PYGM

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred cytosolic localization. Muscle glycogen phosphorylase is a soluble cytosolic enzyme that acts on cytoplasmic glycogen particles, consistent with the TAS/Reactome cytosol annotations below. Reason: Correct subcellular localization for a cytosolic glycogenolytic enzyme; the IBA call is concordant with independent Reactome TAS annotations to the same term.
GO:0005980 glycogen catabolic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred role in glycogen catabolism. This is the central biological process of muscle glycogen phosphorylase, which performs the rate-limiting phosphorolytic step of glycogen breakdown. Reason: Core biological process, well supported by experimental IDA/IMP annotations on this gene and by the enzyme's defined catalytic activity.
GO:0008184 glycogen phosphorylase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred glycogen phosphorylase activity, the defining molecular function of PYGM (EC 2.4.1.1). Reason: Core molecular function; concordant with experimental IDA/IMP annotations and UniProt's experimentally supported catalytic activity.
GO:0004645 1,4-alpha-oligoglucan phosphorylase activity	IEA GO_REF:0000120	MODIFY	Summary: Electronically inferred alpha-1,4-glucan phosphorylase activity (the parent EC 2.4.1.1 activity encompassing glycogen phosphorylase). Correct in essence; the more specific and experimentally supported term for this enzyme is GO:0008184 glycogen phosphorylase activity. Reason: The activity is real but GO:0008184 glycogen phosphorylase activity is the more precise term for the muscle isoform acting physiologically on glycogen; both terms map to the same EC 2.4.1.1 reaction. Retain the specific term as the core molecular function. Proposed replacements: glycogen phosphorylase activity
GO:0005975 carbohydrate metabolic process	IEA GO_REF:0000002	MODIFY	Summary: Broad InterPro-derived carbohydrate metabolism term. Not incorrect, but far less informative than the specific glycogen catabolic process annotation. Reason: Over-general parent term; the specific process for this enzyme is GO:0005980 glycogen catabolic process, which is already annotated experimentally. Proposed replacements: glycogen catabolic process
GO:0008184 glycogen phosphorylase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronically inferred glycogen phosphorylase activity, matching the experimentally established core molecular function. Reason: Correct core molecular function; consistent with IBA, IDA, IMP and TAS annotations to the same term.
GO:0030170 pyridoxal phosphate binding	IEA GO_REF:0000002	ACCEPT	Summary: Pyridoxal-5'-phosphate (PLP) is the essential cofactor of glycogen phosphorylase, covalently attached via a Schiff base to Lys-681, where it participates in the phosphorolysis catalytic mechanism. Reason: Well supported by UniProt (COFACTOR pyridoxal 5'-phosphate; MOD_RES 681 N6-(pyridoxal phosphate)lysine) and by the conserved PLP-binding site of the glycogen phosphorylase family. Retained as a core cofactor-binding function. Supporting Evidence: file:human/PYGM/PYGM-uniprot.txt Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
GO:0005515 protein binding	IPI PMID:24722188 Protein interaction network of alternatively spliced isoform...	MARK AS OVER ANNOTATED	Summary: Interaction detected in a high-throughput isoform interactome screen (interactor PRKAB2, an AMPK regulatory subunit). "Protein binding" is an uninformative molecular function that does not describe the catalytic role of PYGM. Reason: Bare GO:0005515 protein binding conveys no specific functional information and derives from a large-scale interactome dataset. The AMPK-subunit interaction may be biologically relevant to metabolic regulation but is better captured by a specific term than by "protein binding". Retained but flagged as over-annotated per curation guidelines discouraging bare protein binding. Supporting Evidence: PMID:24722188 Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	MARK AS OVER ANNOTATED	Summary: Interactions (PRKAB2, NTAQ1) detected in a proteome-scale human interactome map. Bare "protein binding" is uninformative for this enzyme's function. Reason: Derived from a systematic proteome-scale interactome screen; GO:0005515 does not describe a specific molecular function. Retained but flagged as over-annotated. Supporting Evidence: PMID:25416956 A proteome-scale map of the human interactome network.
GO:0005515 protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	MARK AS OVER ANNOTATED	Summary: Interaction (NTAQ1) reported in a systematic study of interaction disruption by genetic variants. Bare "protein binding" is uninformative. Reason: High-throughput binary interaction data; GO:0005515 conveys no specific function. Retained but flagged as over-annotated. Supporting Evidence: PMID:31515488 Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Interactions (PRKAB2, and the phosphorylase paralogs PYGL and PYGB) detected in the HuRI binary interactome map. Bare "protein binding" is uninformative. Reason: Systematic binary interactome dataset; several partners are paralogous phosphorylases (isoenzyme cross-detection). GO:0005515 conveys no specific molecular function. Retained but flagged as over-annotated. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: Interaction (PYGB, brain phosphorylase paralog) detected in a proteome-scale cell-specific interactome study. Bare "protein binding" is uninformative. Reason: High-throughput affinity-purification interactome data; GO:0005515 conveys no specific function. Retained but flagged as over-annotated. Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
GO:0005515 protein binding	IPI PMID:36217029 A proteome-scale map of the SARS-CoV-2-human contactome.	MARK AS OVER ANNOTATED	Summary: Interaction with a SARS-CoV-2 viral protein (rep/nsp12) reported in a virus-host contactome screen. Bare "protein binding", involving a xeno (viral) partner, is uninformative for PYGM's physiological function. Reason: Viral-host high-throughput interaction dataset; not indicative of a native molecular function of PYGM and captured only as bare protein binding. Retained but flagged as over-annotated. Supporting Evidence: PMID:36217029 A proteome-scale map of the SARS-CoV-2-human contactome.
GO:0004645 1,4-alpha-oligoglucan phosphorylase activity	EXP PMID:1150650 Regulation of glycogen phosphorylase. Role of the peptide re...	MODIFY	Summary: Experimental characterization of skeletal muscle glycogen phosphorylase catalytic and regulatory properties (AMP activation, glucose-6-P inhibition, phosphorylase b to a interconversion). This is the EC 2.4.1.1 alpha-1,4-glucan phosphorylase activity of the enzyme. Reason: Experimentally supported activity, but GO:0008184 glycogen phosphorylase activity is the more precise term for the physiological substrate (glycogen) of the muscle isoform. Both correspond to EC 2.4.1.1. Do not remove an experimental annotation; refine to the specific term. Proposed replacements: glycogen phosphorylase activity Supporting Evidence: PMID:1150650 derived from the NH2-terminal region of skeletal muscle glycogen phosphorylase
GO:0004645 1,4-alpha-oligoglucan phosphorylase activity	EXP PMID:8316268 Molecular genetic heterogeneity of myophosphorylase deficien...	MODIFY	Summary: Functional/catalytic-activity evidence associated with molecular-genetic characterization of myophosphorylase (McArdle disease). Represents the EC 2.4.1.1 alpha-1,4-glucan phosphorylase activity of PYGM. Reason: Correct activity but better represented by the specific term GO:0008184 glycogen phosphorylase activity for this muscle isoform. Experimental annotation refined, not removed. Proposed replacements: glycogen phosphorylase activity Supporting Evidence: PMID:8316268 The myophosphorylase gene has been sequenced and assigned to chromosome 11
GO:0005980 glycogen catabolic process	IDA PMID:1150650 Regulation of glycogen phosphorylase. Role of the peptide re...	ACCEPT	Summary: Direct experimental evidence for the role of skeletal muscle glycogen phosphorylase in glycogen breakdown, via characterization of its catalytic and allosteric properties. Reason: Core biological process supported by direct assay of the muscle enzyme's phosphorolytic activity and its regulation. Supporting Evidence: PMID:1150650 induce the enzymic properties of phosphorylase a
GO:0005980 glycogen catabolic process	IMP PMID:8316268 Molecular genetic heterogeneity of myophosphorylase deficien...	ACCEPT	Summary: Mutational (McArdle disease) evidence linking loss of myophosphorylase function to impaired muscle glycogen catabolism. Loss-of-function PYGM variants cause a block in glycogenolysis (GSD5). Reason: Core biological process; disease-causing loss-of-function variants demonstrate the enzyme's requirement for muscle glycogen breakdown. Supporting Evidence: PMID:8316268 exercise intolerance, muscle cramps, and recurrent
GO:0008184 glycogen phosphorylase activity	IDA PMID:1150650 Regulation of glycogen phosphorylase. Role of the peptide re...	ACCEPT	Summary: Direct assay of skeletal muscle glycogen phosphorylase activity, including its allosteric regulation (AMP activation, cooperative binding, glucose-6-P inhibition) and phosphorylase b to a interconversion. Reason: Core molecular function with direct experimental support in the muscle enzyme. Supporting Evidence: PMID:1150650 the enzyme, normally present as a dimer, associates to a
GO:0008184 glycogen phosphorylase activity	IMP PMID:8316268 Molecular genetic heterogeneity of myophosphorylase deficien...	ACCEPT	Summary: Loss of glycogen phosphorylase activity resulting from disease-causing PYGM mutations (McArdle disease) demonstrates that this gene enables glycogen phosphorylase activity in muscle. Reason: Core molecular function; genotype-phenotype evidence supports the enzymatic role of PYGM. Supporting Evidence: PMID:8316268 The myophosphorylase gene has been sequenced and assigned to chromosome 11
GO:0070062 extracellular exosome	HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres...	MARK AS OVER ANNOTATED	Summary: PYGM was detected by shotgun mass spectrometry among ~900 proteins in exosomes purified from expressed prostatic secretions in urine. This is a high-throughput proteomic co-detection, not evidence of a functional extracellular/exosomal role for this cytosolic muscle enzyme. Reason: Common high-throughput exosome-proteomics detection of an abundant cytosolic protein; it does not reflect the site where PYGM performs its function (cytosolic glycogenolysis). Flagged as over-annotated rather than removed, per policy for experimental (HDA) detection. Supporting Evidence: PMID:23533145 exosome preparations were characterized by a shotgun proteomics procedure
GO:0005829 cytosol	TAS Reactome:R-HSA-453338	ACCEPT	Summary: Reactome-curated cytosolic localization of the PYGM b dimer (AMP-complex reaction). Correct localization for this soluble glycogenolytic enzyme. Reason: Correct core localization; concordant with the IBA cytosol annotation.
GO:0005829 cytosol	TAS Reactome:R-HSA-453342	ACCEPT	Summary: Reactome-curated cytosolic localization of the PYGM b dimer (AMP-binding reaction). Correct localization. Reason: Correct core localization; concordant with the IBA and other TAS cytosol annotations.
GO:0005829 cytosol	TAS Reactome:R-HSA-71541	ACCEPT	Summary: Reactome-curated cytosolic localization of PYGM associated with its phosphorylation (b to a conversion) by the cytosolic phosphorylase kinase complex. Reason: Correct core localization; the enzyme and its activating kinase act in the cytosol.
GO:0005977 glycogen metabolic process	TAS PMID:9633816 Molecular diagnosis of McArdle disease: revised genomic stru...	MODIFY	Summary: Traceable author statement placing myophosphorylase in glycogen metabolism. Correct but general; the specific role of PYGM is in the catabolic branch (glycogen breakdown). Reason: The broad glycogen metabolic process is a parent of the more precise GO:0005980 glycogen catabolic process, which is already experimentally annotated and better reflects PYGM's directional (glycogenolytic) role. Proposed replacements: glycogen catabolic process Supporting Evidence: PMID:9633816 caused by mutations in the muscle glycogen phosphorylase gene
GO:0008184 glycogen phosphorylase activity	TAS PMID:9633816 Molecular diagnosis of McArdle disease: revised genomic stru...	ACCEPT	Summary: Traceable author statement supporting the glycogen phosphorylase activity of myophosphorylase, in the context of McArdle disease molecular diagnosis. Reason: Core molecular function; concordant with the experimental IDA/IMP and IBA/IEA annotations to the same term. Supporting Evidence: PMID:9633816 caused by mutations in the muscle glycogen phosphorylase gene

Gene Description

Existing Annotations Review

Core Functions

Muscle glycogen phosphorylase catalyzes the rate-limiting phosphorolytic cleavage of alpha-1,4-glycosidic bonds at glycogen non-reducing ends, releasing glucose-1-phosphate, using a covalently bound pyridoxal-5'-phosphate cofactor.

The enzyme performs the committed, rate-limiting step of muscle glycogenolysis, mobilizing stored glycogen to supply glucose-1-phosphate for glycolytic ATP production during exercise; its loss causes McArdle disease.

Glycogen phosphorylase requires pyridoxal-5'-phosphate as an essential cofactor, covalently bound via a Schiff base to an active-site lysine (Lys-681), for catalysis.

References

📚 Additional Documentation

Notes

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