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evolution
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glycogenin is a member of the GT8 family of glycosyltransferases with a GT-A architecture
evolution
the Pacific oyster has three isozymes of glycogenin: CgGN-alpha, CgGN-beta, and CgGN-gamma. Functional motif architecture analysis shows that CgGN is structurally similar to mammalian glycogenin-1. All three CgGN isoforms contain the key domain of glycosyltransferase and the C-terminal domain
evolution
unlike mice, humans and other primates have a second variant of glycogenin called glycogenin-2, which is mainly expressed in the liver
evolution
unlike mice, humans and other primates have a second variant of glycogenin called glycogenin-2, which is mainly expressed in the liver
malfunction
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glycogen depletion in skeletal muscle is a result of a non-functional glycogenin-1 due to a Thr83Met substitution in glycogenin-1
malfunction
the glycogenin-1 mutation T82M causes glycogenosis. Substitution of Thr82 for serine but not for valine restores the maximum extent of autoglucosylation as well as transglucosylation and UDP-glucose hydrolysis rate, structure analysis, overview
malfunction
the Thr83Met mutation, which causes glycogen storage disease XV, is conformationally locked in the ground state and catalytically inactive
malfunction
analysis of GYG2 deletion phenotype and effects on glucose metabolism and/or glycogen synthesis, GYG2 deletion mutant phenotype overview, liver histopathology and enzyme expression level, overview
malfunction
glycogenin-2 is unable to glucosylate inactive glycogenin-1, at least not an enzymatically inactivated Thr83Met glycogenin-1 mutant, recently identified in a patient with severe glycogen depletion
malfunction
complete lack of glycogenin-1 is usually associated with late onset muscle weakness, indicating that lack of glycogenin-1 has no major impact on muscle energy metabolism. The muscle weakness that appears later in life is associated with muscle fiber degeneration, replacement of muscle tissue by fat and fibrous connective tissue explains the weakness. Several recessive pathogenic mutations have been identified in the glycogenin-1 gene, GYG1. Complete absence of glycogenin-1 protein secondary tobi-allelic truncating mutations in GYG1 causes a rare muscle disease that is characterized by accumulation of glycogen. This glycogen is, in addition to lack of a glycogenin-1 core, abnormal with regard to its ultrastructure. Many glycogen particles show uneven size and irregular shape, and some of the storage material has a fibrillar structure. A more severe heart disease associated with missense GYG1 mutations has been described in several individuals. Muscle glycogen depletion caused by truncating mutations in GYS1, which encodes the ubiquitously expressed glycogen synthase, does not result in a compensatory upregulation of the liver glycogen synthase isoform. In patients with total lack of glycogen due to muscle glycogen synthase deficiency, glycogenin-1 is present in similar quantities as in normal individuals
malfunction
etiology and pathogenesis of a late-onset myopathy associated with glycogenin-1 deficiency, overview. Two siblings heterozygous for two mutations in the glycogenin-1 gene, one 1-base deletion and one missense mutation, are analyzed. They show remarkably different clinical expression of the disease. There is no clear correlation between the genotype and the phenotypic expression even within the same family. Glycogenin-1 deficiency should be considered as a differential diagnosis in middle-aged and elderly individuals with slowly progressive myopathy, and it may present with highly variable distribution of weakness and wasting. Phenotypes, detailed overview
malfunction
glycogen storage disease (GSD) type XV is a rare disease caused by mutations in the GYG1 gene that codes for the core molecule of muscle glycogen, glycogenin 1. Nonetheless, glycogen is present in muscles of glycogenin 1-deficient patients due to activity of glycogenin 2. Apart from occurrence of polyglucosan (PG) bodies in few fibers, glycogen appears normal in most cells, and the concentration is normal in patients with GSD type XV. Analysis of formation of glycogen and changes in glycogen metabolism in patients with GSD type XV, overview
malfunction
glycogenin inactivation in mice results in an increased amount of glycogen and not glycogen depletion. Overproduction of glycogen secondary to glycogenin deficiency is associated with altered metabolism, affecting mainly oxidative muscle fibers and causing impaired endurance. Glycogenin KO mice show accumulation of glycogen instead of glycogen depletion, and no protein that functions as a substitute for glycogenin has been identified. The lack of glycogenin is associated with reduced endurance and a metabolic shift toward glycolytic metabolism in the otherwise fatigue-resistant oxidative muscle fibers. The results from the mouse glycogenin KO experiments support the concept that glycogenin is not mandatory for glycogen synthesis, although deficiency causes metabolic impairment with reduced endurance
malfunction
muscle glycogen depletion caused by truncating mutations in GYS1, which encodes the ubiquitously expressed glycogen synthase, does not result in a compensatory upregulation of the liver glycogen synthase isoform
physiological function
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glycogenin is a self-glycosylating protein primer that initiates glycogen granule formation
physiological function
Asp162 is the residue involved in the activation step of the glucose transfer reaction mechanism
physiological function
glycogenin initiates the synthesis of a maltosaccharide chain covalently attached to itself on Tyr195 via a stepwise glucosylation reaction, priming glycogen synthesis
physiological function
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glycogenin-1 initiates the glycogen synthesis in skeletal muscle by the autocatalytic formation of a short oligosaccharide at tyrosine 195
physiological function
glycogen synthesis is initiated by self-glucosylation of the glycosyltransferases glycogenin-1 and -2 that, in the presence of UDP-glucose, form both the first glucose-O-tyrosine linkage, and then stepwise add a series of alpha1,4-linked glucoses to a growing chain of variable length. The self-glucosylation endpoint is only 0-4 glucose units on Tyr228 of glycogenin-2. The glucosylation of glycogenin-2 is enhanced to 2-4 glucose units by the presence of enzymatically active glycogenin-1
physiological function
glycogen synthesis is initiated by self-glucosylation of the glycosyltransferases glycogenin-1 and -2 that, in the presence of UDP-glucose, form both the first glucose-O-tyrosine linkage, and then stepwise add a series of alpha1,4-linked glucoses to a growing chain of variable length. The self-glucosylation endpoint is the incorporation of 4-8 glucose units on Tyr195 of glycogenin-1
physiological function
glycogenin-1 is a constitutively active enzyme so does not represent a point of regulation
physiological function
glycogenin-2 is dispensable for liver glycogen synthesis and glucagon-stimulated glucose release. Glycogenin-2 is not required for liver glycogen synthesis and glucagon-stimulated glucose release
physiological function
enzyme glycogenin 2 compensates for glycogenin 1 in human skeletal muscles of GYG1-deficient mutants. No expression of GYG2 occurs in wild-type skeletal muscle, but glycogenin 2 is detected in the patients, much stronger in the more affected patient 2 than in patient 1
physiological function
glycogenin 1 protein forms the core of glycogen in skeletal and cardiac muscle
physiological function
glycogenin is a core protein in glycogen particles and functions as a glycosyl transferase with the ability to autoglucosylate
physiological function
glycogenin is a core protein in glycogen particles and functions as a glycosyl transferase with the ability to autoglucosylate. A primer protein is dispensable for glycogen synthesis. Glycogenin appears to have a role in the regulation of glycogen content
physiological function
high glycogen levels in the Pacific oyster (Crassostrea gigas) contribute to its flavor, quality, and hardiness. Glycogenin (CgGN) is the priming glucosyltransferase that initiates glycogen biosynthesis. mRNA expression is closely related to glycogen content and CgGS expression
additional information
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aggregation might be an explanation for the incomplete autoglucosylation of wild-type glycogenin-1
additional information
hGYG1 ccurs in two distinct states, the ground state and the active state, the two states are interchangeable during catalysis and involve conformational rearrangements in three regions that influence active site accessibility, overview
additional information
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hGYG1 ccurs in two distinct states, the ground state and the active state, the two states are interchangeable during catalysis and involve conformational rearrangements in three regions that influence active site accessibility, overview
additional information
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interaction and binding of wild-type full-length enzyme and truncated mutant CeGN34 to glycogen synthase, the CeGS-CeGN34 interaction is required for glycogen formation, overview
additional information
the recombinant glycogen synthase-glycogenin-1 complex GYS1:GN1 is functional and exhibits both allosteric and phospho-dependent regulatio, activation of GYS1:GN1 complex by GYS1 dephosphorylationn
additional information
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the recombinant glycogen synthase-glycogenin-1 complex GYS1:GN1 is functional and exhibits both allosteric and phospho-dependent regulatio, activation of GYS1:GN1 complex by GYS1 dephosphorylationn
additional information
muscle glycogenin contains a single tyrosine, Tyr194, in covalent linkage with the first sugar unit, glucose, beta-phenyl-D-glucopyranoside (beta-PhGlc), confirming that tyrosine is fundamental for glycogen formation. Analysis of the mechanism for the early stages of the biosynthesis of glycogen. This macromolecule structure (PDB ID 3U2U) is constructed via the covalent attachment of glucose units to glycogenin, which remains covalently bonded to Tyr194 in a mature glycogen molecule. Isolation of the Tyr194 side chain in covalent linkage with glucose, of beta-phenyl-D-glucopyranoside, and examined the influence that the substitution of the tyrosine with different interacting reactants has on the preferred interaction sites, preferred interaction site for both alpha- and beta-Glc at body temperature is the 4-OH group of beta-PhGl, overview. The phenolic substituent of tyrosine is ideal, as it provides a rigid structure, acting as a hook for glucose, and the aromatic ring provides a tantalizing interacting environment that most molecules find entropically more favourable. The ability of glycogenin to elongate its glucan chain may reflect structural constraints both in the amino acid and at the catalytic site