fadD18 Resolved · high auto-curated

H37Rv Rv3513c · MTBC0 - · 218 aa · 3945092–3945748 (-) · RefSeq NP_218030.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)fatty-acid--CoA ligase FadD18
MTBC0 PGAP re-annotation
Revised (this work)Fatty-acid--CoA ligase FadD18. Pfam: 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.

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 I6YGC8 TrEMBL · unreviewed · Inferred from homology
UniProt nameProbable fatty-acid-CoA ligase FadD18

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Q Secondary metabolites biosynthesis, transport and catabolism
Preferred namefadD19
eggNOG descriptionCOG0318 Acyl-CoA synthetases (AMP-forming) AMP-acid ligases II
Orthologous groupCOG0318
EC number EC 6.2.1.42
KEGG orthology K18688
Gene Ontology (17) GO:0003674, GO:0005488, GO:0005515, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005777, GO:0042579, GO:0043226, GO:0043227, GO:0043229 +5 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 0.49 · purifying
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)

PfamAccessioni-EvalueResiduesDescription
AMP-binding_CPF13193.13 2.4e-16116–191 AMP-binding enzyme C-terminal domain

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: fadD22 (p-hydroxybenzoyl--AMP ligase), high confidence from genomic context alone (score 769 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2948c fadD22 p-hydroxybenzoyl--AMP ligase 769 769 ctx cooccurence:769
Rv0099 fadD10 fatty-acid--CoA ligase FadD10 767 767 ctx cooccurence:767
Rv3506 fadD17 long-chain-fatty-acid--CoA ligase FadD17 853 765 ctx cooccurence:764 textmining:402
Rv1750c fadD1 fatty-acid--CoA ligase FadD1 774 761 ctx cooccurence:760
Rv0719 rplF 50S ribosomal protein L6 695 695 experimental:402 database:510
Rv1527c pks5 polyketide synthase 782 681
Rv3825c pks2 phthioceranic/hydroxyphthioceranic acid synthase 705 680
Rv2940c mas multifunctional mycocerosic acid synthase 705 680
Rv2048c pks12 polyketide synthase 705 680
Rv2933 ppsC phthiocerol synthesis polyketide synthase type I PpsC 704 679
Rv3800c pks13 polyketide synthase 670 637
Rv2380c mbtE peptide synthetase 651 636 experimental:465
Rv2946c pks1 polyketide synthase 663 631
Rv1661 pks7 polyketide synthase 631 610
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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): fatty-acid--CoA ligase FadD18
  • Pfam (hmmscan --cut_ga): AMP-binding_C PF13193.13 (E=2e-16)
  • (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_218030.1)
  • Domains: Pfam-A via hmmscan --cut_ga — 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 I6YGC8 (TrEMBL, unreviewed; Inferred from homology)
  • 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 fadD22
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3513c|fadD18
MAASLSENLSCHSSNMCRLSGNAATNLERPGEEPPGDRCTRRQAVRPARTLAKKGNIPVGYYKDEKKTAETFRTINGVRYAIPGDYAQVEEDGTVTMLGRGSVSINSGGEKVYPEEVEAALKGHPDVFDALVVGVPDPRYGQQVAAVVQARPGCRPSLAELDSFVRSEIAGYKVPRSLWFVDEVKRSPAGKPDYRWAKEQTEARPADDVHAGHVTSGS