mbtE Resolved · high auto-curated
H37Rv Rv2380c · MTBC0 - ·
1682 aa · 2662067–2667115 (-) ·
RefSeq NP_216896.3
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | peptide synthetase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Peptide synthetase. Pfam: AMP-binding (PF00501.35), AMP-binding_C (PF13193.13), PP-binding (PF00550.32), Condensation (PF00668.26). |
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 |
I6Y0L1
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Peptide synthetase MbtE |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | mbtE |
| eggNOG description | Peptide synthetase |
| Orthologous group | COG1020 |
| KEGG orthology |
K04789
|
| 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 | 0.352 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 15 synonymous, 15 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 |
|---|---|---|---|---|
AMP-binding | PF00501.35 | 4.5e-83 | 447–779 | AMP-binding enzyme |
AMP-binding_C | PF13193.13 | 9.0e-08 | 838–917 | AMP-binding enzyme C-terminal domain |
PP-binding | PF00550.32 | 3.0e-16 | 943–1007 | Phosphopantetheine attachment site |
Condensation | PF00668.26 | 1.9e-73 | 1028–1471 | Condensation domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mbtB (phenyloxazoline synthase), high confidence from genomic context alone (score 999 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2377c mbtH hyp |
hypothetical protein | 999 | 1000 ctx | neighborhood:799 cooccurence:754 coexpression:887 experimental:972 textmining:835 |
Rv2383c mbtB |
phenyloxazoline synthase | 999 | 999 ctx | neighborhood:756 coexpression:992 textmining:718 |
Rv2382c mbtC |
polyketide synthetase | 999 | 995 ctx | neighborhood:696 fusion:753 cooccurence:506 coexpression:848 textmining:882 |
Rv2524c fas |
fatty acid synthase | 996 | 990 ctx | neighborhood:417 coexpression:689 experimental:895 database:549 textmining:658 |
Rv2379c mbtF |
peptide synthetase | 993 | 990 ctx | neighborhood:799 coexpression:914 |
Rv2378c mbtG |
L-lysine N6-monooxygenase | 997 | 983 ctx | neighborhood:801 coexpression:887 textmining:881 |
Rv2381c mbtD |
polyketide synthetase | 995 | 978 ctx | neighborhood:503 cooccurence:597 coexpression:870 textmining:817 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 983 | 973 ctx | neighborhood:526 cooccurence:482 coexpression:648 experimental:721 textmining:407 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 983 | 973 ctx | neighborhood:526 cooccurence:476 coexpression:650 experimental:721 textmining:407 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 983 | 973 ctx | neighborhood:526 cooccurence:485 coexpression:651 experimental:721 textmining:422 |
Rv1527c pks5 |
polyketide synthase | 982 | 972 ctx | neighborhood:526 cooccurence:472 coexpression:650 experimental:721 textmining:407 |
Rv2048c pks12 |
polyketide synthase | 980 | 966 ctx | neighborhood:526 coexpression:649 experimental:721 textmining:447 |
Rv3800c pks13 |
polyketide synthase | 979 | 965 ctx | neighborhood:508 coexpression:805 experimental:473 textmining:435 |
Rv1529 fadD24 |
fatty-acid--CoA ligase FadD24 | 958 | 957 ctx | fusion:697 cooccurence:687 experimental:465 |
Rv1521 fadD25 |
fatty-acid--CoA ligase FadD25 | 957 | 955 ctx | fusion:692 cooccurence:682 experimental:465 |
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): AMP-binding PF00501.35 (E=4e-83), AMP-binding_C PF13193.13 (E=9e-08), PP-binding PF00550.32 (E=3e-16), Condensation PF00668.26 (E=2e-73)
- (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_216896.3)
- Domains: Pfam-A via hmmscan --cut_ga — AMP-binding (PF00501.35), AMP-binding_C (PF13193.13), PP-binding (PF00550.32), Condensation (PF00668.26)
- 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 I6Y0L1 (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 —
262 functional partner(s); context anchor
mbtB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2380c|mbtE MWFVQMADPSGALLNICVSYRITGDIDLARLRDAVNAVARRHRILRTTYPVGDDGVAQPTVHADLRPGWTQYDLTDLSQRAQRLRLEVLAQREFCAPFELSRDAPLRITVVRTAADEHVLLLVAHHIAWDDGSWRVFFTDLTQAYSRADLGADLGPEHRPSAASGPDTTEADLNYWRAIMADPPEPLELPGPAGTCVPTSWRAARATLRLPADTAARVATMAKNTGCTPYMVLLAAFGALVHRYTHSDDFLVAAPVLNRGAGTEDAIGYFGNTVAMRLRPQSAMSFRELLTATRDIASGAFAHQRINLDRVVRELNPDRRHGAERMTRVSFGFREPDGGGFNPPGIECERYDLRSNITQLPLGFMVEFDRAGVLVEAEHLVEILEPALAKQMLRHFGVLLDNALAAPDNTLSGLALMDERDAARLREVSRGERFDTPVKTLVDLVNEQTTRTPDATAVVYEGQHFTYHDLNEASNRLGHWLIEQGIGSEDRVAVLLDKSPDLIVTALGVVKSGAVYVPVDPSYPQDRLDFILADCDAKLVLRTPVRELAGYRSDDPTDADRIRPLRPDNTAYLIYTSGTTGLPKGVAVPHRPVAEYFVWFKGEYDVDDTDRLLQVASPSFDVSIAEIFGTLACGARMVIPRPGGLTDIGYLTALLRDEGITAMHFVPSLLGLFLSLPGVSQWRTLQRVPIGGEPLPGEVADKFHATFDALLHNFYGPTETVINASRFKVVGPQGTRIVPIGRPKINTTMHLLDDSLQPVPTGVIGEIYIGGTHVAYGYHRRAGLTAERFVADPFNPGSRMYRSGDLARRNADGDIEFVGRADEQVKIRGFRIELGDVAAAIAVDPTVGQAVVVVSDLPRLGKSLVGYVTPAAGGDGPADVGVDLDRIRARVAAALPEYMLPAAYVVLDEIPITAHGKIDRAALPEPQIASDTEFRAPQTATERRLAQLFGELLGRDRVGADDSFFDLGGHSLLATKLVAAVRNAFGVDVGVREIFEFATVTALAGHIDTLDSDSARPRLTRVDHDGPVRLSSSQMRSWFNYRFDGPNAVNNIPFAAALHGPCDTNAFAAAITDVVARHEILRTVYREIGGVPHQIIQPPAEVPVRCAAGSDAAWLRAELNNERGYVFDLETDWPIRAALLSTPEQTVLSLVVHHIAGDHWSAGVLFTDLLTAYRARSTGQRPSWAPLPVQYADYSVWQSALLDDGAGIVGPQRDYWIRQLGGLAGETGLRPDFPRPALLSGAGDAVEFRLGAAIRDKLAAVSRDLGVTEFMLLQAAVAVVLHKAGGGVDVPIGAPVAGRSEANLDQLIGFFINIVVLRNDLRGNPTLREVLQRTRQMALAAYAHQDLPFDQVVEAVNPQRSLSRNPLFDIVVHVREQMPQDHVIDTGPDGDTTLRVLEPTFDAAQADLSVNFFACGDEYRGHVIYRTELYERATAQRFADWLVRVVEAFADRPDQPLREVEMVSAQARRRILDRSNAGAGTARVYLLDDALKPVPVGVVGDVYYGGGPAVGARLARPSETATRFVADPFAAQPGSRLYRNGERGVWKADGQLELLAEIERLPTAQAAPVPAEPADTETERALAAILADVLEVGEVGRYDDFFNLGGDSILATQVAARARDGGIPLTARMVFEHPVLCELAAAVDAKPHVEAEPDDKHHAPMSTSGLSPDELSALTASWDQWP