Rv2949c Family assigned · medium auto-curated
H37Rv Rv2949c · MTBC0 mtbc0_003131 ·
199 aa · 3321146–3321745 (-) ·
RefSeq NP_217465.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | chorismate pyruvate-lyase |
|---|---|
| MTBC0 PGAP re-annotation | chorismate pyruvate-lyase family protein |
| Revised (this work) | Chorismate pyruvate-lyase family protein. Pfam: Rv2949c-like (PF01947.22). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WIC5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Chorismate pyruvate-lyase |
| EC (curated) |
EC 4.1.3.40
|
| Curated function | Removes the pyruvyl group from chorismate to provide 4-hydroxybenzoate (4HB). Involved in the synthesis of glycosylated p-hydroxybenzoic acid methyl esters (p-HBADs) and phenolic glycolipids (PGL) that play important roles in the pathogenesis of mycobacterial infections. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| eggNOG description | Responsible for the direct conversion of chorismate to p-hydroxybenzoate, the substrate used in the production of glycosylated p-hydroxybenzoic acid methyl esters and structurally related phenolphthiocerol glycolipids. in M. tuberculosis, this is the sole enzymatic source of p- hydroxybenzoic acid |
| Orthologous group | COG3161 |
| EC number |
EC 4.1.3.40
|
| KEGG orthology |
K03181
|
| KEGG pathways |
map00130, map01100, map01110
|
| KEGG modules |
M00117
|
| Gene Ontology (34) |
GO:0003674, GO:0003824, GO:0006082, GO:0008150, GO:0008152, GO:0008813, GO:0009058, GO:0009273, GO:0009987, GO:0016043, GO:0016053, GO:0016829 +22 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 | 0.855 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 7 missense, 1 nonsense, 0 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.20% of strains (290) · clonal |
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 |
|---|---|---|---|---|
Rv2949c-like | PF01947.22 | 4.8e-12 | 24–173 | Chorismate pyruvate-lyase Rv2949c-like |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: fadD22 (p-hydroxybenzoyl--AMP ligase), high confidence from genomic context alone (score 981 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2948c fadD22 |
p-hydroxybenzoyl--AMP ligase | 987 | 981 ctx | neighborhood:739 coexpression:839 database:500 |
Rv2950c fadD29 |
long-chain-fatty-acid--AMP ligase FadD29 | 983 | 976 ctx | neighborhood:835 coexpression:860 |
Rv2947c pks15 |
polyketide synthase | 949 | 939 ctx | neighborhood:746 coexpression:770 |
Rv3215 entC |
isochorismate synthase | 910 | 901 | database:900 |
Rv0948c |
chorismate mutase | 821 | 810 | database:800 |
Rv1885c |
chorismate mutase | 820 | 809 | database:800 |
Rv1609 trpE |
anthranilate synthase component I | 818 | 808 | database:800 |
Rv2540c aroF |
chorismate synthase | 808 | 801 | database:800 |
Rv1600 hisC1 |
histidinol-phosphate aminotransferase | 800 | 801 | database:800 |
Rv3772 hisC2 |
histidinol-phosphate aminotransferase | 800 | 800 | database:800 |
Rv2231c cobC |
aminotransferase | 800 | 800 | database:800 |
Rv2946c pks1 |
polyketide synthase | 816 | 778 ctx | neighborhood:767 |
Rv0355c PPE8 |
PPE family protein PPE8 | 767 | 767 ctx | cooccurence:766 |
Rv3347c PPE55 |
PPE family protein PPE55 | 765 | 766 ctx | cooccurence:764 |
Rv3343c PPE54 |
PPE family protein PPE54 | 764 | 765 ctx | cooccurence:757 |
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 pyruvate-lyase
- MTBC0 PGAP product: chorismate pyruvate-lyase family protein
- Pfam (hmmscan --cut_ga): Rv2949c-like PF01947.22 (E=5e-12)
- (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_217465.1)
- Domains: Pfam-A via hmmscan --cut_ga — Rv2949c-like (PF01947.22)
- 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
COG3161 - Curated reference: UniProt P9WIC5 (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 —
117 functional partner(s); context anchor
fadD22 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003131|Rv2949c| MTECFLSDQEIRKLNRDLRILIAANGTLTRVLNIVADDEVIVQIVKQRIHDVSPKLSEFEQLGQVGVGRVLQRYIILKGRNSEHLFVAAESLIAIDRLPAAIITRLTQTNDPLGEVMAASHIETFKEEAKVWVGDLPGWLALHGYQNSRKRAVARRYRVISGGQPIMVVTEHFLRSVFRDAPHEEPDRWQFSNAITLAR