fadD6 Resolved · high auto-curated
H37Rv Rv1206 · MTBC0 mtbc0_001294 ·
597 aa · 1357774–1359567 (+) ·
RefSeq NP_215722.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | fatty-acid--CoA ligase FadD6 |
|---|---|
| MTBC0 PGAP re-annotation | long-chain-acyl-CoA synthetase FadD6 |
| Revised (this work) | Long-chain-acyl-CoA synthetase FadD6. 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 |
O05307
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Medium/long-chain-fatty-acid--CoA ligase FadD6 |
| 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). May play a role in the uptake of fatty acids by trapping them metabolically as CoA esters. May also play an important role in the channeling of fatty acids into triacylglycerol (TAG) for use by Mycobacterium during its dormancy. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolismQ Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | fadD6 |
| eggNOG description | Activates fatty acids by binding to coenzyme A |
| Orthologous group | COG0318 |
| KEGG orthology |
K00666
|
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 | 0.528 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 3 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 | 1.3e-58 | 53–405 | AMP-binding enzyme |
AMP-binding_C | PF13193.13 | 9.8e-10 | 473–549 | AMP-binding enzyme C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: gpgS (glucosyl-3-phosphoglycerate synthase), high confidence from genomic context alone (score 818 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1205 log hyp |
hypothetical protein | 853 | 853 ctx | neighborhood:811 |
Rv1208 gpgS |
glucosyl-3-phosphoglycerate synthase | 818 | 818 ctx | neighborhood:796 |
Rv1207 folP2 |
dihydropteroate synthase | 798 | 798 ctx | neighborhood:796 |
Rv1210 tagA |
DNA-3-methyladenine glycosylase I TagA | 756 | 756 ctx | neighborhood:756 |
Rv1209 hyp |
hypothetical protein | 728 | 728 ctx | neighborhood:728 |
Rv0719 rplF |
50S ribosomal protein L6 | 696 | 696 | experimental:402 database:510 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 707 | 682 | |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 709 | 681 | |
Rv2048c pks12 |
polyketide synthase | 706 | 680 | |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 705 | 680 | |
Rv1527c pks5 |
polyketide synthase | 705 | 680 | |
Rv3800c pks13 |
polyketide synthase | 706 | 638 | |
Rv2946c pks1 |
polyketide synthase | 664 | 632 | |
Rv1661 pks7 |
polyketide synthase | 633 | 612 | |
Rv1181 pks4 |
polyketide beta-ketoacyl synthase | 633 | 612 |
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 FadD6
- MTBC0 PGAP product: long-chain-acyl-CoA synthetase FadD6
- Pfam (hmmscan --cut_ga): AMP-binding PF00501.35 (E=1e-58), AMP-binding_C PF13193.13 (E=1e-09)
- (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_215722.1)
- 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 O05307 (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 —
81 functional partner(s); context anchor
gpgS - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001294|Rv1206|fadD6 MSDYYGGAHTTVRLIDLATRMPRVLADTPVIVRGAMTGLLARPNSKASIGTVFQDRAARYGDRVFLKFGDQQLTYRDANATANRYAAVLAARGVGPGDVVGIMLRNSPSTVLAMLATVKCGAIAGMLNYHQRGEVLAHSLGLLDAKVLIAESDLVSAVAECGASRGRVAGDVLTVEDVERFATTAPATNPASASAVQAKDTAFYIFTSGTTGFPKASVMTHHRWLRALAVFGGMGLRLKGSDTLYSCLPLYHNNALTVAVSSVINSGATLALGKSFSASRFWDEVIANRATAFVYIGEICRYLLNQPAKPTDRAHQVRVICGNGLRPEIWDEFTTRFGVARVCEFYAASEGNSAFINIFNVPRTAGVSPMPLAFVEYDLDTGDPLRDASGRVRRVPDGEPGLLLSRVNRLQPFDGYTDPVASEKKLVRNAFRDGDCWFNTGDVMSPQGMGHAAFVDRLGDTFRWKGENVATTQVEAALASDQTVEECTVYGVQIPRTGGRAGMAAITLRAGAEFDGQALARTVYGHLPGYALPLFVRVVGSLAHTTTFKSRKVELRNQAYGADIEDPLYVLAGPDEGYVPYYAEYPEEVSLGRRPQG