pks2 Resolved · high auto-curated
H37Rv Rv3825c · MTBC0 mtbc0_004054 ·
2126 aa · 4317335–4323715 (-) ·
RefSeq NP_218342.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | phthioceranic/hydroxyphthioceranic acid synthase |
|---|---|
| MTBC0 PGAP re-annotation | phthioceranic/hydroxyphthioceranic acid synthase |
| Revised (this work) | Phthioceranic/hydroxyphthioceranic acid synthase. Pfam: ketoacyl-synt (PF00109.33), Thiolase_N (PF00108.30), 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), 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), 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 |
P9WQE9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Phthioceranic/hydroxyphthioceranic acid synthase |
| EC (curated) |
EC 2.3.1.287
|
| Curated function | Involved in sulfolipid-1 biosynthesis. Catalyzes the synthesis of the hepta- and octamethyl phthioceranic and hydroxyphthioceranic acids, the methyl-branched acyl constituents of sulfolipids. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | pks2 |
| 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 (67) |
GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0006082, GO:0006629, GO:0006631, GO:0006633, GO:0006873 +55 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 | 0.294 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 35 synonymous, 29 missense, 0 nonsense, 2 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 0.31% of strains (447) · clonal |
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 | 4.9e-98 | 26–274 | Beta-ketoacyl synthase, N-terminal domain |
Thiolase_N | PF00108.30 | 8.1e-07 | 186–227 | Thiolase, N-terminal domain |
Ketoacyl-synt_C | PF02801.29 | 7.4e-35 | 282–395 | Beta-ketoacyl synthase, C-terminal domain |
KAsynt_C_assoc | PF16197.12 | 4.8e-14 | 408–513 | Ketoacyl-synthetase C-terminal extension |
CurL-like_PKS_C | PF22621.3 | 2.1e-13 | 468–531 | CurL-like, PKS C-terminal |
RhiE-like_linker | PF22336.3 | 5.9e-11 | 471–538 | RhiE-like, KS-MAT linker domain |
Acyl_transf_1 | PF00698.27 | 1.8e-101 | 553–869 | Acyl transferase domain |
PKS_DH_N | PF21089.4 | 2.9e-22 | 914–1011 | Polyketide synthase dehydratase domain |
PS-DH | PF14765.13 | 2.0e-23 | 1044–1188 | Polyketide synthase dehydratase N-terminal domain |
ADH_N | PF08240.18 | 5.9e-10 | 1452–1524 | Alcohol dehydrogenase GroES-like domain |
ADH_zinc_N | PF00107.33 | 1.4e-22 | 1577–1694 | Zinc-binding dehydrogenase |
ADH_zinc_N_2 | PF13602.13 | 2.6e-21 | 1610–1748 | Zinc-binding dehydrogenase |
KR | PF08659.17 | 1.1e-58 | 1772–1950 | KR domain |
adh_short | PF00106.32 | 4.4e-08 | 1775–1929 | short chain dehydrogenase |
PP-binding | PF00550.32 | 7.1e-09 | 2045–2109 | 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 |
Rv2243 fabD |
malonyl CoA-acyl carrier protein transacylase | 996 | 996 | coexpression:750 experimental:960 database:549 |
Rv2383c mbtB |
phenyloxazoline synthase | 998 | 995 ctx | neighborhood:544 cooccurence:438 coexpression:937 experimental:721 textmining:763 |
Rv2048c pks12 |
polyketide synthase | 996 | 992 ctx | neighborhood:544 coexpression:423 experimental:965 textmining:630 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 996 | 992 ctx | neighborhood:544 coexpression:425 experimental:965 textmining:612 |
Rv3824c papA1 |
acyltransferase | 998 | 991 ctx | neighborhood:665 coexpression:888 experimental:721 textmining:831 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 996 | 990 ctx | neighborhood:544 coexpression:425 experimental:965 textmining:613 |
Rv1527c pks5 |
polyketide synthase | 995 | 990 ctx | neighborhood:544 coexpression:421 experimental:965 textmining:610 |
Rv3153 nuoI |
NADH-quinone oxidoreductase subunit I | 990 | 987 | coexpression:418 experimental:953 database:564 |
Rv3147 nuoC |
NADH-quinone oxidoreductase subunit C | 990 | 987 | coexpression:457 experimental:951 database:564 |
Rv0101 nrp |
peptide synthetase Nrp | 994 | 986 ctx | neighborhood:544 cooccurence:531 coexpression:794 experimental:721 textmining:617 |
Rv1181 pks4 |
polyketide beta-ketoacyl synthase | 988 | 980 ctx | neighborhood:544 coexpression:798 experimental:795 textmining:451 |
Rv2380c mbtE |
peptide synthetase | 983 | 973 ctx | neighborhood:526 cooccurence:476 coexpression:650 experimental:721 textmining:407 |
Rv3146 nuoB |
NADH-quinone oxidoreductase subunit B | 979 | 972 | coexpression:408 experimental:899 database:564 |
Rv2946c pks1 |
polyketide synthase | 988 | 966 ctx | neighborhood:544 experimental:864 textmining:673 |
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: phthioceranic/hydroxyphthioceranic acid synthase
- MTBC0 PGAP product: phthioceranic/hydroxyphthioceranic acid synthase
- Pfam (hmmscan --cut_ga): ketoacyl-synt PF00109.33 (E=5e-98), Thiolase_N PF00108.30 (E=8e-07), Ketoacyl-synt_C PF02801.29 (E=7e-35), KAsynt_C_assoc PF16197.12 (E=5e-14), CurL-like_PKS_C PF22621.3 (E=2e-13), RhiE-like_linker PF22336.3 (E=6e-11), Acyl_transf_1 PF00698.27 (E=2e-101), PKS_DH_N PF21089.4 (E=3e-22), PS-DH PF14765.13 (E=2e-23), ADH_N PF08240.18 (E=6e-10), ADH_zinc_N PF00107.33 (E=1e-22), ADH_zinc_N_2 PF13602.13 (E=3e-21), KR PF08659.17 (E=1e-58), adh_short PF00106.32 (E=4e-08), PP-binding PF00550.32 (E=7e-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_218342.1)
- Domains: Pfam-A via hmmscan --cut_ga — ketoacyl-synt (PF00109.33), Thiolase_N (PF00108.30), 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), 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), 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 P9WQE9 (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 —
651 functional partner(s); context anchor
fas - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_004054|Rv3825c|pks2 MGLGSAASGTGADRGAWTLAEPRVTPVAVIGMACRLPGGIDSPELLWKALLRGDDLITEVPPDRWDCDEFYDPQPGVPGRTVCKWGGFLDNPADFDCEFFGIGEREAIAIDPQQRLLLETSWEAMEHAGLTQQTLAGSATGVFAGVTHGDYTMVAADAKQLEEPYGYLGNSFSMASGRVAYAMRLHGPAITVDTACSSGLTAVHMACRSLHEGESDVALAGGVALMLEPRKAAAGSALGMLSPTGRCRAFDVAADGFVSGEGCAVVVLKRLPDALADGDRILAVIRGTSANQDGHTVNIATPSQPAQVAAYRAALAAGGVDAATVGMVEAHGPGTPIGDPIEYASVSEVYGVDGPCALASVKTNFGHTQSTAGVLGLIKVVLALKHGVVPRNLHFTRLPDEIAGITTNLFVPEVTTPWPTNGRQVPRRAAVSSYGFSGTNVHAVVEQAPQTEAQPHAASTPPTGTPALFTLSASSADALRQTAQRLTDWIQQHADSLVLSDLAYTLARRRTHRSVRTAVIASSVDELIAGLGEVADGDTVYQPAVGQDDRGPVWLFSGQGSQWAAMGADLLTNESVFAATVAELEPLIAAESGFSVTEAMTAPETVTGIDRVQPTIFAMQVALAATMAAYGVRPGAVIGHSMGESAAAVVAGVLSAEDGVRVICRRSKLMATIAGSAAMASVELPALAVQSELTALGIDDVVVAVVTAPQSTVIAGGTESVRKLVDIWERRDVLARAVAVDVASHSPQVDPILDELIAALADLNPKAPEIPYYSATLFDPREAPACDARYWADNLRHTVRFSAAVRSALDDGYRVFAELSPHPLLTHAVDQIAGSVGMPVAALAGMRREQPLPLGLRRLLTDLHNAGAAVDFSVLCPQGRLVDAPLPAWSHRFLFYDREGVDNRSPGGSTVAVHPLLGAHVRLPEEPERHAWQADVGTATLPWLGDHRIHNVAALPGAAYCEMALSAARAVLGEQSEVRDMRFEAMLLLDDQTPVSTVATVTSPGVVDFAVEALQEGVGHHLRRASAVLQQVSGECEPPAYDMASLLEAHPCRVDGEDLRRQFDKHGVQYGPAFTGLAVAYVAEDATATMLAEVALPGSIRSQQGLYAIHPALLDACFQSVGAHPDSQSVGSGLLVPLGVRRVRAYAPVRTARYCYTRVTKVELVGVEADIDVLDAHGTVLLAVCGLRIGTGVSERDKHNRVLNERLLTIEWHQRELPEMDPSGAGKWLLISDCAASDVTATRLADAFREHSAACTTMRWPLHDDQLAAADQLRDQVGSDEFSGVVVLTGSNTGTPHQGSADRGAEYVRRLVGIARELSDLPGAVPRMYVVTRGAQRVLADDCVNLEQGGLRGLLRTIGAEHPHLRATQIDVDEQTGVEQLARQLLATSEEDETAWRDNEWYVARLCPTPLRPQERRTIVADHQQSGMRLQIRTPGDMQTIELAAFHRVPPGPGQIEVAVRASSVNFADVLIAFGRYPSFEGHLPQLGTDFAGVVTAVGPGVTDHKVGDHVGGMSPNGCWGTFVTCDARLAATLPPGLGDAQAAAVTTAHATAWYGLHELARIRAGDTVLIHSGTGGVGQAAIAIARAAGAEIFATAGTPQRRELLRNMGIEHVYDSRSIEFAEQIRRDTNGRGVDVVLNSVTGAAQLAGLKLLAFRGRFVEIGKRDIYGDTKLGLFPFRRNLSFYAVDLGLLSATHPEELRDLLGTVYRLTAAGELPMPQSTHYPLVEAATAIRVMGNAEHTGKLVLHIPQTGKSLVTLPPEQAQVFRPDGSYIITGGLGGLGLFLAEKMAAAGCGRIVLNSRTQPTQKMRETIEAIAAMGSEVVVECGDIAQPGTAERLVATAVATGLPVRGVLHAAAVVEDATLANITDELLARDWAPKVHGAWELHEATSGQPLDWFCLFSSAAALTGSPGQSAYSAANSWLDAFAHWRQAQGLPATAIAWGAWSDIGQLGWWSASPARASALEESNYTAITPDEGAYAFEALLRHNRVYTGYAPVIGAPWLVAFAERSRFFEVFSSSNGSGTSKFRVELNELPRDEWPARLRQLVAEQVSLILRRTVDPDRPLPEYGLDSLGALELRTRIETETGIRLAPKNVSATVRGLADHLYEQLAPDDAPAAALSSQ