pks4 Resolved · high auto-curated
H37Rv Rv1181 · MTBC0 - ·
1582 aa · 1315234–1319982 (+) ·
RefSeq NP_215697.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | polyketide beta-ketoacyl synthase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Polyketide beta-ketoacyl synthase. Pfam: 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), 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 |
A0A089QRB9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Mycolipanoate synthase |
| EC (curated) |
EC 2.3.1.252
|
| Curated function | Polyketide synthase involved in the biosynthesis of methyl-branched fatty acids such as mycolipanoic, mycolipenic (phthienoic) and mycolipodienoic acids required for the synthesis of a major class of polyacylated trehaloses. Catalyzes the elongation of CoA esters of long-chain fatty acids by incorporation of three methylmalonyl (but not malonyl) residues, to form trimethyl-branched fatty-acids. |
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 (101) |
GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0006066, GO:0006082, GO:0006629, GO:0006631, GO:0006633 +89 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 | 0.41 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 14 synonymous, 16 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 |
|---|---|---|---|---|
Acyl_transf_1 | PF00698.27 | 5.7e-98 | 35–351 | Acyl transferase domain |
PKS_DH_N | PF21089.4 | 2.5e-21 | 395–493 | Polyketide synthase dehydratase domain |
PS-DH | PF14765.13 | 6.4e-24 | 521–673 | Polyketide synthase dehydratase N-terminal domain |
SpnB_Rossmann | PF22953.4 | 3.6e-11 | 733–876 | Polyketide synthase extender module SpnB, Rossmann fold domain |
ADH_N | PF08240.18 | 6.3e-10 | 922–1003 | Alcohol dehydrogenase GroES-like domain |
ADH_zinc_N | PF00107.33 | 1.0e-21 | 1047–1157 | Zinc-binding dehydrogenase |
ADH_zinc_N_2 | PF13602.13 | 3.0e-20 | 1079–1218 | Zinc-binding dehydrogenase |
KR | PF08659.17 | 4.3e-60 | 1242–1420 | KR domain |
adh_short | PF00106.32 | 9.0e-09 | 1245–1400 | short chain dehydrogenase |
PP-binding | PF00550.32 | 6.5e-09 | 1507–1570 | 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:812 experimental:999 database:549 textmining:736 |
Rv1180 pks3 |
polyketide beta-ketoacyl synthase | 999 | 1000 ctx | neighborhood:646 fusion:806 cooccurence:756 coexpression:862 database:900 |
Rv1182 papA3 |
acyltransferase papA3 | 997 | 989 ctx | neighborhood:648 coexpression:917 experimental:473 textmining:786 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 990 | 983 ctx | neighborhood:544 experimental:795 database:720 textmining:445 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 988 | 980 ctx | neighborhood:544 coexpression:798 experimental:795 textmining:451 |
Rv2383c mbtB |
phenyloxazoline synthase | 993 | 978 ctx | neighborhood:544 coexpression:876 experimental:473 textmining:707 |
Rv2947c pks15 |
polyketide synthase | 982 | 964 ctx | fusion:829 cooccurence:749 textmining:532 |
Rv2243 fabD |
malonyl CoA-acyl carrier protein transacylase | 971 | 963 | coexpression:601 experimental:787 database:549 |
Rv0101 nrp |
peptide synthetase Nrp | 968 | 947 | coexpression:767 experimental:473 textmining:424 |
Rv2048c pks12 |
polyketide synthase | 969 | 945 ctx | neighborhood:544 experimental:795 textmining:471 |
Rv2382c mbtC |
polyketide synthetase | 937 | 930 ctx | fusion:681 cooccurence:742 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 958 | 929 ctx | neighborhood:544 experimental:795 textmining:443 |
Rv1527c pks5 |
polyketide synthase | 958 | 928 ctx | neighborhood:544 experimental:795 textmining:439 |
Rv2932 ppsB |
phthiocerol synthesis polyketide synthase type I PpsB | 940 | 915 ctx | neighborhood:481 database:720 |
Rv3800c pks13 |
polyketide synthase | 957 | 903 ctx | neighborhood:544 coexpression:676 textmining:582 |
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 beta-ketoacyl synthase
- Pfam (hmmscan --cut_ga): Acyl_transf_1 PF00698.27 (E=6e-98), PKS_DH_N PF21089.4 (E=2e-21), PS-DH PF14765.13 (E=6e-24), SpnB_Rossmann PF22953.4 (E=4e-11), ADH_N PF08240.18 (E=6e-10), ADH_zinc_N PF00107.33 (E=1e-21), ADH_zinc_N_2 PF13602.13 (E=3e-20), KR PF08659.17 (E=4e-60), adh_short PF00106.32 (E=9e-09), 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_215697.1)
- Domains: Pfam-A via hmmscan --cut_ga — 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), 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 A0A089QRB9 (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 —
455 functional partner(s); context anchor
fas - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv1181|pks4 MTASSFDELSAALRDVAGDQIPYQPAVGHDDRGPVWVFSGQGSQWPGMGTELLVAEPVFAATVAAMEPVIARESGFSVTEAMSAPQTVSGIDRVQPTIFAVQVALAAALKSYGVRPGAIIGHSLGEAAAAVVAGALSLHDGLRVICRRSRLMSRIAGSGAMASVELPGQQVLSELAIRGISDVVLSVVASPTSTVVGGATQSIRDLVAAWEQQDVLAREVAVDVASHTPQVDPILDELLEVLAEVDPTAPEIPYYSATLWDPRERPSFTGEYWVENLRYTVRFAAAVQAALKDGYRVFGELAPHPLLTYAVEQNAASLDMPIATLAAMRRGEQLPFGLRGFVADVHNAGAKVDFSVQYPDGRLVDAPLPSWTHRTLMLSREDSHRSHTGAVQAVHPLLGAHVHLLEEPERHVWQAGVGTGAHPWLGDHRIHNVAAFPGAAYCEMALAAARTTLGELSEVRDIKFEQTLLLDEQTVVSSAATIAAPGILQFAVESHQEGEPARRASAMLHALEEMPQPPGYDTNALTAAHESSMSGEELRKMFNSLGIQYGPAFSGLVAVHTARGDVTTVLAEVALPGAIRSQQSAYASHPALLDACFQSVLVHPEVQKATVGGLMLPVGVRRLRNYHSTRSAHYCLARVTSSSRAGECEADLDVFDQAGTVLLTVEGLRLAAGISEHERANRVFDERLLTIEWERGELPEVPQIDAGSWLLLSASEADPLTAQLADALNAVGAQSTSVASASDVAQLRSLLGGRLTGVVVVTGPPTGGLTQCGRDYVSQLVGIARELAELPGEPPRLFVVTRSAASVLPSDLANLEQAGLRGLMRVIDSEHPHLGATAIDVDNDETVAALVASQLQSGSQEDETAWRNGIWYTARLRPGPLRPAERRTAVVEYRRDGMRLQIRTPGDLESLEFVTFDRVAPGPGEIEVAVTASSVNFADVLVAFGRYPTFEGYRQQLGIDFAGVVTAVGPDVTEHRIGDHVGGMSANGCWSTFVRCDARLAVTLPPELPVAAAAAVPTASATAWYALHDLARICSDDKVLIHSGTGGVGQAAIAIARAAGCEIFATAGSAQRRQLLHDMGVEHVYDSRSTEFAEQIRGDTDGYGVDVVLNSLPGAAQRAGIELLAFGGRFVEIGKRDIYGDTRLGLFPFRRNLSLYAVDLALLTHSHPHTVRRLLKTVYQHTVEGTLPVPQTTHYPIHDAAVAIRLVGGAGHTGKVVLDVPRTGEGVAVVPPEQVRTSRPDGAYLVTGGLGGLGLFLAGELAAAGCGRIVLNSRSTPSPHATRVIERLRAAGADIQVECGDIADAATAHRVVAVATASGLPVRGVLHAAAVVEDATLANVTDELIDRCWAPKVHGAWNIHRATAAQPLEWFCLFSSAAALVGSPGQGAYAAANSWLDAFAHWRRAQGLPATSIAWGAWAEIGRATALAEGTGAAIAPAEGARAFQTLLRYGRAYSGYAPIMGTPWLTAFAQRSRFAEAFHATGQNQPATGKFLAELGSLPREEWPRTVRRLVSDQISLLLRRTIDPDRPLSDYGLDSLGNLELRTRIETETGIRVSPTKITTVRGLAEHVCDELAAAQSAPV