Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | long-chain-fatty-acid--CoA ligase FadD15 |
|---|
| MTBC0 PGAP re-annotation | long-chain fatty acid--CoA ligase |
|---|
| Revised (this work) | Long-chain fatty acid--CoA ligase. Pfam: AMP-binding (PF00501.35), AMP-binding_C_3 (PF23562.3). |
|---|
Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53521
SwissProt · reviewed
· Evidence at protein level
|
|---|
| UniProt name | Long-chain-fatty-acid--CoA ligase FadD15 |
|---|
| EC (curated) |
EC 6.2.1.3
|
|---|
| Curated function | Catalyzes the activation of 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. |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
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| Preferred name | fadD15 |
|---|
| eggNOG description | long-chain-fatty-acid--CoA ligase |
|---|
| Orthologous group | COG1022 |
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| EC number |
EC 6.2.1.3
|
|---|
| KEGG orthology |
K01897
|
|---|
| KEGG pathways |
map00061, map00071, map01100, map01212, map02024, map03320, map04146, map04216, map04714, map04920
|
|---|
| KEGG modules |
M00086
|
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| Gene Ontology (40) |
GO:0001676, GO:0003674, GO:0003824, GO:0004467, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0006082, GO:0006629, GO:0006631, GO:0008150 +28 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 |
1.209 · diversifying/relaxed
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
4 synonymous, 11 missense, 3 nonsense, 3 frameshift
|
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| Disruption |
6 distinct premature-stop/frameshift site(s); most common in
17.64% of strains
(25622) · convergent
|
|---|
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 |
7.1e-73 | 28–426 |
AMP-binding enzyme |
AMP-binding_C_3 | PF23562.3 |
3.5e-17 | 463–599 |
AMP-binding enzyme C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv2524c fas |
fatty acid synthase |
952 |
933 |
database:900 |
Rv1550 fadD11 |
fatty-acid--CoA ligase FadD11 |
923 |
923 |
database:900 |
Rv0214 fadD4 |
fatty-acid--CoA ligase FadD4 |
924 |
922 |
database:900 |
Rv3097c lipY |
triacylglycerol lipase Lip |
809 |
803 |
database:800 |
Rv2185c TB16.3 hyp |
hypothetical protein |
679 |
679 ctx |
neighborhood:669 |
Rv2184c hyp |
hypothetical protein |
670 |
670 ctx |
neighborhood:649 |
Rv1389 gmk |
guanylate kinase |
648 |
648 |
database:591 |
Rv2183c hyp |
hypothetical protein |
623 |
623 ctx |
neighborhood:622 |
Rv0009 ppiA |
iron-regulated peptidyl-prolyl cis-trans isomerase PpiA |
617 |
616 |
database:428 |
Rv2186c hyp |
hypothetical protein |
607 |
607 ctx |
neighborhood:605 |
Rv2582 ppiB |
peptidyl-prolyl cis-trans isomerase B |
501 |
502 |
database:428 |
Rv1363c |
membrane protein |
502 |
500 |
|
Rv1362c |
membrane protein |
496 |
494 |
|
Rv3492c |
Mce associated protein |
527 |
491 |
|
Rv0178 |
Mce associated membrane protein |
493 |
491 |
|
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: long-chain-fatty-acid--CoA ligase FadD15
- MTBC0 PGAP product: long-chain fatty acid--CoA ligase
- Pfam (hmmscan --cut_ga): AMP-binding PF00501.35 (E=7e-73), AMP-binding_C_3 PF23562.3 (E=4e-17)
- (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_216703.1)
- Domains: Pfam-A via hmmscan --cut_ga — AMP-binding (PF00501.35), AMP-binding_C_3 (PF23562.3)
- 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
COG1022
- Curated reference: UniProt
O53521
(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 —
54 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002322|Rv2187|fadD15
MREISVPAPFTVGEHDNVAAMVFEHERDDPDYVIYQRLIDGVWTDVTCAEAANQIRAAALGLISLGVQAGDRVVIFSATRYEWAILDFAILAVGAVTVPIYETSSAEQVRWVLQDSEAVVLFAETDSHATMVAELSGSVPALREVLQIAGSGPNALDRLTEAGASVDPAELTARLAALRSTDPATLIYTSGTTGRPKGCQLTQSNLVHEIKGARAYHPTLLRKGERLLVFLPLAHVLARAISMAAFHSKVTVGFTSDIKNLLPMLAVFKPTVVVSVPRVFEKVYNTAEQNAANAGKGRIFAIAAQTAVDWSEACDRGGPGLLLRAKHAVFDRLVYRKLRAALGGNCRAAVSGGAPLGARLGHFYRGAGLTIYEGYGLSETSGGVAISQFNDLKIGTVGKPVPGNSLRIADDGELLVRGGVVFSGYWRNEQATTEAFTDGWFKTGDLGAVDEDGFLTITGRKKEIIVTAGGKNVAPAVLEDQLRAHPLISQAVVVGDAKPFIGALITIDPEAFEGWKQRNSKTAGASVGDLATDPDLIAEIDAAVKQANLAVSHAESIRKFRILPVDFTEDTGELTPTMKVKRKVVAEKFASDIEAIYNKE
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