PYGL

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: Glycogen phosphorylase is a soluble cytosolic enzyme; UniProt records the subcellular location as Cytoplasm, cytosol, and this IBA is concordant with Reactome TAS and UniProt-SubCell IEA assignments. Reason: Cytosol is the correct and well-supported site of action for this cytosolic glycogenolytic enzyme. Supporting Evidence: file:human/PYGL/PYGL-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0005980 glycogen catabolic process	IBA GO_REF:0000033	ACCEPT	Summary: PYGL catalyzes the rate-limiting step of glycogen breakdown, so glycogen catabolic process is its core biological process. This is the correct level of specificity and is supported across the phylogenetic tree of glycogen phosphorylases. Reason: Glycogen catabolic process is the precise, core biological process of the enzyme; well supported by IBA, experimental data and UniProt. Supporting Evidence: PMID:22225877 Glycogen phosphorylase (GP) catalyzes the rate-limiting step in glycogen catabolism and plays a key role in maintaining cellular and organismal glucose homeostasis.
GO:0008184 glycogen phosphorylase activity	IBA GO_REF:0000033	ACCEPT	Summary: Glycogen phosphorylase activity is the defining molecular function of PYGL. The IBA is concordant with direct experimental measurement of catalytic activity on human liver GP and with the EC 2.4.1.1 assignment. Reason: This is the core catalytic molecular function of the gene product, supported by phylogeny and by direct assay. Supporting Evidence: PMID:22225877 Glycogen phosphorylase (GP) catalyzes phosphorolytic cleavage of glycogen to produce glucose-1-phosphate for glucose-dependent tissues when body glucose is scarce.
GO:0004645 1,4-alpha-oligoglucan phosphorylase activity	IEA GO_REF:0000120	ACCEPT	Summary: This is the EC 2.4.1.1 / RHEA:41732 catalytic activity term (the parent of glycogen phosphorylase activity), assigned by automated pipelines from InterPro and the RHEA reaction. It correctly describes the phosphorolysis of alpha-1,4 glucan bonds and is experimentally confirmed for the human enzyme. Reason: Correct EC-mapped catalytic activity term; consistent with the experimentally determined reaction and with the more specific glycogen phosphorylase activity term also annotated. Supporting Evidence: file:human/PYGL/PYGL-uniprot.txt EC=2.4.1.1 {ECO:0000269\|PubMed:22225877}
GO:0005829 cytosol	IEA GO_REF:0000044	ACCEPT	Summary: Cytosol assigned automatically from the UniProt subcellular-location vocabulary (SL-0091), consistent with the curated Cytoplasm, cytosol location and with the IBA and Reactome TAS cytosol annotations. Reason: Correct localization for this cytosolic enzyme. Supporting Evidence: file:human/PYGL/PYGL-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0005975 carbohydrate metabolic process	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: Broad InterPro-derived process term. It is correct but much more general than the specific glycogen catabolic process that captures PYGL's actual role. Reason: Not wrong, but a high-level parent superseded by the specific glycogen catabolic process annotation; retained as a general, non-core term. Supporting Evidence: PMID:22225877 Glycogen phosphorylase (GP) catalyzes phosphorolytic cleavage of glycogen to produce glucose-1-phosphate for glucose-dependent tissues when body glucose is scarce.
GO:0005977 glycogen metabolic process	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ARBA machine-learning process term. Correct but a general parent of glycogen catabolic process, which is the precise role of the enzyme. Reason: Correct but general; the specific glycogen catabolic process term is the core BP. Retained as a broad, non-core annotation. Supporting Evidence: PMID:22225877 GP activity plays an important role in glucose homeostasis and glycogen metabolism.
GO:0008184 glycogen phosphorylase activity	IEA GO_REF:0000120	ACCEPT	Summary: Automated assignment of the core catalytic molecular function from InterPro/ARBA and mouse ortholog, redundant with and confirmed by the IBA and experimental (IDA/IMP/EXP) annotations to the same term. Reason: Correctly captures the defining catalytic activity of PYGL. Supporting Evidence: PMID:22225877 Glycogen phosphorylase (GP) catalyzes phosphorolytic cleavage of glycogen to produce glucose-1-phosphate for glucose-dependent tissues when body glucose is scarce.
GO:0030170 pyridoxal phosphate binding	IEA GO_REF:0000002	ACCEPT	Summary: Pyridoxal 5'-phosphate is the essential cofactor of glycogen phosphorylase, covalently bound via a Schiff base to Lys681. This InterPro-based IEA is strongly supported by the curated cofactor annotation and multiple crystal structures. Reason: PLP binding is a genuine, essential cofactor-binding function of the enzyme (Lys681 pyridoxal-phosphate attachment site). Supporting Evidence: file:human/PYGL/PYGL-uniprot.txt Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	MARK AS OVER ANNOTATED	Summary: Interaction detected in a large-scale binary interactome map; the GOA with/from is PYGB (P11216), the brain glycogen phosphorylase isoform. The bare protein binding term is uninformative about function. Reason: Bare protein binding gives no functional insight; the underlying PYGB interaction reflects glycogen-phosphorylase isoform association captured more informatively by the identical protein binding (homodimer) annotation. Retained but flagged as over-annotation per curation guidelines.
GO:0005515 protein binding	IPI PMID:25910212 Widespread macromolecular interaction perturbations in human...	MARK AS OVER ANNOTATED	Summary: Interaction from a systematic interactome-perturbation study; with/from is PYGB (P11216). The bare protein binding term is uninformative. Reason: Uninformative protein binding term; the PYGB partner reflects glycogen phosphorylase isoform association rather than a distinct function. Retained but flagged as over-annotation.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Interactions from a reference human binary interactome; with/from are PYGB (P11216) and PYGM (P11217), the other glycogen phosphorylase isoforms. The bare protein binding term is uninformative. Reason: Uninformative protein binding term; the PYGB/PYGM partners reflect glycogen phosphorylase isoform association. Retained but flagged as over-annotation.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: Interaction from a cell-specific interactome-remodeling map; with/from is PYGB (P11216). The bare protein binding term is uninformative. Reason: Uninformative protein binding term; PYGB partner reflects glycogen phosphorylase isoform association. Retained but flagged as over-annotation.
GO:0005980 glycogen catabolic process	IEA GO_REF:0000107	ACCEPT	Summary: Automated orthology-based transfer (from mouse Pygl, Q9ET01) of the core glycogen catabolic process, redundant with and confirmed by the IBA annotation to the same term. Reason: Correctly captures the core biological process of the enzyme; concordant with the IBA and with experimental evidence. Supporting Evidence: PMID:22225877 Glycogen phosphorylase (GP) catalyzes the rate-limiting step in glycogen catabolism and plays a key role in maintaining cellular and organismal glucose homeostasis.
GO:0004645 1,4-alpha-oligoglucan phosphorylase activity	EXP PMID:22225877 Acetylation negatively regulates glycogen phosphorylase by r...	ACCEPT	Summary: Zhang et al. directly assayed the phosphorolytic activity of purified human GP, establishing the EC 2.4.1.1 catalytic activity experimentally. This is the EC-mapped parent of glycogen phosphorylase activity. Reason: Experimentally supported core catalytic function; the enzyme phosphorolyses alpha-1,4 glucan bonds to yield glucose-1-phosphate. Supporting Evidence: PMID:22225877 Glycogen phosphorylase (GP) catalyzes phosphorolytic cleavage of glycogen to produce glucose-1-phosphate for glucose-dependent tissues when body glucose is scarce.
GO:0005536 D-glucose binding	IDA PMID:10980448 Human liver glycogen phosphorylase inhibitors bind at a new ...	ACCEPT	Summary: Crystallographic study of human liver glycogen phosphorylase; glucose is a physiological allosteric inhibitor that binds the enzyme and stabilizes the inactive conformation. The cached record is abstract-only, so the full ligand-binding detail read by the curator is not directly quotable here. Reason: D-glucose binding is a genuine, physiologically relevant ligand-binding function (product/end-product feedback inhibitor) demonstrated structurally for the human enzyme; experimental IDA, deferring to the full text read by the curator. Supporting Evidence: PMID:10980448 functions allosterically by stabilizing the inactive
GO:0005536 D-glucose binding	IDA PMID:12204691 Structure-activity analysis of the purine binding site of hu...	ACCEPT	Summary: Structure-activity study of human liver GP allosteric sites by crystallography and SPR. D-glucose binding is a genuine allosteric-ligand function; cached record is abstract-only. Reason: Experimentally supported ligand-binding function of the human enzyme; duplicate of the other D-glucose binding IDA, deferring to full text read by the curator. Supporting Evidence: PMID:12204691 regulated by multiple interacting allosteric sites, each of which is a potential
GO:0042802 identical protein binding	IPI PMID:10980448 Human liver glycogen phosphorylase inhibitors bind at a new ...	ACCEPT	Summary: PYGL is enzymatically active as a homodimer, as established by the crystal structures of human liver GP (with/from P06737, self-interaction). This is the functionally relevant, informative self-association. Reason: The homodimer is the biologically active unit of glycogen phosphorylase; identical protein binding correctly and informatively captures the self-association (unlike bare protein binding). Supporting Evidence: file:human/PYGL/PYGL-uniprot.txt SUBUNIT: Homodimer; enzymatically active
GO:0005576 extracellular region	TAS Reactome:R-HSA-6798748	MARK AS OVER ANNOTATED	Summary: Assigned via a Reactome neutrophil-degranulation/secretory-granule exocytosis module. PYGL is a cytosolic glycogenolytic enzyme; its presence in the extracellular region reflects secretome/degranulation cataloguing rather than a site of function. Reason: PYGL functions in the cytosol; extracellular localization is a bystander catalog assignment from a degranulation pathway, not a functional location. Supporting Evidence: file:human/PYGL/PYGL-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0005576 extracellular region	TAS Reactome:R-HSA-6800434	MARK AS OVER ANNOTATED	Summary: Same as the other extracellular-region assignment, from a Reactome ficolin-rich granule exocytosis module. Not a functional location for this cytosolic enzyme. Reason: Bystander secretome/degranulation catalog assignment; PYGL acts in the cytosol. Supporting Evidence: file:human/PYGL/PYGL-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0034774 secretory granule lumen	TAS Reactome:R-HSA-6798748	MARK AS OVER ANNOTATED	Summary: From a Reactome secretory-granule exocytosis module. PYGL is cytosolic; granule-lumen localization is a bystander proteomic/degranulation catalog assignment, not a functional site. Reason: Not a functional location for this cytosolic glycogenolytic enzyme. Supporting Evidence: file:human/PYGL/PYGL-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:1904813 ficolin-1-rich granule lumen	TAS Reactome:R-HSA-6800434	MARK AS OVER ANNOTATED	Summary: From a Reactome ficolin-rich granule exocytosis module. As with the other granule/extracellular assignments, this is a bystander catalog location, not the functional site of the cytosolic enzyme. Reason: Not a functional location for this cytosolic glycogenolytic enzyme. Supporting Evidence: file:human/PYGL/PYGL-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0070062 extracellular exosome	HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres...	MARK AS OVER ANNOTATED	Summary: PYGL was detected among ~900 proteins in a shotgun proteomic survey of exosomes from prostatic secretions in urine. This is a high-throughput proteome-cataloguing localization, not evidence of a functional exosomal role for this cytosolic enzyme. Reason: Detection in an exosome proteome catalog does not indicate a functional site; PYGL acts in the cytosol. Supporting Evidence: PMID:23533145 In pooled EPS-urine exosome samples, ~900 proteins were detected.
GO:0008184 glycogen phosphorylase activity	IDA PMID:22225877 Acetylation negatively regulates glycogen phosphorylase by r...	ACCEPT	Summary: Zhang et al. directly measured the glycogen phosphorylase catalytic activity of purified human GP (and its regulation by acetylation/PP1), providing direct experimental evidence for this core molecular function. Reason: Direct experimental demonstration of the core catalytic activity of PYGL. Supporting Evidence: PMID:22225877 Glycogen phosphorylase (GP) catalyzes phosphorolytic cleavage of glycogen to produce glucose-1-phosphate for glucose-dependent tissues when body glucose is scarce.
GO:0005829 cytosol	TAS Reactome:R-HSA-453339	ACCEPT	Summary: Reactome cytosol assignment for the glycogenolysis reaction (glycogen + phosphate to glucose-1-phosphate). This is the correct functional location for PYGL. Reason: Cytosol is the correct site of the glycogenolytic reaction catalyzed by PYGL; concordant with IBA and UniProt. Supporting Evidence: file:human/PYGL/PYGL-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0005829 cytosol	TAS Reactome:R-HSA-71588	ACCEPT	Summary: Reactome cytosol assignment for the phosphorylase b to a interconversion reaction. Correct functional location. Reason: Cytosol is the correct site of action; concordant with IBA and UniProt. Supporting Evidence: file:human/PYGL/PYGL-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0005829 cytosol	TAS Reactome:R-HSA-71590	ACCEPT	Summary: Reactome cytosol assignment for glycogen limit-dextrin formation with release of glucose-1-phosphate. Correct functional location. Reason: Cytosol is the correct site of the glycogenolytic reaction; concordant with IBA and UniProt. Supporting Evidence: file:human/PYGL/PYGL-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0002060 purine nucleobase binding	IDA PMID:12204691 Structure-activity analysis of the purine binding site of hu...	MARK AS OVER ANNOTATED	Summary: Derived from a crystallographic/SPR structure-activity screen of ligands at the purine allosteric inhibitor site of human liver GP, a drug-discovery target site. This binding is real structurally but peripheral to the enzyme's biological function. Reason: Purine-nucleobase binding reflects a pharmacological/inhibitor-screen site rather than a core physiological binding function; retained but flagged as over-annotation. Not removed, as it is an experimental IDA. Supporting Evidence: PMID:12204691 compounds that bind to the purine allosteric inhibitor site.
GO:0005524 ATP binding	IDA PMID:10949035 Activation of human liver glycogen phosphorylase by alterati...	ACCEPT	Summary: ATP is a physiological allosteric inhibitor of glycogen phosphorylase, binding at the nucleotide (AMP) allosteric site; UniProt records inhibition by ATP among the allosteric controls. The cited crystallographic study of the active/inactive human liver GP is abstract-only in the cache. Reason: ATP binding at the allosteric nucleotide site is a genuine regulatory binding function of the enzyme (ATP inhibits GP); experimental IDA, deferring to the full text read by the curator. Supporting Evidence: file:human/PYGL/PYGL-uniprot.txt being activated by AMP and inhibited by ATP,
GO:0005977 glycogen metabolic process	IMP PMID:10980448 Human liver glycogen phosphorylase inhibitors bind at a new ...	KEEP AS NON CORE	Summary: Involvement in glycogen metabolism supported by structural/functional study of the human liver enzyme. This is a correct but general parent of the specific glycogen catabolic process, which better captures PYGL's role. Reason: Correct but general; glycogen catabolic process is the precise core BP. Retained as non-core. Supporting Evidence: PMID:10980448 Glycogen phosphorylases catalyze the breakdown of glycogen to glucose-1-phosphate for glycolysis.
GO:0005977 glycogen metabolic process	IMP PMID:17705025 High frequency of missense mutations in glycogen storage dis...	KEEP AS NON CORE	Summary: GSD6 patients with PYGL mutations show impaired mobilization of glucose from glycogen, implicating PYGL in glycogen metabolism. Correct but a general parent of the specific glycogen catabolic process. Reason: Correct but general; glycogen catabolic process is the precise core BP. Retained as non-core. Supporting Evidence: PMID:17705025 reduced ability to mobilize glucose from glycogen
GO:0008184 glycogen phosphorylase activity	IMP PMID:10980448 Human liver glycogen phosphorylase inhibitors bind at a new ...	ACCEPT	Summary: Study of the human liver enzyme (active and inactive forms) supports its glycogen phosphorylase catalytic activity. Redundant with the IDA/EXP/IBA annotations to the same core function. Reason: Correctly captures the core catalytic activity of PYGL. Supporting Evidence: PMID:10980448 Glycogen phosphorylases catalyze the breakdown of glycogen to glucose-1-phosphate for glycolysis.
GO:0008184 glycogen phosphorylase activity	IMP PMID:17705025 High frequency of missense mutations in glycogen storage dis...	ACCEPT	Summary: GSD6-causing missense mutations in PYGL impair enzyme activity, supporting that PYGL enables glycogen phosphorylase activity. Concordant with the core catalytic function. Reason: Disease mutations that reduce enzyme activity support this core molecular function. Supporting Evidence: PMID:17705025 reduced ability to mobilize glucose from glycogen
GO:0008184 glycogen phosphorylase activity	IMP PMID:9529348 Mutations in the liver glycogen phosphorylase gene (PYGL) un...	ACCEPT	Summary: First identification of PYGL mutations in Hers disease patients, demonstrating that PYGL encodes the liver glycogen phosphorylase whose deficiency abolishes activity. Supports this core molecular function. Reason: Disease-causing loss-of-function mutations in PYGL support that it enables glycogen phosphorylase activity. Supporting Evidence: PMID:9529348 Deficiency of glycogen phosphorylase in the liver gives rise to glycogen-storage disease type VI (Hers disease; MIM 232700).
GO:0016208 AMP binding	IDA PMID:10949035 Activation of human liver glycogen phosphorylase by alterati...	ACCEPT	Summary: AMP is the classical physiological allosteric activator of glycogen phosphorylase; the crystal structure of human liver GP in complex with AMP was solved (UniProt records AMP-binding residues 43-45, 76, 310), and UniProt notes activation by AMP. A genuine, physiologically important ligand-binding function. Reason: AMP binding at the allosteric activator site is a core regulatory binding function of the enzyme; supported by structure and by curated binding-site annotation. Supporting Evidence: file:human/PYGL/PYGL-uniprot.txt being activated by AMP and inhibited by ATP,
GO:0016208 AMP binding	IDA PMID:10980448 Human liver glycogen phosphorylase inhibitors bind at a new ...	ACCEPT	Summary: Structural study of human liver GP; AMP is the physiological allosteric activator that binds the nucleotide effector site. Duplicate of the other AMP binding IDA; a core regulatory binding function. Reason: AMP binding at the allosteric activator site is a genuine, physiologically important binding function of the enzyme. Supporting Evidence: file:human/PYGL/PYGL-uniprot.txt being activated by AMP and inhibited by ATP,
GO:0019842 vitamin binding	IDA PMID:12204691 Structure-activity analysis of the purine binding site of hu...	MARK AS OVER ANNOTATED	Summary: Vitamin binding here refers to the bound pyridoxal 5'-phosphate cofactor (a vitamin B6 derivative) seen in the crystal structures. This is a very general term that is captured more precisely by the pyridoxal phosphate binding annotation. Reason: Overly general term; the specific and informative pyridoxal phosphate binding term already annotated supersedes it. Retained but flagged. Supporting Evidence: file:human/PYGL/PYGL-uniprot.txt Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
GO:0032052 bile acid binding	IDA PMID:12204691 Structure-activity analysis of the purine binding site of hu...	MARK AS OVER ANNOTATED	Summary: Derived from the same crystallographic/SPR ligand screen of the purine allosteric inhibitor site. Bile-acid binding at a drug-target allosteric pocket is a pharmacological observation, not a physiological function of the enzyme. Reason: Reflects binding of screened ligands at a drug-discovery allosteric site rather than a biological function; retained but flagged as over-annotation. Not removed, as it is an experimental IDA. Supporting Evidence: PMID:12204691 compounds that bind to the purine allosteric inhibitor site.
GO:0042593 glucose homeostasis	IMP PMID:17705025 High frequency of missense mutations in glycogen storage dis...	KEEP AS NON CORE	Summary: GSD6 caused by PYGL deficiency presents with fasting hypoglycemia, demonstrating that PYGL contributes to organismal glucose homeostasis by mobilizing glucose from hepatic glycogen. This is a physiological, systemic role downstream of the core enzymatic function. Reason: Genuine organismal/physiological role, but downstream of and secondary to the core glycogen catabolic/enzymatic function; retained as non-core. Supporting Evidence: PMID:17705025 reduced ability to mobilize glucose from glycogen

Gene Description

Existing Annotations Review

Core Functions

Binds pyridoxal 5'-phosphate as an essential covalent cofactor (via a Schiff base to Lys681), which is required for the phosphorolytic catalytic mechanism of glycogen phosphorylase.

References

📚 Additional Documentation

Notes

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