menA Resolved · high auto-curated

H37Rv Rv0534c · MTBC0 mtbc0_000563 · 292 aa · 629113–629991 (-) · RefSeq NP_215048.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)1,4-dihydroxy-2-naphthoate octaprenyltransferase
MTBC0 PGAP re-annotation1%2C4-dihydroxy-2-naphthoate polyprenyltransferase
Revised (this work)1%2C4-dihydroxy-2-naphthoate polyprenyltransferase. Pfam: UbiA (PF01040.24).

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

Curated reference (UniProt)

UniProt P9WIP3 SwissProt · reviewed · Evidence at protein level
UniProt name1,4-dihydroxy-2-naphthoate octaprenyltransferase
EC (curated) EC 2.5.1.74
Curated functionConversion of 1,4-dihydroxy-2-naphthoate (DHNA) to demethylmenaquinone (DMK). Can use a variety of allylic isoprenyl diphosphates as substrates but has a requirement for at least three isoprene units.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category H Coenzyme transport and metabolism
Preferred namemenA
eggNOG descriptionBelongs to the MenA family. Type 1 subfamily
Orthologous groupCOG1575
EC number EC 2.5.1.74
KEGG orthology K02548
KEGG pathways map00130, map01100, map01110
KEGG modules M00116
Gene Ontology (35) GO:0003674, GO:0003824, GO:0004659, GO:0006732, GO:0006733, GO:0006743, GO:0006744, GO:0006766, GO:0006775, GO:0008150, GO:0008152, GO:0009058 +23 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 0.808 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 2 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
UbiAPF01040.24 8.7e-2520–250 UbiA prenyltransferase family

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

Closest characterised functional partner: menB (1,4-dihydroxy-2-naphthoyl-CoA synthase), high confidence from genomic context alone (score 810 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1847 esterase 981 904 database:900 textmining:813
Rv0558 menH demethylmenaquinone methyltransferase 961 904 database:900 textmining:614
Rv0548c menB 1,4-dihydroxy-2-naphthoyl-CoA synthase 938 810 ctx cooccurence:767 textmining:688
Rv0555 menD bifunctional 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase/2-oxoglutarate decarboxylase 850 800 ctx cooccurence:766
Rv0535 pnp 5'-methylthioadenosine phosphorylase 792 792 ctx neighborhood:791
Rv0536 galE3 UDP-glucose 4-epimerase GalE 792 792 ctx neighborhood:791
Rv0533c fabH 3-oxoacyl-ACP synthase III 790 790 ctx neighborhood:785
Rv0553 menC muconate cycloisomerase 720 650 ctx cooccurence:589
Rv0542c menE 2-succinylbenzoic acid--CoA ligase 809 469 textmining:657
Rv3215 entC isochorismate synthase 640 222 textmining:556
Rv1602 hisH imidazole glycerol phosphate synthase subunit HisH 408 203
Rv0561c menJ oxidoreductase 708 186 textmining:656
Rv2715 hydrolase 806 153 textmining:781
Rv1938 ephB epoxide hydrolase EphB 697 151 textmining:658
Rv0560c benzoquinone methyltransferase 465 61 textmining:454

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: 1,4-dihydroxy-2-naphthoate octaprenyltransferase
  • MTBC0 PGAP product: 1%2C4-dihydroxy-2-naphthoate polyprenyltransferase
  • Pfam (hmmscan --cut_ga): UbiA PF01040.24 (E=9e-25)
  • (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_215048.1)
  • Domains: Pfam-A via hmmscan --cut_ga — UbiA (PF01040.24)
  • 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 COG1575
  • Curated reference: UniProt P9WIP3 (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 — 18 functional partner(s); context anchor menB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000563|Rv0534c|menA
MASFAQWVSGARPRTLPNAIAPVVAGTGAAAWLHAAVWWKALLALAVAVALVIGVNYANDYSDGIRGTDDDRVGPVRLVGSRLATPRSVLTAAMTSLALGALAGLVLALLSAPWLIAVGAICIAGAWLYTGGSKPYGYAGFGELAVFVFFGPVAVLGTQYTQALRVDWVGLAQAVATGALSCSVLVANNLRDIPTDARADKITLAVRLGDARTRMLYQGLLAVAGVLTFVLMLATPWCVVGLVAAPLALRAAGPVRSGRGGRELIPVLRDTGLAMLVWALAVAGALAFGQLS