HKDC1

The HKDC1 gene is oriented in a head-to-tail arrangement next to the HK1 gene on chromosome 10.^[7][8] This arrangement, along with its amino acid sequence similarity to HK1, suggests that HKDC1 and HK1 derived from the same precursor via a tandem gene duplication event.^[6][7][8] The similarity between HKDC1 and HK1 may have obscured its discovery in earlier screens for vertebrate hexokinases.^[6] Unlike the HK2 pseudogene, HKDC1 contains an intact open reading frame of 917 residues. It is conserved across animal species, indicating that it encodes a functional protein. Moreover, the encoded protein contains conserved glucose-binding sites in its N- and C-terminal domains as well as an ATP-binding site in its C-terminal domain, indicating that its C-terminal is capable of hexokinase activity.^[7][8]

As the recently identified fifth isoform of hexokinase, HKDC1 catalyzes the rate-limiting and first obligatory step of glucose metabolism, which is the ATP-dependent phosphorylation of glucose to G6P.^[9] Though its particular biological function remains unclear, HKDC1 has been suggested to play a more major role in glucose metabolism during pregnancy, as the mother would need to provide enough energy for both herself and the fetus.^[6][7] HKDC1 is ubiquitously expressed, with the highest levels of expression in pharynx, thymus, colon, esophagus, and eye tissue.^[7][8]