ppsD Resolved · high auto-curated
H37Rv Rv2934 · MTBC0 mtbc0_003117 ·
1827 aa · 3283245–3288728 (+) ·
RefSeq NP_217450.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | phthiocerol synthesis polyketide synthase type I PpsD |
|---|---|
| MTBC0 PGAP re-annotation | phthiocerol type I polyketide synthase PpsD |
| Revised (this work) | Phthiocerol type I polyketide synthase PpsD. Pfam: ketoacyl-synt (PF00109.33), Ketoacyl-synt_C (PF02801.29), KAsynt_C_assoc (PF16197.12), Acyl_transf_1 (PF00698.27), PKS_DH_N (PF21089.4), PS-DH (PF14765.13), KR (PF08659.17), adh_short (PF00106.32), adh_short_C2 (PF13561.13), PP-binding (PF00550.32). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WQE3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Phenolphthiocerol/phthiocerol polyketide synthase subunit D |
| 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 | ppsD |
| eggNOG description | polyketide synthase |
| Orthologous group | COG1028 |
| EC number |
EC 2.3.1.111, EC 2.3.1.252
|
| KEGG orthology |
K11628, K12431, K12432, K12433, K12442, K12443
|
| Gene Ontology (62) |
GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005886, GO:0006066, GO:0006082, GO:0006629, GO:0006631, GO:0006633, GO:0006725, GO:0008150 +50 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 | 0.623 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 20 synonymous, 35 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 | 2.6e-100 | 36–285 | Beta-ketoacyl synthase, N-terminal domain |
Ketoacyl-synt_C | PF02801.29 | 3.1e-41 | 293–411 | Beta-ketoacyl synthase, C-terminal domain |
KAsynt_C_assoc | PF16197.12 | 3.0e-11 | 415–518 | Ketoacyl-synthetase C-terminal extension |
Acyl_transf_1 | PF00698.27 | 5.6e-100 | 566–873 | Acyl transferase domain |
PKS_DH_N | PF21089.4 | 2.0e-22 | 910–1016 | Polyketide synthase dehydratase domain |
PS-DH | PF14765.13 | 2.9e-33 | 1038–1197 | Polyketide synthase dehydratase N-terminal domain |
KR | PF08659.17 | 3.3e-56 | 1439–1616 | KR domain |
adh_short | PF00106.32 | 1.0e-09 | 1442–1588 | short chain dehydrogenase |
adh_short_C2 | PF13561.13 | 3.1e-09 | 1449–1596 | Enoyl-(Acyl carrier protein) reductase |
PP-binding | PF00550.32 | 9.7e-08 | 1714–1779 | Phosphopantetheine attachment site |
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 998 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 998 | 998 ctx | neighborhood:785 coexpression:862 experimental:408 database:900 |
Rv2935 ppsE |
phthiocerol synthesis polyketide synthase type I PpsE | 997 | 998 ctx | neighborhood:774 coexpression:860 database:900 |
Rv2932 ppsB |
phthiocerol synthesis polyketide synthase type I PpsB | 987 | 986 ctx | neighborhood:780 database:900 |
Rv2931 ppsA |
phthiocerol synthesis polyketide synthase type I PpsA | 983 | 981 ctx | neighborhood:778 database:900 |
Rv2930 fadD26 |
fatty-acid--CoA ligase FadD26 | 976 | 960 ctx | neighborhood:774 database:650 textmining:430 |
Rv2938 drrC |
daunorubicin ABC transporter permease DrrC | 964 | 959 ctx | neighborhood:787 coexpression:815 |
Rv2937 drrB |
daunorubicin ABC transporter permease DrrB | 965 | 958 ctx | neighborhood:787 coexpression:810 |
Rv2936 drrA |
daunorubicin ABC transporter ATP-binding protein DrrA | 955 | 952 ctx | neighborhood:760 coexpression:810 |
Rv2939 papA5 |
phthiocerol/phthiodiolone dimycocerosyl transferase | 949 | 924 ctx | neighborhood:614 coexpression:733 |
Rv2928 tesA |
thioesterase TesA | 885 | 880 ctx | cooccurence:725 database:500 |
Rv1181 pks4 |
polyketide beta-ketoacyl synthase | 836 | 828 | database:720 |
Rv2950c fadD29 |
long-chain-fatty-acid--AMP ligase FadD29 | 810 | 810 | database:650 |
Rv0101 nrp |
peptide synthetase Nrp | 824 | 780 ctx | cooccurence:513 coexpression:415 |
Rv1180 pks3 |
polyketide beta-ketoacyl synthase | 744 | 744 | database:720 |
Rv1660 pks10 |
chalcone synthase | 776 | 730 | database:720 |
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 PpsD
- MTBC0 PGAP product: phthiocerol type I polyketide synthase PpsD
- Pfam (hmmscan --cut_ga): ketoacyl-synt PF00109.33 (E=3e-100), Ketoacyl-synt_C PF02801.29 (E=3e-41), KAsynt_C_assoc PF16197.12 (E=3e-11), Acyl_transf_1 PF00698.27 (E=6e-100), PKS_DH_N PF21089.4 (E=2e-22), PS-DH PF14765.13 (E=3e-33), KR PF08659.17 (E=3e-56), adh_short PF00106.32 (E=1e-09), adh_short_C2 PF13561.13 (E=3e-09), PP-binding PF00550.32 (E=1e-07)
- (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_217450.1)
- Domains: Pfam-A via hmmscan --cut_ga — ketoacyl-synt (PF00109.33), Ketoacyl-synt_C (PF02801.29), KAsynt_C_assoc (PF16197.12), Acyl_transf_1 (PF00698.27), PKS_DH_N (PF21089.4), PS-DH (PF14765.13), KR (PF08659.17), adh_short (PF00106.32), adh_short_C2 (PF13561.13), PP-binding (PF00550.32)
- 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
COG1028 - Curated reference: UniProt P9WQE3 (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 —
66 functional partner(s); context anchor
ppsC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003117|Rv2934|ppsD MTSLAERAAQLSPNARAALARELVRAGTTFPTDICEPVAVVGIGCRFPGNVTGPESFWQLLADGVDTIEQVPPDRWDADAFYDPDPSASGRMTTKWGGFVSDVDAFDADFFGITPREAVAMDPQHRMLLEVAWEALEHAGIPPDSLSGTRTGVMMGLSSWDYTIVNIERRADIDAYLSTGTPHCAAVGRIAYLLGLRGPAVAVDTACSSSLVAIHLACQSLRLRETDVALAGGVQLTLSPFTAIALSKWSALSPTGRCNSFDANADGFVRGEGCGVVVLKRLADAVRDQDRVLAVVRGSATNSDGRSNGMTAPNALAQRDVITSALKLADVTPDSVNYVETHGTGTVLGDPIEFESLAATYGLGKGQGESPCALGSVKTNIGHLEAAAGVAGFIKAVLAVQRGHIPRNLHFTRWNPAIDASATRLFVPTESAPWPAAAGPRRAAVSSFGLSGTNAHVVVEQAPDTAVAAAGGMPYVSALNVSGKTAARVASAAAVLADWMSGPGAAAPLADVAHTLNRHRARHAKFATVIARDRAEAIAGLRALAAGQPRVGVVDCDQHAGGPGRVFVYSGQGSQWASMGQQLLANEPAFAKAVAELDPIFVDQVGFSLQQTLIDGDEVVGIDRIQPVLVGMQLALTELWRSYGVIPDAVIGHSMGEVSAAVVAGALTPEQGLRVITTRSRLMARLSGQGAMALLELDADAAEALIAGYPQVTLAVHASPRQTVIAGPPEQVDTVIAAVATQNRLARRVEVDVASHHPIIDPILPELRSALADLTPQPPSIPIISTTYESAQPVADADYWSANLRNPVRFHQAVTAAGVDHNTFIEISPHPVLTHALTDTLDPDGSHTVMSTMNRELDQTLYFHAQLAAVGVAASEHTTGRLVDLPPTPWHHQRFWVTDRSAMSELAATHPLLGAHIEMPRNGDHVWQTDVGTEVCPWLADHKVFGQPIMPAAGFAEIALAAASEALGTAADAVAPNIVINQFEVEQMLPLDGHTPLTTQLIRGGDSQIRVEIYSRTRGGEFCRHATAKVEQSPRECAHAHPEAQGPATGTTVSPADFYALLRQTGQHHGPAFAALSRIVRLADGSAETEISIPDEAPRHPGYRLHPVVLDAALQSVGAAIPDGEIAGSAEASYLPVSFETIRVYRDIGRHVRCRAHLTNLDGGTGKMGRIVLINDAGHIAAEVDGIYLRRVERRAVPLPLEQKIFDAEWTESPIAAVPAPEPAAETTRGSWLVLADATVDAPGKAQAKSMADDFVQQWRSPMRRVHTADIHDESAVLAAFAETAGDPEHPPVGVVVFVGGASSRLDDELAAARDTVWSITTVVRAVVGTWHGRSPRLWLVTGGGLSVADDEPGTPAAASLKGLVRVLAFEHPDMRTTLVDLDITQDPLTALSAELRNAGSGSRHDDVIAWRGERRFVERLSRATIDVSKGHPVVRQGASYVVTGGLGGLGLVVARWLVDRGAGRVVLGGRSDPTDEQCNVLAELQTRAEIVVVRGDVASPGVAEKLIETARQSGGQLRGVVHAAAVIEDSLVFSMSRDNLERVWAPKATGALRMHEATADCELDWWLGFSSAASLLGSPGQAAYACASAWLDALVGWRRASGLPAAVINWGPWSEVGVAQALVGSVLDTISVAEGIEALDSLLAADRIRTGVARLRADRALVAFPEIRSISYFTQVVEELDSAGDLGDWGGPDALADLDPGEARRAVTERMCARIAAVMGYTDQSTVEPAVPLDKPLTELGLDSLMAVRIRNGARADFGVEPPVALILQGASLHDLTADLMRQLGLNDPDPALNNADTIRDRARQRAAARHGAAMRRRPKPEVQGG