zwf1 Resolved · high auto-curated

H37Rv Rv1121 · MTBC0 - · 466 aa · 1243707–1245107 (+) · RefSeq YP_177789.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)glucose-6-phosphate 1-dehydrogenase
MTBC0 PGAP re-annotation
Revised (this work)Glucose-6-phosphate 1-dehydrogenase. Pfam: G6PD_N (PF00479.29), G6PD_C (PF02781.22).

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 P9WN71 SwissProt · reviewed · Evidence at protein level
UniProt nameGlucose-6-phosphate 1-dehydrogenase 1
EC (curated) EC 1.1.1.49
Curated functionCatalyzes the oxidation of glucose 6-phosphate to 6-phosphogluconolactone.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category G Carbohydrate transport and metabolism
Preferred namezwf1
eggNOG descriptionCatalyzes the oxidation of glucose 6-phosphate to 6- phosphogluconolactone
Orthologous groupCOG0364
EC number EC 1.1.1.363, EC 1.1.1.49
KEGG orthology K00036
KEGG pathways map00030, map00480, map01100, map01110, map01120, map01130, map01200, map05230
KEGG modules M00004, M00006, M00008
Gene Ontology (6) GO:0005575, GO:0005623, GO:0005886, GO:0016020, GO:0044464, GO:0071944

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 0.677 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 7 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.17% of strains (252) · 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)

PfamAccessioni-EvalueResiduesDescription
G6PD_NPF00479.29 2.6e-4013–178 Glucose-6-phosphate dehydrogenase, NAD binding domain
G6PD_CPF02781.22 9.5e-88183–452 Glucose-6-phosphate dehydrogenase, C-terminal domain

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

Closest characterised functional partner: devB (6-phosphogluconolactonase), high confidence from genomic context alone (score 998 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1445c devB 6-phosphogluconolactonase 999 998 ctx fusion:827 cooccurence:755 coexpression:482 database:900 textmining:749
Rv1122 gnd2 6-phosphogluconate dehydrogenase (decarboxylating) 984 980 ctx neighborhood:851 fusion:454 cooccurence:754
Rv0946c pgi glucose-6-phosphate isomerase 974 952 coexpression:482 database:900 textmining:497
Rv1844c gnd1 6-phosphogluconate dehydrogenase 973 928 ctx cooccurence:733 coexpression:658 textmining:650
Rv1447c zwf2 glucose-6-phosphate 1-dehydrogenase 926 916 database:900
Rv1436 gap glyceraldehyde 3-phosphate dehydrogenase 951 899 coexpression:436 database:800 textmining:540
Rv3068c pgmA phosphoglucomutase PgmA 921 890 database:800
Rv1617 pykA pyruvate kinase 899 847 database:800
Rv0489 gpm1 2,3-bisphosphoglycerate-dependent phosphoglycerate mutase 851 832 database:800
Rv1438 tpi triosephosphate isomerase 871 818 database:800
Rv0363c fba fructose-bisphosphate aldolase 836 815 database:800
Rv2702 ppgK polyphosphate glucokinase 862 812 database:800
Rv0650 sugar kinase 895 811 database:800 textmining:473
Rv2241 aceE pyruvate dehydrogenase E1 component 830 809 database:800
Rv2455c korA 2-oxoglutarate oxidoreductase subunit KorA 807 808 database:800

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): glucose-6-phosphate 1-dehydrogenase
  • Pfam (hmmscan --cut_ga): G6PD_N PF00479.29 (E=3e-40), G6PD_C PF02781.22 (E=9e-88)
  • (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_177789.1)
  • Domains: Pfam-A via hmmscan --cut_ga — G6PD_N (PF00479.29), G6PD_C (PF02781.22)
  • 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 COG0364
  • Curated reference: UniProt P9WN71 (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 — 49 functional partner(s); context anchor devB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv1121|zwf1
MVDGGGGASDLLVIFGITGDLARKMTFRALYRLERHQLLDCPILGVASDDMSVGQLVKWARESIGRTEKIDDAVFDRLAGRLSYLHGDVTDSQLYDSLAELIGSACRPLYYLEMPPALFAPIVENLANVRLLERARVAVEKPFGHDLASALELNARLRAVLGEDQILRVDHFLGKQPVVELEYLRFANQALAELWDRNSISEIHITMAEDFGVEDRGKFYDAVGALRDVVQNHLLQVLALVTMEPPVGSSADDLNDKKAEVFRAMAPLDPDRCVRGQYLGYTEVAGVASDSATETYVALRTEIDNWRWAGVPIFVRAGKELPAKVTEVRLFLRRVPALAFLPNRRPAEPNQIVLRIDPDPGMRLQISAHTDDSWRDIHLDSSFAVDLGEPIRPYERLLYAGLVGDHQLFAREDSIEQTWRIVQPLLDNPGEIHRYDRGSWGPEAAQSLLRGHRGWQSPWLPRGTDA