fadA5 Resolved · high auto-curated
H37Rv Rv3546 · MTBC0 mtbc0_003763 ·
391 aa · 4009234–4010409 (+) ·
RefSeq NP_218063.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | acetyl-CoA acetyltransferase FadA |
|---|---|
| MTBC0 PGAP re-annotation | steroid 3-ketoacyl-CoA thiolase |
| Revised (this work) | Steroid 3-ketoacyl-CoA thiolase. Pfam: Thiolase_N (PF00108.30), Thiolase_C (PF02803.25). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6XHI4
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Steroid 3-ketoacyl-CoA thiolase |
| EC (curated) |
EC 2.3.1.16
|
| Curated function | Involved in the beta-oxidation of the cholesterol side chain. It is important for utilization of cholesterol as a sole carbon source in vitro and for full virulence in the chronic stage of mouse lung infection. Catalyzes the thiolysis of 3,22-dioxochol-4-en-24-oyl-CoA to yield 3-oxo-4-pregnene-20-carboxyl-CoA (3-OPC-CoA) and acetyl-CoA. Also able to use acetoacetyl-CoA (AcAcCoA) as substrate. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
|---|---|
| Preferred name | fadA5 |
| eggNOG description | Belongs to the thiolase family |
| 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 (73) |
GO:0003674, GO:0003676, GO:0003723, GO:0003729, GO:0003824, GO:0003988, GO:0005488, GO:0005515, GO:0005575, GO:0005622, GO:0005623, GO:0005737 +61 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 | 0.115 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
Thiolase_N | PF00108.30 | 5.1e-52 | 5–260 | Thiolase, N-terminal domain |
Thiolase_C | PF02803.25 | 9.0e-39 | 269–390 | 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 981 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0860 fadB |
fatty oxidation protein FadB | 996 | 996 | coexpression:697 experimental:804 database:942 |
Rv0468 fadB2 |
3-hydroxybutyryl-CoA dehydrogenase | 981 | 981 ctx | cooccurence:451 coexpression:426 experimental:412 database:900 |
Rv1715 fadB3 |
3-hydroxybutyryl-CoA dehydrogenase FadB | 982 | 978 ctx | cooccurence:409 coexpression:428 experimental:412 database:900 |
Rv3543c fadE29 |
acyl-CoA dehydrogenase FadE29 | 995 | 944 ctx | neighborhood:778 database:500 textmining:919 |
Rv3542c chsH2 hyp |
hypothetical protein | 964 | 943 ctx | neighborhood:778 coexpression:427 experimental:508 |
Rv3544c fadE28 |
acyl-CoA dehydrogenase FadE28 | 988 | 942 ctx | neighborhood:778 database:500 textmining:815 |
Rv3667 acs |
acetyl-CoAsynthetase | 950 | 941 | coexpression:415 database:900 |
Rv1837c glcB |
malate synthase | 927 | 924 | database:900 |
Rv3710 leuA |
2-isopropylmalate synthase | 925 | 923 | database:900 |
Rv1323 fadA4 |
acetyl-CoA acetyltransferase | 923 | 923 | database:900 |
Rv2503c scoB |
succinyl-CoA:3-ketoacid-CoA transferase subunit B | 927 | 922 | database:900 |
Rv0243 fadA2 |
acetyl-CoA acetyltransferase FadA | 925 | 922 | database:900 |
Rv2504c scoA |
succinyl-CoA:3-ketoacid-CoA transferase subunit A | 924 | 921 | database:900 |
Rv1074c fadA3 |
beta-ketoacyl CoA thiolase FadA | 916 | 916 | database:900 |
Rv0859 fadA |
acyltransferase | 913 | 914 | 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
- Legacy H37Rv annotation: acetyl-CoA acetyltransferase FadA
- MTBC0 PGAP product: steroid 3-ketoacyl-CoA thiolase
- Pfam (hmmscan --cut_ga): Thiolase_N PF00108.30 (E=5e-52), Thiolase_C PF02803.25 (E=9e-39)
- (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_218063.1)
- Domains: Pfam-A via hmmscan --cut_ga — Thiolase_N (PF00108.30), 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 I6XHI4 (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 —
152 functional partner(s); context anchor
fadB2 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003763|Rv3546|fadA5 MGYPVIVEATRSPIGKRNGWLSGLHATELLGAVQKAVVDKAGIQSGLHAGDVEQVIGGCVTQFGEQSNNISRVAWLTAGLPEHVGATTVDCQCGSGQQANHLIAGLIAAGAIDVGIACGIEAMSRVGLGANAGPDRSLIRAQSWDIDLPNQFEAAERIAKRRGITREDVDVFGLESQRRAQRAWAEGRFDREISPIQAPVLDEQNQPTGERRLVFRDQGLRETTMAGLGELKPVLEGGIHTAGTSSQISDGAAAVLWMDEAVARAHGLTPRARIVAQALVGAEPYYHLDGPVQSTAKVLEKAGMKIGDIDIVEINEAFASVVLSWARVHEPDMDRVNVNGGAIALGHPVGCTGSRLITTALHELERTDQSLALITMCAGGALSTGTIIERI