The S-100 family of calcium-activated proteins interact with a range of target proteins to modulate biological signaling pathways. Numerous cancer cell lines overexpress the plasminogen receptor S-100A10 on the extracellular cell surface, where it forms a heterotetrameric complex with Annexin II, though this association is not required for plasma membrane localization or binding and activation of plasminogen. Additionally, S-100A10 acts as a cellular chaperone for hepatitis B (Hep B) virus polymerase. Hep B virus polymerase normally localizes to the cytoplasm only, though in the presence of S-100A10 a portion relocates to the nucleus, implying a role for S-100A10 and intracellular calcium in the process of viral replication.