pks3 Resolved · high auto-curated
H37Rv Rv1180 · MTBC0 - ·
488 aa · 1313725–1315191 (+) ·
RefSeq NP_215696.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | polyketide beta-ketoacyl synthase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Polyketide beta-ketoacyl 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 |
A0A089QRB9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Mycolipanoate synthase |
| EC (curated) |
EC 2.3.1.252
|
| Curated function | Polyketide synthase involved in the biosynthesis of methyl-branched fatty acids such as mycolipanoic, mycolipenic (phthienoic) and mycolipodienoic acids required for the synthesis of a major class of polyacylated trehaloses. Catalyzes the elongation of CoA esters of long-chain fatty acids by incorporation of three methylmalonyl (but not malonyl) residues, to form trimethyl-branched fatty-acids. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | pks2 |
| eggNOG description | polyketide synthase |
| Orthologous group | COG0604 |
| EC number |
EC 2.3.1.111, EC 2.3.1.252
|
| KEGG orthology |
K11628, K12431, K12432, K12433, K12442, K12443
|
| Gene Ontology (34) |
GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0006082, GO:0006629, GO:0006631, GO:0006633, GO:0008150, GO:0008152, GO:0008610, GO:0009058 +22 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 | 0.724 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 6 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 | 2.0e-93 | 8–256 | Beta-ketoacyl synthase, N-terminal domain |
Thiolase_N | PF00108.30 | 1.3e-06 | 162–205 | Thiolase, N-terminal domain |
Ketoacyl-synt_C | PF02801.29 | 9.9e-39 | 264–377 | Beta-ketoacyl synthase, C-terminal domain |
KAsynt_C_assoc | PF16197.12 | 2.3e-10 | 388–474 | Ketoacyl-synthetase C-terminal extension |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: pks4 (polyketide beta-ketoacyl synthase), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1181 pks4 |
polyketide beta-ketoacyl synthase | 999 | 1000 ctx | neighborhood:646 fusion:806 cooccurence:756 coexpression:862 database:900 |
Rv1663 pks17 |
polyketide synthase | 981 | 980 ctx | fusion:900 cooccurence:772 |
Rv2946c pks1 |
polyketide synthase | 971 | 968 ctx | fusion:828 cooccurence:760 |
Rv1182 papA3 |
acyltransferase papA3 | 963 | 927 ctx | neighborhood:513 coexpression:815 textmining:528 |
Rv3777 |
oxidoreductase | 917 | 916 ctx | fusion:899 |
Rv3141 fadB4 |
NADPH quinone oxidoreductase FadB | 915 | 914 ctx | fusion:898 |
Rv2380c mbtE |
peptide synthetase | 915 | 911 ctx | fusion:739 cooccurence:532 |
Rv2383c mbtB |
phenyloxazoline synthase | 925 | 909 ctx | fusion:671 coexpression:406 |
Rv1912c fadB5 |
oxidoreductase FadB | 906 | 906 ctx | fusion:888 |
Rv0101 nrp |
peptide synthetase Nrp | 877 | 870 ctx | cooccurence:548 coexpression:414 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 860 | 851 | experimental:408 database:720 |
Rv2379c mbtF |
peptide synthetase | 815 | 808 ctx | fusion:504 cooccurence:482 |
Rv0166 fadD5 |
fatty-acid--CoA ligase FadD5 | 798 | 799 ctx | fusion:650 |
Rv1529 fadD24 |
fatty-acid--CoA ligase FadD24 | 790 | 790 ctx | fusion:520 |
Rv2381c mbtD |
polyketide synthetase | 782 | 783 ctx | cooccurence:773 |
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 beta-ketoacyl synthase
- Pfam (hmmscan --cut_ga): ketoacyl-synt PF00109.33 (E=2e-93), Thiolase_N PF00108.30 (E=1e-06), Ketoacyl-synt_C PF02801.29 (E=1e-38), KAsynt_C_assoc PF16197.12 (E=2e-10)
- (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_215696.1)
- 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
COG0604 - Curated reference: UniProt A0A089QRB9 (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 —
76 functional partner(s); context anchor
pks4 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv1180|pks3 MRTATATSVAVIGMACRLPGGIDSPQRLWEALLRGDDLVGEIPADRWDANVYYDPEPGVPGRSVSRWGAFLDDVGGFDCDFFGLTEREATAIDPQHRLLLEVSWEAIEHAGVDPATLAESQTGVFVGLTHGDYELLSADCGAAEGPYGFTGTSNSFASGRVAYTLGLHGPAVTVDTACSSGLTAVHQACRSLDDGESDLALAGGVVVTLEPRKSVSGSLQGMLSPTGRCHAFDEAADGFVSGEGCVVLLLKRLPDAVRDGDRVLAIVRGTAANQDGRTVNIAAPSAQAQIAVYQQALAAAGVEASTVGMVEAHGTGTPVGDPVEYASLAAVYGTEGPCALTSVKTNFGHLQSASGPLGLMKTILALRHGVVPQNLHFCRLPDQLAEIDTELFVPQANTSWPDNTGQPRRAAVSSYGMSGTNVHAILEQAPVSEPAASGPELTPEAGGLALFPVSATSAEQLHVTAARLADWVDQNGNAGSRVSMRDLG