mbtB Resolved · high auto-curated
H37Rv Rv2383c · MTBC0 mtbc0_002535 ·
1414 aa · 2695786–2700030 (-) ·
RefSeq NP_216899.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | phenyloxazoline synthase |
|---|---|
| MTBC0 PGAP re-annotation | phenyloxazoline synthase MbtB |
| Revised (this work) | Phenyloxazoline synthase MbtB. Pfam: Condensation (PF00668.26), AMP-binding (PF00501.35), AMP-binding_C (PF13193.13), PP-binding (PF00550.32), Thioesterase (PF00975.27). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WQ63
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Phenyloxazoline synthase MbtB |
| EC (curated) |
EC 6.3.2.-
|
| Curated function | Involved in the initial steps of the mycobactin biosynthetic pathway. Putatively couples activated salicylic acid with serine or threonine and cyclizes this precursor to the hydroxyphenyloxazoline ring system present in this class of siderophores. Essential for growth in macrophages. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | mbtB |
| eggNOG description | Condensation domain |
| Orthologous group | COG1020 |
| KEGG orthology |
K04788
|
| 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 | 0.79 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 10 synonymous, 22 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 | 8.7e-27 | 100–441 | Condensation domain |
AMP-binding | PF00501.35 | 6.4e-80 | 558–904 | AMP-binding enzyme |
AMP-binding_C | PF13193.13 | 2.1e-06 | 959–1031 | AMP-binding enzyme C-terminal domain |
PP-binding | PF00550.32 | 1.8e-13 | 1065–1131 | Phosphopantetheine attachment site |
Thioesterase | PF00975.27 | 7.6e-66 | 1190–1411 | Thioesterase domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mbtA (2,3-dihydroxybenzoate-AMP ligase), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2384 mbtA |
2,3-dihydroxybenzoate-AMP ligase | 999 | 1000 ctx | neighborhood:784 coexpression:999 experimental:699 textmining:761 |
Rv3800c pks13 |
polyketide synthase | 999 | 1000 ctx | neighborhood:544 coexpression:999 experimental:473 textmining:745 |
Rv2377c mbtH hyp |
hypothetical protein | 999 | 999 ctx | neighborhood:756 cooccurence:650 coexpression:971 experimental:564 textmining:864 |
Rv2380c mbtE |
peptide synthetase | 999 | 999 ctx | neighborhood:756 coexpression:992 textmining:718 |
Rv2382c mbtC |
polyketide synthetase | 999 | 998 ctx | neighborhood:882 fusion:697 coexpression:913 textmining:942 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 998 | 995 ctx | neighborhood:544 cooccurence:438 coexpression:937 experimental:721 textmining:763 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 998 | 995 ctx | neighborhood:544 cooccurence:435 coexpression:937 experimental:721 textmining:761 |
Rv1527c pks5 |
polyketide synthase | 998 | 995 ctx | neighborhood:544 cooccurence:437 coexpression:937 experimental:721 textmining:745 |
Rv2048c pks12 |
polyketide synthase | 998 | 994 ctx | neighborhood:544 coexpression:937 experimental:721 textmining:745 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 998 | 994 ctx | neighborhood:544 coexpression:937 experimental:721 textmining:752 |
Rv0101 nrp |
peptide synthetase Nrp | 997 | 993 ctx | neighborhood:544 coexpression:979 textmining:647 |
Rv2381c mbtD |
polyketide synthetase | 998 | 991 ctx | neighborhood:800 cooccurence:504 coexpression:897 textmining:859 |
Rv3215 entC |
isochorismate synthase | 997 | 991 ctx | neighborhood:544 coexpression:982 textmining:696 |
Rv0405 pks6 |
membrane bound polyketide synthase | 992 | 982 ctx | neighborhood:544 coexpression:876 experimental:473 textmining:581 |
Rv2379c mbtF |
peptide synthetase | 990 | 982 ctx | neighborhood:721 coexpression:910 textmining:515 |
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: phenyloxazoline synthase
- MTBC0 PGAP product: phenyloxazoline synthase MbtB
- Pfam (hmmscan --cut_ga): Condensation PF00668.26 (E=9e-27), AMP-binding PF00501.35 (E=6e-80), AMP-binding_C PF13193.13 (E=2e-06), PP-binding PF00550.32 (E=2e-13), Thioesterase PF00975.27 (E=8e-66)
- (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_216899.1)
- Domains: Pfam-A via hmmscan --cut_ga — Condensation (PF00668.26), AMP-binding (PF00501.35), AMP-binding_C (PF13193.13), PP-binding (PF00550.32), Thioesterase (PF00975.27)
- 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 P9WQ63 (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 —
198 functional partner(s); context anchor
mbtA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002535|Rv2383c|mbtB MVHATACSEIIRAEVAELLGVRADALHPGANLVGQGLDSIRMMSLVGRWRRKGIAVDFATLAATPTIEAWSQLVSAGTGVAPTAVAAPGDAGLSQEGEPFPLAPMQHAMWVGRHDHQQLGGVAGHLYVEFDGARVDPDRLRAAATRLALRHPMLRVQFLPDGTQRIPPAAGSRDFPISVADLRHVAPDVVDQRLAGIRDAKSHQQLDGAVFELALTLLPGERTRLHVDLDMQAADAMSYRILLADLAALYDGREPPALGYTYREYRQAIEAEETLPQPVRDADRDWWAQRIPQLPDPPALPTRAGGERDRRRSTRRWHWLDPQTRDALFARARARGITPAMTLAAAFANVLARWSASSRFLLNLPLFSRQALHPDVDLLVGDFTSSLLLDVDLTGARTAAARAQAVQEALRSAAGHSAYPGLSVLRDLSRHRGTQVLAPVVFTSALGLGDLFCPDVTEQFGTPGWIISQGPQVLLDAQVTEFDGGVLVNWDVREGVFAPGVIDAMFTHQVDELLRLAAGDDAWDAPSPSALPAAQRAVRAALNGRTAAPSTEALHDGFFRQAQQQPDAPAVFASSGDLSYAQLRDQASAVAAALRAAGLRVGDTVAVLGPKTGEQVAAVLGILAAGGVYLPIGVDQPRDRAERILATGSVNLALVCGPPCQVRVPVPTLLLADVLAAAPAEFVPGPSDPTALAYVLFTSGSTGEPKGVEVAHDAAMNTVETFIRHFELGAADRWLALATLECDMSVLDIFAALRSGGAIVVVDEAQRRDPDAWARLIDTYEVTALNFMPGWLDMLLEVGGGRLSSLRAVAVGGDWVRPDLARRLQVQAPSARFAGLGGATETAVHATIFEVQDAANLPPDWASVPYGVPFPNNACRVVADSGDDCPDWVAGELWVSGRGIARGYRGRPELTAERFVEHDGRTWYRTGDLARYWHDGTLEFVGRADHRVKISGYRVELGEIEAALQRLPGVHAAAATVLPGGSDVLAAAVCVDDAGVTAESIRQQLADLVPAHMIPRHVTLLDRIPFTDSGKIDRAEVGALLAAEVERSGDRSAPYAAPRTVLQRALRRIVADILGRANDAVGVHDDFFALGGDSVLATQVVAGIRRWLDSPSLMVADMFAARTIAALAQLLTGREANADRLELVAEVYLEIANMTSADVMAALDPIEQPAQPAFKPWVKRFTGTDKPGAVLVFPHAGGAAAAYRWLAKSLVANDVDTFVVQYPQRADRRSHPAADSIEALALELFEAGDWHLTAPLTLFGHCMGAIVAFEFARLAERNGVPVRALWASSGQAPSTVAASGPLPTADRDVLADMVDLGGTDPVLLEDEEFVELLVPAVKADYRALSGYSCPPDVRIRANIHAVGGNRDHRISREMLTSWETHTSGRFTLSHFDGGHFYLNDHLDAVARMVSADVR