Essential serine/threonine-protein kinase that plays different role in the viral life cycle (PubMed:1560522, PubMed:1602551). Phosphorylates the host small ribosomal protein RACK1 thereby customizing the ribosomes to a state optimal for viral mRNAs (which contain poly-A leaders) but not for host mRNAs (PubMed:28636603). Facilitates viral DNA replication by inhibiting host BANF1, a cellular host defense responsive to foreign DNA (PubMed:18005698, PubMed:1602551). Phosphorylates host BANF1 on serine and threonine residues; this leads to BANF1 relocalization to the cytoplasm, loss of dimerization and impaired DNA binding activity (PubMed:24600006). Indeed, BANF1 activity depends on its DNA-binding property which is blocked by VPK1-mediated phosphorylation (PubMed:18005698). Required for viral intermediate genes expression, probably by inhibiting host BANF1 (PubMed:11287554, PubMed:23891157). Modulates cellular responses via host JUN by two different mechanisms, either by direct phosphorylation or by modulation of upstream JIP1-MAPK complexes (PubMed:16840345). Seems to participate in the accumulation/processing of late proteins and thus in virion maturation (PubMed:26223647). In addition, inhibits B12 repressive activity on viral DNA replication via a phosphorylation-dependent mechanism (PubMed:31341052). ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein] ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein] Interacts with host JIP1; this interaction increases the amount of MAPK bound to JIP1 and subsequently increases the activity of transcription factors, such as JUN, that respond to these complexes. Interacts with protein B12; this interaction inhibits the repressive activity of B12 pseudokinase on viral replication factory formation (PubMed:31341052). Localizes in cytoplasmic viral factories and is a minor component of the virion. Expressed early in the viral replication cycle. Autophosphorylated. Up to 650-fold decreased virus production. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. Poxviruses subfamily.