Annexins

Annexins are a family of calcium-dependent phospholipid-binding proteins found in the cytosol and associated with intracellular and plasma membranes. They share a conserved core consisting of four annexin repeats that fold into a curved, membrane-binding structure. The N-terminal region is variable among family members and modulates localization, interactions, and regulatory functions. In most cells, annexins translocate to membranes in response to increases in intracellular calcium, where they can associate with various organelle and plasma-membrane surfaces. Some annexins can form lattice-like assemblies on membranes and participate in signaling networks through protein–protein interactions.

Annexins participate in a broad range of membrane-related processes. They are involved in vesicle trafficking, exocytosis and endocytosis, membrane fusion and fission, lipid bilayer organization, and calcium signaling. They can act as scaffolds or regulators, linking membranes to the cytoskeleton and to signaling pathways. In many contexts, annexins contribute to membrane repair after mechanical or chemical injury, helping reseal damaged membranes. Some members are secreted via non-classical pathways and function extracellularly, where they can influence inflammation and coagulation.

Notable members include Annexin A1, which has anti-inflammatory roles, and Annexin A2, which forms a Ca2+-regulated heterotetramer with S100A10 and participates in plasminogen activation at the cell surface. Annexin A5 binds phosphatidylserine exposed on apoptotic cells and is widely used as a marker of apoptosis in research and clinical pathology. The annexin family is conserved across many eukaryotes, with multiple paralogs in vertebrates.

In humans, the family comprises numerous members (commonly ANXA1–ANXA11), each with tissue-specific expression and overlapping yet distinct functional roles in membranes and signaling.