Thymidine Kinase 2: Proteins and Enzymes

The mitochondrial deoxyribonucleotide (dNTP) pool is separated from the cytosolic pool because the mitochondria inner membrane is impermeable to charged molecules. The mitochondrial pool is maintained by either import of cytosolic dNTPs through dedicated transporters or by salvaging deoxynucleosides within the mitochondria; apparently, enzymes of the de novo dNTP synthesis pathway are not present in the mitochondria. In nonreplicating cells, where cytosolic dNTP synthesis is downregulated, mtDNA synthesis depends solely on the mitochondrial salvage pathway enzymes, the deoxyribonucleoside kinases. Two of the 4 human deoxyribonucleoside kinases, deoxyguanosine kinase (DGK) and thymidine kinase-2, are expressed in mitochondria. Human DGK, encoded by the DGUOK gene (MIM 601465), efficiently phosphorylates deoxyguanosine and deoxyadenosine, whereas TK2 phosphorylates deoxythymidine, deoxycytidine, and deoxyuridine. Thymidine kinase-2 (TK2) is a deoxyribonucleoside kinase that phosphorylates thymidine, deoxycytidine, and deoxyuridine, and also phosphorylates antiviral and anticancer nucleoside analogs.[supplied by OMIM]