fadD3 Resolved · high auto-curated
H37Rv Rv3561 · MTBC0 mtbc0_003778 ·
507 aa · 4025314–4026837 (+) ·
RefSeq NP_218078.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | fatty-acid--CoA ligase FadD3 |
|---|---|
| MTBC0 PGAP re-annotation | 3-((3aS%2C4S%2C7aS)-7a-methyl-1%2C5-dioxo-octahydro-1H-inden-4-yl)propanoate--CoA ligase FadD3 |
| Revised (this work) | 3-((3aS%2C4S%2C7aS)-7a-methyl-1%2C5-dioxo-octahydro-1H-inden-4-yl)propanoate--CoA ligase FadD3. 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 |
P96843
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | 3-[(3aS,4S,7aS)-7a-methyl-1,5-dioxo-octahydro-1H-inden-4-yl]propanoyl:CoA ligase |
| EC (curated) |
EC 6.2.1.41
|
| Curated function | Involved in the catabolism of the rings C and D of cholesterol. Catalyzes the ATP-dependent CoA thioesterification of 3aalpha-H-4alpha(3'-propanoate)-7abeta-methylhexahydro-1,5-indanedione (HIP) to yield HIP-CoA. It can also use the hydroxylated analogs of HIP, 5alpha-OH HIP and 1beta-OH HIP. It requires that the side chain at C17 is completely removed. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolismQ Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | fadD3 |
| eggNOG description | COG0318 Acyl-CoA synthetases (AMP-forming) AMP-acid ligases II |
| Orthologous group | COG0318 |
| EC number |
EC 6.2.1.41
|
| KEGG orthology |
K18687
|
| KEGG pathways |
map00984, map01100, map01120
|
| 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 | 0.278 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 13 synonymous, 10 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 | 3.1e-80 | 14–371 | AMP-binding enzyme |
AMP-binding_C | PF13193.13 | 1.5e-19 | 422–497 | AMP-binding enzyme C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: fadE31 (acyl-CoA dehydrogenase FadE31), high confidence from genomic context alone (score 973 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3562 fadE31 |
acyl-CoA dehydrogenase FadE31 | 990 | 973 ctx | neighborhood:801 coexpression:838 textmining:676 |
Rv3559c |
oxidoreductase | 969 | 969 ctx | neighborhood:588 coexpression:815 database:500 |
Rv3563 fadE32 |
acyl-CoA dehydrogenase FadE32 | 985 | 957 ctx | neighborhood:801 coexpression:793 textmining:685 |
Rv3564 fadE33 |
acyl-CoA dehydrogenase FadE33 | 969 | 955 ctx | neighborhood:801 coexpression:783 |
Rv3565 aspB |
aspartate aminotransferase AspB | 945 | 944 ctx | neighborhood:801 coexpression:732 |
Rv3560c fadE30 |
acyl-CoA dehydrogenase FadE30 | 978 | 937 ctx | neighborhood:588 coexpression:825 textmining:668 |
Rv3569c hsaD |
4,5-9,10-diseco-3-hydroxy-5,9,17-trioxoandrosta-1(10),2-diene-4-oate hydrolase | 954 | 923 | database:900 textmining:432 |
Rv3550 echA20 |
enoyl-CoA hydratase EchA20 | 977 | 883 | coexpression:841 textmining:818 |
Rv3552 |
CoA-transferase subunit beta | 881 | 877 | coexpression:810 |
Rv3551 |
CoA-transferase subunit alpha | 894 | 860 | coexpression:811 |
Rv3553 |
oxidoreductase | 909 | 808 | coexpression:805 textmining:547 |
Rv3549c |
short-chain type dehydrogenase/reductase | 798 | 794 | coexpression:735 |
Rv0719 rplF |
50S ribosomal protein L6 | 694 | 694 | experimental:402 database:510 |
Rv1180 pks3 |
polyketide beta-ketoacyl synthase | 685 | 685 ctx | fusion:457 |
Rv1527c pks5 |
polyketide synthase | 707 | 682 |
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 FadD3
- MTBC0 PGAP product: 3-((3aS%2C4S%2C7aS)-7a-methyl-1%2C5-dioxo-octahydro-1H-inden-4-yl)propanoate--CoA ligase FadD3
- Pfam (hmmscan --cut_ga): AMP-binding PF00501.35 (E=3e-80), 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_218078.1)
- 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 P96843 (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 —
112 functional partner(s); context anchor
fadE31 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003778|Rv3561|fadD3 MINDLRTVPAALDRLVRQLPDHTALIAEDRRFTSTELRDAVYGAAAALIALGVEPADRVAIWSPNTWHWVVACLAIHHAGAAVVPLNTRYTATEATDILDRAGAPVLFAAGLFLGADRAAGLDRAALPALRHVVRVPVEADDGTWDEFIATGAGALDAVAARAAAVAPQDVSDILFTSGTTGRSKGVLCAHRQSLSASASWAANGKITSDDRYLCINPFFHNFGYKAGILACLQTGATLIPHVTFDPLHALRAIERHRITVLPGPPTIYQSLLDHPARKDFDLSSLRFAVTGAATVPVVLVERMQSELDIDIVLTAYGLTEANGMGTMCRPEDDAVTVATTCGRPFADFELRIADDGEVLLRGPNVMVGYLDDTEATAAAIDADGWLHTGDIGAVDQAGNLRITDRLKDMYICGGFNVYPAEVEQVLARMDGVADAAVIGVPDQRLGEVGRAFVVARPGTGLDEASVIAYTREHLANFKTPRSVRFVDVLPRNAAGKVSKPQLRELG