ispD Resolved · high auto-curated
H37Rv Rv3582c · MTBC0 mtbc0_003801 ·
231 aa · 4048021–4048716 (-) ·
RefSeq NP_218099.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase |
|---|---|
| MTBC0 PGAP re-annotation | 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase |
| Revised (this work) | 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase. Pfam: IspD (PF01128.26), CTP_transf_3 (PF02348.26), NTP_transf_3 (PF12804.14). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WKG9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase |
| EC (curated) |
EC 2.7.7.60
|
| Curated function | Catalyzes the formation of 4-diphosphocytidyl-2-C-methyl-D-erythritol from CTP and 2-C-methyl-D-erythritol 4-phosphate (MEP). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
|---|---|
| Preferred name | ispD |
| eggNOG description | Catalyzes the formation of 4-diphosphocytidyl-2-C- methyl-D-erythritol from CTP and 2-C-methyl-D-erythritol 4- phosphate (MEP) |
| Orthologous group | COG1211 |
| EC number |
EC 2.7.7.60
|
| KEGG orthology |
K00991
|
| KEGG pathways |
map00900, map01100, map01110, map01130
|
| KEGG modules |
M00096
|
| Gene Ontology (73) |
GO:0000166, GO:0000287, GO:0001882, GO:0001884, GO:0002135, GO:0003674, GO:0003824, GO:0005488, GO:0005575, GO:0005623, GO:0005886, GO:0006081 +61 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 | 0.264 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 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 |
|---|---|---|---|---|
IspD | PF01128.26 | 2.1e-86 | 8–230 | 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase |
CTP_transf_3 | PF02348.26 | 5.3e-06 | 9–150 | Cytidylyltransferase |
NTP_transf_3 | PF12804.14 | 1.8e-09 | 10–135 | MobA-like NTP transferase domain |
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 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3581c ispF |
2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase | 999 | 1000 ctx | neighborhood:882 fusion:900 cooccurence:770 coexpression:949 textmining:965 |
Rv2870c dxr |
1-deoxy-D-xylulose 5-phosphate reductoisomerase | 998 | 977 ctx | cooccurence:762 database:900 textmining:957 |
Rv1011 ispE |
4-diphosphocytidyl-2C-methyl-D-erythritol kinase | 998 | 974 ctx | cooccurence:730 database:900 textmining:949 |
Rv3583c carD |
RNA polymerase-binding transcription factor CarD | 955 | 887 ctx | neighborhood:865 textmining:622 |
Rv3579c rlmB |
23S rRNA (guanosine(2251)-2'-O)-methyltransferase RlmB | 800 | 800 ctx | neighborhood:799 |
Rv3580c cysS1 |
cysteine--tRNA ligase | 800 | 800 ctx | neighborhood:799 |
Rv2868c gcpE |
4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (flavodoxin) | 986 | 762 ctx | cooccurence:751 textmining:948 |
Rv1110 lytB2 |
4-hydroxy-3-methylbut-2-enyl diphosphate reductase | 910 | 761 ctx | cooccurence:750 textmining:642 |
Rv3382c lytB1 |
4-hydroxy-3-methylbut-2-enyl diphosphate reductase | 945 | 759 ctx | cooccurence:749 textmining:785 |
Rv3586 disA |
DNA integrity scanning protein DisA | 691 | 692 ctx | neighborhood:491 coexpression:419 |
Rv3585 radA |
DNA repair protein RadA | 710 | 665 ctx | neighborhood:453 coexpression:412 |
Rv2682c dxs1 |
1-deoxy-D-xylulose 5-phosphate synthase | 969 | 659 ctx | cooccurence:619 textmining:915 |
Rv3379c dxs2 |
1-deoxy-D-xylulose-5-phosphate synthase | 799 | 618 ctx | cooccurence:577 textmining:496 |
Rv3584 lpqE |
lipoprotein LpqE | 450 | 451 ctx | neighborhood:448 |
Rv2881c cdsA |
phosphatidate cytidylyltransferase | 430 | 224 |
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: 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase
- MTBC0 PGAP product: 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase
- Pfam (hmmscan --cut_ga): IspD PF01128.26 (E=2e-86), CTP_transf_3 PF02348.26 (E=5e-06), NTP_transf_3 PF12804.14 (E=2e-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_218099.1)
- Domains: Pfam-A via hmmscan --cut_ga — IspD (PF01128.26), CTP_transf_3 (PF02348.26), NTP_transf_3 (PF12804.14)
- 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
COG1211 - Curated reference: UniProt P9WKG9 (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 —
26 functional partner(s); context anchor
ispF - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003801|Rv3582c|ispD MVREAGEVVAIVPAAGSGERLAVGVPKAFYQLDGQTLIERAVDGLLDSGVVDTVVVAVPADRTDEARQILGHRAMIVAGGSNRTDTVNLALTVLSGTAEPEFVLVHDAARALTPPALVARVVEALRDGYAAVVPVLPLSDTIKAVDANGVVLGTPERAGLRAVQTPQGFTTDLLLRSYQRGSLDLPAAEYTDDASLVEHIGGQVQVVDGDPLAFKITTKLDLLLAQAIVRG