ANXA4 - Annexin A4 | Elisa - Clia - Antibody - Protein

Background:

Annexin A4, also known as ANXA4, is a protein encoded by the ANXA4 gene in humans. It belongs to a family of calcium-dependent phospholipid-binding proteins called annexins. These proteins are involved in various cellular processes, including membrane trafficking, ion channel regulation, and apoptosis. Annexin A4 consists of about 318 amino acids and has a molecular weight of approximately 35 kDa. ANXA4 has a high affinity for binding to negatively charged phospholipids, particularly phosphatidylserine. This binding is calcium-dependent, meaning it requires calcium ions to occur. ANXA4 is primarily found in the cytoplasm and associated with the plasma membrane. It can also localize to intracellular vesicles.ANXA4 has roles in membrane organization and dynamics. It is involved in the regulation of membrane structure and function. Some studies suggest that ANXA4 may play a role in intracellular signaling pathways. For example, it may be involved in the regulation of cell growth and differentiation. Annexin family proteins, including ANXA4, have been implicated in the regulation of apoptosis. They can influence the process of programmed cell death, either by promoting or inhibiting it depending on the cellular contex. ANXA4 has been studied in various diseases, including cancer. Alterations in ANXA4 expression or function have been linked to certain types of cancer, though the exact role in cancer progression is still being investigated.

Protein Structure:

• Core Domain: ANXA4 consists of a conserved core domain made up of four annexin repeats, each containing about 70 amino acids. These repeats form a convex structure that binds calcium ions and a concave structure that interacts with phospholipids.
• N-terminal Domain: The N-terminal domain of ANXA4 is unique and less conserved among different annexin family members. It is involved in specific protein-protein interactions and can undergo post-translational modifications such as phosphorylation.

Classification and Subtypes:

ANXA4 is classified under the annexin family, which includes multiple proteins such as ANXA1, ANXA2, ANXA3, and ANXA5. While there are no specific subtypes of ANXA4, its functional state can be influenced by calcium binding and post-translational modifications.

Function and Biological Significance:

• Membrane Repair: ANXA4 plays a crucial role in the repair of cellular membranes. Upon cellular injury, it binds to the membrane in a calcium-dependent manner to facilitate membrane resealing.
• Vesicle Trafficking: ANXA4 is involved in vesicle trafficking and fusion, contributing to processes like exocytosis and endocytosis.
• Cell Signaling: ANXA4 participates in intracellular signaling pathways by forming complexes with other proteins at the plasma membrane, thus influencing cellular responses to external stimuli.
• Inflammation: ANXA4 modulates inflammatory responses by affecting the activity of phospholipase A2, an enzyme involved in the production of inflammatory mediators.
• Anticoagulation: ANXA4 exhibits anticoagulant properties by binding to phospholipid surfaces and inhibiting the assembly of procoagulant complexes.

Interactions:

• Protein-Protein Interactions: ANXA4 interacts with various proteins, including cytoskeletal proteins, enzymes, and receptors. These interactions are critical for its role in membrane dynamics and cellular signaling.
• Phospholipids: ANXA4 binds to phospholipids in a calcium-dependent manner, which is essential for its function in membrane repair and vesicle trafficking.

Clinical Issues:

• Cancer: Aberrant expression of ANXA4 is associated with several types of cancer, including ovarian, colorectal, and gastric cancers. Overexpression of ANXA4 is often linked to increased tumor aggressiveness, metastasis, and resistance to chemotherapy.
• Kidney Diseases: ANXA4 is implicated in kidney function and disorders such as acute kidney injury and chronic kidney disease. It may play a role in the cellular response to renal injury and the regulation of renal cell survival.
• Lung Diseases: Given its expression in lung epithelial cells, ANXA4 is involved in lung physiology and pathology, including lung injury and repair mechanisms.

Summary:

Annexin A4 (ANXA4) is a multifunctional protein involved in membrane repair, vesicle trafficking, cell signaling, and inflammation. Its ability to bind phospholipids in a calcium-dependent manner and interact with various proteins allows it to participate in numerous cellular processes. ANXA4's role in cancer, kidney diseases, and lung diseases underscores its clinical significance. Alterations in ANXA4 expression and function can contribute to disease progression, making it a potential biomarker and therapeutic target. Understanding the mechanisms and interactions of ANXA4 is crucial for developing strategies to modulate its activity in pathological conditions.