menC Resolved · high auto-curated

H37Rv Rv0553 · MTBC0 mtbc0_000582 · 326 aa · 648041–649021 (+) · RefSeq NP_215067.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)muconate cycloisomerase
MTBC0 PGAP re-annotationo-succinylbenzoate synthase
Revised (this work)O-succinylbenzoate synthase. Pfam: Enolase_like_N (PF18374.7), MR_MLE_C (PF13378.13).

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

Curated reference (UniProt)

UniProt P9WJP3 SwissProt · reviewed · Evidence at protein level
UniProt nameo-succinylbenzoate synthase
EC (curated) EC 4.2.1.113
Curated functionConverts 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate (SHCHC) to 2-succinylbenzoate (OSB).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category H Coenzyme transport and metabolism
Preferred namemenC
eggNOG descriptionConverts 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1- carboxylate (SHCHC) to 2-succinylbenzoate (OSB)
Orthologous groupCOG4948
EC number EC 4.2.1.113
KEGG orthology K02549
KEGG pathways map00130, map01100, map01110
KEGG modules M00116
Gene Ontology (2) GO:0008150, GO:0040007

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 0.257 · purifying
Polymorphic sites (≥ 0.1% of strains) 3 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
Enolase_like_NPF18374.7 3.9e-2717–68 Enolase N-terminal domain-like
MR_MLE_CPF13378.13 4.0e-34103–288 Enolase C-terminal domain-like

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

Closest characterised functional partner: menD (bifunctional 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase/2-oxoglutarate decarboxylase), high confidence from genomic context alone (score 960 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0555 menD bifunctional 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase/2-oxoglutarate decarboxylase 997 960 ctx neighborhood:817 cooccurence:598 database:500 textmining:945
Rv0542c menE 2-succinylbenzoic acid--CoA ligase 954 955 database:900
Rv0552 hyp hypothetical protein 902 902 ctx neighborhood:881
Rv0554 bpoC non-heme bromoperoxidase BpoC 887 882 ctx neighborhood:882
Rv0548c menB 1,4-dihydroxy-2-naphthoyl-CoA synthase 974 862 ctx neighborhood:631 cooccurence:641 textmining:825
Rv0551c fadD8 fatty-acid--CoA ligase FadD8 802 802 ctx neighborhood:780
Rv0557 mgtA GDP-mannose-dependent alpha-mannosyltransferase 756 756 ctx neighborhood:756
Rv0556 transmembrane protein 704 704 ctx neighborhood:704
Rv0534c menA 1,4-dihydroxy-2-naphthoate octaprenyltransferase 720 650 ctx cooccurence:589
Rv0558 menH demethylmenaquinone methyltransferase 943 567 ctx neighborhood:567 textmining:874
Rv1930c hyp hypothetical protein 548 548 ctx neighborhood:544
Rv1931c transcriptional regulator 544 544 ctx neighborhood:544
Rv0547c oxidoreductase 542 542 ctx neighborhood:539
Rv3683 hyp hypothetical protein 433 433 ctx cooccurence:433
Rv2033c hyp hypothetical protein 401 401

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: muconate cycloisomerase
  • MTBC0 PGAP product: o-succinylbenzoate synthase
  • Pfam (hmmscan --cut_ga): Enolase_like_N PF18374.7 (E=4e-27), MR_MLE_C PF13378.13 (E=4e-34)
  • (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_215067.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Enolase_like_N (PF18374.7), MR_MLE_C (PF13378.13)
  • 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 COG4948
  • Curated reference: UniProt P9WJP3 (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 — 26 functional partner(s); context anchor menD
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000582|Rv0553|menC
MIPVLPPLEALLDRLYVVALPMRVRFRGITTREVALIEGPAGWGEFGAFVEYQSAQACAWLASAIETAYCAPPPVRRDRVPINATVPAVAAAQVGEVLARFPGARTAKVKVAEPGQSLADDIERVNAVRELVPMVRVDANGGWGVAEAVAAAAALTADGPLEYLEQPCATVAELAELRRRVDVPIAADESIRKAEDPLAVVRAQAADIAVLKVAPLGGISALLDIAARIAVPVVVSSALDSAVGIAAGLTAAAALPELDHACGLGTGGLFEEDVAEPAAPVDGFLAVARTTPDPARLQALGAPPQRRQWWIDRVKACYSLLVPSFG