fadD31 Resolved · high auto-curated

H37Rv Rv1925 · MTBC0 mtbc0_002039 · 620 aa · 2196203–2198065 (+) · RefSeq NP_216441.2

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)fatty-acid--CoA ligase FadD31
MTBC0 PGAP re-annotationfatty-acid--AMP ligase FAAL31/FadD31
Revised (this work)Fatty-acid--AMP ligase FAAL31/FadD31. Pfam: AMP-binding (PF00501.35).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt I6Y7V6 TrEMBL · unreviewed · Evidence at protein level
UniProt nameAcyl-AMP synthetase

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Q Secondary metabolites biosynthesis, transport and catabolism
Preferred namefadD31
eggNOG descriptionFatty-acid--CoA ligase
Orthologous groupCOG0318
EC number EC 2.7.7.95, EC 6.2.1.51
KEGG orthology K00666, K12423, K12425, K12426, K12427, K12428, K21059

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 0.294 · purifying
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 5 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 1.9e-4568–448 AMP-binding enzyme

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

Closest characterised functional partner: mbtE (peptide synthetase), high confidence from genomic context alone (score 925 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2380c mbtE peptide synthetase 928 925 ctx fusion:584 cooccurence:605 experimental:465
Rv2379c mbtF peptide synthetase 796 795 ctx cooccurence:570
Rv3800c pks13 polyketide synthase 799 779 ctx cooccurence:404
Rv0101 nrp peptide synthetase Nrp 762 750 ctx cooccurence:600
Rv2933 ppsC phthiocerol synthesis polyketide synthase type I PpsC 765 745
Rv2940c mas multifunctional mycocerosic acid synthase 762 742
Rv3825c pks2 phthioceranic/hydroxyphthioceranic acid synthase 761 741
Rv1527c pks5 polyketide synthase 757 737
Rv0405 pks6 membrane bound polyketide synthase 746 734
Rv2932 ppsB phthiocerol synthesis polyketide synthase type I PpsB 736 721
Rv2931 ppsA phthiocerol synthesis polyketide synthase type I PpsA 726 715
Rv0719 rplF 50S ribosomal protein L6 698 699 experimental:402 database:510
Rv1180 pks3 polyketide beta-ketoacyl synthase 685 686
Rv2048c pks12 polyketide synthase 705 680
Rv2382c mbtC polyketide synthetase 690 679

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 FadD31
  • MTBC0 PGAP product: fatty-acid--AMP ligase FAAL31/FadD31
  • Pfam (hmmscan --cut_ga): AMP-binding PF00501.35 (E=2e-45)
  • (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_216441.2)
  • Domains: Pfam-A via hmmscan --cut_ga — AMP-binding (PF00501.35)
  • 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 I6Y7V6 (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 — 81 functional partner(s); context anchor mbtE
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002039|Rv1925|fadD31
MNDGSRQELRVRSGLLQIEDCLDADGGIALPAGTTLISLIERNIKYVGDLVAYRYLDHARSAAGCALEVTWTQFGMRLAAIGAHVQRFAGPGDRVAILAPQGIDYVCGFYAAIKAGTVAVPLFAPELPGHAERLDTALRDSEPAVILTTAAAKNAVEGFLNNVPRLRKPTVLVIDQIPDREGELFVPVELDIDAVSHLQYTSGSTRPPVGVEITHRAVGTNLVQMILSIDLLNRNTHGVSWLPLYHDMGLSMIGFPAVYGGHSTLMSPTAFVRRPLRWIQALSEGSRTGRVVTAAPNFAYEWAAQRGLPAQGDDVDLSNVVLIIGSEPVSIDAVTTFNKAFAPYGLPRTAFKPSYGIAEATLLVATIDHAAEPTVVYLDPEQLGAGHATRVAPDAPNAVVHVSCGHVARSLWAVIVDPDTGPEAGAELPDGEIGEVWLQGDNVARGYWGRPEETRMTFGARLQSPLAEGSHADGSAIDDTWLRTGDLGVYLDGELYITGRIADLLTIDGRNHYPQDIEATAAEASPMVRRGYITAFTVPASDGDDRNQRLVIIAERAAGTSRSDPRPALDAIRAAVCNRHGLSVADLSFLPAGAIPRTTSGKLARQACRAQYLSGRLGVH