ANXA2 - Annexin A2 (receptor) | Elisa - Clia - Antibody - Protein

Background:

Annexin A2 or ANXA2, is a multifunctional protein that plays diverse roles in cellular processes. ANXA2 is a member of the annexin family, known for its calcium-dependent phospholipid-binding properties. ANXA2 is involved in membrane organization and dynamics. It can bind to phospholipids in the cell membrane, affecting its structure and function.ANXA2 has roles in endocytosis, the process by which cells absorb molecules from the external environment, and exocytosis, the release of molecules from cells. ANXA2 plays a role in the regulation of fibrinolysis, It interacts with plasminogen and tissue plasminogen activator (tPA) to promote the conversion of plasminogen to plasmin, an enzyme that degrades fibrin.ANXA2 also acts as a receptor for several proteins. ANXA2 forms a complex with tPA, aiding in the conversion of plasminogen to plasmin, which is crucial for fibrinolysis. S100A10 (P11) forms a heterotetrameric complex with ANXA2, which has implications in processes such as membrane organization and exocytosis.ANXA2 is expressed in various tissues, including the brain, heart, kidney, and liver. Its expression pattern suggests roles in these tissues, particularly in processes related to membrane dynamics and cellular signaling.

Protein Structure:

• Core Domain: ANXA2 contains a conserved core domain made up of four annexin repeats. These repeats are responsible for calcium-dependent phospholipid binding.
• N-terminal Domain: ANXA2 has a unique N-terminal domain that facilitates its interactions with other proteins and post-translational modifications such as phosphorylation and acetylation. This domain is critical for its diverse functional roles.

Classification and Subtypes:

ANXA2 belongs to the annexin family, which includes several other proteins (e.g., ANXA1, ANXA3, ANXA5). While there are no subtypes of ANXA2, it can exist in different functional forms:

• Monomeric ANXA2: Functions independently in various cellular processes.
• Heterotetrameric Form: ANXA2 often forms a complex with S100A10 (p11), creating a heterotetramer that has distinct functions, particularly in membrane dynamics and cellular signaling.

Function and Biological Significance:

• Membrane Dynamics: ANXA2 plays a critical role in membrane-related processes such as endocytosis, exocytosis, and membrane repair. It helps in the organization of membrane domains and the formation of lipid rafts.
• Cytoskeletal Interactions: ANXA2 interacts with the actin cytoskeleton, contributing to cell shape, motility, and adhesion.
• Cellular Signaling: ANXA2 is involved in various signaling pathways, including those regulating cell growth and apoptosis. It also participates in the assembly of signaling complexes at the plasma membrane.
• Angiogenesis and Coagulation: ANXA2 is crucial for angiogenesis (the formation of new blood vessels) and the regulation of coagulation, promoting plasminogen activation and fibrinolysis.

Interactions:

• Protein-Protein Interactions: ANXA2 interacts with several proteins, including S100A10, actin, and various signaling molecules. The ANXA2-S100A10 complex is particularly important for membrane dynamics and signal transduction.
• Phospholipids: ANXA2 binds to phospholipids in a calcium-dependent manner, which is essential for its role in membrane organization and vesicle trafficking.

Clinical Issues:

• Cancer: ANXA2 is implicated in various cancers, including breast, lung, and colorectal cancers. It is often overexpressed in tumors and is associated with increased cell proliferation, invasion, and metastasis. ANXA2's role in angiogenesis also supports tumor growth and vascularization.
• Inflammatory Diseases: ANXA2 is involved in inflammatory responses and has been linked to conditions such as rheumatoid arthritis and inflammatory bowel disease. Its regulation of plasminogen activation and fibrinolysis can influence inflammation and tissue remodeling.
• Vascular Diseases: Given its role in angiogenesis and coagulation, ANXA2 is associated with vascular diseases. Abnormal ANXA2 function or expression can contribute to atherosclerosis, thrombosis, and other vascular disorders.

Summary:

Annexin A2 (ANXA2) is a multifunctional protein that plays critical roles in membrane dynamics, cytoskeletal interactions, and cellular signaling. Its ability to bind phospholipids in a calcium-dependent manner and form complexes with other proteins, such as S100A10, enables it to participate in various physiological processes, including angiogenesis and coagulation. ANXA2 is implicated in several clinical conditions, particularly cancer and inflammatory diseases, where its altered expression and function can contribute to disease progression. Understanding ANXA2's mechanisms and interactions is essential for developing therapeutic strategies targeting its activity in pathological conditions.