gnd1 Resolved · high auto-curated

H37Rv Rv1844c · MTBC0 - · 485 aa · 2093731–2095188 (-) · RefSeq YP_177848.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)6-phosphogluconate dehydrogenase
MTBC0 PGAP re-annotation
Revised (this work)6-phosphogluconate dehydrogenase. Pfam: NAD_binding_2 (PF03446.22), 6PGD (PF00393.25).

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 Q79FJ2 TrEMBL · unreviewed · Evidence at protein level
UniProt name6-phosphogluconate dehydrogenase, decarboxylating
EC (curated) EC 1.1.1.44
Curated functionCatalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate and CO(2), with concomitant reduction of NADP to NADPH.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category G Carbohydrate transport and metabolism
Preferred namegnd
eggNOG descriptionCatalyzes the oxidative decarboxylation of 6- phosphogluconate to ribulose 5-phosphate and CO(2), with concomitant reduction of NADP to NADPH
Orthologous groupCOG0362
EC number EC 1.1.1.343, EC 1.1.1.44
KEGG orthology K00033
KEGG pathways map00030, map00480, map01100, map01110, map01120, map01130, map01200
KEGG modules M00004, M00006

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 0.605 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 9 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 10.18% of strains (14784) · 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
NAD_binding_2PF03446.22 2.0e-4612–183 NAD binding domain of 6-phosphogluconate dehydrogenase
6PGDPF00393.25 3.2e-125188–476 6-phosphogluconate dehydrogenase, C-terminal domain

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

Closest characterised functional partner: zwf1 (glucose-6-phosphate 1-dehydrogenase), high confidence from genomic context alone (score 928 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1445c devB 6-phosphogluconolactonase 958 942 database:900
Rv1121 zwf1 glucose-6-phosphate 1-dehydrogenase 973 928 ctx cooccurence:733 coexpression:658 textmining:650
Rv1408 rpe ribulose-phosphate 3-epimerase 951 928 database:900
Rv1447c zwf2 glucose-6-phosphate 1-dehydrogenase 962 927 ctx cooccurence:723 coexpression:659 textmining:505
Rv1122 gnd2 6-phosphogluconate dehydrogenase (decarboxylating) 916 916 database:900
Rv2465c rpiB ribose-5-phosphate isomerase B 919 908 database:900
Rv1449c tkt transketolase 897 855 coexpression:780
Rv1845c blaR sensor-transducer protein BlaR 848 848 ctx neighborhood:841
Rv1843c guaB1 inosine-5'-monophosphate dehydrogenase 847 846 ctx neighborhood:836
Rv1448c tal transaldolase 887 811 coexpression:757 textmining:430
Rv1846c blaI transcriptional repressor BlaI 760 761 ctx neighborhood:748
Rv1841c hyp hypothetical protein 733 734 ctx neighborhood:719
Rv1842c hyp hypothetical protein 731 732 ctx neighborhood:719
Rv1837c glcB malate synthase 668 620 ctx neighborhood:610
Rv1836c hyp hypothetical protein 570 570 ctx neighborhood:563

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): 6-phosphogluconate dehydrogenase
  • Pfam (hmmscan --cut_ga): NAD_binding_2 PF03446.22 (E=2e-46), 6PGD PF00393.25 (E=3e-125)
  • (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_177848.1)
  • Domains: Pfam-A via hmmscan --cut_ga — NAD_binding_2 (PF03446.22), 6PGD (PF00393.25)
  • 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 COG0362
  • Curated reference: UniProt Q79FJ2 (TrEMBL, unreviewed; 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 — 70 functional partner(s); context anchor zwf1
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv1844c|gnd1
MSSSESPAGIAQIGVTGLAVMGSNIARNFARHGYTVAVHNRSVAKTDALLKEHSSDGKFVRSETIPEFLAALEKPRRVLIMVKAGEATDADAVINELADAMEPGDIIIDGGNALYTDTMRREKAMRERGLHFVGAGISGGEEGALNGPSIMPGGPAESYQSLGPLLEEISAHVDGVPCCTHIGPDGSGHFVKMVHNGIEYSDMQLIGEAYQLMRDGLGLTAPAIADVFTEWNNGDLDSYLVEITAEVLRQTDAKTGKPLVDVIVDRAEQKGTGRWTVKSALDLGVPVTGIAEAVFARALSGSVGQRSAASGLASGKLGEQPADPATFTEDVRQALYASKIVAYAQGFNQIQAGSAEFGWDITPGDLATIWRGGCIIRAKFLNHIKEAFDASPNLASLIVAPYFRGAVESAIDSWRRVVSTAAQLGIPTPGFSSALSYYDALRTARLPAALTQAQRDFFGAHTYGRIDEPGKFHTLWSSDRTEVPV