fabH Resolved · high auto-curated
H37Rv Rv0533c · MTBC0 mtbc0_000562 ·
335 aa · 628024–629031 (-) ·
RefSeq NP_215047.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 3-oxoacyl-ACP synthase III |
|---|---|
| MTBC0 PGAP re-annotation | beta-ketoacyl-ACP synthase III |
| Revised (this work) | Beta-ketoacyl-ACP synthase III. Pfam: Thiolase_N (PF00108.30), ACP_syn_III (PF08545.17), ACP_syn_III_C (PF08541.17). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WNG3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Mycobacterial beta-ketoacyl-[acyl-carrier-protein] synthase III |
| EC (curated) |
EC 2.3.1.301
|
| Curated function | Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP. Catalyzes the first condensation reaction which initiates fatty acid synthesis and may therefore play a role in governing the total rate of fatty acid production. Possesses both acetoacetyl-ACP synthase and acetyl transacylase activities. Possesses a clear preference for long-chain acyl-CoA substrates rather than acyl-ACP primers. Its substrate specificity determines the biosynthesis of mycolic acid fatty acid chain, which is characteristic of mycobacterial cell wall. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
|---|---|
| Preferred name | fabH |
| eggNOG description | Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP. Catalyzes the first condensation reaction which initiates fatty acid synthesis and may therefore play a role in governing the total rate of fatty acid production. Possesses both acetoacetyl-ACP synthase and acetyl transacylase activities. Its substrate specificity determines the biosynthesis of branched- chain and or straight-chain of fatty acids |
| Orthologous group | COG0332 |
| EC number |
EC 2.3.1.180
|
| KEGG orthology |
K00648, K11608
|
| KEGG pathways |
map00061, map01100, map01212
|
| KEGG modules |
M00082, M00083
|
| Gene Ontology (83) |
GO:0000062, GO:0000166, GO:0003674, GO:0003824, GO:0004312, GO:0004315, GO:0005488, GO:0006082, GO:0006139, GO:0006163, GO:0006629, GO:0006631 +71 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 | 1.037 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 3 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 |
|---|---|---|---|---|
Thiolase_N | PF00108.30 | 4.5e-06 | 46–154 | Thiolase, N-terminal domain |
ACP_syn_III | PF08545.17 | 8.4e-23 | 116–193 | 3-Oxoacyl-[acyl-carrier-protein (ACP)] synthase III |
ACP_syn_III_C | PF08541.17 | 1.6e-30 | 242–332 | 3-Oxoacyl-[acyl-carrier-protein (ACP)] synthase III C terminal |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: fas (fatty acid synthase), high confidence from genomic context alone (score 986 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2524c fas |
fatty acid synthase | 996 | 986 ctx | neighborhood:447 coexpression:975 textmining:739 |
Rv0904c accD3 |
acetyl-CoAcarboxylase carboxyl transferase subunit beta | 993 | 984 | coexpression:969 textmining:587 |
Rv2243 fabD |
malonyl CoA-acyl carrier protein transacylase | 994 | 940 ctx | cooccurence:748 coexpression:733 textmining:915 |
Rv2245 kasA |
3-oxoacyl-ACP synthase 1 | 988 | 922 ctx | cooccurence:750 coexpression:678 textmining:860 |
Rv2246 kasB |
3-oxoacyl-ACP synthase 2 | 988 | 920 ctx | cooccurence:745 coexpression:678 textmining:860 |
Rv1484 inhA |
NADH-dependent enoyl-[ACP | 976 | 852 ctx | cooccurence:549 coexpression:646 textmining:850 |
Rv0534c menA |
1,4-dihydroxy-2-naphthoate octaprenyltransferase | 790 | 790 ctx | neighborhood:785 |
Rv0716 rplE |
50S ribosomal protein L5 | 713 | 714 | coexpression:714 |
Rv3285 accA3 |
bifunctional protein acetyl-/propionyl-CoA carboxylase subunit alpha AccA | 760 | 678 ctx | cooccurence:484 |
Rv0701 rplC |
50S ribosomal protein L3 | 674 | 675 | coexpression:674 |
Rv2501c accA1 |
acetyl/propionyl-CoA carboxylase subuit alpha | 677 | 642 ctx | cooccurence:430 |
Rv1483 fabG1 |
3-oxoacyl-ACP reductase FabG | 872 | 637 ctx | cooccurence:570 textmining:665 |
Rv3462c infA |
translation initiation factor IF-1 | 606 | 606 | coexpression:530 |
Rv2244 acpM |
meromycolate extension acyl carrier protein | 871 | 600 | textmining:693 |
Rv1415 ribA2 |
bifunctional riboflavin biosynthesis GTP cyclohydrolase II/3,4-dihydroxy-2-butanone 4-phosphate synthase | 596 | 596 | coexpression:412 |
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: 3-oxoacyl-ACP synthase III
- MTBC0 PGAP product: beta-ketoacyl-ACP synthase III
- Pfam (hmmscan --cut_ga): Thiolase_N PF00108.30 (E=5e-06), ACP_syn_III PF08545.17 (E=8e-23), ACP_syn_III_C PF08541.17 (E=2e-30)
- (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_215047.1)
- Domains: Pfam-A via hmmscan --cut_ga — Thiolase_N (PF00108.30), ACP_syn_III (PF08545.17), ACP_syn_III_C (PF08541.17)
- 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
COG0332 - Curated reference: UniProt P9WNG3 (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 —
83 functional partner(s); context anchor
fas - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000562|Rv0533c|fabH MTEIATTSGARSVGLLSVGAYRPERVVTNDEICQHIDSSDEWIYTRTGIKTRRFAADDESAASMATEACRRALSNAGLSAADIDGVIVTTNTHFLQTPPAAPMVAASLGAKGILGFDLSAGCAGFGYALGAAADMIRGGGAATMLVVGTEKLSPTIDMYDRGNCFIFADGAAAVVVGETPFQGIGPTVAGSDGEQADAIRQDIDWITFAQNPSGPRPFVRLEGPAVFRWAAFKMGDVGRRAMDAAGVRPDQIDVFVPHQANSRINELLVKNLQLRPDAVVANDIEHTGNTSAASIPLAMAELLTTGAAKPGDLALLIGYGAGLSYAAQVVRMPKG