pks12 Resolved · high auto-curated
H37Rv Rv2048c · MTBC0 mtbc0_002181 ·
4151 aa · 2323144–2335599 (-) ·
RefSeq NP_216564.2
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | polyketide synthase |
|---|---|
| MTBC0 PGAP re-annotation | type I polyketide synthase |
| Revised (this work) | Type I polyketide synthase. Pfam: Ketoacyl-synt_C (PF02801.29), KAsynt_C_assoc (PF16197.12), CurL-like_PKS_C (PF22621.3), RhiE-like_linker (PF22336.3), Acyl_transf_1 (PF00698.27), PKS_DH_N (PF21089.4), ADH_N (PF08240.18), ADH_zinc_N (PF00107.33), KR (PF08659.17), Epimerase (PF01370.28), PP-binding (PF00550.32), ketoacyl-synt (PF00109.33), PS-DH (PF14765.13), SpnB_Rossmann (PF22953.4), ADH_zinc_N_2 (PF13602.13), adh_short (PF00106.32). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6XD69
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Mycoketide-CoA synthase |
| EC (curated) |
EC 2.3.1.295
|
| Curated function | Involved in the synthesis of beta-D-mannosyl phosphomycoketide (MPM), an antigenic mycobacterial polyketide. Binds a fatty acyl-CoA as a starter unit, and extends it by five rounds of alternative additions of malonyl-CoA and methylmalonyl-CoA extender units. Depending on the starter unit, the enzyme forms mycoketide-CoAs of different lengths. Shows preference for small-/medium-chain starter fatty acyl substrates. Uses a hybrid modularly iterative mechanism, by forming a supramolecular assembly to perform repetitive cycles of iterations. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | pks12 |
| eggNOG description | polyketide synthase |
| Orthologous group | COG0604 |
| KEGG orthology |
K12436
|
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 | 0.336 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 51 synonymous, 47 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_C | PF02801.29 | 1.2e-42 | 289–407 | Beta-ketoacyl synthase, C-terminal domain |
KAsynt_C_assoc | PF16197.12 | 7.9e-12 | 410–524 | Ketoacyl-synthetase C-terminal extension |
CurL-like_PKS_C | PF22621.3 | 7.3e-09 | 476–533 | CurL-like, PKS C-terminal |
RhiE-like_linker | PF22336.3 | 5.6e-07 | 476–539 | RhiE-like, KS-MAT linker domain |
Acyl_transf_1 | PF00698.27 | 1.1e-94 | 559–880 | Acyl transferase domain |
PKS_DH_N | PF21089.4 | 1.1e-27 | 926–1026 | Polyketide synthase dehydratase domain |
ADH_N | PF08240.18 | 2.9e-09 | 1384–1440 | Alcohol dehydrogenase GroES-like domain |
ADH_zinc_N | PF00107.33 | 7.0e-14 | 1504–1593 | Zinc-binding dehydrogenase |
KR | PF08659.17 | 8.7e-60 | 1680–1858 | KR domain |
Epimerase | PF01370.28 | 3.7e-07 | 1682–1822 | NAD dependent epimerase/dehydratase family |
PP-binding | PF00550.32 | 4.4e-14 | 1971–2034 | Phosphopantetheine attachment site |
ketoacyl-synt | PF00109.33 | 6.2e-96 | 2057–2304 | Beta-ketoacyl synthase, N-terminal domain |
PS-DH | PF14765.13 | 1.0e-24 | 3063–3214 | Polyketide synthase dehydratase N-terminal domain |
SpnB_Rossmann | PF22953.4 | 2.9e-36 | 3250–3368 | Polyketide synthase extender module SpnB, Rossmann fold domain |
ADH_zinc_N_2 | PF13602.13 | 3.1e-22 | 3570–3700 | Zinc-binding dehydrogenase |
adh_short | PF00106.32 | 3.4e-09 | 3711–3869 | short chain dehydrogenase |
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 |
Rv2243 fabD |
malonyl CoA-acyl carrier protein transacylase | 996 | 996 | coexpression:752 experimental:960 database:549 |
Rv2383c mbtB |
phenyloxazoline synthase | 998 | 994 ctx | neighborhood:544 coexpression:937 experimental:721 textmining:745 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 997 | 993 ctx | neighborhood:544 coexpression:437 experimental:965 textmining:631 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 997 | 993 ctx | neighborhood:544 coexpression:446 experimental:965 textmining:630 |
Rv1527c pks5 |
polyketide synthase | 997 | 992 ctx | neighborhood:544 coexpression:429 experimental:965 textmining:662 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 996 | 992 ctx | neighborhood:544 coexpression:423 experimental:965 textmining:630 |
Rv3147 nuoC |
NADH-quinone oxidoreductase subunit C | 990 | 988 | coexpression:460 experimental:951 database:564 |
Rv3153 nuoI |
NADH-quinone oxidoreductase subunit I | 990 | 988 | coexpression:427 experimental:953 database:564 |
Rv0101 nrp |
peptide synthetase Nrp | 994 | 983 ctx | neighborhood:544 cooccurence:444 coexpression:794 experimental:721 textmining:661 |
Rv3146 nuoB |
NADH-quinone oxidoreductase subunit B | 979 | 972 | coexpression:413 experimental:899 database:564 |
Rv2946c pks1 |
polyketide synthase | 989 | 971 ctx | neighborhood:544 coexpression:554 experimental:864 textmining:657 |
Rv2047c hyp |
hypothetical protein | 990 | 968 ctx | neighborhood:811 coexpression:763 textmining:711 |
Rv2380c mbtE |
peptide synthetase | 980 | 966 ctx | neighborhood:526 coexpression:649 experimental:721 textmining:447 |
Rv3148 nuoD |
NADH-quinone oxidoreductase subunit D | 972 | 964 | experimental:905 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: polyketide synthase
- MTBC0 PGAP product: type I polyketide synthase
- Pfam (hmmscan --cut_ga): Ketoacyl-synt_C PF02801.29 (E=1e-42), KAsynt_C_assoc PF16197.12 (E=8e-12), CurL-like_PKS_C PF22621.3 (E=7e-09), RhiE-like_linker PF22336.3 (E=6e-07), Acyl_transf_1 PF00698.27 (E=1e-94), PKS_DH_N PF21089.4 (E=1e-27), ADH_N PF08240.18 (E=3e-09), ADH_zinc_N PF00107.33 (E=7e-14), KR PF08659.17 (E=9e-60), Epimerase PF01370.28 (E=4e-07), PP-binding PF00550.32 (E=4e-14), ketoacyl-synt PF00109.33 (E=6e-96), PS-DH PF14765.13 (E=1e-24), SpnB_Rossmann PF22953.4 (E=3e-36), ADH_zinc_N_2 PF13602.13 (E=3e-22), adh_short PF00106.32 (E=3e-09)
- (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_216564.2)
- Domains: Pfam-A via hmmscan --cut_ga — Ketoacyl-synt_C (PF02801.29), KAsynt_C_assoc (PF16197.12), CurL-like_PKS_C (PF22621.3), RhiE-like_linker (PF22336.3), Acyl_transf_1 (PF00698.27), PKS_DH_N (PF21089.4), ADH_N (PF08240.18), ADH_zinc_N (PF00107.33), KR (PF08659.17), Epimerase (PF01370.28), PP-binding (PF00550.32), ketoacyl-synt (PF00109.33), PS-DH (PF14765.13), SpnB_Rossmann (PF22953.4), ADH_zinc_N_2 (PF13602.13), adh_short (PF00106.32)
- 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 I6XD69 (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 —
652 functional partner(s); context anchor
fas - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002181|Rv2048c|pks12 MVDQLQHATEALRKALVQVERLKRTNRALLERSSEPIAIVGMSCRFPGGVDSPEGLWQMVADARDVMSEFPTDRGWDLAGLFDPDPDVRHKSYARTGGFVDGVADFDPAFFGISPSEALAMDPQHRMLLELSWEALERAGIDPTGLRGSATGVFAGLIVGGYGMLAEEIEGYRLTGMTSSVASGRVAYVLGLEGPAVSVDTACSSSLVALHMAVGSLRSGECDLALAGGVTVNATPTVFVEFSRHRGLAPDGRCKPYAGRADGVGWSEGGGMLVLQRLSDARRLGHPVLAVVVGSAVNQDGASNGLTAPNGPSQQRVVRAALANAGLSAAEVDVVEGHGTGTTLGDPIEAQALLATYGQDRGEPGEPLWLGSVKSNMGHTQAAAGVAGVIKMVLAMRHELLPATLHVDVPSPHVDWSAGAVELLTAPRVWPAGARTRRAGVSSFGISGTNAHVIIEAVPVVPRREAGWAGPVVPWVVSAKSESALRGQAARLAAYVRGDDGLDVADVGWSLAGRSVFEHRAVVVGGDRDRLLAGLDELAGDQLGGSVVRGTATAAGKTVFVFPGQGSQWLGMGIELLDTAPAFAQQIDACAEAFAEFVDWSLVDVLRGAPGAPGLDRVDVVQPVLFAVMVSLAELWKSVAVHPDAVIGHSQGEIAAAYVAGALSLRDAARVVTLRSKLLAGLAGPGGMVSIACGADQARDLLAPFGDRVSIAVVNGPSAVVVSGEVGALEELIAVCSTKELRTRRIEVDYASHSVEVEAIRGPLAEALSGIEPRSTRTVFFSTVTGNRLDTAGLDADYWYRNVRQTVLFDQAVRNACEQGYRTFIESSPHPALITGVEETFAACTDGDSEAIVVPTLGRGDGGLHRFLLSAASAFVAGVAVNWRGTLDGAGYVELPTYAFDKRRFWLSAEGSGADVSGLGLGASEHPLLGAVVDLPASGGVVLTGRLSPNVQPWLADHAVSDVVLFPGTGFVELAIRAGDEVGCSVLDELTLAAPLLLPATGSVAVQVVVDAGRDSNSRGVSIFSRADAQAGWLLHAEGILRPGSVEPGADLSVWPPAGAVTVDVADGYERLATRGYRYGPAFRGLTAMWARGEEIFAEVRLPEAAGGVGGFGVHPALLDAVLHAVVIAGDPDELALPFAWQGVSLHATGASAVRARIAPAGPSAVSVELADGLGLPVLSVASMVARPVTERQLLAAVSGSGPDRLFEVIWSPASAATSPGPTPAYQIFESVAADQDPVAGSYVRSHQALAAVQSWLTDHESGVLVVATRGAMALPREDVADLAGAAVWGLVRSAQTEHPGRIVLVDSDAATDDAAIAMALATGEPQVVLRGGQVYTARVRGSRAADAILVPPGDGPWRLGLGSAGTFENLRLEPVPNADAPLGPGQVRVAMRAIAANFRDIMITLGMFTHDALLGGEGAGVVVEVGPGVTEFSVGDSVFGFFPDGSGTLVAGDVRLLLPMPADWSYAEAAAISAVFTTAYYAFIHLADVQPGQRVLIHAGTGGVGMAAVQLARHLGLEVFATASKGKWDTLRAMGFDDDHISDSRSLEFEDKFRAATGGRGFDVVLDSLAGEFVDASLRLVAPGGVFLEMGKTDIRDPGVIAQQYPGVRYRAFDLFEPGRPRMHQYMLELATLFGDGVLRPLPVTTFDVRRAPAALRYLSQARHTGKVVMLMPGSWAAGTVLITGGTGMAGSAVARHVVARHGVRNLVLVSRRGPDAPGAAELVAELAAAGAQVQVVACDAADRAALAKVIADIPVQHPLSGVIHTAGALDDAVVMSLTPDRVDVVLRSKVDAAWHLHELTRDLDVSAFVMFSSMAGLVGSSGQANYAAANSFLDALAAHRRAHGLPAISLGWGLWDQASAMTGGLDAADLARLGREGVLALSTAEALELFDTAMIVDEPFLAPARIDLTALRAHAVAVPPMFSDLASAPTRRQVDDSVAAAKSKSALAHRLHGLPEAEQHAVLLGLVRLHIATVLGNITPEAIDPDKAFQDLGFDSLTAVEMRNRLKSATGLSLSPTLIFDYPTPNRLASYIRTELAGLPQEIKHTPAVRTTSEDPIAIVGMACRYPGGVNSPDDMWDMLIQGRDVLSEFPADRGWDLAGLYNPDPDAAGACYTRTGGFVDGVGDFDPAFFGVGPSEALAMDPQQRMLLELSWEALERAGIDPTGLRGSATGVFAGVMTQGYGMFAAEPVEGFRLTGQLSSVASGRVAYVLGLEGPAVSVDTACSSSLVALHMAVGSLRSGECDLALAGGVTVNATPDIFVEFSRWRGLSPDGRCKAFAAAADGTGFSEGGGMLVLQRLSDARRLGHPVLAVVVGSAVNQDGASNGLTAPNGPSQQRVVRAALANAGLSAAEVDVVEGHGTGTTLGDPIEAQALLATYGQDRGEPGEPLWLGSVKSNMGHTQAAAGVAGVIKMVLAMRHELLPATLHVDVPSPHVDWSAGAVELLTAPRVWPAGARTRRAGVSSFGISGTNAHVIIEAVPVVPRREAGWAGPVVPWVVSAKSESALRGQAARLAAYVRGDDGLDVADVGWSLAGRSVFEHRAVVVGGDRDRLLAGLDELAGDQLGGSVVRGTATAAGKTVFVFPGQGSQWLGMGMGLHAGYPVFAEAFNTVVGELDRHLLRPLREVMWGHDENLLNSTEFAQPALFAVEVALFRLLGSWGVRPDFVMGHSIGELSAAHVAGVLSLENAAVLVAARGRLMQALPAGGAMVAVQAAEEEVRPLLSAEVDIAAVNGPASLVISGAQNAVAAVADQLRADGRRVHQLAVSHAFHSPLMDPMIDEFAAVAAGIAIGRPTIGVISNVTGQLAGDDFGSAAYWRRHIRQAVRFADSVRFAQAAGGSRFLEVGPSGGLVASIEESLPDVAVTTMSALRKDRPEPATLTNAVAQGFVTGMDLDWRAVVGEAQFVELPTYAFQRRRFWLSGDGVAADAAGLGLAASEHALLGAVIDLPASGGVVLTGRLSPSVQGWLADHSVAGVTIFPGAGFVELAIRAGDEVGCGVVDELTLAAPLVLPASGSVAVQVVVNGPDESGVRGVSVYSRGDVGTGWVLHAEGALRAGSAEPTADLAMWPPAGAVPVEVADGYQQLAERGYGYGPAFRGLTAMWRRGDEVFAEVALPADAGVSVTGFGVHPVLLDAALHAVVLSAESAERGQGSVLVPFSWQGVSLHAAGASAVRARIAPVGPSAVSIELADGLGLPVLSVASMLARPVTDQQLRAAVSSSGPDRLFEVTWSPQPSAAVEPLPVCAWGTTEDSAAVVFESVPLAGDVVAGVYAATSSVLDVLQSWLTRDGAGVLVVMTRGAVALPGEDVTDLAGAAVWGLVRSAQTEHPGRIVLVDSDAPLDDSALAAVVTTGEPQVLWRRGEVYTARVHGSRAVGGLLVPPSDRPWRLAMSTAGTFENLRLELIPDADAPLGPGQVRVAVSAIAANFRDVMIALGLYPDPDAVMGVEACGVVIETSLNKGSFAVGDRVMGLFPEGTGTVASTDQRLLVKVPAGWSHTAAATTSVVFATAHYALVDLAAARSGQRVLIHAGTGGVGMAAVQLARHLGLEVFATASKGKWDTLRAMGFDDDHISDSRSLEFEDKFRAATGGRGFDVVLDSLAGEFVDASLRLVAPGGVFLEMGKTDIRDPGVIAQQYPGVRYRAFDLFEAGPDRIAQILAELATLFGDGVLRPLPVTTFDVRCAPAALRYLSQARHTGKVVMLMPGSWAAGTVLITGGTGMAGSAVARHVVARHGVRNLVLVSRRGPDAPGAAELVAELAAAGAQVQVVACDAADRAALAKVIADIPVQHPLSGVIHTAGALDDAVVMSLTPDRVDVVLRSKVDAAWHLHELTRDLDVSAFVMFSSMAGLVGSSGQANYAAANSFLDALAAHRRAHGLPAISLGWGLWDQASAMTGGLATVDFKRFARDGIVAMSSADALQLFDTAMIVDEPFMLPAHIDFAALKVKFDGGTLPPMFVDLINAPTRRQVDDSLAAAKSKSALLQRLEGLPEDEQHAVLLDLVRSHIATVLGSASPEAIDPDRAFQELGFDSLTAVEMRNRLKSATGLALSPTLIFDYPNSAALAGYMRRELLGSSPQDTSAVAAGEAELQRIVASIPVKRLRQAGVLDLLLALANETETSGQDPALAPTAEQEIADMDLDDLVNAAFRNDDE