mbtC Resolved · high auto-curated
H37Rv Rv2382c · MTBC0 mtbc0_002534 ·
444 aa · 2694462–2695796 (-) ·
RefSeq NP_216898.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | polyketide synthetase |
|---|---|
| MTBC0 PGAP re-annotation | polyketide synthetase MbtC |
| Revised (this work) | Polyketide synthetase MbtC. Pfam: ketoacyl-synt (PF00109.33), Thiolase_N (PF00108.30), Ketoacyl-synt_C (PF02801.29). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P71718
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Polyketide synthetase MbtC |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | mbtC |
| eggNOG description | Belongs to the beta-ketoacyl-ACP synthases family |
| Orthologous group | COG3321 |
| KEGG orthology |
K04790
|
| 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 | 0.215 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 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 |
|---|---|---|---|---|
ketoacyl-synt | PF00109.33 | 2.2e-81 | 5–254 | Beta-ketoacyl synthase, N-terminal domain |
Thiolase_N | PF00108.30 | 9.2e-08 | 166–210 | Thiolase, N-terminal domain |
Ketoacyl-synt_C | PF02801.29 | 1.3e-35 | 262–378 | Beta-ketoacyl synthase, C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mbtB (phenyloxazoline synthase), high confidence from genomic context alone (score 998 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2383c mbtB |
phenyloxazoline synthase | 999 | 998 ctx | neighborhood:882 fusion:697 coexpression:913 textmining:942 |
Rv2380c mbtE |
peptide synthetase | 999 | 995 ctx | neighborhood:696 fusion:753 cooccurence:506 coexpression:848 textmining:882 |
Rv2381c mbtD |
polyketide synthetase | 998 | 993 ctx | neighborhood:773 cooccurence:773 coexpression:860 textmining:806 |
Rv2379c mbtF |
peptide synthetase | 997 | 986 ctx | neighborhood:721 fusion:465 cooccurence:454 coexpression:810 textmining:816 |
Rv1663 pks17 |
polyketide synthase | 981 | 980 ctx | fusion:900 cooccurence:773 |
Rv2946c pks1 |
polyketide synthase | 979 | 979 ctx | fusion:881 cooccurence:766 |
Rv1181 pks4 |
polyketide beta-ketoacyl synthase | 937 | 930 ctx | fusion:681 cooccurence:742 |
Rv3777 |
oxidoreductase | 916 | 916 ctx | fusion:900 |
Rv3141 fadB4 |
NADPH quinone oxidoreductase FadB | 915 | 915 ctx | fusion:899 |
Rv1912c fadB5 |
oxidoreductase FadB | 914 | 913 ctx | fusion:897 |
Rv2384 mbtA |
2,3-dihydroxybenzoate-AMP ligase | 982 | 854 ctx | neighborhood:771 textmining:883 |
Rv2378c mbtG |
L-lysine N6-monooxygenase | 989 | 851 ctx | neighborhood:755 coexpression:415 textmining:932 |
Rv0101 nrp |
peptide synthetase Nrp | 851 | 842 ctx | cooccurence:482 coexpression:428 |
Rv2386c mbtI |
salicylate synthase | 978 | 825 | coexpression:819 textmining:880 |
Rv1529 fadD24 |
fatty-acid--CoA ligase FadD24 | 799 | 792 ctx | fusion:557 |
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: polyketide synthetase MbtC
- Pfam (hmmscan --cut_ga): ketoacyl-synt PF00109.33 (E=2e-81), Thiolase_N PF00108.30 (E=9e-08), Ketoacyl-synt_C PF02801.29 (E=1e-35)
- (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_216898.1)
- Domains: Pfam-A via hmmscan --cut_ga — ketoacyl-synt (PF00109.33), Thiolase_N (PF00108.30), Ketoacyl-synt_C (PF02801.29)
- 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
COG3321 - Curated reference: UniProt P71718 (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 —
73 functional partner(s); context anchor
mbtB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002534|Rv2382c|mbtC MSDNDPVVIVGLAIEAPGGVETADDYWTLLSEQREGLGPFPTDRGWALRELFDGSRRNGFKPIHNLGGFLSSATTFDPEFFRISPREATAMDPQQRVGLRVAWRTLENSGINPDDLAGHDVGCYVGASALEYGPALTEFSHHSGHLITGTSLGVISGRIAYTLDLAGPALTVDTSCSSALAAFHTAVQAIRAGDCDLALAGGVCVMGTPGYFVEFSKQHALSDDGHCRPYSAHASGTAWAEGAAMFLLQRRSRATADRRRVLAEVRASCLNSDGLSDGLTAPSGDAQTRLLRRAIAQAAVVPADVGMVEGHGTATRLGDRTELRSLAASYGTAPAGRGPLLGSVKSNIGHAQAAAGGLGLVKVILAAQHAAIPPTLHVDEPSREIDWEKQGLRLADKLTPWRAVDGWRTAAVSAFGMSGTNSHVIVSMPDTVSAPERGPECGEV