6-phosphogluconate dehydrogenase (decarboxylating; EC 1.1.1.44) is the third enzyme and the second NADPH-producing step of the oxidative branch of the pentose phosphate pathway. It catalyses the oxidative decarboxylation of 6-phospho-D-gluconate to D-ribulose-5-phosphate and CO2, reducing NADP+ to NADPH. The enzyme is a cytosolic homodimer with a shared NADP-binding site between subunits. Its product ribulose-5-phosphate feeds the non-oxidative branch of the pathway, ultimately supplying ribose-5-phosphate for nucleotide biosynthesis, while the NADPH it generates supports reductive biosynthesis and cellular antioxidant defence.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004616 phosphogluconate dehydrogenase (decarboxylating) activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (PAN-GO) inference of the diagnostic catalytic activity of PGD, the third oxidative-PPP enzyme (EC 1.1.1.44). This is the core molecular function and is directly supported by biochemical and structural work on the human enzyme. Reason: Correct core molecular function, confirmed by direct experimental evidence on human PGD and by the UniProt catalytic-activity record. Supporting Evidence: file:human/PGD/PGD-uniprot.txt Catalyzes the oxidative decarboxylation of 6-phosphogluconate PMID:3965621 6-Phosphogluconate dehydrogenase has been purified from human brain |
| GO:0009051 pentose-phosphate shunt, oxidative branch | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference that PGD acts in the oxidative branch of the pentose phosphate pathway. PGD is the terminal (third) enzyme of this branch, generating ribulose-5-phosphate + CO2 + NADPH. Reason: Correct core biological process; PGD is definitionally an oxidative-PPP enzyme. Supporting Evidence: PMID:31586547 The third enzyme in the pathway, 6PGD, converts 6PG to ribulose-5-phosphate (Ru-5-P) and produces NADPH. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of cytosolic localization, consistent with UniProt subcellular location (Cytoplasm) and with the enzyme's role in cytosolic glucose metabolism. Reason: PGD is a soluble cytosolic enzyme; localization is correct and represents where it functions. Supporting Evidence: file:human/PGD/PGD-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0050661 NADP binding | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of NADP binding, a component activity of the enzyme. PGD binds NADP+ as cofactor; the crystal structures show an NADP-binding Rossmann fold with the dinucleotide shared between dimeric partners. Reason: Correct and supported by X-ray structures of human PGD in complex with NADP and by UniProt binding-site features. It is a molecular-function component of the catalytic activity rather than the diagnostic function itself. Supporting Evidence: file:human/PGD/PGD-uniprot.txt X-RAY CRYSTALLOGRAPHY (2.53 ANGSTROMS) IN COMPLEX WITH NADP |
| GO:0004616 phosphogluconate dehydrogenase (decarboxylating) activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic (InterPro/RHEA/EC) assignment of the catalytic activity, mapping EC 1.1.1.44 and RHEA:10116 to PGD. Duplicate of the experimentally supported core MF. Reason: Correct catalytic activity assignment; consistent with the diagnostic domain architecture (6PGD family) and the UniProt EC/RHEA cross-references. Supporting Evidence: file:human/PGD/PGD-uniprot.txt Reaction=6-phospho-D-gluconate + NADP(+) = D-ribulose 5-phosphate + CO2 |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt keyword/SubCell mapping to cytoplasm. Correct but less specific than the cytosol annotations. Reason: Consistent with the UniProt subcellular location; cytoplasm is a correct (if broader) parent of cytosol. Supporting Evidence: file:human/PGD/PGD-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0006098 pentose-phosphate shunt | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic assignment of the pentose phosphate pathway (parent of the oxidative branch). Correct but more general than the oxidative-branch term. Reason: Accurate parent process; PGD is a PPP enzyme. The more specific oxidative-branch term (GO:0009051) captures its precise role. Supporting Evidence: file:human/PGD/PGD-uniprot.txt PATHWAY: Carbohydrate degradation; pentose phosphate pathway |
| GO:0050661 NADP binding | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic (InterPro IPR006115, 6PGDH_NADP-bd) inference of NADP binding. Duplicate of the IBA NADP-binding annotation. Reason: Correct cofactor-binding activity, supported by the NADP-binding domain and crystal structures of the human enzyme. Supporting Evidence: file:human/PGD/PGD-uniprot.txt IPR006115; 6PGDH_NADP-bd |
| GO:0005829 cytosol | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl orthology-based transfer of cytosolic localization. Duplicate of the IBA/TAS cytosol annotations. Reason: Correct cytosolic localization, consistent across evidence lines. Supporting Evidence: file:human/PGD/PGD-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0006739 NADP+ metabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl orthology transfer reflecting that PGD reduces NADP+ to NADPH during catalysis. A general process term consistent with the enzyme's cofactor chemistry. Reason: The reaction consumes NADP+ and produces NADPH, so PGD participates in NADP+/NADPH metabolism. Broad but not wrong. Supporting Evidence: file:human/PGD/PGD-uniprot.txt with concomitant reduction of NADP |
| GO:0006740 NADPH regeneration | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl orthology transfer capturing PGD's role in NADPH production, the second NADPH-generating step of the oxidative PPP. Reason: PGD generates NADPH, a principal metabolic output of the oxidative PPP, supporting reductive biosynthesis and redox homeostasis. Supporting Evidence: PMID:31586547 The third enzyme in the pathway, 6PGD, converts 6PG to ribulose-5-phosphate (Ru-5-P) and produces NADPH. |
| GO:0009051 pentose-phosphate shunt, oxidative branch | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic assignment of oxidative-branch PPP involvement. Duplicate of the IBA oxidative-branch annotation and the core process of the gene. Reason: Correct core biological process for PGD. Supporting Evidence: file:human/PGD/PGD-uniprot.txt ribulose 5-phosphate from D-glucose 6-phosphate (oxidative stage): step |
| GO:0019521 D-gluconate metabolic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: UniProt keyword (Gluconate utilization) / Ensembl transfer. PGD's substrate is 6-phospho-D-gluconate, a phosphorylated gluconate derivative, so this term is a keyword-driven generalization of the substrate. Reason: Not wrong (the substrate is a gluconate phosphate), but "D-gluconate metabolic process" is a keyword-derived generalization; the precise role is captured by the oxidative-PPP process terms. Retained as non-core. Supporting Evidence: file:human/PGD/PGD-uniprot.txt Gluconate utilization |
| GO:0030246 carbohydrate binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl orthology-transferred generic binding term. This is an uninformative reflection of the enzyme binding its phosphosugar substrate rather than a distinct lectin-like carbohydrate-binding function. Reason: Generic substrate binding is already subsumed by the catalytic activity (GO:0004616). Carbohydrate binding implies a lectin-type function that PGD does not have; it is an over-annotation of ordinary substrate engagement. Supporting Evidence: file:human/PGD/PGD-uniprot.txt Reaction=6-phospho-D-gluconate + NADP(+) = D-ribulose 5-phosphate + CO2 |
| GO:0031406 carboxylic acid binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl orthology-transferred generic binding term reflecting that the substrate 6-phospho-D-gluconate is a carboxylic acid. Not an informative independent molecular function. Reason: Redundant with, and less informative than, the catalytic activity; ordinary substrate binding should not be annotated as a standalone molecular function. Supporting Evidence: file:human/PGD/PGD-uniprot.txt Reaction=6-phospho-D-gluconate + NADP(+) = D-ribulose 5-phosphate + CO2 |
| GO:0004616 phosphogluconate dehydrogenase (decarboxylating) activity | IDA PMID:23153533 Phosphoglycerate mutase 1 coordinates glycolysis and biosynt... | ACCEPT | Summary: Direct assay of recombinant human 6PGD, which converts 6-phosphogluconate to ribulose 5-phosphate in the presence of NADP+; the study also determined 6PGD/substrate binding and crystallized the human enzyme. Reason: Experimental (IDA) confirmation of the core catalytic activity of human PGD. Supporting Evidence: PMID:23153533 6-phosphogluconate dehydrogenase (6PGD), an enzyme that also produces NADPH while converting 6-phosphogluconate into ribulose 5-phosphate in the presence of NADP+ |
| GO:0004616 phosphogluconate dehydrogenase (decarboxylating) activity | IDA PMID:3965621 Human brain 6-phosphogluconate dehydrogenase: purification a... | ACCEPT | Summary: Enzyme purified from human brain with defined kinetic mechanism using NADP+ and 6-phosphogluconate as substrates, releasing CO2, ribulose 5-phosphate and NADPH. Reason: Direct experimental (IDA) confirmation of the catalytic activity on the human enzyme. Supporting Evidence: PMID:3965621 6-Phosphogluconate dehydrogenase has been purified from human brain |
| GO:0005829 cytosol | TAS Reactome:R-HSA-71299 | ACCEPT | Summary: Reactome traceable assertion placing PGD's decarboxylation reaction in the cytosol. Consistent with all other localization evidence. Reason: Correct cytosolic localization from a curated pathway source. Supporting Evidence: file:human/PGD/PGD-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9761846 | ACCEPT | Summary: Reactome traceable assertion (NFE2L2-dependent PGD gene expression context) placing PGD in the cytosol. Duplicate cytosol localization. Reason: Correct cytosolic localization from a curated pathway source. Supporting Evidence: file:human/PGD/PGD-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0009051 pentose-phosphate shunt, oxidative branch | IMP PMID:31586547 Ξ³-6-Phosphogluconolactone, a Byproduct of the Oxidative Pent... | ACCEPT | Summary: Knockdown of 6PGD reduces oxidative-PPP flux, NADPH/NADP+ ratio and its product ribulose-5-phosphate, establishing PGD's functional involvement in the oxidative branch of the PPP. Reason: Experimental (IMP) support that PGD activity is required for oxidative-PPP output; consistent with its identity as the third oxiPPP enzyme. Supporting Evidence: PMID:31586547 knockdown of 6PGD resulted in increased phosphorylation levels of AMPK and ACC1 in cancer cells PMID:31586547 The third enzyme in the pathway, 6PGD, converts 6PG to ribulose-5-phosphate (Ru-5-P) and produces NADPH. |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | MARK AS OVER ANNOTATED | Summary: High-throughput mass-spectrometry detection of PGD in exosomes isolated from expressed prostatic secretions in urine (a shotgun proteome of about 900 proteins). PGD is an abundant cytosolic enzyme commonly recovered as a passenger in vesicle proteomes. Reason: Proteomic detection in an exosome preparation does not indicate that extracellular exosome is a functional location of this cytosolic housekeeping enzyme; it reflects co-purification of an abundant protein. Not core; not removed because the protein was genuinely detected. Supporting Evidence: PMID:23533145 In pooled EPS-urine exosome samples, ~900 proteins were detected. |
| GO:0005634 nucleus | HDA PMID:21630459 Proteomic characterization of the human sperm nucleus. | MARK AS OVER ANNOTATED | Summary: High-throughput detection of PGD among 403 proteins in a purified human sperm nucleus proteome. PGD is a soluble cytosolic enzyme with no established nuclear function. Reason: Large-scale proteomic identification in a nuclear fraction does not establish a biological nuclear localization for this abundant cytosolic enzyme; likely co-purification. Retained (not removed) as a genuine detection but flagged as over-annotation. Supporting Evidence: PMID:21630459 different proteins have been identified from the isolated sperm nuclei |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | MARK AS OVER ANNOTATED | Summary: High-throughput MS detection of PGD in a 1132-protein human urinary exosome proteome. Consistent with recovery of an abundant cytosolic enzyme in vesicle preps. Reason: Proteomic co-purification, not a functional extracellular-exosome localization for this cytosolic enzyme. Supporting Evidence: PMID:19056867 analysis identified 1132 proteins unambiguously |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | MARK AS OVER ANNOTATED | Summary: High-throughput MS detection of PGD in a 539-protein B-cell-derived exosome proteome. Abundant cytosolic enzyme recovered as an exosomal passenger. Reason: Proteomic co-purification, not a functional extracellular-exosome localization. Supporting Evidence: PMID:20458337 identified 539 proteins, including known and not |
| GO:0004616 phosphogluconate dehydrogenase (decarboxylating) activity | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence-similarity (ISS) transfer of the catalytic activity from an ortholog (UniProtKB P00349). Duplicate of the experimentally supported core MF. Reason: Correct catalytic activity, redundantly supported by direct experimental evidence on the human enzyme. Supporting Evidence: file:human/PGD/PGD-uniprot.txt Belongs to the 6-phosphogluconate dehydrogenase family |
| GO:0006098 pentose-phosphate shunt | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence-similarity transfer of PPP involvement. Correct but more general than the oxidative-branch term. Reason: Accurate parent process; captured more specifically by GO:0009051. Supporting Evidence: file:human/PGD/PGD-uniprot.txt PATHWAY: Carbohydrate degradation; pentose phosphate pathway |
| GO:0009051 pentose-phosphate shunt, oxidative branch | IDA PMID:3858849 6-Phosphogluconolactonase deficiency, a hereditary erythrocy... | UNDECIDED | Summary: This IDA on the oxidative-PPP branch cites Beutler et al. 1985, whose abstract concerns hereditary deficiency of 6-phosphogluconolactonase (PGLS, EC 3.1.1.31), the second oxidative-PPP enzyme, and its interaction with G6PD deficiency, rather than PGD itself. The cached record is abstract-only. Reason: PGD's involvement in the oxidative branch of the PPP is well established by other annotations, but this specific reference (abstract-only) is about a different oxiPPP enzyme (PGLS/6-phosphogluconolactonase), so its support for a PGD annotation cannot be verified from the available text. Per policy, not removing an experimental annotation whose full text is unavailable; flagged as undecided pending the full text. Supporting Evidence: PMID:3858849 Partial deficiency of 6-phosphogluconolactonase (EC 3.1.1.31) of the erythrocytes was discovered as an autosomal dominant disorder. |
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