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

📄 View Raw YAML

id: P06737
gene_symbol: PYGL
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: PYGL is the liver isoform of glycogen phosphorylase, the rate-limiting
  enzyme of glycogenolysis. It is a pyridoxal-5'-phosphate-dependent homodimeric enzyme
  that phosphorolytically cleaves the alpha-1,4-glycosidic bonds at the non-reducing
  ends of glycogen, releasing glucose-1-phosphate, and stops about four residues short
  of alpha-1,6 branch points (which are then processed by the glycogen debranching
  enzyme). Activity is controlled allosterically (activated by AMP; inhibited by ATP,
  ADP and glucose-6-phosphate) and covalently by interconversion between an inactive
  phosphorylase b and an active phosphorylase a form via phosphorylation of Ser15 by
  phosphorylase kinase and dephosphorylation by protein phosphatase 1. The enzyme acts
  in the cytosol, predominantly in the liver, where it liberates glucose from stored
  glycogen to maintain blood glucose during fasting. Loss-of-function variants cause
  glycogen storage disease type VI (Hers disease), characterized by hepatomegaly and
  usually mild fasting hypoglycemia.
alternative_products:
- name: '1'
  id: P06737-1
- name: '2'
  id: P06737-2
  sequence_note: VSP_045339
existing_annotations:
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    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.
    action: ACCEPT
    reason: Cytosol is the correct and well-supported site of action for this
      cytosolic glycogenolytic enzyme.
    supported_by:
    - reference_id: file:human/PYGL/PYGL-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Cytoplasm, cytosol"
- term:
    id: GO:0005980
    label: glycogen catabolic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    reason: Glycogen catabolic process is the precise, core biological process of the
      enzyme; well supported by IBA, experimental data and UniProt.
    supported_by:
    - reference_id: PMID:22225877
      supporting_text: Glycogen phosphorylase (GP) catalyzes the rate-limiting step
        in glycogen catabolism and plays a key role in maintaining cellular and
        organismal glucose homeostasis.
- term:
    id: GO:0008184
    label: glycogen phosphorylase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: This is the core catalytic molecular function of the gene product,
      supported by phylogeny and by direct assay.
    supported_by:
    - reference_id: PMID:22225877
      supporting_text: Glycogen phosphorylase (GP) catalyzes phosphorolytic cleavage
        of glycogen to produce glucose-1-phosphate for glucose-dependent tissues when
        body glucose is scarce.
- term:
    id: GO:0004645
    label: 1,4-alpha-oligoglucan phosphorylase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: Correct EC-mapped catalytic activity term; consistent with the
      experimentally determined reaction and with the more specific glycogen
      phosphorylase activity term also annotated.
    supported_by:
    - reference_id: file:human/PYGL/PYGL-uniprot.txt
      supporting_text: EC=2.4.1.1 {ECO:0000269|PubMed:22225877}
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    reason: Correct localization for this cytosolic enzyme.
    supported_by:
    - reference_id: file:human/PYGL/PYGL-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Cytoplasm, cytosol"
- term:
    id: GO:0005975
    label: carbohydrate metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Not wrong, but a high-level parent superseded by the specific glycogen
      catabolic process annotation; retained as a general, non-core term.
    supported_by:
    - reference_id: PMID:22225877
      supporting_text: Glycogen phosphorylase (GP) catalyzes phosphorolytic cleavage
        of glycogen to produce glucose-1-phosphate for glucose-dependent tissues when
        body glucose is scarce.
- term:
    id: GO:0005977
    label: glycogen metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: ARBA machine-learning process term. Correct but a general parent of
      glycogen catabolic process, which is the precise role of the enzyme.
    action: KEEP_AS_NON_CORE
    reason: Correct but general; the specific glycogen catabolic process term is the
      core BP. Retained as a broad, non-core annotation.
    supported_by:
    - reference_id: PMID:22225877
      supporting_text: GP activity plays an important role in glucose homeostasis and
        glycogen metabolism.
- term:
    id: GO:0008184
    label: glycogen phosphorylase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: Correctly captures the defining catalytic activity of PYGL.
    supported_by:
    - reference_id: PMID:22225877
      supporting_text: Glycogen phosphorylase (GP) catalyzes phosphorolytic cleavage
        of glycogen to produce glucose-1-phosphate for glucose-dependent tissues when
        body glucose is scarce.
- term:
    id: GO:0030170
    label: pyridoxal phosphate binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: PLP binding is a genuine, essential cofactor-binding function of the enzyme
      (Lys681 pyridoxal-phosphate attachment site).
    supported_by:
    - reference_id: file:human/PYGL/PYGL-uniprot.txt
      supporting_text: Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25910212
  qualifier: enables
  review:
    summary: Interaction from a systematic interactome-perturbation study; with/from
      is PYGB (P11216). The bare protein binding term is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative protein binding term; the PYGB partner reflects glycogen
      phosphorylase isoform association rather than a distinct function. Retained but
      flagged as over-annotation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative protein binding term; the PYGB/PYGM partners reflect
      glycogen phosphorylase isoform association. Retained but flagged as
      over-annotation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: Interaction from a cell-specific interactome-remodeling map; with/from is
      PYGB (P11216). The bare protein binding term is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative protein binding term; PYGB partner reflects glycogen
      phosphorylase isoform association. Retained but flagged as over-annotation.
- term:
    id: GO:0005980
    label: glycogen catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    reason: Correctly captures the core biological process of the enzyme; concordant
      with the IBA and with experimental evidence.
    supported_by:
    - reference_id: PMID:22225877
      supporting_text: Glycogen phosphorylase (GP) catalyzes the rate-limiting step
        in glycogen catabolism and plays a key role in maintaining cellular and
        organismal glucose homeostasis.
- term:
    id: GO:0004645
    label: 1,4-alpha-oligoglucan phosphorylase activity
  evidence_type: EXP
  original_reference_id: PMID:22225877
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: Experimentally supported core catalytic function; the enzyme phosphorolyses
      alpha-1,4 glucan bonds to yield glucose-1-phosphate.
    supported_by:
    - reference_id: PMID:22225877
      supporting_text: Glycogen phosphorylase (GP) catalyzes phosphorolytic cleavage
        of glycogen to produce glucose-1-phosphate for glucose-dependent tissues when
        body glucose is scarce.
- term:
    id: GO:0005536
    label: D-glucose binding
  evidence_type: IDA
  original_reference_id: PMID:10980448
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:10980448
      supporting_text: functions allosterically by stabilizing the inactive
- term:
    id: GO:0005536
    label: D-glucose binding
  evidence_type: IDA
  original_reference_id: PMID:12204691
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:12204691
      supporting_text: regulated by multiple interacting allosteric sites, each of
        which is a potential
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:10980448
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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).
    supported_by:
    - reference_id: file:human/PYGL/PYGL-uniprot.txt
      supporting_text: "SUBUNIT: Homodimer; enzymatically active"
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6798748
  qualifier: located_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: PYGL functions in the cytosol; extracellular localization is a bystander
      catalog assignment from a degranulation pathway, not a functional location.
    supported_by:
    - reference_id: file:human/PYGL/PYGL-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Cytoplasm, cytosol"
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6800434
  qualifier: located_in
  review:
    summary: Same as the other extracellular-region assignment, from a Reactome
      ficolin-rich granule exocytosis module. Not a functional location for this
      cytosolic enzyme.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bystander secretome/degranulation catalog assignment; PYGL acts in the
      cytosol.
    supported_by:
    - reference_id: file:human/PYGL/PYGL-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Cytoplasm, cytosol"
- term:
    id: GO:0034774
    label: secretory granule lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6798748
  qualifier: located_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: Not a functional location for this cytosolic glycogenolytic enzyme.
    supported_by:
    - reference_id: file:human/PYGL/PYGL-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Cytoplasm, cytosol"
- term:
    id: GO:1904813
    label: ficolin-1-rich granule lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6800434
  qualifier: located_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: Not a functional location for this cytosolic glycogenolytic enzyme.
    supported_by:
    - reference_id: file:human/PYGL/PYGL-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Cytoplasm, cytosol"
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:23533145
  qualifier: located_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: Detection in an exosome proteome catalog does not indicate a functional
      site; PYGL acts in the cytosol.
    supported_by:
    - reference_id: PMID:23533145
      supporting_text: In pooled EPS-urine exosome samples, ~900 proteins were
        detected.
- term:
    id: GO:0008184
    label: glycogen phosphorylase activity
  evidence_type: IDA
  original_reference_id: PMID:22225877
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: Direct experimental demonstration of the core catalytic activity of PYGL.
    supported_by:
    - reference_id: PMID:22225877
      supporting_text: Glycogen phosphorylase (GP) catalyzes phosphorolytic cleavage
        of glycogen to produce glucose-1-phosphate for glucose-dependent tissues when
        body glucose is scarce.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-453339
  qualifier: located_in
  review:
    summary: Reactome cytosol assignment for the glycogenolysis reaction (glycogen +
      phosphate to glucose-1-phosphate). This is the correct functional location for
      PYGL.
    action: ACCEPT
    reason: Cytosol is the correct site of the glycogenolytic reaction catalyzed by
      PYGL; concordant with IBA and UniProt.
    supported_by:
    - reference_id: file:human/PYGL/PYGL-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Cytoplasm, cytosol"
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-71588
  qualifier: located_in
  review:
    summary: Reactome cytosol assignment for the phosphorylase b to a interconversion
      reaction. Correct functional location.
    action: ACCEPT
    reason: Cytosol is the correct site of action; concordant with IBA and UniProt.
    supported_by:
    - reference_id: file:human/PYGL/PYGL-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Cytoplasm, cytosol"
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-71590
  qualifier: located_in
  review:
    summary: Reactome cytosol assignment for glycogen limit-dextrin formation with
      release of glucose-1-phosphate. Correct functional location.
    action: ACCEPT
    reason: Cytosol is the correct site of the glycogenolytic reaction; concordant
      with IBA and UniProt.
    supported_by:
    - reference_id: file:human/PYGL/PYGL-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Cytoplasm, cytosol"
- term:
    id: GO:0002060
    label: purine nucleobase binding
  evidence_type: IDA
  original_reference_id: PMID:12204691
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:12204691
      supporting_text: compounds that bind to the purine allosteric inhibitor site.
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IDA
  original_reference_id: PMID:10949035
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: file:human/PYGL/PYGL-uniprot.txt
      supporting_text: being activated by AMP and inhibited by ATP,
- term:
    id: GO:0005977
    label: glycogen metabolic process
  evidence_type: IMP
  original_reference_id: PMID:10980448
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Correct but general; glycogen catabolic process is the precise core BP.
      Retained as non-core.
    supported_by:
    - reference_id: PMID:10980448
      supporting_text: Glycogen phosphorylases catalyze the breakdown of glycogen to
        glucose-1-phosphate for glycolysis.
- term:
    id: GO:0005977
    label: glycogen metabolic process
  evidence_type: IMP
  original_reference_id: PMID:17705025
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Correct but general; glycogen catabolic process is the precise core BP.
      Retained as non-core.
    supported_by:
    - reference_id: PMID:17705025
      supporting_text: reduced ability to mobilize glucose from glycogen
- term:
    id: GO:0008184
    label: glycogen phosphorylase activity
  evidence_type: IMP
  original_reference_id: PMID:10980448
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: Correctly captures the core catalytic activity of PYGL.
    supported_by:
    - reference_id: PMID:10980448
      supporting_text: Glycogen phosphorylases catalyze the breakdown of glycogen to
        glucose-1-phosphate for glycolysis.
- term:
    id: GO:0008184
    label: glycogen phosphorylase activity
  evidence_type: IMP
  original_reference_id: PMID:17705025
  qualifier: enables
  review:
    summary: GSD6-causing missense mutations in PYGL impair enzyme activity,
      supporting that PYGL enables glycogen phosphorylase activity. Concordant with the
      core catalytic function.
    action: ACCEPT
    reason: Disease mutations that reduce enzyme activity support this core molecular
      function.
    supported_by:
    - reference_id: PMID:17705025
      supporting_text: reduced ability to mobilize glucose from glycogen
- term:
    id: GO:0008184
    label: glycogen phosphorylase activity
  evidence_type: IMP
  original_reference_id: PMID:9529348
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: Disease-causing loss-of-function mutations in PYGL support that it enables
      glycogen phosphorylase activity.
    supported_by:
    - reference_id: PMID:9529348
      supporting_text: Deficiency of glycogen phosphorylase in the liver gives rise to
        glycogen-storage disease type VI (Hers disease; MIM 232700).
- term:
    id: GO:0016208
    label: AMP binding
  evidence_type: IDA
  original_reference_id: PMID:10949035
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: file:human/PYGL/PYGL-uniprot.txt
      supporting_text: being activated by AMP and inhibited by ATP,
- term:
    id: GO:0016208
    label: AMP binding
  evidence_type: IDA
  original_reference_id: PMID:10980448
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: AMP binding at the allosteric activator site is a genuine, physiologically
      important binding function of the enzyme.
    supported_by:
    - reference_id: file:human/PYGL/PYGL-uniprot.txt
      supporting_text: being activated by AMP and inhibited by ATP,
- term:
    id: GO:0019842
    label: vitamin binding
  evidence_type: IDA
  original_reference_id: PMID:12204691
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: Overly general term; the specific and informative pyridoxal phosphate
      binding term already annotated supersedes it. Retained but flagged.
    supported_by:
    - reference_id: file:human/PYGL/PYGL-uniprot.txt
      supporting_text: Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
- term:
    id: GO:0032052
    label: bile acid binding
  evidence_type: IDA
  original_reference_id: PMID:12204691
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:12204691
      supporting_text: compounds that bind to the purine allosteric inhibitor site.
- term:
    id: GO:0042593
    label: glucose homeostasis
  evidence_type: IMP
  original_reference_id: PMID:17705025
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Genuine organismal/physiological role, but downstream of and secondary to
      the core glycogen catabolic/enzymatic function; retained as non-core.
    supported_by:
    - reference_id: PMID:17705025
      supporting_text: reduced ability to mobilize glucose from glycogen
core_functions:
- description: Pyridoxal-5'-phosphate-dependent glycogen phosphorylase that catalyzes
    the rate-limiting step of glycogenolysis, phosphorolytically cleaving alpha-1,4
    glycosidic bonds at the non-reducing ends of glycogen to release glucose-1-phosphate,
    acting as an active homodimer in the cytosol and allosterically activated by AMP.
  molecular_function:
    id: GO:0008184
    label: glycogen phosphorylase activity
  directly_involved_in:
  - id: GO:0005980
    label: glycogen catabolic process
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: PMID:22225877
    supporting_text: Glycogen phosphorylase (GP) catalyzes phosphorolytic cleavage
      of glycogen to produce glucose-1-phosphate for glucose-dependent tissues when
      body glucose is scarce.
  - reference_id: file:human/PYGL/PYGL-uniprot.txt
    supporting_text: "SUBCELLULAR LOCATION: Cytoplasm, cytosol"
- description: 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.
  molecular_function:
    id: GO:0030170
    label: pyridoxal phosphate binding
  directly_involved_in:
  - id: GO:0005980
    label: glycogen catabolic process
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: file:human/PYGL/PYGL-uniprot.txt
    supporting_text: Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10949035
  title: Activation of human liver glycogen phosphorylase by alteration of the secondary
    structure and packing of the catalytic core.
  findings: []
- id: PMID:10980448
  title: Human liver glycogen phosphorylase inhibitors bind at a new allosteric site.
  findings: []
- id: PMID:12204691
  title: Structure-activity analysis of the purine binding site of human liver glycogen
    phosphorylase.
  findings: []
- id: PMID:17705025
  title: High frequency of missense mutations in glycogen storage disease type VI.
  findings: []
- id: PMID:22225877
  title: Acetylation negatively regulates glycogen phosphorylase by recruiting protein
    phosphatase 1.
  findings: []
- id: PMID:23533145
  title: In-depth proteomic analyses of exosomes isolated from expressed prostatic
    secretions in urine.
  findings: []
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
- id: PMID:25910212
  title: Widespread macromolecular interaction perturbations in human genetic disorders.
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
- id: PMID:9529348
  title: Mutations in the liver glycogen phosphorylase gene (PYGL) underlying glycogenosis
    type VI.
  findings: []
- id: Reactome:R-HSA-453339
  title: poly((1,4)-alpha-glucosyl) glycogenin-2 + n orthophosphate => glycogenin-2
    + n D-glucose 1-phosphate [PYGL]
  findings: []
- id: Reactome:R-HSA-6798748
  title: Exocytosis of secretory granule lumen proteins
  findings: []
- id: Reactome:R-HSA-6800434
  title: Exocytosis of ficolin-rich granule lumen proteins
  findings: []
- id: Reactome:R-HSA-71588
  title: glycogen phosphorylase (PYGL) dimer b + 2 ATP => glycogen phosphorylase (PYGL)
    dimer a + 2 ADP
  findings: []
- id: Reactome:R-HSA-71590
  title: glycogen-glycogenin-2 + n orthophosphate => limit dextrin-glycogenin-2 +
    n D-glucose 1-phosphate [PYGL]
  findings: []

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

PYGL (Glycogen phosphorylase, liver form) — review notes

Core biology (from UniProt P06737 + literature)

Disease

Annotation review reasoning

📄 View Raw YAML