fadD19 Resolved · high auto-curated
H37Rv Rv3515c · MTBC0 - ·
548 aa · 3950824–3952470 (-) ·
RefSeq YP_177983.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | acyl-CoA synthetase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Acyl-CoA synthetase. Pfam: AMP-binding (PF00501.35), AMP-binding_C (PF13193.13). |
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 |
P9WQ51
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Medium/long-chain-fatty-acid--CoA/3-oxocholest-4-en-26-oate--CoA ligase |
| EC (curated) |
EC 6.2.1.2, EC 6.2.1.3, EC 6.2.1.42
|
| Curated function | Catalyzes the activation of medium/long-chain fatty acids as acyl-coenzyme A (acyl-CoA), which are then transferred to the multifunctional polyketide synthase (PKS) type III for further chain extension. Also involved in the degradation of cholesterol via the degradation of the side chains of C-24 branched-chain sterols. Catalyzes the ATP-dependent CoA thioesterification of the sterol 3-oxocholest-4-en-26-oate to yield 3-oxocholest-4-en-26-oyl-CoA. It can also use 3beta-hydroxy-5-cholesten-26-oate. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolismQ Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | fadD19 |
| eggNOG description | COG0318 Acyl-CoA synthetases (AMP-forming) AMP-acid ligases II |
| Orthologous group | COG0318 |
| EC number |
EC 6.2.1.42
|
| KEGG orthology |
K18688
|
| Gene Ontology (52) |
GO:0001676, GO:0003674, GO:0003824, GO:0004467, GO:0005575, GO:0005618, GO:0005623, GO:0006082, GO:0006629, GO:0006631, GO:0008150, GO:0008152 +40 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 | 1.95 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 6 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 |
|---|---|---|---|---|
AMP-binding | PF00501.35 | 5.2e-61 | 12–385 | AMP-binding enzyme |
AMP-binding_C | PF13193.13 | 1.2e-15 | 446–521 | AMP-binding enzyme C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: fadE26 (acyl-CoA dehydrogenase FadE26), high confidence from genomic context alone (score 816 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3504 fadE26 |
acyl-CoA dehydrogenase FadE26 | 936 | 816 ctx | cooccurence:538 database:500 textmining:669 |
Rv3545c cyp125 |
steroid C26-monooxygenase | 908 | 807 | database:670 textmining:546 |
Rv3516 echA19 |
enoyl-CoA hydratase EchA19 | 964 | 789 ctx | neighborhood:607 textmining:836 |
Rv3522 ltp4 |
lipid transfer protein | 955 | 751 ctx | cooccurence:685 textmining:829 |
Rv1750c fadD1 |
fatty-acid--CoA ligase FadD1 | 816 | 749 ctx | cooccurence:748 |
Rv3521 hyp |
hypothetical protein | 878 | 745 ctx | cooccurence:733 textmining:543 |
Rv3541c chsH1 hyp |
hypothetical protein | 741 | 741 ctx | cooccurence:703 |
Rv3542c chsH2 hyp |
hypothetical protein | 710 | 711 ctx | cooccurence:663 |
Rv0719 rplF |
50S ribosomal protein L6 | 694 | 694 | experimental:402 database:510 |
Rv1527c pks5 |
polyketide synthase | 706 | 681 | |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 706 | 680 | |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 712 | 679 | |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 704 | 679 | |
Rv2048c pks12 |
polyketide synthase | 704 | 679 | |
Rv3505 fadE27 |
acyl-CoA dehydrogenase FadE27 | 882 | 660 | database:500 textmining:668 |
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): acyl-CoA synthetase
- Pfam (hmmscan --cut_ga): AMP-binding PF00501.35 (E=5e-61), AMP-binding_C PF13193.13 (E=1e-15)
- (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 YP_177983.1)
- Domains: Pfam-A via hmmscan --cut_ga — AMP-binding (PF00501.35), AMP-binding_C (PF13193.13)
- 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
COG0318 - Curated reference: UniProt P9WQ51 (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 —
136 functional partner(s); context anchor
fadE26 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3515c|fadD19 MAVALNIADLAEHAIDAVPDRVAVICGDEQLTYAQLEDKANRLAHHLIDQGVQKDDKVGLYCRNRIEIVIAMLGIVKAGAILVNVNFRYVEGELRYLFDNSDMVALVHERRYADRVANVLPDTPHVRTILVVEDGSDQDYRRYGGVEFYSAIAAGSPERDFGERSADAIYLLYTGGTTGFPKGVMWRHEDIYRVLFGGTDFATGEFVKDEYDLAKAAAANPPMIRYPIPPMIHGATQSATWMALFSGQTTVLAPEFNADEVWRTIHKHKVNLLFFTGDAMARPLVDALVKGNDYDLSSLFLLASTAALFSPSIKEKLLELLPNRVITDSIGSSETGFGGTSVVAAGQAHGGGPRVRIDHRTVVLDDDGNEVKPGSGMRGVIAKKGNIPVGYYKDEKKTAETFRTINGVRYAIPGDYAQVEEDGTVTMLGRGSVSINSGGEKVYPEEVEAALKGHPDVFDALVVGVPDPRYGQQVAAVVQARPGCRPSLAELDSFVRSEIAGYKVPRSLWFVDEVKRSPAGKPDYRWAKEQTEARPADDVHAGHVTSGG