fadD8 Resolved · high auto-curated
H37Rv Rv0551c · MTBC0 mtbc0_000580 ·
571 aa · 644647–646362 (-) ·
RefSeq NP_215065.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | fatty-acid--CoA ligase FadD8 |
|---|---|
| MTBC0 PGAP re-annotation | fatty-acid--CoA ligase FadD8 |
| Revised (this work) | Fatty-acid--CoA ligase FadD8. 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.
Curated reference (UniProt)
| UniProt |
O06417
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Medium/long-chain-fatty-acid--CoA ligase FadD8 |
| EC (curated) |
EC 6.2.1.2, EC 6.2.1.3
|
| Curated function | Catalyzes the activation of medium/long-chain fatty acids as acyl-coenzyme A (acyl-CoA). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolismQ Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | fadD8 |
| eggNOG description | Activates fatty acids by binding to coenzyme A |
| Orthologous group | COG0318 |
| KEGG orthology |
K00666
|
| Gene Ontology (17) |
GO:0003674, GO:0005488, GO:0005515, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005777, GO:0042579, GO:0043226, GO:0043227, GO:0043229 +5 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 | 0.808 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 7 missense, 0 nonsense, 2 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 0.26% of strains (373) · 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 | 1.3e-69 | 59–420 | AMP-binding enzyme |
AMP-binding_C | PF13193.13 | 7.6e-20 | 470–552 | AMP-binding enzyme C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: menC (muconate cycloisomerase), high confidence from genomic context alone (score 802 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0553 menC |
muconate cycloisomerase | 802 | 802 ctx | neighborhood:780 |
Rv0552 hyp |
hypothetical protein | 792 | 793 ctx | neighborhood:784 |
Rv0719 rplF |
50S ribosomal protein L6 | 695 | 695 | experimental:402 database:510 |
Rv1527c pks5 |
polyketide synthase | 717 | 693 | |
Rv2048c pks12 |
polyketide synthase | 705 | 680 | |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 704 | 679 | |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 704 | 679 | |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 704 | 679 | |
Rv2947c pks15 |
polyketide synthase | 667 | 668 ctx | fusion:427 |
Rv0554 bpoC |
non-heme bromoperoxidase BpoC | 661 | 660 ctx | neighborhood:614 |
Rv0548c menB |
1,4-dihydroxy-2-naphthoyl-CoA synthase | 670 | 656 ctx | neighborhood:654 |
Rv3800c pks13 |
polyketide synthase | 668 | 635 | |
Rv1663 pks17 |
polyketide synthase | 651 | 634 ctx | fusion:406 |
Rv0547c |
oxidoreductase | 641 | 632 ctx | neighborhood:630 |
Rv2946c pks1 |
polyketide synthase | 663 | 631 |
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 FadD8
- MTBC0 PGAP product: fatty-acid--CoA ligase FadD8
- Pfam (hmmscan --cut_ga): AMP-binding PF00501.35 (E=1e-69), AMP-binding_C PF13193.13 (E=8e-20)
- (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_215065.1)
- 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 O06417 (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 —
96 functional partner(s); context anchor
menC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000580|Rv0551c|fadD8 MSTAGDDAVGVPPACGGRSDAVGVPQLARESGAMRDQDCSGELLRSPTHNGHLLVGALKRHQNKPVLFLGDTRLTGGQLADRISQYIQAFEALGAGTGVAVGLLSLNRPEVLMIIGAGQARGYRRTALHPLGSLADHAYVLNDAGISSLIIDPNPMFVERALALLEQVDSLQQILTIGPVPDALKHVAVDLSAEAAKYQPQPLVAADLPPDQVIGLTYTGGTTGKPKGVIGTAQSIATMTSIQLAEWEWPANPRFLMCTPLSHAGAAFFTPTVIKGGEMIVLAKFDPAEVLRIIEEQRITATMLVPSMLYALLDHPDSHTRDLSSLETVYYGASAINPVRLAEAIRRFGPIFAQYYGQSEAPMVITYLAKGDHDEKRLTSCGRPTLFARVALLDEHGKPVKQGEVGEICVSGPLLAGGYWNLPDETSRTFKDGWLHTGDLAREDSDGFYYIVDRVKDMIVTGGFNVFPREVEDVVAEHPAVAQVCVVGAPDEKWGEAVTAVVVLRSNAARDEPAIEAMTAEIQAAVKQRKGSVQAPKRVVVVDSLPLTGLGKPDKKAVRARFWEGAGRAVG