menD Resolved · high auto-curated
H37Rv Rv0555 · MTBC0 mtbc0_000584 ·
554 aa · 649849–651513 (+) ·
RefSeq NP_215069.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | bifunctional 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase/2-oxoglutarate decarboxylase |
|---|---|
| MTBC0 PGAP re-annotation | 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylic-acid synthase |
| Revised (this work) | 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylic-acid synthase. Pfam: TPP_enzyme_N (PF02776.24). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WK11
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate synthase |
| EC (curated) |
EC 2.2.1.9
|
| Curated function | Catalyzes the thiamine diphosphate-dependent decarboxylation of 2-oxoglutarate and the subsequent addition of the resulting succinic semialdehyde-thiamine pyrophosphate anion to isochorismate to yield 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate (SEPHCHC). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | menD |
| eggNOG description | Catalyzes the thiamine diphosphate-dependent decarboxylation of 2-oxoglutarate and the subsequent addition of the resulting succinic semialdehyde-thiamine pyrophosphate anion to isochorismate to yield 2-succinyl-5-enolpyruvyl-6-hydroxy-3- cyclohexene-1-carboxylate (SEPHCHC) |
| Orthologous group | COG1165 |
| EC number |
EC 2.2.1.9
|
| KEGG orthology |
K02551
|
| KEGG pathways |
map00130, map01100, map01110
|
| KEGG modules |
M00116
|
| Gene Ontology (8) |
GO:0005575, GO:0005623, GO:0005886, GO:0008150, GO:0016020, GO:0040007, GO:0044464, GO:0071944
|
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 | 0.049 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 8 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 |
|---|---|---|---|---|
TPP_enzyme_N | PF02776.24 | 1.3e-20 | 7–122 | Thiamine pyrophosphate enzyme, N-terminal TPP binding domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: menC (muconate cycloisomerase), high confidence from genomic context alone (score 960 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3215 entC |
isochorismate synthase | 995 | 962 | database:900 textmining:888 |
Rv0553 menC |
muconate cycloisomerase | 997 | 960 ctx | neighborhood:817 cooccurence:598 database:500 textmining:945 |
Rv0556 |
transmembrane protein | 884 | 884 ctx | neighborhood:882 |
Rv0548c menB |
1,4-dihydroxy-2-naphthoyl-CoA synthase | 992 | 881 ctx | neighborhood:419 cooccurence:770 textmining:935 |
Rv0554 bpoC |
non-heme bromoperoxidase BpoC | 854 | 849 ctx | neighborhood:820 |
Rv0557 mgtA |
GDP-mannose-dependent alpha-mannosyltransferase | 888 | 800 ctx | neighborhood:800 textmining:468 |
Rv0534c menA |
1,4-dihydroxy-2-naphthoate octaprenyltransferase | 850 | 800 ctx | cooccurence:766 |
Rv0552 hyp |
hypothetical protein | 683 | 683 ctx | neighborhood:682 |
Rv0542c menE |
2-succinylbenzoic acid--CoA ligase | 719 | 677 ctx | cooccurence:530 |
Rv0558 menH |
demethylmenaquinone methyltransferase | 982 | 643 ctx | neighborhood:641 textmining:953 |
Rv3909 hyp |
hypothetical protein | 555 | 556 ctx | cooccurence:530 |
Rv1931c |
transcriptional regulator | 544 | 544 ctx | neighborhood:544 |
Rv1930c hyp |
hypothetical protein | 544 | 544 ctx | neighborhood:544 |
Rv0551c fadD8 |
fatty-acid--CoA ligase FadD8 | 558 | 534 ctx | neighborhood:530 |
Rv2386c mbtI |
salicylate synthase | 518 | 506 | database:500 |
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: bifunctional 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase/2-oxoglutarate decarboxylase
- MTBC0 PGAP product: 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylic-acid synthase
- Pfam (hmmscan --cut_ga): TPP_enzyme_N PF02776.24 (E=1e-20)
- (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_215069.1)
- Domains: Pfam-A via hmmscan --cut_ga — TPP_enzyme_N (PF02776.24)
- 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
COG1165 - Curated reference: UniProt P9WK11 (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 —
25 functional partner(s); context anchor
menC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000584|Rv0555|menD MNPSTTQARVVVDELIRGGVRDVVLCPGSRNAPLAFALQDADRSGRIRLHVRIDERTAGYLAIGLAIGAGAPVCVAMTSGTAVANLGPAVVEANYARVPLIVLSANRPYELLGTGANQTMEQLGYFGTQVRASISLGLAEDAPERTSALNATWRSATCRVLAAATGARTANAGPVHFDIPLREPLVPDPEPLGAVTPPGRPAGKPWTYTPPVTFDQPLDIDLSVDTVVISGHGAGVHPNLAALPTVAEPTAPRSGDNPLHPLALPLLRPQQVIMLGRPTLHRPVSVLLADAEVPVFALTTGPRWPDVSGNSQATGTRAVTTGAPRPAWLDRCAAMNRHAIAAVREQLAAHPLTTGLHVAAAVSHALRPGDQLVLGASNPVRDVALAGLDTRGIRVRSNRGVAGIDGTVSTAIGAALAYEGAHERTGSPDSPPRTIALIGDLTFVHDSSGLLIGPTEPIPRSLTIVVSNDNGGGIFELLEQGDPRFSDVSSRIFGTPHDVDVGALCRAYHVESRQIEVDELGPTLDQPGAGMRVLEVKADRSSLRQLHAAIKAAL