Glucose-6-phosphatase catalytic subunit gene family

Abstract

Glucose-6-phosphatase catalyzes the hydrolysis of glucose 6-phosphate (G6P) to glucose and inorganic phosphate. It is a multicomponent system located in the endoplasmic reticulum that comprises several integral membrane proteins, namely a catalytic subunit (G6PC) and transporters for G6P, inorganic phosphate, and glucose. The G6PC gene family contains three members, designated G6PC, G6PC2, and G6PC3. The tissue-specific expression patterns of these genes differ, and mutations in all three genes have been linked to distinct diseases in humans. This minireview discusses the disease association and transcriptional regulation of the G6PC genes as well as the biological functions of the encoded proteins.

FIGURE 1.

Model of the glucose-6-phosphatase multicomponent enzyme system. G6P enters the ER lumen through a G6P transporter. Once hydrolyzed to Glc and P_i by the G6PC, the products of the reaction return to the cytosol through specific transporters. Recent data suggest that the same protein transports both G6P and P_i.

FIGURE 2.

Comparison of transcription factors binding the G6pc and G6pc2 promoters. The proximal G6pc promoter binds multiple transcription factors, including HNF-1, Foxo1, the glucocorticoid receptor (GR), Foxa2, HNF-6, HNF-4, and Sp1/3. Some of the glucocorticoid receptor-binding sites overlap binding sites for Foxo1 and Foxa2. The proximal G6pc2 promoter also binds multiple transcription factors, including Pax-6, Pdx-1, Foxa2, MafA, and δEF1. At the G6pc2 promoter, E-Box 1 binds BETA-2, E-Box 2 binds USF-1 and -2, and the factor binding E-Box 3 is unknown. The diagrams are not drawn to scale.