Linear schematic of an E2 protein

The E2 protein plays multiple roles in the viral life cycle. E2 is the major transcriptional regulator of the virus and can both activate and repress viral transcription by specifically binding to consensus motifs in the viral genome (ACCNNNNNNGGT or ACCGNNNNCGGT). E2 also initiates viral DNA replication by loading the E1 helicase protein onto the replication origin. E2 maintains the viral genome as an extrachromosomal replicon by tethering it to the host chromosomes. E2 proteins are approximately 400 to 500 residues long. They consist of an N-terminal transactivation domain of about 200 amino acids and a C-terminal DNA binding and dimerization domain of about 100 amino acids. The region between is designated the “hinge” and varies in both length and sequence composition. Shorter E2 products containing sequences from the C-terminal region are expressed from many papillomaviruses.