aroF Resolved · high auto-curated

H37Rv Rv2540c · MTBC0 mtbc0_002706 · 401 aa · 2886097–2887302 (-) · RefSeq NP_217056.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)chorismate synthase
MTBC0 PGAP re-annotationchorismate synthase
Revised (this work)Chorismate synthase. Pfam: Chorismate_synt (PF01264.27).

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

Curated reference (UniProt)

UniProt P9WPY1 SwissProt · reviewed · Evidence at protein level
UniProt nameChorismate synthase
EC (curated) EC 4.2.3.5
Curated functionCatalyzes the anti-1,4-elimination of the C-3 phosphate and the C-6 proR hydrogen from 5-enolpyruvylshikimate-3-phosphate (EPSP) to yield chorismate, which is the branch point compound that serves as the starting substrate for the three terminal pathways of aromatic amino acid biosynthesis. This reaction introduces a second double bond into the aromatic ring system.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
Preferred namearoC
eggNOG descriptionCatalyzes the anti-1,4-elimination of the C-3 phosphate and the C-6 proR hydrogen from 5-enolpyruvylshikimate-3-phosphate (EPSP) to yield chorismate, which is the branch point compound that serves as the starting substrate for the three terminal pathways of aromatic amino acid biosynthesis. This reaction introduces a second double bond into the aromatic ring system
Orthologous groupCOG0082
EC number EC 4.2.3.5
KEGG orthology K01736
KEGG pathways map00400, map01100, map01110, map01130, map01230
KEGG modules M00022
Gene Ontology (63) GO:0000166, GO:0003674, GO:0003824, GO:0004107, GO:0005488, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0006082, GO:0006520 +51 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 0.062 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 6 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
Chorismate_syntPF01264.27 1.3e-1192–367 Chorismate synthase

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

Closest characterised functional partner: aroB (3-dehydroquinate synthase), high confidence from genomic context alone (score 994 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2538c aroB 3-dehydroquinate synthase 999 994 ctx neighborhood:882 cooccurence:751 coexpression:813 textmining:922
Rv3227 aroA 3-phosphoshikimate 1-carboxyvinyltransferase 995 989 ctx cooccurence:508 coexpression:770 database:900 textmining:561
Rv2539c aroK shikimate kinase 997 980 ctx neighborhood:882 cooccurence:756 textmining:863
Rv2455c korA 2-oxoglutarate oxidoreductase subunit KorA 968 967 experimental:965
Rv0948c chorismate mutase 975 965 coexpression:644 database:900
Rv1885c chorismate mutase 974 965 coexpression:643 database:900
Rv1609 trpE anthranilate synthase component I 968 948 database:900 textmining:410
Rv2537c aroD 3-dehydroquinate dehydratase 947 912 ctx neighborhood:882 textmining:420
Rv2386c mbtI salicylate synthase 944 910 ctx cooccurence:441 database:800 textmining:410
Rv3215 entC isochorismate synthase 935 910 ctx cooccurence:548 database:800
Rv1005c pabB para-aminobenzoate synthase component I 918 910 ctx cooccurence:433 database:800
Rv2552c aroE shikimate 5-dehydrogenase 981 909 ctx neighborhood:544 cooccurence:679 coexpression:427 textmining:804
Rv0013 trpG anthranilate synthase component II 917 901 ctx cooccurence:412 database:800
Rv3754 tyrA prephenate dehydrogenase TyrA 944 809 coexpression:709 textmining:719
Rv2949c chorismate pyruvate-lyase 808 801 database:800

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: chorismate synthase
  • MTBC0 PGAP product: chorismate synthase
  • Pfam (hmmscan --cut_ga): Chorismate_synt PF01264.27 (E=1e-119)
  • (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_217056.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Chorismate_synt (PF01264.27)
  • 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 COG0082
  • Curated reference: UniProt P9WPY1 (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 — 63 functional partner(s); context anchor aroB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002706|Rv2540c|aroF
MLRWITAGESHGRALVAVVEGMVAGVHVTSADIADQLARRRLGYGRGARMTFERDAVTVLSGIRHGSTLGGPIAIEIGNTEWPKWETVMAADPVDPAELADVARNAPLTRPRPGHADYAGMLKYGFDDARPVLERASARETAARVAAGTVARAFLRQALGVEVLSHVISIGASAPYEGPPPRAEDLPAIDASPVRAYDKAAEADMIAQIEAAKKDGDTLGGVVEAVALGLPVGLGSFTSGDHRLDSQLAAAVMGIQAIKGVEIGDGFQTARRRGSRAHDEMYPGPDGVVRSTNRAGGLEGGMTNGQPLRVRAAMKPISTVPRALATVDLATGDEAVAIHQRSDVCAVPAAGVVVETMVALVLARAALEKFGGDSLAETQRNIAAYQRSVADREAPAARVSG