GYS2

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004373 alpha-1,4-glucan glucosyltransferase (UDP-glucose donor) activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred glycogen synthase catalytic activity (EC 2.4.1.11); this is the core molecular function of GYS2 and is well supported by direct enzyme characterization of the human liver enzyme. Reason: The IBA transfer across the glycogen synthase orthologue set correctly assigns the committed catalytic step of glycogen elongation, adding UDP-glucose-derived glucosyl units in alpha-1,4 linkage to a growing chain. Directly supported by the UniProt functional and catalytic-activity annotation and by enzyme characterization of the purified human liver enzyme. Supporting Evidence: file:human/GYS2/GYS2-uniprot.txt transfers the glycosyl residue from UDP-Glc to the non-reducing end of PMID:1731614 the rat and human liver glycogen synthases were similar in their pH profile, in their kinetic constants for the substrate UDP-glucose and the activator glucose 6-phosphate
GO:0005978 glycogen biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: GYS2 is a central enzyme of the glycogen biosynthetic process, extending glycogen chains during hepatic glycogen storage. Reason: Correct core biological process. GYS2 acts within glycogen synthesis together with glycogenin and the branching enzyme; the UniProt pathway annotation places it in glycogen biosynthesis, and loss of GYS2 causes deficient hepatic glycogen (GSD 0a). Supporting Evidence: file:human/GYS2/GYS2-uniprot.txt PATHWAY: Glycan biosynthesis; glycogen biosynthesis.
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: Cytoplasmic localization inferred phylogenetically; consistent with the known cytosolic activity of glycogen synthase. Reason: Glycogen synthase is a soluble cytosolic enzyme active in the cytoplasm as part of the glycogen synthase-glycogenin complex. Cytoplasm is a correct (if broad) location; the more specific cytosol annotations are also present. Supporting Evidence: file:human/GYS2/GYS2-uniprot.txt heterooctamer composed of a tetramer of GS and 2 dimers of glycogenin,
GO:0004373 alpha-1,4-glucan glucosyltransferase (UDP-glucose donor) activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assignment of the core UDP-glucose:glycogen glucosyltransferase activity (EC 2.4.1.11, RHEA:18549) via combined IEA methods. Reason: Redundant with, and consistent with, the experimentally supported core catalytic function. The EC/RHEA mapping matches the UniProt catalytic activity. Supporting Evidence: file:human/GYS2/GYS2-uniprot.txt transfers the glycosyl residue from UDP-Glc to the non-reducing end of
GO:0005978 glycogen biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assignment of glycogen biosynthetic process, consistent with the core role of GYS2. Reason: Redundant with the IBA/IDA/IMP glycogen biosynthesis annotations and correct for GYS2. Supporting Evidence: file:human/GYS2/GYS2-uniprot.txt PATHWAY: Glycan biosynthesis; glycogen biosynthesis.
GO:0061547 glycogen synthase activity, transferring glucose-1-phosphate	IEA GO_REF:0000117	ACCEPT	Summary: Captures the minor phosphoglucose-incorporation side reaction of glycogen synthase, in which a glucose-phosphate is occasionally transferred, introducing phosphomonoesters into glycogen. Reason: This is a genuine, documented low-frequency capability of glycogen synthase (GYS1/GYS2): roughly one phosphorylated glucose is incorporated per ten thousand glucose units, and laforin (EPM2A) normally removes these phosphate groups. The ARBA electronic assignment of this specific activity is biologically appropriate for GYS2, so it is kept rather than removed; it is a minor side activity relative to the core UDP-glucose donor elongation. Supporting Evidence: Reactome:R-HSA-3780994 Glycogen synthase 2 (GYS2) catalyzes the incorporation of phosphoglucose into the glycogen-GYG1 molecules with which it is associated in a cytosolic glycogen granule.
GO:0005829 cytosol	IEA GO_REF:0000107	ACCEPT	Summary: Cytosolic localization transferred electronically from the mouse orthologue; consistent with the soluble cytosolic nature of glycogen synthase. Reason: GYS2 is a soluble cytosolic enzyme. Cytosol is the correct, specific compartment and is corroborated by multiple TAS (Reactome) and ISS annotations. Supporting Evidence: Reactome:R-HSA-3780994 Glycogen synthase 2 (GYS2) catalyzes the incorporation of phosphoglucose into the glycogen-GYG1 molecules with which it is associated in a cytosolic glycogen granule.
GO:0005978 glycogen biosynthetic process	TAS Reactome:R-HSA-3322077	ACCEPT	Summary: Reactome traceable assignment placing GYS2 in the glycogen synthesis pathway, where it catalyzes the linear alpha-1,4 extension of the glucose oligomer. Reason: Correct core biological process, curated from the Reactome "Glycogen synthesis" pathway, which explicitly identifies glycogen synthase as the enzyme catalyzing linear chain extension. Supporting Evidence: Reactome:R-HSA-3322077 the linear extension of the glucose oligomer catalyzed by glycogen synthase, and the formation of branches catalyzed by glycogen branching enzyme, are unique to glycogen synthesis
GO:0004373 alpha-1,4-glucan glucosyltransferase (UDP-glucose donor) activity	EXP PMID:9691087 Mutations in the liver glycogen synthase gene in children wi...	ACCEPT	Summary: Experimental support for glycogen synthase catalytic activity of GYS2: GSD-0 disease variants expressed in COS7 cells showed severely impaired activity, establishing GYS2 as the catalytic liver glycogen synthase. Reason: The disease-mutation study functionally demonstrates that GYS2 encodes an active liver glycogen synthase whose activity is abolished/severely reduced by loss-of-function variants. Core catalytic function. Supporting Evidence: PMID:9691087 Expression of the mutated enzymes in COS7 cells indicated severely impaired GS activity. In conclusion, the results demonstrate that GSD-0 is caused by different mutations in the GYS2 gene.
GO:0004373 alpha-1,4-glucan glucosyltransferase (UDP-glucose donor) activity	IMP PMID:9691087 Mutations in the liver glycogen synthase gene in children wi...	ACCEPT	Summary: Mutational (IMP) evidence that GYS2 confers glycogen synthase activity: loss-of-function variants abolish enzyme activity in patients and in a heterologous expression assay. Reason: Consistent with the EXP annotation from the same study; the impaired activity of GYS2 mutants supports the core catalytic function assignment. Supporting Evidence: PMID:9691087 GS activity in the liver of the affected children was extremely low or nil, resulting in subnormal glycogen content.
GO:0005978 glycogen biosynthetic process	IMP PMID:9691087 Mutations in the liver glycogen synthase gene in children wi...	ACCEPT	Summary: Mutational evidence that GYS2 is required for hepatic glycogen biosynthesis: GYS2 deficiency causes subnormal liver glycogen content (GSD type 0). Reason: Loss of GYS2 function reduces hepatic glycogen synthesis, directly implicating the gene in the glycogen biosynthetic process. Core biological process. Supporting Evidence: PMID:9691087 GS activity in the liver of the affected children was extremely low or nil, resulting in subnormal glycogen content.
GO:0061547 glycogen synthase activity, transferring glucose-1-phosphate	TAS Reactome:R-HSA-3780994	ACCEPT	Summary: Reactome-curated minor activity in which GYS2 incorporates phosphoglucose into glycogen, the origin of glycogen phosphomonoesters. Reason: Curated from the Reactome reaction describing GYS2-catalyzed incorporation of phosphoglucose into glycogen. This is a real, well-documented low-rate side activity of glycogen synthase; kept as a genuine molecular capability, minor relative to the core UDP-glucose donor elongation. Supporting Evidence: Reactome:R-HSA-3780994 Glycogen synthase 2 (GYS2) catalyzes the incorporation of phosphoglucose into the glycogen-GYG1 molecules with which it is associated in a cytosolic glycogen granule.
GO:0005829 cytosol	TAS Reactome:R-HSA-3858506	ACCEPT	Summary: Reactome traceable assignment of cytosolic localization for GYS2. Reason: GYS2 is a soluble cytosolic enzyme; cytosol is the correct compartment. This Reactome annotation derives from the GSD-0 (defective GYS2) reaction context. Supporting Evidence: Reactome:R-HSA-3780994 the glycogen-GYG1 molecules with which it is associated in a cytosolic glycogen granule
GO:0005829 cytosol	TAS Reactome:R-HSA-3322019	ACCEPT	Summary: Reactome traceable assignment of cytosolic localization for GYS2. Reason: Duplicate cytosol assignment from a Reactome glycogen-synthesis reaction; correct compartment for this soluble enzyme. Supporting Evidence: Reactome:R-HSA-3780994 the glycogen-GYG1 molecules with which it is associated in a cytosolic glycogen granule
GO:0005829 cytosol	TAS Reactome:R-HSA-3322009	ACCEPT	Summary: Reactome traceable assignment of cytosolic localization for GYS2. Reason: Duplicate cytosol assignment from a Reactome glycogen-synthesis reaction; correct compartment for this soluble enzyme. Supporting Evidence: Reactome:R-HSA-3780994 the glycogen-GYG1 molecules with which it is associated in a cytosolic glycogen granule
GO:0005829 cytosol	TAS Reactome:R-HSA-3322014	ACCEPT	Summary: Reactome traceable assignment of cytosolic localization for GYS2. Reason: Duplicate cytosol assignment from a Reactome glycogen-synthesis reaction; correct compartment for this soluble enzyme. Supporting Evidence: Reactome:R-HSA-3780994 the glycogen-GYG1 molecules with which it is associated in a cytosolic glycogen granule
GO:0005829 cytosol	TAS Reactome:R-HSA-3322016	ACCEPT	Summary: Reactome traceable assignment of cytosolic localization for GYS2. Reason: Duplicate cytosol assignment from a Reactome glycogen-synthesis reaction; correct compartment for this soluble enzyme. Supporting Evidence: Reactome:R-HSA-3780994 the glycogen-GYG1 molecules with which it is associated in a cytosolic glycogen granule
GO:0005829 cytosol	TAS Reactome:R-HSA-3780994	ACCEPT	Summary: Reactome traceable assignment of cytosolic localization for GYS2. Reason: Cytosol assignment from the Reactome GYS2 phosphoglucose-incorporation reaction, which explicitly places GYS2 in a cytosolic glycogen granule. Supporting Evidence: Reactome:R-HSA-3780994 the glycogen-GYG1 molecules with which it is associated in a cytosolic glycogen granule
GO:0005829 cytosol	TAS Reactome:R-HSA-3780995	ACCEPT	Summary: Reactome traceable assignment of cytosolic localization for GYS2. Reason: Duplicate cytosol assignment from a Reactome glycogen-metabolism reaction; correct compartment for this soluble enzyme. Supporting Evidence: Reactome:R-HSA-3780994 the glycogen-GYG1 molecules with which it is associated in a cytosolic glycogen granule
GO:0005829 cytosol	TAS Reactome:R-HSA-3780997	ACCEPT	Summary: Reactome traceable assignment of cytosolic localization for GYS2. Reason: Duplicate cytosol assignment from a Reactome glycogen-metabolism reaction; correct compartment for this soluble enzyme. Supporting Evidence: Reactome:R-HSA-3780994 the glycogen-GYG1 molecules with which it is associated in a cytosolic glycogen granule
GO:0005829 cytosol	TAS Reactome:R-HSA-3781011	ACCEPT	Summary: Reactome traceable assignment of cytosolic localization for GYS2. Reason: Duplicate cytosol assignment from a Reactome glycogen-metabolism reaction; correct compartment for this soluble enzyme. Supporting Evidence: Reactome:R-HSA-3780994 the glycogen-GYG1 molecules with which it is associated in a cytosolic glycogen granule
GO:0005829 cytosol	TAS Reactome:R-HSA-3781021	ACCEPT	Summary: Reactome traceable assignment of cytosolic localization for GYS2. Reason: Duplicate cytosol assignment from a Reactome glycogen-metabolism reaction; correct compartment for this soluble enzyme. Supporting Evidence: Reactome:R-HSA-3780994 the glycogen-GYG1 molecules with which it is associated in a cytosolic glycogen granule
GO:0005829 cytosol	TAS Reactome:R-HSA-3878762	ACCEPT	Summary: Reactome traceable assignment of cytosolic localization for GYS2. Reason: Duplicate cytosol assignment from a Reactome glycogen-metabolism reaction; correct compartment for this soluble enzyme. Supporting Evidence: Reactome:R-HSA-3780994 the glycogen-GYG1 molecules with which it is associated in a cytosolic glycogen granule
GO:0009749 response to glucose	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Response to glucose transferred by sequence similarity from the yeast glycogen synthase orthologue (Saccharomyces cerevisiae Gsy2, UniProtKB:P17625). Plausible for a glucose-storage enzyme but peripheral to the core catalytic role and not experimentally verified in human GYS2. Reason: Glycogen synthase activity is downstream of glucose availability and glucose-6-phosphate (its allosteric activator), so a role in the cellular response to glucose is biologically plausible. However, this is an ISS transfer from a distant fungal orthologue rather than a direct human observation, and it describes a regulatory/physiological context rather than the committed catalytic function; retained as a non-core annotation. Supporting Evidence: file:human/GYS2/GYS2-uniprot.txt ACTIVITY REGULATION: Allosteric activation by glucose-6-phosphate
GO:0004373 alpha-1,4-glucan glucosyltransferase (UDP-glucose donor) activity	ISS GO_REF:0000024	ACCEPT	Summary: Core glycogen synthase catalytic activity transferred by sequence similarity from the yeast orthologue; concordant with the human enzyme's characterized activity. Reason: Consistent with the experimental, IBA, and IEA assignments of the core UDP-glucose:glycogen glucosyltransferase activity. Supporting Evidence: file:human/GYS2/GYS2-uniprot.txt transfers the glycosyl residue from UDP-Glc to the non-reducing end of
GO:0004373 alpha-1,4-glucan glucosyltransferase (UDP-glucose donor) activity	IDA PMID:1731614 Comparative characterization of human and rat liver glycogen...	ACCEPT	Summary: Direct enzyme characterization of purified human liver glycogen synthase, establishing its UDP-glucose-dependent, glucose-6-phosphate-activated glycogen synthase activity. Reason: Westphal and Nuttall purified human liver glycogen synthase to near homogeneity and characterized its kinetics for UDP-glucose and its activation by glucose-6-phosphate. This is direct experimental evidence for the core catalytic function of GYS2. Supporting Evidence: PMID:1731614 The human enzyme, purified to near homogeneity, had a specific activity of 40 U/mg protein compared with 20 U/mg protein for the rat enzyme. file:human/GYS2/GYS2-uniprot.txt transfers the glycosyl residue from UDP-Glc to the non-reducing end of
GO:0005737 cytoplasm	ISS GO_REF:0000024	ACCEPT	Summary: Cytoplasmic localization transferred by sequence similarity from the yeast orthologue; correct broad compartment for this soluble enzyme. Reason: Glycogen synthase is a soluble cytoplasmic/cytosolic enzyme. Cytoplasm is a correct, broader location; the more specific cytosol annotations are also retained. Supporting Evidence: file:human/GYS2/GYS2-uniprot.txt heterooctamer composed of a tetramer of GS and 2 dimers of glycogenin,
GO:0005829 cytosol	ISS GO_REF:0000024	ACCEPT	Summary: Cytosolic localization transferred by sequence similarity from the yeast orthologue; correct specific compartment. Reason: Cytosol is the correct, specific compartment for GYS2 and is corroborated by TAS (Reactome), IEA, and the IBA cytoplasm annotations. Supporting Evidence: Reactome:R-HSA-3780994 the glycogen-GYG1 molecules with which it is associated in a cytosolic glycogen granule
GO:0005856 cytoskeleton	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Cytoskeleton localization transferred by sequence similarity from Saccharomyces cerevisiae glycogen synthase (Gsy2, UniProtKB:P17625). This reflects the fungal enzyme's association with cortical structures and is not supported for human liver GYS2. Reason: This is an ISS transfer from a distant fungal orthologue. Human liver GYS2 is a soluble cytosolic enzyme that assembles with glycogenin into the glycogen synthase-glycogenin complex; there is no experimental evidence that it is a cytoskeletal protein. The localization appears over-propagated from the yeast source rather than reflecting human biology. Supporting Evidence: file:human/GYS2/GYS2-uniprot.txt heterooctamer composed of a tetramer of GS and 2 dimers of glycogenin,
GO:0005938 cell cortex	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Cell cortex localization transferred by sequence similarity from yeast glycogen synthase (UniProtKB:P17625); not supported for human liver GYS2. Reason: As with the cytoskeleton and cortical actin cytoskeleton annotations, this is an ISS transfer from the fungal orthologue reflecting yeast-specific cortical association. Human GYS2 is a soluble cytosolic component of the glycogen synthase-glycogenin complex, with no evidence of cell cortex localization; over-annotation. Supporting Evidence: file:human/GYS2/GYS2-uniprot.txt heterooctamer composed of a tetramer of GS and 2 dimers of glycogenin,
GO:0005978 glycogen biosynthetic process	ISS GO_REF:0000024	ACCEPT	Summary: Glycogen biosynthetic process transferred by sequence similarity from the yeast orthologue; correct core process for GYS2. Reason: Redundant with the IBA/IDA/IMP/TAS glycogen biosynthesis annotations and correct for the committed glycogen elongation enzyme. Supporting Evidence: file:human/GYS2/GYS2-uniprot.txt PATHWAY: Glycan biosynthesis; glycogen biosynthesis.
GO:0005978 glycogen biosynthetic process	IDA PMID:1731614 Comparative characterization of human and rat liver glycogen...	ACCEPT	Summary: Direct characterization of purified human liver glycogen synthase supports its role in hepatic glycogen synthesis. Reason: Westphal and Nuttall characterized the human liver enzyme and framed it as an important enzyme in liver glycogen synthesis, providing direct experimental support for involvement in the glycogen biosynthetic process. Supporting Evidence: PMID:1731614 Since glycogen synthase is an important enzyme in liver glycogen synthesis, the characterization of this enzyme in the human will help provide insight regarding human liver glycogen synthesis.
GO:0030864 cortical actin cytoskeleton	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Cortical actin cytoskeleton localization transferred by sequence similarity from yeast glycogen synthase (UniProtKB:P17625); not supported for human liver GYS2. Reason: This ISS transfer from the fungal orthologue reflects the yeast enzyme's association with cortical actin patches and does not represent human GYS2 biology. Human liver GYS2 is a soluble cytosolic enzyme; there is no evidence for cortical actin cytoskeleton localization. Over-propagated annotation from a distant orthologue. Supporting Evidence: file:human/GYS2/GYS2-uniprot.txt heterooctamer composed of a tetramer of GS and 2 dimers of glycogenin,

Gene Description

Existing Annotations Review

Core Functions

Liver glycogen synthase: transfers glucose from UDP-glucose to the non-reducing end of a growing glycogen chain, forming alpha-1,4-glycosidic linkages, thereby elongating glycogen during hepatic glycogen storage.

References

📚 Additional Documentation

Notes

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