dxs1 Resolved · high auto-curated

H37Rv Rv2682c · MTBC0 - · 638 aa · 2998052–2999968 (-) · RefSeq YP_177898.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)1-deoxy-D-xylulose 5-phosphate synthase
MTBC0 PGAP re-annotation
Revised (this work)1-deoxy-D-xylulose 5-phosphate synthase. Pfam: DXP_synthase_N (PF13292.12), TPP_enzyme_C (PF02775.27), Transket_pyr (PF02779.30), Transketolase_C (PF02780.26).

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 P9WNS3 SwissProt · reviewed · Evidence at protein level
UniProt name1-deoxy-D-xylulose-5-phosphate synthase
EC (curated) EC 2.2.1.7
Curated functionCatalyzes the acyloin condensation reaction between C atoms 2 and 3 of pyruvate and glyceraldehyde 3-phosphate to yield 1-deoxy-D-xylulose-5-phosphate (DXP).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category F Nucleotide transport and metabolism
Preferred namedxs
eggNOG descriptionCatalyzes the acyloin condensation reaction between C atoms 2 and 3 of pyruvate and glyceraldehyde 3-phosphate to yield 1-deoxy-D-xylulose-5-phosphate (DXP)
Orthologous groupCOG1154
EC number EC 2.2.1.7
KEGG orthology K01662
KEGG pathways map00730, map00900, map01100, map01110, map01130
KEGG modules M00096
Gene Ontology (52) GO:0000287, GO:0003674, GO:0003824, GO:0005488, GO:0006081, GO:0006082, GO:0006090, GO:0006629, GO:0006644, GO:0006720, GO:0006793, GO:0006796 +40 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 0.095 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 11 synonymous, 3 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_synthase_NPF13292.12 1.4e-1082–278 1-deoxy-D-xylulose-5-phosphate synthase
TPP_enzyme_CPF02775.27 1.1e-04106–174 Thiamine pyrophosphate enzyme, C-terminal TPP binding domain
Transket_pyrPF02779.30 6.0e-45315–476 Transketolase, pyrimidine binding domain
Transketolase_CPF02780.26 4.7e-26500–612 Transketolase, C-terminal domain

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: dxr (1-deoxy-D-xylulose 5-phosphate reductoisomerase), high confidence from genomic context alone (score 977 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2870c dxr 1-deoxy-D-xylulose 5-phosphate reductoisomerase 998 977 ctx cooccurence:747 database:900 textmining:931
Rv3379c dxs2 1-deoxy-D-xylulose-5-phosphate synthase 908 905 database:900
Rv0417 thiG thiazole synthase 963 900 database:900 textmining:650
Rv1110 lytB2 4-hydroxy-3-methylbut-2-enyl diphosphate reductase 935 830 ctx cooccurence:706 coexpression:415 textmining:635
Rv2868c gcpE 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (flavodoxin) 942 776 ctx cooccurence:752 textmining:755
Rv3581c ispF 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase 971 756 ctx cooccurence:735 textmining:889
Rv3382c lytB1 4-hydroxy-3-methylbut-2-enyl diphosphate reductase 929 721 ctx cooccurence:701 textmining:756
Rv3582c ispD 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase 969 659 ctx cooccurence:619 textmining:915
Rv2683 hyp hypothetical protein 644 645 ctx neighborhood:645
Rv1011 ispE 4-diphosphocytidyl-2C-methyl-D-erythritol kinase 937 590 ctx cooccurence:575 textmining:853
Rv2684 arsA arsenic-transport integral membrane protein ArsA 543 543 ctx neighborhood:542
Rv1694 tlyA 16S/23S rRNA (cytidine-2'-O)-methyltransferase TlyA 469 469 coexpression:439
Rv2685 arsB1 arsenic-transport integral membrane protein ArsB 420 421 ctx neighborhood:412
Rv1695 ppnK inorganic polyphosphate/ATP-NAD kinase 615 414
Rv1415 ribA2 bifunctional riboflavin biosynthesis GTP cyclohydrolase II/3,4-dihydroxy-2-butanone 4-phosphate synthase 466 197

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): 1-deoxy-D-xylulose 5-phosphate synthase
  • Pfam (hmmscan --cut_ga): DXP_synthase_N PF13292.12 (E=1e-108), TPP_enzyme_C PF02775.27 (E=1e-04), Transket_pyr PF02779.30 (E=6e-45), Transketolase_C PF02780.26 (E=5e-26)
  • (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_177898.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DXP_synthase_N (PF13292.12), TPP_enzyme_C (PF02775.27), Transket_pyr (PF02779.30), Transketolase_C (PF02780.26)
  • 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 COG1154
  • Curated reference: UniProt P9WNS3 (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 — 37 functional partner(s); context anchor dxr
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2682c|dxs1
MLQQIRGPADLQHLSQAQLRELAAEIREFLIHKVAATGGHLGPNLGVVELTLALHRVFDSPHDPIIFDTGHQAYVHKMLTGRSQDFATLRKKGGLSGYPSRAESEHDWVESSHASAALSYADGLAKAFELTGHRNRHVVAVVGDGALTGGMCWEALNNIAASRRPVIIVVNDNGRSYAPTIGGVADHLATLRLQPAYEQALETGRDLVRAVPLVGGLWFRFLHSVKAGIKDSLSPQLLFTDLGLKYVGPVDGHDERAVEVALRSARRFGAPVIVHVVTRKGMGYPPAEADQAEQMHSTVPIDPATGQATKVAGPGWTATFSDALIGYAQKRRDIVAITAAMPGPTGLTAFGQRFPDRLFDVGIAEQHAMTSAAGLAMGGLHPVVAIYSTFLNRAFDQIMMDVALHKLPVTMVLDRAGITGSDGASHNGMWDLSMLGIVPGIRVAAPRDATRLREELGEALDVDDGPTALRFPKGDVGEDISALERRGGVDVLAAPADGLNHDVLLVAIGAFAPMALAVAKRLHNQGIGVTVIDPRWVLPVSDGVRELAVQHKLLVTLEDNGVNGGAGSAVSAALRRAEIDVPCRDVGLPQEFYEHASRSEVLADLGLTDQDVARRITGWVAALGTGVCASDAIPEHLD