Rv3382c Resolved · high auto-curated
H37Rv Rv3382c · MTBC0 - ·
329 aa · 3796448–3797437 (-) ·
RefSeq YP_177967.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 4-hydroxy-3-methylbut-2-enyl diphosphate reductase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | 4-hydroxy-3-methylbut-2-enyl diphosphate reductase. Pfam: LYTB (PF02401.24). |
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 |
P9WKF9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | 4-hydroxy-3-methylbut-2-enyl diphosphate reductase 1 |
| EC (curated) |
EC 1.17.7.4
|
| Curated function | Catalyzes the conversion of 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate (HMBPP) into a mixture of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Acts in the terminal step of the DOXP/MEP pathway for isoprenoid precursor biosynthesis. Has a reduced activity compared with LytB2. Is unable to functionally complement the loss of lytB2 in M.tuberculosis. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolismM Cell wall / membrane / envelope biogenesis
|
|---|---|
| Preferred name | ispH |
| eggNOG description | Catalyzes the conversion of 1-hydroxy-2-methyl-2-(E)- butenyl 4-diphosphate (HMBPP) into a mixture of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Acts in the terminal step of the DOXP MEP pathway for isoprenoid precursor biosynthesis |
| Orthologous group | COG0761 |
| EC number |
EC 1.17.7.4
|
| KEGG orthology |
K03527
|
| KEGG pathways |
map00900, map01100, map01110, map01130
|
| KEGG modules |
M00096
|
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 | n/a |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 0 synonymous, 4 missense, 1 nonsense, 1 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 0.19% of strains (273) · clonal |
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 |
|---|---|---|---|---|
LYTB | PF02401.24 | 3.2e-93 | 20–301 | LytB protein |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: idsB (polyprenyl synthetase IdsB), high confidence from genomic context alone (score 988 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3383c idsB |
polyprenyl synthetase IdsB | 995 | 988 ctx | neighborhood:833 database:900 textmining:673 |
Rv2868c gcpE |
4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (flavodoxin) | 996 | 978 ctx | cooccurence:766 database:900 textmining:839 |
Rv1630 rpsA |
30S ribosomal protein S1 | 911 | 908 ctx | fusion:900 |
Rv1110 lytB2 |
4-hydroxy-3-methylbut-2-enyl diphosphate reductase | 913 | 907 | database:900 |
Rv2173 idsA2 |
geranylgeranyl pyrophosphate synthetase IdsA | 983 | 906 | database:900 textmining:828 |
Rv3398c idsA1 |
multifunctional dimethylallyltransferase/geranyltranstransferase/farnesyltranstransferase | 968 | 906 | database:900 textmining:675 |
Rv1745c idi |
isopentenyl-diphosphate delta-isomerase | 945 | 901 | database:900 textmining:477 |
Rv1086 |
(2Z,6E)-farnesyl diphosphate synthase | 907 | 901 | database:900 |
Rv3379c dxs2 |
1-deoxy-D-xylulose-5-phosphate synthase | 984 | 835 ctx | neighborhood:493 cooccurence:685 textmining:908 |
Rv3581c ispF |
2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase | 964 | 780 ctx | cooccurence:764 textmining:844 |
Rv2870c dxr |
1-deoxy-D-xylulose 5-phosphate reductoisomerase | 957 | 777 ctx | cooccurence:767 textmining:817 |
Rv3582c ispD |
2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase | 945 | 759 ctx | cooccurence:749 textmining:785 |
Rv2682c dxs1 |
1-deoxy-D-xylulose 5-phosphate synthase | 929 | 721 ctx | cooccurence:701 textmining:756 |
Rv1011 ispE |
4-diphosphocytidyl-2C-methyl-D-erythritol kinase | 873 | 714 ctx | cooccurence:705 textmining:577 |
Rv3381c |
Rv3381c, (MTV004.39c), len: 108 aa. Putative Transposase for IS6110 (fragment). Identical to many other M. tuberculosis IS6110 transposase s | 549 | 549 ctx | neighborhood:547 |
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-hydroxy-3-methylbut-2-enyl diphosphate reductase
- Pfam (hmmscan --cut_ga): LYTB PF02401.24 (E=3e-93)
- (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 YP_177967.1)
- Domains: Pfam-A via hmmscan --cut_ga — LYTB (PF02401.24)
- 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
COG0761 - Curated reference: UniProt P9WKF9 (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 —
22 functional partner(s); context anchor
idsB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3382c| MAEVFVGPVAQGYASGEVTVLLASPRSFCAGVERAIETVKRVLDVAEGPVYVRKQIVHNTVVVAELRDRGAVFVEDLDEIPDPPPPGAVVVFSAHGVSPAVRAGADERGLQVVDATCPLVAKVHAEAARFAARGDTVVFIGHAGHEETEGTLGVAPRSTLLVQTPADVAALNLPEGTQLSYLTQTTLALDETADVIDALRARFPTLGQPPSEDICYATTNRQRALQSMVGECDVVLVIGSCNSSNSRRLVELAQRSGTPAYLIDGPDDIEPEWLSSVSTIGVTAGASAPPRLVGQVIDALRGYASITVVERSIATETVRFGLPKQVRAQ