Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

2.4.1.11

Official Name

glycogen(starch) synthase

Name from literature

glycogen synthase

Pathway from literature

nonoxidative pathway/glycogen synthesis of skeletal muscle

Pathway from KEGG

Cellular Processes; Endocrine System; Insulin signaling pathway; map04910

Carbohydrate Metabolism; Starch and sucrose metabolism; map00500

Organisms

Human (9606)

Genome localization

19q13.3[2997 ], 12p12.2[2998 ],

Comments

The accepted name varies according to the source of the enzyme and the nature of its synthetic product (cf. EC 2.4.1.1, phosphorylase). Glycogen synthase from animal tissues is a complex of a catalytic subunit and the protein glycogenin. The enzyme requires glucosylated glycogenin as a primer; this is the reaction product of EC 2.4.1.186 (glycogenin glucosyltransferase). A similar enzyme utilizes ADP-glucose (EC 2.4.1.21, starch synthase).

Rate-limiting Description

"As the GPI-PLC reaction is rate limiting, the efficiency of the two-step anchor cleavage was significantly increased when insulin was present together with glucose as compared to glucose alone." (10684630)

"Protein targeting to glycogen/PPP1R5 has recently been identified as a potential regulator of glycogen synthase, the rate-limiting enzyme of the insulin-induced glycogenesis." (10222257)

Regulatory Information

Upstream transcription factor

22933

Regulatory type

Detail

allosteric;

"Glucose-6-phosphate is a potent allosteric activator of GS.#Deletion analysis shows that the region comprising amino acids 555-633 of human MGS, which encompasses an Arg-rich cluster involved in the allosteric activation of the enzyme by Glc6P, is crucial for its nuclear concentration and aggregation." (16115820#15955076)

phosphorylation;

"Data show that myotubes defective in glycogen synthase (GS) activity express insulin-responsive glycogen synthase kinase-3alpha, suggesting that failure of insulin to decrease GS phosphorylation involves abnormal activity of another kinase or phosphatase." (15194499#15855312)

phosphorylation;

P13807

phosphorylation;

P54840

phosphorylation;

P13807:from_uniprot:11_Phosphoserine

phosphorylation;

P13807:from_uniprot:641_Phosphoserine

phosphorylation;

P13807:from_uniprot:645_Phosphoserine

phosphorylation;

P13807:from_uniprot:649_Phosphoserine

phosphorylation;

P13807:from_uniprot:653_Phosphoserine

phosphorylation;

P13807:from_uniprot:657_Phosphoserine

phosphorylation;

P13807:from_uniprot:698_Phosphoserine

phosphorylation;

P13807:from_uniprot:710_Phosphoserine

phosphorylation;

P13807:from_uniprot:8_Phosphoserine; by PKA

phosphorylation;

P54840:from_uniprot:11_Phosphoserine

phosphorylation;

P54840:from_uniprot:6_Phosphoserine

phosphorylation;

P54840:from_uniprot:626_Phosphothreonine

phosphorylation;

P54840:from_uniprot:641_Phosphoserine

phosphorylation;

P54840:from_uniprot:645_Phosphoserine

phosphorylation;

P54840:from_uniprot:649_Phosphoserine

phosphorylation;

P54840:from_uniprot:653_Phosphoserine

phosphorylation;

P54840:from_uniprot:657_Phosphoserine

phosphorylation;

P54840:from_uniprot:8_Phosphoserine; by PKA

transcriptional level;TNF alpha

"n summary, both acute and prolonged treatment with TNF alpha up-regulate glucose uptake activity in cultured human muscle cells, but reduce GS activity. Increased skeletal muscle glucose uptake in conditions of TNF alpha excess may serve as a compensatory mechanism in the insulin resistance of type 2 diabetes." (9832415)

transcriptional level; c-Jun N-terminal kinase (JNK)

"We further demonstrate that in turn, the redox-dependent activation of JNK1 feeds back and inhibits the activity of the metabolic enzymes glycogen synthase kinase 3beta and glycogen synthase." (10982848)

transcriptional level;TNF-alpha

"These studies demonstrate that TNF, if present during differentiation, decreases insulin-stimulated rates of storage of glucose as glycogen and total GS activity but does not downregulate the insulin-signaling system to GS. More generally, TNF also inhibits differentiation of human muscle cells in culture." (11334414)

interact with TF;SIRT2(22933)

"Large-scale mapping of human protein-protein interactions by mass spectrometry." (17353931)

Gene ontology

Gene ontology

GO:0005978 (P) glycogen biosynthetic process [P54840, P13807 ];
GO:0042803 (F) protein homodimerization activity [P54840 ];
GO:0005829 (C) cytosol [P54840, P13807 ];
GO:0043265 (C) ectoplasm [P54840 ];
GO:0030864 (C) cortical actin cytoskeleton [P54840 ];
GO:0004373 (F) glycogen (starch) synthase activity [P54840, P13807 ];
GO:0009749 (P) response to glucose stimulus [P54840 ];
GO:0005625 (C) soluble fraction [P54840 ];
GO:0005626 (C) insoluble fraction [P54840 ];
GO:0005515 (F) protein binding [P13807 ];

Disease relevance

Disease

Defects in GYS1 are the cause of muscle glycogen storage disease type 0 (GSD0b) [MIM:611556];
also called muscle glycogen synthase deficiency. GSD0 is a metabolic disorder characterized by fasting hypoglycemia presenting in infancy or early childhood. The role of muscle glycogen is to provide critical energy during bursts of activity and sustained muscle work [P13807 ];

Defects in GYS2 are the cause of glycogen storage disease type 0 (GSD0) [MIM:240600];
also known as liver glycogen synthase deficiency. GSD0 is a metabolic disorder characterized by fasting hypoglycemia presenting in infancy or early childhood and accompanied by high blood ketones and low alanine and lactate concentrations. Although feeding relieves symptoms, it often results in postprandial hyperglycemia and hyperlactatemia [P54840 ];

Links

SwissProt

P13807; P54840

Entrez Gene

2997; 2998

HPRD

00722; 00721



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  Last Modified: 2009-03-24  
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