Information on EC 2.4.1.11 - glycogen(starch) synthase

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The expected taxonomic range for this enzyme is: Eukaryota, Archaea

EC NUMBER
COMMENTARY
2.4.1.11
-
RECOMMENDED NAME
GeneOntology No.
glycogen(starch) synthase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
UDP-glucose + [(1->4)-alpha-D-glucosyl]n = UDP + [(1->4)-alpha-D-glucosyl]n+1
show the reaction diagram
reaction mechanism
-
UDP-glucose + [(1->4)-alpha-D-glucosyl]n = UDP + [(1->4)-alpha-D-glucosyl]n+1
show the reaction diagram
reaction mechanism
-
UDP-glucose + [(1->4)-alpha-D-glucosyl]n = UDP + [(1->4)-alpha-D-glucosyl]n+1
show the reaction diagram
reaction mechanism
-
UDP-glucose + [(1->4)-alpha-D-glucosyl]n = UDP + [(1->4)-alpha-D-glucosyl]n+1
show the reaction diagram
reaction mechanism
-
UDP-glucose + [(1->4)-alpha-D-glucosyl]n = UDP + [(1->4)-alpha-D-glucosyl]n+1
show the reaction diagram
glycogen synthase performs a stepwise SNi-like mechanism, involving the concerted departure of the leaving group and the attack of the incoming nucleophile, via ion-pair intermediate 1,5-anhydro-D-arabino-hex-1-enitol or its tautomeric form, 1,5-anhydro-D-fructose, bound at the catalytic site. Even in the absence of a glucosyl acceptor, glycogen synthase promotes the formation of the cationic intermediate, which, by eliminating the proton of the adjacent C2 carbon atom, yields 1,5-anhydro-D-arabino-hex-1-enitol, overview
-
UDP-glucose + [(1->4)-alpha-D-glucosyl]n = UDP + [(1->4)-alpha-D-glucosyl]n+1
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
hexosyl group transfer
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
glycogen biosynthesis II (from UDP-D-Glucose)
-
Starch and sucrose metabolism
-
SYSTEMATIC NAME
IUBMB Comments
UDP-glucose:glycogen 4-alpha-D-glucosyltransferase
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).
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
GBSS
A8V967
-
glucosyltransferase, uridine diphosphoglucose-glycogen
-
-
-
-
glycogen synthase
-
-
glycogen synthase
-
-
glycogen synthase
-
-
glycogen synthase 2
-
-
glycogen synthase-2
-
-
glycogen synthetase (starch)
-
-
-
-
granule-bound starch synthase
A8V967
-
GSY2p
-
-
-
-
Gys-2
-
-
GYS1
P13807
-
GYS1
E0X6R2
gene name
GYS1
Sus scrofa Meishan
E0X6R2
gene name
-
GYS2
E0X6R4
gene name
GYS2
Sus scrofa Meishan
E0X6R4
gene name
-
UDP-glucose-glycogen glucosyltransferase
-
-
-
-
UDP-glycogen synthase
-
-
-
-
UDPG-glycogen synthetase
-
-
-
-
UDPG-glycogen transglucosylase
-
-
-
-
uridine diphosphoglucose-glycogen glucosyltransferase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9014-56-6
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
swine parasite
-
-
Manually annotated by BRENDA team
; granule-bound starch synthase
SwissProt
Manually annotated by BRENDA team
muscle-specific glycogen synthase GYS1
UniProt
Manually annotated by BRENDA team
patient with glycogen storage disease type 0
-
-
Manually annotated by BRENDA team
patients with obesity and type 2 diabetes mellitus
-
-
Manually annotated by BRENDA team
patients with polycystic ovary syndrome
-
-
Manually annotated by BRENDA team
patients with type 2 diabetes
-
-
Manually annotated by BRENDA team
male rhesus monkey
-
-
Manually annotated by BRENDA team
sea mussel
-
-
Manually annotated by BRENDA team
strain FGSC424, eild type
-
-
Manually annotated by BRENDA team
Neurospora crassa FGSC424
strain FGSC424, eild type
-
-
Manually annotated by BRENDA team
rainbow trout
-
-
Manually annotated by BRENDA team
sheep
-
-
Manually annotated by BRENDA team
diabetic rats
-
-
Manually annotated by BRENDA team
insulin-resistant
-
-
Manually annotated by BRENDA team
Sprague Dawley, rat
-
-
Manually annotated by BRENDA team
glycogen deficient mutant strain and wild-type
-
-
Manually annotated by BRENDA team
GYS1; gene GYS1
UniProt
Manually annotated by BRENDA team
GYS2; gene GYS2
UniProt
Manually annotated by BRENDA team
Sus scrofa Meishan
GYS1; gene GYS1
UniProt
Manually annotated by BRENDA team
Sus scrofa Meishan
GYS2; gene GYS2
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
evolution
-
glycogen synthase homologues in bacteria and archaea lack regulation, while the eukaryotic enzymes are inhibited by protein kinase mediated phosphorylation and activated by protein phosphatases and D-glucose 6-phosphate binding
metabolism
-
glycogen synthase intrinsic activity is strongly dependent on glycogen levels. Regulation involves associated dephosphorylation at sites 2 + 2a, 3a, and 3a + 3b. There exist several glycogen metabolism regulatory mechanisms based on glycogen synthase intracellular compartmentalization. After exhausting exercise, epinephrine-induced protein kinase A activation leads to glycogen synthase site 1b phosphorylation targeting the enzyme to intramyofibrillar glycogen particles, which are preferentially used during muscle contraction. When phosphorylated at sites 2 + 2a, glycogen synthase is preferentially associated with subsarcolemmal and intermyofibrillar glycogen particles. After overnight low muscle glycogen level and/or in response to exhausting exercise-induced glycogenolysis, glycogen synthase is associated with spherical structures at the I-band of sarcomeres
metabolism
-
in healthy subjects, adrenaline infusion increases blood glucose concentration by approximately 50%, but a hyperinsulinemic clamp normalizes blood glucose within 30 minutes. Insulin increases glycogen synthase fractional activity and decreases glycogen synthase Ser641 and Ser645,649,653,657 phosphorylation. In the presence of adrenaline, insulin does neither activate glycogen synthase nor dephosphorylate glycogen synthase Ser641. glycogen synthase Ser7 phosphorylation is not influenced by adrenaline. Adrenaline increases plasma lactate concentration, and muscle glycogen content is reduced in skeletal muscle the day after adrenaline infusion
physiological function
-
a mutant strain defective in adenylyl cyclase activity accumulates, during vegetative growth, glycogen levels much higher than the wild type strain. The gsn transcript is not increased in this strain but the GSN protein is less phosphorylated in vitro, and therefore more active
physiological function
E0X6R2, E0X6R4, -
glycogen synthase catalyzes the key step of glycogen synthesis and plays an important role in glycogen metabolism in liver and muscle, phosphorylation sites regulate the activity of the enzyme; glycogen synthase catalyzes the key step of glycogen synthesis and plays an important role in glycogen metabolism in liver and muscle, phosphorylation sites regulate the activity of the enzyme. Transcriptional regulation of GYS1 during myogenic differentiation in porcine satellite cells, overview. Effect of insulin is primarily mediated via posttranscriptional control the porcine glycogen synthase. Insulin promotes dephosphorylation of glycogen synthase in differentiated porcine satellite cells
physiological function
Sus scrofa Meishan
-
glycogen synthase catalyzes the key step of glycogen synthesis and plays an important role in glycogen metabolism in liver and muscle, phosphorylation sites regulate the activity of the enzyme; glycogen synthase catalyzes the key step of glycogen synthesis and plays an important role in glycogen metabolism in liver and muscle, phosphorylation sites regulate the activity of the enzyme. Transcriptional regulation of GYS1 during myogenic differentiation in porcine satellite cells, overview. Effect of insulin is primarily mediated via posttranscriptional control the porcine glycogen synthase. Insulin promotes dephosphorylation of glycogen synthase in differentiated porcine satellite cells
-
metabolism
F2Q6J8, -
synthesis and degradation of trehalose and glycogen in insects involving glycogen synthase, overview
additional information
-
in the basal activity state and D-glucose 6-phosphate activated state, the enzyme is assembled into an unusual tetramer by an insertion unique to the eukaryotic enzymes, and this subunit interface is rearranged by the binding of D-glucose 6-phosphate, which frees the active site cleft and facilitates catalysis. Structure function in enzyme regulation, overview
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ADP-glucose + (1,4-alpha-D-glucosyl)n
ADP + (1,4-alpha-D-glucosyl)n+1
show the reaction diagram
-
-
-
-
?
ADP-glucose + (1,4-alpha-D-glucosyl)n
ADP + (1,4-alpha-D-glucosyl)n+1
show the reaction diagram
-
the enzyme can use ADP-glucose or UDP-glucose as donor substrate
-
-
?
ADP-glucose + (1,4-alpha-D-glucosyl)n
ADP + (1,4-alpha-D-glucosyl)n+1
show the reaction diagram
A8V967, -
Cyanophora paradoxa synthesizes amylose with a granule-bound starch synthase displaying a preference for UDP-glucose
-
-
?
ADP-glucose + glycogen
? + ADP
show the reaction diagram
-
-
-
-
?
ADP-glucose + glycogen
ADP + ?
show the reaction diagram
A8V967, -
-
-
-
?
ADP-glucose + glycogen
ADP + ?
show the reaction diagram
-
-
with granule-bound starch synthase, ADP-glucose is used at less than 2% of the activity with UDP-glucose
-
?
dTDP-glucose + (1,4-alpha-D-glucosyl)n
dTDP + (1,4-alpha-D-glucosyl)n+1
show the reaction diagram
-
-
-
-
?
UDP-glucose + (1,4-alpha-D-glucosyl)n
UDP + (1,4-alpha-D-glucosyl)n+1
show the reaction diagram
-
-
-
-
?
UDP-glucose + (1,4-alpha-D-glucosyl)n
UDP + (1,4-alpha-D-glucosyl)n+1
show the reaction diagram
-
-
-
-
?
UDP-glucose + (1,4-alpha-D-glucosyl)n
UDP + (1,4-alpha-D-glucosyl)n+1
show the reaction diagram
-
conjugated bile acids regulate hepatocyte glycogen synthase activity in vitro and in vivo via Galphai signaling
-
-
?
UDP-glucose + (1,4-alpha-D-glucosyl)n
UDP + (1,4-alpha-D-glucosyl)n+1
show the reaction diagram
-
the enzyme can use ADP-glucose or UDP-glucose as donor substrate
-
-
?
UDP-glucose + (1,4-alpha-D-glucosyl)n
UDP + (1,4-alpha-D-glucosyl)n+1
show the reaction diagram
A8V967, -
Cyanophora paradoxa synthesizes amylose with a granule-bound starch synthase displaying a preference for UDP-glucose
-
-
?
UDP-glucose + amylopectin
UDP + ?
show the reaction diagram
-
-
-
-
?
UDP-glucose + amylopectin
UDP + amylose + ?
show the reaction diagram
A8V967, -
enzyme polymerizes glucose residues to the outer chains of amylopectin. These chains subsequently are cleaved off amylopectin to generate mature amylose
-
-
?
UDP-glucose + glucose
? + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
-
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
greater affinity to low molecular mass glycoproteins
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
transfers glucose to glycogen as well as to its phosphorylase limit dextrin, but not to its beta-amylase dextrin, glucose, maltose and maltotriose are not acceptors
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
important role in initial stages of glycogen biogenesis
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
glycogen production
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
glycogen production
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
Neurospora crassa FGSC424
-
-
-
-
?
UDP-glucose + glycogen
ADP + glycogen
show the reaction diagram
-
increased insulin receptor signaling and glycogen synthase activity contribute to the synergistic effect of exercise on insulin action
-
-
?
UDP-glucose + glycogen
UDP + glycogen
show the reaction diagram
-
glucose starvation results in UDP-glucose deficiency and inactivation of glycogen synthase
-
-
?
UDP-glucose + glycogen
UDP + ?
show the reaction diagram
A8V967, -
-
-
-
?
UDP-glucose + glycogen
UDP + ?
show the reaction diagram
-
UDP-glucose is preferred substrate for granule-bound starch synthase and low and high mobility isoforms of starch synthase
-
-
?
UDP-glucose + maltohexaose
? + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + maltopentaose
? + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + maltotetraose
? + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + maltotriose
UDP + amylose
show the reaction diagram
A8V967, -
-
-
-
?
UDP-glucose + starch
starch + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + [(1->4)-alpha-D-glucosyl]n
UDP + [(1->4)-alpha-D-glucosyl]n+1
show the reaction diagram
-
-
-
-
?
UDP-glucose + [(1->4)-alpha-D-glucosyl]n
UDP + [(1->4)-alpha-D-glucosyl]n+1
show the reaction diagram
-
-
-
-
?
UDP-glucose + [(1->4)-alpha-D-glucosyl]n
UDP + [(1->4)-alpha-D-glucosyl]n+1
show the reaction diagram
F2Q6J8, -
-
-
-
?
UDP-glucose + [(1->4)-alpha-D-glucosyl]n
UDP + [(1->4)-alpha-D-glucosyl]n+1
show the reaction diagram
E0X6R2, E0X6R4, -
-
-
-
?
UDP-glucose + [(1->4)-alpha-D-glucosyl]n
UDP + [(1->4)-alpha-D-glucosyl]n+1
show the reaction diagram
-
glycogen synthase reacts with its glucosyl donor substrate, uridine 5'-diphosphoglucose to produce the scission of the covalent bond between the terminal phosphate oxygen of UDP and the sugar ring. UDP presence in the active site of the enzyme of a glucose-like derivative that lacks the exocyclic oxygen attached to the anomeric carbon
-
-
?
UDP-glucose + [(1->4)-alpha-D-glucosyl]n
UDP + [(1->4)-alpha-D-glucosyl]n+1
show the reaction diagram
Sus scrofa Meishan
E0X6R2, E0X6R4
-
-
-
?
GDP-glucose + (1,4-alpha-D-glucosyl)n
GDP + (1,4-alpha-D-glucosyl)n+1
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
a point mutation in the UDP-glucose diphosphorylase gene results in decreases of UDP-glucose. Chronically low UDP-glucose levels in cells result in inactivation of glycogen synthase, owing to loss of the ability of glycogen synthase to bind UDP-glucose - non-substrate-dependent control of glycogen synthase
-
-
-
additional information
?
-
-
key enzyme in regulation of glycogen synthesis, controlled by multisite phosphorylation, phosphorylation of Ser640 by DYRK family protein kinases causes strong inactivation of glycogen synthase, functionally important site 3a in glycogen synthase by protein kinases from the DYRK family may be involved in a mechanism for the regulation of glycogen synthesis
-
-
-
additional information
?
-
-
O-GlcNAc has a role in the regulation of glycogen synthase both in normoglycemia and diabetes
-
-
-
additional information
?
-
Q8MJ26
one mechanism by which peroxisome proliferator-activated receptor-alpha agonist treatment improves whole body insulin sensitivity is by increasing skeletal muscle GS total activity
-
-
-
additional information
?
-
-
glycogen synthase 2 is a novel target gene of peroxisome proliferator-activated receptors
-
-
-
additional information
?
-
A8V967, -
enzyme is able to use both ADP-glucose and UDP-glucose but displays a sixfold higher Vmax with UDP-glucose
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
UDP-glucose + (1,4-alpha-D-glucosyl)n
UDP + (1,4-alpha-D-glucosyl)n+1
show the reaction diagram
A8V967, -
Cyanophora paradoxa synthesizes amylose with a granule-bound starch synthase displaying a preference for UDP-glucose
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
-
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
important role in initial stages of glycogen biogenesis
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
glycogen production
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
-
glycogen production
-
-
?
UDP-glucose + glycogen
ADP + glycogen
show the reaction diagram
-
increased insulin receptor signaling and glycogen synthase activity contribute to the synergistic effect of exercise on insulin action
-
-
?
UDP-glucose + glycogen
UDP + glycogen
show the reaction diagram
-
glucose starvation results in UDP-glucose deficiency and inactivation of glycogen synthase
-
-
?
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
Neurospora crassa FGSC424
-
-
-
-
?
UDP-glucose + [(1->4)-alpha-D-glucosyl]n
UDP + [(1->4)-alpha-D-glucosyl]n+1
show the reaction diagram
-
-
-
-
?
UDP-glucose + [(1->4)-alpha-D-glucosyl]n
UDP + [(1->4)-alpha-D-glucosyl]n+1
show the reaction diagram
-
-
-
-
?
UDP-glucose + [(1->4)-alpha-D-glucosyl]n
UDP + [(1->4)-alpha-D-glucosyl]n+1
show the reaction diagram
F2Q6J8, -
-
-
-
?
UDP-glucose + [(1->4)-alpha-D-glucosyl]n
UDP + [(1->4)-alpha-D-glucosyl]n+1
show the reaction diagram
E0X6R2, E0X6R4, -
-
-
-
?
UDP-glucose + [(1->4)-alpha-D-glucosyl]n
UDP + [(1->4)-alpha-D-glucosyl]n+1
show the reaction diagram
Sus scrofa Meishan
E0X6R2, E0X6R4
-
-
-
?
additional information
?
-
-
a point mutation in the UDP-glucose diphosphorylase gene results in decreases of UDP-glucose. Chronically low UDP-glucose levels in cells result in inactivation of glycogen synthase, owing to loss of the ability of glycogen synthase to bind UDP-glucose - non-substrate-dependent control of glycogen synthase
-
-
-
additional information
?
-
-
key enzyme in regulation of glycogen synthesis, controlled by multisite phosphorylation, phosphorylation of Ser640 by DYRK family protein kinases causes strong inactivation of glycogen synthase, functionally important site 3a in glycogen synthase by protein kinases from the DYRK family may be involved in a mechanism for the regulation of glycogen synthesis
-
-
-
additional information
?
-
-
O-GlcNAc has a role in the regulation of glycogen synthase both in normoglycemia and diabetes
-
-
-
additional information
?
-
Q8MJ26
one mechanism by which peroxisome proliferator-activated receptor-alpha agonist treatment improves whole body insulin sensitivity is by increasing skeletal muscle GS total activity
-
-
-
additional information
?
-
-
glycogen synthase 2 is a novel target gene of peroxisome proliferator-activated receptors
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Ca2+
-
stimulates interconversion of D to I from
Ca2+
-
no influence on activity
Ca2+
-
activation in presence of glucose 6-phosphate
CaSO4
-
to a lesser extent, absence of glucose-6-phosphate
Cl-
-
activation
CoSO4
-
absence of glucose-6-phosphate
FeSO4
-
to a lesser extent, absence of glucose-6-phosphate
KCl
-
activation in presence of glucose 6-phosphate
Li+
-
wild-type but not mutant enzyme
Li+
-
activation
Li+
-
-
Mg2+
-
no influence on activity
Mg2+
-
stimulates D form but not I form
Mg2+
-
no influence on activity
Mg2+
-
activation in presence of glucose 6-phosphate
Mg2+
-
activation
Mg2+
-
required
MgCl2
-
10 mM, NaF inhibits activation
MgSO4
-
to a lesser extent, absence of glucose-6-phosphate
Mn2+
-
stimulates interconversion of D to I form
Mn2+
-
no influence on activity
Mn2+
-
activation in presence of glucose 6-phosphate
MnSO4
-
absence of glucose-6-phosphate
Na+
-
activation
Na2SO4
-
low concentrations
NaCl
-
activation in presence of glucose 6-phosphate
NH4Cl
-
activation in presence of glucose 6-phosphate
NiSO4
-
absence of glucose-6-phosphate
MnSO4
-
MnSO4-dependent glucose transfer is catalyzed by a non-glucose 6-phosphate dependent form of the enzyme
additional information
-
5fold stimulation by divalent anions
additional information
-
no divalent cation requirement, no activation by Fe3+
additional information
-
regulation of enzyme activity
additional information
-
-
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(NH4)2SO4
-
20% inactivation at 20 mM
1,5-gluconolactone
-
-
2,3-diphosphoglyceric acid
-
high concentrations
2-mercaptoethanol
-
high concentrations
adenine nucleotides
-
-
ADP-glucose
-
competitive with UDPglucose
ATP
-
50% inhibition at 5 mM
ATP
-
not inhibitory
ATP
-
almost complete inhibition at 5 mM
beta-Glycerophosphate
-
-
Caffeine
-
10-50 mM
calyculin A
-
-
D-glucose-1-phosphate
-
-
dithiobis-(2-nitrobenzoic acid)
-
77% inactivation at 1 mM
dithiothreitol
-
high concentrations
epinephrine
-
leads to phosphorylation of enzyme
ethanol
-
traces inactivate the enzyme
fructose 1,6-diphosphate
-
high concentrations
Glucagon
-
leads to phosphorylation of enzyme
glucosamine
-
high concentrations during cultivation
glucose
-
50% inhibition at 50 mM
glucose
-
high concentrations during cultivation
Insulin
-
pre-treatment of cells inhibits, 0.001 mM isoproterenol reverses inhibition
-
iodoacetate
-
not inhibitory
iodoacetate
-
10% inactivation at 10 mM
Iodobenzoate
-
22% inactivation at 1 mM
-
KCN
-
58% inhibition at 0.1 M
Mg2+
-
above 2 mM
microcystin
-
-
-
N-ethylmaleimide
-
83% inactivation at 3 mM
Na2SO4
-
high concentrations
NaCl
-
above 100 mM
NaCl
-
48% activity at 0.3 M
Nucleoside phosphates
-
overview
okadaic acid
-
-
Oxytocin
-
leads to phosphorylation of enzyme
p-chloromercuribenzoate
-
90% inactivation at 0.01 mM, dithiothreitol reverses
phenylmercuric acetate
-
-
phloridzin
-
50% inhibition at 3.3 mM
Phorbol esters
-
-
phosphate
-
inhibition of synthase D
phosphate
-
high concentrations
phosphate
-
strong inhibitor
phosphate
-
Mg2+, Ca2+ or Mn2+ relieves inhibition
phosphate
-
-
phosphate
-
10-100 mM
phosphate
-
0.8-2 mM
phosphate
-
UDP-glucose reverses inhibition of newborn enzyme
potassium borate
-
80% inhibition at 0.2 M
SO42-
-
strong inhibitor
SO42-
-
Mg2+, Ca2+ or Mn2+ relieves inhibition
SO42-
-
10-100 mM
theophylline
-
10-50 mM
Trehalose phosphate
-
59% inhibition at 10 mM
UDP
-
31% inhibition at 1 mM
UDP
-
50% inhibition at 0.05 mM
UDP
-
50% inhibition at 0.03 mM
UDP
-
competitive to UDP-glucose, noncompetitive to glycogen
UDP
-
0.003-0.013 mM, competitive with UDP-glucose
UDP-galactose
-
-
UDP-glucose
-
-
UDP-glucose
-
competitive with ADP-glucose
UDP-pyridoxal
-
36% activity at 0.1 mM
UMP
-
high concentrations, competitive
UMP
-
competitive with UDP-glucose
uridine 5'-phosphate
-
50% inhibition
UTP
-
competitive with UDP-glucose
UTP
-
affects glucose-6-phosphate binding
Vasopressin
-
leads to phosphorylation of enzyme
additional information
-
not inhibitory: EDTA, iodoacetic acid, thioglycolate, trypsin and chymotrypsin decrease activity to 60% within 60 min
-
additional information
-
the eukaryotic enzyme is inhibited by protein kinase mediated phosphorylation, four arginine residues of a regulatory helix regulate the response to phosphorylation. When Thr668 is phosphorylated, Arg580 and Arg581 play a role in stabilizing the inhibited conformation by directly interacting with the phosphate group at or near the N-terminus of the regulatory helix, possibly near one of the sulfate binding sites in our basal state structure
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2,3-diphosphoglyceric acid
-
low concentrations
2-deoxyglucose 6-phosphate
-
stimulates interconversion of D to I form
aspartate
-
increased uptake leads to activation
Bile acids
-
enhance the activity of the insulin receptor and glycogen synthase in primary hepatocytes
bisperoxyvanadium 1,10-phenanthroline
-
phosphatidylinositol 3-kinase inhibitor wortmannin and rapamycin inhibits activation
D-glucose
-
low concentrations during cultivation
D-glucose
-
phosphatidylinositol 3-kinase inhibitor wortmannin inhibits activation
Dihydroxyacetone
-
increase of activity
fructose
-
increase of activity
fructose 1,6-diphosphate
-
low concentrations
galactose
-
increase of activity
galactose 6-phosphate
-
stimulates interconversion of D to I form
galactose 6-phosphate
-
57% of the glucose-6-phosphate activation
galactose 6-phosphate
-
-
glucosamine
-
low concentrations during cultivation
glucosamine 6-phosphate
-
stimulates interconversion of D to I form
glucosamine 6-phosphate
-
50% of the glucose-6-phosphate activation
glucose 6-phosphate
-
synthase D, i.e. phosphorylated form, is glucose 6-phosphate dependent, synthase I, i.e. dephosphorylated form, is glucose 6-phosphate independent, interconversion of D and I forms and vice versa
glucose 6-phosphate
-
synthase D, i.e. phosphorylated form, is glucose 6-phosphate dependent, synthase I, i.e. dephosphorylated form, is glucose 6-phosphate independent, interconversion of D and I forms and vice versa
glucose 6-phosphate
-
synthase D, i.e. phosphorylated form, is glucose 6-phosphate dependent, synthase I, i.e. dephosphorylated form, is glucose 6-phosphate independent, interconversion of D and I forms and vice versa
glucose 6-phosphate
-
synthase D, i.e. phosphorylated form, is glucose 6-phosphate dependent, synthase I, i.e. dephosphorylated form, is glucose 6-phosphate independent, interconversion of D and I forms and vice versa
glucose 6-phosphate
-
synthase D, i.e. phosphorylated form, is glucose 6-phosphate dependent, synthase I, i.e. dephosphorylated form, is glucose 6-phosphate independent, interconversion of D and I forms and vice versa
glucose 6-phosphate
-
1.5fold
glucose 6-phosphate
-
-
glucose 6-phosphate
-
stimulates at UDP-glucose concentration of 0.4 mM; synthase D, i.e. phosphorylated form, is glucose 6-phosphate dependent, synthase I, i.e. dephosphorylated form, is glucose 6-phosphate independent, interconversion of D and I forms and vice versa
glucose 6-phosphate
-
dependent on
glucose 6-phosphate
-
glucose-6-phosphate dependent form is inactive in vivo
glucose 6-phosphate
-
synthase D, i.e. phosphorylated form, is glucose 6-phosphate dependent, synthase I, i.e. dephosphorylated form, is glucose 6-phosphate independent, interconversion of D and I forms and vice versa
glucose 6-phosphate
-
synthase D, i.e. phosphorylated form, is glucose 6-phosphate dependent, synthase I, i.e. dephosphorylated form, is glucose 6-phosphate independent, interconversion of D and I forms and vice versa
glucose 6-phosphate
-
-
glucose 6-phosphate
-
dependent on
glucose 6-phosphate
-
-
glucose 6-phosphate
-
2fold activation in vivo and 10fold activation in vitro
glucose 6-phosphate
-
enzyme from cells cultivated in low glucose concentrations is more sensitive to glucose 6-phosphate
glucose 6-phosphate
-
-
glucose 6-phosphate
-
-
glucose-6-phosphate
-
D-glucose 6-phosphate binding structure, Arg580 forms an interaction with the 6-phosphate of D-glucose 6-phosphate, overview. The eukaryotic enzyme is activated by protein phosphatases and D-glucose 6-phosphate binding. The enzyme's response to D-glucose 6-phosphate is controlled by Arg583 and Arg587, while four additional arginine residues present within the same regulatory helix regulate the response to phosphorylation
glutamate
-
increased uptake leads to activation
glycogen
-
-
Insulin
-
phosphatidylinositol 3-kinase inhibitor wortmannin inhibits activation
-
Insulin
-
increased activity after insulin infusion
-
Insulin
-
stimulation can be decreased with antisense oligonucleotides
-
Insulin
-
high concentration of glucose inhibit stimulation
-
Insulin
-
inhibits phosphorylation by kinases and synthase phospatase
-
Insulin
-
stimulation of activity. In patients with type 1 diabetes glycogen synthase activity remains unchanged versus control, and insulin does not stimulate the enzyme activity. In patients with type 2 diabetes a significant decrease in glycogen synthase activity is accompanied by the decrease in the effect of peptides, giving the following order of their efficiency: insulin = IGF-1> relaxin. In myometrium of pregnant women with gestational treated and untreated diabetes, glycogen synthase activity decreases, the effect of insulin is weaker, whereas the effects of relaxin and IGF-1increase thus giving the following order of their efficiency: relaxin > IGF-1> insulin. Insulin therapy of type 1 diabetes incompletely restores sensitivity of the enzymes to the peptide actions
-
insulin-like growth factor 1
-
stimulation of activity. In patients with type 2 diabetes a significant decrease in glycogen synthase activity is accompanied by the decrease in the effect of peptides, giving the following order of their efficiency: insulin = IGF-1> relaxin. In myometrium of pregnant women with gestational treated and untreated diabetes, glycogen synthase activity decreases, the effect of insulin is weaker, whereas the effects of relaxin and IGF-1increase thus giving the following order of their efficiency: relaxin > IGF-1 > insulin. Insulin therapy of type 1 diabetes incompletely restores sensitivity of the enzymes to the peptide actions
-
Mannose
-
increase of activity
phosphate
-
e.g. sugar phosphates, inorganic phosphate, nucleoside phosphates, activation of synthase I
phosphate
-
below 2 mM
proline
-
increased uptake leads to activation
Propionate
-
significant activation
relaxin
-
stimulation of activity. In patients with type 2 diabetes a significant decrease in glycogen synthase activity is accompanied by the decrease in the effect of peptides, giving the following order of their efficiency: insulin = IGF-1 > relaxin. In myometrium of pregnant women with gestational treated and untreated diabetes, glycogen synthase activity decreases, the effect of insulin is weaker, whereas the effects of relaxin and IGF-1 increase thus giving the following order of their efficiency: relaxin > IGF-1 > insulin. Insulin therapy of type 1 diabetes incompletely restores sensitivity of the enzymes to the peptide actions
-
ribose 5-phosphate
-
stimulates interconversion of D to I form
SO42-
-
stimulatory effect increases as the enzyme becomes more phosphorylated
staurosporine
-
-
xylitol
-
increase of activity
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
4.1
-
ADP-glucose
-
80C, pH 5.0
4.3
-
ADP-glucose
-
-
8
-
ADP-glucose
A8V967, -
pH 7.5, 35C
11.5
-
ADP-glucose
-
high-mobility isoform
46.9
-
ADP-glucose
-
low-mobility isoform
2
-
Amylopectin
-
high-mobility isoform
10
-
Amylopectin
-
low-mobility isoform
4
-
dTDP-glucose
-
80C, pH 5.0
3.9
-
GDP-glucose
-
80C, pH 5.0
2.4
-
glycogen
-
low-mobility isoform
0.0005
-
UDP-glucose
-
presence of glucose 6-phosphate
0.0015
-
UDP-glucose
-
absence of glucose 6-phosphate
0.021
-
UDP-glucose
-
alpha state
0.021
-
UDP-glucose
-
-
0.033
-
UDP-glucose
-
synthase I, 25C, presence of glucose 6-phosphate
0.05
-
UDP-glucose
-
with Na2SO4, form I
0.081
-
UDP-glucose
-
under physiological conditions
0.082
-
UDP-glucose
-
synthase I, 37C, presence of glucose 6-phosphate
0.11
-
UDP-glucose
-
without Na2SO4, form I
0.113
-
UDP-glucose
-
synthase I, 25C, absence of glucose 6-phosphate
0.26
0.34
UDP-glucose
-
without glucose-6-phosphate
0.27
-
UDP-glucose
-
with Na2SO4, form II
0.31
0.32
UDP-glucose
-
value independent of glucose 6-phosphate concentration
0.31
0.32
UDP-glucose
-
UDP-glucose, synthase D
0.33
0.34
UDP-glucose
-
with glucose-6-phosphate
0.4
1.1
UDP-glucose
-
value dependent on glucose 6-phosphate
0.415
0.416
UDP-glucose
-
synthase D, value independent of presence of glucose 6-phosphate
0.508
-
UDP-glucose
-
synthase I, 37C, absence of glucose 6-phosphate
0.57
1.25
UDP-glucose
-
value dependent on the presence of glucose 6-phosphate
0.72
-
UDP-glucose
-
without Na2SO4, form II
0.87
-
UDP-glucose
-
-
0.9
-
UDP-glucose
-
-
1.4
-
UDP-glucose
-
-
2.4
7.2
UDP-glucose
-
dependent on glucose-6-phosphate
2.4
-
UDP-glucose
-
-
2.8
-
UDP-glucose
-
synthase I
4.1
-
UDP-glucose
-
-
4.1
-
UDP-glucose
-
80C, pH 5.0
10.7
-
UDP-glucose
-
high-mobility isoform
15
-
UDP-glucose
A8V967, -
pH 7.5, 35C
21.3
-
UDP-glucose
-
low-mobility isoform
4.6
-
glycogen
-
high-mobility isoform
additional information
-
additional information
-
overview
-
additional information
-
additional information
-
dependence on glucose 6-phosphate concentration
-
additional information
-
additional information
-
glycogen: 3.5 mg/ml
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
values for phosphorylated enzyme forms
-
additional information
-
additional information
-
regulation by phosphorylation
-
additional information
-
additional information
-
regulation by phosphorylation
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
regulation by phosphorylation
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
dependence on glucose 6-phosphate concentration
-
additional information
-
additional information
-
dependent on enzyme form and pH
-
additional information
-
additional information
-
dependence on glucose 6-phosphate concentration
-
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
580
-
adenine
-
80C, pH 5.0
5.4
-
ADP
-
80C, pH 5.0
22
-
ADP-glucose
-
-
3.7
-
AMP
-
80C, pH 5.0
290
-
D-glucose
-
80C, pH 5.0
120
-
D-glucose-1-phosphate
-
80C, pH 5.0
5.4
-
UDP
-
80C, pH 5.0
17
-
UDP-galactose
-
80C, pH 5.0
18
-
UDP-glucose
-
-
0.043
-
UMP
-
-
6.5
-
UMP
-
80C, pH 5.0
90
-
uridine
-
80C, pH 5.0
0.017
-
UTP
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
3
-
-
synthase D
4.3
-
-
-
4.7
-
-
-
9.83
-
-
synthase I
11.3
-
-
synthase I
14.13
-
-
-
21
25
-
synthase I
21
-
-
synthase D
21
-
-
synthase I
22
-
-
presence of 20 mM glucose 6-phosphate
30
35
-
synthase D
63
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
assay method
additional information
-
-
assay based on ESI-mass spectrometry enables detection of submicromolar quantities of substrate, thus requiring even lower concentrations of protein and is amenable to high throughput screening methods
additional information
-
-
measurement of glycogen synthase activity in crude extracts by capillary electrophoresis
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.5
9.2
-
synthase D, presence of glucose 6-phosphate
6.7
-
-
synthase I, enzyme form 1, absence of Na2SO4
6.8
9.2
-
synthase I, presence of glucose 6-phosphate
7
8.5
-
synthase D, absence of glucose 6-phosphate
7
-
-
synthase I
7
-
-
synthase I, broad pH optimum
7
-
-
assay at
7.1
-
-
synthase I, enzyme form 2, absence of Na2SO4
7.2
8
-
synthase I, absence of glucose 6-phosphate
7.2
-
-
synthase D, MOPS buffer
7.4
-
-
glucose 6-phosphate independent form
7.5
-
-
absence of glucose 6-phosphate
7.5
-
-
-
7.7
-
-
synthase I, enzyme form 1, presence of Na2SO4
7.8
-
-
absence of glucose 6-phosphate
7.8
-
-
assay at
7.8
-
E0X6R2, E0X6R4, -
assay at; assay at
8
-
-
brain enzyme
8
-
-
synthase I, enzyme form 2, presence of Na2SO4
8.3
-
-
glucose 6-phosphate dependent form
8.4
-
-
muscle enzyme
8.5
-
-
synthase I, narrow pH optimum
8.8
-
-
presence of glucose 6-phosphate
9.5
-
-
low-mobility isoform
10
-
-
high-mobility isoform
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
22
-
-
assay at room temperature
25
-
-
both low-mobility isoform and high-mobility isoform
37
-
-
-
37
-
E0X6R2, E0X6R4, -
assay at; assay at
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
-
-
human enzyme has no activity above 50C, rat enzyme is active up to at least 60C
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.78
-
E0X6R2, E0X6R4, -
GYS1, sequence calculation
5.84
-
F2Q6J8, -
sequence calculation
6.46
-
E0X6R2, E0X6R4, -
GYS2, sequence calculation
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
synthetic peroxisome proliferator-activated receptor beta/delta, and gamma agonists markedly up-regulate Gys-2 mRNA and protein expression in mouse 3T3-L1 adipocytes
Manually annotated by BRENDA team
-
expression of Gys-2 is significantly reduced in adipose tissue of peroxisome proliferator-activated receptor alpha-/-, peroxisome proliferator-activated receptor beta/delta-/- and peroxisome proliferator-activated receptor gamma+/- mice
Manually annotated by BRENDA team
E0X6R2, E0X6R4, -
subcutaneous, expression of GYS2; subcutaneous, GYS1
Manually annotated by BRENDA team
Sus scrofa Meishan
-
subcutaneous, expression of GYS2
-
Manually annotated by BRENDA team
F2Q6J8, -
larval
Manually annotated by BRENDA team
E0X6R2, E0X6R4, -
GYS1
Manually annotated by BRENDA team
-
hypoxia activates glycogen synthase in fed rat myocardium through a combination of rapid glycogenolysis, elevated local glucose 6-phosphate content, and increased protein phosphatase 1 activity, and fasting attenuates this action independent of local glucose 6-phosphate content. Activation of glycogen synthase in myocardium induced by intermittent hypoxia is much lower in fasted than in fed rats
Manually annotated by BRENDA team
-
strong expression, relative levels of Cg-GYS transcripts appear highest in October corresponding to glycogen storage and resting period
Manually annotated by BRENDA team
E0X6R2, E0X6R4, -
high expression level of GYS1; high expression level of GYS1
Manually annotated by BRENDA team
Sus scrofa Meishan
-
high expression level of GYS1
-
Manually annotated by BRENDA team
-
5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside positively regulates glycogen synthase activity and LDL receptor expression through Raf-1/MEK/p42/44MAPK/p90RSK/GSK-3 signaling cascade
Manually annotated by BRENDA team
-
upon rapamycin treatment, the overexpression of constitutively active Akt-1 in Hep-G2 cells leads to an increase in the phosphorylation of Akt (Ser 473) and, an increase in the GS and PP-1 activities, in contrast to a decrease in Akt phosphorylation and GS and PP-1 activities in parental HepG2 cells
Manually annotated by BRENDA team
-
insulin receptor substrate (IRS) protein 1 knockdown reduces the glycogen synthase activity in parental HepG2 cells. It is upregulated in HepG2-CA-Akt/PKB cells
Manually annotated by BRENDA team
-
primary culture
Manually annotated by BRENDA team
-
reduction in glucose production in primary hepatocytes by the overexpression of the mutant GYS2. The elevation of liver glycogen synthase activity in primary hepatocytes reduces glucose production by shunting gluconeogenic precursors into glycogen rather than by stimulating direct glucose incorporation into glycogen
Manually annotated by BRENDA team
E0X6R2, E0X6R4, -
GYS1
Manually annotated by BRENDA team
Sus scrofa Meishan
-
GYS1
-
Manually annotated by BRENDA team
-
strong expression, relative levels of Cg-GYS transcripts appear highest in October corresponding to glycogen storage and resting period
Manually annotated by BRENDA team
E0X6R2, E0X6R4, -
GYS1; high expression level of GYS2
Manually annotated by BRENDA team
Sus scrofa Meishan
-
GYS1; high expression level of GYS2
-
Manually annotated by BRENDA team
-
glycolytic glioma cells with active glycogen synthase are sensitive to phosphatase and tensin homolog (PTEN) and inhibitors of phosphatidylinositol-3 kinase and gluconeogenesis
Manually annotated by BRENDA team
E0X6R2, E0X6R4, -
GYS1
Manually annotated by BRENDA team
-
contraction activates glycogen synthase in muscles from dexamethasone-treated rats
Manually annotated by BRENDA team
-
in low glycogen, basal and insulin-stimulated glycogen synthesis and glycogen synthase activation is higher and glycogen synthase phosphorylation (Ser645, Ser649, Ser653, Ser657) lower than in normal glycogen. Muscles with high glycogen show lower insulin-stimulated glycogen synthesis and glycogen synthase activation than normal glycogen despite similar dephosphorylation
Manually annotated by BRENDA team
-
of insulin-resistant, fat-fed rats and chow-fed controls, either maintained in the basal state or after a euglycaemichyperinsulinaemic clamp
Manually annotated by BRENDA team
-
basal glycogen synthase activity in muscle lacking rictor is increased to that of insulin-stimulated controls. A decrease in basal levels of phosphorylated glycogen synthase at a GSK-3/protein phosphatase 1 (glycogen-associated protein phosphatase 1)-regulated site in rictor knockout muscle is observed. This change in glycogen synthase phosphorylation is associated with an increase in the catalytic activity of glycogen-associated glycogen-associated protein phosphatase 1 but not increased GSK-3 inactivation
Manually annotated by BRENDA team
Neurospora crassa FGSC424
-
vegetative
-
Manually annotated by BRENDA team
E0X6R2, E0X6R4, -
GYS1
Manually annotated by BRENDA team
Sus scrofa Meishan
-
GYS1
-
Manually annotated by BRENDA team
-
in distal tubular cells, adiponectin through luminal ADIPOR1 activates AMPK, leading to the inhibition of glycogen synthase. During hyperglycemia, this regulation is altered, which may explain, at least in part, the accumulation of large glycogen deposits
Manually annotated by BRENDA team
E0X6R2, E0X6R4, -
GYS1
Manually annotated by BRENDA team
-
slowtwitch (soleus) and fast-twitch (epitrochlearis) muscle. Improved insulin-stimulated glucose uptake and glycogen synthase activation after adrenaline infusion
Manually annotated by BRENDA team
-
sucrose feeding does not alter muscle glycogen concentration but provokes a small reduction in the glycogen synthase activity ratio (-/+ glucose-6-phosphate) in red but not in white gastrocnemius. Dexamethasone administration augments glycogen concentration and reduces glycogen synthase activity ratio in both muscle fiber types
Manually annotated by BRENDA team
-
elevated glycogen synthase activity in Polysaccharide Storage Myopathy horses. A gain of function mutation in GYS1 results in a glycogenosis
Manually annotated by BRENDA team
E0X6R2, E0X6R4, -
longissimus dorsi muscle, high expression level of GYS1
Manually annotated by BRENDA team
Sus scrofa Meishan
-
longissimus dorsi muscle, high expression level of GYS1
-
Manually annotated by BRENDA team
E0X6R2, E0X6R4, -
GYS1
Manually annotated by BRENDA team
E0X6R2, E0X6R4, -
GYS1
Manually annotated by BRENDA team
F2Q6J8, -
larval
Manually annotated by BRENDA team
-
glycolytic glioma cells with active glycogensynthase are sensitive to phosphatase and tensin homolog (PTEN) and inhibitors of phosphatidylinositol-3 kinase and gluconeogenesis
Manually annotated by BRENDA team
E0X6R2, E0X6R4, -
GYS1
Manually annotated by BRENDA team
Sus scrofa Meishan
-
GYS1
-
Manually annotated by BRENDA team
F2Q6J8, -
larval
Manually annotated by BRENDA team
additional information
F2Q6J8, -
tissue distribution in tissues from the developmental stages from the first-instar larvae to fifth-instar to pupae and expression pattern, overview
Manually annotated by BRENDA team
additional information
E0X6R2, E0X6R4, -
tissue expression pattern of GYS1, GYS1 is upregulated during porcine myogenic cell differentiation; tissue expression pattern of GYS2
Manually annotated by BRENDA team
additional information
Sus scrofa Meishan
-
tissue expression pattern of GYS2
-
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
longitudinal sarcoplasmic reticulum membrane membrane
Manually annotated by BRENDA team
additional information
Q8MJ26
neither glycogen synthase activity nor glycogen synthase protein are present in the cytosolic fraction of subfractionated skeletal muscle obtained after an overnight fast or after 90 min of insulin infusion during a hyperinsulinemic euglycemic clamp in healthy or in insulin-resistant monkeys. Glycogen synthase activity, glycogen synthase protein, and glycogen are present in all other fractions. In vivo insulin regulation of skeletal muscle glycogen synthase activity does not involve changes in the subcellular localization of glycogen synthase. One mechanism by which peroxisome proliferator-activated receptor-alpha agonist treatment improves whole body insulin sensitivity is by increasing skeletal muscle GS total activity
-
Manually annotated by BRENDA team
additional information
-
initial localization of glycogen synthase in a soluble pool plays an important role in glycogen synthesis, and that its sequestration in an insulin-resistant insoluble pool may explain in part the reduced glycogen synthesis caused by lipid oversupply
-
Manually annotated by BRENDA team
additional information
-
existence of several glycogen metabolism regulatory mechanisms based on glycogen synthase intracellular compartmentalization. After exhausting exercise, epinephrine-induced protein kinase A activation leads to glycogen synthase site 1b phosphorylation targeting the enzyme to intramyofibrillar glycogen particles, which are preferentially used during muscle contraction. When phosphorylated at sites 2 + 2a, GS is preferentially associated with subsarcolemmal and intermyofibrillar glycogen particles. After overnight low muscle glycogen level and/or in response to exhausting exercise-induced glycogenolysis, glycogen synthase is associated with spherical structures at the I-band of sarcomeres
-
Manually annotated by BRENDA team
additional information
F2Q6J8, -
the enzyme contains no signal peptide, putative cleavage sites, and transmembrane domain
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain FostersO)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
87000
-
-
calculated from amino acids residues
100000
-
-
gel filtration
170000
-
-
synthase I, sucrose density gradient centrifugation
183000
-
-
synthase D, sucrose density gradient centrifugation
270000
-
-
sucrose density gradient centrifugation
274000
312000
-
sucrose density gradient centrifugation
280000
-
-
gel filtration
300000
310000
-
gel filtration
300000
310000
-
sedimentation equilibrium
300000
400000
-
gel filtration
340000
-
-
native enzyme
377000
-
-
high speed sedimentation equilibrium centrifugation
390000
-
-
sucrose density gradient centrifugation
390000
-
-
sucrose density gradient centrifugation
410000
-
-
native PAGE
410000
-
-
gel filtration
420000
-
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 85000, SDS-PAGE
?
-
x * 85000, synthase I, SDS-PAGE; x * 90000, synthase D, SDS-PAGE
?
-
x * 80000-85000, SDS-PAGE
?
-
x * 77000-80000, SDS-PAGE
?
-
x * 84000, SDS-PAGE
?
-
x * 80000-93000
?
-
x * 110000, SDS-PAGE, granule-bound starch synthase
?
F2Q6J8, -
x * 76190, about, sequence calculation
?
E0X6R2, E0X6R4, -
x * 80600, about, GYS2, sequence calculation; x * 83700, about, GYS1, sequence calculation
?
Sus scrofa Meishan
-
x * 80600, about, GYS2, sequence calculation; x * 83700, about, GYS1, sequence calculation
-
dimer
-
2 * 85000, SDS-PAGE
dimer
-
2 * 50000, SDS-PAGE
tetramer
-
4 * 99000, SDS-PAGE
tetramer
-
4 * 76000-83000, SDS-PAGE
tetramer
-
4 * 85000
tetramer
-
4 * 88000, SDS-PAGE
tetramer
-
4 * 77000, SDS-PAGE
trimer
-
3 * 88000-90000, SDS-PAGE
trimer
-
homotrimeric protein. The contacts between subunits, which only involve the N-terminal domains, do not restrict the movements of the corresponding C-domains, likely required for catalysis
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
phosphoprotein
-
incorporation of 1.3 pmol phosphate per mol enzyme; phosphorylation leads to loss of activity; phosphorylation of glucose-6-phosphate independent enzyme, i.e. I enzyme, results in glucose-6-phosphate dependent enzyme, i.e. D enzyme
phosphoprotein
-
incorporation of 1-3 phosphates per subunit; phosphorylation leads to loss of activity; phosphorylation of glucose-6-phosphate independent enzyme, i.e. I enzyme, results in glucose-6-phosphate dependent enzyme, i.e. D enzyme
phosphoprotein
-
phosphorylation at 3 different sites
phosphoprotein
-
phosphorylation fails to convert between D and I form
phosphoprotein
-
interconversion of D form to I form is Mn2+ dependent
phosphoprotein
-
in healthy subjects, adrenaline infusion increases blood glucose concentration by approximately 50%, but a hyperinsulinemic clamp normalizes blood glucose within 30 minutes. Insulin increases glycogen synthase fractional activity and decreases glycogen synthase Ser641 and Ser645,649,653,657 phosphorylation. In the presence of adrenaline, insulin does neither activate glycogen synthase nor dephosphorylate glycogen synthase Ser641. Glycogen synthase Ser7 phosphorylation is not influenced by adrenaline. Adrenaline increases plasma lactate concentration, and muscle glycogen content is reduced in skeletal muscle the day after adrenaline infusion
phosphoprotein
-
-
phosphoprotein
-
-
phosphoprotein
-
phosphorylation of glucose-6-phosphate independent enzyme, i.e. I enzyme, results in glucose-6-phosphate dependent enzyme, i.e. D enzyme
phosphoprotein
-
0.8 phosphates per subunit
phosphoprotein
-
0.3 mol per mol enzyme
phosphoprotein
-
incorporation of 1.13 mol phosphate per subunit; phosphorylation leads to loss of activity
phosphoprotein
-
phosphorylation at more than 10 sites; phosphorylation leads to loss of activity; phosphorylation of glucose-6-phosphate independent enzyme, i.e. I enzyme, results in glucose-6-phosphate dependent enzyme, i.e. D enzyme
phosphoprotein
-
phosphorylated by Ca2+-calmodulin dependent protein kinase in fast-twitch skeletal muscle. Phosphorylation does not affect glycogen synthase activity by itself, but it might be necessary for the modulation of glycogen synthase by other protein kinases
phosphoprotein
-
covalent phosphorylation
phosphoprotein
-
-
phosphoprotein
-
phosphorylation of enzyme a into b leads to an altered enzyme activity in adult rats, newborn rat enzyme does not show b into a transformation
phosphoprotein
-
0.8 phosphates per subunit
phosphoprotein
-
-
phosphoprotein
-
in the absence of insulin, glycogen synthase Ser645, Ser649, Ser653, and Ser657 phosphorylation is similar in soleus muscles from control and dexamethasone-treated rats. In epitrochlearis, glycogen synthase phosphorylation is slightly elevated in muscles from dexamethasone-treated rats. Contraction decreases glycogen synthase Ser645, Ser649, Ser653, and Ser657 phosphorylation in soleus to a similar low level in muscles from control and dexamethasone-treated rats. In epitrochlearis muscles, contraction also decreases glycogen synthase phosphorylation to a low level in muscles from control and dexamethasone-treated rats. In soleus and epitrochlearis muscles, the combination of contraction and insulin does not decrease glycogen synthase phosphorylation more than contraction alone
phosphoprotein
-
in low glycogen, basal and insulin-stimulated glycogen synthesis and glycogen synthase activation is higher and glycogen synthase phosphorylation (Ser645, Ser649, Ser653, Ser657) lower than in normal glycogen. Muscles with high glycogen show lower insulin-stimulated glycogen synthesis and glycogen synthase activation than normal glycogen despite similar dephosphorylation
phosphoprotein
-
-
phosphoprotein
-
incorporation of 3 phosphates per subunit; phosphorylation leads to loss of activity; phosphorylation of glucose-6-phosphate independent enzyme, i.e. I enzyme, results in glucose-6-phosphate dependent enzyme, i.e. D enzyme
phosphoprotein
-
incorporation of 1.4 phosphate groups per subunit
phosphoprotein
-
0.7-0.9 mol phosphate per mol protein; phosphorylation leads to loss of activity
phosphoprotein
-
the eukaryotic enzymes are inhibited by protein kinase mediated phosphorylation and activated by protein phosphatases and glucose-6-phosphate binding, regulation, overview
phosphoprotein
F2Q6J8, -
the enzyme harbors a C-terminal cluster of phosphorylation sites, but no N-terminal phosphorylation sites
phosphoprotein
E0X6R2, E0X6R4, -
regulatory sites of GYS1 that undergo reversible phosphorylation are identified: two of them, sites 2 and 2a, are located near the N-terminus, while the remaining seven sites, 3a, 3b, 3c, 4, 5, 1a, and 1b, are found within the C-terminus. Insulin promotes dephosphorylation of glycogen synthase in differentiated porcine satellite cells; regulatory sites of GYS2 that undergo reversible phosphorylation are identified: two of them, sites 2 and 2a, are located near the N-terminus, while the remaining seven sites, 3a, 3b, 3c, 4, and 5 are found within the C-terminus, GYS2 does not contain sites 1a and 1b
phosphoprotein
Sus scrofa Meishan
-
regulatory sites of GYS1 that undergo reversible phosphorylation are identified: two of them, sites 2 and 2a, are located near the N-terminus, while the remaining seven sites, 3a, 3b, 3c, 4, 5, 1a, and 1b, are found within the C-terminus. Insulin promotes dephosphorylation of glycogen synthase in differentiated porcine satellite cells; regulatory sites of GYS2 that undergo reversible phosphorylation are identified: two of them, sites 2 and 2a, are located near the N-terminus, while the remaining seven sites, 3a, 3b, 3c, 4, and 5 are found within the C-terminus, GYS2 does not contain sites 1a and 1b
-
phosphoprotein
-
multiple phosphorylations on serine residues leads to inactivation; phosphorylation leads to loss of activity; phosphorylation of glucose-6-phosphate independent enzyme, i.e. I enzyme, results in glucose-6-phosphate dependent enzyme, i.e. D enzyme
additional information
-
no covalently attached amino sugars, 2% carbohydrate
glycoprotein
F2Q6J8, -
the enzyme has two potential N-glycosylation sites at residues 520 and 577
additional information
F2Q6J8, -
the enzyme contains no signal peptide, putative cleavage sites, and transmembrane domain
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
crystals from the protein and from its selenomethionyl variant are grown in 100 mM sodium citrate pH 5.6 containing 20% PEG and 20% dioxane by hanging drop vapour-diffusion method at 20C. Crystals grow in thin needles, diffract to 3.5 A resolution and belong to space group C2, with unit-cell parameters a = 202 A, b = 73 A, c = 149 A, beta = 131
-
purified recombinant enzyme in complex with UDP-Glc, sitting drop vapor diffusion method, 0.002 ml of 5 mg/ml protein in 50-mM Tris-HCl, pH 7.4, with 10 mM UDP-Glc is mixed with 0.002 ml reservoir solution containing 0.1-M sodium citrate, pH 4.0, and 20-28% 2-methyl-2,4-pentanediol, 2 months, 20C, X-ray diffraction structure determination and analysis at 2.5 A resolution, molecular replacement
-
sitting drop vapor diffusion method
-
purified recombinant His-tagged enzyme, basal state and glucose-6-phosphate activated state Gsy2p, X-ray diffraction structure determination and analysis at 3.0 A and 2.4 A, respectively, modeling
-
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.8
7.6
-
-
7.4
8.4
-
sensitive to small changes in pH in the presence of Mg2+
additional information
-
-
overview: stability in various buffer systems
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
25
-
-
stable in imidazole or beta-glycerophosphate buffer, instable in Tris or glycylglycine buffer
30
-
-
instable above
30
-
-
stable up to 60 min
37
-
-
inactivation in a few h
37
-
-
inactivation can partially protected by glucose-6-phosphate
42
-
-
inactivation after 30 min, sulfate protects
50
-
-
inactivation above
60
-
-
inactivation above
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
albumin is essential during lyophilization, lyophilized enzyme is stable for years
-
dithiothreitol stabilizes
-
glucose 6-phosphate stabilizes
-
glycogen stabilizes
-
phosphate stabilizes
-
spontaneous, temperature-dependent inactivation caused by irreversible conformational changes
-
sulfate stabilizes
-
UDP stabilizes
-
glycogen stabilizes
-
UDP-glucose stabilizes
-
freezing leads to loss of activity
-
sulfate stabilizes
-
Li+ increases hepatic glycogen synthase stability though a proteasome-related mechanism
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-80C, 50 mM glycerophosphate buffer, pH 7.0, 2 mM EDTA, 40 mM 2-mercaptoethanol, 10% sucrose
-
-70C, at least 6 months
-
-70C, stable for at least 3 months
-
-70C, stable up to 6 months
-
liquid N2, 50 mM Tris/HCl buffer, pH 7.0, 1 mM DTT, 50% glycerol
-
-20C, 1% w/v bovine serum albumin, 2 weeks
-
-20C, 45 mM Tris/HCl buffer, pH 7.5, 1 mM DTT, 10% glycerol, several months
-
-20C, glycogen-free or glycogen-containing enzyme, lyophilized, more than 3 years, solubilized enzyme several weeks
-
-85C, stable for several months
-
4C, 24 h stable
-
-20C, 3 weeks, 55-100% loss of activity
-
-15C, stable for 1 month in 5 mg/ml glycogen and 33% glycerol
-
-60C, stable for 2 months
-
-70C, beta-glycerophosphate buffer, 1 year
-
4C, stable for 1 week in 5 mg/ml glycogen
-
4C, stable for several days
-
-80C, with 5 mM glucose-6-phosphate, stable for at least 4 to 6 months
-
-20C, 45 mM Tris/HCl buffer, pH 7.5, 1 mM 2-mercaptoethanol, 10% glycerol, several months
-
-20C, stable for several months
-
-70C, 50 mM Tris/HCl buffer, pH 7.8, 25% v/v glycerol, 5 mM EDTA, 2 mM EGTA, 1 mM DTT, 6 months
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
the COOH-terminal fragment of glycogenin can be used as an effective high affinity reagent for the purification of glycogen synthase from skeletal muscle and liver
-
His6-tagged recombinant proteins
-
recombinant His-tagged wild-type and mutant Gsy2 proteins from Escherichia coli strain BL21(DE3) by nickel affinity and anion exchange chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
fusion with green fluorescence protein
-
expression in Escherichia coli
-
expression in Escherichia coli strain BL21(DE3)/pG-Tf2
-
expression of His-tagged wild-type and mutant Gsy2 proteins in Escherichia coli strain BL21(DE3)
-
cDNA and amino acid sequence determination and analysis, phylogenetic analysis and tree
F2Q6J8, -
gene GYS1, in silico cloning, DNA and amino acid sequence determination and analysis, promoter determination and analysis, quantitative real-time RT-PCR tissue expression analysis; gene GYS2, in silico cloning, DNA and amino acid sequence determination and analysis, promoter determination and analysis, quantitative real-time RT-PCR tissue expression analysis
E0X6R2, E0X6R4, -
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
heat-shock down-regulates gsn gene transcription in wild-type as well as in mutants deficient in adenylyl cyclase activity and a temperature-sensitive mutant defective in the regulatory subunit of protein kinase A
-
under starvation conditions, glycogen synthase transcript expression rapidly decreases with increasing starvation time
F2Q6J8, -
insulin does not significantly affect the transcription of GYS1
E0X6R2, E0X6R4, -
expression level of GYS1 is upregulated from proliferation to differentiation in the porcine satellite cells
E0X6R2, E0X6R4, -
insulin does not significantly affect the transcription of GYS1
Sus scrofa Meishan
-
-
expression level of GYS1 is upregulated from proliferation to differentiation in the porcine satellite cells
Sus scrofa Meishan
-
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
E510A
-
no enzyme activity
R243X
-
mutation identified in a patient with glycogen storage disease type 0, together with frameshift mutation 966_967delGA/insC introducing a stop codon 21 amino acids downstream from the site of the mutation and leading to loss of 51% of the C-terminal portion of the protein. Patient is heterozygous for the mutations and presents with fasting hypoglycemia and postprandial hyperglycemia
S10A
-
phosphorylation mutant. Mutation does not cause singnificant changes in the activation state
S640A
-
phosphorylation mutant, moderate increase in the activity ratio
S644A
-
phosphorylation mutant, moderate increase in the activity ratio
S648A
-
phosphorylation mutant. Mutation does not cause singnificant changes in the activation state
S652A
-
phosphorylation mutant. Mutation does not cause singnificant changes in the activation state
S656A
-
phosphorylation mutant. Mutation does not cause singnificant changes in the activation state
S7A
-
phosphorylation mutant, large increase in the activity ratio both in soluble and insoluble fraction. Enzyme is almost fully active and able to induce glycogen deposition in primary hepatocytes incubated in the absence of glucose and in FTO2B cells, a cell line that does not normallysynthesize glycogen. Mutation is also sufficient to trigger the aggregation and translocation of liver glycogen synthase from the cytoplasm to the hepatocyte cell cortex in the absence of glucose
S7A/E509A
-
phosphorylation and active site mutant. Translocation of liver glycogen synthase from the cytoplasm to the hepatocyte cell cortex in the absence of glucose is not observed
S7A/S10A
-
phosphorylation double mutant, large increase in the activity ratio both in soluble and insoluble fraction
S7A/S640A
-
phosphorylation double mutant, large increase in the activity ratio both in soluble and insoluble fraction
S7A/S644A
-
phosphorylation double mutant, large increase in the activity ratio both in soluble and insoluble fraction
S7A/S648A
-
phosphorylation double mutant, large increase in the activity ratio both in soluble and insoluble fraction
S7A/S652A
-
phosphorylation double mutant, large increase in the activity ratio both in soluble and insoluble fraction
S7A/S656A
-
phosphorylation double mutant, large increase in the activity ratio both in soluble and insoluble fraction
H167A
-
1.1% of wild-type activity
K118A
-
1.5% of wild-type activity
K274A
-
0.2% of wild-type activity
K289A/K291A/R297A
-
46.4% of wild-type activity
K30A
-
100.6% of wild-type activity
K359A
-
122.3% of wild-type activity
K369A/R375A
-
46.8% of wild-type activity
K390A/R391A
-
109.7% of wild-type activity
K425A/R426A/R433A
-
1.2% of wild-type activity
R179A/R181A/R182A
-
39.1% of wild-type activity
R198A
-
0.4% of wild-type activity
R19A
-
161% of wild-type activity
R229A/R234A
-
7.2% of wild-type activity
R319A/K325A
-
0.2% of wild-type activity
R336A/K342A
-
55.9% of wild-type activity
R459A
-
30.1% of wild-type activity
R470A/K472A
-
0.6% of wild-type activity
R496A
-
145% of wild-type activity
R555A/R556A/K558A
-
0.3% of wild-type activity
R579A/R580A/R582A
-
36.2% of wild-type activity
R580A
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
R580A/R581A
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
R580A/R581A/R583A
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme. The triple mutant enzyme is resistant to inhibition by Pho85p/Pcl10p phosphorylation
R586A/R558A/R591A
-
71.1% of wild-type activity
R587A/R589A/R592A
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
R589A/R592A
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
R609A/R615A
-
125.8% of wild-type activity
S650D
-
97.8% of wild type activity
S650D/S654D
-
140.3% of wild type activity
S650D/S654D/S667D
-
110.8% of wild type activity
S650D/T667D
-
91.4% of wild type activity
S654D
-
96.2% of wild type activity
S654D/T667D
-
116.5% of wild type activity
T667D
-
68.6% of wild type activity
W510A
-
1.7% of wild-type activity
E518A
-
6% enzyme activity
additional information
P13807
identification of homozygous two base pair deletion in exon 2, c.162-163delAG resulting in muscle-specific glycogen synthase deficiency. Mutation is predicted to result in a protein frameshift that alters the amino acid sequence after the mutation and terminates prematurely. Patient presents with abnormal mitochondrial ultrastructure and pre-ragged red fibres, predominance of type I oxidative fibres in the muscle and depletion of glycogen stores
K599A
-
47.7% of wild-type activity
additional information
-
generation of a wild-type 640 truncation mutant with increased activity compared to the wild-type, and of point mutation variants with nonphospho- and phospho-peptides ligated, which alters the mutant activities, overview
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
-
insulin, insiulin-like growth factor 1 and relaxin stimulate the enzymatic activity. In patients with type 1 diabetes glycogen synthase activity remains unchanged versus control, and insulin does not stimulate the enzyme activity. In patients with type 2 diabetes a significant decrease in glycogen synthase activity is accompanied by the decrease in the effect of peptides, giving the following order of their efficiency: insulin = IGF-1 > relaxin. In myometrium of pregnant women with gestational treated and untreated diabetes, glycogen synthase activity decreases, the effect of insulin is weaker, whereas the effects of relaxin and IGF-1 increase thus giving the following order of their efficiency: relaxin > IGF-1 > insulin. Insulin therapy of type 1 diabetes incompletely restores sensitivity of the enzymes to the peptide actions
medicine
-
mutation R243X has been identified in a patient with glycogen storage disease type 0, together with frameshift mutation 966_967delGA/insC introducing a stop codon 21 amino acids downstream from the site of the mutation and leading to loss of 51% of the C-terminal portion of the protein. Patient is heterozygous for the mutations and presents with fasting hypoglycemia and postprandial hyperglycemia
medicine
-
in patients with polycystic ovary syndrome, reduced insulin-mediated glucose disposal is associated with a lower insulin-stimulated glycogen synthase activity, explained by absent insulin-mediated dephosphorylation of glycogen synthase at the NH2-terminal sites 2 + 2a, whereas dephosphorylation at the COOH-terminal sites 3a + 3b is intact in polycystic ovary syndrome subjects. Insulin activation of glycogen synthase is dependent on dephosphorylation of sites 3a + 3b in women with polycystic ovary syndrome. No significant abnormalities in glycogen synthaseK-3 or -3 are found. Pioglitazone treatment improves insulin-stimulated glucose metabolism and glycogen synthase activity in polycystic ovary syndrome and restores the ability of insulin to dephosphorylate glycogen synthase at sites 2 and 2a
medicine
-
glycogen synthase activity correlates inversely with phosphorylation of glycogen synthase sites 2 + 2a and 3a. Insulin significantly decreases 2 + 2a phosphorylation in lean subjects only and induces a larger dephosphorylation at site 3 in lean compared with obese subjects. The exaggerated insulin resistance in type 2 diabetes mellitus compared with obese subjects is not reflected by differences in site 3 phosphorylation but is accompanied by a significantly higher site 1b phosphorylation during insulin stimulation. Hyperphosphorylation of another Ca2/calmodulin-dependent kinase-II target, phospholamban-Thr17, is also evident in type 2 diabetes mellitus. Dephosphorylation of glycogen synthase by phosphatase treatment fully restores glycogen synthase activity in all groups
medicine
P13807
patient with muscle-specific glycogen synthase deficiency due to homozygous two base pair deletion in exon 2, c.162-163delAG. Mutation is predicted to result in a protein frameshift that alters the amino acid sequence after the mutation and terminates prematurely. Patient presents with abnormal mitochondrial ultrastructure and pre-ragged red fibres, predominance of type I oxidative fibres in the muscle and depletion of glycogen stores
medicine
-
old compared to young rats maintained ad libitum on a standard diet have reduced glycogen synthase activity, lower muscle glycogen synthase protein levels, increased phosphorylation of glycogen synthase at site 3a with less activation in soleus muscle. Age-associated impairments in glycogen synthase protein and activation-phosphorylation are also shown in tibialis anterior muscle. There is an age-associated reduction in glycogen phosphorylase activity level in soleus, while brain/muscle isoforms of glycogen phosphorylase protein levels are higher. Calorie restriciton does not alter glycogen synthase or glycogen phosphatase activity/protein levels in young rats. Calorie restriction hinders age-related decreases in glycogen synthase activity/protein, unrelated to glycogen synthase mRNA levels, and glycogen synthase inactivation-phosphorylation
nutrition
-
calorie restriciton does not alter glycogen synthase or glycogen phosphatase activity/protein levels in young rats. Calorie restriction hinders age-related decreases in glycogen synthase activity/protein, unrelated to glycogen synthase mRNA levels, and glycogen synthase inactivation-phosphorylation