fadD26 Resolved · high auto-curated
H37Rv Rv2930 · MTBC0 mtbc0_003113 ·
583 aa · 3264694–3266445 (+) ·
RefSeq NP_217446.2
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | fatty-acid--CoA ligase FadD26 |
|---|---|
| MTBC0 PGAP re-annotation | long-chain-fatty-acid--AMP ligase FAAL26/FadD26 |
| Revised (this work) | Long-chain-fatty-acid--AMP ligase FAAL26/FadD26. 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 |
P9WQ43
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Long-chain-fatty-acid--AMP ligase FadD26 |
| EC (curated) |
EC 6.2.1.59
|
| Curated function | Catalyzes the activation of long-chain fatty acids as acyl-adenylates (acyl-AMP), which are then transferred to the multifunctional polyketide synthase PpsA for further chain extension. Catalyzes the adenylation of the long-chain fatty acids eicosanoate (C20) or docosanoate (C22), and potentially the very-long-chain fatty acid lignocerate (C24). Involved in the biosynthesis of phthiocerol dimycocerosate (DIM A) and phthiodiolone dimycocerosate (DIM B). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolismQ Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | fadD26 |
| 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 (77) |
GO:0003674, GO:0003824, GO:0005575, GO:0005623, GO:0005886, GO:0006066, GO:0006082, GO:0006629, GO:0006631, GO:0006633, GO:0008150, GO:0008152 +65 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 | 0.613 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 9 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 | 8.5e-59 | 12–417 | AMP-binding enzyme |
AMP-dom_DIP2-like | PF23024.2 | 1.3e-07 | 465–574 | Disco-interacting protein 2-like, AMP domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ppsA (phthiocerol synthesis polyketide synthase type I PpsA), high confidence from genomic context alone (score 994 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2931 ppsA |
phthiocerol synthesis polyketide synthase type I PpsA | 998 | 994 ctx | neighborhood:801 coexpression:825 database:650 textmining:814 |
Rv2932 ppsB |
phthiocerol synthesis polyketide synthase type I PpsB | 995 | 993 ctx | neighborhood:801 coexpression:779 database:650 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 978 | 970 ctx | neighborhood:797 database:650 |
Rv2935 ppsE |
phthiocerol synthesis polyketide synthase type I PpsE | 983 | 960 ctx | neighborhood:780 database:650 textmining:597 |
Rv2934 ppsD |
phthiocerol synthesis polyketide synthase type I PpsD | 976 | 960 ctx | neighborhood:774 database:650 textmining:430 |
Rv2380c mbtE |
peptide synthetase | 902 | 898 ctx | fusion:685 experimental:465 |
Rv2947c pks15 |
polyketide synthase | 847 | 836 ctx | fusion:625 |
Rv2936 drrA |
daunorubicin ABC transporter ATP-binding protein DrrA | 897 | 784 ctx | neighborhood:767 textmining:546 |
Rv2937 drrB |
daunorubicin ABC transporter permease DrrB | 844 | 778 ctx | neighborhood:770 |
Rv2938 drrC |
daunorubicin ABC transporter permease DrrC | 841 | 776 ctx | neighborhood:765 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 879 | 775 | textmining:484 |
Rv0405 pks6 |
membrane bound polyketide synthase | 774 | 760 | |
Rv2382c mbtC |
polyketide synthetase | 756 | 748 ctx | fusion:468 |
Rv1180 pks3 |
polyketide beta-ketoacyl synthase | 844 | 738 ctx | fusion:418 textmining:431 |
Rv1664 pks9 |
polyketide synthase | 734 | 735 ctx | fusion:418 |
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 FadD26
- MTBC0 PGAP product: long-chain-fatty-acid--AMP ligase FAAL26/FadD26
- Pfam (hmmscan --cut_ga): AMP-binding PF00501.35 (E=8e-59), AMP-dom_DIP2-like PF23024.2 (E=1e-07)
- (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_217446.2)
- 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 P9WQ43 (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 —
86 functional partner(s); context anchor
ppsA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003113|Rv2930|fadD26 MPVTDRSVPSLLQERADQQPDSTAYTYIDYGSDPKGFADSLTWSQVYSRACIIAEELKLCGLPGDRVAVLAPQGLEYVLAFLGALQAGFIAVPLSTPQYGIHDDRVSAVLQDSKPVAILTTSSVVGDVTKYAASHDGQPAPVVVEVDLLDLDSPRQMPAFSRQHTGAAYLQYTSGSTRTPAGVIVSHTNVIANVTQSMYGYFGDPAKIPTGTVVSWLPLYHDMGLILGICAPLVARRRAVLMSPMSFLRRPARWMQLLATSGRCFSAAPNFAFELAVRRTSDQDMAGLDLRDVVGIVSGSERIHVATVRRFIERFAPYNLSPTAIRPSYGLAEATLYVAAPEAGAAPKTVRFDYEQLTAGQARPCGTDGSVGTELISYGSPDPSSVRIVNPETMVENPPGVVGEIWVHGDHVTMGYWQKPKQTAQVFDAKLVDPAPAAPEGPWLRTGDLGVISDGELFIMGRIKDLLIVDGRNHYPDDIEATIQEITGGRAAAIAVPDDITEQLVAIIEFKRRGSTAEEVMLKLRSVKREVTSAISKSHSLRVADLVLVSPGSIPITTSGKIRRSACVERYRSDGFKRLDVAV