zwf2 Resolved · high auto-curated

H37Rv Rv1447c · MTBC0 mtbc0_001549 · 514 aa · 1634786–1636330 (-) · RefSeq NP_215963.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)glucose-6-phosphate 1-dehydrogenase
MTBC0 PGAP re-annotationglucose-6-phosphate dehydrogenase
Revised (this work)Glucose-6-phosphate 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.

Curated reference (UniProt)

UniProt P9WN73 SwissProt · reviewed · Evidence at protein level
UniProt nameGlucose-6-phosphate 1-dehydrogenase 2
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 namezwf
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) pseudogene candidate

pN/pS 0.328 · purifying
Polymorphic sites (≥ 0.1% of strains) 7 synonymous, 6 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 1.45% of strains (2106) · 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 2.3e-6532–215 Glucose-6-phosphate dehydrogenase, NAD binding domain
G6PD_CPF02781.22 6.1e-114217–512 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 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1445c devB 6-phosphogluconolactonase 999 1000 ctx neighborhood:811 fusion:899 cooccurence:762 coexpression:691 database:900 textmining:711
Rv1448c tal transaldolase 983 966 ctx neighborhood:881 coexpression:521 textmining:516
Rv0946c pgi glucose-6-phosphate isomerase 977 952 coexpression:480 database:900 textmining:550
Rv1449c tkt transketolase 982 949 ctx neighborhood:865 coexpression:439 textmining:674
Rv1844c gnd1 6-phosphogluconate dehydrogenase 962 927 ctx cooccurence:723 coexpression:659 textmining:505
Rv1446c opcA OXPP cycle protein OpcA 955 927 ctx neighborhood:811 coexpression:417 textmining:419
Rv1121 zwf1 glucose-6-phosphate 1-dehydrogenase 926 916 database:900
Rv1122 gnd2 6-phosphogluconate dehydrogenase (decarboxylating) 935 910 ctx fusion:643 cooccurence:718
Rv1436 gap glyceraldehyde 3-phosphate dehydrogenase 953 898 coexpression:428 database:800 textmining:560
Rv3068c pgmA phosphoglucomutase PgmA 933 890 database:800 textmining:419
Rv1617 pykA pyruvate kinase 915 847 database:800 textmining:470
Rv0489 gpm1 2,3-bisphosphoglycerate-dependent phosphoglycerate mutase 850 831 database:800
Rv0363c fba fructose-bisphosphate aldolase 865 815 database:800
Rv1438 tpi triosephosphate isomerase 891 814 database:800 textmining:440
Rv2702 ppgK polyphosphate glucokinase 848 811 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

  • Legacy H37Rv annotation: glucose-6-phosphate 1-dehydrogenase
  • MTBC0 PGAP product: glucose-6-phosphate dehydrogenase
  • Pfam (hmmscan --cut_ga): G6PD_N PF00479.29 (E=2e-65), G6PD_C PF02781.22 (E=6e-114)
  • (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_215963.1)
  • 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 P9WN73 (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

>mtbc0_001549|Rv1447c|zwf2
MKPAHAAASWRNPLRDKRDKRLPRIAGPCGMVIFGVTGDLARKKVMPAVYDLANRGLLPPTFSLVGFARRDWSTQDFGQVVYNAVQEHCRTPFRQQNWDRLAEGFRFVPGTFDDDDAFAQLAETLEKLDAERGTGGNHAFYLAIPPKSFPVVCEQLHKSGLARPQGDRWSRVVIEKPFGHDLASARELNKAVNAVFPEEAVFRIDHYLGKETVQNILALRFANQLFDPIWNAHYVDHVQITMAEDIGLGGRAGYYDGIGAARDVIQNHLMQLLALTAMEEPVSFHPAALQAEKIKVLSATRLAEPLDQTTSRGQYAAGWQGGEKVVGLLDEEGFAEDSTTETFAAITLEVDTRRWAGVPFYLRTGKRLGRRVTEIALVFRRAPHLPFDATMTDELGTNAMVIRVQPDEGVTLRFGSKVPGTAMEVRDVNMDFSYGSAFAEDSPEAYERLILDVLLGEPSLFPVNAEVELAWEILDPALEHWAAHGTPDAYEAGTWGPESSLEMLRRTGREWRRP