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) (PubMed:6477520, PubMed:12513690, PubMed:24187134). Compared to other hexokinases, has a weak affinity for D-glucose, and is effective only when glucose is abundant (PubMed:6477520). Mainly expressed in pancreatic beta cells and the liver and constitutes a rate-limiting step in glucose metabolism in these tissues (By similarity). 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 (By similarity). In pancreas, plays an important role in modulating insulin secretion (By similarity). In liver, helps to facilitate the uptake and conversion of glucose by acting as an insulin-sensitive determinant of hepatic glucose usage (By similarity). Required to provide D-glucose 6-phosphate for the synthesis of glycogen (By similarity). Mediates the initial step of glycolysis by catalyzing phosphorylation of D-glucose to D-glucose 6-phosphate (PubMed:6477520, PubMed:12513690). ATP + D-hexose = ADP + D-hexose 6-phosphate + H(+) ATP + D-fructose = ADP + D-fructose 6-phosphate + H(+) ATP + D-glucose = ADP + D-glucose 6-phosphate + H(+) ATP + D-mannose = ADP + D-mannose 6-phosphate + H(+) Subject to allosteric regulation (By similarity). Low glucose and high fructose-6-phosphate triggers association with the inhibitor GCKR followed by sequestration in the nucleus (PubMed:10456334). Carbohydrate metabolism; hexose metabolism. Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 1/4. Monomer (By similarity). Interacts with MIDN; the interaction occurs preferentially at low glucose levels and results in inhibition of hexokinase activity (PubMed:24187134). Interacts with GCKR; leading to sequestration in the nucleus (PubMed:10456334, PubMed:16542652). Under low glucose concentrations, associates with GCKR and the inactive complex is recruited to the hepatocyte nucleus. A number of isoforms are produced by alternative promoter usage. The use of alternative promoters apparently enables the type IV hexokinase gene to be regulated by insulin in the liver and glucose in the beta cell. This may constitute an important feedback loop for maintaining glucose homeostasis. Expression is restricted to the liver and pancreatic islets (at protein level). Belongs to the hexokinase family.