fadD25 Resolved · high auto-curated
H37Rv Rv1521 · MTBC0 mtbc0_001628 ·
583 aa · 1722111–1723862 (+) ·
RefSeq NP_216037.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | fatty-acid--CoA ligase FadD25 |
|---|---|
| MTBC0 PGAP re-annotation | fatty-acid--AMP ligase FAAL25/FadD25 |
| Revised (this work) | Fatty-acid--AMP ligase FAAL25/FadD25. Pfam: AMP-binding (PF00501.35), AMP-dom_DIP2-like (PF23024.2). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WQ45
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Putative fatty-acid--CoA ligase fadD25 |
| EC (curated) |
EC 6.2.1.-
|
UniProt still lists this protein as Putative fatty-acid--CoA ligase fadD25; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolismQ Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | fadD25 |
| eggNOG description | Activates fatty acids by binding to coenzyme A |
| Orthologous group | COG0318 |
| EC number |
EC 2.7.7.95, EC 6.2.1.51
|
| KEGG orthology |
K00666, K12423, K12425, K12426, K12427, K12428, K21059
|
| Gene Ontology (35) |
GO:0003674, GO:0003824, GO:0005575, GO:0005623, GO:0005886, GO:0006082, GO:0006629, GO:0006631, GO:0006633, GO:0008150, GO:0008152, GO:0008610 +23 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 | 0.444 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 8 missense, 0 nonsense, 2 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 0.24% of strains (351) · clonal |
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 | 7.2e-56 | 13–419 | AMP-binding enzyme |
AMP-dom_DIP2-like | PF23024.2 | 3.4e-08 | 467–578 | Disco-interacting protein 2-like, AMP domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mbtE (peptide synthetase), high confidence from genomic context alone (score 955 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2380c mbtE |
peptide synthetase | 957 | 955 ctx | fusion:692 cooccurence:682 experimental:465 |
Rv2379c mbtF |
peptide synthetase | 869 | 868 ctx | fusion:506 cooccurence:642 |
Rv2947c pks15 |
polyketide synthase | 813 | 813 ctx | fusion:585 |
Rv0101 nrp |
peptide synthetase Nrp | 806 | 797 ctx | cooccurence:662 |
Rv2383c mbtB |
phenyloxazoline synthase | 789 | 767 ctx | fusion:510 |
Rv1180 pks3 |
polyketide beta-ketoacyl synthase | 761 | 762 ctx | fusion:454 |
Rv0405 pks6 |
membrane bound polyketide synthase | 771 | 760 | |
Rv2932 ppsB |
phthiocerol synthesis polyketide synthase type I PpsB | 772 | 759 | |
Rv2382c mbtC |
polyketide synthetase | 761 | 753 ctx | fusion:474 |
Rv1527c pks5 |
polyketide synthase | 769 | 747 | |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 768 | 746 | |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 765 | 745 | |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 765 | 741 | |
Rv1664 pks9 |
polyketide synthase | 730 | 731 ctx | fusion:408 |
Rv2931 ppsA |
phthiocerol synthesis polyketide synthase type I PpsA | 736 | 726 |
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: fatty-acid--CoA ligase FadD25
- MTBC0 PGAP product: fatty-acid--AMP ligase FAAL25/FadD25
- Pfam (hmmscan --cut_ga): AMP-binding PF00501.35 (E=7e-56), AMP-dom_DIP2-like PF23024.2 (E=3e-08)
- (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_216037.1)
- Domains: Pfam-A via hmmscan --cut_ga — AMP-binding (PF00501.35), AMP-dom_DIP2-like (PF23024.2)
- 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 P9WQ45 (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 —
84 functional partner(s); context anchor
mbtE - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001628|Rv1521|fadD25 MSVVESSLPGVLRERASFQPNDKALTFIDYERSWDGVEETLTWSQLYRRTLNLAAQLREHGSTGDRALILAPQSLDYVVSFIASLQAGIVAVPLSIPQGGAHDERTVSVFADTAPAIVLTASSVVDNVVEYVQPQPGQNAPAVIEVDRLDLDARPSSGSRSAAHGHPDILYLQYTSGSTRTPAGVMVSNKNLFANFEQIMTSYYGVYGKVAPPGSTVVSWLPFYHDMGFVLGLILPILAGIPAVLTSPIGFLQRPARWIQMLASNTLAFTAAPNFAFDLASRKTKDEDMEGLDLGGVHGILNGSERVQPVTLKRFIDRFAPFNLDPKAIRPSYGMAEATVYVATRKAGQPPKIVQFDPQKLPDGQAERTESDGGTPLVSYGIVDTQLVRIVDPDTGIERPAGTIGEIWVHGDNVAIGYWQKPEATERTFSATIVNPSEGTPAGPWLRTGDSGFLSEGELFIMGRIKDLLIVYGRNHSPDDIEATIQTISPGRCAAIAVSEHGAEKLVAIIELKKKDESDDEAAERLGFVKREVTSAISKSHGLSVADLVLVSPGSIPITTSGKIRRAQCVELYRQDEFTRLDA