fadD10 Resolved · high auto-curated
H37Rv Rv0099 · MTBC0 - ·
540 aa · 108156–109778 (+) ·
RefSeq NP_214613.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | fatty-acid--CoA ligase FadD10 |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Fatty-acid--CoA ligase FadD10. 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 |
P9WQ55
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Medium/long-chain-fatty-acid--[acyl-carrier-protein] ligase FadD10 |
| EC (curated) |
EC 6.2.1.20, EC 6.2.1.47
|
| Curated function | Acyl:acyl-carrier protein ligase involved in the biosynthesis of a unique class of isonitrile lipopeptides (INLPs) that seem to function as virulence factors in M.tuberculosis and to play a role in metal acquisition. Catalyzes the activation of medium/long-chain fatty acids as acyl-adenylates (acyl-AMP), which are then transferred to the phosphopantetheine arm of the acyl-carrier protein (ACP) Rv0100. Can use octanoate (C8), decanoate (C10), dodecanoate (C12), tetradecanoate (C14) and hexadecanoate (C16), but not hexanoate (C6) in vitro. Long chain saturated fatty acids are the preferred subst. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolismQ Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | fadD10 |
| eggNOG description | AMP-binding enzyme C-terminal domain |
| Orthologous group | COG0318 |
| KEGG orthology |
K12422
|
| Gene Ontology (6) |
GO:0005575, GO:0005623, GO:0005886, GO:0016020, GO:0044464, GO:0071944
|
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 | 0.159 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 9 synonymous, 4 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 | 5.4e-58 | 21–389 | AMP-binding enzyme |
AMP-binding_C | PF13193.13 | 1.5e-10 | 439–519 | AMP-binding enzyme C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: nrp (peptide synthetase Nrp), high confidence from genomic context alone (score 989 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0101 nrp |
peptide synthetase Nrp | 991 | 989 ctx | neighborhood:882 coexpression:876 |
Rv0097 |
oxidoreductase | 994 | 985 ctx | neighborhood:785 cooccurence:530 coexpression:866 textmining:661 |
Rv0100 hyp |
hypothetical protein | 996 | 983 ctx | neighborhood:882 coexpression:860 textmining:803 |
Rv0098 fcoT |
fatty acyl CoA thioesterase FcoT | 988 | 967 ctx | neighborhood:776 coexpression:860 textmining:656 |
Rv0096 PPE1 |
PPE family protein PPE1 | 979 | 959 ctx | neighborhood:719 coexpression:860 textmining:511 |
Rv3513c fadD18 |
fatty-acid--CoA ligase FadD18 | 767 | 767 ctx | cooccurence:767 |
Rv0719 rplF |
50S ribosomal protein L6 | 696 | 696 | experimental:402 database:510 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 742 | 680 | |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 723 | 680 | |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 705 | 680 | |
Rv2048c pks12 |
polyketide synthase | 704 | 679 | |
Rv1527c pks5 |
polyketide synthase | 704 | 679 | |
Rv1181 pks4 |
polyketide beta-ketoacyl synthase | 699 | 660 | |
Rv3800c pks13 |
polyketide synthase | 727 | 638 | |
Rv2380c mbtE |
peptide synthetase | 651 | 635 | experimental:465 |
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): fatty-acid--CoA ligase FadD10
- Pfam (hmmscan --cut_ga): AMP-binding PF00501.35 (E=5e-58), AMP-binding_C PF13193.13 (E=1e-10)
- (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_214613.1)
- 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 P9WQ55 (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 —
91 functional partner(s); context anchor
nrp - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0099|fadD10 MGGKKFQAMPQLPSTVLDRVFEQARQQPEAIALRRCDGTSALRYRELVAEVGGLAADLRAQSVSRGSRVLVISDNGPETYLSVLACAKLGAIAVMADGNLPIAAIERFCQITDPAAALVAPGSKMASSAVPEALHSIPVIAVDIAAVTRESEHSLDAASLAGNADQGSEDPLAMIFTSGTTGEPKAVLLANRTFFAVPDILQKEGLNWVTWVVGETTYSPLPATHIGGLWWILTCLMHGGLCVTGGENTTSLLEILTTNAVATTCLVPTLLSKLVSELKSANATVPSLRLVGYGGSRAIAADVRFIEATGVRTAQVYGLSETGCTALCLPTDDGSIVKIEAGAVGRPYPGVDVYLAATDGIGPTAPGAGPSASFGTLWIKSPANMLGYWNNPERTAEVLIDGWVNTGDLLERREDGFFYIKGRSSEMIICGGVNIAPDEVDRIAEGVSGVREAACYEIPDEEFGALVGLAVVASAELDESAARALKHTIAARFRRESEPMARPSTIVIVTDIPRTQSGKVMRASLAAAATADKARVVVRG