The influenza virus contains a segmented RNA genome with eight negative-sense segments encoding 11 proteins. The influenza virus polymerase is a heterotrimeric complex comprised by the protein subunits: PA, PB1, and PB2. It plays central roles in the viral life cycle and is directly responsible for RNA synthesis for both viral replication and transcription.

The PA subunit can be cleaved into two independent domains: a smaller N-terminal domain with cap-dependent endonuclease activity and a larger C-terminal domain that mediates the interaction with PB1. Structural domains comprising this superfamily share the structure of the N-terminal endonuclease domain of PA PMID:19587036,PMID:22876177,PMID:26976575.