mbtI Resolved · high auto-curated

H37Rv Rv2386c · MTBC0 - · 450 aa · 2678653–2680005 (-) · RefSeq YP_177877.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)salicylate synthase
MTBC0 PGAP re-annotation
Revised (this work)Salicylate synthase. Pfam: Chorismate_bind (PF00425.25).

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 P9WFX1 SwissProt · reviewed · Evidence at protein level
UniProt nameSalicylate synthase
EC (curated) EC 4.2.99.21, EC 5.4.4.2, EC 5.4.99.5
Curated functionInvolved in the incorporation of salicylate into the virulence-conferring salicylate-based siderophore mycobactin. Catalyzes the initial conversion of chorismate to yield the intermediate isochorismate (isochorismate synthase activity), and the subsequent elimination of the enolpyruvyl side chain to give salicylate (isochorismate pyruvate-lyase activity). In the absence of magnesium, MbtI displays a chorismate mutase activity and converts chorismate to prephenate.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category H Coenzyme transport and metabolism
Q Secondary metabolites biosynthesis, transport and catabolism
Preferred namembtI
eggNOG descriptionconversion of chorismate to
Orthologous groupCOG1169
EC number EC 4.2.99.21, EC 5.4.4.2
KEGG orthology K04781
KEGG pathways map01053, map01110, map01130
Gene Ontology (146) GO:0000162, GO:0000287, GO:0003674, GO:0003824, GO:0004049, GO:0004106, GO:0005488, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005886 +134 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 0.727 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 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
Chorismate_bindPF00425.25 2.4e-69185–438 chorismate binding enzyme

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

Closest characterised functional partner: trpG (anthranilate synthase component II), high confidence from genomic context alone (score 993 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0013 trpG anthranilate synthase component II 996 993 ctx fusion:529 cooccurence:770 coexpression:694 experimental:788 textmining:479
Rv2192c trpD anthranilate phosphoribosyltransferase 991 984 ctx cooccurence:762 coexpression:694 experimental:778 textmining:506
Rv2384 mbtA 2,3-dihydroxybenzoate-AMP ligase 998 971 ctx fusion:838 coexpression:810 textmining:946
Rv1611 trpC indole-3-glycerol phosphate synthase 973 957 ctx cooccurence:766 coexpression:646 experimental:461 textmining:416
Rv2383c mbtB phenyloxazoline synthase 996 932 coexpression:866 textmining:946
Rv3215 entC isochorismate synthase 942 929 database:900
Rv1612 trpB tryptophan synthase subunit beta 953 925 ctx cooccurence:737 coexpression:691 textmining:411
Rv1613 trpA tryptophan synthase subunit alpha 958 922 ctx cooccurence:761 coexpression:648 textmining:487
Rv2540c aroF chorismate synthase 944 910 ctx cooccurence:441 database:800 textmining:410
Rv2552c aroE shikimate 5-dehydrogenase 902 865 database:800
Rv1609 trpE anthranilate synthase component I 872 857 database:800
Rv3402c hyp hypothetical protein 913 831 coexpression:831 textmining:510
Rv2382c mbtC polyketide synthetase 978 825 coexpression:819 textmining:880
Rv0948c chorismate mutase 836 811 database:800
Rv1885c chorismate mutase 835 811 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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): salicylate synthase
  • Pfam (hmmscan --cut_ga): Chorismate_bind PF00425.25 (E=2e-69)
  • (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 YP_177877.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Chorismate_bind (PF00425.25)
  • 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 COG1169
  • Curated reference: UniProt P9WFX1 (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 — 41 functional partner(s); context anchor trpG
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2386c|mbtI
MSELSVATGAVSTASSSIPMPAGVNPADLAAELAAVVTESVDEDYLLYECDGQWVLAAGVQAMVELDSDELRVIRDGVTRRQQWSGRPGAALGEAVDRLLLETDQAFGWVAFEFGVHRYGLQQRLAPHTPLARVFSPRTRIMVSEKEIRLFDAGIRHREAIDRLLATGVREVPQSRSVDVSDDPSGFRRRVAVAVDEIAAGRYHKVILSRCVEVPFAIDFPLTYRLGRRHNTPVRSFLLQLGGIRALGYSPELVTAVRADGVVITEPLAGTRALGRGPAIDRLARDDLESNSKEIVEHAISVRSSLEEITDIAEPGSAAVIDFMTVRERGSVQHLGSTIRARLDPSSDRMAALEALFPAVTASGIPKAAGVEAIFRLDECPRGLYSGAVVMLSADGGLDAALTLRAAYQVGGRTWLRAGAGIIEESEPEREFEETCEKLSTLTPYLVARQ