lytB2 Resolved · high auto-curated
H37Rv Rv1110 · MTBC0 - ·
335 aa · 1236185–1237192 (+) ·
RefSeq YP_177788.1
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 |
P9WKG1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | 4-hydroxy-3-methylbut-2-enyl diphosphate reductase 2 |
| 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 higher activity compared with LytB2. Is essential for M.tuberculosis growth in vitro. |
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 | 0.355 · 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 |
|---|---|---|---|---|
LYTB | PF02401.24 | 1.1e-97 | 28–305 | LytB protein |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: gcpE (4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (flavodoxin)), high confidence from genomic context alone (score 979 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2868c gcpE |
4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (flavodoxin) | 992 | 979 ctx | cooccurence:766 database:900 textmining:648 |
Rv1630 rpsA |
30S ribosomal protein S1 | 912 | 909 ctx | fusion:900 |
Rv3382c lytB1 |
4-hydroxy-3-methylbut-2-enyl diphosphate reductase | 913 | 907 | database:900 |
Rv2173 idsA2 |
geranylgeranyl pyrophosphate synthetase IdsA | 970 | 906 | database:900 textmining:702 |
Rv3398c idsA1 |
multifunctional dimethylallyltransferase/geranyltranstransferase/farnesyltranstransferase | 964 | 906 | database:900 textmining:641 |
Rv3383c idsB |
polyprenyl synthetase IdsB | 957 | 906 | database:900 textmining:566 |
Rv1086 |
(2Z,6E)-farnesyl diphosphate synthase | 909 | 904 | database:900 |
Rv1745c idi |
isopentenyl-diphosphate delta-isomerase | 945 | 901 | database:900 textmining:477 |
Rv2682c dxs1 |
1-deoxy-D-xylulose 5-phosphate synthase | 935 | 830 ctx | cooccurence:706 coexpression:415 textmining:635 |
Rv1107c xseB |
exodeoxyribonuclease VII small subunit | 808 | 788 ctx | neighborhood:782 |
Rv1108c xseA |
exodeoxyribonuclease VII large subunit | 788 | 787 ctx | neighborhood:782 |
Rv1109c hyp |
hypothetical protein | 785 | 785 ctx | neighborhood:782 |
Rv1488 hyp |
hypothetical protein | 783 | 783 | coexpression:783 |
Rv2115c mpa |
proteasome-associated ATPase | 783 | 783 | coexpression:783 |
Rv2870c dxr |
1-deoxy-D-xylulose 5-phosphate reductoisomerase | 907 | 781 ctx | cooccurence:766 textmining:594 |
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=1e-97)
- (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_177788.1)
- 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 P9WKG1 (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 —
34 functional partner(s); context anchor
gcpE - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv1110|lytB2 MVPTVDMGIPGASVSSRSVADRPNRKRVLLAEPRGYCAGVDRAVETVERALQKHGPPVYVRHEIVHNRHVVDTLAKAGAVFVEETEQVPEGAIVVFSAHGVAPTVHVSASERNLQVIDATCPLVTKVHNEARRFARDDYDILLIGHEGHEEVVGTAGEAPDHVQLVDGVDAVDQVTVRDEDKVVWLSQTTLSVDETMEIVGRLRRRFPKLQDPPSDDICYATQNRQVAVKAMAPECELVIVVGSRNSSNSVRLVEVALGAGARAAHLVDWADDIDSAWLDGVTTVGVTSGASVPEVLVRGVLERLAECGYDIVQPVTTANETLVFALPRELRSPR