Cytidine/uridine monophosphate kinase 2 (CMPK2)

Cytidine/uridine monophosphate kinase 2 (CMPK2) is a mitochondrial enzyme involved in the salvage pathway of pyrimidine nucleotide synthesis, catalyzing the phosphorylation of dUMP, dCMP, CMP, and UMP, as well as several pyrimidine nucleoside analogs, using ATP as a phosphate donor. Unlike the ubiquitously expressed cytosolic UCK1, CMPK2 has a more restricted expression pattern and mediates key roles in cellular dNTP synthesis, immune response modulation, and suppression of viral replication, in part through participation in interferon-stimulated pathways. Overexpression of CMPK2 is associated with certain cancers and neuroinflammatory states, and its kinase activity is critical for activating several anticancer and antiviral nucleoside analog prodrugs. CMPK2 also enables the production of oxidized mitochondrial DNA fragments, which can activate the NLRP3 inflammasome and contribute to inflammatory processes.

Other names

UMP-CMP kinase 2, mitochondrialUMP/CMP kinase 2UMP-CMPK2TYKiNucleoside-diphosphate kinaseCytidylate kinase 2Thymidine monophosphate kinase 2TMPK2IBGC10NDKNucleoside-diphosphate kinase, mitochondrialUMPKUMPK2

Phosphorylation (activation) of nucleoside analog prodrugs, converting them to active triphosphate forms - Inhibition (or depletion) of pyrimidine salvage pathway, reducing dNTP synthesis required for DNA/RNA synthesis in rapidly dividing cells (e.g., cancer) - Suppression of viral replication via metabolic restriction or direct interference with viral polymerase activity (in cooperation with viperin and ddhCTP)