Disease relevance of GYG1

• Rabbit muscle glycogenin was expressed at high levels in Escherichia coli and purified close to homogeneity in a procedure that involved binding to a UDP-agarose affinity column [1].
• The role of glycogenin in glycogen synthesis and non-insulin dependent diabetes mellitus [2].

High impact information on GYG1

• The conserved motif in the Cl- channel P1 region may constitute a 'signature' sequence for an anion-selective ion pore by analogy with the homologous GYG sequence that is essential for selectivity in voltage-gated potassium ion (K+) channel pores [3].
• The same tyrosine residue is glycosylated whether glycogenin is isolated as a complex with the catalytic subunit of glycogen synthase, or covalently attached to glycogen [4].
• It is suggested that glycogen oscillates, according to glucose supply and energy demand, between the macroglycogen and proglycogen, but not usually the glycogenin, forms [5].
• Glycogenin has the ability to glucosylate molecules other than itself and to hydrolyze UDPglucose [5].
• The discovery of glycogenin as a self-glucosylating protein that primes glycogen synthesis has significantly increased our understanding of the structure and metabolism of this storage polysaccharide [5].

Biological context of GYG1

• By using rabbit skeletal muscle glycogenin as a bait, cDNAs encoding three different proteins were isolated from the human skeletal muscle cDNA library [6].
• Overall, GN-2 has 40-45% identity to muscle glycogenin but is 72% identical over a 200-residue segment thought to contain the catalytic domain [7].
• The biogenesis of glycogen involves a specific initiation event mediated by the initiator protein, glycogenin, which undergoes self-glucosylation to generate an oligosaccharide primer from which the glycogen molecule grows [1].
• We have sequenced the cDNA coding for human muscle glycogenin and have deduced the corresponding amino acid sequence [8].
• The human intron-containing gene for glycogenin maps to chromosome 3, band q24 [8].

Anatomical context of GYG1

• We describe the characterization of novel forms of glycogenin, designated glycogenin-2 (GN-2), encoded by a second gene that is expressed preferentially in certain tissues, including liver, heart, and pancreas [7].
• The new protein, glycogenin-2, had several properties similar biochemically to the muscle isoform, glycogenin-1, but unlike glycogenin-1, stable expression in fibroblasts led to a significant overaccumulation of glycogen [9].
• Northern blot analysis revealed that glycogenin-1 gene transcription is differentially regulated in the C2C12 mouse muscle cell line [10].
• The transcriptional activity of the glycogenin-1 gene was investigated by transient transfection of the 5'-flanking region in HepG2 cells and C2C12 myoblasts and myotubes [10].
• At term, glycogenin was most abundant in the endothelium of fetal vessels [11].

Associations of GYG1 with chemical compounds

• Analysis of peptide fragments by mass spectroscopy indicated that the recombinant glycogenin was already glucosylated at Tyr-194 and contained from 1 to 8 glucose residues attached [1].
• Characterization of rabbit skeletal muscle glycogenin. Tyrosine 194 is essential for function [1].
• Kinetically controlled incubation of FA and the tripeptide Gly-Tyr-Gly (GYG) with horseradish peroxidase and H2O2 yielded a range of new cross-linked products [12].
• In Shaker-group potassium channels the presence of a tyrosine residue, just downstream of the pore signature sequence GYG, determines sensitivity to tetraethylammonium (TEA) [13].
• While there is no evidence that CDP-glucose is a natural substrate for glycogenin, it has the advantage over UDP-glucose in that it can be used specifically to detect and assay glycogenin in the presence of glycogen synthase because CDP-glucose, unlike UDP-glucose, is not a substrate for the synthase [14].

Physical interactions of GYG1

• Mutation of Tyr-196 in glycogenin-2 to a Phe residue abolished the ability of glycogenin-2 to self-glucosylate but not to interact with glycogenin-1 [15].

Other interactions of GYG1

• GNIP, a novel protein that binds and activates glycogenin, the self-glucosylating initiator of glycogen biosynthesis [6].
• Over regions of protein sequence similarity, the GYG2 gene structure is similar to that of the other glycogenin gene, GYG [16].
• By means of the polymerase chain reaction and fluorescence in situ hybridization, we have found the chromosomal location of the gene coding for glycogenin [8].
• The exercise-diet manipulation exerted a significant effect on transcription of all carbohydrate-related genes, with an increase in GLUT4 and glycogenin mRNA abundance and a reduction in PDK-4 transcription after HIGH-CHO (all P < 0.05) [17].
• In conclusion, the co-expression of glycogenin with GLUT3 might enable glycogen-storing cells to exchange glucose quite effectively according to prevailing metabolic demands of glycogen synthesis or degradation [11].

Analytical, diagnostic and therapeutic context of GYG1

• Physical interaction between GNIP2 and glycogenin was confirmed by co-immunoprecipitation, and in addition GNIP2 was shown to stimulate glycogenin self-glucosylation 3-4-fold [6].
• Quantitative RT-PCR showed elevated glycogenin mRNA at 120 min followed by increases in protein levels at 300 min [18].
• The present study investigated the expression of glycogenin, the protein primer for glycogen synthesis, and the high affinity glucose transporter isoform GLUT3 as a further potential regulator of cellular glycogen metabolism, in first trimester and term human placenta using immunohistochemistry and Western blotting [11].
• Measurement of glycogenin utilization for glycogen synthesis in type II diabetic cells by use of a specific immunoassay for APO-glycogenin [19].

References