ppsE Resolved · high auto-curated
H37Rv Rv2935 · MTBC0 mtbc0_003118 ·
1488 aa · 3288734–3293200 (+) ·
RefSeq NP_217451.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | phthiocerol synthesis polyketide synthase type I PpsE |
|---|---|
| MTBC0 PGAP re-annotation | phthiocerol type I polyketide synthase PpsE |
| Revised (this work) | Phthiocerol type I polyketide synthase PpsE. 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), Condensation (PF00668.26). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WQE1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Phenolphthiocerol/phthiocerol polyketide synthase subunit E |
| EC (curated) |
EC 2.3.1.292
|
| Curated function | Part of the PpsABCDE complex involved in the biosynthesis of the lipid core common to phthiocerols and phenolphthiocerols by successive additions of malonyl-CoA or methylmalonyl-CoA extender units. PpsA can accept as substrate the activated forms of either icosanoyl (C20), docosanoyl (C22) or lignoceroyl (C24) groups from FadD26, or a (4-hydroxyphenyl)-C17 or (4-hydroxyphenyl)-C19 fatty acyl from FadD29. PpsA initiates the biosynthesis and extends its substrate using a malonyl-CoA extender unit. The PpsB and PpsC proteins add the second and third malonyl-CoA extender units. PpsD adds an (R)-me. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | ppsE |
| eggNOG description | synthase |
| Orthologous group | COG1020 |
| KEGG orthology |
K12444
|
| Gene Ontology (53) |
GO:0003674, GO:0003824, GO:0004312, GO:0004315, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005886, GO:0006082, GO:0006629 +41 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 | 0.595 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 13 synonymous, 22 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 | 7.4e-73 | 6–261 | Beta-ketoacyl synthase, N-terminal domain |
Ketoacyl-synt_C | PF02801.29 | 2.3e-42 | 270–389 | Beta-ketoacyl synthase, C-terminal domain |
KAsynt_C_assoc | PF16197.12 | 4.7e-15 | 392–500 | Ketoacyl-synthetase C-terminal extension |
CurL-like_PKS_C | PF22621.3 | 3.8e-08 | 456–517 | CurL-like, PKS C-terminal |
Acyl_transf_1 | PF00698.27 | 3.2e-49 | 551–864 | Acyl transferase domain |
PP-binding | PF00550.32 | 5.3e-14 | 938–1000 | Phosphopantetheine attachment site |
Condensation | PF00668.26 | 8.4e-25 | 1027–1358 | Condensation domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ppsC (phthiocerol synthesis polyketide synthase type I PpsC), high confidence from genomic context alone (score 999 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 999 | 999 ctx | neighborhood:881 coexpression:862 experimental:408 database:900 |
Rv2934 ppsD |
phthiocerol synthesis polyketide synthase type I PpsD | 997 | 998 ctx | neighborhood:774 coexpression:860 database:900 |
Rv2931 ppsA |
phthiocerol synthesis polyketide synthase type I PpsA | 991 | 989 ctx | neighborhood:798 database:900 |
Rv2932 ppsB |
phthiocerol synthesis polyketide synthase type I PpsB | 990 | 988 ctx | neighborhood:798 database:900 |
Rv2937 drrB |
daunorubicin ABC transporter permease DrrB | 989 | 982 ctx | neighborhood:874 coexpression:860 textmining:458 |
Rv2936 drrA |
daunorubicin ABC transporter ATP-binding protein DrrA | 993 | 981 ctx | neighborhood:867 coexpression:860 textmining:672 |
Rv2938 drrC |
daunorubicin ABC transporter permease DrrC | 982 | 974 ctx | neighborhood:823 coexpression:860 |
Rv2930 fadD26 |
fatty-acid--CoA ligase FadD26 | 983 | 960 ctx | neighborhood:780 database:650 textmining:597 |
Rv2939 papA5 |
phthiocerol/phthiodiolone dimycocerosyl transferase | 991 | 954 ctx | neighborhood:622 cooccurence:436 coexpression:803 textmining:821 |
Rv1663 pks17 |
polyketide synthase | 950 | 948 ctx | fusion:737 cooccurence:762 |
Rv2928 tesA |
thioesterase TesA | 958 | 888 ctx | cooccurence:742 database:500 textmining:648 |
Rv0101 nrp |
peptide synthetase Nrp | 856 | 847 ctx | cooccurence:594 coexpression:415 |
Rv2950c fadD29 |
long-chain-fatty-acid--AMP ligase FadD29 | 870 | 815 | database:650 |
Rv1181 pks4 |
polyketide beta-ketoacyl synthase | 845 | 812 | database:720 |
Rv2383c mbtB |
phenyloxazoline synthase | 823 | 784 | coexpression:409 |
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: phthiocerol synthesis polyketide synthase type I PpsE
- MTBC0 PGAP product: phthiocerol type I polyketide synthase PpsE
- Pfam (hmmscan --cut_ga): ketoacyl-synt PF00109.33 (E=7e-73), Ketoacyl-synt_C PF02801.29 (E=2e-42), KAsynt_C_assoc PF16197.12 (E=5e-15), CurL-like_PKS_C PF22621.3 (E=4e-08), Acyl_transf_1 PF00698.27 (E=3e-49), PP-binding PF00550.32 (E=5e-14), Condensation PF00668.26 (E=8e-25)
- (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_217451.1)
- 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), Condensation (PF00668.26)
- 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
COG1020 - Curated reference: UniProt P9WQE1 (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 —
74 functional partner(s); context anchor
ppsC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003118|Rv2935|ppsE MSIPENAIAVVGMAGRFPGAKDVSAFWSNLRRGKESIVTLSEQELRDAGVSDKTLADPAYVRRAPLLDGIDEFDAGFFGFPPLAAQVLDPQHRLFLQCAWHALEDAGADPARFDGSIGVYGTSSPSGYLLHNLLSHRDPNAVLAEGLNFDQFSLFLQNDKDFLATRISHAFNLRGPSIAVQTACSSSLVAVHLACLSLLSGECDMALAGGSSLCIPHRVGYFTSPGSMVSAVGHCRPFDVRADGTVFGSGVGLVVLKPLAAAIDAGDRIHAVIRGSAINNDGSAKMGYAAPNPAAQADVIAEAHAVSGIDSSTVSYVECHGTGTPLGDPIEIQGLRAAFEVSQTSRSAPCVLGSVKSNIGHLEVAAGIAGLIKTILCLKNKALPATLHYTSPNPELRLDQSPFVVQSKYGPWECDGVRRAGVSSFGVGGTNAHVVLEEAPAEASEVSAHAEPAGPQVILLSAQTAAALGESRTALAAALETQDGPRLSDVAYTLARRRKHNVTMAAVVHDREHAATVLRAAEHDNVFVGEAAHDGEHGDRADAAPTSDRVVFLFPGQGAQHVGMAKGLYDTEPVFAQHFDTCAAGFRDETGIDLHAEVFDGTATDLERIDRSQPALFTVEYALAKLVDTFGVRAGAYIGYSTGEYIAATLAGVFDLQTAIKTVSLRARLMHESPPGAMVAVALGPDDVTQYLPPEVELSAVNDPGNCVVAGPKDQIRALRQRLTEAGIPVRRVRATHAFHTSAMDPMLGQFQEFLSRQQLRPPRTPLLSNLTGSWMSDQQVVDPASWTRQISSPIRFADELDVVLAAPSRILVEVGPGGSLTGSAMRHPKWSTTHRTVRLMRHPLQDVDDRDTFLRALGELWSAGVEVDWTPRRPAVPHLVSLPGYPFARQRHWVEPNHTVWAQAPGANNGSPAGTADGSTAATVDAARNGESQTEVTLQRIWSQCLGVSSVDRNANFFDLGGDSLMAISIAMAAANEGLTITPQDLYEYPTLASLTAAVDASFASSGLAKPPEAQANPAVPPNVTYFLDRGLRDTGRCRVPLILRLDPKIGLPDIRAVLTAVVNHHDALRLHLVGNDGIWEQHIAAPAEFTGLSNRSVPDGVAAGSPEERAAVLGILAELLEDQTDPNAPLAAVHIAAAHGGPHYLCLAIHAMVTDDSSRQILATDIVTAFGQRLAGEEITLEPVSTGWREWSLRCAALATHPAALDTRSYWIENSTKATLWLADALPNAHTAHPPRADELTKLSSTLSVEQTSELDDGRRRFRRSIQTILLAALGRTIAQTVGEGVVAVELEGEGRSVLRPDVDLRRTVGWFTTYYPVPLACATGLGALAQLDAVHNTLKSVPHYGIGYGLLRYVYAPTGRVLGAQRTPDIHFRYAGVIPELPSGDAPVQFDSDMTLPVREPIPGMGHAIELRVYRFGGSLHLDWWYDTRRIPAATAEALERTFPLALSALIQEAIAAEHTEHDDSEIVGEPEAGALVDLSSMDAG