dxs2 Resolved · high auto-curated

H37Rv Rv3379c · MTBC0 - · 536 aa · 3793257–3794867 (-) · RefSeq NP_217896.1

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), 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 O50408 TrEMBL · unreviewed · Inferred from homology
UniProt name1-deoxy-D-xylulose-5-phosphate synthase
EC (curated) EC 2.2.1.7

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category H Coenzyme transport and metabolism
Preferred namedxs
eggNOG description1-deoxy-D-xylulose-5-phosphate synthase
Orthologous groupCOG1154
EC number EC 2.2.1.7
KEGG orthology K01662
KEGG pathways map00730, 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 0.639 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 9 missense, 0 nonsense, 2 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 61.62% of strains (89472) · reference-fixed

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 3.7e-501–128 1-deoxy-D-xylulose-5-phosphate synthase
Transket_pyrPF02779.30 2.2e-42212–372 Transketolase, pyrimidine binding domain
Transketolase_CPF02780.26 1.8e-23396–509 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 974 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2870c dxr 1-deoxy-D-xylulose 5-phosphate reductoisomerase 993 974 ctx cooccurence:729 database:900 textmining:742
Rv2682c dxs1 1-deoxy-D-xylulose 5-phosphate synthase 908 905 database:900
Rv0417 thiG thiazole synthase 938 901 database:900 textmining:410
Rv3382c lytB1 4-hydroxy-3-methylbut-2-enyl diphosphate reductase 984 835 ctx neighborhood:493 cooccurence:685 textmining:908
Rv3378c diterpene synthase 934 803 ctx neighborhood:801 textmining:680
Rv3377c type B diterpene cyclase 937 801 ctx neighborhood:801 textmining:697
Rv2868c gcpE 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (flavodoxin) 911 766 ctx cooccurence:744 textmining:637
Rv3581c ispF 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase 853 731 ctx cooccurence:715 textmining:477
Rv1110 lytB2 4-hydroxy-3-methylbut-2-enyl diphosphate reductase 818 707 ctx cooccurence:688 textmining:408
Rv3582c ispD 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase 799 618 ctx cooccurence:577 textmining:496
Rv1011 ispE 4-diphosphocytidyl-2C-methyl-D-erythritol kinase 835 529 ctx cooccurence:514 textmining:666
Rv3383c idsB polyprenyl synthetase IdsB 829 465 ctx neighborhood:407 textmining:694
Rv1694 tlyA 16S/23S rRNA (cytidine-2'-O)-methyltransferase TlyA 455 455 coexpression:424
Rv3380c Probable transposase; Rv3380c, (MTV004.38c), len: 328 aa. Probable transposase subunit for IS6110. Identical to many other M. tuberculosis I 883 433 ctx neighborhood:429 textmining:803
Rv3381c Rv3381c, (MTV004.39c), len: 108 aa. Putative Transposase for IS6110 (fragment). Identical to many other M. tuberculosis IS6110 transposase s 431 431 ctx neighborhood:429

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=4e-50), Transket_pyr PF02779.30 (E=2e-42), Transketolase_C PF02780.26 (E=2e-23)
  • (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_217896.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DXP_synthase_N (PF13292.12), 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 O50408 (TrEMBL, unreviewed; Inferred from homology)
  • 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 dxr
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3379c|dxs2
MFDTGHQTYPHKLLTGRGKDFATLRQADGLSGYPNRHESPHDWVENSHASVSLAWVDGIAKALALQGQCDRRVIAVIGDGALTGGVAWEGLNNLGAATRPVIVVLNDNGRSYDPTAGALAAHLEELRVGTPRGPNLFENMGFTYIGPVDGHNIPDTCAVLRKAAAAARPVVVHAVTSKGRGYPPAEADERDHMHACGVVDIATGLASTPSQRSWTDVFEDEIARIADDRSDVVGLTAAMRLPTGLGALSRRYPHRVFDSGIAEQHLLASAAGLAAAGTHPVVAVYSTFLHRAFDQLLFDIGLHRLPVTLVLDRAGVTGPDGPSHHGLWDLALLACVPGFQIACPRDAPRLRQQLRTAIATAAPTAVRFPKGAPGEPITAEHTIGGLDVLHTPPPHWRPDVLLVAVGAMSRPCMDAARCLSEEQIGVTVVDPQWVWPISPALTELAGRHRITVCVEDAIADVGIGAHLSHHIGRTHPRTRTYTLGLPPAYIPHASRDHILSSHGLTGPAIRIRCKSLLNALHEVPGPEDHPDSGDSY