ANXA1
Description
The ANXA1 (annexin A1) is a protein-coding gene located on chromosome 9.
Annexin A1, also known as lipocortin I, is a protein that is encoded by the ANXA1 gene in humans. Annexin A1 belongs to the annexin family of Ca2+-dependent phospholipid-binding proteins that have a molecular weight of approximately 35,000 to 40,000 Dalton and are preferentially located on the cytosolic face of the plasma membrane. Annexin A1 protein has an apparent relative molecular mass of 40 kDa with phospholipase A2 inhibitory activity. Glucocorticoids (such as budesonide, cortisol, and beclomethasone) are a class of endogenous or synthetic anti-inflammatory steroid hormones that bind to the glucocorticoid receptor (GR), which is present in almost every vertebrate animal cell. They are used in medicine to treat diseases caused by an overactive immune system, including allergies, asthma, autoimmune diseases, and sepsis. Because they suppress inflammatory pathways, long-term use of glucocorticoid drugs can lead to side-effects such as immunodeficiency and adrenal insufficiency. The main mechanism of glucocorticoids' anti-inflammatory effects is to increase the synthesis and function of annexin A1. Annexin A1 both suppresses phospholipase A2, thereby blocking eicosanoid production, and inhibits various leukocyte inflammatory events (epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst, etc.). In other words, glucocorticoids not only suppress immune response, but also inhibit the two main products of inflammation, prostaglandins and leukotrienes. They inhibit prostaglandin synthesis at the level of phospholipase A2 as well as at the level of cyclooxygenase/PGE isomerase (COX-1 and COX-2), the latter effect being much like that of NSAIDs, potentiating the anti-inflammatory effect.
ANXA1 plays crucial roles in both innate and adaptive immunity. It acts as an effector in glucocorticoid-mediated responses, regulating the inflammatory process and exhibiting anti-inflammatory activity (PubMed:8425544). ANXA1 participates in the downregulation of the early phase of the inflammatory response mediated by glucocorticoids (By similarity). ANXA1 contributes to adaptive immunity by enhancing signaling cascades triggered by T-cell activation, regulating differentiation and proliferation of activated T-cells (PubMed:17008549). It promotes the differentiation of T-cells into Th1 cells and negatively regulates differentiation into Th2 cells (PubMed:17008549), with no effect on unstimulated T cells (PubMed:17008549). ANXA1 negatively regulates hormone exocytosis through the activation of formyl peptide receptors and reorganization of the actin cytoskeleton (PubMed:19625660).
ANXA1 is also known as ANX1, LPC1.
