3.9 F13 protein aids active membrane fusion of monkeypox virus 1. Ca 2+ activates the Mg 2+ -dependent serine protein kinase and phosphatase of F13. Based on the results of this research, the E protein F13 of the monkeypox virus is a GTPase that possesses GAP and GEF domains, GTP/GDP binding domains, GTPase domains, and PPM domains but no GDI active region. The GTP and GDP binding domains are partially overlapped by the Protein Kinase and PPM domains, which are also Mg2+ active domains. E protein, F13 from the monkeypox virus is also Ca-dependent and has multiple EF hand domain motifs. Once the EF-hand is bound to Ca2+, the Serine Protein Kinase (and PI3K Kinase) and PPM domains are revealed. Ca2+ activates F13, which then functions as a serine protein kinase and phosphatase dependent on Mg2+. For the E protein F13 of the monkeypox virus to work as a GTPase, the PPM domain must be exposed and Mg2+ must bind to it.