fadD21 Resolved · high auto-curated
H37Rv Rv1185c · MTBC0 mtbc0_001273 ·
578 aa · 1334218–1335954 (-) ·
RefSeq NP_215701.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | fatty-acid--CoA ligase FadD21 |
|---|---|
| MTBC0 PGAP re-annotation | fatty-acid--AMP ligase FAAL21/FadD21 |
| Revised (this work) | Fatty-acid--AMP ligase FAAL21/FadD21. 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 |
P9WQ49
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Putative fatty-acid--CoA ligase FadD21 |
| EC (curated) |
EC 6.2.1.-
|
UniProt still lists this protein as Putative fatty-acid--CoA ligase FadD21; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolismQ Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | fadD21 |
| 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 (35) |
GO:0003674, GO:0003824, GO:0005575, GO:0005623, GO:0005886, GO:0006082, GO:0006629, GO:0006631, GO:0006633, GO:0008150, GO:0008152, GO:0008610 +23 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 | 0.915 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 11 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 | 6.5e-54 | 11–414 | AMP-binding enzyme |
AMP-dom_DIP2-like | PF23024.2 | 9.0e-08 | 462–571 | 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 909 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2380c mbtE |
peptide synthetase | 913 | 909 ctx | fusion:718 experimental:465 |
Rv2947c pks15 |
polyketide synthase | 821 | 822 ctx | fusion:598 |
Rv1180 pks3 |
polyketide beta-ketoacyl synthase | 920 | 781 ctx | fusion:472 textmining:653 |
Rv0405 pks6 |
membrane bound polyketide synthase | 781 | 770 | |
Rv2932 ppsB |
phthiocerol synthesis polyketide synthase type I PpsB | 779 | 767 | |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 888 | 758 | textmining:556 |
Rv2382c mbtC |
polyketide synthetase | 760 | 752 ctx | fusion:476 |
Rv1527c pks5 |
polyketide synthase | 770 | 747 | |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 766 | 746 | |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 792 | 745 | |
Rv1664 pks9 |
polyketide synthase | 742 | 742 ctx | fusion:427 |
Rv2379c mbtF |
peptide synthetase | 736 | 733 ctx | fusion:499 |
Rv2931 ppsA |
phthiocerol synthesis polyketide synthase type I PpsA | 767 | 730 | |
Rv3800c pks13 |
polyketide synthase | 747 | 722 | |
Rv2383c mbtB |
phenyloxazoline synthase | 736 | 708 |
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 FadD21
- MTBC0 PGAP product: fatty-acid--AMP ligase FAAL21/FadD21
- Pfam (hmmscan --cut_ga): AMP-binding PF00501.35 (E=6e-54), AMP-dom_DIP2-like PF23024.2 (E=9e-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_215701.1)
- 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 P9WQ49 (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
mbtE - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001273|Rv1185c|fadD21 MSDSSVLSLLRERAGLQPDDAAFTYIDYEQDWAGITETLTWSEVFRRTRIVAHEVRRHCTTGDRAVILAPQGLAYIAAFLGSMQAGAIAVPLSVPQIGSHDERVSAVLADASPSVILTTSAVAEAVAEHIHRPNTNNVGPIIEIDSLDLTGNSPSFRVKDLPSAAYLQYTSGSTRAPAGVMISHRNLQANFQQLMSNYFGDRNGVAPPDTTIVSWLPFYHDMGLVLGIIAPILGGYRSELTSPLAFLQRPARWLHSLANGSPSWSAAPNFAFELAVRKTTDADIEGLDLGNVLGITSGAERVHPNTLSRFCNRFAPYNFREDMIRPSYGLAEATLYVASRNSGDKPEVVYFEPDKLSTGSANRCEPKTGTPLLSYGMPTSPTVRIVDPDTCIECPAGTIGEIWVKGDNVAEGYWNKPDETRHTFGAMLVHPSAGTPDGSWLRTGDLGFLSEDEMFIVGRMKDMLIVYGRNHYPEDIESTVQEITGGRVAAISVPVDHTEKLVTVIELKLLGDSAGEAMDELDVIKNNVTAAISRSHGLNVADLVLVPPGSIPTTTSGKIRRAACVEQYRLQQFTRLDG