menB Resolved · high auto-curated

H37Rv Rv0548c · MTBC0 - · 314 aa · 639012–639956 (-) · RefSeq NP_215062.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)1,4-dihydroxy-2-naphthoyl-CoA synthase
MTBC0 PGAP re-annotation
Revised (this work)1,4-dihydroxy-2-naphthoyl-CoA synthase. Pfam: ECH_1 (PF00378.26), ECH_2 (PF16113.11).

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 P9WNP5 SwissProt · reviewed · Evidence at protein level
UniProt name1,4-dihydroxy-2-naphthoyl-CoA synthase
EC (curated) EC 4.1.3.36
Curated functionConverts o-succinylbenzoyl-CoA (OSB-CoA) to 1,4-dihydroxy-2-naphthoyl-CoA (DHNA-CoA).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category H Coenzyme transport and metabolism
Preferred namemenB
eggNOG descriptionBelongs to the enoyl-CoA hydratase isomerase family. MenB subfamily
Orthologous groupCOG0447
EC number EC 4.1.3.36
KEGG orthology K01661
KEGG pathways map00130, map01100, map01110
KEGG modules M00116
Gene Ontology (40) GO:0003674, GO:0003824, GO:0005575, GO:0005623, GO:0005886, GO:0006732, GO:0008150, GO:0008152, GO:0008935, GO:0009058, GO:0009108, GO:0009233 +28 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 n/a
Polymorphic sites (≥ 0.1% of strains) 0 synonymous, 4 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
ECH_1PF00378.26 5.9e-4848–308 Enoyl-CoA hydratase/isomerase
ECH_2PF16113.11 4.9e-1449–249 Enoyl-CoA hydratase/isomerase

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

Closest characterised functional partner: menE (2-succinylbenzoic acid--CoA ligase), high confidence from genomic context alone (score 971 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0542c menE 2-succinylbenzoic acid--CoA ligase 994 971 ctx cooccurence:569 database:900 textmining:816
Rv1847 esterase 974 927 database:900 textmining:659
Rv0555 menD bifunctional 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase/2-oxoglutarate decarboxylase 992 881 ctx neighborhood:419 cooccurence:770 textmining:935
Rv0553 menC muconate cycloisomerase 974 862 ctx neighborhood:631 cooccurence:641 textmining:825
Rv0534c menA 1,4-dihydroxy-2-naphthoate octaprenyltransferase 938 810 ctx cooccurence:767 textmining:688
Rv0544c transmembrane protein 677 677 ctx neighborhood:667
Rv0547c oxidoreductase 662 662 ctx neighborhood:657
Rv0551c fadD8 fatty-acid--CoA ligase FadD8 670 656 ctx neighborhood:654
Rv0554 bpoC non-heme bromoperoxidase BpoC 642 629 ctx neighborhood:623
Rv0552 hyp hypothetical protein 614 615 ctx neighborhood:615
Rv3039c echA17 enoyl-CoA hydratase EchA17 587 587 ctx cooccurence:584
Rv0456c echA2 enoyl-CoA hydratase EchA2 547 547 ctx cooccurence:546
Rv3373 echA18 enoyl-CoA hydratase 494 494 ctx cooccurence:489
Rv1449c tkt transketolase 432 433 coexpression:433
Rv0545c pitA low-affinity inorganic phosphate transporter 430 430

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): 1,4-dihydroxy-2-naphthoyl-CoA synthase
  • Pfam (hmmscan --cut_ga): ECH_1 PF00378.26 (E=6e-48), ECH_2 PF16113.11 (E=5e-14)
  • (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_215062.1)
  • Domains: Pfam-A via hmmscan --cut_ga — ECH_1 (PF00378.26), ECH_2 (PF16113.11)
  • 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 COG0447
  • Curated reference: UniProt P9WNP5 (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 — 29 functional partner(s); context anchor menE
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0548c|menB
MVAPAGEQGRSSTALSDNPFDAKAWRLVDGFDDLTDITYHRHVDDATVRVAFNRPEVRNAFRPHTVDELYRVLDHARMSPDVGVVLLTGNGPSPKDGGWAFCSGGDQRIRGRSGYQYASGDTADTVDVARAGRLHILEVQRLIRFMPKVVICLVNGWAAGGGHSLHVVCDLTLASREYARFKQTDADVGSFDGGYGSAYLARQVGQKFAREIFFLGRTYTAEQMHQMGAVNAVAEHAELETVGLQWAAEINAKSPQAQRMLKFAFNLLDDGLVGQQLFAGEATRLAYMTDEAVEGRDAFLQKRPPDWSPFPRYF