Multiple members of the same evolutionary family of calcium-binding proteins share the EF-hand calcium-binding domain (EF-hand, IPR002048). When Ca 2+ binds to the EF hand motif, the protein undergoes conformational changes that can either activate or deactivate the protein(s) downstream. Pairs or larger groups are the norm form for EF-hand. Cell polarity and migration are just two of the processes that the cadherin with the CADG domain (IPR006644) controls. Hemolysin-type calcium-binding proteins (HCBPs) have a domain called the HCBP related domain (PF06594), which is unique to bacteria. The P/Homo domain (IPR002884) is found in a family of calcium-dependent endoproteases known as prohormone-preprotein convertases (PCs). P-protein (for proteolytic) activity is required for the degradation and excretion of hormone peptides and secretory proteins. Even mammalian furin (SPC1/PACE; EC 3.4.21.75) has a P/Homo domain. The local MEME tools were used to compare the sequences of various skin-and bacteria EF-hand -related bacteria to that of the monkeypox virus E protein F13. Table shows that the F13 protein of the monkeypox virus E has the EF-hand, CADG, HCBP related, and P/Homo motifs. Proteins with the motifs EF-hand A-F, CADG A, HCBP related A, and P/Homo A are located in the F13 protein region. Calcium ionophore (Ca2+) is found to be required for both receptor binding and membrane fusion. Both the CADG domain and the HCBP related domain found in E protein F13 indicate that it is responsible for cadherin and hemolysin functions, respectively. Similarly to animal furin, E protein has the P/Homo. It suggests that after binding Ca2+, virus will be able to self-cleave in the same way that furin does.