ispE Resolved · high auto-curated
H37Rv Rv1011 · MTBC0 - ·
306 aa · 1130191–1131111 (+) ·
RefSeq NP_215527.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 4-diphosphocytidyl-2C-methyl-D-erythritol kinase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | 4-diphosphocytidyl-2C-methyl-D-erythritol kinase. Pfam: GHMP_kinases_N (PF00288.33), GHMP_kinases_C (PF08544.19). |
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 |
P9WKG7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase |
| EC (curated) |
EC 2.7.1.148
|
| Curated function | Catalyzes the phosphorylation of the position 2 hydroxy group of 4-diphosphocytidyl-2C-methyl-D-erythritol. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
F Nucleotide transport and metabolism
|
|---|---|
| Preferred name | ispE |
| eggNOG description | Catalyzes the phosphorylation of the position 2 hydroxy group of 4-diphosphocytidyl-2C-methyl-D-erythritol |
| Orthologous group | COG1947 |
| EC number |
EC 2.7.1.148
|
| KEGG orthology |
K00919
|
| KEGG pathways |
map00900, map01100, map01110, map01130
|
| KEGG modules |
M00096
|
| Gene Ontology (15) |
GO:0003674, GO:0003824, GO:0006793, GO:0006796, GO:0008150, GO:0008152, GO:0009987, GO:0016301, GO:0016310, GO:0016740, GO:0016772, GO:0016773 +3 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 | 0.569 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 3 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 |
|---|---|---|---|---|
GHMP_kinases_N | PF00288.33 | 5.0e-18 | 70–148 | GHMP kinases N terminal domain |
GHMP_kinases_C | PF08544.19 | 1.2e-09 | 207–280 | GHMP kinases C terminal |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ispF (2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase), high confidence from genomic context alone (score 978 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3581c ispF |
2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase | 998 | 978 ctx | cooccurence:756 database:900 textmining:956 |
Rv3582c ispD |
2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase | 998 | 974 ctx | cooccurence:730 database:900 textmining:949 |
Rv1010 ksgA |
rRNA small subunit methyltransferase A | 990 | 932 ctx | neighborhood:633 fusion:813 textmining:870 |
Rv2870c dxr |
1-deoxy-D-xylulose 5-phosphate reductoisomerase | 987 | 772 ctx | cooccurence:758 textmining:948 |
Rv2868c gcpE |
4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (flavodoxin) | 983 | 755 ctx | cooccurence:747 textmining:935 |
Rv1110 lytB2 |
4-hydroxy-3-methylbut-2-enyl diphosphate reductase | 886 | 728 ctx | cooccurence:718 textmining:600 |
Rv1012 hyp |
hypothetical protein | 728 | 728 ctx | neighborhood:727 |
Rv1013 pks16 |
polyketide synthase | 739 | 726 ctx | neighborhood:724 |
Rv3382c lytB1 |
4-hydroxy-3-methylbut-2-enyl diphosphate reductase | 873 | 714 ctx | cooccurence:705 textmining:577 |
Rv1009 rpfB |
resuscitation-promoting factor RpfB | 804 | 638 ctx | neighborhood:633 textmining:480 |
Rv2682c dxs1 |
1-deoxy-D-xylulose 5-phosphate synthase | 937 | 590 ctx | cooccurence:575 textmining:853 |
Rv3379c dxs2 |
1-deoxy-D-xylulose-5-phosphate synthase | 835 | 529 ctx | cooccurence:514 textmining:666 |
Rv1008 tatD |
deoxyribonuclease TatD | 850 | 463 ctx | neighborhood:461 textmining:733 |
Rv3923c rnpA |
ribonuclease P protein component | 447 | 448 | coexpression:403 |
Rv1292 argS |
arginine--tRNA ligase | 438 | 438 | coexpression:406 |
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): 4-diphosphocytidyl-2C-methyl-D-erythritol kinase
- Pfam (hmmscan --cut_ga): GHMP_kinases_N PF00288.33 (E=5e-18), GHMP_kinases_C PF08544.19 (E=1e-09)
- (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_215527.1)
- Domains: Pfam-A via hmmscan --cut_ga — GHMP_kinases_N (PF00288.33), GHMP_kinases_C (PF08544.19)
- 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
COG1947 - Curated reference: UniProt P9WKG7 (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 —
45 functional partner(s); context anchor
ispF - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv1011|ispE MPTGSVTVRVPGKVNLYLAVGDRREDGYHELTTVFHAVSLVDEVTVRNADVLSLELVGEGADQLPTDERNLAWQAAELMAEHVGRAPDVSIMIDKSIPVAGGMAGGSADAAAVLVAMNSLWELNVPRRDLRMLAARLGSDVPFALHGGTALGTGRGEELATVLSRNTFHWVLAFADSGLLTSAVYNELDRLREVGDPPRLGEPGPVLAALAAGDPDQLAPLLGNEMQAAAVSLDPALARALRAGVEAGALAGIVSGSGPTCAFLCTSASSAIDVGAQLSGAGVCRTVRVATGPVPGARVVSAPTEV