ppsC Resolved · high auto-curated
H37Rv Rv2933 · MTBC0 mtbc0_003116 ·
2188 aa · 3276682–3283248 (+) ·
RefSeq NP_217449.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | phthiocerol synthesis polyketide synthase type I PpsC |
|---|---|
| MTBC0 PGAP re-annotation | phthiocerol type I polyketide synthase PpsC |
| Revised (this work) | Phthiocerol type I polyketide synthase PpsC. Pfam: ketoacyl-synt (PF00109.33), Ketoacyl-synt_C (PF02801.29), Acyl_transf_1 (PF00698.27), PKS_DH_N (PF21089.4), PS-DH (PF14765.13), ADH_N (PF08240.18), ADH_zinc_N (PF00107.33), ADH_zinc_N_2 (PF13602.13), 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 |
P96202
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Phenolphthiocerol/phthiocerol polyketide synthase subunit C |
| 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 |
C Energy production and conversionQ Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | ppsC |
| 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 (63) |
GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0006066, GO:0006082, GO:0006629, GO:0006631, GO:0006633, GO:0006725 +51 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 | 0.358 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 16 synonymous, 16 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 | 1.8e-97 | 35–288 | Beta-ketoacyl synthase, N-terminal domain |
Ketoacyl-synt_C | PF02801.29 | 2.7e-41 | 296–413 | Beta-ketoacyl synthase, C-terminal domain |
Acyl_transf_1 | PF00698.27 | 7.0e-108 | 572–890 | Acyl transferase domain |
PKS_DH_N | PF21089.4 | 6.4e-21 | 928–1029 | Polyketide synthase dehydratase domain |
PS-DH | PF14765.13 | 4.8e-23 | 1057–1220 | Polyketide synthase dehydratase N-terminal domain |
ADH_N | PF08240.18 | 1.7e-08 | 1485–1552 | Alcohol dehydrogenase GroES-like domain |
ADH_zinc_N | PF00107.33 | 3.8e-22 | 1607–1714 | Zinc-binding dehydrogenase |
ADH_zinc_N_2 | PF13602.13 | 5.5e-24 | 1639–1778 | Zinc-binding dehydrogenase |
KR | PF08659.17 | 7.3e-63 | 1802–1980 | KR domain |
adh_short | PF00106.32 | 8.3e-12 | 1805–1961 | short chain dehydrogenase |
adh_short_C2 | PF13561.13 | 4.8e-10 | 1812–1960 | Enoyl-(Acyl carrier protein) reductase |
PP-binding | PF00550.32 | 1.8e-11 | 2077–2141 | 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:544 coexpression:974 experimental:999 database:604 textmining:745 |
Rv2935 ppsE |
phthiocerol synthesis polyketide synthase type I PpsE | 999 | 999 ctx | neighborhood:881 coexpression:862 experimental:408 database:900 |
Rv2934 ppsD |
phthiocerol synthesis polyketide synthase type I PpsD | 998 | 998 ctx | neighborhood:785 coexpression:862 experimental:408 database:900 |
Rv2932 ppsB |
phthiocerol synthesis polyketide synthase type I PpsB | 998 | 996 ctx | neighborhood:892 experimental:458 database:900 textmining:545 |
Rv2243 fabD |
malonyl CoA-acyl carrier protein transacylase | 996 | 996 | coexpression:750 experimental:960 database:549 |
Rv2383c mbtB |
phenyloxazoline synthase | 998 | 994 ctx | neighborhood:544 coexpression:937 experimental:721 textmining:752 |
Rv2048c pks12 |
polyketide synthase | 997 | 993 ctx | neighborhood:544 coexpression:437 experimental:965 textmining:631 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 996 | 992 ctx | neighborhood:544 coexpression:456 experimental:965 textmining:614 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 996 | 992 ctx | neighborhood:544 coexpression:425 experimental:965 textmining:612 |
Rv1527c pks5 |
polyketide synthase | 996 | 992 ctx | neighborhood:544 coexpression:425 experimental:965 textmining:619 |
Rv2931 ppsA |
phthiocerol synthesis polyketide synthase type I PpsA | 994 | 992 ctx | neighborhood:813 experimental:414 database:900 |
Rv3153 nuoI |
NADH-quinone oxidoreductase subunit I | 990 | 987 | coexpression:415 experimental:953 database:564 |
Rv3147 nuoC |
NADH-quinone oxidoreductase subunit C | 989 | 987 | coexpression:455 experimental:951 database:564 |
Rv0101 nrp |
peptide synthetase Nrp | 994 | 985 ctx | neighborhood:544 cooccurence:503 coexpression:794 experimental:721 textmining:616 |
Rv1181 pks4 |
polyketide beta-ketoacyl synthase | 990 | 983 ctx | neighborhood:544 experimental:795 database:720 textmining:445 |
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 PpsC
- MTBC0 PGAP product: phthiocerol type I polyketide synthase PpsC
- Pfam (hmmscan --cut_ga): ketoacyl-synt PF00109.33 (E=2e-97), Ketoacyl-synt_C PF02801.29 (E=3e-41), Acyl_transf_1 PF00698.27 (E=7e-108), PKS_DH_N PF21089.4 (E=6e-21), PS-DH PF14765.13 (E=5e-23), ADH_N PF08240.18 (E=2e-08), ADH_zinc_N PF00107.33 (E=4e-22), ADH_zinc_N_2 PF13602.13 (E=5e-24), KR PF08659.17 (E=7e-63), adh_short PF00106.32 (E=8e-12), adh_short_C2 PF13561.13 (E=5e-10), PP-binding PF00550.32 (E=2e-11)
- (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_217449.1)
- Domains: Pfam-A via hmmscan --cut_ga — ketoacyl-synt (PF00109.33), Ketoacyl-synt_C (PF02801.29), Acyl_transf_1 (PF00698.27), PKS_DH_N (PF21089.4), PS-DH (PF14765.13), ADH_N (PF08240.18), ADH_zinc_N (PF00107.33), ADH_zinc_N_2 (PF13602.13), 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
COG0604 - Curated reference: UniProt P96202 (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 —
637 functional partner(s); context anchor
fas - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003116|Rv2933|ppsC MTAATPDRRAIITEALHKIDDLTARLEIAEKSSSEPIAVIGMGCRFPGGVNNPEQFWDLLCAGRSGIVRVPAQRWDADAYYCDDHTVPGTICSTEGGFLTSWQPDEFDAEFFSISPREAAAMDPQQRLLIEVAWEALEDAGVPQHTIRGTQTSVFVGVTAYDYMLTLAGRLRPVDLDAYIPTGNSANFAAGRLAYILGARGPAVVIDTACSSSLVAVHLACQSLRGRESDMALVGGTNLLLSPGPSIACSRWGMLSPEGRCKTFDASADGYVRGEGAAVVVLKRLDDAVRDGNRILAVVRGSAVNQDGASSGVTVPNGPAQQALLAKALTSSKLTAADIDYVEAHGTGTPLGDPIELDSLSKVFSDRAGSDQLVIGSVKTNLGHLEAAAGVAGLMKAVLAVHNGYIPRHLNFHQLTPHASEAASRLRIAADGIDWPTTGRPRRAGVSSFGVSGTNAHVVIEQAPDPMAAAGTEPQRGPVPAVSTLVVFGKTAPRVAATASVLADWLDGPGAAVPLADVAHTLNHHRARQTRFGTVAAVDRRQAVIGLRALAAGQSAPGVVAPREGSIGGGTVFVYSGRGSQWAGMGRQLLADEPAFAAAIAELEPEFVAQGGFSLRDVIAGGKELVGIEQIQLGLIGMQLALTALWRSYGVTPDAVIGHSMGEVAAAVVAGALTPAQGLRVTAVRSRLMAPLSGQGTMALLELDAEATEALIADYPEVSLGIYASPRQTVISGPPLLIDELIDKVRQQNGFATRVNIEVAPHNPAMDALQPAMRSELADLTPQPPTIPIISTTYADLGISLGSGPRFDAEHWATNMRNPVRFHQAIAHAGADHHTFIEISAHPLLTHSISDTLRASYDVDNYLSIGTLQRDAHDTLEFHTNLNTTHTTHPPQTPHPPEPHPVLPTTPWQHTQHWITATSAAYHRPDTHPLLGVGVTDPTNGTRVWESELDPDLLWLADHVIDDLVVLPGAAYAEIALAAATDTFAVEQDQPWMISELDLRQMLHVTPGTVLVTTLTGDEQRCQVEIRTRSGSSGWTTHATATVARAEPLAPLDHEGQRREVTTADLEDQLDPDDLYQRLRGAGQQHGPAFQGIVGLAVTQAGVARAQVRLPASARTGSREFMLHPVMMDIALQTLGATRTATDLAGGQDARQGPSSNSALVVPVRFAGVHVYGDITRGVRAVGSLAAAGDRLVGEVVLTDANGQPLLVVDEVEMAVLGSGSGATELTNRLFMLEWEPAPLEKTAEATGALLLIGDPAAGDPLLPALQSSLRDRITDLELASAADEATLRAAISRTSWDGIVVVCPPRANDESMPDEAQLELARTRTLLVASVVETVTRMGARKSPRLWIVTRGAAQFDAGESVTLAQTGLRGIARVLTFEHSELNTTLVDIEPDGTGSLAALAEELLAGSEADEVALRDGQRYVNRLVPAPTTTSGDLAAEARHQVVNLDSSGASRAAVRLQIDQPGRLDALNVHEVKRGRPQGDQVEVRVVAAGLNFSDVLKAMGVYPGLDGAAPVIGGECVGYVTAIGDEVDGVEVGQRVIAFGPGTFGTHLGTIADLVVPIPDTLADNEAATFGVAYLTAWHSLCEVGRLSPGERVLIHSATGGVGMAAVSIAKMIGARIYTTAGSDAKREMLSRLGVEYVGDSRSVDFADEILELTDGYGVDVVLNSLAGEAIQRGVQILAPGGRFIELGKKDVYADASLGLAALAKSASFSVVDLDLNLKLQPARYRQLLQHILQHVADGKLEVLPVTAFSLHDAADAFRLMASGKHTGKIVISIPQHGSIEAIAAPPPLPLVSRDGGYLIVGGMGGLGFVVARWLAEQGAGLIVLNGRSAPSDEVAAAIAELNASGSRIEVITGDITEPDTAERLVRAVEDAGFRLAGVVHSAMVLADEIVLNMTDSAARRVFAPKVTGSWRLHVATAARDVDWWLTFSSAAALLGTPGQGAYAAANSWVDGLVAHRRSAGLPAVGINWGPWADVGRAQFFKDLGVEMINAEQGLAAMQAVLTADRGRTGVFSLDARQWFQSFPAVAGSSLFAKLHDSAARKSGQRRGGGAIRAQLDALDAAERPGHLASAIADEIRAVLRSGDPIDHHRPLETLGLDSLMGLELRNRLEASLGITLPVALVWAYPTISDLATALCERMDYATPAAAQEISDTEPELSDEEMDLLADLVDASELEAATRGES