fadA4 Resolved · high auto-curated
H37Rv Rv1323 · MTBC0 - ·
389 aa · 1485862–1487031 (+) ·
RefSeq NP_215839.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | acetyl-CoA acetyltransferase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Acetyl-CoA acetyltransferase. Pfam: Thiolase_N (PF00108.30), ketoacyl-synt (PF00109.33), Thiolase_C (PF02803.25). |
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 |
P9WG69
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable acetyl-CoA acetyltransferase |
| EC (curated) |
EC 2.3.1.9
|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
|---|---|
| Preferred name | fadA4 |
| eggNOG description | Catalyzes the synthesis of acetoacetyl coenzyme A from two molecules of acetyl coenzyme A. It can also act as a thiolase, catalyzing the reverse reaction and generating two-carbon units from the four-carbon product of fatty acid oxidation |
| Orthologous group | COG0183 |
| EC number |
EC 2.3.1.9
|
| KEGG orthology |
K00626
|
| KEGG pathways |
map00071, map00072, map00280, map00310, map00362, map00380, map00620, map00630, map00640, map00650, map00720, map00900, map01100, map01110, map01120, map01130, map01200, map01212, map02020
|
| KEGG modules |
M00088, M00095, M00373, M00374, M00375
|
| Gene Ontology (57) |
GO:0003674, GO:0003824, GO:0003988, GO:0005575, GO:0005576, GO:0005623, GO:0005886, GO:0006082, GO:0006629, GO:0006631, GO:0006635, GO:0008150 +45 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 | 1.709 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 5 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 | 1.7e-96 | 1–258 | Thiolase, N-terminal domain |
ketoacyl-synt | PF00109.33 | 1.4e-04 | 66–119 | Beta-ketoacyl synthase, N-terminal domain |
Thiolase_C | PF02803.25 | 2.8e-43 | 267–387 | Thiolase, C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: fadB2 (3-hydroxybutyryl-CoA dehydrogenase), high confidence from genomic context alone (score 984 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0860 fadB |
fatty oxidation protein FadB | 998 | 996 | coexpression:698 experimental:804 database:942 textmining:580 |
Rv0468 fadB2 |
3-hydroxybutyryl-CoA dehydrogenase | 985 | 984 ctx | cooccurence:515 coexpression:432 experimental:412 database:900 |
Rv1715 fadB3 |
3-hydroxybutyryl-CoA dehydrogenase FadB | 982 | 981 ctx | cooccurence:495 coexpression:427 experimental:412 database:900 |
Rv3667 acs |
acetyl-CoAsynthetase | 944 | 941 | coexpression:416 database:900 |
Rv1837c glcB |
malate synthase | 941 | 933 | database:900 |
Rv3710 leuA |
2-isopropylmalate synthase | 926 | 924 | database:900 |
Rv2503c scoB |
succinyl-CoA:3-ketoacid-CoA transferase subunit B | 973 | 923 | database:900 textmining:672 |
Rv0859 fadA |
acyltransferase | 928 | 923 | database:900 |
Rv3546 fadA5 |
acetyl-CoA acetyltransferase FadA | 923 | 923 | database:900 |
Rv0243 fadA2 |
acetyl-CoA acetyltransferase FadA | 923 | 923 | database:900 |
Rv2504c scoA |
succinyl-CoA:3-ketoacid-CoA transferase subunit A | 962 | 922 | database:900 textmining:537 |
Rv3556c fadA6 |
acetyl-CoA acetyltransferase FadA | 926 | 921 | database:900 |
Rv1074c fadA3 |
beta-ketoacyl CoA thiolase FadA | 920 | 920 | database:900 |
Rv0753c mmsA |
methylmalonate-semialdehyde dehydrogenase | 914 | 911 | database:900 |
Rv2495c bkdC |
branched-chain keto acid dehydrogenase E2 component | 911 | 908 | database:900 |
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): acetyl-CoA acetyltransferase
- Pfam (hmmscan --cut_ga): Thiolase_N PF00108.30 (E=2e-96), ketoacyl-synt PF00109.33 (E=1e-04), Thiolase_C PF02803.25 (E=3e-43)
- (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_215839.1)
- Domains: Pfam-A via hmmscan --cut_ga — Thiolase_N (PF00108.30), ketoacyl-synt (PF00109.33), Thiolase_C (PF02803.25)
- 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
COG0183 - Curated reference: UniProt P9WG69 (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 —
139 functional partner(s); context anchor
fadB2 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv1323|fadA4 MIVAGARTPIGKLMGSLKDFSASELGAIAIKGALEKANVPASLVEYVIMGQVLTAGAGQMPARQAAVAAGIGWDVPALTINKMCLSGIDAIALADQLIRAREFDVVVAGGQESMTKAPHLLMNSRSGYKYGDVTVLDHMAYDGLHDVFTDQPMGALTEQRNDVDMFTRSEQDEYAAASHQKAAAAWKDGVFADEVIPVNIPQRTGDPLQFTEDEGIRANTTAAALAGLKPAFRGDGTITAGSASQISDGAAAVVVMNQEKAQELGLTWLAEIGAHGVVAGPDSTLQSQPANAINKALDREGISVDQLDVVEINEAFAAVALASIRELGLNPQIVNVNGGAIAVGHPLGMSGTRITLHAALQLARRGSGVGVAALCGAGGQGDALILRAG