menJ Resolved · high auto-curated
H37Rv Rv0561c · MTBC0 mtbc0_000590 ·
408 aa · 655080–656306 (-) ·
RefSeq NP_215075.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | oxidoreductase |
|---|---|
| MTBC0 PGAP re-annotation | menaquinone reductase |
| Revised (this work) | Menaquinone reductase. Pfam: FAD_binding_3 (PF01494.26), Pyr_redox_2 (PF07992.21), Lycopene_cycl (PF05834.19), FAD_oxidored (PF12831.14), FAD_binding_2 (PF00890.31), GIDA (PF01134.29), NAD_binding_8 (PF13450.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WNY9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Menaquinone reductase |
| EC (curated) |
EC 1.3.99.38
|
| Curated function | Catalyzes the reduction of a single double bond in the isoprenoid tail of menaquinone (MK-9) in M.tuberculosis, likely the beta-isoprene unit, forming the predominant form of menaquinone found in mycobacteria, MK-9(II-H2). Is required for M.tuberculosis survival in host macrophages. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | menJ |
| eggNOG description | geranylgeranyl reductase |
| Orthologous group | COG0644 |
| EC number |
EC 1.3.99.38
|
| KEGG orthology |
K21401
|
| Gene Ontology (31) |
GO:0003674, GO:0003824, GO:0005575, GO:0005618, GO:0005623, GO:0006732, GO:0008150, GO:0008152, GO:0009058, GO:0009108, GO:0009233, GO:0009234 +19 more
|
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 | 0.285 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 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 |
|---|---|---|---|---|
FAD_binding_3 | PF01494.26 | 2.7e-15 | 7–181 | FAD binding domain |
Pyr_redox_2 | PF07992.21 | 4.0e-10 | 8–162 | Pyridine nucleotide-disulphide oxidoreductase |
Lycopene_cycl | PF05834.19 | 2.2e-08 | 8–300 | Lycopene cyclase protein |
FAD_oxidored | PF12831.14 | 3.2e-07 | 8–144 | FAD dependent oxidoreductase |
FAD_binding_2 | PF00890.31 | 4.2e-05 | 8–37 | FAD binding domain |
GIDA | PF01134.29 | 8.3e-05 | 8–36 | Glucose inhibited division protein A |
NAD_binding_8 | PF13450.13 | 4.4e-05 | 11–39 | NAD(P)-binding Rossmann-like domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0560c (benzoquinone methyltransferase), high confidence from genomic context alone (score 745 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3029c fixA |
electron transfer flavoprotein subunit beta | 779 | 750 | experimental:652 |
Rv0560c |
benzoquinone methyltransferase | 901 | 745 ctx | neighborhood:707 textmining:630 |
Rv0562 grcC1 |
polyprenyl-diphosphate synthase GrcC | 751 | 736 ctx | neighborhood:620 |
Rv0563 htpX |
protease HtpX | 715 | 715 ctx | neighborhood:714 |
Rv0559c hyp |
hypothetical protein | 849 | 684 ctx | neighborhood:684 textmining:543 |
Rv3028c fixB |
electron transfer flavoprotein subunit alpha | 632 | 583 | experimental:446 |
Rv2062c cobN |
cobalamin biosynthesis protein CobN | 516 | 452 | coexpression:434 |
Rv3806c ubiA |
decaprenyl-phosphate phosphoribosyltransferase | 501 | 434 | |
Rv2850c |
magnesium chelatase | 584 | 427 | coexpression:408 |
Rv0989c grcC2 |
polyprenyl-diphosphate synthase GrcC | 446 | 413 | |
Rv0958 |
magnesium chelatase | 412 | 357 | |
Rv3397c phyA |
phytoene synthase | 417 | 339 | |
Rv2110c prcB |
proteasome subunit beta | 512 | 241 | |
Rv2109c prcA |
proteasome subunit alpha | 589 | 239 | textmining:483 |
Rv0534c menA |
1,4-dihydroxy-2-naphthoate octaprenyltransferase | 708 | 186 | textmining:656 |
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: oxidoreductase
- MTBC0 PGAP product: menaquinone reductase
- Pfam (hmmscan --cut_ga): FAD_binding_3 PF01494.26 (E=3e-15), Pyr_redox_2 PF07992.21 (E=4e-10), Lycopene_cycl PF05834.19 (E=2e-08), FAD_oxidored PF12831.14 (E=3e-07), FAD_binding_2 PF00890.31 (E=4e-05), GIDA PF01134.29 (E=8e-05), NAD_binding_8 PF13450.13 (E=4e-05)
- (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_215075.1)
- Domains: Pfam-A via hmmscan --cut_ga — FAD_binding_3 (PF01494.26), Pyr_redox_2 (PF07992.21), Lycopene_cycl (PF05834.19), FAD_oxidored (PF12831.14), FAD_binding_2 (PF00890.31), GIDA (PF01134.29), NAD_binding_8 (PF13450.13)
- 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
COG0644 - Curated reference: UniProt P9WNY9 (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 —
23 functional partner(s); context anchor
Rv0560c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000590|Rv0561c|menJ MSVDDSADVVVVGAGPAGSAAAAWAARAGRDVLVIDTATFPRDKPCGDGLTPRAVAELHQLGLGKWLADHIRHRGLRMSGFGGEVEVDWPGPSFPSYGSAVARLELDDRIRKVAEDTGARMLLGAKAVAVHHDSSRRVVSLTLADGTEVGCRQLIVADGARSPLGRKLGRRWHRETVYGVAVRGYLSTAYSDDPWLTSHLELRSPDGAVLPGYGWIFPLGNGEVNIGVGALSTSRRPADLALRPLISYYTDLRRDEWGFTGQPRAVSSALLPMGGAVSGVAGSNWMLIGDAAACVNPLNGEGIDYGLETGRLAAELLDSRDLARLWPSLLADRYGRGFSVARRLALLLTFPRFLPTTGPITMRSTALMNIAVRVMSNLVTDDDRDWVARVWRGGGQLSRLVDRRPPFS