pks1 Resolved · high auto-curated
H37Rv Rv2946c · MTBC0 - ·
1616 aa · 3291503–3296353 (-) ·
RefSeq NP_217462.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | polyketide synthase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Polyketide synthase. Pfam: CurL-like_PKS_C (PF22621.3), Acyl_transf_1 (PF00698.27), PKS_DH_N (PF21089.4), PS-DH (PF14765.13), SpnB_Rossmann (PF22953.4), ADH_N (PF08240.18), ADH_zinc_N (PF00107.33), ADH_zinc_N_2 (PF13602.13), KR (PF08659.17), adh_short (PF00106.32), Epimerase (PF01370.28), 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.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
P96285
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Putative inactive phenolphthiocerol synthesis polyketide synthase type I Pks1 |
| Curated function | May play a role in phthiocerol biosynthesis. |
UniProt still lists this protein as Putative inactive phenolphthiocerol synthesis polyketide synthase type I Pks1; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | pks1 |
| eggNOG description | synthase |
| Orthologous group | COG0604 |
| EC number |
EC 2.3.1.261
|
| KEGG orthology |
K12430, K12440, K12441
|
| Gene Ontology (24) |
GO:0005575, GO:0005623, GO:0005886, GO:0006629, GO:0008150, GO:0008152, GO:0008610, GO:0009058, GO:0009273, GO:0009987, GO:0016020, GO:0016043 +12 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 | 0.794 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 12 synonymous, 26 missense, 0 nonsense, 8 frameshift |
| Disruption | 8 distinct premature-stop/frameshift site(s); most common in 6.12% of strains (8880) · convergent |
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 |
|---|---|---|---|---|
CurL-like_PKS_C | PF22621.3 | 4.5e-08 | 2–60 | CurL-like, PKS C-terminal |
Acyl_transf_1 | PF00698.27 | 2.0e-61 | 86–395 | Acyl transferase domain |
PKS_DH_N | PF21089.4 | 4.9e-29 | 445–545 | Polyketide synthase dehydratase domain |
PS-DH | PF14765.13 | 1.3e-30 | 567–718 | Polyketide synthase dehydratase N-terminal domain |
SpnB_Rossmann | PF22953.4 | 1.0e-33 | 767–886 | Polyketide synthase extender module SpnB, Rossmann fold domain |
ADH_N | PF08240.18 | 1.1e-09 | 929–986 | Alcohol dehydrogenase GroES-like domain |
ADH_zinc_N | PF00107.33 | 4.0e-13 | 1048–1140 | Zinc-binding dehydrogenase |
ADH_zinc_N_2 | PF13602.13 | 3.1e-18 | 1084–1215 | Zinc-binding dehydrogenase |
KR | PF08659.17 | 2.0e-60 | 1228–1407 | KR domain |
adh_short | PF00106.32 | 1.2e-14 | 1229–1389 | short chain dehydrogenase |
Epimerase | PF01370.28 | 4.2e-05 | 1230–1374 | NAD dependent epimerase/dehydratase family |
adh_short_C2 | PF13561.13 | 1.3e-09 | 1256–1388 | Enoyl-(Acyl carrier protein) reductase |
PP-binding | PF00550.32 | 6.0e-15 | 1524–1585 | 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:906 experimental:999 database:549 textmining:745 |
Rv2947c pks15 |
polyketide synthase | 999 | 999 ctx | neighborhood:787 fusion:865 cooccurence:771 coexpression:754 textmining:819 |
Rv2382c mbtC |
polyketide synthetase | 979 | 979 ctx | fusion:881 cooccurence:766 |
Rv2383c mbtB |
phenyloxazoline synthase | 994 | 978 ctx | neighborhood:544 coexpression:881 experimental:473 textmining:745 |
Rv2048c pks12 |
polyketide synthase | 989 | 971 ctx | neighborhood:544 coexpression:554 experimental:864 textmining:657 |
Rv2243 fabD |
malonyl CoA-acyl carrier protein transacylase | 978 | 970 | coexpression:671 experimental:787 database:549 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 989 | 968 ctx | neighborhood:544 experimental:864 textmining:680 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 988 | 968 ctx | neighborhood:544 experimental:864 textmining:654 |
Rv1180 pks3 |
polyketide beta-ketoacyl synthase | 971 | 968 ctx | fusion:828 cooccurence:760 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 988 | 966 ctx | neighborhood:544 experimental:864 textmining:673 |
Rv1527c pks5 |
polyketide synthase | 987 | 966 ctx | neighborhood:544 experimental:864 textmining:652 |
Rv0101 nrp |
peptide synthetase Nrp | 984 | 960 ctx | neighborhood:544 coexpression:768 experimental:473 textmining:616 |
Rv2948c fadD22 |
p-hydroxybenzoyl--AMP ligase | 951 | 934 ctx | neighborhood:799 |
Rv3800c pks13 |
polyketide synthase | 970 | 915 ctx | neighborhood:544 coexpression:693 textmining:666 |
Rv0310c hyp |
hypothetical protein | 931 | 903 | coexpression:450 experimental:594 database:561 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): polyketide synthase
- Pfam (hmmscan --cut_ga): CurL-like_PKS_C PF22621.3 (E=4e-08), Acyl_transf_1 PF00698.27 (E=2e-61), PKS_DH_N PF21089.4 (E=5e-29), PS-DH PF14765.13 (E=1e-30), SpnB_Rossmann PF22953.4 (E=1e-33), ADH_N PF08240.18 (E=1e-09), ADH_zinc_N PF00107.33 (E=4e-13), ADH_zinc_N_2 PF13602.13 (E=3e-18), KR PF08659.17 (E=2e-60), adh_short PF00106.32 (E=1e-14), Epimerase PF01370.28 (E=4e-05), adh_short_C2 PF13561.13 (E=1e-09), PP-binding PF00550.32 (E=6e-15)
- (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_217462.1)
- Domains: Pfam-A via hmmscan --cut_ga — CurL-like_PKS_C (PF22621.3), Acyl_transf_1 (PF00698.27), PKS_DH_N (PF21089.4), PS-DH (PF14765.13), SpnB_Rossmann (PF22953.4), ADH_N (PF08240.18), ADH_zinc_N (PF00107.33), ADH_zinc_N_2 (PF13602.13), KR (PF08659.17), adh_short (PF00106.32), Epimerase (PF01370.28), 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 P96285 (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 —
512 functional partner(s); context anchor
fas - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2946c|pks1 MISARSAEALTAQAGRLMAHVQANPGLDPIDVGCSLASRSVFEHRAVVVGASREQLIAGLAGLAAGEPGAGVAVGQPGSVGKTVVVFPGQGAQRIGMGRELYGELPVFAQAFDAVADELDRHLRLPLRDVIWGADADLLDSTEFAQPALFAVEVASFAVLRDWGVLPDFVMGHSVGELAAAHAAGVLTLADAAMLVVARGRLMQALPAGGAMVAVAASEDEVEPLLGEGVGIAAINAPESVVISGAQAAANAIADRFAAQGRRVHQLAVSHAFHSPLMEPMLEEFARVAARVQAREPQLGLVSNVTGELAGPDFGSAQYWVDHVRRPVRFADSARHLQTLGATHFIEAGPGSGLTGSIEQSLAPAEAMVVSMLGKDRPELASALGAAGQVFTTGVPVQWSAVFAGSGGRRVQLPTYAFQRRRFWETPGADGPADAAGLGLGATEHALLGAVVERPDSDEVVLTGRLSLADQPWLADHVVNGVVLFPGAGFVELVIRAGDEVGCALIEELVLAAPLVMHPGVGVQVQVVVGAADESGHRAVSVYSRGDQSQGWLLNAEGMLGVAAAETPMDLSVWPPEGAESVDISDGYAQLAERGYAYGPAFQGLVAIWRRGSELFAEVVAPGEAGVAVDRMGMHPAVLDAVLHALGLAVEKTQASTETRLPFCWRGVSLHAGGAGRVRARFASAGADAISVDVCDATGLPVLTVRSLVTRPITAEQLRAAVTAAGGASDQGPLEVVWSPISVVSGGANGSAPPAPVSWADFCAGSDGDASVVVWELESAGGQASSVVGSVYAATHTALEVLQSWLGADRAATLVVLTHGGVGLAGEDISDLAAAAVWGMARSAQAENPGRIVLIDTDAAVDASVLAGVGEPQLLVRGGTVHAPRLSPAPALLALPAAESAWRLAAGGGGTLEDLVIQPCPEVQAPLQAGQVRVAVAAVGVNFRDVVAALGMYPGQAPPLGAEGAGVVLETGPEVTDLAVGDAVMGFLGGAGPLAVVDQQLVTRVPQGWSFAQAAAVPVVFLTAWYGLADLAEIKAGESVLIHAGTGGVGMAAVQLARQWGVEVFVTASRGKWDTLRAMGFDDDHIGDSRTCEFEEKFLAVTEGRGVDVVLDSLAGEFVDASLRLLVRGGRFLEMGKTDIRDAQEIAANYPGVQYRAFDLSEAGPARMQEMLAEVRELFDTRELHRLPVTTWDVRCAPAAFRFMSQARHIGKVVLTMPSALADRLADGTVVITGATGAVGGVLARHLVGAYGVRHLVLASRRGDRAEGAAELAADLTEAGAKVQVVACDVADRAAVAGLFAQLSREYPPVRGVIHAAGVLDDAVITSLTPDRIDTVLRAKVDAAWNLHQATSDLDLSMFALCSSIAATVGSPGQGNYSAANAFLDGLAAHRQAAGLAGISLAWGLWEQPGGMTAHLSSRDLARMSRSGLAPMSPAEAVELFDAALAIDHPLAVATLLDRAALDARAQAGALPALFSGLARRPRRRQIDDTGDATSSKSALAQRLHGLAADEQLELLVGLVCLQAAAVLGRPSAEDVDPDTEFGDLGFDSLTAVELRNRLKTATGLTLPPTVIFDHPTPTAVAEYVAQQMSGSRPTESGDPTSQVVEPAAAEVSVHA