fadD13 Resolved · high auto-curated
H37Rv Rv3089 · MTBC0 mtbc0_003283 ·
503 aa · 3477125–3478636 (+) ·
RefSeq NP_217605.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | long chain-fatty-acid--CoA ligase FadD13 |
|---|---|
| MTBC0 PGAP re-annotation | long-chain-fatty-acid--CoA ligase FadD13 |
| Revised (this work) | Long-chain-fatty-acid--CoA ligase FadD13. 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 |
P9WQ37
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Long-chain-fatty-acid--CoA ligase FadD13 |
| EC (curated) |
EC 6.2.1.3
|
| Curated function | Required for maintaining the appropriate mycolic acid composition and permeability of the envelope on its exposure to acidic pH. 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. It has preference for the fatty acid with long chain length in the following order: hexacosanoic acid (C26), tetracosanoic acid (C24) and palmitic acid (C16). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolismQ Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | fadD13 |
| eggNOG description | COG0318 Acyl-CoA synthetases (AMP-forming) AMP-acid ligases II |
| Orthologous group | COG0318 |
| 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
|
| Gene Ontology (31) |
GO:0003674, GO:0003824, GO:0004321, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0008150, GO:0009268, GO:0009628 +19 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 | 0.144 · 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 | 3.6e-84 | 9–363 | AMP-binding enzyme |
AMP-binding_C | PF13193.13 | 1.3e-19 | 413–487 | AMP-binding enzyme C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: tgs4 (diacyglycerol O-acyltransferase), high confidence from genomic context alone (score 983 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3088 tgs4 |
diacyglycerol O-acyltransferase | 997 | 983 ctx | neighborhood:882 coexpression:860 textmining:833 |
Rv3087 |
diacyglycerol O-acyltransferase | 989 | 972 ctx | neighborhood:801 coexpression:863 textmining:656 |
Rv3086 adhD |
alcohol dehydrogenase D | 983 | 955 ctx | neighborhood:693 coexpression:860 textmining:650 |
Rv3084 lipR |
acetyl-hydrolase LipR | 988 | 953 ctx | neighborhood:616 coexpression:866 textmining:759 |
Rv3083 mymA |
FAD-containing monooxygenase MymA | 989 | 945 ctx | neighborhood:616 coexpression:862 textmining:809 |
Rv3085 sadH |
oxidoreductase SadH | 973 | 945 ctx | neighborhood:616 coexpression:863 textmining:542 |
Rv2947c pks15 |
polyketide synthase | 770 | 729 ctx | fusion:531 |
Rv1180 pks3 |
polyketide beta-ketoacyl synthase | 719 | 699 ctx | fusion:477 |
Rv0719 rplF |
50S ribosomal protein L6 | 695 | 695 | experimental:402 database:510 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 707 | 682 | |
Rv1527c pks5 |
polyketide synthase | 705 | 680 | |
Rv2048c pks12 |
polyketide synthase | 705 | 680 | |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 743 | 679 | |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 704 | 679 | |
Rv1663 pks17 |
polyketide synthase | 689 | 674 ctx | fusion: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
- Legacy H37Rv annotation: long chain-fatty-acid--CoA ligase FadD13
- MTBC0 PGAP product: long-chain-fatty-acid--CoA ligase FadD13
- Pfam (hmmscan --cut_ga): AMP-binding PF00501.35 (E=4e-84), AMP-binding_C PF13193.13 (E=1e-19)
- (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_217605.1)
- 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 P9WQ37 (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 —
92 functional partner(s); context anchor
tgs4 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003283|Rv3089|fadD13 MKNIGWMLRQRATVSPRLQAYVEPSTDVRMTYAQMNALANRCADVLTALGIAKGDRVALLMPNSVEFCCLFYGAAKLGAVAVPINTRLAAPEVSFILSDSGSKVVIYGAPSAPVIDAIRAQADPPGTVTDWIGADSLAERLRSAAADEPAVECGGDDNLFIMYTSGTTGHPKGVVHTHESVHSAASSWASTIDVRYRDRLLLPLPMFHVAALTTVIFSAMRGVTLISMPQFDATKVWSLIVEERVCIGGAVPAILNFMRQVPEFAELDAPDFRYFITGGAPMPEALIKIYAAKNIEVVQGYALTESCGGGTLLLSEDALRKAGSAGRATMFTDVAVRGDDGVIREHGEGEVVIKSDILLKEYWNRPEATRDAFDNGWFRTGDIGEIDDEGYLYIKDRLKDMIISGGENVYPAEIESVIIGVPGVSEVAVIGLPDEKWGEIAAAIVVADQNEVSEQQIVEYCGTRLARYKLPKKVIFAEAIPRNPTGKILKTVLREQYSATVPK