mbtF Resolved · high auto-curated
H37Rv Rv2379c · MTBC0 - ·
1461 aa · 2657700–2662085 (-) ·
RefSeq NP_216895.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | peptide synthetase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Peptide synthetase. Pfam: Condensation (PF00668.26), AMP-binding (PF00501.35), AMP-binding_C (PF13193.13), PP-binding (PF00550.32). |
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 |
O05819
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Peptide synthetase MbtF |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | mbtF |
| eggNOG description | Peptide synthetase |
| Orthologous group | COG1020 |
| KEGG orthology |
K04780, K04792
|
| KEGG pathways |
map01053
|
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 | 0.369 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 8 synonymous, 8 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 |
|---|---|---|---|---|
Condensation | PF00668.26 | 1.2e-59 | 17–455 | Condensation domain |
AMP-binding | PF00501.35 | 4.9e-69 | 477–813 | AMP-binding enzyme |
AMP-binding_C | PF13193.13 | 9.1e-08 | 870–943 | AMP-binding enzyme C-terminal domain |
PP-binding | PF00550.32 | 3.9e-09 | 970–1031 | Phosphopantetheine attachment site |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mbtE (peptide synthetase), high confidence from genomic context alone (score 990 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2377c mbtH hyp |
hypothetical protein | 999 | 997 ctx | neighborhood:834 cooccurence:763 coexpression:867 experimental:564 textmining:847 |
Rv2380c mbtE |
peptide synthetase | 993 | 990 ctx | neighborhood:799 coexpression:914 |
Rv2382c mbtC |
polyketide synthetase | 997 | 986 ctx | neighborhood:721 fusion:465 cooccurence:454 coexpression:810 textmining:816 |
Rv2378c mbtG |
L-lysine N6-monooxygenase | 997 | 986 ctx | neighborhood:881 coexpression:868 textmining:820 |
Rv2383c mbtB |
phenyloxazoline synthase | 990 | 982 ctx | neighborhood:721 coexpression:910 textmining:515 |
Rv2381c mbtD |
polyketide synthetase | 994 | 970 ctx | neighborhood:495 cooccurence:548 coexpression:845 textmining:814 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 933 | 922 ctx | cooccurence:451 coexpression:466 experimental:721 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 933 | 922 ctx | cooccurence:449 coexpression:469 experimental:721 |
Rv1527c pks5 |
polyketide synthase | 932 | 922 ctx | cooccurence:445 coexpression:469 experimental:721 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 931 | 920 ctx | cooccurence:434 coexpression:471 experimental:721 |
Rv2048c pks12 |
polyketide synthase | 920 | 908 | coexpression:469 experimental:721 |
Rv3800c pks13 |
polyketide synthase | 914 | 888 | coexpression:659 experimental:473 |
Rv2384 mbtA |
2,3-dihydroxybenzoate-AMP ligase | 918 | 874 | coexpression:685 |
Rv1529 fadD24 |
fatty-acid--CoA ligase FadD24 | 873 | 872 ctx | fusion:506 cooccurence:651 |
Rv0405 pks6 |
membrane bound polyketide synthase | 874 | 868 ctx | cooccurence:510 coexpression:442 experimental:473 |
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): peptide synthetase
- Pfam (hmmscan --cut_ga): Condensation PF00668.26 (E=1e-59), AMP-binding PF00501.35 (E=5e-69), AMP-binding_C PF13193.13 (E=9e-08), PP-binding PF00550.32 (E=4e-09)
- (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_216895.1)
- Domains: Pfam-A via hmmscan --cut_ga — Condensation (PF00668.26), AMP-binding (PF00501.35), AMP-binding_C (PF13193.13), PP-binding (PF00550.32)
- 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
COG1020 - Curated reference: UniProt O05819 (TrEMBL, unreviewed; 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 —
95 functional partner(s); context anchor
mbtE - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2379c|mbtF MGPVAVTRADARGAIDDVMALSPLQQGLFSRATLVAAESGSEAAEADPYVIAMAADAAGPLDIALLRDCAAAMLTRHPNLRASFLHGNLSRPVQVIPSSAEVLWRHVRAHPSEVGALAAEERRRRFDVGRGPLIRFLLIELPDECWHLVIVAHHIVIDGWSLPLFVSELLALYRAGGHVAALPAAPRPYRDYIGWLAGRDQTASRAMWADHLNGLDGPTLLSPALADTPVQPGIPGRTEVRLDREATAELADAARTRGVTISTLVQMAWATTLSAFTGRGDVTFGVTVSGRPSELSGVETMIGLFINTVPLRVRLDARATVGGQCAVLQRQFAMLRDHSYLGFNEFRAIAGIGEMFDTLLVYENFPPGEVVGTAEFVANGVTFRPVALESLSHFPVTVAAHRSTGELTLLVEVLDGALGTMAPESLGRRVLAVLQRLVSRWDRPLRDVDILLDGEHDPTAPGLPDVTTSAPAVHTRFAEIAAAQPDSVAVSWADGQLTYRELDALADRLATGLRRADVSRETPVAVALSRGPRYVAAMLAVLKAGGMIVPLDPAMPGERVAEILRQTSAPVVIDEGVFAASVGADILEEDRAITVPVDQAAYVIFTSGTTGTPKGVIGTHRALSAYADDHIERVLRPAAQRLGRPLRIAHAWSFTFDAAWQPLVALLDGHAVHIVDDHRQRDAGALVEAIDRFGLDMIDTTPSMFAQLHNAGLLDRAPLAVLALGGEALGAATWRMIQQNCARTAMTAFNCYGPTETTVEAVVAAVAEHARPVIGRPTCTTRAYVMDSWLRPVPDGVAGELYLAGAQLTRGYLGRPAETAARFVAEPNGRGSRMYRTGDVVRRLPDGGLEFLGRSDDQVKIRGFRVEPGEIAAVLNGHHAVHGCHVTARGHASGPRLTAYVAGGPQPPPVAELRAMLLERLPRYLVPHHIVVLDELPLTPHGKIDENALAAINVTEGPATPPQTPTELVLAEAFADVMETSNVDVTAGFLQMGLDSIVALSVVQAARRRGIALRARLMVECDTIRELAAAIDSDAAWQAPANDAGEPIPVLPNTHWLYEYGDPRRLAQTEVIRLPDRITRERLDAVLAAVVDGHEVLRCRFDRDAMALVAQPKTDILSEVWVSGELVTAVAEQTLGALASLDPQAGRLLSAVWLREPDGPGVLVLTAHVLAMDPASWRIVLGELDAGLHALAAGRAPSPARENTSYRQWSRLLAQRAKALDSVDFWVAELEGADPPLGARRVAPQTDRVGELAITMSISDADLTARLLSTGRSMTDLLATAAARMVTAWRRQRGQQTPAPLLALETHGRADVHVDKTADTSDTVGLLSAIYPLRIHCDGATDFARIPGSGIDYGLLRYLRADTAERLRAHREPQLLLNYLGSLHVGVGDLAVDRALLADVGQLPEPEQPVRHELTVLAALLGPADAPVLATRWRTLPDILSADDVATLQSLWQGALAEITA