fadD29 Resolved · high auto-curated
H37Rv Rv2950c · MTBC0 - ·
619 aa · 3300596–3302455 (-) ·
RefSeq NP_217466.3
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | long-chain-fatty-acid--AMP ligase FadD29 |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Long-chain-fatty-acid--AMP ligase FadD29. Pfam: AMP-binding (PF00501.35), AMP-dom_DIP2-like (PF23024.2). |
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 |
P95141
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | 4-hydroxyphenylalkanoate adenylyltransferase |
| EC (curated) |
EC 6.2.1.51
|
| Curated function | Catalyzes the activation of long-chain fatty acids as acyl-adenylates (acyl-AMP), which are then transferred to the multifunctional polyketide synthase PpsA for further chain extension. Involved in the biosynthesis of phenolphthiocerol, which is an important intermediate in the biosynthesis of phenolic glycolipid (PGL), also called mycosid B. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolismQ Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | fadD29 |
| eggNOG description | Catalyzes the activation of the long-chain fatty acids (C22-24 fatty acids) as acyl-adenylates (acyl-AMP), which are then transferred to the multifunctional polyketide synthase PpsA for further chain extension. Involved in the biosynthesis of phenolphthiocerol, which is an important intermediate in the biosynthesis of phenolic glycolipid (mycosid B) |
| 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 (55) |
GO:0003674, GO:0003824, GO:0005575, GO:0005623, GO:0005886, GO:0006066, GO:0006082, GO:0006629, GO:0006631, GO:0006633, GO:0008150, GO:0008152 +43 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 | 0.737 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 10 missense, 1 nonsense, 3 frameshift |
| Disruption | 4 distinct premature-stop/frameshift site(s); most common in 1.03% of strains (1489) · convergent |
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 | 2.0e-60 | 47–453 | AMP-binding enzyme |
AMP-dom_DIP2-like | PF23024.2 | 5.4e-08 | 501–612 | Disco-interacting protein 2-like, AMP domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2949c (chorismate pyruvate-lyase), high confidence from genomic context alone (score 976 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2949c |
chorismate pyruvate-lyase | 983 | 976 ctx | neighborhood:835 coexpression:860 |
Rv2947c pks15 |
polyketide synthase | 976 | 974 ctx | neighborhood:675 fusion:461 coexpression:726 |
Rv2948c fadD22 |
p-hydroxybenzoyl--AMP ligase | 954 | 939 ctx | neighborhood:666 coexpression:791 |
Rv2380c mbtE |
peptide synthetase | 891 | 886 ctx | fusion:649 experimental:465 |
Rv2946c pks1 |
polyketide synthase | 917 | 877 ctx | neighborhood:703 |
Rv2932 ppsB |
phthiocerol synthesis polyketide synthase type I PpsB | 903 | 876 | database:650 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 876 | 866 | database:650 |
Rv2931 ppsA |
phthiocerol synthesis polyketide synthase type I PpsA | 875 | 861 | database:650 |
Rv2379c mbtF |
peptide synthetase | 848 | 847 ctx | fusion:436 cooccurence:635 |
Rv2935 ppsE |
phthiocerol synthesis polyketide synthase type I PpsE | 870 | 815 | database:650 |
Rv2934 ppsD |
phthiocerol synthesis polyketide synthase type I PpsD | 810 | 810 | database:650 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 784 | 763 | |
Rv0405 pks6 |
membrane bound polyketide synthase | 802 | 742 | |
Rv1180 pks3 |
polyketide beta-ketoacyl synthase | 735 | 736 ctx | fusion:416 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 769 | 729 |
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 FadD29
- Pfam (hmmscan --cut_ga): AMP-binding PF00501.35 (E=2e-60), AMP-dom_DIP2-like PF23024.2 (E=5e-08)
- (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_217466.3)
- Domains: Pfam-A via hmmscan --cut_ga — AMP-binding (PF00501.35), AMP-dom_DIP2-like (PF23024.2)
- 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 P95141 (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
Rv2949c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2950c|fadD29 MKTNSSFHAAGEVATQPAWGTGEQAAQPLNGSTSRFAMSESSLADLLQKAASQYPNRAAYKFIDYDTDPAGFTETVTWWQVHRRAMIVAEELWIYASSGDRVAILAPQGLEYIIAFMGVLQAGLIAVPLPVPQFGIHDERISSALRDSAPSIILTTSSVIDEVTTYAPHACAAQGQSAPIVVAVDALDLSSSRALDPTRFERPSTAYLQYTSGSTRAPAGVVLSHKNVITNCVQLMSDYIGDSEKVPSTPVSWLPFYHDMGLMLGIILPMINQDTAVLMSPMAFLQRPARWMQLLAKHRAQISSAPNFGFELAVRRTSDDDMAGLDLGHVRTIVTGAERVNVATLRRFTERFAPFNLSETAIRPSYGLAEATVYVATAGPGRAPKSVCFDYQQLSVGQAKRAENGSEGANLVSYGAPRASTVRIVDPETRMENPAGTVGEIWVQGDNVGLGYWRNPQQTEATFRARLVTPSPGTSEGPWLRTGDLGVIFEGELFITGRIKELLVVDGANHYPEDIEATIQEITGGRVVAIAVPDDRTEKLVTIIELMKRGRTDEEEKNRLRTVKREVASAISRSHRLRVADVVMVAPGSIPVTTSGKVRRSASVERYLHHEFSRLDAMA