gcpE Resolved · high auto-curated
H37Rv Rv2868c · MTBC0 mtbc0_003050 ·
387 aa · 3200034–3201197 (-) ·
RefSeq NP_217384.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (flavodoxin) |
|---|---|
| MTBC0 PGAP re-annotation | flavodoxin-dependent (E)-4-hydroxy-3-methylbut-2-enyl-diphosphate synthase |
| Revised (this work) | Flavodoxin-dependent (E)-4-hydroxy-3-methylbut-2-enyl-diphosphate synthase. Pfam: GcpE (PF04551.20), GcpE_C (PF26540.1). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WKG3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase |
| EC (curated) |
EC 1.17.7.3
|
| Curated function | Converts 2C-methyl-D-erythritol 2,4-cyclodiphosphate (ME-2,4cPP) into 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
|---|---|
| Preferred name | ispG |
| eggNOG description | Converts 2C-methyl-D-erythritol 2,4-cyclodiphosphate (ME-2,4cPP) into 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate |
| Orthologous group | COG0821 |
| EC number |
EC 1.17.7.1, EC 1.17.7.3
|
| KEGG orthology |
K03526
|
| KEGG pathways |
map00900, map01100, map01110, map01130
|
| KEGG modules |
M00096
|
| Gene Ontology (47) |
GO:0003674, GO:0003824, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0006081, GO:0006082, GO:0006090, GO:0006629, GO:0006644, GO:0006720 +35 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 | 0.582 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 5 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 |
|---|---|---|---|---|
GcpE | PF04551.20 | 1.0e-102 | 21–261 | GcpE TIM-barrel domain |
GcpE_C | PF26540.1 | 1.4e-31 | 276–362 | GcpE protein C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: lytB2 (4-hydroxy-3-methylbut-2-enyl diphosphate reductase), high confidence from genomic context alone (score 979 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1110 lytB2 |
4-hydroxy-3-methylbut-2-enyl diphosphate reductase | 992 | 979 ctx | cooccurence:766 database:900 textmining:648 |
Rv3581c ispF |
2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase | 998 | 978 ctx | cooccurence:774 database:900 textmining:936 |
Rv3382c lytB1 |
4-hydroxy-3-methylbut-2-enyl diphosphate reductase | 996 | 978 ctx | cooccurence:766 database:900 textmining:839 |
Rv2870c dxr |
1-deoxy-D-xylulose 5-phosphate reductoisomerase | 997 | 968 ctx | neighborhood:865 cooccurence:772 textmining:928 |
Rv2867c |
GCN5-like N-acetyltransferase | 842 | 842 ctx | neighborhood:807 |
Rv2869c rip |
zinc metalloprotease | 816 | 817 ctx | neighborhood:808 |
Rv2682c dxs1 |
1-deoxy-D-xylulose 5-phosphate synthase | 942 | 776 ctx | cooccurence:752 textmining:755 |
Rv3379c dxs2 |
1-deoxy-D-xylulose-5-phosphate synthase | 911 | 766 ctx | cooccurence:744 textmining:637 |
Rv3582c ispD |
2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase | 986 | 762 ctx | cooccurence:751 textmining:948 |
Rv1011 ispE |
4-diphosphocytidyl-2C-methyl-D-erythritol kinase | 983 | 755 ctx | cooccurence:747 textmining:935 |
Rv2580c hisS |
histidine--tRNA ligase | 712 | 676 | coexpression:649 |
Rv2864c |
penicillin-binding lipoprotein | 556 | 556 ctx | neighborhood:544 |
Rv2873 mpt83 |
cell surface lipoprotein | 554 | 554 ctx | neighborhood:550 |
Rv2871 vapB43 |
antitoxin VapB43 | 527 | 526 ctx | neighborhood:526 |
Rv2872 vapC43 |
ribonuclease VapC43 | 519 | 519 ctx | neighborhood:519 |
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: 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (flavodoxin)
- MTBC0 PGAP product: flavodoxin-dependent (E)-4-hydroxy-3-methylbut-2-enyl-diphosphate synthase
- Pfam (hmmscan --cut_ga): GcpE PF04551.20 (E=1e-102), GcpE_C PF26540.1 (E=1e-31)
- (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_217384.1)
- Domains: Pfam-A via hmmscan --cut_ga — GcpE (PF04551.20), GcpE_C (PF26540.1)
- 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
COG0821 - Curated reference: UniProt P9WKG3 (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 —
31 functional partner(s); context anchor
lytB2 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003050|Rv2868c|gcpE MTVGLGMPQPPAPTLAPRRATRQLMVGNVGVGSDHPVSVQSMCTTKTHDVNSTLQQIAELTAAGCDIVRVACPRQEDADALAEIARHSQIPVVADIHFQPRYIFAAIDAGCAAVRVNPGNIKEFDGRVGEVAKAAGAAGIPIRIGVNAGSLDKRFMEKYGKATPEALVESALWEASLFEEHGFGDIKISVKHNDPVVMVAAYELLAARCDYPLHLGVTEAGPAFQGTIKSAVAFGALLSRGIGDTIRVSLSAPPVEEVKVGNQVLESLNLRPRSLEIVSCPSCGRAQVDVYTLANEVTAGLDGLDVPLRVAVMGCVVNGPGEAREADLGVASGNGKGQIFVRGEVIKTVPEAQIVETLIEEAMRLAAEMGEQDPGATPSGSPIVTVS