fadD32 Resolved · high auto-curated
H37Rv Rv3801c · MTBC0 - ·
637 aa · 4261153–4263066 (-) ·
RefSeq NP_218318.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | long-chain-fatty-acid--AMP ligase FadD32 |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Long-chain-fatty-acid--AMP ligase FadD32. Pfam: AMP-binding (PF00501.35). |
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 |
O53580
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Long-chain-fatty-acid--AMP ligase FadD32 |
| EC (curated) |
EC 6.2.1.20
|
| Curated function | Involved in the biosynthesis of mycolic acids. Catalyzes the activation of long-chain fatty acids as acyl-adenylates (acyl-AMP), which are then transferred to the phosphopantetheine arm of the polyketide synthase Pks13 for further chain extension. Can use dodecanoate (C12), tetradecanoate (C14) and hexadecanoate (C16). In vitro, displays a preference for long-chain over medium and short-chain fatty acid substrates. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolismQ Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | fadD32 |
| 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 (48) |
GO:0003674, GO:0003824, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0006082, GO:0006629, GO:0006631, GO:0006633, GO:0008150, GO:0008152 +36 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 | 0.401 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 6 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 | 8.4e-51 | 34–439 | AMP-binding enzyme |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: pks13 (polyketide synthase), high confidence from genomic context alone (score 994 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3800c pks13 |
polyketide synthase | 999 | 994 ctx | neighborhood:881 cooccurence:413 coexpression:838 textmining:977 |
Rv3799c accD4 |
propionyl-CoA carboxylase subunit beta AccD | 997 | 974 ctx | neighborhood:881 coexpression:761 textmining:924 |
Rv2380c mbtE |
peptide synthetase | 868 | 862 ctx | fusion:587 experimental:465 |
Rv3802c |
membrane protein | 838 | 779 ctx | neighborhood:719 |
Rv2379c mbtF |
peptide synthetase | 777 | 775 ctx | cooccurence:575 |
Rv2846c efpA |
MFS-type transporter EfpA | 823 | 770 | coexpression:770 |
Rv3285 accA3 |
bifunctional protein acetyl-/propionyl-CoA carboxylase subunit alpha AccA | 917 | 763 | coexpression:759 textmining:667 |
Rv0101 nrp |
peptide synthetase Nrp | 756 | 744 ctx | cooccurence:588 |
Rv2932 ppsB |
phthiocerol synthesis polyketide synthase type I PpsB | 756 | 742 | |
Rv0405 pks6 |
membrane bound polyketide synthase | 753 | 741 | |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 760 | 740 | |
Rv2947c pks15 |
polyketide synthase | 766 | 732 ctx | fusion:402 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 753 | 732 | |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 750 | 729 | |
Rv1527c pks5 |
polyketide synthase | 748 | 727 |
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): long-chain-fatty-acid--AMP ligase FadD32
- Pfam (hmmscan --cut_ga): AMP-binding PF00501.35 (E=8e-51)
- (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_218318.1)
- Domains: Pfam-A via hmmscan --cut_ga — AMP-binding (PF00501.35)
- 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 O53580 (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 —
101 functional partner(s); context anchor
pks13 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3801c|fadD32 MFVTGESGMAYHNPFIVNGKIRFPANTNLVRHVEKWAKVRGDKLAYRFLDFSTERDGVARDILWSDFSARNRAVGARLQQVTQPGDRVAILCPQNLDYLISFFGALYSGRIAVPLFDPAEPGHVGRLHAVLDDCAPSTILTTTDSAEGVRKFIRARSAKERPRVIAVDAVPTEVAATWQQPEANEETVAYLQYTSGSTRIPSGVQITHLNLPTNVVQVLNALEGQEGDRGVSWLPFFHDMGLITVLLASVLGHSFTFMTPAAFVRRPGRWIRELARKPGETGGTFSAAPNFAFEHAAVRGVPRDDEPPLDLSNVKGILNGSEPVSPASMRKFFEAFAPYGLKQTAVKPSYGLAEATLFVSTTPMDEVPTVIHVDRDELNNQRFVEVAADAPNAVAQVSAGKVGVSEWAVIVDADTASELPDGQIGEIWLHGNNLGTGYWGKEEESAQTFKNILKSRISESRAEGAPDDALWVRTGDYGTYFKDHLYIAGRIKDLVIIDGRNHYPQDLECTAQESTKALRVGYAAAFSVPANQLPQTVFDDSHAGLKFDPEDTSEQLVIVGERAAGTHKLDHQPIVDDIRAAIAVGHGVTVRDVLLVSAGTIPRTSSGKIGRRACRAAYLDGSLRSGVGSPTVFATSD