Recombinant Human Glucokinase (GCK)

Uniprot Id

P35557

Target Species

Human

Target Name

GCK

Target Full Name

Hexokinase-4

Target Function

Catalyzes the phosphorylation of hexose, such as D-glucose, D-fructose and D-mannose, to hexose 6-phosphate (D-glucose 6-phosphate, D-fructose 6-phosphate and D-mannose 6-phosphate, respectively). Compared to other hexokinases, has a weak affinity for D-glucose, and is effective only when glucose is abundant. Mainly expressed in pancreatic beta cells and the liver and constitutes a rate-limiting step in glucose metabolism in these tissues. Since insulin secretion parallels glucose metabolism and the low glucose affinity of GCK ensures that it can change its enzymatic activity within the physiological range of glucose concentrations, GCK acts as a glucose sensor in the pancreatic beta cell. In pancreas, plays an important role in modulating insulin secretion. In liver, helps to facilitate the uptake and conversion of glucose by acting as an insulin-sensitive determinant of hepatic glucose usage. Required to provide D-glucose 6-phosphate for the synthesis of glycogen. Mediates the initial step of glycolysis by catalyzing phosphorylation of D-glucose to D-glucose 6-phosphate.

Target Involvement

Maturity-onset diabetes of the young 2 (MODY2); Familial hyperinsulinemic hypoglycemia 3 (HHF3); Diabetes mellitus, non-insulin-dependent (NIDDM); Diabetes mellitus, permanent neonatal (PNDM)

Target Subcellular Location

Cytoplasm. Nucleus. Mitochondrion.

Target Protein Families

Hexokinase family

Target Synonyms

ATP:D-hexose 6-phosphotransferase; FGQTL3; GCK; GK; GLK; Glucokinase; Hexokinase D pancreatic isozyme; Hexokinase type IV; Hexokinase-4; Hexokinase-D; HHF3; HK IV; HK4; HKIV; HXK4_HUMAN; HXKP; LGLK; MODY2

Target Background

This gene encodes a member of the hexokinase family of proteins. Hexokinases phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways. In contrast to other forms of hexokinase, this enzyme is not inhibited by its product glucose-6-phosphate but remains active while glucose is abundant. The use of multiple promoters and alternative splicing of this gene result in distinct protein isoforms that exhibit tissue-specific expression in the pancreas and liver. In the pancreas, this enzyme plays a role in glucose-stimulated insulin secretion, while in the liver, this enzyme is important in glucose uptake and conversion to glycogen. Mutations in this gene that alter enzyme activity have been associated with multiple types of diabetes and hyperinsulinemic hypoglycemia.