ppsA Resolved · high auto-curated
H37Rv Rv2931 · MTBC0 mtbc0_003114 ·
1876 aa · 3266442–3272072 (+) ·
RefSeq NP_217447.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | phthiocerol synthesis polyketide synthase type I PpsA |
|---|---|
| MTBC0 PGAP re-annotation | phthiocerol type I polyketide synthase PpsA |
| Revised (this work) | Phthiocerol type I polyketide synthase PpsA. 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), KR (PF08659.17), 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 |
P9WQE7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Phenolphthiocerol/phthiocerol polyketide synthase subunit A |
| 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 | ppsA |
| eggNOG description | synthase |
| Orthologous group | COG1020 |
| EC number |
EC 2.3.1.261
|
| KEGG orthology |
K12430, K12440, K12441
|
| Gene Ontology (87) |
GO:0000036, GO:0003674, GO:0003824, GO:0004312, GO:0004315, GO:0004316, GO:0005488, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737 +75 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 | 0.362 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 26 synonymous, 27 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 | 3.0e-98 | 102–351 | Beta-ketoacyl synthase, N-terminal domain |
Ketoacyl-synt_C | PF02801.29 | 2.7e-45 | 359–477 | Beta-ketoacyl synthase, C-terminal domain |
KAsynt_C_assoc | PF16197.12 | 6.5e-16 | 480–584 | Ketoacyl-synthetase C-terminal extension |
Acyl_transf_1 | PF00698.27 | 1.7e-124 | 632–950 | Acyl transferase domain |
PKS_DH_N | PF21089.4 | 6.2e-08 | 995–1079 | Polyketide synthase dehydratase domain |
KR | PF08659.17 | 2.4e-60 | 1491–1683 | KR domain |
PP-binding | PF00550.32 | 1.1e-16 | 1767–1832 | Phosphopantetheine attachment site |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: fas (fatty acid synthase), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2524c fas |
fatty acid synthase | 999 | 1000 ctx | neighborhood:511 coexpression:777 experimental:994 database:549 textmining:519 |
Rv2932 ppsB |
phthiocerol synthesis polyketide synthase type I PpsB | 997 | 996 ctx | neighborhood:800 coexpression:802 database:900 |
Rv2930 fadD26 |
fatty-acid--CoA ligase FadD26 | 998 | 994 ctx | neighborhood:801 coexpression:825 database:650 textmining:814 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 994 | 992 ctx | neighborhood:813 experimental:414 database:900 |
Rv2935 ppsE |
phthiocerol synthesis polyketide synthase type I PpsE | 991 | 989 ctx | neighborhood:798 database:900 |
Rv2934 ppsD |
phthiocerol synthesis polyketide synthase type I PpsD | 983 | 981 ctx | neighborhood:778 database:900 |
Rv2383c mbtB |
phenyloxazoline synthase | 990 | 979 ctx | neighborhood:544 coexpression:877 experimental:473 textmining:591 |
Rv2243 fabD |
malonyl CoA-acyl carrier protein transacylase | 964 | 961 | coexpression:604 experimental:787 database:549 |
Rv0101 nrp |
peptide synthetase Nrp | 964 | 950 ctx | cooccurence:562 coexpression:767 experimental:473 |
Rv2928 tesA |
thioesterase TesA | 934 | 907 ctx | cooccurence:705 database:500 |
Rv2380c mbtE |
peptide synthetase | 884 | 873 ctx | cooccurence:557 coexpression:446 experimental:473 |
Rv2950c fadD29 |
long-chain-fatty-acid--AMP ligase FadD29 | 875 | 861 | database:650 |
Rv3147 nuoC |
NADH-quinone oxidoreductase subunit C | 862 | 857 | coexpression:427 experimental:472 database:564 |
Rv1181 pks4 |
polyketide beta-ketoacyl synthase | 884 | 852 | database:720 |
Rv3153 nuoI |
NADH-quinone oxidoreductase subunit I | 857 | 851 | coexpression:402 experimental:473 database:564 |
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 PpsA
- MTBC0 PGAP product: phthiocerol type I polyketide synthase PpsA
- Pfam (hmmscan --cut_ga): ketoacyl-synt PF00109.33 (E=3e-98), Ketoacyl-synt_C PF02801.29 (E=3e-45), KAsynt_C_assoc PF16197.12 (E=7e-16), Acyl_transf_1 PF00698.27 (E=2e-124), PKS_DH_N PF21089.4 (E=6e-08), KR PF08659.17 (E=2e-60), PP-binding PF00550.32 (E=1e-16)
- (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_217447.1)
- 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), KR (PF08659.17), 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
COG1020 - Curated reference: UniProt P9WQE7 (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 —
234 functional partner(s); context anchor
fas - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003114|Rv2931|ppsA MTGSISGEADLRHWLIDYLVTNIGCTPDEVDPDLSLADLGVSSRDAVVLSGELSELLGRTVSPIDFWEHPTINALAAYLAAPEPSPDSDAAVKRGARNSLDEPIAVVGMGCRFPGGISCPEALWDFLCERRSSISQVPPQRWQPFEGGPPEVAAALARTTRWGSFLPDIDAFDAEFFEISPSEADKMDPQQRLLLEVAWEALEHAGIPPGTLRRSATGVFAGACLSEYGAMASADLSQVDGWSNSGGAMSIIANRLSYFLDLRGPSVAVDTACSSSLVAIHLACQSLRTQDCHLAIAAGVNLLLSPAVFRGFDQVGALSPTGQCRAFDATADGFVRGEGAGVVVLKRLTDAQRDGDRVLAVICGSAVNQDGRSNGLMAPNPAAQMAVLRAAYTNAGMQPSEVDYVEAHGTGTLLGDPIEARALGTVLGRGRPEDSPLLIGSVKTNLGHTEAAAGIAGFIKTVLAVQHGQIPPNQHFETANPHIPFTDLRMKVVDTQTEWPATGHPRRAGVSSFGFGGTNAHVVIEQGQEVRPAPGQGLSPAVSTLVVAGKTMQRVSATAGMLADWMEGPGADVALADVAHTLNHHRSRQPKFGTVVARDRTQAIAGLRALAAGQHAPGVVNPAEGSPGPGTVFVYSGRGSQWAGMGRQLLADEPAFAAAVAELEPVFVEQAGFSLHDVLANGEELVGIEQIQLGLIGMQLALTELWCSYGVRPDLVIGHSMGEVAAAVVAGALTPAEGLRVTATRSRLMAPLSGQGGMALLELDAPTTEALIADFPQVTLGIYNSPRQTVIAGPTEQIDELITRVRARDRFASRVNIEVAPHNPAMDALQPAMRSELADLTPRTPTIGIISTTYADLHTQPVFDAEHWATNMRNPVHFQQAIASAGSGADGAYHTFIEISAHPLLTQAIIDTLHSAQPGARYTSLGTLQRDTDDVVTFRTNLNKAHTIHPPHTPHPPEPHPPIPTTPWQHTRHWITTKYPAGSVGSAPRAGTLLGQHTTVATVSASPPSHLWQARLAPDAKPYQGGHRFHQVEVVPASVVLHTILSAATELGYSALSEVRFEQPIFADRPRLIQVVADNRAISLASSPAAGTPSDRWTRHVTAQLSSSPSDSASSLNEHHRANGQPPERAHRDLIPDLAELLAMRGIDGLPFSWTVASWTQHSSNLTVAIDLPEALPEGSTGPLLDAAVHLAALSDVADSRLYVPASIEQISLGDVVTGPRSSVTLNRTAHDDDGITVDVTVAAHGEVPSLSMRSLRYRALDFGLDVGRAQPPASTGPVEAYCDATNFVHTIDWQPQTVPDATHPGAEQVTHPGPVAIIGDDGAALCETLEGAGYQPAVMSDGVSQARYVVYVADSDPAGADETDVDFAVRICTEITGLVRTLAERDADKPAALWILTRGVHESVAPSALRQSFLWGLAGVIAAEHPELWGGLVDLAINDDLGEFGPALAELLAKPSKSILVRRDGVVLAPALAPVRGEPARKSLQCRPDAAYLITGGLGALGLLMADWLADRGAHRLVLTGRTPLPPRRDWQLDTLDTELRRRIDAIRALEMRGVTVEAVAADVGCREDVQALLAARDRDGAAPIRGIIHAAGITNDQLVTSMTGDAVRQVMWPKIGGSQVLHDAFPPGSVDFFYLTASAAGIFGIPGQGSYAAANSYLDALARARRQQGCHTMSLDWVAWRGLGLAADAQLVSEELARMGSRDITPSEAFTAWEFVDGYDVAQAVVVPMPAPAGADGSGANAYLLPARNWSVMAATEVRSELEQGLRRIIAAELRVPEKELDTDRPFAELGLNSLMAMAIRREAEQFVGIELSATMLFNHPTVKSLASYLAKRVAPHDVSQDNQISALSSSAGSVLDSLFDRIESAPPEAERSV