entC Resolved · high auto-curated
H37Rv Rv3215 · MTBC0 mtbc0_003421 ·
372 aa · 3614396–3615514 (+) ·
RefSeq NP_217731.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | isochorismate synthase |
|---|---|
| MTBC0 PGAP re-annotation | isochorismate synthase |
| Revised (this work) | Isochorismate 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.
Curated reference (UniProt)
| UniProt |
P9WFW9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Putative isochorismate synthase MenF |
| EC (curated) |
EC 5.4.4.2
|
| Curated function | Catalyzes the conversion of chorismate to isochorismate. |
UniProt still lists this protein as Putative isochorismate synthase MenF; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolismQ Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | entC |
| eggNOG description | Isochorismate synthase |
| Orthologous group | COG1169 |
| EC number |
EC 5.4.4.2
|
| KEGG orthology |
K02361, K02552
|
| KEGG pathways |
map00130, map01053, map01100, map01110, map01130
|
| KEGG modules |
M00116
|
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 | 0.055 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 7 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
Chorismate_bind | PF00425.25 | 8.2e-71 | 97–360 | chorismate binding enzyme |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mbtB (phenyloxazoline synthase), high confidence from genomic context alone (score 991 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2383c mbtB |
phenyloxazoline synthase | 997 | 991 ctx | neighborhood:544 coexpression:982 textmining:696 |
Rv0555 menD |
bifunctional 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase/2-oxoglutarate decarboxylase | 995 | 962 | database:900 textmining:888 |
Rv2386c mbtI |
salicylate synthase | 942 | 929 | database:900 |
Rv2384 mbtA |
2,3-dihydroxybenzoate-AMP ligase | 947 | 926 ctx | cooccurence:404 coexpression:854 |
Rv2540c aroF |
chorismate synthase | 935 | 910 ctx | cooccurence:548 database:800 |
Rv2949c |
chorismate pyruvate-lyase | 910 | 901 | database:900 |
Rv0013 trpG |
anthranilate synthase component II | 897 | 894 ctx | fusion:587 cooccurence:745 |
Rv3214 gpm2 |
phosphoglycerate mutase | 888 | 882 ctx | neighborhood:881 |
Rv1885c |
chorismate mutase | 906 | 871 | database:800 |
Rv0948c |
chorismate mutase | 887 | 870 | database:800 |
Rv2552c aroE |
shikimate 5-dehydrogenase | 880 | 862 | database:800 |
Rv1609 trpE |
anthranilate synthase component I | 866 | 854 | database:800 |
Rv3800c pks13 |
polyketide synthase | 864 | 809 | coexpression:782 |
Rv3772 hisC2 |
histidinol-phosphate aminotransferase | 812 | 805 | database:800 |
Rv2231c cobC |
aminotransferase | 810 | 804 | 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: isochorismate synthase
- MTBC0 PGAP product: isochorismate synthase
- Pfam (hmmscan --cut_ga): Chorismate_bind PF00425.25 (E=8e-71)
- (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_217731.1)
- 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 P9WFW9 (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 —
49 functional partner(s); context anchor
mbtB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003421|Rv3215|entC MSAHVATLHPEPPFALCGPRGTLIARGVRTRYCDVRAAQAALRSGTAPILLGALPFDVSRPAALMVPDGVLRARKLPDWPTGPLPKVRVAAALPPPADYLTRIGRARDLLAAFDGPLHKVVLARAVQLTADAPLDARVLLRRLVVADPTAYGYLVDLTSAGNDDTGAALVGASPELLVARSGNRVMCKPFAGSAPRAADPKLDAANAAALASSAKNRHEHQLVVDTMRVALEPLCEDLTIPAQPQLNRTAAVWHLCTAITGRLRNISTTAIDLALALHPTPAVGGVPTKAATELIAELEGDRGFYAGAVGWCDGRGDGHWVVSIRCAQLSADRRAALAHAGGGIVAESDPDDELEETTTKFATILTALGVEQ