CMPK2
Description
The CMPK2 (cytidine/uridine monophosphate kinase 2) is a protein-coding gene located on chromosome 2.
CMPK2 is a mitochondrial nucleotide monophosphate kinase that is essential for the salvage synthesis of deoxyribonucleoside triphosphates (dNTPs). This enzyme plays a critical role in both innate immunity and antiviral defense. CMPK2 mediates immunomodulatory and antiviral activities through both interferon (IFN)-dependent and IFN-independent pathways. It inhibits the replication of various viruses, including flaviviruses and coronaviruses. CMPK2 works in concert with viperin/RSAD2 and ddhCTP to suppress the replication of several coronaviruses by inhibiting the activity of their RNA-dependent RNA polymerase. In the case of flaviviruses, CMPK2 restricts RNA translation when localized to the mitochondria, independent of its kinase activity. CMPK2 can phosphorylate dUMP, dCMP, CMP, UMP, and monophosphates of the pyrimidine nucleoside analogs ddC, dFdC, araC, BVDU, and FdUrd using ATP as a phosphate donor. It exhibits the highest efficacy for dUMP, followed by dCMP, while CMP and UMP are poor substrates. CMPK2 plays a vital role in controlling mitochondrial DNA synthesis by providing the necessary deoxyribonucleotides. CMPK2-dependent mitochondrial DNA synthesis is required for the production of oxidized mitochondrial DNA fragments upon exposure to NLRP3 activators. These oxidized mtDNA fragments then associate with the NLRP3 inflammasome complex in the cytosol, which is essential for its activation.
CMPK2 is also known as NDK, TMPK2, TYKi, UMP-CMPK2.
Associated Diseases
- alopecia
- hemoglobin D disease
- cholesterol-ester transfer protein deficiency
- hypertriglyceridemia 2
- hemoglobin E disease
