pks15 Resolved · high auto-curated
H37Rv Rv2947c · MTBC0 - ·
496 aa · 3296350–3297840 (-) ·
RefSeq NP_217463.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | polyketide synthase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Polyketide synthase. Pfam: ketoacyl-synt (PF00109.33), Thiolase_N (PF00108.30), Ketoacyl-synt_C (PF02801.29), KAsynt_C_assoc (PF16197.12). |
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 |
P96284
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Putative inactive phenolphthiocerol synthesis polyketide synthase type I Pks15 |
UniProt still lists this protein as Putative inactive phenolphthiocerol synthesis polyketide synthase type I Pks15; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | pks15/1 |
| eggNOG description | polyketide synthase |
| Orthologous group | COG3321 |
| EC number |
EC 2.3.1.261
|
| KEGG orthology |
K12430
|
| Gene Ontology (35) |
GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0006629, GO:0006643, GO:0006664, GO:0008150, GO:0008152, GO:0008610, GO:0009058 +23 more
|
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 | 0.581 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 10 missense, 0 nonsense, 4 frameshift |
| Disruption | 4 distinct premature-stop/frameshift site(s); most common in 43.53% of strains (63205) · 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 | 9.5e-99 | 47–294 | Beta-ketoacyl synthase, N-terminal domain |
Thiolase_N | PF00108.30 | 2.5e-06 | 206–248 | Thiolase, N-terminal domain |
Ketoacyl-synt_C | PF02801.29 | 1.5e-44 | 302–419 | Beta-ketoacyl synthase, C-terminal domain |
KAsynt_C_assoc | PF16197.12 | 3.0e-09 | 422–477 | Ketoacyl-synthetase C-terminal extension |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: pks1 (polyketide synthase), high confidence from genomic context alone (score 999 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2946c pks1 |
polyketide synthase | 999 | 999 ctx | neighborhood:787 fusion:865 cooccurence:771 coexpression:754 textmining:819 |
Rv1663 pks17 |
polyketide synthase | 981 | 980 ctx | fusion:900 cooccurence:774 |
Rv2950c fadD29 |
long-chain-fatty-acid--AMP ligase FadD29 | 976 | 974 ctx | neighborhood:675 fusion:461 coexpression:726 |
Rv2948c fadD22 |
p-hydroxybenzoyl--AMP ligase | 980 | 973 ctx | neighborhood:774 coexpression:817 |
Rv1181 pks4 |
polyketide beta-ketoacyl synthase | 982 | 964 ctx | fusion:829 cooccurence:749 textmining:532 |
Rv2949c |
chorismate pyruvate-lyase | 949 | 939 ctx | neighborhood:746 coexpression:770 |
Rv2380c mbtE |
peptide synthetase | 924 | 920 ctx | fusion:771 cooccurence:523 |
Rv3777 |
oxidoreductase | 916 | 916 ctx | fusion:900 |
Rv3141 fadB4 |
NADPH quinone oxidoreductase FadB | 916 | 915 ctx | fusion:899 |
Rv2383c mbtB |
phenyloxazoline synthase | 926 | 910 ctx | fusion:666 coexpression:406 |
Rv1912c fadB5 |
oxidoreductase FadB | 905 | 905 ctx | fusion:887 |
Rv0101 nrp |
peptide synthetase Nrp | 881 | 874 ctx | fusion:422 cooccurence:538 coexpression:412 |
Rv2930 fadD26 |
fatty-acid--CoA ligase FadD26 | 847 | 836 ctx | fusion:625 |
Rv0166 fadD5 |
fatty-acid--CoA ligase FadD5 | 836 | 828 ctx | fusion:702 |
Rv1185c fadD21 |
fatty-acid--CoA ligase FadD21 | 821 | 822 ctx | fusion:598 |
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): ketoacyl-synt PF00109.33 (E=1e-98), Thiolase_N PF00108.30 (E=3e-06), Ketoacyl-synt_C PF02801.29 (E=2e-44), KAsynt_C_assoc PF16197.12 (E=3e-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_217463.1)
- Domains: Pfam-A via hmmscan --cut_ga — ketoacyl-synt (PF00109.33), Thiolase_N (PF00108.30), Ketoacyl-synt_C (PF02801.29), KAsynt_C_assoc (PF16197.12)
- 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 P96284 (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 —
70 functional partner(s); context anchor
pks1 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2947c|pks15 MIEEQRTMSVEGADQQSEKLFHYLKKVAVELDETRARLREYEQRATEPVAVVGIGCRFPGGVDGPDGLWDVVSAGRDVVSEFPTDRGWDVEGLYDPDPDAEGKTYTRWGAFLDDATGFDAGFFGIAPSEVLAMDPQQRLMLEVSWEALEHAGIDPLSLRGSATGVYTGIFAASYGNRDTGGLQGYGLTGTSISVASGRVSYVLGLQGPAVSVDTACSSSLVAIHWAMSSLRSGECDLALAGGVTVMGLPSIFVGFSRQRGLAADGRCKAFAAAADGTGWGEGAGVVVLERLSDARRLGHSVLAVVRGSAVNQDGASNGLTAPNGLAQQRVIQVALANAGLSAADVDVVEAHGTATTLGDPIEAQALLSTYGQGGPAEQPLWVGSIKSNMGHTQAAAGVAGVIKMVQAMRHGVMPATLHVDEPSPRVDWTSGAVSVLTEAREWSVDGRPRRAAVSSFGISGTNAHLILEEAPVPAPAEAPVEASESTGGRGRRWCRG