fadD12 Resolved · high auto-curated
H37Rv Rv1427c · MTBC0 mtbc0_001527 ·
535 aa · 1611665–1613272 (-) ·
RefSeq NP_215943.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | acyl-CoA synthetase |
|---|---|
| MTBC0 PGAP re-annotation | acyl-CoA ligase FadD12 |
| Revised (this work) | Acyl-CoA ligase FadD12. 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 |
O06831
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Long-chain-fatty-acid--CoA ligase FadD13 |
| EC (curated) |
EC 6.2.1.3
|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolismQ Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | fadD12 |
| eggNOG description | PFAM AMP-dependent synthetase and ligase |
| 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 | 2.475 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 7 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 | 1.6e-61 | 47–400 | AMP-binding enzyme |
AMP-binding_C | PF13193.13 | 3.1e-23 | 448–523 | AMP-binding enzyme C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: lipO (esterase LipO), high confidence from genomic context alone (score 986 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1426c lipO |
esterase LipO | 996 | 986 ctx | neighborhood:882 coexpression:866 textmining:755 |
Rv1428c hyp |
hypothetical protein | 949 | 949 ctx | neighborhood:882 coexpression:533 |
Rv2380c mbtE |
peptide synthetase | 710 | 696 | experimental:465 |
Rv0719 rplF |
50S ribosomal protein L6 | 696 | 696 | experimental:402 database:510 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 705 | 680 | |
Rv1527c pks5 |
polyketide synthase | 705 | 680 | |
Rv2048c pks12 |
polyketide synthase | 705 | 680 | |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 704 | 679 | |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 704 | 679 | |
Rv1429 hyp |
hypothetical protein | 642 | 642 ctx | neighborhood:587 |
Rv3800c pks13 |
polyketide synthase | 670 | 637 | |
Rv2946c pks1 |
polyketide synthase | 663 | 631 | |
Rv1661 pks7 |
polyketide synthase | 630 | 609 | |
Rv1181 pks4 |
polyketide beta-ketoacyl synthase | 629 | 608 | |
Rv2932 ppsB |
phthiocerol synthesis polyketide synthase type I PpsB | 628 | 606 |
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: acyl-CoA synthetase
- MTBC0 PGAP product: acyl-CoA ligase FadD12
- Pfam (hmmscan --cut_ga): AMP-binding PF00501.35 (E=2e-61), AMP-binding_C PF13193.13 (E=3e-23)
- (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_215943.1)
- 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 O06831 (TrEMBL, unreviewed; 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 —
84 functional partner(s); context anchor
lipO - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001527|Rv1427c|fadD12 MRIRQAFGLIATMRRAGLIAPLRPDRYLRIVAAMRREGMGFTAGFAGAARRCPDRPGLIDELGTLTWRQLDERGNALAAALQALPAGPPRVVGIMCRNHRGFVDALLAVNRIGAHILLLNTSFAGPALAEVVTREGVDTVVYDEEFSATVDRALAEKPQATRIVAWTDEDHDLTVEKLVAAHAGRRPEHTGSHGKVILLTSGTTGTPKGARHSGGGIGTLKAILDRTPWRAEEVTVIVAPMFHAWGFSQLVLASSLACTIVTRRRFDPEATLDLIDRHHATGLVVVPVMFDRIMDLPAEIRNRYDGRSLRFAAASGSRMRPDVVIAFMDQFGDVIYNNYNATEAGMIATATPADLRTAPDTAGRPAEGTEIRILDQQFTEVPTGEVGTIYVRNDSQFDGYTSGAAKDFHAGFMSSGDVGYLDENGRLFVVGRDDEMIVSGGENIYPIEVEKTLATHPDVAEAAVIGVDDQQYGQRLAAFVVLKPGVSATPETLKQHVRDNLANYKVPRDIAVLDELPRGITGKILRTELQSRVGS