Protein that acts both as a host restriction factor involved in defense response to virus and as a regulator of DNA end resection at stalled replication forks (     , ). Has deoxynucleoside triphosphate (dNTPase) activity, which is required to restrict infection by viruses, such as HIV-1: dNTPase activity reduces cellular dNTP levels to levels too low for retroviral reverse transcription to occur, blocking early-stage virus replication in dendritic and other myeloid cells (      ). Likewise, suppresses LINE-1 retrotransposon activity ( ). Not able to restrict infection by HIV-2 virus; because restriction activity is counteracted by HIV-2 viral protein Vpx (, ). In addition to virus restriction, dNTPase activity acts as a regulator of DNA precursor pools by regulating dNTP pools . Phosphorylation at Thr-592 acts as a switch to control dNTPase-dependent and -independent functions: it inhibits dNTPase activity and ability to restrict infection by viruses, while it promotes DNA end resection at stalled replication forks ( , ). Functions during S phase at stalled DNA replication forks to promote the resection of gapped or reversed forks: acts by stimulating the exonuclease activity of MRE11, activating the ATR-CHK1 pathway and allowing the forks to restart replication . Its ability to promote degradation of nascent DNA at stalled replication forks is required to prevent induction of type I interferons, thereby preventing chronic inflammation (, ). Ability to promote DNA end resection at stalled replication forks is independent of dNTPase activity . Enhances immunoglobulin hypermutation in B-lymphocytes by promoting transversion mutation (By similarity).
Subcellular locations: Nucleus, Chromosome
Localizes to sites of DNA double-strand breaks in response to DNA damage.
Expressed in heart, skeletal muscle, spleen, liver, small intestine, placenta, lung and peripheral blood leukocytes . No expression is seen in brain and thymus .