annexin

Annexin is a family of calcium-dependent phospholipid-binding proteins found in many eukaryotes. In humans, the family includes multiple ANXA genes (ANXA1–ANXA11), and all members share a conserved C-terminal core domain made up of four short, homologous repeats of about 70 amino acids that form a curved, membrane-binding surface. The N-terminal regions are more variable and influence localization and protein interactions. Annexins are typically cytosolic but translocate to membranes when intracellular calcium rises, enabling rapid responses to signaling events.

Calcium binding to loops within the core domain triggers conformational changes that allow binding to negatively charged phospholipids, especially phosphatidylserine, on membranes. This interaction can be reversible and is often regulated by other factors such as phosphorylation or interaction with cytoskeletal components. Annexins can associate with plasma membranes, endosomes, lysosomes, and other organelles, participating in membrane curvature, vesicle fusion, and membrane repair.

Functionally, annexins participate in membrane trafficking, exocytosis and endocytosis, cytoskeletal organization, and signaling. They serve as scaffolds for protein complexes and can modulate inflammatory and coagulation pathways. For example, Annexin A1 exerts anti-inflammatory effects; Annexin A2 forms a heterotetramer with S100A10 and promotes plasminogen activation; Annexin A5 binds phosphatidylserine on the surface of apoptotic cells and is widely used as a marker of apoptosis.

Because of their roles in membrane dynamics and cell signaling, annexins are studied as potential biomarkers and therapeutic targets in cancer, cardiovascular disease, and neurodegenerative disorders. They are also used as research tools, with Annexin V staining being a standard method for detecting apoptotic cells in flow cytometry and microscopy.