pks8 Resolved · high auto-curated
H37Rv Rv1662 · MTBC0 - ·
1602 aa · 1881704–1886512 (+) ·
RefSeq NP_216178.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | polyketide synthase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Polyketide synthase. Pfam: Docking (PF08990.17), ketoacyl-synt (PF00109.33), Thiolase_N (PF00108.30), Ketoacyl-synt_C (PF02801.29), KAsynt_C_assoc (PF16197.12), CurL-like_PKS_C (PF22621.3), RhiE-like_linker (PF22336.3), Acyl_transf_1 (PF00698.27), PKS_DH_N (PF21089.4), PS-DH (PF14765.13), SpnB_Rossmann (PF22953.4), ADH_N (PF08240.18), ADH_zinc_N (PF00107.33), ADH_zinc_N_2 (PF13602.13). |
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 |
O65933
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | Probable polyketide synthase Pks8 |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | pks8 |
| eggNOG description | polyketide synthase |
| Orthologous group | COG0604 |
| KEGG orthology |
K12435
|
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) pseudogene candidate
| pN/pS | 0.572 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 18 synonymous, 28 missense, 0 nonsense, 2 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 5.13% of strains (7444) · 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 |
|---|---|---|---|---|
Docking | PF08990.17 | 1.3e-07 | 7–30 | Erythronolide synthase docking domain |
ketoacyl-synt | PF00109.33 | 4.5e-96 | 34–281 | Beta-ketoacyl synthase, N-terminal domain |
Thiolase_N | PF00108.30 | 1.0e-06 | 188–235 | Thiolase, N-terminal domain |
Ketoacyl-synt_C | PF02801.29 | 2.2e-42 | 289–404 | Beta-ketoacyl synthase, C-terminal domain |
KAsynt_C_assoc | PF16197.12 | 2.4e-12 | 407–526 | Ketoacyl-synthetase C-terminal extension |
CurL-like_PKS_C | PF22621.3 | 2.5e-09 | 477–534 | CurL-like, PKS C-terminal |
RhiE-like_linker | PF22336.3 | 2.2e-07 | 477–544 | RhiE-like, KS-MAT linker domain |
Acyl_transf_1 | PF00698.27 | 7.3e-63 | 561–872 | Acyl transferase domain |
PKS_DH_N | PF21089.4 | 5.2e-25 | 921–1020 | Polyketide synthase dehydratase domain |
PS-DH | PF14765.13 | 2.5e-25 | 1044–1189 | Polyketide synthase dehydratase N-terminal domain |
SpnB_Rossmann | PF22953.4 | 7.5e-31 | 1217–1330 | Polyketide synthase extender module SpnB, Rossmann fold domain |
ADH_N | PF08240.18 | 1.0e-09 | 1373–1449 | Alcohol dehydrogenase GroES-like domain |
ADH_zinc_N | PF00107.33 | 1.7e-10 | 1491–1582 | Zinc-binding dehydrogenase |
ADH_zinc_N_2 | PF13602.13 | 1.1e-06 | 1527–1582 | Zinc-binding dehydrogenase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: pks17 (polyketide synthase), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1663 pks17 |
polyketide synthase | 999 | 1000 ctx | neighborhood:792 fusion:899 cooccurence:774 coexpression:816 database:900 textmining:883 |
Rv1661 pks7 |
polyketide synthase | 981 | 979 ctx | neighborhood:748 coexpression:863 experimental:433 |
Rv1664 pks9 |
polyketide synthase | 967 | 965 ctx | neighborhood:781 coexpression:806 |
Rv2383c mbtB |
phenyloxazoline synthase | 940 | 891 ctx | neighborhood:544 cooccurence:456 coexpression:409 textmining:478 |
Rv1527c pks5 |
polyketide synthase | 907 | 868 | experimental:791 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 905 | 868 | experimental:791 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 901 | 868 | experimental:791 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 904 | 867 | experimental:791 |
Rv2048c pks12 |
polyketide synthase | 883 | 841 | experimental:791 |
Rv0101 nrp |
peptide synthetase Nrp | 869 | 828 ctx | cooccurence:565 coexpression:421 |
Rv2928 tesA |
thioesterase TesA | 781 | 761 ctx | cooccurence:714 |
Rv2380c mbtE |
peptide synthetase | 805 | 748 ctx | cooccurence:527 |
Rv3800c pks13 |
polyketide synthase | 793 | 707 | coexpression:425 |
Rv2379c mbtF |
peptide synthetase | 680 | 661 ctx | cooccurence:474 |
Rv1181 pks4 |
polyketide beta-ketoacyl synthase | 701 | 652 | experimental:433 |
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): polyketide synthase
- Pfam (hmmscan --cut_ga): Docking PF08990.17 (E=1e-07), ketoacyl-synt PF00109.33 (E=5e-96), Thiolase_N PF00108.30 (E=1e-06), Ketoacyl-synt_C PF02801.29 (E=2e-42), KAsynt_C_assoc PF16197.12 (E=2e-12), CurL-like_PKS_C PF22621.3 (E=3e-09), RhiE-like_linker PF22336.3 (E=2e-07), Acyl_transf_1 PF00698.27 (E=7e-63), PKS_DH_N PF21089.4 (E=5e-25), PS-DH PF14765.13 (E=2e-25), SpnB_Rossmann PF22953.4 (E=7e-31), ADH_N PF08240.18 (E=1e-09), ADH_zinc_N PF00107.33 (E=2e-10), ADH_zinc_N_2 PF13602.13 (E=1e-06)
- (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_216178.1)
- Domains: Pfam-A via hmmscan --cut_ga — Docking (PF08990.17), ketoacyl-synt (PF00109.33), Thiolase_N (PF00108.30), Ketoacyl-synt_C (PF02801.29), KAsynt_C_assoc (PF16197.12), CurL-like_PKS_C (PF22621.3), RhiE-like_linker (PF22336.3), Acyl_transf_1 (PF00698.27), PKS_DH_N (PF21089.4), PS-DH (PF14765.13), SpnB_Rossmann (PF22953.4), ADH_N (PF08240.18), ADH_zinc_N (PF00107.33), ADH_zinc_N_2 (PF13602.13)
- 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
COG0604 - Curated reference: UniProt O65933 (TrEMBL, unreviewed; Predicted)
- 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 —
78 functional partner(s); context anchor
pks17 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv1662|pks8 MSGTTTHVDYLKRLTADLRRTRRRLSDLEAKLSEPVAVVGMGCRYPGGVDSPETLWELVAQGRDAVSDFPADRGWDVDGLFDPDPDACGKMYTRRGTFLEHAGDFDAGFFGIGPSEALAMDPQQRLLLEVSWEALERTGIDPTKLRGSATGVFAGVIHAGYGGQLSGELEGYGLTGSTLSVASGRVAYVLGLEGPAVSVDTACSSSLVALHLAVQSLRSGECDLALAGGVTVMATPAAFVEFSRQRALARDGRCKVYAGAADGTAWSEGAGVLVVERLVDARRLGHPVLALVRGSAVNQDGASNGLTAPNGPSQQRVIRAALASARLRAVEVDVVEGHGTGTMLGDPIEAQALLATYGQDRVEPLWLGSIKSNIGHTSAAAGVAGVIKMVQAMRHGVMPKTLHVDVPTPHVDWSVGAVSLLTQPRAWSVHGRPRRAGVSSFGISGTNAHVILEQAPVVESVVPEVASPTAASAVPWVLSARSEQALAGQAQRLLAFVAANPDLDPIDVGWSLVKTRAMFEHRAVVVGADRGALLAGLAALAAGESGAGVAVGRARSVGKTVFVFPGQGAQWVGMGAQLYAELPLFALAFDAVAEELDRHLRLPLRNVLWEGDEALLTSTEFAQPALFAIEVALATLLQHWGISPDFLIGHSVGEIAAAHLAGVLSLTDAAGLVAARGRLMAELPAGGVMVVVAASEEEVLPVLVDGANLAAVNAPHSVVVSGCEAAVSDIADHFARRGRRVHRLAVSHAFHSLLMEPMLAEFTRIAAGISVSKPRIPLVSNVTGQMAGAGYGDGQYWVEHARRPVRFAEGVQLLNAVGATRFVEVGPGGGLTALVEQSLPLGEALSVAMMRREHPEVSSVLGAVATLFTAGAQMDWPAVFGSPGRRIELPTYAFQRQRYWLPPTSAGSADISGVGLLAARHGLLGAVVEQPDSDVVVLTGRLSVGEQRWLADHVIAGVVLLAGAAFVELALRAADQVDCGVVEELTVVTPLVLPTVGGVQLQVVVGVGEMGQRPVSIYSRNAESDSGWVLHARGVLGAKAVAPAADLSVWPPLGAAPVDVDGAYQRFAELGYEYGRAFQGLTAMWRRESELFADVAVPDDVDVTLSGFGIHPLVLDAALHAMGMVGEQAATMLPFSWQGVSLHAAGASRVRARIAPAGDGTVSVELADQAGLPVLSVQALVMRSVSSQLLSAAVAAADAAGRGLLEVAWLPVELAHNDISADLVVWELESFQDGVGPVYSATHRVLVALQSWLAQERAGRLVVLTQGSVGQDATNLAGAAVWGLVRSAQAEHPGRVMLVDSDGSMDVGDVIGCGEEQLMIRNGTAYAARLAQLRPQPILQLPDTNSGWRLVAGGAGALEDLTLASCPAKELAPGQVRIEVRALGVNFRDVLVALGIYPGAAELGAEGAGVVTEVGPGVTGLAVGDPVMGLLGVAGSEAVVDARLVVKLPNRWPLTDAAGVPVVFLTAYYALRVLAQVQPGESVLVHAAAGGVGMAAVQLARLWGLEVFATASRGKWDTLHTMGCDNTHVADSRTLAFEETFWLTTEGRGVDVVLNSLAGEFTDASLRLLPRGGRFIEMGKTEFGTPRSLPRTILGWPTGLST