ANXA5 - Annexin A5 | Elisa - Clia - Antibody - Protein

Background:

Annexin A5, also known as ANXA5 or annexin V, is a protein encoded by the ANXA5 gene in humans. Like other annexins, it is a calcium-dependent phospholipid-binding protein. Annexin A5 consists of about 320 amino acids with a molecular weight of approximately 35 kDa. Annexin A5, similar to other annexins, has a high affinity for binding to phospholipids, particularly phosphatidylserine (PS). This binding occurs in the presence of calcium ions. Annexin A5 is primarily found in the cytoplasm, but it can translocate to the cell membrane in response to increased intracellular calcium levels. During apoptosis, phosphatidylserine is translocated from the inner to the outer leaflet of the plasma membrane. Annexin A5 can bind to these exposed PS molecules on the surface of apoptotic cells, making it a valuable tool in detecting and quantifying apoptosis in cell cultures and tissues. Annexin A5 has also been shown to inhibit blood coagulation. It can bind to phospholipids on the surface of activated platelets, thereby interfering with the coagulation cascade. Studies suggest that Annexin A5 may have anti-inflammatory effects by modulating immune responses. It may influence the production of inflammatory mediators and cytokines. Annexin A5 has been studied in the context of pregnancy and fertility. It is involved in processes such as placental development and the prevention of immune rejection of the fetus. Annexin A5 may also play a role in intracellular signaling pathways, though the specifics are still being investigated. Due to its ability to bind to apoptotic cells, Annexin A5 is used in research and clinical settings for imaging apoptotic cells. Radiolabeled Annexin A5 can be used in techniques such as positron emission tomography (PET) to visualize cell death in diseases like cancer and cardiovascular disorders.

Protein Structure:

• Core Domain: ANXA5 contains a conserved core domain with four annexin repeats, each capable of binding calcium ions. These repeats form a structure that can bind to phospholipid membranes.
• N-terminal Domain: The N-terminal domain is unique and can interact with specific proteins or undergo post-translational modifications, influencing ANXA5’s functional diversity.

Classification and Subtypes:

ANXA5 belongs to the annexin family, which includes several other proteins like ANXA1, ANXA2, ANXA3, and ANXA4. There are no specific subtypes of ANXA5, but its activity and function can be modulated by different calcium concentrations and post-translational modifications.

Function and Biological Significance:

• Anticoagulation: ANXA5 is well-known for its anticoagulant properties. It binds to phospholipid surfaces, thereby inhibiting the assembly of procoagulant enzyme complexes, which helps prevent blood clotting.
• Apoptosis: During apoptosis, ANXA5 binds to phosphatidylserine, a phospholipid that becomes exposed on the outer leaflet of the cell membrane of apoptotic cells. This property is utilized in assays for detecting apoptotic cells.
• Cell Signaling: ANXA5 interacts with cell signaling pathways, modulating cellular responses to external stimuli.
• Membrane Repair: ANXA5 contributes to the repair of damaged cell membranes by binding to the site of injury and facilitating the resealing process.
• Inflammation: It has a role in the inflammatory response, potentially by modulating the activity of phospholipase A2 and other enzymes involved in producing inflammatory mediators.

Interactions:

• Phospholipids: ANXA5 binds to phospholipids in the presence of calcium ions, particularly phosphatidylserine, which is exposed on the surface of apoptotic cells.
• Proteins: It interacts with various intracellular proteins, influencing processes such as membrane repair, vesicle trafficking, and signal transduction.

Clinical Issues:

• Cancer: Altered expression of ANXA5 has been observed in several cancers, including breast, ovarian, and colorectal cancers. It can affect tumor progression, metastasis, and response to treatment.
• Cardiovascular Diseases: Due to its anticoagulant properties, ANXA5 is implicated in cardiovascular diseases. It may serve as a marker for conditions like atherosclerosis and myocardial infarction.
• Autoimmune Diseases: ANXA5 can be targeted by autoantibodies in certain autoimmune diseases, leading to conditions such as antiphospholipid syndrome, which increases the risk of thrombosis.
• Fertility: ANXA5 is involved in placental function, and its dysregulation can affect fertility and pregnancy outcomes.

Summary:

Annexin A5 (ANXA5) is a multifunctional protein crucial for processes such as anticoagulation, apoptosis, membrane repair, and inflammation. Its ability to bind phospholipid membranes in a calcium-dependent manner and interact with various proteins underscores its importance in cellular physiology. Clinically, ANXA5 is significant in cancer, cardiovascular diseases, autoimmune conditions, and reproductive health. Understanding its mechanisms and interactions is essential for leveraging its potential as a biomarker and therapeutic target in various diseases.