kasB Resolved · high auto-curated

H37Rv Rv2246 · MTBC0 - · 438 aa · 2519396–2520712 (+) · RefSeq NP_216762.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)3-oxoacyl-ACP synthase 2
MTBC0 PGAP re-annotation
Revised (this work)3-oxoacyl-ACP synthase 2. Pfam: ketoacyl-synt (PF00109.33), Thiolase_N (PF00108.30), Ketoacyl-synt_C (PF02801.29).

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 P9WQD7 SwissProt · reviewed · Evidence at protein level
UniProt name3-oxoacyl-[acyl-carrier-protein] synthase 2
EC (curated) EC 2.3.1.294
Curated functionPart of the mycobacterial fatty acid elongation system FAS-II, which is involved in mycolic acid biosynthesis. Catalyzes the elongation of long chain acyl-ACP substrates by the addition of two carbons from malonyl-ACP to an acyl acceptor. Involved in extension of the mycolate chains to full lengths and produces longer chain multiunsaturated hydrocarbons averaging 54 carbons in length. Essential for resistance to macrophage antimicrobial activity.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Q Secondary metabolites biosynthesis, transport and catabolism
Preferred namefabF
eggNOG descriptionBelongs to the beta-ketoacyl-ACP synthases family
Orthologous groupCOG0304
EC number EC 2.3.1.179
KEGG orthology K09458, K11609
KEGG pathways map00061, map00780, map01100, map01212
KEGG modules M00083, M00572
Gene Ontology (61) GO:0001666, GO:0003674, GO:0003824, GO:0004312, GO:0004315, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0006082, GO:0006629, GO:0006631 +49 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 0.069 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 1 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)

PfamAccessioni-EvalueResiduesDescription
ketoacyl-syntPF00109.33 1.1e-5234–273 Beta-ketoacyl synthase, N-terminal domain
Thiolase_NPF00108.30 1.4e-07166–220 Thiolase, N-terminal domain
Ketoacyl-synt_CPF02801.29 1.4e-34283–395 Beta-ketoacyl synthase, C-terminal domain

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: fabD (malonyl CoA-acyl carrier protein transacylase), high confidence from genomic context alone (score 997 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2243 fabD malonyl CoA-acyl carrier protein transacylase 999 997 ctx neighborhood:758 cooccurence:769 coexpression:941 textmining:930
Rv2245 kasA 3-oxoacyl-ACP synthase 1 977 977 ctx neighborhood:836 coexpression:860
Rv2247 accD6 acetyl-/propionyl-CoA carboxylase subunit beta 996 976 ctx neighborhood:836 coexpression:860 textmining:841
Rv0904c accD3 acetyl-CoAcarboxylase carboxyl transferase subunit beta 983 976 coexpression:961
Rv2244 acpM meromycolate extension acyl carrier protein 996 956 ctx neighborhood:836 coexpression:463 experimental:408 textmining:929
Rv0533c fabH 3-oxoacyl-ACP synthase III 988 920 ctx cooccurence:745 coexpression:678 textmining:860
Rv1663 pks17 polyketide synthase 923 918 coexpression:443 experimental:785
Rv1527c pks5 polyketide synthase 928 900 coexpression:491 experimental:785
Rv2940c mas multifunctional mycocerosic acid synthase 926 900 coexpression:491 experimental:785
Rv2933 ppsC phthiocerol synthesis polyketide synthase type I PpsC 927 899 coexpression:486 experimental:785
Rv3825c pks2 phthioceranic/hydroxyphthioceranic acid synthase 925 899 coexpression:485 experimental:785
Rv2048c pks12 polyketide synthase 925 899 coexpression:488 experimental:785
Rv1484 inhA NADH-dependent enoyl-[ACP 982 840 ctx cooccurence:477 coexpression:689 textmining:896
Rv3285 accA3 bifunctional protein acetyl-/propionyl-CoA carboxylase subunit alpha AccA 846 806 ctx cooccurence:650 coexpression:450
Rv1483 fabG1 3-oxoacyl-ACP reductase FabG 913 794 ctx cooccurence:658 textmining:598

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): 3-oxoacyl-ACP synthase 2
  • Pfam (hmmscan --cut_ga): ketoacyl-synt PF00109.33 (E=1e-52), Thiolase_N PF00108.30 (E=1e-07), Ketoacyl-synt_C PF02801.29 (E=1e-34)
  • (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_216762.1)
  • Domains: Pfam-A via hmmscan --cut_ga — ketoacyl-synt (PF00109.33), Thiolase_N (PF00108.30), Ketoacyl-synt_C (PF02801.29)
  • 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 COG0304
  • Curated reference: UniProt P9WQD7 (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 — 116 functional partner(s); context anchor fabD
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2246|kasB
MGVPPLAGASRTDMEGTFARPMTELVTGKAFPYVVVTGIAMTTALATDAETTWKLLLDRQSGIRTLDDPFVEEFDLPVRIGGHLLEEFDHQLTRIELRRMGYLQRMSTVLSRRLWENAGSPEVDTNRLMVSIGTGLGSAEELVFSYDDMRARGMKAVSPLTVQKYMPNGAAAAVGLERHAKAGVMTPVSACASGAEAIARAWQQIVLGEADAAICGGVETRIEAVPIAGFAQMRIVMSTNNDDPAGACRPFDRDRDGFVFGEGGALLLIETEEHAKARGANILARIMGASITSDGFHMVAPDPNGERAGHAITRAIQLAGLAPGDIDHVNAHATGTQVGDLAEGRAINNALGGNRPAVYAPKSALGHSVGAVGAVESILTVLALRDQVIPPTLNLVNLDPEIDLDVVAGEPRPGNYRYAINNSFGFGGHNVAIAFGRY