MTBC Gene Atlas

fadD34 Resolved · high auto-curated

H37Rv Rv0035 · MTBC0 - · 562 aa · 37259–38947 (+) · RefSeq YP_177686.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)fatty-acid--CoA ligase FadD34
MTBC0 PGAP re-annotation—
Revised (this work)Fatty-acid--CoA ligase FadD34. 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.

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 L7N699 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable fatty-acid-CoA ligase FadD34

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Q Secondary metabolites biosynthesis, transport and catabolism
eggNOG descriptionAMP-binding enzyme
Orthologous groupCOG0318

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 1.426 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 21 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.13% of strains (192) · clonal

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 7.8e-4719–392 AMP-binding enzyme

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

Closest characterised functional partner: acpA (acyl carrier protein AcpA), high confidence from genomic context alone (score 987 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0033 acpA acyl carrier protein AcpA 987 987 ctx neighborhood:882 coexpression:865
Rv0034 hyp hypothetical protein 982 983 ctx neighborhood:882 coexpression:860
Rv0032 bioF2 8-amino-7-oxononanoate synthase 970 970 ctx neighborhood:781 coexpression:863
Rv2380c mbtE peptide synthetase 829 822 ctx cooccurence:536 experimental:465
Rv1918c PPE35 PPE family protein PPE35 744 744 coexpression:744
Rv2933 ppsC phthiocerol synthesis polyketide synthase type I PpsC 745 723
Rv0101 nrp peptide synthetase Nrp 714 699 ctx cooccurence:554
Rv0719 rplF 50S ribosomal protein L6 696 696 experimental:402 database:510
Rv2383c mbtB phenyloxazoline synthase 720 691 ctx cooccurence:421
Rv3825c pks2 phthioceranic/hydroxyphthioceranic acid synthase 722 681
Rv0405 pks6 membrane bound polyketide synthase 696 681
Rv1527c pks5 polyketide synthase 706 680
Rv2048c pks12 polyketide synthase 706 680
Rv2940c mas multifunctional mycocerosic acid synthase 705 680
Rv3800c pks13 polyketide synthase 708 679

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): fatty-acid--CoA ligase FadD34
  • Pfam (hmmscan --cut_ga): AMP-binding PF00501.35 (E=8e-47)
  • (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 YP_177686.1)
  • 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 L7N699 (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 acpA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0035|fadD34
MTAALLSPAIAWQQISACTDRTLTITCEDSEVISYQDLIARAAACIPPLRRLDLKRGEPVLITAHTNLEFLSCFLGLMLHGAVPVPIPPREALKTTERFMTRLGPLLRHHRVLICTPAEHDEIRAAASTDCQISRFTALAEAGDEQFGRATAQQLADTATADWPLCTLDDDAYVQYTSGSTAAPRGVVITYRNLLSNMRAMAVGSQFQHGDVMGSWLPLHHDMGLVGSLFAALFNSVSAVFTTPHRFLYDPLGFLRLLTSSGATHTFMPNFALEWLINAYHRRGADIEGIDLHKMRRLIIASEPVHAEGMRRFAATFAGVGLAPTALGSGYGLAEATVAVSMSAPNTGFRTETHAAAEVVTGGRVLPGYEVRIDAAPGARAGTIKLRGDSVAAKAYVGGKKLDALDEEGFCDTHDLGFLVDDEIVILGRQDEVFIVHGENRFPYDIEFIIRGESEQHRTKVACFGVNERVVVVLESPLDSIIDKAEADRLRCQVVAATGLQLDELITVRRGAIPTTTSGKLKRRAVAQAYRDGTLPRLATHAWTADPDSAPKTTRSSLEGAH