dxr Resolved · high auto-curated

H37Rv Rv2870c · MTBC0 mtbc0_003052 · 413 aa · 3202436–3203677 (-) · RefSeq NP_217386.2

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)1-deoxy-D-xylulose 5-phosphate reductoisomerase
MTBC0 PGAP re-annotation1-deoxy-D-xylulose-5-phosphate reductoisomerase
Revised (this work)1-deoxy-D-xylulose-5-phosphate reductoisomerase. Pfam: DXP_reductoisom (PF02670.23), DXP_redisom_C (PF08436.18), DXPR_C (PF13288.13).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt P9WNS1 SwissProt · reviewed · Evidence at protein level
UniProt name1-deoxy-D-xylulose 5-phosphate reductoisomerase
EC (curated) EC 1.1.1.267
Curated functionCatalyzes the NADPH-dependent rearrangement and reduction of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methyl-D-erythritol 4-phosphate (MEP).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Preferred namedxr
eggNOG descriptionCatalyzes the NADP-dependent rearrangement and reduction of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methyl-D-erythritol 4-phosphate (MEP)
Orthologous groupCOG0743
EC number EC 1.1.1.267
KEGG orthology K00099
KEGG pathways map00900, map01100, map01110, map01130
KEGG modules M00096
Gene Ontology (61) GO:0000166, GO:0000287, GO:0003674, GO:0003824, GO:0005488, GO:0006081, GO:0006082, GO:0006090, GO:0006629, GO:0006644, GO:0006720, GO:0006721 +49 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 0.092 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 1 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)

PfamAccessioni-EvalueResiduesDescription
DXP_reductoisomPF02670.23 1.0e-3515–135 1-deoxy-D-xylulose 5-phosphate reductoisomerase
DXP_redisom_CPF08436.18 2.5e-34147–230 1-deoxy-D-xylulose 5-phosphate reductoisomerase C-terminal domain
DXPR_CPF13288.13 1.2e-36263–380 DXP reductoisomerase C-terminal domain

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 977 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3582c ispD 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase 998 977 ctx cooccurence:762 database:900 textmining:957
Rv2682c dxs1 1-deoxy-D-xylulose 5-phosphate synthase 998 977 ctx cooccurence:747 database:900 textmining:931
Rv3379c dxs2 1-deoxy-D-xylulose-5-phosphate synthase 993 974 ctx cooccurence:729 database:900 textmining:742
Rv2868c gcpE 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (flavodoxin) 997 968 ctx neighborhood:865 cooccurence:772 textmining:928
Rv2869c rip zinc metalloprotease 953 934 ctx neighborhood:882 coexpression:464
Rv2867c GCN5-like N-acetyltransferase 801 801 ctx neighborhood:795
Rv3581c ispF 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase 988 792 ctx cooccurence:773 textmining:948
Rv1110 lytB2 4-hydroxy-3-methylbut-2-enyl diphosphate reductase 907 781 ctx cooccurence:766 textmining:594
Rv3382c lytB1 4-hydroxy-3-methylbut-2-enyl diphosphate reductase 957 777 ctx cooccurence:767 textmining:817
Rv1011 ispE 4-diphosphocytidyl-2C-methyl-D-erythritol kinase 987 772 ctx cooccurence:758 textmining:948
Rv2361c uppS decaprenyl diphosphate synthase 919 732 coexpression:687 textmining:713
Rv2881c cdsA phosphatidate cytidylyltransferase 816 714 coexpression:666
Rv2873 mpt83 cell surface lipoprotein 711 712 ctx neighborhood:711
Rv1086 (2Z,6E)-farnesyl diphosphate synthase 811 702 coexpression:691
Rv1087A Rv1087A, len: 106 aa (fragment). Conserved hypothetical protein, highly similar to C-terminus of near ORF O53434|YA86_MYCTU|Rv1086|MT1118|MT 725 696 coexpression:685

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: 1-deoxy-D-xylulose 5-phosphate reductoisomerase
  • MTBC0 PGAP product: 1-deoxy-D-xylulose-5-phosphate reductoisomerase
  • Pfam (hmmscan --cut_ga): DXP_reductoisom PF02670.23 (E=1e-35), DXP_redisom_C PF08436.18 (E=3e-34), DXPR_C PF13288.13 (E=1e-36)
  • (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_217386.2)
  • Domains: Pfam-A via hmmscan --cut_ga — DXP_reductoisom (PF02670.23), DXP_redisom_C (PF08436.18), DXPR_C (PF13288.13)
  • 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 COG0743
  • Curated reference: UniProt P9WNS1 (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 — 57 functional partner(s); context anchor ispD
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003052|Rv2870c|dxr
MTNSTDGRADGRLRVVVLGSTGSIGTQALQVIADNPDRFEVVGLAAGGAHLDTLLRQRAQTGVTNIAVADEHAAQRVGDIPYHGSDAATRLVEQTEADVVLNALVGALGLRPTLAALKTGARLALANKESLVAGGSLVLRAARPGQIVPVDSEHSALAQCLRGGTPDEVAKLVLTASGGPFRGWSAADLEHVTPEQAGAHPTWSMGPMNTLNSASLVNKGLEVIETHLLFGIPYDRIDVVVHPQSIIHSMVTFIDGSTIAQASPPDMKLPISLALGWPRRVSGAAAACDFHTASSWEFEPLDTDVFPAVELARQAGVAGGCMTAVYNAANEEAAAAFLAGRIGFPAIVGIIADVLHAADQWAVEPATVDDVLDAQRWARERAQRAVSGMASVAIASTAKPGAAGRHASTLERS