mbtD Resolved · high auto-curated
H37Rv Rv2381c · MTBC0 mtbc0_002533 ·
1004 aa · 2691448–2694462 (-) ·
RefSeq NP_216897.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | polyketide synthetase |
|---|---|
| MTBC0 PGAP re-annotation | mycobactin polyketide synthase MbtD |
| Revised (this work) | Mycobactin polyketide synthase MbtD. Pfam: Acyl_transf_1 (PF00698.27), KR (PF08659.17), adh_short (PF00106.32), Epimerase (PF01370.28), PP-binding (PF00550.32). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P71719
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Polyketide synthetase MbtD |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolismQ Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | mbtD |
| eggNOG description | polyketide synthase |
| Orthologous group | COG0236 |
| KEGG orthology |
K04791
|
| 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 | 0.365 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 8 synonymous, 7 missense, 1 nonsense, 0 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.34% of strains (493) · clonal |
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 |
|---|---|---|---|---|
Acyl_transf_1 | PF00698.27 | 1.7e-50 | 99–409 | Acyl transferase domain |
KR | PF08659.17 | 2.6e-34 | 669–840 | KR domain |
adh_short | PF00106.32 | 9.9e-10 | 669–826 | short chain dehydrogenase |
Epimerase | PF01370.28 | 1.8e-06 | 669–797 | NAD dependent epimerase/dehydratase family |
PP-binding | PF00550.32 | 2.4e-09 | 920–976 | Phosphopantetheine attachment site |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mbtC (polyketide synthetase), high confidence from genomic context alone (score 993 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2382c mbtC |
polyketide synthetase | 998 | 993 ctx | neighborhood:773 cooccurence:773 coexpression:860 textmining:806 |
Rv2383c mbtB |
phenyloxazoline synthase | 998 | 991 ctx | neighborhood:800 cooccurence:504 coexpression:897 textmining:859 |
Rv2380c mbtE |
peptide synthetase | 995 | 978 ctx | neighborhood:503 cooccurence:597 coexpression:870 textmining:817 |
Rv2379c mbtF |
peptide synthetase | 994 | 970 ctx | neighborhood:495 cooccurence:548 coexpression:845 textmining:814 |
Rv2378c mbtG |
L-lysine N6-monooxygenase | 982 | 909 ctx | neighborhood:502 coexpression:785 textmining:813 |
Rv0101 nrp |
peptide synthetase Nrp | 844 | 814 ctx | cooccurence:572 coexpression:438 |
Rv2947c pks15 |
polyketide synthase | 796 | 796 ctx | cooccurence:773 |
Rv2386c mbtI |
salicylate synthase | 926 | 784 | coexpression:780 textmining:673 |
Rv1180 pks3 |
polyketide beta-ketoacyl synthase | 782 | 783 ctx | cooccurence:773 |
Rv2928 tesA |
thioesterase TesA | 706 | 694 ctx | cooccurence:644 |
Rv2384 mbtA |
2,3-dihydroxybenzoate-AMP ligase | 929 | 636 ctx | neighborhood:559 textmining:814 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 639 | 616 | experimental:408 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 639 | 616 | experimental:408 |
Rv1527c pks5 |
polyketide synthase | 638 | 616 | experimental:408 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 640 | 614 | experimental:408 |
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: polyketide synthetase
- MTBC0 PGAP product: mycobactin polyketide synthase MbtD
- Pfam (hmmscan --cut_ga): Acyl_transf_1 PF00698.27 (E=2e-50), KR PF08659.17 (E=3e-34), adh_short PF00106.32 (E=1e-09), Epimerase PF01370.28 (E=2e-06), PP-binding PF00550.32 (E=2e-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_216897.1)
- Domains: Pfam-A via hmmscan --cut_ga — Acyl_transf_1 (PF00698.27), KR (PF08659.17), adh_short (PF00106.32), Epimerase (PF01370.28), 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
COG0236 - Curated reference: UniProt P71719 (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 —
74 functional partner(s); context anchor
mbtC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002533|Rv2381c|mbtD MAPKQLPDGRVAVLLSAHAEELIGPDARAIADYLERFPATTVTEVARQLRKTRRVRRHRAVLRAADRLELAEGLRALAAGREHPLIARSSLGSAPRQAFVFPGQGGHWPGMGAVAYRELPTYRTATDTCAAAFAAAGVDSPLPYLIAPPGTDERQAFCEIEIEGAQFVHAVALAEVWRSCGVLPDLTVGHSLGEVAAAYLAGSITLSDAVAVVAARANVVGRLPGRYAVAALGIGEQDASALIATTGGWLELSVVNASSTVAVSGERQAVAAIVDTVRSSGHFARGITVGFPVHTSVLESLRDELCEQLPDSEFMEAPVQFIGGTTGDVVAPGTTFGDYWYANLRHTVRFDRAVESAIRCGARAFIEISAHPALLFAIGQNCEGAANLPDGPAVLVGSARRGERFVDALSANIVSAAVADPGYPWGDLGGDPLDGDVDLSGFPNAPMRAVPMWAHPEPLPPVSGLTIAVERWERMVPSTPVAGRHRHLAVLDLGAHRALAQTLCAAIDSHPDTELSAARDAELILVIAPDFEHTDAVRAAGALADLVGAGLLDYPMHIGARCQSVCLVTVGAEQVDAADAVPSAGQAALAAMHRSIGFEHPEQTFSHLDLPSWDLDPVLGVSVITAVLRGFGETALRGSVNGYTLFERTLADAPAVPNWSLDSGVLDDVVVTGGAGAIGMHYARYLAEHGARRIVLLSRRAADQATVAMLRKQHGTVIVSPPCDITDPTQLSAIAAEYGGVGASLIVHAAGSVISGTAPGVTSAAVVDNFAAKVLGLAQMIELWPLRPDVRTLLCSSVMGVWGGHGVVAYSAANRLLDVMAAQLRAQGRHCVAVKWGLWQAPKAGEPARGIADAVTIARVERSGLRQMAPQQAIEASLHEFTVDPLVFAADAARLQMLLDSRQFERYEGPTDPNLTIVDAVRTQLAAVLGIPQAGEVNLQESLFDLGVDSMLALDLRNRLKRSIGATVSLATLMGDITGDGLVAKLEDADERSHTAQKVDISRD