pks13 Resolved · high auto-curated
H37Rv Rv3800c · MTBC0 mtbc0_004028 ·
1733 aa · 4280055–4285256 (-) ·
RefSeq NP_218317.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | polyketide synthase |
|---|---|
| MTBC0 PGAP re-annotation | polyketide synthase Pks13 |
| Revised (this work) | Polyketide synthase Pks13. Pfam: PP-binding (PF00550.32), ketoacyl-synt (PF00109.33), Thiolase_N (PF00108.30), Ketoacyl-synt_C (PF02801.29), KAsynt_C_assoc (PF16197.12), Acyl_transf_1 (PF00698.27), Thioesterase (PF00975.27). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6X8D2
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Polyketide synthase Pks13 |
| EC (curated) |
EC 2.3.1.-
|
| Curated function | Involved in the biosynthesis of mycolic acids. Forms, with FadD32, the initiation module of the mycolic condensation system. Synthesizes, in coupled reaction with FadD32, the biosynthetic precursors of mycolic acids, alpha-alkyl beta-ketoacids, via the condensation of two long chain fatty acid derivatives, a very long meromycoloyl-AMP and a shorter 2-carboxyacyl-CoA. The acyl chain of the acyl-AMP produced by FadD32 is specifically transferred onto the N-terminal ACP domain of Pks13, and then transferred onto the KS domain. The extender unit carboxyacyl-CoA is specifically loaded onto the AT d. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | pks13 |
| eggNOG description | synthase |
| Orthologous group | COG0236 |
| KEGG orthology |
K12437
|
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 | 0.264 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 22 synonymous, 17 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 |
|---|---|---|---|---|
PP-binding | PF00550.32 | 1.8e-10 | 25–91 | Phosphopantetheine attachment site |
ketoacyl-synt | PF00109.33 | 1.4e-86 | 118–366 | Beta-ketoacyl synthase, N-terminal domain |
Thiolase_N | PF00108.30 | 5.0e-07 | 277–316 | Thiolase, N-terminal domain |
Ketoacyl-synt_C | PF02801.29 | 7.3e-44 | 374–491 | Beta-ketoacyl synthase, C-terminal domain |
KAsynt_C_assoc | PF16197.12 | 1.4e-11 | 494–553 | Ketoacyl-synthetase C-terminal extension |
Acyl_transf_1 | PF00698.27 | 5.5e-56 | 713–1036 | Acyl transferase domain |
Thioesterase | PF00975.27 | 7.6e-18 | 1470–1565 | Thioesterase domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mbtB (phenyloxazoline synthase), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2377c mbtH hyp |
hypothetical protein | 999 | 1000 ctx | neighborhood:400 coexpression:915 experimental:999 textmining:496 |
Rv2383c mbtB |
phenyloxazoline synthase | 999 | 1000 ctx | neighborhood:544 coexpression:999 experimental:473 textmining:745 |
Rv2524c fas |
fatty acid synthase | 999 | 1000 ctx | neighborhood:544 coexpression:840 experimental:994 database:549 textmining:767 |
Rv0101 nrp |
peptide synthetase Nrp | 998 | 997 ctx | neighborhood:544 coexpression:983 experimental:473 textmining:586 |
Rv3801c fadD32 |
long-chain-fatty-acid--AMP ligase FadD32 | 999 | 994 ctx | neighborhood:881 cooccurence:413 coexpression:838 textmining:977 |
Rv3799c accD4 |
propionyl-CoA carboxylase subunit beta AccD | 996 | 976 ctx | neighborhood:881 coexpression:810 textmining:864 |
Rv2243 fabD |
malonyl CoA-acyl carrier protein transacylase | 987 | 976 | coexpression:677 experimental:787 database:549 textmining:524 |
Rv1663 pks17 |
polyketide synthase | 977 | 968 ctx | fusion:688 cooccurence:758 coexpression:470 |
Rv2380c mbtE |
peptide synthetase | 979 | 965 ctx | neighborhood:508 coexpression:805 experimental:473 textmining:435 |
Rv1527c pks5 |
polyketide synthase | 987 | 959 ctx | neighborhood:544 coexpression:803 experimental:414 textmining:720 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 987 | 959 ctx | neighborhood:544 coexpression:807 experimental:414 textmining:703 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 986 | 959 ctx | neighborhood:544 coexpression:804 experimental:414 textmining:691 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 986 | 958 ctx | neighborhood:544 coexpression:803 experimental:414 textmining:694 |
Rv2048c pks12 |
polyketide synthase | 991 | 957 ctx | neighborhood:544 coexpression:803 experimental:414 textmining:812 |
Rv2384 mbtA |
2,3-dihydroxybenzoate-AMP ligase | 969 | 940 | coexpression:917 textmining:512 |
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: polyketide synthase
- MTBC0 PGAP product: polyketide synthase Pks13
- Pfam (hmmscan --cut_ga): PP-binding PF00550.32 (E=2e-10), ketoacyl-synt PF00109.33 (E=1e-86), Thiolase_N PF00108.30 (E=5e-07), Ketoacyl-synt_C PF02801.29 (E=7e-44), KAsynt_C_assoc PF16197.12 (E=1e-11), Acyl_transf_1 PF00698.27 (E=5e-56), Thioesterase PF00975.27 (E=8e-18)
- (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_218317.1)
- Domains: Pfam-A via hmmscan --cut_ga — PP-binding (PF00550.32), ketoacyl-synt (PF00109.33), Thiolase_N (PF00108.30), Ketoacyl-synt_C (PF02801.29), KAsynt_C_assoc (PF16197.12), Acyl_transf_1 (PF00698.27), Thioesterase (PF00975.27)
- 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
COG0236 - Curated reference: UniProt I6X8D2 (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 —
378 functional partner(s); context anchor
mbtB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_004028|Rv3800c|pks13 MADVAESQENAPAERAELTVPEMRQWLRNWVGKAVGKAPDSIDESVPMVELGLSSRDAVAMAADIEDLTGVTLSVAVAFAHPTIESLATRIIEGEPETDLAGDDAEDWSRTGPAERVDIAIVGLSTRFPGEMNTPEQTWQALLEGRDGITDLPDGRWSEFLEEPRLAARVAGARTRGGYLKDIKGFDSEFFAVAKTEADNIDPQQRMALELTWEALEHARIPASSLRGQAVGVYIGSSTNDYSFLAVSDPTVAHPYAITGTSSSIIANRVSYFYDFHGPSVTIDTACSSSLVAIHQGVQALRNGEADVVVAGGVNALITPMVTLGFDEIGAVLAPDGRIKSFSADADGYTRSEGGGMLVLKRVDDARRDGDAILAVIAGSAVNHDGRSNGLIAPNQDAQADVLRRAYKDAGIDPRTVDYIEAHGTGTILGDPIEAEALGRVVGRGRPADRPALLGAVKTNVGHLESAAGAASMAKVVLALQHDKLPPSINFAGPSPYIDFDAMRLKMITTPTDWPRYGGYALAGVSSFGFGGANAHVVVREVLPRDVVEKEPEPEPEPKAAAEPAEAPTLAGHALRFDEFGNIITDSAVAEEPEPELPGVTEEALRLKEAALEELAAQEVTAPLVPLAVSAFLTSRKKAAAAELADWMQSPEGQASSLESIGRSLSRRNHGRSRAVVLAHDHDEAIKGLRAVAAGKQAPNVFSVDGPVTTGPVWVLAGFGAQHRKMGKSLYLRNEVFAAWIEKVDALVQDELGYSVLELILDDAQDYGIETTQVTIFAIQIALGELLRHHGAKPAAVIGQSLGEAASAYFAGGLSLRDATRAICSRSHLMGEGEAMLFGEYIRLMALVEYSADEIREVFSDFPDLEVCVYAAPTQTVIGGPPEQVDAILARAEAEGKFARKFATKGASHTSQMDPLLGELTAELQGIKPTSPTCGIFSTVHEGRYIKPGGEPIHDVEYWKKGLRHSVYFTHGIRNAVDSGHTTFLELAPNPVALMQVALTTADAGLHDAQLIPTLARKQDEVSSMVSTMAQLYVYGHDLDIRTLFSRASGPQDYANIPPTRFKRKEHWLPAHFSGDGSTYMPGTHVALPDGRHVWEYAPRDGNVDLAALVRAAAAHVLPDAQLTAAEQRAVPGDGARLVTTMTRHPGGASVQVHARIDESFTLVYDALVSRAGSESVLPTAVGAATAIAVADGAPVAPETPAEDADAETLSDSLTTRYMPSGMTRWSPDSGETIAERLGLIVGSAMGYEPEDLPWEVPLIELGLDSLMAVRIKNRVEYDFDLPPIQLTAVRDANLYNVEKLIEYAVEHRDEVQQLHEHQKTQTAEEIARAQAELLHGKVGKTEPVDSEAGVALPSPQNGEQPNPTGPALNVDVPPRDAAERVTFATWAIVTGKSPGGIFNELPRLDDEAAAKIAQRLSERAEGPITAEDVLTSSNIEALADKVRTYLEAGQIDGFVRTLRARPEAGGKVPVFVFHPAGGSTVVYEPLLGRLPADTPMYGFERVEGSIEERAQQYVPKLIEMQGDGPYVLVGWSLGGVLAYACAIGLRRLGKDVRFVGLIDAVRAGEEIPQTKEEIRKRWDRYAAFAEKTFNVTIPAIPYEQLEELDDEGQVRFVLDAVSQSGVQIPAGIIEHQRTSYLDNRAIDTAQIQPYDGHVTLYMADRYHDDAIMFEPRYAVRQPDGGWGEYVSDLEVVPIGGEHIQAIDEPIIAKVGEHMSRALGQIEADRTSEVGKQ