MTBC Gene Atlas

fadD2 Resolved · high auto-curated

H37Rv Rv0270 · MTBC0 mtbc0_000287 · 560 aa · 324949–326631 (+) · RefSeq NP_214784.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)fatty-acid--CoA ligase FadD2
MTBC0 PGAP re-annotationlong-chain-fatty-acid--CoA ligase FadD2
Revised (this work)Long-chain-fatty-acid--CoA ligase FadD2. 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 P95227 TrEMBL · unreviewed · Evidence at protein level
UniProt nameLong-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 metabolism
Q Secondary metabolites biosynthesis, transport and catabolism
Preferred namefadD2
eggNOG descriptionActivates fatty acids by binding to coenzyme A
Orthologous groupCOG0318
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 0.226 · purifying
Polymorphic sites (≥ 0.1% of strains) 12 synonymous, 8 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-bindingPF00501.35 3.0e-7469–428 AMP-binding enzyme
AMP-binding_CPF13193.13 1.2e-20476–551 AMP-binding enzyme C-terminal domain

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

Closest characterised functional partner: fadD11 (fatty-acid--CoA ligase FadD11), medium confidence from genomic context alone (score 642 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0719 rplF 50S ribosomal protein L6 696 696 experimental:402 database:510
Rv3825c pks2 phthioceranic/hydroxyphthioceranic acid synthase 708 684
Rv2048c pks12 polyketide synthase 706 680
Rv1527c pks5 polyketide synthase 705 680
Rv2940c mas multifunctional mycocerosic acid synthase 705 680
Rv2933 ppsC phthiocerol synthesis polyketide synthase type I PpsC 704 679
Rv1550 fadD11 fatty-acid--CoA ligase FadD11 654 642 ctx cooccurence:627
Rv3800c pks13 polyketide synthase 670 638
Rv2946c pks1 polyketide synthase 663 631
Rv2380c mbtE peptide synthetase 637 620 experimental:465
Rv1181 pks4 polyketide beta-ketoacyl synthase 630 609
Rv1661 pks7 polyketide synthase 630 609
Rv2932 ppsB phthiocerol synthesis polyketide synthase type I PpsB 628 606
Rv0308 integral membrane protein 602 601 database:500
Rv3807c decaprenylphosphoryl-5-phosphoribose phosphatase 602 600 database:500

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 FadD2
  • MTBC0 PGAP product: long-chain-fatty-acid--CoA ligase FadD2
  • Pfam (hmmscan --cut_ga): AMP-binding PF00501.35 (E=3e-74), AMP-binding_C PF13193.13 (E=1e-20)
  • (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_214784.1)
  • 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 P95227 (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 — 82 functional partner(s); context anchor fadD11
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000287|Rv0270|fadD2
MPNLTDLPGQAVSKLQKSIGQYVARGTAELHYLRKIIESGAIGLEPPLNYAALAADIRKWGEVGMLPSHNARRAPNRAAVIDEEGTLTFSELDEAAHAVANGLLAKGVRAGDGVAILARNHRWFVIANYGAARVGARIILLNSEFSGPQIKEVSDREGAKVIIYDDEYTKAVSLAQPPLGKLRALGVNPDDDKPSGSSDETLAELIAHSSTAPAPKASRRASIIILTSGTTGTPKGANRNTPPTLAPIGGILSHVPFKAGEVTLLPSPMFHALGYMHAALAMFLGSTLVLRRRFKPALVLEDIEKHKATSMVVVPVMLSRILDQLEKTEPKPDLSSLKIVFVSGSQLGAELATRALGDLGPVIYNMYGSTEVAFATIAGPKDLQFNPSTVGPVVKGVTVKILDENGNEVPQGAVGRIFVGNAFPFEGYTGGGGKQIIDGLLSSGDVGYFDERGLLYVSGRDDEMIVSGGENVFPAEVEDLISGHPDVVEAAAIGVDDKEFGARLRAFVVKKPGADLDEDTIKQYVRDHLARYKVPREVIFLDELPRNPTGKVLKRELRKL