mbtG Resolved · high auto-curated
H37Rv Rv2378c · MTBC0 mtbc0_002530 ·
431 aa · 2680601–2681896 (-) ·
RefSeq NP_216894.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | L-lysine N6-monooxygenase |
|---|---|
| MTBC0 PGAP re-annotation | NADPH-dependent L-lysine N(6)-monooxygenase MbtG |
| Revised (this work) | NADPH-dependent L-lysine N(6)-monooxygenase MbtG. Pfam: Lys_Orn_oxgnase (PF13434.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WKF7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | L-lysine N6-monooxygenase MbtG |
| EC (curated) |
EC 1.14.13.59
|
| Curated function | Flavoprotein monooxygenase required for N-hydroxylation of the two acylated lysine residues during mycobactin assembly, thus producing the hydroxamate groups necessary for iron sequestration. Is also able, but less efficiently, to hydroxylate L-lysine (non acylated) in vitro. Shows 5-fold preference for using acetylated lysine over lysine. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | mbtG |
| eggNOG description | Involved in the biogenesis of the hydroxyphenyloxazoline-containing siderophore mycobactins. this hydroxylase is possibly required for N-hydroxylation of the two lysine residues at some stage during mycobactin assembly catalytic activity L-lysine O(2) N6-hydroxy- L-lysine H(2)O. no information can be found if this enzyme is NADPH dependent or independent |
| Orthologous group | COG3486 |
| KEGG orthology |
K04793
|
| KEGG pathways |
map01053
|
| Gene Ontology (41) |
GO:0003674, GO:0003824, GO:0004497, GO:0006518, GO:0006725, GO:0006807, GO:0008150, GO:0008152, GO:0009058, GO:0009237, GO:0009712, GO:0009987 +29 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 | 1.049 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 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 |
|---|---|---|---|---|
Lys_Orn_oxgnase | PF13434.13 | 5.8e-10 | 88–284 | L-lysine 6-monooxygenase/L-ornithine 5-monooxygenase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mbtF (peptide synthetase), high confidence from genomic context alone (score 986 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2377c mbtH hyp |
hypothetical protein | 996 | 990 ctx | neighborhood:882 coexpression:915 textmining:701 |
Rv2379c mbtF |
peptide synthetase | 997 | 986 ctx | neighborhood:881 coexpression:868 textmining:820 |
Rv2380c mbtE |
peptide synthetase | 997 | 983 ctx | neighborhood:801 coexpression:887 textmining:881 |
Rv2383c mbtB |
phenyloxazoline synthase | 996 | 930 ctx | neighborhood:756 cooccurence:426 coexpression:476 textmining:948 |
Rv2381c mbtD |
polyketide synthetase | 982 | 909 ctx | neighborhood:502 coexpression:785 textmining:813 |
Rv2382c mbtC |
polyketide synthetase | 989 | 851 ctx | neighborhood:755 coexpression:415 textmining:932 |
Rv1349 irtB |
iron ABC transporter ATP-binding protein/permease IrtB | 882 | 827 | coexpression:729 |
Rv1347c mbtK |
lysine N-acetyltransferase MbtK | 921 | 794 ctx | cooccurence:410 coexpression:583 textmining:635 |
Rv0955 |
integral membrane protein | 767 | 767 ctx | cooccurence:767 |
Rv0256c PPE2 |
PPE family protein PPE2 | 754 | 755 ctx | cooccurence:754 |
Rv0236c aftD |
alpha-(1->3)-arabinofuranosyltransferase | 749 | 750 ctx | cooccurence:746 |
Rv3604c |
transmembrane protein | 737 | 737 ctx | cooccurence:737 |
Rv1159 pimE |
polyprenol-phosphate-mannose-dependent alpha-(1-2)-phosphatidylinositol pentamannoside mannosyltransferase | 698 | 698 ctx | cooccurence:698 |
Rv0452 |
transcriptional regulator | 677 | 677 ctx | cooccurence:677 |
Rv1348 irtA |
iron ABC transporter ATP-binding protein/permease IrtA | 767 | 638 ctx | cooccurence:546 |
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: L-lysine N6-monooxygenase
- MTBC0 PGAP product: NADPH-dependent L-lysine N(6)-monooxygenase MbtG
- Pfam (hmmscan --cut_ga): Lys_Orn_oxgnase PF13434.13 (E=6e-10)
- (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_216894.1)
- Domains: Pfam-A via hmmscan --cut_ga — Lys_Orn_oxgnase (PF13434.13)
- 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
COG3486 - Curated reference: UniProt P9WKF7 (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 —
68 functional partner(s); context anchor
mbtF - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002530|Rv2378c|mbtG MNPTLAVLGAGAKAVAVAAKASVLRDMGVDVPDVIAVERIGVGANWQASGGWTDGAHRLGTSPEKDVGFPYRSALVPRRNAELDERMTRYSWQSYLIATASFAEWIDRGRPAPTHRRWSQYLAWVADHIGLKVIHGEVERLAVTGDRWALCTHETTVQADALMITGPGQAEKSLLPGNPRVLSIAQFWDRAAGHDRINAERVAVIGGGETAASMLNELFRHRVSTITVISPQVTLFTRGEGFFENSLFSDPTDWAALTFDERRDALARTDRGVFSATVQEALLADDRIHHLRGRVAHAVGRQGQIRLTLSTNRGSENFETVHGFDLVIDGSGADPLWFTSLFSQHTLDLLELGLGGPLTADRLQEAIGYDLAVTDVTPKLFLPTLSGLTQGPGFPNLSCLGLLSDRVLGAGIFTPTKHNDTRRSGEHQSFR