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Information on EC 2.4.1.11 - glycogen(starch) synthase and Organism(s) Homo sapiens

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EC Tree
     2 Transferases
         2.4 Glycosyltransferases
             2.4.1 Hexosyltransferases
                2.4.1.11 glycogen(starch) synthase
IUBMB 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).
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Homo sapiens
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
glycogen synthase, gbssi, granule-bound starch synthase, starch synthase i, granule bound starch synthase, gsy2p, glycogen synthase 2, gys-2, cg-gys, tvag_258220, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glucosyltransferase, uridine diphosphoglucose-glycogen
-
-
-
-
glycogen synthase
-
-
glycogen synthetase (starch)
-
-
-
-
GSY2p
-
-
-
-
UDP-glucose-glycogen glucosyltransferase
-
-
-
-
UDP-glycogen synthase
-
-
-
-
UDPG-glycogen synthetase
-
-
-
-
UDPG-glycogen transglucosylase
-
-
-
-
uridine diphosphoglucose-glycogen glucosyltransferase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
UDP-alpha-D-glucose + [(1->4)-alpha-D-glucosyl]n = UDP + [(1->4)-alpha-D-glucosyl]n+1
show the reaction diagram
reaction mechanism
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hexosyl group transfer
-
-
-
-
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).
CAS REGISTRY NUMBER
COMMENTARY hide
9014-56-6
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
UDP-glucose + glycogen
UDP + glycogen
show the reaction diagram
-
increased insulin receptor signaling and glycogen synthase activity contribute to the synergistic effect of exercise on insulin action
-
-
?
[beta-32P]-UDP-glucose + glycogen
[beta-32P]-glycogen + UDP
show the reaction diagram
-
-
-
-
?
[U-14C]-UDP-glucose + glycogen
[14C]-glycogen + UDP
show the reaction diagram
-
-
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
UDP-glucose + glycogen
glycogen + UDP
show the reaction diagram
UDP-glucose + glycogen
UDP + glycogen
show the reaction diagram
-
increased insulin receptor signaling and glycogen synthase activity contribute to the synergistic effect of exercise on insulin action
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
-
activation in presence of glucose 6-phosphate
CaSO4
-
to a lesser extent, absence of glucose-6-phosphate
CoSO4
-
absence of glucose-6-phosphate
FeSO4
-
to a lesser extent, absence of glucose-6-phosphate
KCl
-
activation in presence of glucose 6-phosphate
Mg2+
-
activation in presence of glucose 6-phosphate
MgSO4
-
to a lesser extent, absence of glucose-6-phosphate
Mn2+
-
activation in presence of glucose 6-phosphate
MnSO4
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
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(NH4)2SO4
-
20% inactivation at 20 mM
2-mercaptoethanol
-
high concentrations
Caffeine
-
10-50 mM
dithiothreitol
-
high concentrations
ethanol
-
traces inactivate the enzyme
Mg2+
-
toxic
Na2SO4
-
high concentrations
NaCl
-
48% activity at 0.3 M
phosphate
SO42-
theophylline
-
10-50 mM
UDP-pyridoxal
-
36% activity at 0.1 mM
UMP
-
competitive with UDP-glucose
UTP
-
competitive with UDP-glucose
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
galactose 6-phosphate
glucosamine 6-phosphate
-
50% of the glucose-6-phosphate activation
glucose 6-phosphate
Insulin
-
insulin-like growth factor 1
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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
-
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
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.021 - 1.25
UDP-glucose
additional information
additional information
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.043
UMP
-
-
0.017
UTP
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
14.13
-
-
21
-
synthase I
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5 - 9.2
-
synthase D, presence of glucose 6-phosphate
6.8 - 9.2
-
synthase I, presence of glucose 6-phosphate
7 - 8.5
-
synthase D, absence of glucose 6-phosphate
7 - 9
-
synthase I
7.2 - 8
-
synthase I, absence of glucose 6-phosphate
8.8
-
synthase D
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30 - 40
-
-
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
human enzyme has no activity above 50°C, rat enzyme is active up to at least 60°C
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
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
-
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
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
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
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
GYS1_HUMAN
737
0
83786
Swiss-Prot
other Location (Reliability: 2)
GYS2_HUMAN
703
0
80989
Swiss-Prot
other Location (Reliability: 4)
A0A024RAU5_HUMAN
703
0
80957
TrEMBL
other Location (Reliability: 4)
Q53ER0_HUMAN
737
0
83858
TrEMBL
other Location (Reliability: 2)
M0QYU1_HUMAN
113
0
13274
TrEMBL
other Location (Reliability: 5)
B7Z806_HUMAN
657
0
75113
TrEMBL
Mitochondrion (Reliability: 5)
B7Z8P0_HUMAN
235
0
26901
TrEMBL
Mitochondrion (Reliability: 5)
A8K6K7_HUMAN
737
0
83814
TrEMBL
other Location (Reliability: 2)
B7Z6I6_HUMAN
681
0
77557
TrEMBL
other Location (Reliability: 2)
B7Z255_HUMAN
370
0
42127
TrEMBL
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
390000
-
sucrose density gradient centrifugation
410000
-
gel filtration
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
-
x * 80000-85000, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
E510A
-
no enzyme activity
E518A
-
6% 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
additional information
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.8 - 7.6
-
-
488424
7.4 - 8.4
-
sensitive to small changes in pH in the presence of Mg2+
488424
additional information
-
overview: stability in various buffer systems
488406
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
50
-
inactivation above
GENERAL STABILITY
ORGANISM
UNIPROT
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
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 45 mM Tris/HCl buffer, pH 7.5, 1 mM DTT, 10% glycerol, several months
-
-20°C, glycogen-free or glycogen-containing enzyme, lyophilized, more than 3 years, solubilized enzyme several weeks
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Sf9 insect cells
-
fusion with green fluorescence protein
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Westphal, S.A.; Nuttall, F.Q.
Comparative characterization of human and rat liver glycogen synthase
Arch. Biochem. Biophys.
292
479-486
1992
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Plesner, L.; Plesner, I.; Esmann, V.
Purification and steady state kinetic mechanism of glycogen synthase-D from human polymorpho-nuclear leukocytes
Mol. Cell. Biochem.
12
45-61
1976
Homo sapiens
Manually annotated by BRENDA team
Solling, H.
Studies on the allosteric properties of glycogen synthase I
Eur. J. Biochem.
94
231-242
1979
Homo sapiens
Manually annotated by BRENDA team
Solling, H.; Esmann, V.
Purification and properties of glycogen synthase I from human leukocytes
Eur. J. Biochem.
81
119-128
1977
Homo sapiens
Manually annotated by BRENDA team
Huang, K.P.; Robinson, J.C.
Purification and properties of the glucose-6-phosphate-dependent form of human placental glycogen synthase
Arch. Biochem. Biophys.
175
583-589
1976
Homo sapiens
Manually annotated by BRENDA team
Moses, S.W.; Bashan, N.; Gutman, A.
Properties of glycogen synthetase in erythrocytes
Eur. J. Biochem.
30
205-210
1972
Homo sapiens
Manually annotated by BRENDA team
Cid, E.; Gomis, R.R.; Geremia, R.A.; Guinovart, J.J.; Ferrer, J.C.
Identification of two essential glutamic acid residues in glycogen synthase
J. Biol. Chem.
275
33614-33621
2000
Homo sapiens
Manually annotated by BRENDA team
Jiao, Y.; Shashkina, E.; Shashkin, P.; Hansson, A.; Katz, A.
Manganese sulfate-dependent glycosylation of endogenous glycoproteins in human skeletal muscle is catalyzed by a nonglucose 6-P-dependent glycogen synthase and not glycogenin
Biochim. Biophys. Acta
1427
1-12
1999
Homo sapiens
Manually annotated by BRENDA team
Park, K.S.; Ciaraldi, T.P.; Carter, L.; Mudaliar, S.; Nikoulina, S.E.; Webster, N.J.G.; Henry, R.R.
Induction of insulin resistance in human skeletal muscle cells by downregulation of glycogen synthase protein expression
Metab. Clin. Exp.
49
962-968
2000
Homo sapiens
Manually annotated by BRENDA team
Christ-Roberts, C.Y.; Pratipanawatr, T.; Pratipanawatr, W.; Berria, R.; Belfort, R.; Mandarino, L.J.
Increased insulin receptor signaling and glycogen synthase activity contribute to the synergistic effect of exercise on insulin action
J. Appl. Physiol.
95
2519-2529
2003
Homo sapiens
Manually annotated by BRENDA team
Beckner, M.E.; Gobbel, G.T.; Abounader, R.; Burovic, F.; Agostino, N.R.; Laterra, J.; Pollack, I.F.
Glycolytic glioma cells with active glycogen synthase are sensitive to PTEN and inhibitors of PI3K and gluconeogenesis
Lab. Invest.
85
1457-1470
2005
Homo sapiens
Manually annotated by BRENDA team
Wang, H.M.; Mehta, S.; Bansode, R.; Huang, W.; Mehta, K.D.
AICAR positively regulate glycogen synthase activity and LDL receptor expression through Raf-1/MEK/p42/44MAPK/p90RSK/GSK-3 signaling cascade
Biochem. Pharmacol.
75
457-467
2008
Homo sapiens
Manually annotated by BRENDA team
Varma, S.; Shrivastav, A.; Changela, S.; Khandelwal, R.L.
Long-term effects of rapamycin treatment on insulin mediated phosphorylation of Akt/PKB and glycogen synthase activity
Exp. Cell Res.
314
1281-1291
2008
Homo sapiens
Manually annotated by BRENDA team
Varma, S.; Khandelwal, R.L.
Overexpression of Akt1 upregulates glycogen synthase activity and phosphorylation of mTOR in IRS-1 knockdown HepG2 cells
J. Cell. Biochem.
103
1424-1437
2008
Homo sapiens
Manually annotated by BRENDA team
Kuznetsova, L.; Chistyakova, O.
The regulation of glucose-6-phosphate dehydrogenase and glycogen synthase activities by peptides of insulin superfamily in myometrium of pregnant women and its impairments in different types of diabetes mellitus
Biochemistry
3
311-316
2009
Homo sapiens
Manually annotated by BRENDA team
Soggia, A.P.; Correa-Giannella, M.L.; Fortes, M.A.; Luna, A.M.; Pereira, M.A.
A novel mutation in the glycogen synthase 2 gene in a child with glycogen storage disease type 0
BMC Med. Genet.
11
003
2010
Homo sapiens
Manually annotated by BRENDA team
Prats, C.; Helge, J.W.; Nordby, P.; Qvortrup, K.; Ploug, T.; Dela, F.; Wojtaszewski, J.F.
Dual regulation of muscle glycogen synthase during exercise by activation and compartmentalization
J. Biol. Chem.
284
15692-15700
2009
Homo sapiens
Manually annotated by BRENDA team
Glintborg, D.; Hojlund, K.; Andersen, N.R.; Hansen, B.F.; Beck-Nielsen, H.; Wojtaszewski, J.F.
Impaired insulin activation and dephosphorylation of glycogen synthase in skeletal muscle of women with polycystic ovary syndrome is reversed by pioglitazone treatment
J. Clin. Endocrinol. Metab.
93
3618-3626
2008
Homo sapiens
Manually annotated by BRENDA team
Hojlund, K.; Birk, J.B.; Klein, D.K.; Levin, K.; Rose, A.J.; Hansen, B.F.; Nielsen, J.N.; Beck-Nielsen, H.; Wojtaszewski, J.F.
Dysregulation of glycogen synthase COOH- and NH2-terminal phosphorylation by insulin in obesity and type 2 diabetes mellitus
J. Clin. Endocrinol. Metab.
94
4547-4556
2009
Homo sapiens
Manually annotated by BRENDA team
Jensen, J.; Ruge, T.; Lai, Y.C.; Svensson, M.K.; Eriksson, J.W.
Effects of adrenaline on whole-body glucose metabolism and insulin-mediated regulation of glycogen synthase and PKB phosphorylation in human skeletal muscle
Metab. Clin. Exp.
60
215-226
2011
Homo sapiens
Manually annotated by BRENDA team
Cameron, J.M.; Levandovskiy, V.; MacKay, N.; Utgikar, R.; Ackerley, C.; Chiasson, D.; Halliday, W.; Raiman, J.; Robinson, B.H.
Identification of a novel mutation in GYS1 (muscle-specific glycogen synthase) resulting in sudden cardiac death, that is diagnosable from skin fibroblasts
Mol. Genet. Metab.
98
378-382
2009
Homo sapiens (P13807), Homo sapiens
Manually annotated by BRENDA team
Contreras, C.J.; Segvich, D.M.; Mahalingan, K.; Chikwana, V.M.; Kirley, T.L.; Hurley, T.D.; DePaoli-Roach, A.A.; Roach, P.J.
Incorporation of phosphate into glycogen by glycogen synthase
Arch. Biochem. Biophys.
597
21-29
2016
Saccharomyces cerevisiae, Homo sapiens
Manually annotated by BRENDA team