pks5 Resolved · high auto-curated
H37Rv Rv1527c · MTBC0 mtbc0_001634 ·
2108 aa · 1731892–1738218 (-) ·
RefSeq NP_216043.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | polyketide synthase |
|---|---|
| MTBC0 PGAP re-annotation | sulfolipid-1 biosynthesis phthioceranic/hydroxyphthioceranic acid synthase |
| Revised (this work) | Sulfolipid-1 biosynthesis 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 |
O53901
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Mycocerosic acid synthase-like polyketide synthase |
| EC (curated) |
EC 2.3.1.-
|
| Curated function | Polyketide synthase likely involved in the biosynthesis of a polymethyl-branched fatty acid (PMB-FA) that might only be produced during host infection. Is required for the full virulence of M.tuberculosis during host infection. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | pks5 |
| 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 (17) |
GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0008150, GO:0009405, GO:0016020, GO:0030312, GO:0044419 +5 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 | 0.864 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 14 synonymous, 33 missense, 1 nonsense, 6 frameshift |
| Disruption | 7 distinct premature-stop/frameshift site(s); most common in 2.47% of strains (3592) · 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 |
|---|---|---|---|---|
ketoacyl-synt | PF00109.33 | 1.4e-93 | 16–263 | Beta-ketoacyl synthase, N-terminal domain |
Thiolase_N | PF00108.30 | 7.2e-07 | 168–215 | Thiolase, N-terminal domain |
Ketoacyl-synt_C | PF02801.29 | 1.6e-38 | 271–384 | Beta-ketoacyl synthase, C-terminal domain |
KAsynt_C_assoc | PF16197.12 | 4.3e-10 | 395–503 | Ketoacyl-synthetase C-terminal extension |
CurL-like_PKS_C | PF22621.3 | 2.3e-11 | 461–524 | CurL-like, PKS C-terminal |
RhiE-like_linker | PF22336.3 | 8.4e-10 | 464–530 | RhiE-like, KS-MAT linker domain |
Acyl_transf_1 | PF00698.27 | 8.0e-107 | 546–862 | Acyl transferase domain |
PKS_DH_N | PF21089.4 | 1.3e-24 | 905–996 | Polyketide synthase dehydratase domain |
PS-DH | PF14765.13 | 2.2e-20 | 1036–1187 | Polyketide synthase dehydratase N-terminal domain |
ADH_N | PF08240.18 | 5.7e-11 | 1445–1528 | Alcohol dehydrogenase GroES-like domain |
ADH_zinc_N | PF00107.33 | 7.6e-21 | 1570–1685 | Zinc-binding dehydrogenase |
ADH_zinc_N_2 | PF13602.13 | 2.4e-19 | 1603–1741 | Zinc-binding dehydrogenase |
KR | PF08659.17 | 6.6e-57 | 1765–1942 | KR domain |
adh_short | PF00106.32 | 2.4e-08 | 1768–1924 | short chain dehydrogenase |
PP-binding | PF00550.32 | 1.6e-07 | 2029–2093 | 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 | 997 | 996 | coexpression:754 experimental:960 database:549 |
Rv2383c mbtB |
phenyloxazoline synthase | 998 | 995 ctx | neighborhood:544 cooccurence:437 coexpression:937 experimental:721 textmining:745 |
Rv2048c pks12 |
polyketide synthase | 997 | 992 ctx | neighborhood:544 coexpression:429 experimental:965 textmining:662 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 996 | 992 ctx | neighborhood:544 coexpression:425 experimental:965 textmining:619 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 996 | 990 ctx | neighborhood:544 coexpression:426 experimental:965 textmining:611 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 995 | 990 ctx | neighborhood:544 coexpression:421 experimental:965 textmining:610 |
Rv3153 nuoI |
NADH-quinone oxidoreductase subunit I | 990 | 987 | coexpression:414 experimental:953 database:564 |
Rv3147 nuoC |
NADH-quinone oxidoreductase subunit C | 989 | 987 | coexpression:457 experimental:951 database:564 |
Rv0101 nrp |
peptide synthetase Nrp | 994 | 986 ctx | neighborhood:544 cooccurence:529 coexpression:794 experimental:721 textmining:590 |
Rv2380c mbtE |
peptide synthetase | 982 | 972 ctx | neighborhood:526 cooccurence:472 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 | 987 | 966 ctx | neighborhood:544 experimental:864 textmining:652 |
Rv3148 nuoD |
NADH-quinone oxidoreductase subunit D | 972 | 963 | experimental:905 database:564 |
Rv3800c pks13 |
polyketide synthase | 987 | 959 ctx | neighborhood:544 coexpression:803 experimental:414 textmining:720 |
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: sulfolipid-1 biosynthesis phthioceranic/hydroxyphthioceranic acid synthase
- Pfam (hmmscan --cut_ga): ketoacyl-synt PF00109.33 (E=1e-93), Thiolase_N PF00108.30 (E=7e-07), Ketoacyl-synt_C PF02801.29 (E=2e-38), KAsynt_C_assoc PF16197.12 (E=4e-10), CurL-like_PKS_C PF22621.3 (E=2e-11), RhiE-like_linker PF22336.3 (E=8e-10), Acyl_transf_1 PF00698.27 (E=8e-107), PKS_DH_N PF21089.4 (E=1e-24), PS-DH PF14765.13 (E=2e-20), ADH_N PF08240.18 (E=6e-11), ADH_zinc_N PF00107.33 (E=8e-21), ADH_zinc_N_2 PF13602.13 (E=2e-19), KR PF08659.17 (E=7e-57), adh_short PF00106.32 (E=2e-08), PP-binding PF00550.32 (E=2e-07)
- (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_216043.1)
- 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 O53901 (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 —
639 functional partner(s); context anchor
fas - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001634|Rv1527c|pks5 MGKERTKTVDRTRVTPVAVIGMGCRLPGGIDSPDRLWEALLRGDDLVTEIPADRWDIDEYYDPEPGVPGRTDCKWGAYLDNVGDFDPEFFGIGEKEAIAIDPQHRLLLETSWEAMEHGGLTPNQMASRTGVFVGLVHTDYILVHADNQTFEGPYGNTGTNACFASGRVAYAMGLQGPAITVDTACSSGLTAIHLACRSLHDGESDIALAGGVYVMLEPRRFASGSALGMLSATGRCHAFDVSADGFVSGEGCVMLALKRLPDALADGDRILAVIRGTAANQDGHTVNIATPSRSAQVAAYREALDVAGVDPATVGMVEAHGPGTPVGDPIEYASLAEVYGNDGPCALASVKTNFGHTQSAAGALGLMKAVLALQHGVVPQNLHFTALPDKLAAIETNLFVPQEITPWPGADQETPRRAAVSSYGMTGTNVHAIVEQAPVPAPESGAPGDTPATPGIDGALLFALSASSQDALRQTAARLADWVDAQGPELAPADLAYTLARRRGHRPVRTAVLAATTAELTEALREVATGETPYPPAVGQDDRGPVWVFSGQGSQWAGMGADLLATEPVFAATIAAIEPLIAAESGFSVTEAMTAPEVVTGIDRVQPTLFAMQVALAATMKSYGVAPGAVIGHSLGESAAAVVAGALCLEDGVRVICRRSALMTRIAGAGAMASVELPAQQVLSELMARGVNDAVVAVVASPQSTVIGGATQTVRDLVAAWEQRDVLAREVAVDVASHSPQVDPILDELAEALAEISPLQPEIPYYSATSFDPREEPYCDAYYWVDNLRHTVRFAAAVQAALEDGYRVFTELTPHPLLTHAVDQTARSLDMSAAALAGMRREQPLPHGLRALAGDLYAAGAAVDFAVLYPTGRLINAPLPTWNHRRLLLDDTTRRIAHANTVAVHPLLGSHVRLPEEPERHVWQGEVGTVTQPWLADHQIHGAAALPGAAYCEMALAAARAVLGEASEVRDIRFEQMLLLDDETPIGVTATVEAPGVVPLTVETSHDGRYTRQLAAVLHVVREADDAPDQPPQKNIAELLASHPHKVDGAEVRQWLDKRGHRLGPAFAGLVDAYIAEGAGDTVLAEVNLPGPLRSQVKAYGVHPVLLDACFQSVAAHPAVQGMADGGLLLPLGVRRLRSYGSARHARYCCTTVTACGVGVEADLDVLDEHGAVVLAVRGLQLGTGASQASERARVLGERLLSIEWHERELPENSHAEPGAWLLISTCDATDLVAAQLTDALKVHDAQCTTMSWPQRADHAAQAARLRDQLGTGGFTGVFVLTAPQTGDPDAESPVRGGELVKHVVRIAREIPEITAQEPRLYVLTHNAQAVLSGDRPNLEQGGMRGLLRVIGAEHPHLKASYVDVDEQTGAESVARQLLAASGEDETAWRNDQWYTARLCPAPLRPEERQTTVVDHAEAGMRLQIRTPGDLQTLEFAAFDRVPPGPGEIEVAVTASSINFADVLVTFGRYQTLDGRQPQLGTDFAGVVSAVGPGVSELKVGDRVGGMSPNGCWATFVTCDARLATRLPEGLTDAQAAAVTTASATAWYGLQDLARIKAGDKVLIHSATGGVGQAAIAIARAAGAQIYATAGNEKRRDLLRDMGIEHVYDSRSVEFAEQIRRDTAGYGVDIVLNSVTGAAQLAGLKLLALGGRFIEIGKRDIYSNTRLELLPFRRNLAFYGLDLGLMSVSHPAAVRELLSTVYRLTVEGVLPMPQSTHYPLAEAATAIRVMGAAEHTGKLILDVPHAGRSSVVLPPEQARVFRSDGSYIITGGLGGLGLFLAEKMANAGAGRIVLSSRSQPSQKALETIELVRAIGSDVVVECGDIAQPDTADRLVTAATATGLPLRGVLHAAAVVEDATLANITDELIERDWAPKAYGAWQLHRATADQPLDWFCSFSSAAALVGSPGQGAYAAANSWLDTFTHWRRAQDLPATSIAWGAWGQIGRAIAFAEQTGDAIAPEEGAYAFETLLRHNRAYSGYAPVIGSPWLTAFAQHSPFAEKFQSLGQNRSGTSKFLAELVDLPREEWPDRLRRLLSKQVGLILRRTIDTDRLLSEYGLDSLSSQELRARVEAETGIRISATEINTTVRGLADLMCDKLAADRDAPAPA