pks6 Resolved · high auto-curated
H37Rv Rv0405 · MTBC0 - ·
1402 aa · 485731–489939 (+) ·
RefSeq NP_214919.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | membrane bound polyketide synthase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Membrane bound polyketide synthase. Pfam: ketoacyl-synt (PF00109.33), Ketoacyl-synt_C (PF02801.29), KAsynt_C_assoc (PF16197.12), CurL-like_PKS_C (PF22621.3), Acyl_transf_1 (PF00698.27), 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.
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 |
O86335
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable membrane bound polyketide synthase Pks6 |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | pks6 |
| eggNOG description | Thioesterase domain |
| Orthologous group | COG3319 |
| EC number |
EC 2.3.1.111, EC 2.3.1.252
|
| KEGG orthology |
K11628, K12431, K12432, K12433, K12442, K12443
|
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 | 0.785 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 14 synonymous, 30 missense, 2 nonsense, 4 frameshift |
| Disruption | 6 distinct premature-stop/frameshift site(s); most common in 32.11% of strains (46622) · convergent |
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 | 4.8e-89 | 107–346 | Beta-ketoacyl synthase, N-terminal domain |
Ketoacyl-synt_C | PF02801.29 | 9.1e-40 | 354–469 | Beta-ketoacyl synthase, C-terminal domain |
KAsynt_C_assoc | PF16197.12 | 5.5e-15 | 474–597 | Ketoacyl-synthetase C-terminal extension |
CurL-like_PKS_C | PF22621.3 | 7.1e-11 | 548–607 | CurL-like, PKS C-terminal |
Acyl_transf_1 | PF00698.27 | 1.0e-64 | 633–942 | Acyl transferase domain |
PP-binding | PF00550.32 | 3.8e-11 | 1022–1088 | Phosphopantetheine attachment site |
Thioesterase | PF00975.27 | 5.6e-13 | 1178–1392 | Thioesterase domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: fas (fatty acid synthase), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2524c fas |
fatty acid synthase | 999 | 1000 ctx | neighborhood:511 coexpression:776 experimental:994 database:549 textmining:519 |
Rv0404 fadD30 |
long-chain-fatty-acid--AMP ligase FadD30 | 988 | 988 ctx | neighborhood:810 coexpression:810 |
Rv2383c mbtB |
phenyloxazoline synthase | 992 | 982 ctx | neighborhood:544 coexpression:876 experimental:473 textmining:581 |
Rv2243 fabD |
malonyl CoA-acyl carrier protein transacylase | 968 | 962 | coexpression:602 experimental:787 database:549 |
Rv0101 nrp |
peptide synthetase Nrp | 967 | 956 ctx | cooccurence:576 coexpression:769 experimental:473 |
Rv2380c mbtE |
peptide synthetase | 913 | 904 ctx | cooccurence:564 coexpression:446 experimental:473 |
Rv2379c mbtF |
peptide synthetase | 874 | 868 ctx | cooccurence:510 coexpression:442 experimental:473 |
Rv3147 nuoC |
NADH-quinone oxidoreductase subunit C | 862 | 857 | coexpression:429 experimental:472 database:564 |
Rv3153 nuoI |
NADH-quinone oxidoreductase subunit I | 858 | 852 | coexpression:406 experimental:473 database:564 |
Rv3146 nuoB |
NADH-quinone oxidoreductase subunit B | 854 | 846 | coexpression:411 experimental:449 database:564 |
Rv0310c hyp |
hypothetical protein | 855 | 840 | experimental:449 database:561 |
Rv3149 nuoE |
NADH-quinone oxidoreductase subunit E | 838 | 832 | coexpression:416 experimental:449 database:518 |
Rv2928 tesA |
thioesterase TesA | 892 | 820 ctx | cooccurence:700 textmining:428 |
Rv3148 nuoD |
NADH-quinone oxidoreductase subunit D | 798 | 788 | experimental:449 database:564 |
Rv3800c pks13 |
polyketide synthase | 840 | 778 | coexpression:648 |
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): membrane bound polyketide synthase
- Pfam (hmmscan --cut_ga): ketoacyl-synt PF00109.33 (E=5e-89), Ketoacyl-synt_C PF02801.29 (E=9e-40), KAsynt_C_assoc PF16197.12 (E=6e-15), CurL-like_PKS_C PF22621.3 (E=7e-11), Acyl_transf_1 PF00698.27 (E=1e-64), PP-binding PF00550.32 (E=4e-11), Thioesterase PF00975.27 (E=6e-13)
- (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_214919.1)
- Domains: Pfam-A via hmmscan --cut_ga — ketoacyl-synt (PF00109.33), Ketoacyl-synt_C (PF02801.29), KAsynt_C_assoc (PF16197.12), CurL-like_PKS_C (PF22621.3), Acyl_transf_1 (PF00698.27), 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
COG3319 - Curated reference: UniProt O86335 (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 —
235 functional partner(s); context anchor
fas - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0405|pks6 MTDGSVTADKLQKWFREYLSTHIECHPNEVSLDVPIRDLGLKSIDVLAIPGDLGDRFGFCIPDLAVWDNPSANDLIDSLLNQRSADSLRESHGHADRNTQGRGSINEPVAVIGVGCRFPGDIDGPERLWDFLTEKKCAITAYPDRGFTNAGTFAESGGFLKDVAGFDNRFFDIPPDEALRMDPQQRLLLEVSWEALEHAGIIPESLRLSRTGVFVGVSSTDYVRLVSASAQQKSTIWDNTGGSSSIIANRISYFLDIQGPSIVIDTACSSSLVAVHLACRSLSTWDCDIALVGGTNVLISPEPWGGFREAGILSQTGCCHAFDKSADGMVRGEGCGVIVLQRLSDARLEGRRILAILTGSAVNQDGKSNGIMAPNPSAQIGVLENACKSARVDPLEIGYVEAHGTGTSLGDRIEAHALGMVFGRKRPGSGPLMIGSIKPNIGHLEGAAGIAGLIKAVLMVERGSLLPSGGFTEPNPAIPFTELGLRVVDELQEWPVVAGRPRRAGVSSFGFGGTNAHVIVEEAGSVGADTVSGRADVGGSGGGVVAWVISGKTASALAAQAGRLGRYVRARPALDVVDVGYSLVSTRSVFDHRAVVVGQTRDELLAGLAGVVAGRPEAGVVCGVGKPAGKTAFVFAGQGSQWLGMGSELYAAYPVFAEALDAVVDELDRHLRYPLRDVIWGHDQDLLNTTEFAQPALFAVEVALYRLLMSWGVRPGLVLGHSVGELAAAHVAGALCLPDAAMLVAARGRLMQALPAGGAMFAVQAREDEVAPMLGHDVSIAAVNGPASVVISGAHDAVSAIADRLRGQGRRVHRLAVSHAFHSALMEPMIAEFTAVAAELSVGLPTIPVISNVTGQLVADDFASADYWARHIRAVVRFGDSVRSAHCAGASRFIEVGPGGGLTSLIEASLADAQIVSVPTLRKDRPEPVSVMTAAAQGFVSGMGLDWASVFSGYRPKRVELPTYAFQHQKFWLAPAPSVSDPTAAGQIGASDGGAELLASSGFAARLAGRSADEQLAAAIEVVCEHAAAVLGRDGAAGLDAGQAFADSGFNSLSAVELRNRLTAVTAVTLPATAIFDHPTPTELAQYLITQIDGHGSSAAAAANPAERIDALTDLFLQACDAGRDADGWKMVALASNTRERMSSPVRNNVSKNVALLADGISDVVVICIPTLTVLSDQREYRDIANAMTGRHSVYSLTLPGFDSSDALPQNADMIVETVSNAIIDVVGGSCRFVLSGYSSGGVLAYALCSHLSVKHQRNPLGVALIDTYLPSQIANPSMNEGFSPNDTGKGLSREVIRVARMLNRLTATRLTAAATYAAIFQAWEPGRSMAPVLNIVAKDRIATVENLREERINRWRTAAAEAAYSVAEVPGDHFGMMSTSSEAIATEIHDWISGLVRGPHR