PGLS

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred cytosolic localization, consistent with the curated cytosolic/cytoplasmic location of PGLS and its role as a soluble oxidative-PPP enzyme. This represents the core subcellular location and is corroborated by HPA IDA (cytosol) and Reactome. Supporting Evidence: Reactome:R-HSA-71296 Cytosolic 6-phosphogluconolactonase (PGLS) catalyzes the hydrolysis of D-glucono-1,5-lactone 6-phosphate to form 6-phospho-D-gluconate file:human/PGLS/PGLS-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm
GO:0009051 pentose-phosphate shunt, oxidative branch	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred involvement in the oxidative branch of the pentose phosphate pathway. This is the core biological process for PGLS, which catalyses step 2 of the oxidative branch, and is well supported by direct biochemical characterisation of the human enzyme. Supporting Evidence: PMID:11457850 6-Phosphogluconolactonase is the second enzyme of the oxidative branch and
GO:0017057 6-phosphogluconolactonase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred 6-phosphogluconolactonase activity. This is the core molecular function of PGLS and is directly demonstrated for the human enzyme (EC 3.1.1.31; RHEA:12556). Supporting Evidence: PMID:10518023 shown to be 6-phosphogluconolactonase, the enzyme catalyzing the second step of the pentose phosphate pathway
GO:0005737 cytoplasm	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Electronic annotation from the UniProt Subcellular Location mapping (Cytoplasm). This is a correct but broad parent of the more precise cytosol location; keep as a non-core, less-specific localization. Reason: Correct localization but less specific than GO:0005829 (cytosol), which is supported by IBA and HPA IDA and better captures the location of this soluble enzyme. Supporting Evidence: file:human/PGLS/PGLS-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm
GO:0005975 carbohydrate metabolic process	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: InterPro2GO electronic annotation. Correct but very general; PGLS acts in carbohydrate metabolism, but the specific and informative process term is the oxidative pentose-phosphate branch. Keep as a non-core, high-level annotation. Reason: Broad parent process. The precise process (GO:0009051, pentose-phosphate shunt, oxidative branch) is annotated separately and is preferred as core.
GO:0006098 pentose-phosphate shunt	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation to the overall pentose-phosphate shunt. Correct; PGLS participates in the pentose phosphate pathway. This is a valid parent of the more specific oxidative-branch term and is also supported experimentally (PMID:10518023) and by Reactome. Supporting Evidence: file:human/PGLS/PGLS-uniprot.txt PATHWAY: Carbohydrate degradation; pentose phosphate pathway; D-
GO:0009051 pentose-phosphate shunt, oxidative branch	IEA GO_REF:0000117	ACCEPT	Summary: ARBA electronic annotation to the oxidative branch of the pentose phosphate pathway, consistent with the IBA and experimental evidence. Core biological process. Supporting Evidence: PMID:11457850 6-Phosphogluconolactonase is the second enzyme of the oxidative branch and
GO:0017057 6-phosphogluconolactonase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation (ARBA/InterPro/RHEA:12556/EC:3.1.1.31) to the core molecular function. Correct and directly supported by experimental characterisation of the human enzyme. Supporting Evidence: file:human/PGLS/PGLS-uniprot.txt EC=3.1.1.31 {ECO:0000269\|PubMed:10518023}
GO:0005515 protein binding	IPI PMID:21044950 Genome-wide YFP fluorescence complementation screen identifi...	MARK AS OVER ANNOTATED	Summary: Interaction reported from a genome-wide split-YFP (BiFC) complementation screen for regulators of telomere signaling (PGLS scored against a core telomeric protein; IntAct with UniProtKB:Q9NYB0/TERF2IP). This is a high-throughput binary-interaction dataset in which most hits had no prior functional link to the process, and no PGLS-specific functional characterization was performed. The bare term "protein binding" is uninformative about molecular function. Reason: High-throughput interactome hit captured only as the uninformative parent term GO:0005515. Retained (a genuine curated IPI), but not a core molecular function and not indicative of a specific binding role for PGLS. Supporting Evidence: PMID:21044950 we identified over 300 proteins that associated with the six core telomeric proteins
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Binary interaction from the HuRI human all-by-all reference interactome (PGLS-BLMH; IntAct with UniProtKB:Q13867). A systematic proteome-scale Y2H dataset with no PGLS-specific functional follow-up; the bare term "protein binding" is uninformative. Reason: Systematic interactome hit captured only as the uninformative parent term GO:0005515. Retained as a real curated IPI but not a core molecular function. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions
GO:0006098 pentose-phosphate shunt	TAS Reactome:R-HSA-71336	ACCEPT	Summary: Reactome traceable-author-statement annotation placing PGLS in the pentose phosphate pathway. Correct; PGLS catalyses step 2 (conversion of D-glucono-1,5-lactone 6-phosphate to 6-phospho-D-gluconate) of the pathway. Supporting Evidence: Reactome:R-HSA-71336 Conversion of D-glucono-1,5-lactone 6-phosphate to 6-phospho-D-gluconate
GO:0017057 6-phosphogluconolactonase activity	EXP PMID:10518023 Identification of the cDNA encoding human 6-phosphogluconola...	ACCEPT	Summary: Experimental demonstration that the human protein, expressed in E. coli and purified, is 6-phosphogluconolactonase. Direct evidence for the core molecular function. Supporting Evidence: PMID:10518023 The protein was expressed in Escherichia coli, purified and shown to be 6-phosphogluconolactonase, the enzyme catalyzing the second step of the pentose phosphate pathway
GO:0005654 nucleoplasm	IDA GO_REF:0000052	KEEP AS NON CORE	Summary: HPA immunofluorescence detected PGLS in the nucleoplasm in addition to the cytosol. Small soluble metabolic enzymes are frequently detected in the nucleoplasm by immunofluorescence, and no nuclear function of PGLS is described. Keep as a non-core localization. Reason: Immunofluorescence-based localization with no associated nuclear function; the core location is the cytosol. Not removed, as it is a valid curated IDA.
GO:0005829 cytosol	IDA GO_REF:0000052	ACCEPT	Summary: HPA immunofluorescence localizes PGLS to the cytosol, consistent with the IBA, Reactome, and UniProt cytoplasm annotations. Core subcellular location. Supporting Evidence: Reactome:R-HSA-71296 Cytosolic 6-phosphogluconolactonase (PGLS) catalyzes the hydrolysis of D-glucono-1,5-lactone 6-phosphate to form 6-phospho-D-gluconate
GO:0009051 pentose-phosphate shunt, oxidative branch	IMP PMID:31586547 γ-6-Phosphogluconolactone, a Byproduct of the Oxidative Pent...	ACCEPT	Summary: Genetic perturbation (knockdown/knockout) of PGLS in human cancer cells reduces oxidative-PPP flux, decreases 6-phosphogluconate, and causes accumulation of 6-phosphogluconolactone, confirming that PGLS acts within the oxidative branch of the pentose phosphate pathway. The paper's downstream signaling findings (gamma-6PGL to Src/PP2A/AMPK) are consequences of altered oxiPPP metabolite levels, and the annotation correctly uses the metabolic-branch process term. Supporting Evidence: PMID:31586547 The second enzyme in the oxiPPP, 6-phosphogluconolactonase (PGLS), converts 6PGL to PMID:31586547 stable knockdown of PGLS in Group I H1299 and K562 cells as well
GO:0017057 6-phosphogluconolactonase activity	IDA PMID:11457850 NMR spectroscopic analysis of the first two steps of the pen...	ACCEPT	Summary: NMR-based kinetic characterization directly demonstrating 6-phosphogluconolactonase activity of the human enzyme, acting on the delta form of 6-phosphogluconolactone. Direct evidence for the core molecular function. Supporting Evidence: PMID:11457850 6-phosphogluconolactonase activity accelerates hydrolysis of the delta form
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 PGLS in exosomes from expressed prostatic secretions in urine (~900 proteins detected). Abundant cytosolic enzymes are routinely detected in exosome proteomes; this does not indicate a functional extracellular localization. Reason: Bulk proteomic detection in secreted vesicles; not a functional or core localization for a cytosolic metabolic enzyme. Retained as a curated HDA observation. Supporting Evidence: PMID:23533145 In pooled EPS-urine exosome samples, ~900 proteins were detected
GO:0070062 extracellular exosome	HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos...	MARK AS OVER ANNOTATED	Summary: High-throughput mass-spectrometry detection of PGLS in human urinary exosomes. As above, abundant cytosolic enzymes commonly appear in exosome proteomes; not a functional localization. Reason: Bulk proteomic detection in secreted vesicles; not a core localization for this cytosolic enzyme. Supporting Evidence: PMID:19056867 we used LC-MS/MS to profile the proteome of human urinary exosomes
GO:0005829 cytosol	TAS Reactome:R-HSA-71296	ACCEPT	Summary: Reactome traceable-author-statement localizing PGLS to the cytosol, where it catalyses the hydrolysis of D-glucono-1,5-lactone 6-phosphate. Core subcellular location. Supporting Evidence: Reactome:R-HSA-71296 Cytosolic 6-phosphogluconolactonase (PGLS) catalyzes the hydrolysis of D-glucono-1,5-lactone 6-phosphate to form 6-phospho-D-gluconate
GO:0006098 pentose-phosphate shunt	IDA PMID:10518023 Identification of the cDNA encoding human 6-phosphogluconola...	ACCEPT	Summary: Direct evidence placing PGLS in the pentose phosphate pathway as the enzyme catalysing its second step. Correct; a valid parent of the oxidative-branch term. Supporting Evidence: PMID:10518023 shown to be 6-phosphogluconolactonase, the enzyme catalyzing the second step of the pentose phosphate pathway
GO:0017057 6-phosphogluconolactonase activity	IDA PMID:10518023 Identification of the cDNA encoding human 6-phosphogluconola...	ACCEPT	Summary: Direct biochemical demonstration that purified human PGLS has 6-phosphogluconolactonase activity. Core molecular function. Supporting Evidence: PMID:10518023 shown to be 6-phosphogluconolactonase, the enzyme catalyzing the second step of the pentose phosphate pathway

Gene Description

Existing Annotations Review

Core Functions

Hydrolysis of 6-phospho-D-glucono-1,5-lactone to 6-phospho-D-gluconate, the second reaction of the oxidative branch of the pentose phosphate pathway, acting downstream of G6PD and upstream of PGD/6PGD.

References

📚 Additional Documentation

Notes

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