fadD28 Resolved · high auto-curated
H37Rv Rv2941 · MTBC0 mtbc0_003124 ·
580 aa · 3304332–3306074 (+) ·
RefSeq NP_217457.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | long-chain-fatty-acid--AMP ligase FadD28 |
|---|---|
| MTBC0 PGAP re-annotation | fatty-acid--AMP ligase FAAL28/FadD28 |
| Revised (this work) | Fatty-acid--AMP ligase FAAL28/FadD28. 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.
Curated reference (UniProt)
| UniProt |
P9WQ59
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Long-chain-fatty-acid--AMP ligase FadD28 |
| EC (curated) |
EC 6.2.1.49
|
| Curated function | Involved in the biosynthesis of phthiocerol dimycocerosate (PDIM), a cell wall-associated lipid found only in pathogenic mycobacteria. Catalyzes the activation of long-chain fatty acids as acyl-adenylates (acyl-AMP), which are then transferred to the multifunctional polyketide synthase Mas for further chain extension. Probably plays a role in host phagosome maturation arrest (Probable). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolismQ Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | fadD28 |
| 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 (100) |
GO:0002682, GO:0002683, GO:0003674, GO:0003824, GO:0004321, GO:0005575, GO:0005623, GO:0005886, GO:0006082, GO:0006629, GO:0006631, GO:0006633 +88 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 | 0.148 · 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 | 3.7e-54 | 13–415 | AMP-binding enzyme |
AMP-dom_DIP2-like | PF23024.2 | 4.9e-07 | 463–574 | Disco-interacting protein 2-like, AMP domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mbtE (peptide synthetase), high confidence from genomic context alone (score 878 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2380c mbtE |
peptide synthetase | 883 | 878 ctx | fusion:623 experimental:465 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 953 | 867 | database:650 textmining:664 |
Rv2942 mmpL7 |
transmembrane transport protein MmpL7 | 937 | 818 ctx | neighborhood:801 textmining:669 |
Rv2947c pks15 |
polyketide synthase | 813 | 791 ctx | fusion:533 |
Rv1180 pks3 |
polyketide beta-ketoacyl synthase | 840 | 775 ctx | fusion:481 |
Rv2382c mbtC |
polyketide synthetase | 783 | 775 ctx | fusion:522 |
Rv2932 ppsB |
phthiocerol synthesis polyketide synthase type I PpsB | 774 | 761 | |
Rv0405 pks6 |
membrane bound polyketide synthase | 779 | 751 | |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 820 | 745 | |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 818 | 743 | |
Rv1527c pks5 |
polyketide synthase | 764 | 741 | |
Rv2931 ppsA |
phthiocerol synthesis polyketide synthase type I PpsA | 905 | 727 | textmining:667 |
Rv3800c pks13 |
polyketide synthase | 784 | 723 | |
Rv1664 pks9 |
polyketide synthase | 778 | 703 | |
Rv0719 rplF |
50S ribosomal protein L6 | 697 | 698 | experimental:402 database:510 |
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--AMP ligase FadD28
- MTBC0 PGAP product: fatty-acid--AMP ligase FAAL28/FadD28
- Pfam (hmmscan --cut_ga): AMP-binding PF00501.35 (E=4e-54), AMP-dom_DIP2-like PF23024.2 (E=5e-07)
- (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_217457.1)
- 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 P9WQ59 (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 —
86 functional partner(s); context anchor
mbtE - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003124|Rv2941|fadD28 MSVRSLPAALRACARLQPHDPAFTFMDYEQDWDGVAITLTWSQLYRRTLNVAQELSRCGSTGDRVVISAPQGLEYVVAFLGALQAGRIAVPLSVPQGGVTDERSDSVLSDSSPVAILTTSSAVDDVVQHVARRPGESPPSIIEVDLLDLDAPNGYTFKEDEYPSTAYLQYTSGSTRTPAGVVMSHQNVRVNFEQLMSGYFADTDGIPPPNSALVSWLPFYHDMGLVIGICAPILGGYPAVLTSPVSFLQRPARWMHLMASDFHAFSAAPNFAFELAARRTTDDDMAGRDLGNILTILSGSERVQAATIKRFADRFARFNLQERVIRPSYGLAEATVYVATSKPGQPPETVDFDTESLSAGHAKPCAGGGATSLISYMLPRSPIVRIVDSDTCIECPDGTVGEIWVHGDNVANGYWQKPDESERTFGGKIVTPSPGTPEGPWLRTGDSGFVTDGKMFIIGRIKDLLIVYGRNHSPDDIEATIQEITRGRCAAISVPGDRSTEKLVAIIELKKRGDSDQDAMARLGAIKREVTSALSSSHGLSVADLVLVAPGSIPITTSGKVRRGACVEQYRQDQFARLDA