ispF Resolved · high auto-curated
H37Rv Rv3581c · MTBC0 mtbc0_003800 ·
159 aa · 4047545–4048024 (-) ·
RefSeq NP_218098.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase |
|---|---|
| MTBC0 PGAP re-annotation | 2-C-methyl-D-erythritol 2%2C4-cyclodiphosphate synthase |
| Revised (this work) | 2-C-methyl-D-erythritol 2%2C4-cyclodiphosphate synthase. Pfam: YgbB (PF02542.22). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WKG5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase |
| EC (curated) |
EC 4.6.1.12
|
| Curated function | Involved in the biosynthesis of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), two major building blocks of isoprenoid compounds. Catalyzes the conversion of 4-diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate (CDP-ME2P) to 2-C-methyl-D-erythritol 2,4-cyclodiphosphate (ME-CPP) with a corresponding release of cytidine 5-monophosphate (CMP). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
|---|---|
| Preferred name | ispF |
| eggNOG description | Involved in the biosynthesis of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), two major building blocks of isoprenoid compounds. Catalyzes the conversion of 4- diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate (CDP-ME2P) to 2-C-methyl-D-erythritol 2,4-cyclodiphosphate (ME-CPP) with a corresponding release of cytidine 5-monophosphate (CMP) |
| Orthologous group | COG0245 |
| EC number |
EC 2.7.7.60, EC 4.6.1.12
|
| KEGG orthology |
K01770, K12506
|
| KEGG pathways |
map00900, map01100, map01110, map01130
|
| KEGG modules |
M00096
|
| Gene Ontology (23) |
GO:0003674, GO:0003824, GO:0006629, GO:0006720, GO:0006721, GO:0008150, GO:0008152, GO:0008299, GO:0008610, GO:0008685, GO:0009058, GO:0009987 +11 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 | 0.374 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 2 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 |
|---|---|---|---|---|
YgbB | PF02542.22 | 1.2e-52 | 6–155 | YgbB family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ispD (2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3582c ispD |
2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase | 999 | 1000 ctx | neighborhood:882 fusion:900 cooccurence:770 coexpression:949 textmining:965 |
Rv2868c gcpE |
4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (flavodoxin) | 998 | 978 ctx | cooccurence:774 database:900 textmining:936 |
Rv1011 ispE |
4-diphosphocytidyl-2C-methyl-D-erythritol kinase | 998 | 978 ctx | cooccurence:756 database:900 textmining:956 |
Rv3583c carD |
RNA polymerase-binding transcription factor CarD | 877 | 871 ctx | neighborhood:865 |
Rv3579c rlmB |
23S rRNA (guanosine(2251)-2'-O)-methyltransferase RlmB | 808 | 802 ctx | neighborhood:799 |
Rv3580c cysS1 |
cysteine--tRNA ligase | 801 | 802 ctx | neighborhood:799 |
Rv2870c dxr |
1-deoxy-D-xylulose 5-phosphate reductoisomerase | 988 | 792 ctx | cooccurence:773 textmining:948 |
Rv3382c lytB1 |
4-hydroxy-3-methylbut-2-enyl diphosphate reductase | 964 | 780 ctx | cooccurence:764 textmining:844 |
Rv1110 lytB2 |
4-hydroxy-3-methylbut-2-enyl diphosphate reductase | 906 | 776 ctx | cooccurence:762 textmining:600 |
Rv2682c dxs1 |
1-deoxy-D-xylulose 5-phosphate synthase | 971 | 756 ctx | cooccurence:735 textmining:889 |
Rv3379c dxs2 |
1-deoxy-D-xylulose-5-phosphate synthase | 853 | 731 ctx | cooccurence:715 textmining:477 |
Rv3586 disA |
DNA integrity scanning protein DisA | 546 | 546 ctx | neighborhood:509 |
Rv3585 radA |
DNA repair protein RadA | 491 | 491 ctx | neighborhood:453 |
Rv3584 lpqE |
lipoprotein LpqE | 451 | 451 ctx | neighborhood:448 |
Rv0904c accD3 |
acetyl-CoAcarboxylase carboxyl transferase subunit beta | 458 | 436 |
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: 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase
- MTBC0 PGAP product: 2-C-methyl-D-erythritol 2%2C4-cyclodiphosphate synthase
- Pfam (hmmscan --cut_ga): YgbB PF02542.22 (E=1e-52)
- (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_218098.1)
- Domains: Pfam-A via hmmscan --cut_ga — YgbB (PF02542.22)
- 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
COG0245 - Curated reference: UniProt P9WKG5 (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
ispD - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003800|Rv3581c|ispF MNQLPRVGLGTDVHPIEPGRPCWLVGLLFPSADGCAGHSDGDVAVHALCDAVLSAAGLGDIGEVFGVDDPRWQGVSGADMLRHVVVLITQHGYRVGNAVVQVIGNRPKIGWRRLEAQAVLSRLLNAPVSVSATTTDGLGLTGRGEGLAAIATALVVSLR