Mode E collectively points to the generic strategies for damaging and deactivating the host proteins. It could be achieved by protein tagging (i.e., SUMO, ubiquitin), or the activation of viral proteases. Among the cross-taxa Pfam families, some families are associated with specialized proteases (Table S3) . Mode E shows the various routes by which acquired sequences alter key cellular processes. Molecular mimicry in trafficking and the subcellular localization is common to many viruses. For example, Soluble N-ethylmaleimide sensitive factor Attachment Protein (a-SNAP) is a conserved protein among all eukaryotes. It was also found in Canarypox and Fowlpox viruses [51] . These proteins may alter the balance of the vesicular trafficking, docking and the membrane fusion machinery. In autophagy, viral proteins exploit processes such as membrane fusion and protein folding for the benefit of their replication [52] .