mbtN Resolved · high auto-curated

H37Rv Rv1346 · MTBC0 mtbc0_001443 · 386 aa · 1521548–1522708 (+) · RefSeq NP_215862.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)acyl-[acyl-carrier-protein
MTBC0 PGAP re-annotationacyl-ACP dehydrogenase MbtN
Revised (this work)Acyl-ACP dehydrogenase MbtN. Pfam: Acyl-CoA_dh_M (PF02770.25), Acyl-CoA_dh_1 (PF00441.30).

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

Curated reference (UniProt)

UniProt P9WQF9 SwissProt · reviewed · Evidence at protein level
UniProt nameAcyl-[acyl-carrier-protein] dehydrogenase MbtN
EC (curated) EC 1.3.99.-
Curated functionCatalyzes the dehydrogenation at the alpha-beta position of ACP-bound acyl chains. This results in the introduction of a double bond in the lipidic chain, which is further transferred to the epsilon-amino group of lysine residue in the mycobactin core by MbtK.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Preferred namembtN
eggNOG descriptionoxidoreductase activity, acting on the CH-CH group of donors
Orthologous groupCOG1960
KEGG orthology K00257
Gene Ontology (37) GO:0003674, GO:0003824, GO:0006518, GO:0006725, GO:0006807, GO:0008150, GO:0008152, GO:0009058, GO:0009237, GO:0009712, GO:0009987, GO:0016491 +25 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 0.172 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 1 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
Acyl-CoA_dh_MPF02770.25 8.1e-18117–211 Acyl-CoA dehydrogenase, middle domain
Acyl-CoA_dh_1PF00441.30 3.8e-33224–370 Acyl-CoA dehydrogenase, C-terminal domain

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

Closest characterised functional partner: mbtM (long-chain-fatty-acid--ACP ligase MbtM), high confidence from genomic context alone (score 982 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1345 mbtM long-chain-fatty-acid--ACP ligase MbtM 990 982 ctx neighborhood:882 coexpression:817 textmining:484
Rv1344 mbtL acyl carrier protein MbtL 918 918 ctx neighborhood:882
Rv0860 fadB fatty oxidation protein FadB 802 787 coexpression:646
Rv3029c fixA electron transfer flavoprotein subunit beta 779 770 coexpression:405 experimental:418
Rv3028c fixB electron transfer flavoprotein subunit alpha 778 768 coexpression:410 experimental:419
Rv1933c fadE18 acyl-CoA dehydrogenase FadE18 661 661 ctx cooccurence:659
Rv3139 fadE24 acyl-CoA dehydrogenase 644 644 ctx cooccurence:637
Rv0673 echA4 enoyl-CoA hydratase EchA4 658 643
Rv1679 fadE16 acyl-CoA dehydrogenase FadE16 640 641 ctx cooccurence:639
Rv3153 nuoI NADH-quinone oxidoreductase subunit I 651 636
Rv3797 fadE35 acyl-CoA dehydrogenase FadE35 591 592 ctx cooccurence:589
Rv2048c pks12 polyketide synthase 617 587 database:459
Rv2940c mas multifunctional mycocerosic acid synthase 616 585 database:459
Rv3825c pks2 phthioceranic/hydroxyphthioceranic acid synthase 616 585 database:459
Rv2933 ppsC phthiocerol synthesis polyketide synthase type I PpsC 616 585 database:459

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-[acyl-carrier-protein
  • MTBC0 PGAP product: acyl-ACP dehydrogenase MbtN
  • Pfam (hmmscan --cut_ga): Acyl-CoA_dh_M PF02770.25 (E=8e-18), Acyl-CoA_dh_1 PF00441.30 (E=4e-33)
  • (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_215862.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Acyl-CoA_dh_M (PF02770.25), Acyl-CoA_dh_1 (PF00441.30)
  • 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 COG1960
  • Curated reference: UniProt P9WQF9 (SwissProt, reviewed; 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 — 137 functional partner(s); context anchor mbtM
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001443|Rv1346|mbtN
MTAGSDLDDFRGLLAKAFDERVVAWTAEAEAQERFPRQLIEHLGVCGVFDAKWATDARPDVGKLVELAFALGQLASAGIGVGVSLHDSAIAILRRFGKSDYLRDICDQAIRGAAVLCIGASEESGGSDLQIVETEIRSRDGGFEVRGVKKFVSLSPIADHIMVVARSVDHDPTSRHGNVAVVAVPAAQVSVQTPYRKVGAGPLDTAAVCIDTWVPADALVARAGTGLAAISWGLAHERMSIAGQIAASCQRAIGITLARMMSRRQFGQTLFEHQALRLRMADLQARVDLLRYALHGIAEQGRLELRTAAAVKVTAARLGEEVISECMHIFGGAGYLVDETTLGKWWRDMKLARVGGGTDEVLWELVAAGMTPDHDGYAAVVGASKA