransferase |
| EC (curated) |
EC 2.1.1.163
|
| Curated function | Methyltransferase required for the conversion of demethylmenaquinol (DMKH2) to menaquinol (MKH2). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | menG |
| eggNOG description | Methyltransferase required for the conversion of demethylmenaquinol (DMKH2) to menaquinol (MKH2) |
| Orthologous group | COG0500 |
| EC number |
EC 2.1.1.163, EC 2.1.1.201
|
| KEGG orthology |
K03183
|
| KEGG pathways |
map00130, map01100, map01110
|
| KEGG modules |
M00116, M00117
|
| Gene Ontology (8) |
GO:0005575, GO:0005623, GO:0005886, GO:0008150, GO:0016020, GO:0040007, 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 | 0.544 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 3 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 |
|---|---|---|---|---|
Ubie_methyltran | PF01209.25 | 1.4e-58 | 11–227 | ubiE/COQ5 methyltransferase family |
Methyltransf_23 | PF13489.13 | 1.8e-07 | 38–167 | Methyltransferase domain |
Methyltransf_31 | PF13847.13 | 7.5e-10 | 51–196 | Methyltransferase domain |
Methyltransf_25 | PF13649.13 | 3.1e-14 | 55–141 | Methyltransferase domain |
Methyltransf_11 | PF08241.19 | 2.0e-17 | 56–145 | Methyltransferase domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mgtA (GDP-mannose-dependent alpha-mannosyltransferase), high confidence from genomic context alone (score 861 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0534c menA |
1,4-dihydroxy-2-naphthoate octaprenyltransferase | 961 | 904 | database:900 textmining:614 |
Rv0557 mgtA |
GDP-mannose-dependent alpha-mannosyltransferase | 866 | 861 ctx | neighborhood:861 |
Rv0555 menD |
bifunctional 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase/2-oxoglutarate decarboxylase | 982 | 643 ctx | neighborhood:641 textmining:953 |
Rv0556 |
transmembrane protein | 643 | 643 ctx | neighborhood:641 |
Rv0553 menC |
muconate cycloisomerase | 943 | 567 ctx | neighborhood:567 textmining:874 |
Rv0554 bpoC |
non-heme bromoperoxidase BpoC | 526 | 526 ctx | neighborhood:526 |
Rv0562 grcC1 |
polyprenyl-diphosphate synthase GrcC | 519 | 502 ctx | cooccurence:446 |
Rv0552 hyp |
hypothetical protein | 492 | 492 ctx | neighborhood:492 |
Rv0989c grcC2 |
polyprenyl-diphosphate synthase GrcC | 487 | 469 ctx | cooccurence:417 |
Rv1622c cydB |
cytochrome D ubiquinol oxidase subunit II CydB | 457 | 457 | |
Rv1623c cydA |
cytochrome D ubiquinol oxidase subunit I CydA | 495 | 435 ctx | cooccurence:421 |
Rv1523 |
methyltransferase | 425 | 425 ctx | cooccurence:425 |
Rv0548c menB |
1,4-dihydroxy-2-naphthoyl-CoA synthase | 768 | 372 | textmining:647 |
Rv0542c menE |
2-succinylbenzoic acid--CoA ligase | 624 | 364 | textmining:434 |
Rv3215 entC |
isochorismate synthase | 837 | 146 | textmining:818 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): demethylmenaquinone methyltransferase
- Pfam (hmmscan --cut_ga): Ubie_methyltran PF01209.25 (E=1e-58), Methyltransf_23 PF13489.13 (E=2e-07), Methyltransf_31 PF13847.13 (E=7e-10), Methyltransf_25 PF13649.13 (E=3e-14), Methyltransf_11 PF08241.19 (E=2e-17)
- (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 YP_177738.1)
- Domains: Pfam-A via hmmscan --cut_ga — Ubie_methyltran (PF01209.25), Methyltransf_23 (PF13489.13), Methyltransf_31 (PF13847.13), Methyltransf_25 (PF13649.13), Methyltransf_11 (PF08241.19)
- 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
COG0500 - Curated reference: UniProt P9WFR3 (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 —
25 functional partner(s); context anchor
mgtA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0558|menH MSRAALDKDPRDVASMFDGVARKYDLTNTVLSLGQDRYWRRATRSALRIGPGQKVLDLAAGTAVSTVELTKSGAWCVAADFSVGMLAAGAARKVPKVAGDATRLPFGDDVFDAVTISFGLRNVANQQAALREMARVTRPGGRLLVCEFSTPTNALFATAYKEYLMRALPRVARAVSSNPEAYEYLAESIRAWPDQAVLAHQISRAGWSGVRWRNLTGGIVALHAGYKPGKQTPQ